Influence on allograft rejection of thymectomy at different stages of larval development in urodele amphibian Pleurodeles waltlii Michah. (Salamandridae). Thymectomy was performed on the urodele amphibian Pleurodeles waltlii Michah. from the 5th to the 20th week of larval development. Thymectomized animals were allografted at 7 months of age. The results obtained are as follows: (1) Pleurodeles thymectomized before 10 weeks always tolerated allografts: (2) Pleurodeles thymectomized within 11 to 13 weeks generally rejected allografts in a chronic manner, but sometimes tolerated them; (3) normal rejections occurred in Pleurodeles thymectomized at 14 weeks, or later. Stage 52 of the developmental table (10 weeks of age) is a critical "end stage" for the efficiency of thymectomy. The results are confirmed by the fate of second set allografts performed in all these animals.


Synthetic antigens. II. Immunogenic, antigenic and adjuvant properties of a copolymer of styrene and maleic anhydride. Immunogenic, antigenic and adjuvant properties of a polyanionic copolymer of styrene and maleic anhydride (PSM) are described. The results obtained showed that PSM was immunogenic in BALB/c mice when administered without adjuvant, the optimal dose being 0.01 mug/mouse. Antibodies could be detected only by precipitation in gel but not by agglutination. High molecular weight polymer (290 000 daltons) was a stronger immunogen and antigen than copolymers of lower molecular weights (85 000-210 000 daltons). PSM also showed adjuvant activity and enhanced the humoral response of mice against sheep red blood cells. Adjuvanticity was found only when 1 mug of PSM/mouse was applied. The results obtained suggest that PSM interacts with B rather than T cells.


Decrease in microviscosity of lymphocyte surface membrane associated with stimulation induced by concanavalin A. CM factor (CVF) - treated normal mouse serum produced a profound inhibition of the antibvody responses, affecting IgG responses more than IgM, and being T-dependent more than T-independent, but no part of the response being unaffected...


Antigen-induced changes in lymphocyte circulatory patterns. The effect of a splenic or lymph node anti-sheep red blood cell response on lymphocyte migration patterns in mice was studied. It was found that trapping of lymphocytes in these stimulated organs was indiscriminate and was followed by a period of restricted cell entry or localization; furthermore, reduced cell localization in the spleen, during the splenic response,  was accompanied by a reduction in the number of cells localizing in unstimulated brachial and axillary lymph nodes. These results were taken to indicate that major changes occur in lymphocyte circulation during strong splenic immune responses.


Use of formalin-fixed melanoma cells for the detection of antibodies against surface antigens by a micro-immune adherence technique. Established malanoma cell lines were fixed in suspension with 4% formalin and tested for antigenic activity against sera from melanoma patients in a micro-immune adherence test. By incubation of formalin-fixed cells in serum-free medium the unspecific background rosette formation was substantially reduced to below 10%. As could be demonstrated in absorption experiments with viable and formalin-fixed tumor cells, surface antigens reacting with sera from melanoma patients are largely unaffected by formalin treatment.


Isolation and properties of a 7 S rat immunoglobulin different from IgG. A 7 S rat immunoglobulin, of rapid electrophoretic mobility, was characterized and isolated from normal or hyperimmune rat serum and was designated "IgR". This immunoglobulin belongs to a class different from IgG and was originally described as IgA. IgR has a molecular weight of 160 000, is present in the serum and milk as a monomer and is readily absorbed by the intestine of suckling rats. In hyperimmunized animals, about 20% of the antibodies were of the IgR class. IgR is devoid of anaphylactic capacity and no homologies could be established between it and immunoglobulins of other animal species.


Inactivation of hapten-modified bacteriophage by antibody: increased sensitivity of the assay in media containing polyethylene glycol. Inactivation of dinitrophenylated bacteriophage T4 by porcine and rabbit anti-dinitrophenyl (DNP) antibodies was studied by the complex inactivation methods. The inactivation titers increased 20-30 times when polyethylene glycol, mol. wt. 6000, was added to the incubation media. Consequently, the detection of dinitrophenylated serum albumin with the modified bacteriophage could be carried out with higher sensitivity upon addition of polyethylene glycol.


Human lymphoblast cell lines: antibody-dependent cytotoxicity. Five cell lines were isolated after prolonged culture of human buffy coat leukocytes. The cells consisted for the most part of lymphoblasts morphologically similar to those produced by in vivo or in vitro stimulation of small lymphocytes by antigens or mitogens. One of the lines possessed virus-like particles of the Epstein-Barr type. All the established lines were capable of mediating antibody-dependent cytotoxicity (LADC) quantitatively at a level not significantly different from that mediated by freshly isolated, normal human peripheral blood lymphocytes (PBL). The LADC of the lymphoblasts was inhibited by all the human IgG subclasses tested (IgG1, IgG2, IgG3, IgG4) as was the LADC of PBL. It is concluded that, at least so far, the lymphoblasts have retained the properties of the lymphocytes from which they were originally derived as regards their ability to mediate LADC.


Significance of spontaneous autorosettes in rats. Between 10(3) and 10(4) auto-rosette-forming cells (RFC) per 10(6) lymphocytes are observed in lymphoid organs of normal rats in vitro. Counts are significantly higher in the thymus than in other organs. Contrary to what has been previously described in mice, auto-RFC are not inhibited by fresh normal rat serum. The data presented are compatible with the hypothesis that auto-RFC differ from the lymphocytes which recognize only alloerythrocytes according to histocompatibility differences. There is evidence which suggests that autorosette formation is linked to the expression of new determinants on ageing erythrocyte membranes.


A network theory of the immune system.

A network theory of the immune system. The fact that every antibody also has antigenic properties leads to the existence of a functional network of interacting antibodies and lymphocytes in the immune system. With a minimum set of assumptions about the nature of these interactions some of the principal features of the immune response such as normal primary and secondary response, low and high zone tolerance induction, and memory can be reproduced. The low zone tolerance phenomenon plays a central role in our theory, as it is the simplest nontrivial mode of response to an antigenic stimulus. It may be understood as the defeat of the stimulated lymphocyte species against their internal adversaries. The normal response and high zone tolerance induction may be characterized as low zone tolerance on a second and third level of a hierarchy of lymphocyte populations. In particular, the weakness of the primary response is explained in terms of internal struggles which lead to a final suppression of the aggressors, thereby opening the way for an unhindered secondary response.


A human lymphoid cell line with an IgG-like membrane component. A human lymphoid cell ine (S95) with surface-located IgG is described. The line was derived from a patient with Hodgkin's disease and is aneuploid. Its characteristics are suggestive of a malignant B lymphocyte derivation, but no ultimate proof of malignancy can be forwarded. The line produces immunoglobulin (IgG) which appears to be devoid of light chain. The amount of IgG detectable at the cell surface by inhibition of the rosette formation by protein A-coated sheep red blood cells with protein A was 5-10 ng/10(6) cells corresponding to 70 000 - 140 000 molecules/cell. The immunoglobulin is membrane bound. Partial characterization of the IgG-like protein shows that it has a molecular weight of 50 000 Daltons and that the molecule lacks some of the normal gamma-chain determinants.


Separation of complement-dependent and lymphocyte-dependent cytotoxic activity in human sera. Two human sera having both complement-dependent and lymphocyte-dependent antibody activities (CDA, LDA) were applied to isoelectrofocusing columns. Maximum LDA activity for both sera was found focused at a higher pH than maximum CDA activity. The studies suggest that LDA molecules may exist without having complement-dependent activity.


The role of thymus on autosensitization against syngeneic normal and malignant cells. Mouse lymphocytes were exposed to syngeneic fibroblasts and tumor cells in Millipore chambers inserted into the peritoneal cavity of intact and thymectomized mice. Autosensitization to fibroblasts occurred only if the chambers were carried by thymectomized mice. Sensitization to tumor-specific antigens also took place in intact mice. If thymic extract was administered to thymectomized mice autosensitization in the chambers was inhibited.


Influence of metformin on arginine-induced glucagon secretion in human diabetes. The insulin and glucagon responses to arginine infusion were investigated in patients with maturity-onset diabetes under control conditions and during metformin therapy. Metformin did not significantly affect the insulin nor the glucagon response to arginine. These data support the concept that biguanide do not act directly on the islets of Langerhans.


[Chronic hyperammonemia with orotic aciduria: evidence of pyrimidine pathway stimulation (author's transl)]. We have investigated a 3 year old girl with mental and physical retardation, chronic hyperammonemia and orotic aciduria. Plsma glutamine, alanine and proline concentrations were high. Alanine was present in her urine. She excreted only half the urea of control subjects on a similar protein intake. Raising protein intake induced NH4 intoxication with convulsion. Orotic aciduria was present (max: 693 mg/day) and was related to NH4 levels. Red blood cell orotate phosphoribosyl transferase and orotidine decarboxylase activieé were normal, eliminating congenital orotic aciduria, with induction of activity seen on repeated assay during protein load (form 1.37 to 7.5 nmole/109 RBC/hr). Blood ammonia rose with ornithine load, while ornithine levels were twice that of controls. Citrulline was normally metabolized. Although lacking liver assay, we have provided evidence of partial ornithine carbamyl transferase deficiency. The importance of orotic aciduria for ammonia detoxication in partial OCT deficiency is shown, and its possible effect on liver lipoprotein synthesis discussed. Our investigation also confirmed that OCT activity is not present in normal leukocytes rendering them useless for OCT deficiency diagnosis.


[Diabetes and autoimmune diseases (author's transl)]. Recent clinical and immunological data suggest that the classical concept of "idiopathic autoimmune diseases" is to be revised. In a normal population, autoimmunity reactions against thyroid gland, gastric mucosa and adrenals develop slowly with increasing age and are found more frequently in women than in men (at least so far as thyroid antibodies are concerned) as is lowering of the functional activity of T lymphocytes. Diabetes takes its place among a series of factors diminishing immunocyte reactivity, and thus enhancing the development of the autoimmunity process. This may perhaps be promoted in some way by genetic factors, perhaps those which also play a definite though as yet ill-defined role in determining the emergence of diabetes. For the present, diabetes mellitus itself must only rarely be considered a consequence of an autoimmune process and then only in certain insulin-dependent cases. By contrast, diabetes appears frequently to be an other than pancreas, namely thyroid gland, adrenals and gastric mucosa. Awareness of these associations should encourage physicians to seek latent humoral or cellular evidence of autoimmune phenomena in diabetics; this would favor the early recognition of clinically important abnormalities which may accompany the diabetes.


[Proportion of low insulin responders to glucose among the offspring of maturity-onset diabetics (author's transl)]. The insensitivity of B cells to glucose, a characteristic of mild essential glucose intolerance may be estimated in a given individual by the comparison of the immediate plasma insulin response to glucose (0 to 10' plasma insulin area or iG) with that to Tolbutamide (iT). It was shown that iG/iT clearly differentiates between nondiabetics and diabetics, whatever their body weight. All the diabetics had an iT/iT lower than 0,65. A high proportion of the offspring of diabetics had an iG/iT ratio in the diabetic range, whether or not they were diabetic. Among these subjects aged from 10 to 49 and weighing between 90 and 144% of their ideal body weight, the iG/iT ratio was not correlated with age nor with relative body weight while the K value was negatively correlated with age. We were thus able to look for the frequency of a "diabetic" iG/iT ratio in the offspring of diabetics, For this in sibships in which all the sibs had been tested, one subject was selected by randomisation. A "diabetic" iG/iT ratio was observed in 7 of 41 subjects with no family history of diabetes, in 27 of 50 with one parent having clinical, maturity-onset diabetes melitus, and in 15 of 19 subjects with two diabetic parents. These results are not compatible with the hypothesis of recessive transmission of the "low insulin response to glucose" characteristic.


Acute suppressive effect of human growth hormone on insulin release induced by glucagon and tolbutamide in man. The acute effect of human growth hormone on glucagon--and tolbutamide--induced insulin release was investigated in 14 non-obese subjects with normal glucose tolerance. Sixty mn after an i.v. growth hormone infusion of 40 mug/kg per kg body weight, the insulin response to glucagon (10 subjects) as well as to tolbutamide (6 subjects) was significantly suppressed by about 35%, both if the insulin secretion was expressed as change in peak response (p less than 0.05 for both insulinogogues) or as per cent change of the integrated insulin area over 30 minutes (p less than 0.005 and p less than 0.05, respectively). A lesser reduction of glucagon-induced insulin secretion was observed also after smaller doses of growth hormone (10 and 20 mug/kg). The reduction of the insulin response was associated with a significantly smaller blood glucose fall following the glucagon and tolbutamide administration. These results support the hypothesis that growth hormone in vivo has an acute suppressive effect on insulin secretion, and show that this action is not limited to glucose-induced stimulation of the islets.


[Diabetes mellitus under 30 years of age. Results of 18 years experience with oral treatment (author's transl)]. Long term experience with the use of sulfonylurea and/or biguanide oral hypoglycemic agents in patients under the age of 30 years shows the following results: 1) Oral treatment under 30 years of age is effective only for a limited period of time, in the large majority less than 24 months;--2) The success of oral treatment of diabetics and the period of effectiveness is increased if the subject is overweight at the time of discovery of the diabetes mellitus;--3) The type of antidiabetic treatment, i.e., insulin only, oral only, or oral and insulin, does not influence the susceptibility to the complications likely to appear in this age group, such as retinopathy, coronary disease, neuropathies and urinary and dental infections;--4) Poteinuria, peripheral vascular disease and various abnormalities of plasma lipids involving cholesterol and triglycerides, are significantly more common in patients under oral therapy than in those receiving insulin. These findings suggest the necessity for serious reconsideration of therapy as soon as any of these pathological events appear, especially the proteinuria or the lipid  anomalies;--5) The duration of the oral treatment preceding therapeutic insulin does not have influence on the subsequent metabolic disturbance (hypoglycemia, deto-acidosis) and thus on the ultimate control of the diabetic state;--6) The somatic growth of the diabetic child is maintained regardless of the type of treatment as long as it is effective. Growth is interrupted however very early if oral treatment becomes ineffective with regard to control of the diabetes. Monitoring of somatic growth during oral antidiabetic treatment is of obvious importance. An interruption in growth is an indication for insulin therapy even if the diabetic control appears satisfactory;--7) The course and the outcome of pregnancy do not appear to be affected by the use of oral therapy at the time of conception. This holds true also for cases in which oral treatment precedes the use of insulin, the pregnancy having commenced during the course of insulin therapy.


Metabolism of the mouse made obese by a high-fat diet. Lean mice were made obese by feeding, ad libitum, a high-lard diet. They showed an increased fat cell size and number which were maintained when this diet was replaced by the control high-carbohydrate diet for 10 weeks. Obese fed mice showed normal glucose and insulin serum levels, but insulinaemia was elevated after an overnight fast. The insulinaemic response after intraperitoneal injection of glucose was insignificant. Thus hyperinsulinism is not a prerequisite for the development of obesity. High-fat diet influenced, in vitro, glucose metabolism of adipose tissue, liver and muscle: basal lipogenesis was markedly  reduced in adipose tissue and liver, and glucose oxidation was decreased in muscle. Insulin sensitivity was reduced by increased fat cell size. De novo formation of fatty acids in liver and adipose tissue did not contribute to the development of obesity. The increased lipoprotein lipase activity of the large fat cells suggested that obesity resulted from a direct storage of dietary fatty acids esterified by glycerol formed from circulating glucose.


[Comparison of various semi-quantitative tests for determination of urinary glucose in diabetics (author's transl)]. Estimations of urinary glucose in 178 diabetics using 4 tests, Ketodiastix, Tes-Tape, Clinitest 5/10 and Clinitest 2/10 were compared with polarimetric determinitation. Clinitest is more accurate and specific, and as reliable as enzymatic methods. The widened scale of Clinitest 2/10 permits the detection and satisfactory estimation of glycosuria ranging from 0,25% to 5%; it is specially suitable for monitoring the labile insulin dependent diabetes of children or adolescents. Enzymatic methods are suitable for the qualitative detection of glycosuria, for the control of stable, maturity-onset diabetes or to meet the need for rapidly available diagnostic information.


Circadian, circannual and other rhythms in spontaneous nutrient and caloric intake of healthy four-year olds. Intake of total calories, proteins, lipids and carbohydrates was measured individually in four separate groups each of 26 to 29 children studied during different seasons of the year and an additional group of eight children investigated during all seasons. The subjects came from broken homes, had been abandoned or were orphans; 60% were males, 4 +/- 1.5 years of age (mean and standard error) and were of similar body weight and height. They were residents in one of two separate institutions in Nancy, France, living on similar, rigorously enforced schedules unchanged throughout the year. Socio-ecologic synchronization involved "lights-on" at 0700 "lights-out" at 1830, meals at 0800, 100, 1400 and 1800 with food of similar origin and kind, and similar timing of mental and physical activities. Each child was asked at fixed meal times to select spontaneously the kind and amount of food desired, uninfluenced as far as possible by choices of others, and to consume the food in any order. During seven days of adherence to this request, the amounts of protein, lipid, carbohydrate and total calories consumed at each meal were carefully determined for each individual. Time series thus obtained were analyzed according to the mean cosinor method for detecting and characterizing bioperiodic phenomena. A statistically significant circadian rhythm was detected in each of the 4 variables for each day of the best fitting sine function used to approximate the rhythm occurred around noon in almost all the studied circumstances. In other words the spontaneously larger meals were usually taken at 0800 (breakfast) and 1800 (supper). The trough of both lipid and protein spontaneous intake was clustered around 1800 only on Sunday. Cosinor analysis of individual seven-day time series (of each variable of each season) indicated a statistically significant circaseptan (approximately equal to 7-days) rhythm, with a peak occuring on Saturday, Sunday or Monday, but never on Wednesday. Changes in the weekly mean adjusted levels obtained by this method (as well as changes in mean values resulting from other statistical methods) demonstrate: 1) a circannual variation in spontaneous intake of lipids, carbohydrates and calories (protein changes are not statistically significant): 2) a peak of lipid intake, occuring in spring time, and a peak of carbohydrate and calorie intake, occuring in summer time. The probability of both exogenous and endogenous components of these rhythms is suggested.


Surgical considerations of early gastric cancer. Metastasis to lymph nodes was seen more higher rate in protruding lesion, especially in Type IIa and IIa + IIc than in concaving lesion. In view of the metastasis to the secondary regional lymph nodes or the third regional lymph nodes, care should be taken in the eradication of lymph node in early gastric cancer of Type IIc. Five-year survival rate was 88.9% of the resected cases of early gastric cancer.


Studies of the clinical application of serum leucine aminopeptidase (LAP) activity determined with leucinamide as substrate. A new method was presented for the determination of leucine aminopeptidase (LAP). The principle of the method consisted in the measurement of ammonia liberated by the action of LAP with direct colorimetry. Leucine naphthylamide has been widely used as substrate for the determination of LAP (Nap-method), but leucineamide was used (NH3-method) in this study, and the enzyme activities determined by the both methods were compared in various diseases. Serum LAP activity in acute hepatitis was much higher in NH3-method than in Nap-method, but the activity in obstructive jaundice was much higher in the latter than in the former. It was demonstrated that the serum of normal rats and CCl4 treated rats contained isozymes (LAP-I and II) which showed the different substrate specificities toward leucinamide and leucine naphthylamide. LAP-I activity was much higher, but LAP-II activity was much lower in the NH3-method than in the Nap-method. LAP-I activity was remarkably elevated by the NH3-method, but not by the Nap-method in the serum of CCl4 treated rats. The results suggested that leucinamide was preferable substrate for the measurements of activities of serum LAP in the clinical examinations.


Studies on the etiology of milk intolerance in Japanese adults. 1. The incidence of milk intolerance is approximately 19% in Japanese adults when 200 ml of milk is given. However, a much greater incidence was assumed when considered under the criteria of Western standard. 2. The lactase activity was significantly greater in milk drinkers than non-drinkers. And, internationally, the active is higher in those nationalities whose milk consumption is greater. 3. Lactase is an adaptive enzyme and rather easily induced by lactose load feeding in animals. From the data of our own and of the literature, it was further confirmed that environmental factors play a more important role than genetic factors in the etio-pathogenesis of milk intolerance.


Parietal cell antibodies. Part II. Cytotoxic activities of parietal cell antibodies. Experiment 1. The observations on cytotoxic activities of parietal cell antibodies to normal human parietal cells in vitro. Experiment 2. The histochemical changes of rat stomach after administrations of rabbit anti-rat gastric mucosa sera. Cytotoxic activities of P.C.A. to normal parietal cells were demonstrated in vitro. The changes were very similar to those of thyroid cells provoked by Hashimoto serum. The cytotoxic component was found to be immunoglobulin G. Complement was not added. Rabbit anti-rat gastric mucosa sera had no effects on the gastric secretion in rats, but histochemical changes were demonstrated. The changes were transient and returned to the normal state 60 minutes after injection of Anti-RGM sera. Activities of succinic dehydrogenase were most affected, particularly 3 minutes after injection. Decrease of activities gradually recovered to the normal condition. The comparison of C.A.G. with C.Th. was made. By the comparison between C.A.G. and C.Th., and by the results of experiments, the author considers that C.A.G. has the immunologically identical aspects with C.Th.. The author also considers that some immunological mechanisma are playing a role in the pathogenesis of C.A.G.


Parietal cell antibodies. Part I. Clinical and pathological studies of parietal cell antibodies. The incidence of parietal cell antibodies (P.C.A.) in patients with various diseases was investigated by complement fixation test (C.F.T.). The relationship between the incidence of P.C.A. and clinical and pathological findings was also investigated. The incidence of P.C.A. with simple atrophic gastritis was 34.8% in total cases, 29.0% in male and 48.1% in female, respectively. The difference between the sexes was statistically significant (p less than 0.05). The incidence of P.C.A. in superficial gastritis was 37.5%, showing the same incidence as atrophic gastritis. The difference between the two groups was not statistically significant (p less than 0.05). The incidence in patients with hypo- and hyperactivity was 43.0% and 11.8%, respectively. The difference was statistically significant, but that between hypo- and normoacidity was not significant (p less than 0.05). The author postulated the conclusion that the superficial gastritis could be included in the category of atrophic gastritis. The dissociation of correlation of titer of C.F.T. with acidity and histological findings was found. The correlation was more significantly observed with acidity than with histological findings. The relatively high incidences of P.C.A. were noted in patients with peptic ulcer, gastric carcinoma and chronic thyroiditis. The incidence of P.C.A. in other diseases showed the nearly equal incidence to that of other investigators. Three cases of postgastrectomy patients were noted, in which the P.C.A. disappeared four to six months after total or subtotal gastrectomy.


A huge villous tumor of rectum: a case report. Villous tumor of the large intestine was first identified and named by Holmes in 1858. It is said to account for 1.4 to 2.5 per cent of all tumors of the large intestine, but only sporadic cases have been reported in Japan. Although considerably large villous tumors are known to exist, reports refering to them, home and abroad, show that there are no more than 50 known cases which had diameters exceeding 10 cm1). This paper presents one of our recent experience of the tumor whose diameter reached 20 cm.


The constitutional indocyanine green excretory defect--report of four cases. Four cases revealed high retention of ICG test and normal retention of BSP test were reported. The results of liver function test of these cases showed within normal limit except ICG retention. ICG disappearance rate ranged from 0.017 to 0.025, whereas BSP disappearance rate ranged from 0.069 to 0.126. The transfer rate of ICG from plasma to liver markedly decreased by two compartmental analysis of the decay curve and slightly reduced transfer rate of BSP from plasma to liver was also observed. The step on both ICG and BSP disappearance curve was observed during 20 to 25 minutes after the injection in all cases and in repeated observations. The step formation is one of the characteristic changes in these cases. The ICG binding capacity of serum protein decreased in the first peak and increased in the third peak eluted by gel filtration of Sephadex G-200. Light microscopic findings of the liver showed normal histology. The electronmicroscopic findings showed the increase of lipofuscin-like lysosome, modification and paracrystalline like array of mitochondria and increase of reticulum fiber in Disse's space. Father of a case showed ICG retention without BSP retention. From these results it is suggested that these cases are a new type of dye excretory disorder of liver with heredity or constitution.


Leiomyosarcoma of the transverse colon.

Leiomyosarcoma of the transverse colon. A case report of leiomyosarcoma of the transverse colon was presented in view of its rarity of the occurrence. An extra-colonic, mobile abdominal mass showing a rapid growth with mild tenderness was the principal preoperative findings in the patient. The occurrence of malignant tumors in smooth muscles of the colon, not including the rectum, is extremely rare. In review of the references, about thirty cases have been previously reported.


Evaluation of linear gastric ulcer as a precancerous lesion. During the recent 13 years from 1961 to 1973, 21 cases of ulcer-carcinoma satisfying Hauser's pathologic criteria have been found endoscopically, 5 cases (2.6%) of which were mucosal carcinoma accompanying linear ulcer over 30 min in length. In addition, one submucosal carcinoma and 2 cases of sub-early gastric carcinoma, partially invaded into the proper muscle layer, were used for this study. Using these 8 cases and 11 operated ones of benign linear ulcer, we have a comprehensive study of histologic and clinical findings of both groups. As the results, malignant linear ulcer was similar in condition to the benign, either in mother ground or in histologic and clinical findings. Moreover, coexistent carcinoma with all kinds of gastric ulcer and with linear ulcer among them was found in 1.5% and 3.8%, respectively. In a series of controlled group, early gastric carcinoma was found in 2.1% out of 284 cases of no ulcer scar from its follow-up study. Its x2 test revealed no significant difference among these values. However, we might conclude that endoscopical follow-up study of chronic gastric ulcer, especially long linear ulcer, is indispensable for understanding the evaluation of malignant change of ch  ronic gastric ulcer.


Studies of ultramicrostructure in relation to disaccharidase activity in the jejunal mucosa. Ultramicrostructural changes of the mucosa of the small intestine were studied in relation to the alterations of the lactase activity, measuring the height of microvilli by electron microscopy and the enzyme activity by the method of Dahlqvist. Studies with clinical cases revealed that the height of microvilli correlated with the lactase activity significantly (p less than 0.01), and that patients with relatively higher microvilli had a correspondingly higher activity of lactase. In animal experiments an increase of lactase activity by lactose load feeding and low calorie feeding resulted in a raise in the height of microvilli. It was concluded that lactase deficiency in adults and in various gastrointestinal diseases, where no histological abnormality was observed by light microscopy is perhaps due to shortening of the microvilli of the mucosa. It was speculated that the microvillous change and the sequential hypolactasia may be the initial ultramicrostructural and enzymatic alteration in the diffuse disease of the small intestine.


Secretin-like activity in duodenal mucosa and peptic ulcer. The secretin-like activity contained in bioptic specimens of duodenal mucosa was measured by means of bioassay in healthy controls and patients of peptic ulcer. It was found that the activity tended to be increased in duodenal ulcer in comparison with gastric ulcer which did not differ from healthy controls. Possibilities of impaired release and/or increased production of secretin-like substance in duodenal ulcer were discussed.


Immune reaction in the gastric mucosa: passive mucosal anaphylaxis and experimental ulcer. Immune reaction in the gastric mucosa using purified antigen-antibody system was investigated. Applying the technique of PCA on the gastric mucosa of dog, interesting phenomena named "Passive Mucosal Anaphylaxis (PMA) was obtained. The reaction could be produced even by the orally administered antigen. By the direct injection of soluble immune complex into the gastric mucosa, production of experimental ulcer was observed, in which parietal cells were relatively resistent to the immune tissue damage.


Secretory function of the stomach of Japanese with endoscopically normal gastric mucosa. Using gastrin-like AOC-tetrapeptide the secretory function of the stomach of Japanese with endoscopically normal gastric mucosa was examined in a multicenter clinical study. Mean one hour secretion volume, mean maximal acidity, and mean maximal acid output were found to be 129.3 +/- 60.0 ml/hr, 103.7 +/- 32.4 mEq/l, and 9.2 +/- 6.9 mEq/hr respectively. Results were analysed according to sex or age by analysis of variance and compared further with the corresponding data reported in the literature.


Studies on biliary bile acid metabolism in hepato-biliary diseases. Biliary bile acid have been analyzed in patients with various hepato-biliary diseases by thin-layer chromatography, and divided into 4 types of glycine- and taurine-conjugates. The composition of biliary bile acid was different according to the hepatic impairement, and the ratio of glycine-conjugate to taurine-conjugate was decreased in chronic liver diseases. The G/T ratio was 1.49 +/- 0.36 in the control group, but was 0.96 +/- 0.18 in severe liver cirrhosis, and 1.38 +/- 0.44 in chronic active hepatitis. In acute hepatitis, the G/T ratio was low on the initial stage of the diseases, and returned to a normal range upon recovery. There was also a dicrease in the ratio of dihydroxycholic to cholic acid of biliary bile acid in patients with chronic liver diseases. In conclusion, the measurement of bile acid in bile has a diagnostic value for chronic hepatic impairement.


HBc and HBs antigen in hepatocytes.

HBc and HBs antigen in hepatocytes. The relationship between the electron microscopical structures and the immunofluorescent appearance of HB antigen found in the hepatocytes of patients with HB antigenemia was carefully studied, with the purpose to clarify the nature of those structures. The nuclei of hepatocytes, containing numerous virus-like particles, showed positive immunoflourescence by antiserum against the core of Dane particles. The areas in which filamentous structures were observed in the cisternae of endoplasmic reticulums and hyaloplasma, corresponded to orcein or aldehyde-fuchsin positive substances in the light microscope, whereas direct relationship between filamentous structures and HBs antigen was still obscure. Accordingly, it may be concluded that virus-like particles in the nucleus correpond to core and filamentous structures in the cytoplasma correlate with coat protein of hepatitis B virus.


HBs-Ag, HBc-Ag and virus-like particles in liver tissue. Hepatitis B surface antigen (HBs-Ag) and hepatitis B core antigen (HBc-Ag) in hepatic tissue of 3 cases with various liver diseases were investigated by immunofluorescent method. Virus-like particles were demonstrated by electron microscopy in the nuclei of these 3 cases. The localization of HBs-Ag was restricted in cytoplasma or on the surface of hepatocyte, while HBc-Ag was almost in the hepatocytic nuclei. However, there was unexplainable discrepancy between the distribution of HBs-Ag and that of HBc-Ag, as more the former in number and less that latter, of hepatocytes. The size of virus-like particles in nuclei was 22-27 nm in diameter. Most of them were hollow, but some of them were wholly electron dense. Their distribution was various from case to case. Discussion was made on the correlation between the presence of Hepatitis B virus and HBs-Ag or HBc-Ag.


Studies on the inhibition of experimental liver fibrosis. 2. The mechanism of the inhibition of liver fibrosis of rats due to carbon tetrachloride by elastase. In the previous experiments, it was demonstrated that high purity elastase extracted from porcine pancreas remarkably inhibits liver fibrosis of rats having chronic liver injury caused by carbon tetrachloride. This time, with the purpose to clarify the mechanism of inhibition of liver fibrosis by elastase, comparative study was made on the activity of lysosomal enzymes by measuring beta-glucuronidase, cathepsin and collagenolytic activity, with the rats administered with elastase and with those untreated, during the period of development of liver fibrosis and the recovery from it. In addition to it, in vitro experiments were made by having elastase act on the substrate comprising mixed collagen of acid soluble and neutral soluble collagens extracted from the skin of guinea pigs and by observing collagen components by disc electrophoresis. With any lysosomal enzymes, no marked difference was noticed between elastase group and non-administered group and thus the possibility of inhibition of liver fibrosis through activation of lysosomal enzyme by elastase was denied. The results of disc electrophoretic observation of the performance of elastase on collagen revealed that beta-component of collagen is disappeared but alpha-component remained. From the above, inhibition of liver fibrosis by elastase may be due to direct affection of elastase to telopeptide portion of collagen.


Macroamylasemia: clinical and laboratory features in 7 patients. The clinical features of patients with macroamylasemia are diverse. A certain correlation between macroamylasemia and the disease of the pancreas or hepato-biliary system may exist, because among 7 patients in this series 4 patients were diagnosed as acute pancreatitis or relapsing pancreatitis and another patient was performed choledochotomy and manipulation of papilla of Vater may had a effect on pancreas. Among other 2 patients, one was completely symptomless and had no abnormal findings and in another the action of anticancer drugs is suspected. The course of macroamylasemia is usually chronic but in this series one patient had acute transient macroamylasemia and another one had intermittent macroamylasemia during exacerbations of pancreatitis. The serum amylase levels are mostly 2-4 times above normal with one exception (192 Somogyi units) and urinary amylase values are low with one exception (1922 Somogyi units) during exacerbation of pancreatitis. Characteristic zymogram of macroamylase on electrophoresis is also reported.


Histoenzymatic and ultrastructural findings in the human gastric mucosa during fasting. In this study the influence of fasting on the structures in the human gastric mucosa was followed using selective histoenzymological and electronmicroscopic method. The gastrobioptical material of 7 healthy volunteers was examined after 24 to 240 hour fasting. During fasting an increased acid phosphatase activity in the chief cells of the human fundal mucosa was observed. The activity of the nonspecific esterase (naphtyl esterase) in the chief cells decreased mainly after 240 hour fasting. In the electronmicroscopic examination of the chief cells during fasting a multiplication of lysosomes and narrowing of the granular endoplasmic reticulum was observed. In some chief cells during fasting an agglomeration of zymogen granules was seen while in others only a few granules were observed. In the parietal and other cells of the human gastric glands a steatosis, which attained excessive values, was seen after 72 and 240 hours of fasting. We believe that this steatosis occurred mainly on the strength fasting lipemia with the possible participation of other factors. The changes in the mitochondrial structure of the parietal and other cells of the human gastric mucosa were only slightly pronounced. "The decreased" activity of dehydrogenase in the steatotic parietal cells under a histochemical examination may represent only findings caused by the agglomeration of a large amount of lipid drops in the steatotic cells. After 72 and 240 hours of fasting the parietal cells contained collapsed, underdeveloped intracellular canaliculi and narrowed tubulovesicular profiles probably related to the decreased HCl production. Generally it can be said that the observed morphological changes are the consequences of the decreased function of human gastric mucosa cells during fasting and that these regressive changes are reversible and they are caused by an insufficiency of nutrition.


Albumin synthesis and effect of betamethasone on albumin synthesis in perfused liver of normal and CCL4-intoxicated rats. Synthesis of plasma albumin was studied in perfused liver of normal and CCl4-intoxicated rats, using 14C-bicarbonate method. 1. In normal liver, albumin synthesis averaged 5.6 mg/hr/100 g body weight. 2. In CCl4-intoxicated liver, albumin synthesis decreased to 4.6 mg at acute stage, but restored to 5.1 mg at non-septal fibrotic stage. At septal fibrotic, cirrhotic and cirrhotic stage with ascites, the synthesis rate averaged 4.5 mg, 4.1 mg and 3.2 mg, respectively. From these results, it is inferred that albumin synthesis rate decreases in accordance with the progress of the liver injury. 3. Effect of betamethasone on plasma albumin synthesis in perfused rat liver was investigated. Albumin synthesis rate in normal liver averaged 5.4 mg, and after addition of betamethasone, the rate averaged 4.3 mg, 3.3 mg and 2.8 mg, respectively. The rate after addition of betamethasone increased to 7.3 mg, 5.5 mg and 4.5 mg, respectively. From these results obtained, it is inferred that betamethasone increases plasma albumin synthesis in both normal and CCl4-intoxicated liver. 4. In normal liver, actinomycin-D did not inhibit basal albumin synthesis, but inhibited the increase of albumin synthesis by betamethasone, when actinomycin-D was added together with betamethasone. From these facts, it is concluded that betamethasone is able to induce albumin synthesis.


Comparison of detectability of elevated amylase of serum and urine in pancreatic diseases by two amylase assay methods using starch substrates of different digestive rates to pancreatic amylase. Detectability of abnormally high serum and urine amylases was investigated on patients with pancreatic diseases using amylase assays with substrates of different digestive rates to pancreatic amylase. Ratios of amylase activities determined by a chromogenic assay using a Remazolbrilliant Blue R starch (RBB assay) to those by Caraway's assay using a Lintner soluble starch (R/C ratio) were calculated on duodenal and salivary amylases obtained from 16 subjects undergoing a pancreozymin-secretin test. The R/C ratio of the duodenal amylase (M +/- SD = 0.56 +/- 0.12) was significantly higher (p less than 0.01 by F test) than that of the salivary amylase (M +/- SD = 0.36 +/- 0.10). Detectability of above-normal values of serum and urine amylases were compared with two assays in 77 pancreatic patients. The value for serum and urine amylases determined by the RBB and Caraway's assays exceeded the upper limit of normal in 37 and 58% by the RBB assay and 24 and 26% by Caraway's assay, respectively. Degrees of abnormality (ratio of the observed to the upper normal value) in serum and urine amylases were also significantly higher (p less than 0.05 for serum and p less than 0.01 upper for urine) by the RBB assay than by Caraway's assay. The RBB assay was more sensitive than Caraway's assay in detecting elevation of pancreatic amylase in serum and urine.


Gastric ulcer and carcinoma in fundic gland area. The gastric ulcer and carcinoma in the fundic gland area were investigated with the surgically resected cases. 1. The frequency of the ulcer in the fundic gland area was 8.2% of 2194 cases of gastric ulcer and that of carcinoma in this area was 8.4% of 780 cases of gastric carcinoma. These two diseases showed high frequency in the age group of forty to fifty years withpreponderance in female. 2. The ulcers in the fundic gland area usually showed high acidity and high frequency of massive bleeding like as melena and hematemesis comparing with other lesions or the ulcers in other sites. 3. The ratio of the low-differentiated carcinomas to the well-differentiated ones was about 3.7 to 1 in the fundic gland area and 1 to 1.3 in the pyrolic gland area. 4. The frequency of the early gastric carcinomas was 27% and 41% in the fundic and pyrolic gland areas, respectively. 5. In the fundic gland area, as observed in the pyrolic gland area, the low-differentiated carcinomas usually occurred on the non-metaplastic mucosa and the majority of well-differentiated ones were frequently found in association with the intestinal metaplasia. 6. Although the solitary carcinoma in the anterior wall or greater curvature was found not infrequently, the solitary ulcer was not found in these sites in this series.


Detection of hypersensitivity to drugs by lymphocyte cultures in drug-induced allergic hepatitis. Fifty-three out of 70 patients with drug-induced liver injury showed an immunological response to the drug using either the lymphocyte transformation test or the macrophage migration inhibitory test (MI test) or both. Both the separated lymphocyte culture and the microvolume whole blood culture technique are available as assay methods. The latter method is simpler and the results of both methods are comparable. The administration of a synthetic copolymer of polyadenylic and polyuridylic acid (poly A:U) to the culture medium enhances the lymphocyte response to antigen and is therefore very useful to detect weak responses.


The distribution of serotonin-containing cells in the human alimentary tract. The distribution of serotonin-containing cells (SC cells) in the human alimentary tract was studied by means of the fluorescent histochemical method of Falck et al. on surgically resected specimens. No SC cells could be observed in the nonmucosal parts of the alimentary tract and in the squamous cell epithelium of the esophagus. The richest SC cells were observed in the upper portion of the small intestine (namely the duodenum and the jejunum). The rectum was relatively rich in the distribution of SC cells. They moderately distributed in the terminal ileum and the pyloric and cardiac gland region of the stomach. The ascending, transverse, descending and sigmoid colon and the fundic gland region of the stomach showed poor distribution of SC cells. The basal-layer of the mucosa contained generally richer SC cells than the superficial-layer of the mucosa throughout the alimentary tract except for the esophagus. In the pyloric gland region of the stomach, the rectum and the upper portion of the small intestine, often a few SC cells were observed in the basal part of several glands in the transverse section. In contrast, SC cells could be rarely identified in other parts of the alimentary tract even in the basal part of the mucosa. And it was characteristic that SC cells distributed fairly even in the mucosa of the sigmoid colon.


[Effect of a magnetic field on chromosome set and cell division]. An effect of stable magnetic field on karyotype and cell division of human lymphocytes from peripheral blood was studied in tissue culture. Comparative investigations were carried out with lymphocytes, which were treated with magnetic field of different tension (0,179; 0,391 and 0,600 Ts) and continuance (30 sec, 30 and 60 min). Lymphocytes, treated with stable magnetic field, were suspended in donor plasma and immediately cultivated after the treatment. The stable magnetic field was found to have a distinct mutagenic effect on cultivated lymphocytes of human peripheral blood. The increase in structural impairements of chromosomes correlated with tension of magnetic field and continuance of its effect. In structural impairements of chromosomes the chromatid gaps and breaks were more often observed but chromosome ruptures and pericentric clearances occurred more rarely. The effect of stable magnetic field on lymphocytes proliferation was studied. Under weak and transient using of magnetic field the proliferation was stimulated, but in rigid conditions - mitosis and blastic transformation were decreased. Continuous effect of magnetic field with weak tension did not inhibite the blastic transformation but influenced on the survival rate of cells in tissue culture, enhancing their lethality.


[Comparative study of the effectiveness of selection in diploid and autotetraploid populations]. The mitotic activity and ploidy of cells of three strains of cellus tissue by the addition of the culture medium of 0,01; 0,1 and 1 mg/l of phytohemagglutinin was studied. These strains derived from the leaves of haploid, diploid, and tetraploid plants of Lycopersicon, esculentum. The number of dividing cells under the influence of phytohemagglutinin increased by 1;5 and 4% for haploid, diploid and tetraploid strains respectively. The shift of the peak of the mitotic activity at early stages of subculture under the effect of phytohemagglutinin was noticed. Phytohemagglutinin did not change the frequencies of cells of different ploidy in all the strains analysed. A weak mutagenic activity of phytohemagglutinin in the concentrations used was observed. Cells with single bridges were more frequently observed among the aberrant cells.


[Possible association of epilepsy with dizygotic twinning]. The frequency of twinning among 9457 children and abolescents suffering epilepsy and epileptiform syndrom was established to be 1,94%, exceeding that in general population and being particularly high in the group of patients with epilepsy (2,65%). The frequency of stillbirths and deaths in one of the co-twins amounted 18,57%. The proportion of same-sexed and opposite-sexed pairs in the sample examined differs from that in general population, dizygous pair exceeding their number expected.


[Fecundity and embryonal mortality of four inbred strains of mice, BALB/c, B10.CW, A/Sn, CC57W and their hybrids]. The object of this investigation was the potential fecundity of four inbred strains of mice, viz. BALB/c, B10.SW, CC57W, A/Sn and of their different hybrid combinations. The inbred strains studied had different normal ovulation numbers varying from 9,2 to 11,9 and different death-rate of embryos before (10,99-39,49%) and after (9,05-22,47%) the implantation. The numbers of live embryos per female in the strains A/Sn, B10.CW and CC57W were practically equal to one another, but significantly larger than in the strain BALB/c. Interlinear crosses resulted in a considerable decrease of the total embryonic death-rate, while the normal ovulation number did not undergo any changes. The number of live embryos in simple hybrids did not differ significantly from that in the maternal inbred strains. Therefore the heterozygosity of embryos did not affect significantly the potential fecundity of females. The number of surviving embryos per female increased in the cross between the simple hybrids (BALB/cXB10.CW) X (CC57WXA/Sn) to 8,9 +/- 0,37. This heterosis was the result of the total death-rate of embryos down to 14,89%. As it is shown by the comparison of the potential fecundity of pregnant females carrying homo- and heterozygous embryos to that of pregnant hybrid females, the rate of survival of embryos depends more on the genotype of the mother, than on that of the embryos.


[Biochemical-genetic mechanisms of learning. II. Selection for high and low rates of acquiring a motor conditioned reflex]. Using the model of feeding motor conditioned reflex, polymorphism for the rate of the formation of this response was found in a population of laboratory animals. Selection for high and low rate of the formation of this reflex resulted in significant differences in this character between two strains already in the second generation. These differences are maintained in subsequent generations. The existing henerogeneity for the rate of the formation of conditioned response in the population is shown to be genetically determined.


[Mutagenic effect of irradiating different species on the sex cells of male mice. VIII. Frequency of development of reciprocal translocations in the spermatogonia of mice subjected to chronic gamma-irradiation]. The frequency of reciprocal translocations in mice spermatogonia after the exposure to chronic gamma-irradiation at doses of 100, 200, 300, 600, 920 r, at the dose rate of 4,2 r/day was investigated. It was shown that the mutation frequency increased insignificantly with the increase of the radiation dose (y = 0,8+0,0011 x). The comparison of the data obtained with earlier results revealed no changes in the yield of translocations at the reduction of the dose rate from 10 r/day to 4,2 r/day. The investigation of the genetic radiosensitivity of mice spermatogonia after a chronic gamma-irradiation showed a tendency to increase in their radioresistance.


The treatment of pathological fractures with special reference to the use of major prosthetic replacement of bone. Over 26 years 44 major prosthetic replacements have been carried out for tumours and tumorous like conditions of the long bones (including 15 with pathological fractures). There have been 10 deaths (none post-operative). 5 secondary amputations have been carried out for recurrence, breakage or infection.


Regional cerebral blood flow variations in mental alertness. The state of mental alertness preceding a motor task is accompanied by an increase in cerebral blood flow. During the first trials, these changes seem to be chiefly related to ascending reticular impulses. Habituation lateralizes and focalizes changes which are probably due to metabolic modifications in selective expectancy. The factor E of Eysenck seems to have some correlation with the individual variations observed.


[Relation of blood pressure and prevalence of peptic ulcer in an epidemiological study]. On the basis of data from the Epidemiologic Study of Cardiovascular and other chronic diseases which has been carried out among the population of 6460 males, 35-62 years of age in the territory of the Tuzla commune in Yugoslavia, this relationship between peptic ulcer and blood pressure level had been analyzed.


Osteopenia and dysregulation of divalent cations in lithium-treated patients. The bone mineral content (BMC) in both forearms (highly correlated to total body calcium) was measured by photon absorptiometry in a representative sample of manic depressive patients receiving lithium treatment. The mean BMC values were 93% of normal, and the mean increases in serum levels of calcium and magnesium were 2mg/l. The incidences of osteopenia, hypercalcaemia and hypermagnesaemia were 16, 12, and 30%, respectively. These results indicate that lithium-treated manic depressive patients have a disturbance in the mineral metabolism, be it due to the disease or the treatment given.


The dopamine hypothesis of schizophrenia. A critical analysis. The evidence linking dopamine and schizophrenia is reviewed. Surveyed are studies on dopamine metabolites in schizophrenia, the effects of dopamine agonists, antagonists and depletors on schizophrenia  and the action of present treatments of schizophrenia on dopamine. As well, the interrelationship of dopaminergic, cholinergic and gabanergic pathways is examined. It is concluded that the relationship between dopaminergic mechanisms and schizophrenia is nonspecific. The dopamine hypothesis is shown to reflect an attitude towards schizophrenia that emphasizes acute, florid symptoms. It is suggested that researche directed towards studying dopaminergic mechanisms in specific psychopathological symtoms, not syndromes, might prove fruitful.


[Possibilities in the use of samples in dentistry]. The paper describes a feasibility of a useful application of different types of samples in an investigation of epidemiology of caries, gingivitis, periodontal disease and orthodonic disturbances. Also, an illustration of sampling procedure suitable for investigation of epidemiology of diseases of mouth and teeth is presented.


Enzymatic organization of the subcommissural organ. In the subcommissural organ (SCO) of the guinea pig, rat, golden hamster, and mouse the activity and distribution of enzymes related to the energy-supplying metabolism and of some marker enzymes of different cell organelles have been investigated by means of mostly modified histochemical methods. The results were compared with findings in the ciliated ependyma of the ventricular wall and with those in the ependyma of the choroid plexus of the third ventricle. In the ependymal part of the SCO only a moderate activity of hexokinase is observed in its specialized columnar cells whereas a high activity is present both in the ciliated ependyma and the choroid plexus. - The staining pattern of glucose-6-phosphatase is similar to that of hexokinase but this enzyme is found is the SCO only. - Likewise hexokinase, glycogen granules and enzymes related to glycogen metabolism (phosphoglucomutase, uridine-diphosphoglucose pyrophosphorylase, glycogen synthetase and phosphorylase) are regularly found most numerous and active in the nuclear and supra-nuclear area of the ependymal part. These enzymes are less active in both the other ependymal regions. - Uridine-diphosphoglucose dehydrogenase could not be demonstrated in the SCO. The NADP-linked enzymes of the pentose phosphate shunt, glucose-6-phosphate and 6-phosphogluconate dehydrogenase, show a moderate activity which decreases also from the nuclear towards the apical area of the ependymal cells of the SCO. Enzymes of the glycolytic pathway, such as glucosephosphate isomerase, fructose-6-phosphate kinase, fructose-I,6-diphosphate aldolase, glyceraldehyde-3-phosphate and lactate dehydrogenase, are highly active in the SCO and are located mainly in the supranuclear area, too. Fructose-1,6-diphosphatase could not be demonstrated thus indicating that in the SCO the pathway is most probably only glycolytic but not gluconeogenetic. Compared to the ependyma of the ventricular wall and of the choroid plexus, in the SCO the M type subunits of lactate dehydrogenase predominate. Glycolytic enzymes are also very active in the choroid plexus but less in the ciliated ependyma. Compared to the ciliated ependyma and especially to the ependyma of the choroid plexus, the activities of enzymes which are only present in mitochondria (NAD-linked isocitrate dehydrogenase, succinate dehydrogenase, NAD-linked malate dehydrogenase after preextraction, cytochrome oxidase, 3-hydroxybutyrate and glycerolphosphate and glutamate dehydrogenase) are relatively low. Mitochondria are accumulated near the superior pole of the nuclei as well as in the most apical part of the ependymal cells. - The staining pattern of NADP-linked isocitrate and malate dehydrogenase as well as of NADH dehydrogenase suggests that these enzymes are localized both in and out of mitochondria. The extramitochondrial activity of the first two enzymes might be localized in the cytosol. The extramitochondrial activity of NADH dehydrogenase might be localized in the endoplasmic reticulum...


[Immunological examination of patients with undetermined leprosy]. The immunological competence of eleven patients with undetermined leprosy was compared with that of ten normal volunteers of the same age and sex distribution; these controls have not had previous contact with leprosy. The following parameters were studied in peripheral blood cells: 1) percentage of lymphocyte bearing surface immunoglobulins, as revealed by immunofluorescence; 2) percentage of lymphocyte bearing complement receptors, as studied by antibody and complement coated erithrocyte rosetting; 3) percentage of T cells, as revealed by spontaneous sheep erithrocyte rosettes; 4) blastogenic and mytogenic response of cultured lymphocytes to PHA and 5) cell migration inhibition test using lepromine (80 x 10(6) bacilli/ml) as antigen. Skin reactions to lepromine were also assayed. In the six lepromine-positive patients with undetermined leprosy, no major immunological alterations could be detected. On the contrary, the five lepromine-negative patients showed important alterations which could well be considered as precursors of lepromatous leprosy.


[Inactivation of rabies virus by chemical agents]. To study the virucidal activity of several chemical agents available locally in Argentina for rabies virus, was considered to be very useful for physicians treating persons bitten by rabid dogs and for those responsible for the sterilization of rabies contaminated areas. CVS fixed rabies virus suspensions were treated for one minute at room temperature with soaps of different quality, anionic (most of them derivates of dodecyl-bencene-sulfonic acid) and cationic (dodecyl, tetradecyl, hexadecyl-trimethyl-ammonium bromide) detergents, lemon juice, vinegar, hydrochloric acid, sodium carbonate, etc. Most of these agents inactivated 4 logarithms of virus (99.99%) which is approximately the amount of virus present in the saliva of experimentally infected dogs. It is noteworthy that a popular treatment for animal bites in several latin America countries is lemon juice, while the scientific community may still recommend the use of nitric acid which has a definitive necrotic and scarring effect on the treated wound. The need to eliminate organic matter prior to sterilization of contaminated areas because of interference with the virucidal activity of the agents was also confirmed.


The clinical diagnosis of malignant melanoma. The diagnosis of malignant melanoma thus rests upon an appreciation of sometimes subtle but definite signs detectable by careful observation of color, border, and surface of the lesions. Differential diagnosis lies among several cutaneous lesions, neoplastic and nonneoplastic. At times the lesions that are most difficult to distinguish from malignant melanomas are certain pigmented basal cell carcinomas, thrombosed hemangiomas, and certain types of moles. An attempt has been made in this review to describe and illustrate those features of pigmented lesions that are most helpful in diagnosis.


The surgical therapy of malignant melanomas. Survival from malignant melanoma has been serially followed over a long period of time. A summation of this information is seen in Table 5. The steadily improving 5- and 10-yr disease-free intervals in stage I disease probably represents a combination of increased awareness of early lesions and the application of aggressive, initial surgical treatment. The ominous and essentially unchanged prognosis in stage II disease reinforces this goal. Suspicion and gross recognition of early melanoma is essential. Adequate biopsy with the appropriate classification provides the surgeon with insight into the correct therapy. This usually entails wide, three-dimensional excision and wound closure by free skin-grafting. Regional lymphadenectomy is performed whenever anatomical and microscopic conditions dictate the need. The roles of amputation, regional perfusion, and adjuvant therapy require clarification. Studies are being pursued to provide firm data concerning the value of these methods.


The psychologic support of the cancer patient: a medical oncologist's viewpoint. The cancer patient should not be treated differently from other patients. He has the right to good medical care and, especially, sympathetic and constructive psychologic support during all phases of diagnosis, surgery, radiotherapy, and chemotherapy, independent of disease extent or therapeutic response. After the physician has reevaluated his own concepts about cancer and death, he can effectively begin to treat and support his cancer patients. By understanding the individual psychologic problems of cancer patients and their families, a physician can develop an effective psychologic, as well as antineoplastic, treatment program. The family physician has the central role of introducing the cancer patient to his illness and to his oncologic physicians. The surgeon should discuss preoperatively the nature of a patient's problem and the proposed surgical treatment with its possible alterations of bodily function. Postoperatively, he and the family physician should develop a treatment program after appropriate consultation with oncologic subspecialists. If the radiotherapist is consulted and feels radiation therapy is indicated, he should outline his objectives and the possible side effects of therapy. Likewise, the medical oncologist should discuss the potential benefits and possible side effects of anticancer drugs if he feels they should be administered. No one way of supporting the cancer patient is superior. Each patient and his doctors have to develop individual relationships based on honesty, trust, and close communication. A continued commitment to the care of the patient with nurturing of hope and realistic goals is necessary, even when all antineoplastic treatment plans have failed. A satisfactory adjustment of the patient, his family, and the physician as he approaches death can be a natural and beneficial outgrowth of the doctor-patient relationship. Although much attention has been recently focused on the problems of the terminal patient, it is also important to realize that even cured cancer patients may need active psychologic support long after successful antineoplastic therapy has been terminated.


Psychosocial care in malignant diseases of childhood: organizational and structural implications. The desirable level of psychosocial care for the malignant diseases of childhood will not occur spontaneously due to the complexity of the treatment, the numerous skills and specialties involved, and the predictably high level of parental and child needs. A philosophy of total care will require careful and explicit formulation. Once the philosophy is established, the organization and its components must structure the care in such a manner as to assure delivery of total medical-psychosocial management. Specific methods can be incorporated which will support the care deliverers who, in turn, provide the care for the nuclear family unit. Such methods may include parent group meetings, care conference rounds, and emotional-psychologic management conferences as discussed.


Humor manifestations of neoplasms.

Humor manifestations of neoplasms. The exact prevalence of the humoral syndromes associated with neoplasm is not known but it seems clear that they exist more commonly than is realized. Hormonal syndromes are very often seen in patients with carcinoma of the lung. Awareness of the large number of ectopic hormonal syndromes in patients with tumors can lead to early diagnosis, treatment, and herald recurrence. They may be responsible for new signs and symptoms which can be life-shortening. Hormonal causes of clinical deterioration must be considered before concluding that symptoms are due to metastases in patients with neoplastic disease. Tumors are chemically active and the important concept which has had great impact on the diagnosis, treatment, and basic understanding of mechanisms, which are important to endocrinologists and oncologists has been stated by Liddle: "Certain tumors of nonendocrine tissue can produce hormones that are similar to normal hormones except that their production is not appropriately controlled by normal physiologic mechanisms." Survival and quality of life can be reduced in patients with the metabolic complications of these humors. The list of humoral substances released by tumors is growing as technologic advances lead to their detection. Other chemical substances produced by neoplastic tissue may have biologic activity which impacts on the patient's clinical condition and which we cannot recognize, at this time, because the techniques to detect them have not been developed. If there are signs or symptoms of overproduction of a hormone, search for a tumor; if a patient has a tumor, search for biologically active substances.


Role of platelets in hemostasis and thrombosis. Platelets are central to both normal hemostasis and abnormal thrombotic states along with the vessel wall, coagulation elements, and blood flow. The platelets play a pivotal role in the reaction that occurs after vessel injury, during which platelets first adhere to the vessel wall, undergo a release reaction and then aggregate, probably as a result of the materials released from platelets. These processes can be studied by a series of in vitro tests which form the basis of our knowledge of platelets in hemostasis. While the hemostatic plug is usually microscopic in size, this same plug (platelet thrombus) may contribute to the pathogenesis of several arterial diseases such as transient ischemic attacks, sudden blindness, sudden cardiac death and acute respiratory death syndrome. Careful microscopic examinations have shown that platelet aggregates may be found in the microcirculation which could affect vital structures such as the conduction system of the heart. Both anatomic and therapeutic evidence evidence suggests that platelets play a role in venous thrombosis. Recent evidence suggests increased levels of materials known to be released from platelets in patients with both arterial and venous thrombi along with increased platelet coagulant activities in patients with venous thrombosis.


Platelet kinetics--1975.

Platelet kinetics--1975. Studies of platelet kinetics have provided useful information regarding the role of platelets in the pathogenesis of thrombosis and related disorders. Additionally, platelet survival studies have been useful in evaluating the efficacy of drugs that may be useful as platelet inhibitors. Many questions remain, however, and answers are needed before much of the kinetic data can be confidently applied to clinical problems in thrombosis.


[Genesis of islands in the human placenta]. A fetal origin of the isalnds was supposed after light microscopical observations, investigated especially on young placentas. Electron microscopical examination confirm this supposition. The following facts prove, that the islands are products of the trophoblast: 1. The development of Langhans-cells to the differentiated cytotrophoblast, passing the state of the transitional cell type - I have called the differentiated cytotrophoblast "trophocyte". 2. The linkage of the trophocyte to the syncytiotrophoblast of the islands by desmosomes. 3. Definite morphological differences between the trophocytes and the decidual cells. 4. The absence of connective tissue and vessels in the islands.


Comparative histomorphology of the Mauthner cells in some freshwater teleosts. The histomorphological observations are made on the Mauthner cells in eight species of teleosts belonging to six different families. The cells are better developed in Channa punctatus, Heteropneustes fossilis, Labeo rohita, Danio, malabaricus and Puntius ticto. They are symmetrically situated in Nandus nandus and are found to be absent in Mastocembalus armatus. Their position, shape and size vary in different species. The axon cap is well developed in Channa punctatus, Heteropneustes fossilis and carps. The cell body sends lateral and ventral dendrites besides several small dendrites. The lateral dendrite emerges through the axon cap, turns dorsolateral and becomes myelinated to form Mauthner axon. The Mauthner axon extends in the spinal region upto the caudal peduncle and forms synapses with the spinal motoneurons of the front column. There are numerous synapses and end bulbs from the vestibular fibres and VIIIth nerve distributed on the perikaryan of the Mauthner cell body. It is suggested that the Mauthner cells are comparatively well developed in those species in which the tail fin is better utilized for swimming.


Structure of the neurohypophysis and the hypothalamo-hypophysial vascularization in the teleost Channa punctatus Bloch. In C. punctatus the median eminence includes the subterminal region of the hypothalamus and the anterior neurohypophysis. It is formed of ependymal, fibrous and reticular layers as in the tetrapods. Primary capillary plexus extends from the subterminal region to the extremity of the anterior neurohypophysis. Only few portal vessels from the hypothalamus enter in the pars distalis. All the components of pituitary including the pars intermedia are irrigated by the secondary plexus formed from the portal vessels emerging out of the anterior neurohypophysis. The neurosecretory axons and the ependymal cells are in close morphological contact with the primary plexus. Several axons have perivascular endings at the median eminence. Some axons were found to be only silver or aldehyde fuchsin positive whereas some others take up both. The silver positive axons were abundant in the pars distalis and the AF positive ones were more concentrated in the pars intermedia with greater accumulation of neurosecretory material.


[Stereological studies of aging changes in epiglottal cartilage cells]. The topic of these investigations were the aging changes of stereological parameters of the cells in human epiglottal cartilage. 42 sagittally cut epiglottides of all ages were available. By means of a drawing mirror in total 8937 cells had been drawn from the slide on paper and then measured. In detail we determined the volume fraction of cartilagous cells in the total cartilage volume, the complete cell surface area of the cartilage, the surface-to-volume ratio of the cartilagous cells, the numerical density of the cells and their volumes. The results are as follows: 1. The volume fraction of cartilagous cells in the total cartilage volume decreases from birth to senium continuously and, with the exception of a more rapid decline during the first decade, linear too. 2. The collective cell surface area per constant test volume of cartilage shows an exponential decline during life. 3. The surface-to-volume ratio of the cartilagous cells decreases very intensively during the first decades, from the 5th decade it little ranges again. 4. In the same way the numerical density of cells intensively decreases up to the 5th decade, but later on it ranges again. 5. The several volumes of cells show from the age of the newborn up to the 40th year a linear steep rise and afterwards, up to senium, an unequivocal decline. 6. The sizes of the cartilagous cells are not normally distributed, on the contrary, in young slides more than in older ones, one size class very predominates.


Effect of environmental factors on the activity of thyroid gland in an air breathing siluroid fish Heteropneustes fossilis Bloch. 1. Studies on cyclic activity of thyroid in relation to environmental factors were made in an air breathing siluroid fish, H. fossilis. 2. The activity of thyroid gland showed parallelism with water temperature and photoperiod but from the regression analysis it was evident that the effect of photoperiod on thyroid activity is more pronounced than the effect of water temperature. 3. The maximum thyroid activity coincides well with the breeding phase of this animal.


Absorption of horseradish peroxidase by the small intestinal epithelium in postnatal developing rats. After an intraluminal injection of horseradish peroxidase into the small intestine, the localization of peroxidase was studied in neonatal developing and adult rats by means of electron microscopy. Until around the 14th day of the neonatal period absorbed peroxidase granules in the duodenal and jejunal epithelium were abundant in the microvillous membrane, the apical tubulo-vacuolar system, and the Golgi apparatus, and on the lateral cell and basal membranes, and the luminal surfaces of the capillary cells. At the weaning period the tubulo-vacuolar system was absent in the duodenal and jejunal epithelial cells, and at that point absorbed peroxidase was observed in the same sites as in the adult rats: the microvillous membrane, the lateral cell and basal membranes, the Golgi apparatus, and the vesicles and vacuoles of the cytoplasm. During the suckling period, in the ileal epithelial cells exogenous peroxidase was found on the microvilli, in the tubulo-vacuolar system, in the supranuclear vacuole, in the Golgi apparatus, on the lateral cell and basal membranes, and also on the luminal surface of the endothelial cells of blood capillaries. When the tubulo-vacuolar system and the supranuclear vacuole were lost from the ileal cells at the weaning period, no exogenous peroxidase uptake was observed in the absorptive cell of the ileal epithelium.


Mitochondrial origin of centrioles and cilia in some human endocrine neoplasms. Fine structural investigation of surgically removed human pituitary and parathyroid adenomas, pheochromocytomas and bronchial carcinoids revealed a hitherto undetected sequence of events in the formation of centrioles and cilia indicating that mitochondria may serve as their progenitors. The first steps seem to be the disappearance of mitochondrial cristae and a polar accumulation of a fibrillar-granular material with a subsequent increase of electron density of the double mitochondrial membranes and deposition of more electron opaque substance within and around these procentriolar bodies. This process is followed by the disintegration of the double membranes and an asymmetrical division of the electron dense aggregate. The larger part seems to be the precursor of the primary centriole (basal body) whereas the smaller one that of the secondary centriole. Formation of centrioleand rudimentary cilium-like structures was disclosed within the unaltered mitochondrial membranes of oncocytic cells present in two pituitary adenomas and in one pheochromocytoma. Accumulation of procentriolar bodies and mature centrioles, noted in some tumors, may be due to a defect in the process of centriolo- and ciliogenesis. It is conceivable that the mitochondrial genome plays an important role in formation of centrioles and cilia.


On the structure of retina of a fresh-water mullet, Rhinomugil corsula (Mugilidae, Pisces). 1. The structure of the eye-ball of Rhimomugil corsula has been described. 2. A mid-horizontal ridge (band) along the vitreal surface of the retina in each eye of R. corsula has been observed which divides the retina into a superior and an inferior hemispheres probably adapted for aquatic (dim-light vision) and aerial (bright-light vision) vision. 3. The superior hemisphere has been provided with poorly developed choroid gland and scarce pigment in the pigment epithelial cells. 4. The visual cell layer in the retina of the superior hemisphere contains both single and twin cones. They are alternately arranged in parallel rows. 5. The external and internal limiting membranes have been observed in both the hemispheres under light microscope. 6. The outer plexiform layer of the superior hemisphere contains many horizontal cells arranged into four distinct rows. 7. The inferior hemisphere has a well developed choroid gland, and dense pigment in the pigment epithelial cells.


Histomorphological observations on the liver in some freshwater teleosts. Histomorphology of liver is studied in six species of teleost viz., Heteropneustes fossilis, Clarias batrachus, Puntius ticto, Danio malabaricus, Nandus nandus, Chana punctatus. The liver is a bilobed structure usually reddish brown in colour. There are accessory liver lobes in H. fossolis and C. batrachus. The histological examination shows compact mass of oval or polygonel hepatocytes, blood sinusoids and reticuloendothelial cells. In addition several patches of pigmented hepatocytes are also noticed. After partial hepatectomy the changes in liver structure are shrunken nature of hepatocytes, enlarged blood vessels and accumulation of lymphocytes near the cut portion. After biliary obstruction with the help of ligation of bile duct hepatocytes become turgid in appearance within seven days. There is fibrosis of blood vessels as well as bile spaces. The turgidity of hepatocytes increases fifteen days after the ligation so much so that some of them show necrotic appearance. There are numerous bile thrombi noticed after biliary obstruction.


Relationships between mast cells and preterminal nerve fibers. The observations demonstrate that mast cells do not only show intimate morphological associations to peripheral nerve fibers but also contact basement membranes of capillaries and cell surface coats of organ parenchyma cells. Interpreting these results as a neuro-hormonale feedback system mast cells might be regarded as both receptor organs and regulators of metabolism.


[Ontogeny of special endoplasmic reticulum complexes in neurons of the lateral geniculate body in rats]. 1. The ultrastructure of special membranous convolutions (MC) of the endoplasmic reticulum (complex convolutions, KARLSSON 1966), was studied in neurons of the lateral geniculate body in postnatal and adult rats. 2. The MC situated in the perikaryon are often attached to the nuclear membrane. Their average diameter is about 2 mum. Some MC of elongated form are extended over 6 mum. 3. Smaller MC of similar structure occur within basal dendrites, mainly in the environment of large axo-dendritic desmosomoid junctions. 4. The MC consist of smooth double membranes in a laminar or irregular arrangement, and are in connexion with the rough endoplasmic reticulum. 5. After incubation with ethanolic phosphotungstic acid the intermembranous material of the MC is stained in the same high intensity as this is the case with synaptic junctions. 6. The MC are developed by the rough endoplasmic reticulum during the 5 th and 6 th postnatal weeks. 7. The ultrastructure of the MC of both, normal and dark raised rats shows no significant differences.


[Histophysiology of the peripheral vegetative system. With special reference to mast cells]. Basallaminae of Schwanncell ensheathed axons and "naked" axons respectively have contact areas between the endformation of the peripheral vegetative nervious system and gröundsubstance. The latter, however, merges directly in the glycocalyces of connective tissue cells and organ cells. These cells may be related to one another (i.e. microvilli, cell processes, glycocalyces etc.) or will form "neuroeffector areas" together with pre- and terminal peripheral vegetative nerve fibers. On the other hand axon swellings might discharge their neurotransmitter substances into the ground substance in such way the neighbouring cells might be influenced ("synapse on distance"). Mast cells may act as regulators of the relationships in the groundsubstance. This because of the connections of mast cells with the peripheral nervous system and consequently with the CNS and the hormonale system. Thus the vegetative periphery as a whole would form a functional unit.


Studies on cartilage formation. XVI. Chemical and histochemical assay of lipids in the regenerating articular cartilage. The articular surface of the distal part of the femur was removed operatively in dogs, and the regenerating articular surface and the GTC were investigated at different stages from the 7th to the 70th postoperative days. During this period cartilage islets arose in the GTAS, while the GTC transformed to connective tissue. At 7 days the lipid content of the tissue was markedly higher than at the other stages studied. Lipids, predominantly triglycerides, were present in extracellular form as well. From the 20th to the 70th day the PL fraction became predominant and, in addition to the pre-existing lecithin, relatively large quantities of lysolecithin, sphingomyelin, phosphatidyl-ethanolamine, phosphatidyl-serine and phosphatidyl-inositol could be gradually demonstrated. Differences were noted in the time of appearance and binding of PLs between the two types of granulation tissue. As time proceeded, the proportion of saturated fatty acids decreased in favour of unsaturated ones. At 70 days, the GTAS contained fatty acids up to C18. About 50% of the fatty acids consisted of C16:1, C18:2 and C18:1. At the same stage, in the GTC C16:1, C18:1 and C20:1 were present in larger amounts. Of the free fatty acids C16:1, C16 and C18 were in predominance in the GTAS and the proportion of fatty acids having more then one double bonds increased with time. In the GTC C16 and C18:1 were in great majority. According to histochemical evidence, the tissues did not contain extracellular lipids from the 20th postoperative day. In the cells, the presence of glycerides, PLs, lipoproteins and cholesterol was demonstrated. In addition, in cartilage precursors of more advanced maturity, a considerable fatty acid positivity was noted.


Chloragosomes of lumbricidae as specific electron acceptors. In vitro investigations. Measurements of the redox potential values in buffered salt solutions containing body wall homogenate, body wall homogenate with isolated chloragosomes and in both solutions enriched with NAD have shown that chloragosomes are specific electron acceptors which prevent the rapid decrease of the redox potential under anaerobic conditions. The substances responsible for the electron-acceptor activity are most probably identical with the flavins, carotenes and metalloporphyrins present in chloragosomes as shown by the visible absorption spectra of the extracts. The results support the assumption that chloragosomes may play an important role in the metabolism under hypoxic and anoxic conditions.


Functional adaptation of the articular cartilage. The effect of prolonged sparing and prolonged loading of the knee-joint of dogs on the glucosamine, sialic acid, sulphate and hydroxyproline contents of the articular cartilage was investigated. (a) In the articular cartilage of the spared leg the amount of sulphate decreased by 24.7%, while the sialic acid content remained unchanged. Hydroxyproline showed a slight decrease. (b) On increased loading, glucosamine augmented by 53% and sialic acid by 32.5%. No appreciable changes occurred in sulphate and hydroxyproline. It is concluded that an increased loading brings about accumulation of glycoproteins while the amount of sulphated glycosaminoglycans does not change appreciably; the glycoprotein content of the spared articular cartilage remains unchanged, whereas the chondroitin sulphate content decreases considerably.


Ecdysterone and an analogue of juvenile hormone on the autophagy in the cells of fat body of mamestra brassicae. The effect of ecdysterone and a juvenile hormone analogue (JHa) on autophagy and heterophagy was investigated in the fat body cells of the last larval instar of Mamestra brassicae. In the course of normal development autophagic vacuoles and protein granules of heterophagic origin begin to accumulate in these cells, on the 4th and 5th day of the last larval stage respectively. When ecdysterone (10 mug/g body weight) was administered to the larvae for 24 h either on the 1st or on the 2nd day of the last larval stage, autophagic and heterophagic vacuoles appeared in the cells as early as on the 2nd or 3rd days. Autophagy was also observed in the cells of one-or two-day-old last larval fat body after a 5 h incubation in a medium containing 10 mug/ml ecdysterone, in vitro. Ligation of the last thoracic segment resulted in inhibition of metamorphic changes in the fat body lobules of the isolated abdomen. Injection of 10 mug ecdysterone into the isolated abdomen resulted in an appearence of autophagic vacuoles in these cells, too. JHa treatment, when started on the 2nd or 3rd day of the last larval stage, inhibited both auto- and heterophagy and the fat bodies maintained their larval character. Treatment started on the 4th or 5th day proved either ineffective or lethal. It is concluded that the auto- and heterophagy taking place in the larval fat body cells are stimulated by ecdysterone and inhibited by JHa. Experiments performed in vitro or on ligated animals in vivo provided evidence for a direct action of ecdysterone at the cellular level.


Nervous system involvement in systemic lupus erythematosus. In a retrospective analysis of 80 patients with systemic lupus erythematosus (SLE) seen over a 10-year period, 41 (51%) exhibited neurological manifestations. Nervous system involvement was characterized by a significantly greater involvement of black patients (P less than 0-02), a higher incidence of renal failure after the first appearance of neurological features (P less than 0-05), and a significantly worse 10-year survival rate (P less than 0-05). Specific neurological investigations were generally unhelpful in diagnosis. The finding of hypoglycorrhachia in 4 patients was striking and may have pathogenetic significance. The lack of a specific diagnostic test for central nervous system involvement may have hindered recognition of a cerebral abscess in one patient. Treatment with massive doses of corticosteroids was not obviously more effective than treatment with smaller doses. Autopsy findings showed scattered small cerebral infarcts but vasculitis was apparent in only one case.


Peripheral blood lymphocyte response to phytomitogens in systemic lupus erythematosus. The response of peripheral blood lymphocytes to the phytomitogens, PHA, Con A, and PWM, was evaluated in 30 SLE patients and in 30 age, sex, and race-matched controls using dose and time responses. The proliferative response to the three phytomitogens was not depressed in this group of subacute and chronic SLE patients. Active lupus nephritis and a slow acetylator phenotype were associated with a decreased lymphocyte response. The incidence of a slow acetylator phenotype in spontaneous SLE was 68%. In interpreting the lymphocyte response to phytomitogens, the importance of a clear definition of the SLE group under study, the activity of the disease, and treatment status are emphasized.


Value of 17beta-oestradiol in prevention of contracture formation. Male and female rabbits were treated with 17beta-oestradiol during the 9-week development of a contracture in the left hind limb. The right hind limb served as the paired control. Untreated (absolute control) animals received saline injections. After 9 weeks biochemical analyses of water, hexosamine, soluble and total collagen, as well as biomechanical measurements of joint stiffness, were performed on the dissected knees. In all cases 17beta-oestradiol reduced the measured stiffness in the contractures by approximately 50% as compared to the contractures of the untreated animals. 17beta-oestradiol, in addition, partially prevented the loss of water and hexosamine which occurs in untreated contractures. 17beta-oestradiol administration also decreased the content of soluble collagen fractions in the periarticular connective tissue of both the control and experimental knees. The relationship of these biochemical findings to their mechanical consequences is discussed, and the results are related to a working hypothesis of stress- and motion-dependent homoeostasis within periarticular connective tissue.


Controlled trial of synovectomy of knee and metacarpophalangeal joints in rheumatoid arthritis. In a multicentre study patients with rheumatoid arthritis judged by prevailing criteria to be suitable for synovectomy of the knee or metacarpophalangeal (MCP) joints were randomly allocated to one of two groups. One group had the operation, the other was observed without operation from a notional corresponding date. 3 years later the outcome of synovectomy was compared with that of observation without synovectomy. Synovectomy of the knee was followed by significantly less pain and tenderness, smaller effusions, and smaller and less frequent erosions and geodes. By contrast, MCP joints were no better clinically or radiographically than those treated conservatively. The results have been compared with those of two other controlled trials, one concerned with the knee and MCP joints, the other only with MCP joints. In the present trial results were more favourable in the knee but comparable in the MCP joints with those reported in the first of these two trials but less favourable in the MCP joints than those observed in the second.


Serum copper and caeruloplasmin in ankylosing spondylitis, systemic sclerosis, and morphea. Studies of serum copper and caeruloplasmin were performed in patients with ankylosing spondylitis, systemic sclerosis, and morphea. Mean levels of both were raised significantly in ankylosing spondylitis, with the greatest increases in the worst cases. In patients with systemic sclerosis there was a significant increase in the mean level of caeruloplasmin, but not of copper, although both were raised in the 2 patients with the most aggressive disease. No alterations were found in patients with morphea. The values in the patients overlapped considerably with the values in the control subjects. It is thought that the increase in serum copper is probably secondary to the increase in caeruloplasmin which occurs as a nonspecific response to inflammation.


Personality in frozen shoulder.

Personality in frozen shoulder. Fifty-six patients with frozen shoulder have had their personality profiles investigated by means of the Middlesex Hospital Questionnaire. Females showed significantly increased somatic anxiety compared with controls. It is suggested that this may be important both to aetiology and treatment. Males and females should be assessed separately in future studies of frozen shoulder.


A single dose study of trazodone with an assessment of its effect on mood and arousal. 1 A pharmacokinetic study of a single oral dose of a new antidepressant (trazodone) is described, linked to an attempt to measure changes in mood and arousal induced by the drug in normal subjects. 2 The drug had a measurable effect on arousal, but not on mood. It caused bradycardia (compared with placebo) and this persisted through the following night's sleep. This effect has not been completely explained. 3 The technique of mood and arousal measurement employed in this study seems potentially useful.


Effect of long-term phenothiazine treatment on drug metabolism. 1 The half-life of plasma antipyrine was measured in twelve chronic schizophrenic patients during long-term phenothiazine treatment and again following 4-5 weeks on placebo. 2 The mean antipyrine half-life was low during phenothiazine administration (6.1 +/- 4.2 h), rising after withdrawal of drugs to the range reported for untreated subjects by other authors (9.5 +/- 4.2 h). The prolongation of antipyrine half-life following the drug-free period occurred in nine of twelve subjects and the difference was significant for the group at P less than 0.05. 3 The finding suggests that prolonged administration of phenothiazines stimulates the rate of drug metabolism.


Plasma levels and beta-adrenoceptor blockade with acebutolol, practolol and propranolol in man. 1 The degree of beta-adrenoceptor blockade of isoprenaline-induced tachycardia has been determined in three healthy volunteers after the administration of single oral doses of acebutolol, practolol or propranolol. 2 Plasma levels of these drugs were determined either colorimetrically (acebutolol and practolol) or fluorimetrically (propranolol). The colorimetric assay of acebutolol in plasma is fully described but the other drugs were assayed by published methods. 3 The degree of beta-adrenoceptor blockade and the plasma level for acebutolol and practolol were well correlated, whereas in the case of propranolol correlation was poor, due in part to the presence in plasma of active metabolites not detected by the fluorimetric assay. The plasma levels of practolol and propranolol are in agreement with those previously reported. 4 The maximum cardiac beta-adrenoceptor blockade achieved in this study with the respective single oral doses of acebutolol (300 mg), practolol (400 mg) or propranolol (40 mg) were similar in each of the three subjects. Therefore the beta-adrenoceptor blocking potencies of these drugs against isoprenaline-induced tachycardia are inversely related to these doses; indicating that propranolol is 7-8 times more potent than acebutolol and the latter slightly more potent than practolol.


The effect of codeine phosphate on the absorption of ethyl alcohol. The effect of syrup, B.P. and codeine phosphate syrup, B.P.C. on blood alcohol levels was determined in six normal subjects. 2 Treatment with syrup alone had little or no influence on the concentration of ethanol in blood. 3 In contrast, pretreatment with codeine phosphate syrup significantly reduced alcohol absorption, as assessed by the maximum blood levels achieved or the area subtended by the blood concentration-time curve. It is suggested that the diminished absorption of ethanol is related to the pharmacological action of codeine on the stomach. 4 It was considered that the concentration of ethanol in linctuses or syrups containing codeine was unlikely to have any significant effect on the central nervous system.


Changes in drug metabolism with increasing age: 1. warfarin binding and plasma proteins. 1 A decrease was found in the binding capacity of elderly people for warfarin. 2 The decrease in binding correlated with a fall in plasma albumin concentrations. 3 No changes in the association constant were observed.


Changes in drug metabolism with increasing age: 2. phenytoin clearance and protein binding. 1 Comparison of phenytoin clearance showed a marked increase in people over 65 years of age compared with people under 45 years of age. 2 This difference was apparent if phenytoin was given orally or intravenously. 3 Phenytoin clearance correlated inversely with phenytoin binding and plasma albumin, both of which were found to be reduced in the elderly.


A comparison of the efficacy of cyclizine and perhenazine in reducing the emetic effects of morphine and pethidine. 1 The ability of cyclizine (50 mg) and perphenazine (2.5 and 5.0 mg) to counteract the emetic effects of pethidine (100 mg) and morphine (10 and 15 mg) was compared in women undergoing a standard minor operation with a standard anaesthetic. 2 Perphenazine (5.0 mg) was as effective an anti-emetic as cyclizine (50 mg) and both were more effective than perphenazine (2.5 mg). 3 The reduction in vomiting and nausea by cyclizine (50 mg) and perphenazine (5 mg) was approximately the same following pethidine (100 mg) and morphine (10 mg) but much less against the larger dose of morphine. 4 Both anti-emetics had a rapid onset of action but their anti-emetic activity did not last as long as the emetic effect of morphine. 5 Perphenazine (5 mg) was accompanied by an unacceptably high incidence of restlessness. 6 In clinical practice cyclizine (50 mg) is preferred to perphenazine (5 mg) as an anti-emetic.