Chemically defined diet in the treatment of kwashiorkor. The authors report on the treatment of children with kwashiorkor, using Vivonex or Casilan. With Vivonex, all patients were bottle-fed as early as the 2nd or 3rd day, whereas Casilan had to be administered by stomach tube for about a week. Children fed Casilan vomited much more frequently than patients receiving Vivonex. When Casilan was given, the albumin level rose after 8 days, whereas with Vivonex, this did not occur unitl 15 days. On the other hand, only the Vivonex fed children showed an increase of hemoglobin in the first 3 weeks of treatment. With Vivonex, the patients reached their minimum weight much faster and at a lower albumin level than with Casilan. In both groups, the frequency of diarrhea was similar; the relatively high glucose concentration of Vivonex and the disturbance of resorption, even of monosaccharides, which is frequently observed in severe cases of kwashiorkor may be responsible for the diarrhea of the children receiving Vivonex.


[Long term feeding with a chemically defined diet]. The author reports the successful treatment with Vivasorb, the bulk-free, balanced synthetic diet, of patients with severe forms of ulcerative colitis and Crohn's disease, indigenous sprue and condition after small bowel resection, and of one patient with a Cronkhite Canada syndrome. The duration of the treatment was from a few weeks to 34 months. The patients received between 320 and 640 g/day, according to their requirements and their tolerance. Because of the relatively low content of essential fatty acids, long-term exclusive administration of Vivasorb may lead to symptoms of essential fatty acid deficiency, which disappear after the administration of Lipofundin S. The successful treatment of patients with malabsorption syndrome was verified histologically. Particles of mucosa taken from different small bowel sections showed the development of villi after only four weeks of treatment, whereas, before the treatment, subtotal villi atrophy had been observed.


Phagocytosis by macrophages of mycoplasma pneumoniae after opsonization by complement. Mycoplasma pneumoniae cells are not phagocytized by peritoneal macrophages without opsonization. They are taken up after treatment with complement or antibody.


How infection can trigger autoimmunity.

How infection can trigger autoimmunity. The role of infection in the development of autoimmunity is discussed in view of recent advances in the field of immunologic tolerance. Infectious agents may directly damage immune function by impairing the mechanisms of discrimination between self and non-self antigens; alternatively they may "deceive" the immune system by presentation of self-determinants in an immunogenic form or by uncovering of normally sequestered antigenic determinants. The first of these two pathogenetic mechanisms may be responsible for generalized and the second for selective autoimmune reactions. Different clinical conditions are evaluated on the basis of these concepts. The interaction of personal factors with infection and autoimmunity is also taken into consideration.


[Experimental study in rats on the renal compatibility of cephalothin and cephalothin-aminoglycoside combinations (author's transl)]. The possible nephrotoxity of cephalothin and the antibiotic combinations cephalotin-gentamicin and cephalothin-tobramycin was investigated in standardized animal experiments. Toxicity parameters were blood-urea concentration, the urinary enzymes GOT, LDH, MDH and the cell excretion rate, supplemented by histological investigations of the kidneys. Compared with other cephalosporine derivates, the antibiotic cephalothin in a toxic threshold-dose of 3000 mg/kg/day proved to be realtively well tolerated by the kidneys. On comparison with the respective monotherapy, the renal tolerance for cephalothin-aminoglycoside combinations was reduced. The clinical value of these findings is discussed.


Familial clustering of hepatitis B antigen and liver diseases in families with a high incidence of viral hepatitis. In each of 23 families in which two or more cases of acute hepatitis-like jaundice (index cases) occurred, all family members were studied to evaluate HBAg clustering and the incidence of asymptomatic liver disease. There were 49 "index cases" of hepatitis-like jaundice: 38 cases of acute viral hepatitis, 5 of chronic agressive hepatitis and 6 of active cirrhosis. The overall number of members in these families (excluding index cases) was 170 and 155 of which were tested by clinical examination, laboratory tests and needle liver biopsy. In 27 out of the 155 subjects there was evidence of liver diseases (10 non icteric hepatitis cases, 12 CAH cases and 5 cirrhosis cases). HBAg was present in the serum of 19 of these patients, and twof the cirrhotic patients were positive. Furthermore, 33 of the 155 cases were healthy HGAg carriers showing no abnormality in liver function tests. In the majority of these carriers liver histology showed slight damage (pin-head necrosis or portitis) sometimes compatible with resolving viral hepatitis. A long-term follow-up of the HGAg carriers showed that three of these subjects progressed to acute viral hepatitis.


Relationship between the response to complete freund adjuvant, phytohemagglutinin, and subsequent tumor growth in mice. Groups of inbred C3H mice selected on the basis of strong or weak PPD reactions after sensitization with complete Freund adjuvant had significantly different reactions to PHA. The growth rate of a methylcholanthrene-induced tumor, previously shown to elicit a cell-mediated immune response, was significantly different in these two groups of mice. The basis for the marked variation observed between members of an inbred mouse strain in response to CFA is not understood but may bear an important potential relationship to tumor growth.


In vitro reaction of antibodies to ragweed. I. Radioimmunoassay for measuring antibody levels. A radioimmunoassay was developed in which human antibodies to ragweed compete with 125I-labeled rabbit anti-ragweed antibodies for the ragweed antigen coupled to cellulose particles. By means of this test, antibodies to ragweed were determined in 96 sera of treated and untreated patients with ragweed allergy and in 32 sera of nonallergic individuals. Within the applied experimental conditions, it was possible to measure antibodies over a range from 0.4 to 200 mug/ml. In patients receiving immunotherapy, the mean value of the antibodies was 7.2 mug/ml, and in the untreated patients 1.8 mug/ml. Antibodies to ragweed were also found in the sera of nonallergic individuals. It is assumed that this test measures 'total' serum antibodies to ragweed.


Experimental osteomyelitis induced by repeated administration of soluble immune complexes: consideration of the fundamental pathogenesis of osteomyelitis. Morphological changes of blood vessel walls including various kinds of capillaries have been induced by administration of soluble immune complexes. After repeated administrations, those experimental animals who survived the phase of initial anaphylactic shock developed osteomyelitis. In this paper, the formative processes of osteomyelitis will be discussed in relation to Aschoff's definition of inflammation. We will emphasize the importance of the capillarization of the sinusoidal endothelia for the formation of osteomyelitis.


Cellular immune reactivity in vitro and tumor rejection provided by tumor-associated antigens of friend-virus-induced leukemia. Cell-mediated immunity (CMI) and tumor rejection were studied in the Friend virus leukemia system of C57Bl/6 mice. Mice were immunized with Friend leukemia virus (FLV) or X-irradiated FBL-3 leukemic cells and studied temporally for the development of CMI reactivity by assays of 51Cr release lymphocyte cytotoxicity, lymphocyte transformation, migration inhibition, Winn tumor cell neutralization and transplantation rejection. High levels of specific lymphocyte cytotoxicity were observed by day 7 f0llowing FLV infection; this reactivity reached a peak between 17 and 21 days, and returned to background levels by day 36. Further, positive Winn assays were obtained with spleen cells from mice immunized with FLV at times when the mice resisted live FBL-3 tumor challenge. Positive lymphocyte transformation was obtained with spleen cells from mice immunized with FLV or FBL-3, but not with cells from normal mice or mice immune to a syngeneic methycholanthrene-induced tumor, when cultured with papain-soluble FBL-3 or RBL-5 tumor-cell extracts or mitomycin-C (MMC)-treated FBL-3 or RBL-5 cells. Positive reactivity in the lymphocyte transformation assay occurred after reactivity had peaked in the lymphocyte cytotoxicity test. Similar positive macrophage migration inhibition patterns were also obtained with peritoneal exudate cells (PEC) from FLV-immunized mice using papain-solubilized tumor-associated antigen (TAA) from FBL-3 cells. These data suggest that sequential development and modulation of CMI reactivity occurs as observed in different assays following immunization in this system.


Humoral cytotoxicity in melanoma patients and its correlation with the extent and course of the disease. Complement-dependent cytotoxicity against melanoma cells was demonstrated with a microassay in sera from melanoma patients. The response was tumor-specific and histologic type-specific since 16 out of 52 (30%) melanoma patient sera taken before surgery reacted against melanoma cells, whereas 3 out of 43 (7%) control sera, collected from patients with unrelated tumors and from cancer-free individuals, were positive. The serum activity correlated with the clinical stage of the disease since it was detected in 15 out of 40 patients with stage I and II tumors and in 1 of the 12 patients in stage III. Twelve melanoma patients, clinically tumor-free for  to 4 years after surgery, showed no humoral cytotoxicity. A follow-up study of 13 melanoma patients revealed that the cytotoxicity appeared 7-10 days after radical removal of the tumor and that it disappeared if there was no recurrence. The histologic type-specificity was further tested by assaying sera from 16 melanoma and 10 breast-cancer patients simultaneously on both melanoma and breast-cancer cells; a positive reaction was observed in 6 cases of melanoma and in 5 of breast cancer on homologous cells only, in 1 case on the opposite type of cells, and in 3 cases on both types of tumor cells.


Combination of C. parvum and specific immunization against artificial pulmonary metastases in mice. We have studied whether specific immunization administered intraperitoneally can augment the activity of C. parvum (0.25 mg intraperitoneally or intravenously) against intravenously injected cells of a syngeneic fibrosarcoma in C3Hf/Bu mice as expressed by the reduction of pulmonary metastases (nodules, colonies) and/or by the prolongation of the survival of recipients. Combination of specific immunization and C. parvum, applied either before or after IV inoculation of viable tumor cells, was more effective than the single treatments. IV injection of a mixture of heavily irradiated and viable tumor cells gave more tumor nodules in the lungs of normal mice than injection of viable cells alone. The metastasis-enhancing effect of admixed irradiated cells was not found in mice previously treated with C. parvum, and was abolished if the immunostimulant was injected after tumor cells. Generation of lung metastases by IV inoculation of fibrosarcoma cells was reduced in mice already having this tumor in the leg. This concomitant immunity to metastases was increased by treating the recipients with C. parvum, but not with irradiated cells; also, the injection of irradiated cells together with C. parvum did not augment the efficiency of the latter. C. parvum was not as effective in T-cell deprived as in control mice, which suggests that in this system, T-cells are required for optimal anti-tumor activity of this immunostimulant. Specific immunization was not effective in T-cell-deprived mice and did not augment the efficiency of C. parvum.


The effect produced by some carcinogenic nitrosocompounds on organ cultures from human embryonic lung and kidney tissues. Previous works using organ cultures of lung and kidney tissues of mouse, rat and hamster embryos exposed to transplacental action of some carcinogens showed premalignant growth. This paper presents the results of organ culture of human embryonic lung and kidney tissues. Direct action of some carcinogenic nitrosocompounds (N-nitrosomethylurea, dimethylnitrosamine and orthoaminoazotoluene) resulted in higher survival of the treated organ cultures and induced epithelial hyperplasia. The changes depended directly upon the dose of carcinogen employed.


Isolation of tumor-specific antibodies from effusions of ovarian carcinomas. Peritoneal effusions of patients with ovarian cancer contain sizable amounts of free and complexed immunoglobulins. By means of salt precipitation procedures, antibodies were recovered that after purification and concentration displayed a high degree of specificity against ovarian carcinoma cells. In indirect immunofluorescence, immunoglobulins recovered from seven different peritoneal effusions showed bright cytoplasmic staining with tissue cultures and fresh suspensions of ovarian carcinoma cells but not of normal ovaries or non-ovarian tumors. Immunoglobulins isolated from fluids of benign ovarian cysts or from effusions of non-ovarian tumors were negative in immunofluorescence tests. Autologous antibodies recovered from peritoneal effusions will be hopefully utilized in sensitive radioimmunoassay tests that are greatly needed for the early detection of ovarian cancer, the leading cause of death from gynecologic neoplasia.


Preneoplastic changes in rabbit pancreatic duct cells produced by dimethylhydrazine. Permeation catheters containing 40% dimethylhydrazine (DMH) were implanted into the main pancreatic duct of New Zealand white rabbits. The catheters were constructed of silicone polycarbonate with a 4- to 10-day carcinogen release rate. Rabbits implanted with catheters containing DMH showed pancreatic ductal cell hyperplasia, metaplasia and dysplasia with periductal cell infiltration, adenosis and adenoma formation. These changes began approximately 9 to 12 weeks after implantation and persisted for 75 to 80 weeks. Specificity of the delivery system appeared to be excellent in that pathologic effects were observed only in the pancreatic and peripancreatic tissues. Moreover, these effects were probably directly related to the implanted carcinogen since similar maintained effects were not observed in control animals.


A quantitative comparison between in vivo-and in vitro-derived Friend leukemia virus. The biological activities of RNA viruses derived from Friend leukemia cells in culture (TCV) were compared with those of viruses derived from the plasma (PV) of mice infected with Friend leukemia virus (FLV). The comparison was quantitatively based on the actual number of viruses used in each experiment as determined by counting under the electron microscope. Electron microscopy also provided a qualitative assessment of the structural integrity of the concentrated virus particles used in various bioassays. The data shows that the leukemogenic and spleen-focus-forming (SFF) activities of TCV, although demonstrable, are respectively 10(5) and 10(4) lower than those of PV. Moreover, TCV has 10(4) less helper activity (S+L- test) than PV. The level of reverse transcriptase activity is ten times lower in TCV than in PV which indicates that there is little correlation between polymerase activity and the other biological activities measured. The decreased biological activity of the in vitro grown virus is thought to be intrinsic to this type of virus although all extrinsic factors have not been ruled out.


Increased lymphocyte-mediated destruction of tumor cells in microcytotoxicity assays seen after addition of inhibitors of protein synthesis. Two methylcholanthrene (MCA)-induced sarcomas were used as targets in a criss-cross pattern to study lymph-node-cell (LNC)-mediated cytotoxic reactions to tumor-specific antigens in a 26 h microcytotoxicity assay. Destruction of plated tumor cells by syngeneic LNC from specifically tumor-immune or multiparous mice significantly increased when cycloheximide was added during the whole duration of the test. A similar increase was also seen if either cycloheximide or puromycin was added during the last 6 h of the 24 h assay. A slight increase of cytotoxicity was seen if, instead, the mixture of fetal calf serum and LNC was simply replaced by serum-free medium during the last 6 h of the test. The findings suggest that a repair process may occur in target cells contacted by immune LNC or that target cells damaged by contact with immune LNC are more sensitive to further damage by the exposure to certain inhibitors of protein synthesis. Additional mechanisms may contribute to the increased LNC-mediated cytotoxicity seen when cycloheximide is added for the whole duration of the test.


Immune enhancement of the tumorigenicity of hamster brain tumor cells persistently infected with measles virus. Studies were conducted on the tumorigenicity of a hamster brain tumor (HBT) cell line persistently infected with measles virus (MV). This cell population, termed HBT-M, exhibited decreased tumorigenicity in weanling hamsters when implanted intracutaneously. The lowered tumorigenicity of the HBT-M cells could be counteracted by concurrent hydrocortisone treatment restoring the tumor-producing capacity to levels comparable to those of the highly tumorigenic HBT cells. It was also determined that prior immunization of hamsters with MV resulted in enhancement of tumor formation from usually subtumorigenic doses of HBT-M cells. This increase in tumorigenicity appeared to correlate with high titers of MV antibody. Treatment of hamsters with cyclophosphamide resulted in a reduction of MV antibody titers and effected a decrease of HBT-M cell tumorigenicity to control levels. Preliminary studies with passive immunizations indicated that the enhancing factor could be transferred in the sera from hamsters hyperimmunized with MV. These data suggested that MV antibody may potentiate the development of neoplasia of cells persistently infected with MV in a manner similar to the enhancement of tumor growth by blocking antibody.


Antibody-dependent cell-mediated cytotoxic activity in syngeneic moouse ascites tumors. Eight different syngeneic murine ascites tumor preparations were tested for their ability to lyse antibody-coated chicken erythrocytes in an assay for antibody-dependent cell-mediated cytotoxicity (ADCC). All of the tumor preparations demonstrated significant ADCC effector activity, even at effector-cell:target-cell ratios of less than 1:1. In contrast, none of eight in vitro murine tumor-cell lines showed any consistent ability to function as ADCC effector cells. Several cell fractionation experiments were performed to ascertain the nature of the effector cells in the ascites tumors. Adherent cells were removed from tumor preparations by passage of cells over columns of Degalan plastic beads and 19S Fc-receptor-bearing cells were removed by sedimentation of EA rosette-forming cells. Although each of these procedures depleted only a minority of the total cells, all the ADCC activity was simultaneously removed in each case. Depletion of phagocytic cells by treatment of tumor preparations with carbonyl iron and magnetism only slightly diminished the ADCC activity. These results indicate that the ADCC activity associated with ascites tumors is due to effector cells most probably of host origin, but possibly representing an atypical sub-population of tumor cells. The characteristics of the effector cell closely parallel those defined for the major non-phagocytic ADCC effector cell in normal mouse spleen and peritoneal exudate.


Diffuse "essential" normolipemic xanthomatosis. Most types of cutaneous xanthomas are associated with hyperlipidemic states. However, the diffuse normolipemic xanthomatoses have normal lipid blood levels but are often associated with serious hepatic disease or hematologic dyscrasias, especially multiple myeloma. A patient is presented who had "essential" diffuse normolipemic xanthomatosis unassociated with any sytemic disease, and displayed an unusual number of different types of lesions. His condition was clearly different from those of patients reported with xanthoma disseminatum.


Recurrent contact dermatitis caused by mercury in amalgam dental fillings. A metal worker had repeated episodes of contact dermatitis over a period of years. Patch tests with 5% ammoniated mercury were strongly positive but occupational contact could not be proved. Recurrence of the dermatitis one day after amalgam dental fillings had been made and again one year later, this time without new fillings, raised the possibility that it was due to the old amalgam fillings. Removal of all the amalgam fillings resulted in a new outbreak of severe dermatitis; during the 5 years ensuing there has been no recurrence. This case history suggests that contact dermatitis may be caused by not only the mercury in new fillings but also by that in old fillings.


Chronic paronychia in which hair was a foreign body. A patient who worked as a baker and a part-time barber had chronic paronychia. Biopsy revealed the presence of hair in the dermis of the nail fold. This is only the second case of chronic paronychia to be reported in which the dermis contained nonmicrobial exogenous material. Based on experimental work it has been previously suggested that the rounding out of the posterior nail fold in most paronychia is due to the body's reaction to the penetration of debris derived from Candida albicans. However, patients recalcitrant to therapy or those exposed to chemicals or particulate material deserve detailed histologic study.


Erythema nodosum leprosum in Nigeria.

Erythema nodosum leprosum in Nigeria. The occurrence of erythema nodosum leprosum among leprosy patients treated with diamino diphenyl sulfone in an endemic area is not rare, unlike in the leprosy patients treated at Lagos University Teaching Hospital. Two Nigerian patients with this disease are described, in whom this rarity was seen. Recurrent monthly fever with painful skin swellings in lepromatous patients from an edemic area is highly suggestive of erythema nodosum leprosum. The occurrence of this reaction in lepromatous leprosy gives a relatively poor prognosis.


A pattern analysis study of weanling diarrhoeal disease of infants. Methods of pattern analysis based on statistical signal procedures have been applied to (512-day) records of daily defaecation rate obtained in an ensemble of weanling infants. Careful analysis of the records using several different methods has established the potential significance of the signal. A technique of coherent averaging has produced a stable consistent age-dependent baseline of average behaviour, referred to as an average profile. Extensions have been proposed for the application of statistical methods for the acquisition of standard patterns of diarrhoeal behaviour. Numerical low pass filtering the signal allows a dichotomization of cases, the significance of which is confirmed by differences of class average profiles. Removing the class average profile from the records shows that the majority of cases exhibit consistent individual signal patterns; standardized patterns of behaviour can also be discussed. It is tentatively concluded that objective specification of normal and abnormal defaecation behaviour could be based on spontaneous patterns identified in the records. Several methods have been suggested. Methods similar to those applied here would appear, on the evidence of this study, to be applicable to a variety of other longitudinal epidemiological studies.


Factors influencing demand for primary medical care in women aged 20-44 years: a preliminary report. This paper reports on a study designed to relate certain social and psychological variables to demand for medical care in a random sample of female patients aged between 20 and 44 years, in a National Health Service General Practice in the United Kingdom. Women selected for study completed questionnaires on anxiety and on their social characteristics. They also completed a health diary for four weeks, and over 12 months their demand for general practitioner care was recorded. This paper summarizes some of the literature on the subject of utilization behaviour, describes the objectives and methodology, and gives some preliminary results suggesting associations between anxiety, perception of symptoms and demand for primary care.


An epidemiological study of the relationship between occupations and acute herniated lumbar intervertebral discs. A case-control study of the epidemiology of acute herniated lumbar intervertebral discs in the New Haven, Connecticut, area indicates that sedentary occupations increase the risk for herniated lumbar discs, particularly among those aged 35 years and older who have had sedentary jobs for several years. People in occupations requiring prolonged driving of motor vehicles, such as truck drivers, appear to be at particularly high risk. The results of this study provide no evidence that people whose jobs involve heavy manual labour are at greater risk for acute herniated lumbar disc than others of their age and sex.


Distributions of percentage methaemoglobin in several population groups in California. Several epidemiological studies in California have yielded data on percentage methaemoglobin in healthy individuals. The population groups represented include infants, elementary and high school children, and adults. The distributions of values in each group are described, as well as the differences between groups. Factors affecting the distributions are discussed. In the study of infants, the factors assessed include respiratory and gastrointestinal disease, and food and water intake. In schoolchildren, the effect of age and location of residence within Southern California are evaluated, and in adults, smoking, gender and time of day. Among infants in the 31 to 60 day age range, 33 per cent had methaemoglobin levels of 3 per cent or above, while 8 per cent had methaemoglobin levels of 4 per cent or above. Among adults, 15 per cent had levels of 3 per cent or above, while 2 per cent had levels of 4 per cent or above. Among both elementary and high school students, 3 per cent had methaemoglobin levels of 3 per cent or above, while less than 1 per cent had levels of 4 per cent or greater.


Blood pressure and length of stay in Australia of Italian immigrants in the Australian National Blood Pressure Study. Data obtained from 10,975 Australian-born and 1,717 Italian-born subjects aged 30-69 years in one centre of the Australian National Blood Pressure Study revealed that the Italians had lower systolic and diastolic blood pressures compared with Australians of the same age and sex. The Italians' blood pressures rose in successive age groups and at the same rate as in the Australians. After the effect of age was eliminated, the duration of residence of the Italians in Australia had a small but significant association with their blood pressures, possibly indicating exposure to blood pressure-elevating environmental factors in Australia.


A family study of blood pressure in Polynesians. The family aggregation of blood pressure was studied in Tokelau Island children aged 5-14 years and their parents resident on their home islands in 1971. Five hundred and two (97 per cent) of the children had a recorded blood pressure and they formed 210 sibling groups. The sibship similarity of blood pressure z scores adjusted for year of age and sex was examined by analysis of variance between and within sibships in the 133 sibships with more than one member. For both systolic and diastolic pressure a statistically significant sibship similarity exists which is independent of family size, level of pressure, and the sibship similarity of Quetelet Index. The correlation coefficient of the z score of one index child chosen at random and the remaining siblings is 0-14 (n = 282, p = 0-017). Of the parental variables studied the mother's systolic pressure is the best, and only, predictor of the child's systolic z score. These results suggest that in the Tokelau islanders a family similarity of blood pressure is established relatively early in life.


Varicose veins in a population of lowland New Guinea. A survey of varicose veins in a rural area of northern New Guinea showed a very low prevalence in women (0-1 percent in females aged 20 and over) and a modest prevalence in men (5-1 per cent in the same age range). The people lacked factors of diet, body bulk and tight clothing that have been postulated to be important in other populations. Multi-parity, leg trauma and heavy lifting were present but did not accord with the sex difference in prevalence. Sitting habits may be important in the aetiology of varicose veins in this population.


Solar activity and mortality in the United States. Mortality from all causes, from coronary heart disease, and from stroke in the US was studied in relation to solar activity as measured by the geomagnetic index, Ap, on a daily basis for the years 1964-66 and on a monthly basis for the years 1964-71. The data did not support previous assertions by Soviet researchers of an association between solar activity and cardiovascular mortality.


Synthesis of the pentadecapeptide sequence of the active site of rabbit muscle triosephosphate isomerase. The pentadecapeptide fragment, Trp-Val-Leu-Ala-Tyr-Glu-Pro-Val-Trp-Ala-Ile-Gly-Thr-Gly-Lys, which constitutes a part of the active site of rabbit muscle triosephosphate isomerase has been synthesized. It does not exhibit any catalytic activity typical of triosephosphate isomerase.


Syhthesis of peptides by fragment condensation on a solid support. I. Application in preparation of bradykinin. Two tripeptides and one dipeptide, protected except at the carboxyl ends, have been prepared in solution and used as intermediates in a new synthesis of bradykinin on a solid support. Condensation of the two tripeptides to the resin was effected in satisfactroy yield with dicyclohexylcarbodiimide plus N-hydroxysuccinimide. The partial epimerization that might occur by such an approach was explicitly verified to be without practical importance in this case. The crude product contained only traces of impurities and yielded, after purification, bradykinin of high purity. Both the crude and purified bradykinin exhibited full biological activity.


Theory of reversible denaturation of globular proteins. A theoretical method is developed by which the character of the process of protein denaturation (e.g., whether or not it is of the all-or-none type) can be discussed in terms of conformation of native proteins and the forces stabilizing it. An important role is played by a quantity S(H): entropy of a protein molecule in solution in the conformational states with a given value of enthalpy H. It is demonstrated that the all-or-none type denaturation of proteins is a rather direct consequence of the globularity and specificity of the native conformations. Denaturations with significant intermediate states are discussed. Denaturations induced by added denaturants are also discussed.


Spectrophotometric titration of tyrosyl residues in alkaline mesentericopeptidase. At pH 7.0 the alkaline mesentericopeptidase has ultraviolet absorption spectrum with a minimum at 251 nm and a maximum at 280 nm and no visible absorption. From the tyrosine to tryptophan ratio a value of 3 tryptophyl residues per mole of protein is obtained. The molar extinction coefficient at 280 nm is 3.55 X 10(4)M-1cm-1. Spectrophotometric titration studies show that the molecule of mesentericopeptidase contains seven phenolic groups with a pKapp - 9.92 and four to five groups with a pKapp = 11.96. Denaturing agents, such as 5 M guanidine hydrochloride or alkali, normalize the ionization of the tyrosyl residues. There is a good correlation between the spectrophotometric titration data and the results for the reactivities of the tyrosines in mesentericopeptidase towards tetranitromethane. The correlation is explained by the mechanism of nitration. Conclusions about the state of the tyrosyl residues and the three-dimensional structure of mesentericopeptidase are made.


Breathing mode of conformational fluctuations in globular proteins. Globular proteins in the native state are assumed to behave as continuous elastic spheres in the low frequency breathing motions. Reasonable values of Young's modulus E = 10(11) dyne/cm2 and the radius of the sphere ro = 20 A, yield a wave number of 26 cm-1 for the fundamental vibration of the sphere. The peak at around 30 cm-1 in the laser Raman spectra of native alpha-chymotrypsin and pepsin observed by Brown et al. might be assigned to the breathing motion which the native proteins undergo as continuous elastic bodies.


On the 3alpha-hydroxysteroid dehydrogenase from Pseudomonas testosteroni. The effect of denaturing agents. Highly purified preparations of the 3alpha-hydroxysteroid:NAD- oxidoreductase (E.C.1.1.1.50) from Pseudomonas testosteroni (ATCC 11996) which consist of two major isoenzymes, with traces of a third, have been split into two enzymatically inactive polypeptides A and B by the use of sodium dodecylsulphate, urea and guanidinium hydrochloride. Both polypeptides have a molecular weight of 25,000 +/- 2,500 as shown by thin-layer gel chromatography and ultracentrifugations. They differ, however, in charge as shown by electrophoresis on cellulose acetate strips in the presence of 8 M urea. Each of the isoenzymes, have molecular weight of about 50,000 and thus consist of two subunits. The presence of the three isoenzymes may be explained by the following combinations of the subunits, AA, AB and BB. Close to 100% of the original activity towards the three substrates, androsterone tetrahydrocortisone and desoxycholate could be restored within 24 h when the inactivated enzyme was diluted in order to remove the effect of the denaturant.


NMR investigations of proline and its derivatives. 4-Proton magnetic resonance parameters and structure of acetyl-proline amide. The proton magnetic resonance (PMR) spectrum of acetyl-proline amide in D2O solution has been analysed by computer simulation. The spectra of the cis and the trans isomers have been separated and their PMR parameters (chemical shift and coupling constants) are given. Vicinal coupling constants of the pyrrolidine ring are interpreted by means of a Karplus zone relation. The chemical shift effect of the anisotropy of both peptide planes is considered. It follows that both isomers are puckered with Cgamma in an endo position, but the cis isomer is more rigid than the trans isomer, which moreover undergoes a small interconversion of the Cgamma and Cdelta atoms between two extreme spatial positions. The dihedral angle phi has different values in both isomers. Thus, the dihedral angle between the two peptide planes is smaller in the trans isomer than in the cis isomer.


Frequency-dependent diffraction from enzymatic breathing modes. The intensity of the time-dependent Fourier transform of any macro-molecule which contains a cleft of the sort that exists in the protein lysozyme is derived. It is shown that there is a region of this transform in which this intensity varies nearly sinusoidally with time with a frequency equal to that of the macromolecule's breathing mode of vibration, and where, therefore, the diffracted power will be primarily at this single frequency. Observation of this power will allow the experimental determination of the frequency of this mode, which is expected to be much lower than those observable by Raman spectroscopy.


Studies on the conformation and interactions of elastin: nuclear magnetic resonance of the polyhexapeptide. Synthesis, proton magnetic resonance and carbon-13 magnetic resonance characterizations, including complete assignments, are reported for the polyhexapeptide of elastin, HCO-Val(Ala1-Pro2-Gly3-Val4-Gly5-Val6)18-OMe. Temperature dependence of peptide NH chemical shifts and solvent dependence of peptide C-O chemical shifts have been determined in several solvents and have been interpreted in terms of four hydrogen bonded rings for each repeat of the polyhexapeptide. The more stable hydrogen bonded ring is a beta-turn involving Ala1C-O--HN-Val4. More dynamic hydrogen bonds are an 11-atom hydrogen bonded ring Gly3NH--O-C Gly5, a 7-atom hydrogen bonded ring (a gamma-turn) Gly3 C-O--NH-Gly5, and a 23-atom hydrogen bonded ring Val6inH--O-C Val6(i+1). This set of hydrogen bonds results in a right-handed beta-spiral structure with slightly more than two repeats (approximately 2.2) per turn of spiral. The beta-spiral structure is briefly discussed relative to data on the elastic fiber.


Solid phase synthesis and some pharmacological properties of 8-D-homolysine-vasopressin and 1-deamino-8-D-homolysine-vasopressin. 8-DL-Homolysine-vasopressin and its 1-deamino derivative were synthesized by the solid phase method. The desired D-homolysine analogues were obtained by digestion of the mixtures with trypsin and isolation of the peptide components by ion-exchange chromatography. In agreement with earlier observations on vasopressins containing alpha, omega-diamino acids of D configuration the new analogues show very low pressor activities. However, the antidiuretic effects are surprisingly high, thus reversing the known activity trend and making the D-homolysine analogues highly selective antidiuretic agents.


Synthesis of the sequential polypeptide poly[Cys(Acm)-Ser-Phe-Glu-Glu] as a model for hydrolytic enzymes. To construct a possible model of hydrolytic enzymes, the sequential polypeptide H[Cys(Acm)-Ser-Phe-Glu-Glu]nOH, n = 3-110, was prepared by polycondensation of H-Cys(Acm)-Ser(But)-Phe-Glu(OBut)-Glu(OBut)-O Su/1-hydroxybenzotriazole. In a solid state the polypeptide material showed beta-conformation both before and after cleavage of t-butyl protecting groups. The pentapeptide unit was synthetized by the Merrifield method utilizing modifications as follows: Gel phase synthesis on less than 0.5% cross-linked copolystyrene (quasi dissolved state). Centrifugal reactor. Ddz-amino acids, deprotected by 5% trifluoroacetic acid/dichloromethane/15 min. 3-Nitrophthalic anhydride to suppress formation of false sequences. Continuous photometric control of the completion of all operations during synthesis and transesterfication, yielding Ddz-Cys(Acm)-Ser(But)-Phe-Glu-(OBut)-Glu(OBut)-OMe (0.827 g; 53%, m.p. 180-182 degrees).


Binding of pyridoxal 5'-phosphate to bovine serum albumin and albumin fragments obtained after proteolytic hydrolysis. Localization and nature of the primary PLP binding site. The binding of pyridoxal 5'-phosphate (PLP) to bovine serum albumin (BSA), and to large BSA fragments obtained after proteolytic hydrolysis, was investigated in order to study the structure of these fragments in relation to the albumin structure itself, and to get information about the PLP binding sites on albumin. From absorbance and circular dichroism spectra, combined with peptide mapping of the tryptic digests of the reduced PLP-protein complexes, it could be concluded that the primary binding site is localized with the NH2-terminal part of the albumin molecule. The COOH-terminal part contains one or more secondary sites. It appeared that in albumin and in the largest NH2-terminal fragment, the environment of the primary binding site is rather apolar in character. However, in the smallest NH2-terminal fragment this site is more exposed to the solvent. This suggests that the part of the peptide chain which is not common in both fragments has a stabilizing effect on the structure around the primary binding site.


Intrinsic viscosity of ovomucoid in random coil conformation. Ovomucoid is denatured by concentrated solutions of guanidine hydrochloride. The intrinsic viscosities of the glycoprotein in 6 M guanidine hydrochloride in the absence and presence of beta-mercaptoethanol were found to be 8.1 and 16.0 ml/g, respectively. Ovomucoid with disulphide bonds reduced exists in linear random coil conformation. However, the intrinsic viscosity of the randomly coiled protein was less than that predicted from the empirical equations describing the molecular weight dependence of intrinsic viscosities of random coil proteins in 6 M guanidine hydrochloride. On excluding the carbohydrate content of the protein, which is theoretically justified, the calculated intrinsic viscosity interestingly became closer to the measured one. The temperature dependence of the intrinsic viscosity of ovomucoid in linear random coil conformation was studied in the temperature range, 25-55 degrees. The features of the intrinsic viscosity-temperature profile are not comparable with those exhibited by other linear random coil proteins in 6 M guanidine hydrochloride.


[Influencing of acetylation and corticosterone biosynthesis through long-term pantothenic acid deficiency in rats]. The effect of different dietary intake of pantothenic acid (150;100;25 and 0% of the requirement) on the metabolism of rats was studied during 15 months. The ability of the adrenals for synthesis of corticosterone and the rate of acetylation of a sulfonamid (Sulfisomidin) were taken as parameters. The above mentioned parameters were influenced significantly already after two weeks and a pantothenic acid free diet containing the antagonist omega-methyl-pantothenic acid. With a 25% supply of pantothenic acid and without omega-methyl-pantothenic acid it lasted half a year until significant alterations of acetylation could be demonstrated. The synthetic ability of the adrenals for corticosteroids was significantly increased after a year in the 25% group. After the end of the study, this hyperfunctional state was followed by hypofunction, resulting in a significantly reduced ability of synthesis of the glands. Studies of this type were conducted to obrain basic informations for later experiments in human beings.


Metabolism of L-ascorbic acid in rats under in vivo administration of mercury: effect of L-ascorbic acid supplementation. 1. Rats toxicated with mercury showed drastic fall in growth rate and supplementation of L-ascorbic acid to these rats could not reverse this effect. The contents of L-ascorbic acid and of D-glucuronic acid in the urine of the toxicated animals were decreased which could be counteracted by subsequent L-ascorbic acid supplementation. 2. The concentration of L-ascorbic acid in the liver tissues of mercury toxicated rats was decreased markedly and administration of L-ascorbic acid to this group could raise the tissue reserve considerably. 3. Severe damages of the normal histological pattern of the kidney tissues of rats viz. cellular and glomerular degeneration were observed under mercury toxicity. 4. In the liver tissues of the mercury toxicated rats, the rate of L-ascorbic acid synthesis was reduced along with increased catabolism of L-ascorbic acid. Subsequent supplementation of L-ascorbic acid to these toxicated rats was, however, found to be effective in reversing these alterations almost to the basal level.


Presence of cellular retinol and retinoic acid binding proteins in human uterus. Human uterine cells contain two separate soluble proteins, one binding retinol and one binding retinoic acid with high specifity. This suggests that both retinol and retinoic acid may be required for normal uterine function.


Vitamin A alcohol and vitamin A palmitate transfer from ewes to lambs. The effects of pre-partum intravenous injections of vitamin A alcohol and vitamin  palmitate on vitamin A levels in the plasma and livers of newborn lambs and in colostrum were studied with twenty mature Romney ewes. Injecting ewes with 250000 IU of vitamin A alcohol significantly (P less than .05) increased vitamin A levels in the blood (77%) and livers (75%) of newborn lambs. Differences between effect of vitamin A alcohol and vitamin A palmitate on either blood or liver levels in lambs were not significant. Transfer of injected vitamin A to lamb liver was inefficient (0.37% for palmitate, 0.12% for alcohol). There was 52% more vitamin A in colostrum from alcohol-injected than from palmitate-injected ewes. Although consistent with a postulation of preferential mammary transfer of vitamin A alcohol, this difference was not statistically significant (P greater than .05).


Preparation, properties and metabolism of retinoic acid anhydride. A new analogue of vitamin A, viz., retinoic acid anhydride was prepared, for the first time, by the action of thionyl chloride on retinoic acid in benzene containing pyridine. The amhydride was charcterised by its chromatographic properties, elemental analysis, ultraviolet absorption, infrared and nuclear magnetic resonance spectral characteristics. The compound could be readily hydrolysed to retinoic acid both by acid and alkali treatments and reduced by lithium aluminium hydride to vitamin A alcohol (retinol). The spectral changes with antimony trichloride reagent were similar to those observed for retinoic acid. The metabolism of retinoic acid anhydride was found to be similar to that of retinoic acic. When administered either orally or intraperitoneally, the compound promotes growth in vitamin A-deficient rats. Time-course experiments revealed that retinoic acid anhydride is converted into retinoic acid by non-enzymatic hydrolysis and thereby exerts its biological activity. The biopotency of the anhydride was found to be nearly the same as that of the acid. A new method of preparing esters of retinoic acid employing retinoic acid anhydride as an intermediate, has been described.


Effect of hypervitaminoisis A on composition of chick cartilage. 1. Day-old chicks were fed a diet containing one mg of retinyl acetate per kg feed. One group was treated with 18.300 mug retinyl acetate/100 g of body weight/week, whereas the other group served as control. Retinol treatment did not affect weight gain during a 4-weeks observation period. 2. At the end of this period the animals were killed and epiphyseal cartilage of the tibiotarsus examined. Retinol excess decreased ash and hydroxyproline and increased glycosaminoglycans and uronic acid in dry, fat-free cartilage. Sialic acid and hexosamine contents of glycosaminoglycans were elevated without a great change in the proportion of glucosamine and galactosamine. 3. Activity of 5 enzymes degrading glycosaminoglycans was not affected by retinol excess. 4. In hypervitaminotic chicks, uptake of injected radiosulphate by cartilage tissue and incorporation into glycosaminoglycans were enhanced and breakdown retarded.


[Serum picture of vitamin A in healthy persons following a vitamin A palmitate loading]. After oral consumption of 150 000 U vitamin A-palmitate the serum of eight healthy men was hourly determined for vitamin A-concentration. Rapidly ascending to a maximum within three to four hours the concentration returned exponentially to its normal fasting level after 24 hours. The curve could be adapted to the BATEMAN-function. The velocity constants k1 and k2 were equal except for one case. These results were opposite to earlier results of patients with psoriasis vulgaris.


[Vitamin E concentration in blood and tissues of growing pigs fed on varying DL-a-Tocopherylacetate supplements]. The concentration of tocopherols in blood serum, liver and adipose tissue of growing pigs with different vitamin E supply was estimated gas-chromatographically. The animals were fed with a practical diet, supplemented with 0, 5, 15, 25 and 95 ppm dl-alpha-tocopheryl acetate (groups I-V). Based on a naturally vitamin E content of 7.4 and 8.6 mg per kg of the diet the control animals (group I) showed very low tocopherol concentrations of 0.5 mug per ml serum and about 1 mug per g tissue. No clinical vitamin E-deficiency symptoms were observed. The increasing alpha-tocopherol supplements raised the vitamin E contents in a proportional rate, and with high vitamin E supplies the highest quantities of tocopherols were stored in the adipose tissue. When the alpha-tocopherol content in the diet was raised by 1 mg, the concentration in the serum increased by 0.033 mug per ml, in the liver by 0.094 and in the adipose tissue by 0.129 mug per g, respectively (gamma = 0.99). This increase in the concentrations was strongly linear and can be interpreted by constant rates of absorption and retention of alpha-tocopherol in the present investigation. The growth of the pigs was no influenced by the different alpha-tocopherol supplements.


A review of children operated upon because of stenosis of the pelvo-ureteral junction. The authors report the late results of reconstructive surgery on stenosis of the pelvo-ureteral junction in children. 69 patients had been operated during 1965--1970. The results on clinical grounds were good: the infections and pain disappeared and the renal function was normal; however, the operation had no noticeable effect on the hydronephrosis.


Spontaneous rupture of the renal collecting system. Three cases of spontaneous rupture of the collecting system of the kidney are reported on. Organ-saving surgery was feasible in two of them. The etiology and treatment of spontaneous ruptures of the renal pelvis are discussed.


Youssef's syndrome.

Youssef's syndrome. A case of menouria (Youssef's syndrome) following a vesicovaginal fistula repair is presented. The patient had typical clinical features of cyclic hematuria, absence of vaginal bleeding and complete urinary continence. Diagnosis was established by cystoscopy, cystography and hysterosalpingography which disclosed the communication between the bladder and the uterine cavity. Surgical treatment was hysterectomy with the closure of the bladder opening. The authors quote similar cases reported in the literature and attention is also called to the fact that the first case of menouria was reported in the literature by Machado in 1935.


Vascular and morphological changes in the urinary bladder wall after irradiation. Twelve adult rabbits were used to study radiation-induced changes in the urinary bladder by angiographic, microangiographic, light microscopic and scanning electron microscopic methods. Angiographic, microangiographic and light microscopy examinations were performed on 2 animals in which the urinary bladders were not irradiated and on 4 animals in which parts of the bladders received high radiation doses of 60Co. The bladders irradiated in this manner exhibited advanced changes within a shorter time after irradiation than those in an earlier study. In this study a lower dose of irradiation was given over the entire bladder. Otherwise, the radiation changes were similar. Light and scanning electron microscopic studies were carried out on 2 normal and 4 irradiated bladders. In the latter, atrophy of the mucosa, epithelial desquamation, cellular atypisms and ulcerations were observed.


Granulomatous orchitis and spermatic granuloma. One case of granulomatous orchitis and three cases of spermatic granuloma are described and the clinical and pathologic features of the two syndromes are discussed. Since no certain diagnosis is possible on clinical grounds alone, it rests on the evidence of pathology. Both granulomatous orchitis and spermatic granuloma are of practical importance to the specialists, the first being apt to mimic tumours, and the second to tuberculous epididymitis. Histological study, possibly of biopsy specimens, permits to differentiate either process from malignancy and from tuberculosis with certainty. It is to be emphasized that in many cases of chronic epididymitis with clinical suspicion of tuberculosis careful histological search reveals spermatic granuloma. Since the processes under discussion are unresponsive to antibiotics, their therapy is surgical.


Experimental renal hypertension in rats. The present study has been concerned with blood pressure, renal functions and the microscopic changes of the kidney during permanent hypertension induced by unilateral ligation of the renal artery.


Peripheral small vessel involvement in chronic nephritides. Small cutaneous vessels, obtained by ear lobe biopsies, were studied in 14 patients with various chronic nephritides and in 10 normal controls. The capillaries in the group of patients with nephritis were found to undergo two main changes: thickening of the adventitia reticularis and perivascular cellular infiltration in an inverse ratio. This infiltration was seen to be made up of mononuclear cells and an increased number of mast cells in various stages of degranulation. Changes in the basement membrane as seen by electron microscopy are not constant. All of the above changes were absent in the controls and are similar to what has been described in previous studies in both experimental and spontaneous pathologic conditions, such as experimental hypertension, diabetes mellitus, scleroderma, rheumatoid arthritis, etc. Small vessel involvement in chronic nephritides could be part of a process of diffuse microvascular damage that includes the kidneys or it may be related to hypertension or to the biochemical changes which follow uremic and pre-uremic states.


Development of the optic nerve of the rat. Development of the rat optic nerve is studied electron microscopically. By marked bionecrosis, many neuroepithelial cells of the fissure portion of the optic stalk are eliminated immediately following optic cup formation. A small number of the surviving neuroepithelial cells forms the tubular optic stalk. The wall cells of the stalk elongate and proliferate to become a cluster of cells at the retrobulbar region. These cells differentiate into glia cells, astrocytes first and oligodendroglia cells second. Axons invade into the intercellular spaces of the elongating stalk cells which are differentiating into astrocytes. The invading axons are found first in the space at the basal portion of the stalk cells, or the peripheral zone of the optic nerve. Myelination occurs in the later stage of development. The fine processes of the oligodendroglia cells which surround groups of axons, eliminate the cytoplasm, and become the first myelin membrane.


Mechanism of "hypoglycemic" cataract formation in the rat lens. I. The role of hexokinase instability. Lenses from 100 gram albino rats remain clear and possess normal levels of Na+, K+, ATP, and hexokinase activity for 20 hours incubated in medium containing 12 mM glucose. Below 2.0 mM glucose, a cataract forms and there is an abrupt rise in lens Na+ and wet weight, a fall in lens K+, ATP, and hexokinase activity. The cataract is a thin lamellar opacity involving the anterior and posterior surfaces of the lens. If the lens is deprived of glucose for 48 hours, a nuclear cataract forms; the cortex between the superficial lamellar opacity and the nucleus being clear. This experimental cataract bears a striking resemblance to the hypoglycemic cataract seen in children. The thermal deactivation of hexokinase follows rapidly upon the depletion of its substrates (ATP and glucose) and is a primary factor leading to cataract formation. This was established by incubating the lens with 2-deoxyglucose, a competitive inhibitor of lens hexokinase. This compound blocks the entry of glucose into the glycolytic sequence. The cataract formed in its presence is identical morphologically and biochemically to that observed in a glucose-free medium. The effects of 2-deoxyglucose are prevented by increasing the glucose level; this rules out a direct toxic influence of 2-deoxyglucose and further supports the primary role of hexokinase thermolability in the etiology of this experimental cataract. This in vitro system appears to be an excellent experimental model for the study of the human hypoglycemic cataract.


Choline acetyltransferase and acetylcholine esterase activities in normal and biologically fractionated mouse retinas. Radiometric biochemical assays were carried out for choline acetyltransferase (ChAc) and acetylcholine esterase (AChE) in retinas isolated from 90-day-old pigmented mice. The retinas were either normal [(C57Bl (6) and rd/le controls)], or genetically receptorless (rd/le and C3H), or had markedly reduced inner layers due to postnatal treatment of C57Bl (6) mice with monosodium glutamate. The receptorless rd/le retinas were obtained from an inbred hybrid stock that provided littermate contols with normal retinas. Glutamate-damaged retinas were compared to retinas from untreated control animals. Receptorless C3H retinas were compared to both sources of normal retinas. Control retinas had specific activities (millimoles per kilogram dry weight per hour) of 36.5 to 38.5 for ChAc and 2,180 to 2,350 for AChE and total activities per retina (nanomoles per hour) of 23 to 26 for ChAc and 1,360 to 1,160 for AChE, with the higher total values coming from slightly heavier rd/le controls. Receptorless retinas had 44 to 48 times the ChAc specific activity of those from glutamate-treated animals and had 2.4 to 2.5 times that of retinas from control animals. They had five to six times the AChE specific activity of retinas of glutamate-treated animals and 2.4 to 2.5 times that of controls. On a total activity per retina basis, receptorless rd/le retinas had 81 per cent of the ChAc activity and 66 per cent of the AChE activity of those from littermate controls and receptorless C3H retinas had 97 per cent and 98 per cent of the total ChAc and AChE activity of the C57Bl (6) controls, but only 91 per cent and 82 per cent of the same total activities in the heavier rd/le controls. The data are consistent with the view that both enzymes are normally more concentrated in the inner than outer retina, with the disparity being more marked for ChAc.


Arachidonic acid-induced elevation of intraocular pressure and anti-inflammatory agents. Arachidonic acid, a precursor of prostaglandin E2 subconjunctivally injected into rabbit eyes in concentrations of 0.8 to 5 per cent, produced a dose-related rise of intraocular pressure (IOP) similar to the one observed after topical administration of PGE2 in concentrations of 0.001 to 0.1 per cent. Indomethacin, a nonsteroidal anti-inflammatory agent, had an inhibitory effect when administered systemically or topically prior to arachidonic acid. Dose-response relationships were demonstrated by topical and oral administration of Indomethacin which, as expected, had no effect on PGE2. Dexamethasone did not exert any inhibitory effect on the increased IOP following arachidonic acid administration. Indomethacin applied topically readily penetrated into the aqueous humor in concentrations considerably above those appearing in the plasma, which justifies the use of this route of administration. Since prostaglandin (PG) appeared to be implicated in ocular inflammation, these findings underline the specificity of action of Indomethacin and suggest its use in the topical treatment of ocular inflammation.


The circadian rhythm of the intraocular pressure in the New Zealand White rabbit. Most physiologic functions in man as well as in animals have been shown to have a circadian (approximately 24 hour) rhythm. It has been found in both the normal and glaucomatous human eye that the intraocular pressure, which is one of these circadian functions, varies considerably over a 24-hour period. Because of the extensive use of the rabbit in glaucoma research, a detailed study of the intraocular pressure over a 24-hour period was undertaken. Using hourly applanation tonometry for 25 consecutive measurements in ten New Zealand White rabbits (20 eyes), a circadian rhythm of the rabbit intraocular pressure was found. The pressures were lowest at night and rose to their highest values during the day. In addition, the data suggest that the maximum intraocular pressure may be biphasic with maximum values occurring between 0800 and 1100 and 1600 and 1900. Therefore, studies involving the New Zealand White rabbit must take into consideration these 24-hour pressure changes when intraocular pressure measurements are made.


Note on the distribution of iodine-123-labeled indocyanine green in the eye. XVIII. Indocyanine green was excitation labeled with radioactive iodine-123 and the distribution of the labeled dye in the eye structures of animals was determined.


Electron microscopic examinations of a conjunctival squamous cell carcinoma before and during beta-irradiation. An electron microscopic study was performed on a conjunctival squamous cell carcinoma in an 82-year-old man. Biopsies were taken before and during beta-irradiation and the morphologic features of nonirradiated tumor cells were compared to those after application of 10,000 rad. There occur striking changes in the nucleus and the cytoplasm after irradiation. The nuclei show hypertrophic and electron-dense nucleoli as well as altered chromatin structures. The cytoplasm of many cells appears destroyed and contains numerous vacuole-like structures, as well as swollen mitochondria. It is of interest that numerous normal lymphoid cells were present within the irradiated tumor.


A quantitative analysis of extraocular muscle cooperation and squint. The mechanical properties of human extraocular muscles have recently been described. This allows one to use the force-balance equation of mechanics to solve for the complete mechanical state of all six extraocular muscles and the passive orbital tissues in any eye position. This includes each muscle's force, length, innervation, and unit action vector, which describes how its force is distributed to act horizontally, vertically, and in torsion. Most important, this calculation method allows one to predict the tropias that occur in an eye subject to any imaginable form of peripheral pathology. It also permitts, by calculation, an estimation of the correction that might be expected from any sort of muscle surgery. The tight lateral rectus syndrome is used to illustrate the application of the method in diagnosis and surgery. It also offers, for the first time, a quantitative estimate of the multitude of ways in which muscles can interact and interfere with each other when they hold the globe. Two of the results are interesting: because muscles have different lengths and sizes, their innervational participation in a movement can appear to be quite different than their mechanical participation. From an innervational standpoint, the vertical recti and obliques participate equally in vertical gaze. Muscles interfere with each other a good deal and necessitate changes of innervation to counteract these cross-couplings. This causes unexpected dependencies of innervation on eye position and leads, for example, to the fact that the superior rectus innervation in up gaze is just as large in adduction as in abduction.


Genetic analysis of indices of corneal power and corneal astigmatism in human populations with varying incidences of strabismus. Heritability estimates for corneal power were found to be high and similar for two populations which differed in their incidence of esotropia. This similarity suggest (1) that genetic differences for corneal power do not contribute to the difference in heritability for spherical refractive error reported for these populations and (2) that this character is not a critical variable contributing to the pathophysiology of esotropia. Heritability estimates for corneal astigmatism were, in most cases, rather low. The pattern of population and sex differences among heritability estimates was consistent with those previously reported for cylindrical refractive error. These population differences in heritability suggest that they contribute to population differences found for cylindrical refractive error.


Studies of aqueous humor dynamics in man. IV. Effects of pilocarpine upon measurements in young normal volunteers. The acute effects of topical pilocarpine 4 per cent, administered to one eye, have been studied in replicate experiments in young volunteers. One hour after medication administration the intraocular pressure was significantly lower. The magnitude of the reduction exceeded that predicated from the significant increase of true facility of outflow. This is explained by the observation of a significant reduction of calculated aqueous humor flow. Pilocarpine caused a significant increase of pseudofacility, a clinically useful drug effect not previously reported. One hour after medication administration, measured episcleral venous pressure was not different from the pretreatment level.


The characterization of the hexokinases in several tissues of the calf eye. Several tissues from the calf eye were studied so as to determine the characteristics of the hexokinases in each tissue. The corneal stroma, sclera, and vitreous body are devoid of measurable hexokinase activity. The tissue specific activities decrease in the following order: retina, ciliary body, corneal endothelium, lens capsule-epithelium, corneal epithelium, and lens cortex-nucleus. Each tissue possesses Types I and II hexokinase in varying proportions in the soluble and insoluble fractions; latent hexokinase is Type I in all tissues except the retina in which both Types I and II are found in the latent fraction. No hexokinase Type IIa, III, or IV is found in any ocular tissue. Michaelis constants for glucose and MgATP= are similar to those found in extraocular tissues. Except for retinal hexokinase, ocular hexokinases are quite similar to extraocular hexokinases. The activity of retinal hexokinase varies greatly and abruptly with time and with change in buffer composition; in the absence of Na2EDTA, glucose, and -SH compounds, there is a rapid deactivation of hexokinase and a shift of the soluble to the insoluble form. The relevance of these findings to glycolysis in each tissue is discussed.


Contrast and electrolyte dynamics of the intravenous pyelogram. II. Disparities in serum and urine concentrations of meglumine and anion. Intravenous or intra-aortic injections of meglumine iothalamate in dogs indicate a slightly different tissue distribution and excretory pattern of the meglumine cation and the iothalamate anion. Differences in serum and urinary concentrations of these ions suggest some cellular penetration of the meglumine anion. In addition, there seems to be some evidence for both tubular absorption and tubular excretion of meglumine as a minor component in the renal excretion of this ion. No significant differences could be demonstrated for either urinary load or concentration when the sodium salts of iothalamate were compared to the methylglucamine salts.


Failure to induce hypersensitivity reactions to opaque contrast media analogs in guinea pigs. In a further exploration of idiosyncratic reactions to injections of contrast media, a systematic study of immediate or delayed hypersensitivity in guinea pigs injected with contrast media analogs was performed. No evidence of immediate or delayed hypersensitivity could be ascertained to either contrast media analogs alone, or analogs bound to protein carriers. This does not represent conclusive evidence against the notion of antibody formation as a factor in the production of some adverse reactions, but makes such a pathogenesis less likely.


Intravenous cholangiography in different degrees of common bile duct obstruction. An experimental study in the dog. A total of 83 cholangiograms was performed in three cholecystectomized dogs equipped with Thomas cannulas through which complete and different degrees of incomplete common bile duct obstruction were produced. With incomplete common bile duct obstruction, the iodine concentration in the bile necessary for radiographic visualization of the common duct was always obtained for all three tested iodipamide dosages of .3, .6, and 1.2 ml/kg, infused over 30 minutes. The largest dose resulted in the highest biliary iodine concentrations. With increasing obstruction, an increasing delay of the biliary iodipamide excretion was noted. With complete common bile duct obstruction the iodine concentration in the bile necessary for radiographic visualization of the common duct was never obtained, even with an iodipamide dose increased to 1.8 ml/kg and/or prolongation of the contrast material infusion time from 30 minutes to 2 and 6 hours. Nevertheless, the highest biliary iodine concentration in complete common bile duct obstruction resulted with the largest iodipamide dose (1.8 ml/kg) and the shortest infusion time (30 minutes).


Toxicity studies of coronary arteriographic media in dogs. Sequential injections of different contrast material in the canine coronary artery were performed while ventricular pressure and EKG were recorded. Larger volumes of contrast material caused more fibrillation and more drop in pressure. Preliminary myocardial infarction increased pressure effects. Diatrizoate methylglucamine (Renografin-76) caused more fibrillation and lowering of ventricular pressure than iothalamate or metrizoate Coronar. Calcium lessened the ventricular pressure depression from iothalamate.


A stereoradiographic technique and its application to the evaluation of lung casts. Stereoradiographs have been used on occasion for three-dimensional reconstruction and measurement of objects in radiology and radiotherapy. The lack of a good stereoradiographic technique has limited the uses of steroradiographic exposures. In this paper, the principle of the double-image is outlined and a method of applying this principle to stereoradiographic exposures is developed. A computer program has been developed from geometrical considerations to analyze the stereobronchogram and to calculate the dimensions of the objects in question. The applications of this technique are discussed and its use in evaluating lung casts is described.


The endoscopic intrahepatic cholangiogram. Clinicopathologic correlation with postmortem cholangiograms. Endoscopic retrograde cholangiography (ERC) allows visualization of the entire biliary tree. The cholangiographic appearance of the intrahepatic bile ducts has received relatively little attention. This postmortem study was performed to define cholangiographic alterations produced by disease and to aid in the recognition of pathologic intrahepatic cholangiographic patterns produced by ERC. Intrahepatic cholangiographic patterns in the normal biliary tree, hepatic cirrhosis, hepatic infiltrative processes, and hepatic mass lesions are presented.


The use of pedicled omentum in the repair of large vesicovaginal fistulas. Experimental work in dogs. Large vesicovaginal fistulas involving most of the trigone were created in eight dogs. Three weeks postoperatively, pedicled omentum was insinuated between the open bladder and vaginal defects. Bladder continuity was present at 2 weeks and epithelization was complete at 3 weeks postoperatively. There was little morbidity and no mortality.


Computer analysis of factors associated with thrombus formation observed on pullout angiograms. Preliminary communication. A prospective study was instituted to determine both the incidence of postcatheterization arterial thrombus formation and the possibility of a statistically significant correlation between predetermined parameters and the incidence of arterial thrombosis. Pullout angiograms and 12 recorded variables from 176 procedures were studied. Postcatheterization arterial thrombus formation was demonstrated in 9 cases (5%). Statistical analysis by computer showed a statistically significant relationship between 4 factors and postcatheterization thrombosis, viz. catheter/artery ratio, age, catheter diameter, and number of puncture attempts. Total elapsed time of the procedure was not found to be a statistically significant variable. These variables are integrated into a postulate to explain the pathogenesis of postcatheterization thrombus formation seen on pullout angiograms.


An absorbable intravasal stent and a silicone intravasal reversible plug. Report of experiments on animals. The high failure rate of vasovasotomy to restore fertility in vasectomized men prompted this investigation using guinea pigs as the experimental animals. The vasa were divided and absorbable intravasal stents were inserted into the lumens of the vasa at the site of anastomosis. The success or failure to secure patency and reestablish fertility was appraised by histologic sections, vasograms, semen analyses, and breeding tests. A second group of animals had silicone plugs equipped with a detachable central pin placed in both vasa. The design of this procedure was to produce an occlusive azoospermia which might be reversed by removing the central pin. Similar tests were used to establish the effectiveness of this reversible device in producing a temporary sterilization. The procedures were controlled by sham operations and insertion of plugs without pins.


In vitro measurement of respiration of choroid plexus cells in communicating hydrocephalus. Communicating hydrocephalus occurs as a result of inappropriate CSF production in the circumstance of diminished absorption. Ventricular enlargement does not progress as rapidly as the measured normal production of CSF would suggest. Thus, compensatory mechanisms must exist to respond in some manner to the altered pathophysiology. In this experiment the metabolic activity (O2 consumption) of the choroid plexus cells in animals with communicating hydrocephalus was compared with that of normals. The modified Cartesian diver technique of Zeuthen13 was employed. These preliminary measurements show that the metabolic activity of the choroid plexus cells was the same in hydrocephalic animals and normals. Response to experimentally induced increased CSF pressure also showed no difference.


Control of oxalate urolithiasis by DL-alanine. Oxalate urolithiasis in male rats was experimentally induced by feeding a basal diet composed of Purina laboratory chow and 3 per cent glycolic acid. When this basal oxalate calculus-producing diet containing 10 per cent alanine was fed to rats, the incidence of oxalate urolithiasis was markedly reduced. Moreover, when Purina laboratory chow containing 10 per cent alanine was fed to rats which had been on the calculi-producing basal diet for 4 weeks, it appeared that most uroliths were dissolved. Excess intake of alanine increased the concentration of alanine in urine and this apparently aided in the prevention and treatment of urolithiasis.


The composition of the radiologic report. In order to understand and evaluate fully the composition of the radiologic report, an experiment was performed in which eight readers each read the same 100 chest radiographs. The reports were dissected into individual statements, each of which was analyzed for accuracy, statement type (descriptive or etiologic), confidence, and specificity. In addition, each report was evaluated for stylistic factors of succinctness, orderliness, and the use of supplemental comments. Detailed analysis showed the radiologic report to be a series of largely descriptive statements in which confidence level, specificity, and orderliness were associated with the presence of errors in film interpretation. These factors can serve as important markers for identifying error-laden films. The use of specific, etiologic diagnoses in these film readings was limited. The composition of the report was not related to the length of radiologic training beyond the first year of residency. The implications of these findings concerning report composition in light of present day radiologic practice and new, automated radiologic reporting systems were discussed.


Saturation kinetics of iopanoate in the dog. Experiments were carried out in dogs with a modified Thomas cannula in the duodenum through which the common bile duct could be catheterized. Constant intravenous infusion of sodium iopanoate at different infusion rates greater than the apparent excretion maximum revealed linearity of the blood concentration with time above a threshold concentration. When the slopes of the blood curves were plotted against the known infusion rates, a straight line relationship was obtained. The X axis intercept of this straight line represents an apparent transport maximum. This value obtained from the X axis intercept matched closely with the observed excretion maximum determined from bile and urine collection. The slope of this same line equals the inverse of the volume of distribution of the drug. Although previous workers have failed to appreciate an apparent transport maximum for iopanoate, the current studies clearly demonstrate that iopanoate is excreted by a saturable mechanism. Using this technique the apparent transport maximum for iopanoate was evaluated at high and low rates of taurocholate replacement to evaluate the quantitative effect of bile salt on the apparent transport maximum. A five-fold increase in taurocholate replacement led to an average 40% increase in the apparent transport maximum of iopanoate without effecting its volume of distribution significantly.


Effect of transient hydronephrosis on subsequent compensatory renal growth. Apparent augmentation of renal growth occurs in kidneys made temporarily ischemic, or partially obstructed, before contralateral nephrectomy. The study herein was undertaken to investigate the effect of acute complete ureteral occlusion on a subsequent course of renoprival hypertrophy and hypoplasia. Three groups of animals were established. Animals in Group 1 underwent high ligation of the right ureter. Animals in Groups 2 and 3 underwent exposure and manipulation of the right ureter. Forty-eight hours later, animals in Group 1 underwent deligation and contralateral nephrectomy, animals in Group 2 underwent contralateral nephrectomy, and animals in Group 3 underwent sham operation. Animals were then selected 6 and 17 days after their second operative procedure and decapitated; the right kidneys were removed and underwent analysis with respect to wet and dry weight, total RNA, DNA, and protein content. At 6 days and at 17 days, animals in Groups 1 and 2 demonstrated no difference between these groups, although the remaining kidneys from animals in Group 1 and Group 2 were significantly larger than Group 3 animals. When compared to Group 3 animals, wet renal weight at 17 days had increased by 41 per cent, total bulk RNA had increased by 26 per cent, and total bulk DNA had increased by 33 per cent. The data support the clinical impression that transient, complete ureteral obstruction is well tolerated by the normal kidney, and that the metabolic response to obstruction does not hinder recovery after release of obstruction.


The recovery of function of chronically obstructed and infected ureters. Twelve experiments in which intraluminal ureteral pressure, ureteral diameter, aortic blood pressure, and respirations were measured, and in which ureteral wall tension was calculated, were performed on 11 female dogs. These experiments demonstrated that the impairment in ureteral function caused by chronic obstruction and infection could be reversed after surgical correction of the obstruction in conjunction with antibiotic therapy.


Changes in the composition of urinary tract stones. An increase in the average calcium oxalate content and decrease in average calcium phosphate content of stones received for analysis has been noted in a 9-year study. These changes appear to be due to a progressive increase in the number of patients with noninfected upper urinary tract stone and to the gradual elimination of phosphatic stones as a result of improved diagnosis and treatment. Some of the conditions associated with calcium phosphate stones are examined, particularly primary hyperparathyroidism, renal tubular acidosis, and medullary sponge kidney. These results further emphasize the importance of calcium oxalate in idiopathic stone disease and the need for a fuller understanding of the factors influencing calcium oxalate crystallization.


The inhibition of dimethylnitrosamine-induced renal tumorigenesis in NZO/Bl mice by orchiectomy. In NZO inbred mice a single dose of dimethylnitrosamine (DMN) induced kidney tumors in males only; females did not develop kidney tumors even when the dose of DMN was doubled. Orchiectomy before DMN injection abolished the kidney tumor response in male mice. These observations imply that androgens are essential for renal carcinogenesis by DMN in the NZO mouse.


Studies on the feasibility of urinary bladder evacuation by direct spinal cord stimulation. I. Parameters of most effective stimulation. In 30 female dogs, spinal cord stimulation was tested to find the optimal parameters producing good voiding and, hopefully, total bladder emptying. Twelve different electrodes or application modifications were examined. Variable frequencies, stimulus duration, and voltages were applied. Search of the site of highest detrusor response (micturition center) was easily identifiable. It became obvious that electrode design was not of critical importance: the responses were basically the same whether we used the wrap-around electrode, which stimulates an entire level, or the coaxial electrode which theoretically limits the current spread around its minute exposed tip. The stimulation parameters that gave the best results were: 2 to 5 volts; frequency: 10 to 15 cps; duration 1 msec. The site of highest detrusor response was round vertebral level L5 1/2, corresponding to cord level S2-4. Generally, no voiding was obtained because of too high sphincteric contraction during stimulation; it appeared that a sphincteric center overlaps the micturition center in either direction. To achieve successful voiding during stimulation, a separation of these two centers with selective stimulation of the detrusor center is necessary, eleiminating sphincteric contraction.


Studies on the feasibility of urinary bladder evacuation by direct spinal cord stimulation. II. Poststimulus voiding: a way to overcome outflow resistance. Electrical stimulation of the spinal cord micturition center is effective in inducing strong detrusor contraction. Simultaneous sphincteric contraction, however, prevents voiding from occurring. At the end of stimulation a sharp drop in sphincteric activity takes place, with a concomitant and slower drop in intravesical pressure--resulting in a short poststimulus phase where bladder pressure exceeds urethral resistance and a spurt of urine is passed. This brief period was put to use by applying a train of short stimuli of 1-sec duration and separated by 1-sec intervals, following which complete bladder emptying could be obtained in an average time of 30 sec. This poststimulus voiding was constantly observed after high spinal cord transection. It can be accomplished without the need for neurectomy, sphincterectomy, or drug-induced muscular blockade.


alpha-Adrenergic (norepinephrine) effect on antidiuretic hormone activity. The mechanism by which norepinephrine (NE) inhibits the antidiuretic activity of anti-diuretic hormone (ADH) was studied in anesthetized normal and ADH-deficient rats. NE infusion increased aortic blood pressure and resulted in increased urine volume and sodium and potassium excretion without changes in creatinine excretion. p-Aminohippuric acid excretion did not change in normals and rose (from 34 +/- 9 to 51 +/- 11, P less than 0.025) in ADH-deficient rats. Urine osmolality fell in normals (from 363 +/- 29 to 298 +/- 42, P less than 0.05) but not in ADH deficients (from 332 +/- 29 to 363 +/- 26, p less than 0.1). ADH-deficient rats given 50 muU per kg-min of ADH intravenously responded with antidiuresis, including hyperosmolality (from a range of 225 to 240 to a range of 332 to 333, P less than 0.025). When NE was infused at 0.5 mug per kg-min, no inhibition of hyperosmolality was noted but natriuresis and augmented volume excretion occurred. At 1.5 mug per kg-min, NE completely reversed the hyperosmolality induced with ADH. The results suggest that NE-induced pressure diuresis reduces osmolality only when ADH is present in the system and so by competitive inhibition of ADH action on the renal tubule.


Compensatory renal hypertrophy in male dwarf mice. The Snell dwarf mouse (dw/dw) is the result of a single recessive gene that is not sex-linked. The dwarfism is caused by the congenital deficiency of growth hormone, thyrotropin, and prolactin. This unique genetic model was selected to study compensatory renal hypertrophy. Compensatory renal hypertrophy occurred to a significant degree (P less than 0.01) in the unilaterally nephrectomized dwarf mutant (dw/dw), normal heterozygous (dw/DW), and normal homozygous (DW/DW) male littermates. There was no significant difference in the amount of compensatory renal hypertrophy between the groups (P greater than 0.5). These results suggest that three of the anterior pituitary hormones are not necessary for the compensatory hypertrophy response to unilateral nephrectomy.


Immune responses to soluble tumor antigens in various stages of tumor growth. Mice immunized to a syngeneic methylcholanthrene-induced fibrosarcoma by surgical removal of a growing tumor showed specific resistance to challenge with that tumor. An in vivo response to tumor-specific antigens solubilized by hypertonic potassium chloride was measured by 24-hr footpad swelling response in mice immunized to the tumor from which the antigens were extracted. Normal mice given an injection of 5 X 10(6) tumor cells showed significant 24-hr footpad swelling response to solubilized tumor antigens (solubilized from the tumor line injected) 10 days after tumor transfer. The responses were negative 28 days after tumor transfer when tumor diameters were in excess of 1.0 cm. Surgical removal of tumor at this point promptly restored footpad responses within 24 hr. The footpad response is undoubtedly a complex situation. However, continued study of this response correlated with other measures of in vitro with in vivo tumor immunity holds promise not only of understanding the nature of the footpad response itself but also of unraveling some of the immunologic mechanisms of host-tumor interactions.


The effects of 5-fluorouracil on prostatic DNA synthesis. A new animal model has been developed for studying the effects of nonhormonal drugs on the androgen-induced growth of the rat prostate. The antimetabolite 5-fluorouracil caused a 60 per cent reduction of the rate of prostatic DNA synthesis in androgen-stimulated castrate rats. This drug did not decrease the size of the prostate in normal intact animals and did not exhibit significant antiandrogenic activity. Its distribution is primarily in the acid-soluble fraction of the total prostatic homogenate.


Lack of effect of spironolactone on male genital development. Spironolactone, which has been shown to have antiandrogen action in mature male rats, was given to pregnant rats from day 14 of pregnancy until delivery in a dose equivalent to the 400-mg adult human regimen. The male members of the resultant litters were then dissected and examined for evidence of pseudohermaphroditism. No evidence of hypospadias, malformation of Wolffian ducts, or narrowing of anogenital distances was found. In the experimental model used, no evidence of an antiandrogen action of spironolactone was found.


Serum, renal, and urinary lysozyme levels after hypohysectomy. Hypophysectomy is known to cause a rise in the renal lysozyme levels and atrophy of the proximal tubules of the kidney. The present study describes the relationship of serum, urinary, and renal lysozyme levels in hypophysectiomized animals. The renal lysozyme level continued to rise during the first 4 weeks after hypophysectomy and then remained constant while the serum level increased immediately after hypophysectomy and plateaued. Hypophysectomy did not produce lysozymuria for the time periods used in these experiments despite obvious tubular atrophy by the end of the 1st week after hypophysectomy. These data suggest that tubular atrophy must progress to a severe stage before a lysozymuria is produced. Thus the absence of urinary lysozyme activity does not exclude the possibility of proximal tubule injury.


Demonstration of infectious DNA in transformed cells. III. Correlation of detection of infectious DNA-protein complexes with persistence of virus in simian adenovirus SA7-induced tumor cells. Primary tumors induced in newborn hamsters by simian adenovirus SA7 were investigated in transfection experiments. Infectious DNA-protein complexes were readily detected in both the supernatant and pellet fractions obtained by a modified Hirt extraction procedure; DEAE-dextran was required for infectivity to become manifest. Infectivity could be abolished by exposure to DNase, but it was unaffected by SA7-specific antiserum or RNase, and only partially inactivated by trypsin treatment. SA7 tumor cells serially passaged either in tissue culture or in hamsters yielded infectious DNA complexes much less frequently and appeared to evolve into nonyielder cell lines. When large numbers of cells were lysed, intact virus could be recovered from all the primary tumors and from some of the subcultured cell lines. There was a correlation between the persistence of complete virus and the presence of infectious DNA-protein complexes. When the tumor cells carried very small amounts of intact virus, infectious DNA complexes could still be detected; when virus could no longer be detected in the tumor cells, infectious DNA complexes could no longer be found. The results suggest that a portion of the infectious DNA moieties exists as viral DNA-protein complexes in the tumor cells.


Development of Amsacta moorei entomopoxvirus in ovarian and hemocyte cultures from Estigmene acrea larvae. Primary ovarian and hemocyte tissue cultures prepared from Estigmene acrea larvae were infected with Amsacta moorei entomopoxvirus. Infection of cultures was achieved with either purified virus or virus-containing culture medium from infected cultures. Virus replication and formation of virus-containing inclusions (VCI) were similar to that normally observed in vivo except that fewer virions appeared to be occluded in VCI.


RNA polymerase activity of Amsacta moorei entomopox virions. Optimum conditions for in vitro RNA synthesis by the entomopoxvirus from Amsacta moorei, except for a temperature optimum of 26 degrees, were similar to those reported for vaccinia. Incorporation of 3H-ATP in the presence of CTP, GTP and UTP was significantly inhibited by actinomycin D; incorporation of 3H-ATP alone was not. The products formed by incorporation of 3H-ATP alone or with the three other nucleotides contained polyadenylic acid sequences. The sedimentation coefficient of the 3H-ATP-labeled product formed in the presence of CTP, GTP and UTP was reduced from 8-23S to 3-5S after RNase treatment. The product formed from 3H-ATP alone had an apparent sedimentation value of 3-5S.


Arbovirus antibodies in children of rural Guanabara, Brazil. School children living in Guanabara State, Brazil, have been tested for evidence of infection with 16 arboviruses. 3 percent were positive, and in every instance the positive reaction was attributable to St. Louis encephalitis (SLE) virus. Evidence of familial aggregation was observed.


The isolation of cricket paralysis virus from the emperor gum moth, Antheraea eucalypti Scott, and its infectivity towards a range of insect species. Three virus-like particles have been isolated from diseased larvae of Antheraea eucalypti. Serological tests established that one of them was indistinguishable from cricket paralysis virus (CrPV). CrPV isolated from crickets and from Antheraea were cross-infectious, and crickets could acquire lethal doses of the virus by feeding on infected Antheraea larvae. In addition to two species of Teleogryllus, three other species of Orthoptera and nine out of ten species of Lepidoptera tested were susceptible to the virus. It is suggested that CrPV may have originated amongst the Lepidoptera and has been acquired by the field cricket by infectious passage along a food chain.


Lyapunov Redesign of Model Reference Adaptive Control System for long term ventilation of lung. A lyapunov redesign of Model reference adaptive control system for a long term, automatically regulated, ventilatory system is presented. A fixed resistance-capacitance RC analog lung model is used to generate a desirable (reference response) alveolar pressure. The instantaneous difference in alveolar pressures between the patient and its model is fed to an adaptive controller. The controller is designed to adjust the patient's inflating pressure in such a way as to reduce the instantaneous difference in the alveolar pressures to zero. The adaptive control system described can be implemented provided the patient's alveolar pressure is continuously measurable. Unfortunately, this measurement is impossible to realize; therefore, a method to estimate the continuous alveolar pressure of the patient is to be developed. This estimation is achieved indirectly from the identification process of the patient's respiratory parameter. The same Lyapunov redesign is used in this identification process. Digital simulation of the control of the patient's inflating pressure and the identification process, as well as the simulation of the combined system, were performed. The result has demonstrated the ability of this adaptive system to perform in a fast and stable manner.


Selective testicular lesions resulting from continuous prolonged intake of minimal amounts of ethionine. A threshold dose of ethionine was determined which, when administered continuously for up to 10 months, produced testicular lesions in rats but did not interfere with body growth and did not produce histologic lesions in the pancreas. In the liver, only mild fatty changes were observed. Interstitial cells of the testis showed hyperplasia at three to four months, followed by dedifferentiation of these cells in the later stages of the experiment. Complete atrophy of tubules was seen in most segments, but even at 8 and 10 months of ethionine ingestion, well-defined segments revealed intact spermatogenesis in all animals. The hypothetical emergence of a mutant ethionine-resistant spermatogonial stem cell is discussed. When ethionine was withdrawn from the diet at 10 months, incomplete regeneration of tubular epithelium was seen two months later, but the interstitial cells remained of the nondifferentiated type. Fatty changes in the liver, comparable to those observed in male ethionine-treated animals only after castration, are likely to have resulted from dedifferentiation of Leydig cells with concomitant testosterone deficiency. Rats receiving smaller doses of ethionine showed fatty change in the liver although no testicular lesions were recognizable. It is possible that ethionine interfered with synthesis of testosterone before testicular lesions could be demonstrated by light microscopy.


Effect of triiodothyronine on chick embryo heart cells maintained in tissue culture. The effects of L-triiodothyronine (T3) on heart cells were studied in chick embryo heart cells maintained in tissue culture. T3 at a concentration of 3 x 10(-7) M had no effect on the contraction rate of these cells, either acutely or after 24 hr. On the other hand, T3 in concentrations as low as 3 x 10(-9) M stimulated both 2-deoxy-D-(1-3H) glucose uptake and lactic acid production. The effect of T3 on both deoxyglucose uptake and lactic acid production was noticed only after a lag period. Lactic acid production was measured again after removal of T3 from the media, and was found to remain elevated for at least an additional five days.


In vitro cortisone sensitivity of in vivo cortisone-resistant thymocytes. Thymus cells from untreated or hydrocortisone-treated mice were cultured for 20 hr in the presence or absence of a water-soluble glucocorticoid, hydrocortisone sodium succinate. By two independent assays of cell viability or function, virtually all thymocytes from untreated hosts were inactivated by hydrocortisone sodium succinate, whereas most, but not all, thymocytes from hydrocortisone-treated hosts were inactivated. Thus, the thymocytes which survive after treatment of the animal with glucocorticoids are only partially resistant to the effects of glucocorticoids in vitro.


Viability of Vibrio cholerae biotype El Tor and of cholera phage on vegetables. Different vegetables were contaminated with sewage water containing large amounts of El Tor vibrios, and the viability of these vibrios was studied under defined conditions of storage. During the dry season (summer) in Jerusalem, the El Tor vibrios survived for up to 24 hr on parsley, 24 to 30 hr on tomatoes and carrots, 24 to 48 hr on cucumbers, peppers and okra and two to three days on lettuce, when the vegetables were stored at room temperature. The survival time was longer during the rainy season or during storage of the vegetables in a refrigerator. It was also prolonged on damaged vegetables. The El Tor vibrios survived for only a few hours on vegetables exposed to sunlight. The El Tor vibrios survived for 12 to 24 days in experimentally contaminated sewage water, and for up to 10 days in sewage-contaminated soil. The El Tor bacteriophage persisted for up to 36 days on phage-contaminated vegetables.


Cesarean section in a patient with a mitral valve prosthesis. A successful cesarean section performed in a 24-year-old woman with rheumatic heart disease and a Starr-Edwards mitral valve prosthesis is reported. In the 33rd week of pregnancy, previous warfarin sodium therapy was discontinued and dipyridamole therapy instituted. Successful pregnancy and cesarean section in patients with mitral valve prostheses are possible with this regimen.


"True agonadism" and its relation to other forms of sex reversal in males. In a phenotypic (XY karyotype) eunuchoid female aged 24, external genitalia were represented by completely fused underdeveloped scrotolabial folds and a 1-cm-long phallus with phallic urethra. At laparotomy, only rudimentary fallopian tubes and rudimentary wolffian ducts and wolffian body, but no testes, epididymis, uterus or vagina, were found. The patient fulfills the criteria for "true agonadism." This syndrome is considered a distinct form of a wider category of male pseudohermaphroditism, which results from sudden complete testicular arrest taking place not earlier than the second half of the third month of embryonic development.