Effect of insulin-glucose infusions on plasma glucagon levels in fasting diabetics and nondiabetics. The effect of the intravenous infusion of insulin plus glucose on plasma glucagon levels was studied in hyperglycemic fasting adult-type and juvenile-type diabetics and compared with fasting nondiabetics. Adult-type diabetics were given insulin for 2 h at a rate of 0.03 U/kg-min, raising their mean insulin to between 25 and 36 muU/ml; glucagon declined from a base-line value of 71+/-2 (SEM) to 56+/-1 pg/ml at 120 min (P less than 0.001). In juvenile-type diabetics given the same insulin-glucose infusion, glucagon declined from a base-line level of 74+/-8 to 55+/-5 pg/ml at 120 min (P less than 0.05). The absolute glucagon values in the diabetic groups did not differ significantly at any point from the mean glucagon levels in nondiabetics given insulin at the same rate plus enough glucose to maintain normoglycemia. When glucagon was expressed as percent of baseline, however, the normoglycemic nondiabetics exhibited significantly lower values than adult-type diabetics at 90 and 120 min and juvenile-type diabetics at 60 min. In nondiabetics given insulin plus glucose at a rate that caused hyperglycemia averaging between 134 and 160 mg/dl, glucagon fell to 41+/-7 pg/ml at 120 min, significantly below the adult diabetics at 90 and 120 min (P less than 0.01 and less than 0.05) and the juvenile group at 60 min (P less than 0.01). The mean minimal level of 39+/-2 pg/ml was significantly below the adult (P less than 0.001) and juvenile groups (P less than 0.05). When insulin was infused in the diabetic groups at a rate of 0.4 U/kg-min together with glucose, raising mean plasma insulin to between 300 and 600 muU/ml, differences from the hyperglycemic nondiabetics were no longer statistically significant. It is concluded that, contrary to the previously reported lack of insulin effect in diabetics during carbohydrate meals, intravenous administration for 2 h of physiologic amounts of insulin plus glucose is accompanied in unfed diabetics by a substantial decline in plasma glucagon. These levels are significantly above hyperglycemic nondiabetics at certain points but differ from normoglycemic nondiabetics only when expressed as percent of the baseline. At a supraphysiologic rate of insulin infusion in diabetics, these differences disappear.


Heme synthetase deficiency in human protoporphyria. Demonstration of the defect in liver and cultured skin fibroblasts. The final step in heme biosynthesis is chelation of porphyrin with Fe++ catalyzed by the mitochondrial enzyme heme synthetase. We have employed a sensitive radiochemical assay for this enzyme, using 59Fe and deuteroporphyrin or protoporphyrin as substrates. In this method iron is maintained in the ferrous state, oxygen is excluded from the incubation system, and labeled heme product is extracted into ethyl acetate. This assay has been used to measure the activity of heme synthetase in homogenates of liver, obtained by needle biopsy, and in sonicates of human skin fibroblasts, cultured in vitro. In addition, activity of the first enzyme of the heme synthetic pathway, delta-aminolevulinic acid synthetase, has been measured in fibroblast lysates. Lysates of fibroblasts from eight patients with protoporphyria had activities of delta-aminolevulinic acid synthetase which did not differ significantly from those of eight normal fibroblast lines, whereas activity of heme synthetase, with either deuteroporphyrin or protoporphyrin as substrate, was markedly decreased in sonicates of skin fibroblasts from these patients, the mean being 8% of control with deuteroporphyrin and 14% with protoporphyrin as substrate. In homogenates of liver from five patients with protoporphyria, activity of heme synthetase was also significantly less than that found in six patients without prophyria, the mean being 13% of control with protoporphyrin as substrate. These results provide evidence that decreased activity of heme synthetase is the basic defect in the heme synthetic pathway in protoporphyria. This deficiency is probably responsible for protoporphyrin accumulation and hence the biochemical and clinical features observed in protoporphyria.


Effects of low-level lead exposure on pyrimidine 5'-nucleotidase and other erythrocyte enzymes. Possible role of pyrimidine 5'-nucleotidase in the pathogenesis of lead-induced anemia. Similarities between lead-induced anemia and a new hereditary erythorenzymopathy involving pyrimidine-specific 5'-nucleotidase prompted studies of the effects of lead on this and other erythrocyte enzymes. In vitro incubations of normal mature erythrocytes demonstrated that significant inhibition of pyrimidine 5'-nucleotidase occurred in the presence of lead at concentrations that had minimal effects on many other erythrocyte enzymes assayed simultaneously. Similarly, subjects with chronic lead intoxication secondary to industrial exposure exhibited substantial and consistent impairment of erythrocyte pyrimidine-5'-nucleotidase activity. Results suggest that lead-induced deficiency of this enzyme in maturing erythroid elements could, if sufficiently severe, result in induction of basophilic stippling and premature erythrocyte hemolysis analogous to that encountered in the genetically induced enzyme-deficiency syndrome.


Urea synthesis after oral protein ingestion in man. In an attempt to assess hepatic functional capacity, hourly urea production, and corresponding serum amino acid concentrations after the ingestion of single protein meals (60, 120, and 240 g of protein) were evaluated in 18 normal subjects and in 8 patients with liver disease. In normal subjects, the relationship between urea production and serum amino acid concentration was linear (urea production in milligram urea nitrogen/kilogram lean body mass/hour = 6.3 times mg amino acid nitrogen/100 ml minus 20.5 SE of the estimate 6.9, r = 0.74, P less than 0.001), and variation of protein intake from 50 to 150 g/day for 3 days before testing did not change this relationship. The patients demonstrated impairment of urea synthesis proportional to the clinical severity of their liver disease. The potential clinical applications of these findings need to be determined.


Prostaglandin-stimulated bone resorption by rheumatoid synovia. A possible mechanism for bone destruction in rheumatoid arthritis. Synovial tissue from patients with rheumatoid arthritis was maintained in organ culture for 3-14 days. Conditioned media from these synovial cultures contained bone resorption-stimulating activity, measured in vitro by using calcium release from mouse calvaria as the assay system. The synovial cultures also produce prostaglandin E2 (PGE2) as measured by serologic methods. The production of both the bone resorption-stimulating activity and PGE2 was inhibited by more than 90% by treatment of the synovial cultures with indomethacin (5 mug/ml). In contrast, treatment of the synovial cultures with colchicine (0.1 mug/ml) caused a marked and parallel increase in the concentration of both bone resorption-stimulating activity and PGE2 in the conditioned media. The bone resorption-stimulating activity was quantitatively extracted into diethyl ether. Within the limits of experimental error, all of the bone resorption-stimulating activity in medium was accounted for by its content of PGE2, itself a potent osteolytic factor. We conclude that the bone resorption-stimulating activity produced by rheumatoid synovia in culture is PGE2.


Effect of corticosteroids on the human monocyte IgG and complement receptors. A quantitative in vitro assay was employed to directly assess the effect of corticosteroids on the IgG and complement receptor function of human  mononuclear phagocytic cells. In this system corticosteroids were solubilized with cholesterol-phospholipid sonicated dispersions before exposure to mononuclear cells. Solubilized corticosteroids at concentrations between 10(-4) and 10(-3) M inhibited both IgG and complement receptor activity in a dose-response fashion. Inhibition was dependent upon the time of interaction of the mononuclear cells with corticosteroids and was half-maximal by 15 min. The inhibitory effect at all concentrations of hydrocortisone was partially overcome by increasing the number of IgG molecules per erythrocyte. Hydrocortisone also inhibited the binding of erythrocytes coated with both IgG and C3, despite the fact that when both were on the erythrocyte surface a synergistic effect on binding to mononuclear cells was observed. At the steroid concentrations employed, the capacity of mononuclear cells to exclude trypan blue and to take up latex particles and neutral red was unaffected. Mineralocorticoids also inhibited receptor activity, but the sex hormones were less effective. These studies demonstrate an effect of steroid hormones on cell membrane receptor function, and they suggest that an inhibition of the recognition system for IgG and C3 in vivo may explain, in part, the effect of corticosteroids in man.


Pulmonary mechanics by spectral analysis of forced random noise. The magnitude (Zrs) and phase angle (thetars) of the total respiratory impedance (Zrs), from 3 to 45 Hz, were rapidly obtained by a modification of the forced oscillation method, in which a random noise pressure wave is imposed on the respiratory system at the mouth and compared to the induced random flow using Fourier and spectral analysis. No significant amplitude or phase errors were introduced by the instrumentation. 10 normals, 5 smokers, and 5 patients with chronic obstructive lung disease (COPD) were studied. Measurements of Zrs were corrected for the parallel shunt impedance of the mouth, which was independently measured during a Valsalva maneuver, and from which the mechanical properties of the mouth were derived. There were small differences in Zrs between normals and smokers but both behaved approximately like a second-order system with thetars = 0 degree in the range of 5--9 Hz, and thetars in the range of +40 degrees at 20 Hz and +60 degrees at 40 Hz. In COPD, thetars remained more negative (compared to normals and smokers) at all frequencies and crossed 0 between 15 and 29 Hz. Changes in Zrs, similar in those in COPD, were also observed at low lung volumes in normals. These changes, the effects of a bronchodilator in COPD, and deviations of Zrs from second-order behavior in normals, can best be explained by a two-compartment parallel model, in which time-constant discrepancies between the lung parenchyma and compliant airway keep compliant greater than inertial reactance, resulting in a more negative phase angle as frequency is increased.


Biochemical determinants of 5-fluorouracil response in vivo. The role of deoxyuridylate pool expansion. 5-Fluorodeoxyuridine monophosphate (FdUMP), the active metabolite of 5-fluorouracil (5-FU), is a tight-binding inhibitor of thymidylate synthetase, the enzyme which converts dUMP to TMP. Newly developed assays for FdUMP and dUMP were utilized to assess the competitive roles played by these nucleotides in determining the inhibition of TMP synthesis in mice bearing the P1534 ascites tumor. After 5-FU administration, levels of FdUMP reached a dose-dependent peak within 6 h in the ascites tumor and in bone marrow, and declined thereafter in a biphasic manner with an initial t 1/2 of 6 h and a final t 1/2 of 7-9 days. In duodenal mucosa, FdUMP levels were 1.8-2-fold higher than in the other tissues, but elimination was much more rapid. Simultaneous with the fall in FdUMP a progressive accumulation of the competitive substrate dUMP was observed in each tissue after 5-FU; and peak dUMP levels coincided with recovery of thymidylate synthesis, as determined by the incorporation of [3H]deoxyuridine into DNA. In vitro experiments with partially purifed thymidylate synthetase revealed and initial competitive interaction of dUMP and FdUMP, which, at high concentrations of dUMP was capable of markedly slowing the rate of irreversible inactivation of enzyme by FdUMP. These studies were found to be quantitatively consistent with a two-phase model of enzyme inactivation involving an initial competition between dUMP and FdUMP, with subsequent irreversible inactivation of enzyme by covalent linkage to the inhibitor. Recovery of thymidylate synthesis after 5-FU appears to result from both a fall in intracellular levels of inhibitor and a progressive accumulation of the competitive substrate dUMP.


Hypoxanthine-guanine phosphoribosyltransferase. Characterization of a mutant in a patient with gout. The mutation in a young gouty male with a partial deficiency of hypoxanthine-guanine phosphoribosyltransferase has been evaluated. The serum uric acid was 11.8 mg/100 ml, and the urinary uric acid excretion was 1,279 mg/24 h. Erythrocyte hypoxanthine-guanine phosphoribosyltransferase was 34.2 nmol/h/mg, adenine phosphoribosyltransferase was 36.5 nmol/h/mg and phosphoribosylpyrophosphate was 2.6 muM. Hypoxanthine-guanine phosphoribosyltransferase from peripheral leukocytes and cultured diploid skin fibroblasts was within the normal range, but enzyme activity in rectal mucosa was below the normal range. Initial velocity studies of the normal enzyme and the mutant enzyme from erythrocytes with the substrates hypoxanthine, guanine, or phosphoribosylpyrophosphate showed that the Michaelis constants were similar. Product inhibition studies distinguished the mutant enzyme from the normal enzyme. Hyperbolic kinetics with increasing phosphoribosylpyrophosphate were converted to sigmoid kinetics by 0.2 mM GMP with the mutant enzyme but not with the normal enzyme. The mutant erythrocyte hypoxanthine-guanine phosphoribosyltransferase was inactivated normally at 80 degrees C and had a normal half-life in the peripheral circulation. The mol wt of 48,000 was similar to the normal enzyme mol wt of 47,000. With isoelectric focusing, the mutant erythrocyte enzyme had two major peaks with isoelectric pH's of 5.50 and 5.70, in contrast to the isoelectric pH's of 5.76, 5.82, and 6.02 of the normal isozymes. Isoelectric focusing of leukocyte extracts from the patient revealed the presence of the mutant enzyme. Cultured diploid fibroblasts from the propositus appeared to function normally, as shown by the inability to grow in 50-100 muM azaguanine and by the normal incorporation of [14C]hypoxanthine into nucleic acid. In contrast, erythrocytes from the patient displayed abnormal properties, including the increased synthesis of phosphoribosylphyrophosphate and elevated functional activity of orotate phosphoribosyltransferase and orotidylic decarboxylase. These unique kinetic, physical, and functional properties provide support for heterogeneous structural gene mutations in partial deficiencies of hypoxanthine-guanine phosphoribosyltransferase.


Hepatic organic anion uptake in the rat. The hepatic uptake of bilirubin (BR), indocyanine green (ICG), and sulfobromophthalein (BSP) was studied in 350 anesthetized Sprague-Dawley rats by determining the initial plasma disappearance rate (V) of various doses of unlabeled ICG, or of tracer quantities of [3H]BR or [35S]BSP injected into the jugular vein simultaneously with varying amounts of unlabeled BR or BSP. Similar studies were also performed involving the simultaneous injection of potential inhibitors of hepatic uptake. The results indicate that: (a) hepatic uptake determined by direct tissue measurement could be accurately estimated from the plasma disappearance data; (b) saturation of hepatic uptake with increasing dose was readily demonstrated for each of these three organic anions, and in each instance a plot of V versus dose took the form of a rectangular hyperbola analyzable in terms of Michaelis-Menten kinetics; (c) for BR, the saturable uptake process showed a Vmax more than 100 times the normal net transfer rate from plasma to bile; (d) hepatic uptake of BR, BSP, and ICG showed relatively selective, mutually competitive inhibition; glycoholic acid did not inhibit hepatic uptake of any of these substances; and (e) "counter-transport" could be demonstrated for each of the three test substances. These data are compatible with the existence of a carrier-mediated transport process for hepatic uptake of each of these three organic anions and clarify the relationship of hepatic BR uptake to its overall transport from plasma to bile.


Studies on N5-methyltetrahydrofolate-homocystein methyltransferase in normal and leukemia leukocytes. A cobalamin-dependent N5-methyltetra-hydrofolate-homocysteine methyltransferase (methyl-transferase) was demonstrated in unfractioned extracts of human normal and leukemia leukocytes. Activity was substantially reduced in the absence of an added cobalamin derivative. Presumably, this residual activity reflects the endogeneous level of holoenzyme. Enzyme activity was notably higher in lymphoid cells than in myeloid cells. Thus, mean specific activities (+/-SD) were: chronic lymphocytic leukemia lymphocytes, 2.15+/-1.16; normal lymphocytes, 0.91+/-0.59; normal mature granulocytes, 0.15+/-0.10; chronic myelocytic leukemia granulocytes, barely detectable activity. Properties of leukocytes enzymes resembled those of methyltransferases previously studied in bacteria and other animal cells. Granulocytes and chronic myelocytic leukemia cells contain a factor or factors that inhibits Escherichia coli enzyme. The data suggest that the prominence of this cobalamin-dependent enzyme in lymphocytes and other mononuclear cell types may be related to their potential for cell division.


An inhibitor of sodium transport in the urine of dogs with normal renal function. The urine and serum of chronically uremic patients and dogs contain an inhibitor of sodium transport that reduces short-circuit current (SCC) in the toad bladder and produces natriuresis in the rat. The present studies represent an effort to determine whether the same inhibitor is detectable in urine of normal dogs maintained on a dosium intake varying from 3 to 258 meq/day. Observations were made with and without fludrocortisone. The same Sephadex G-25 gel filtration fraction previously shown to contain the "uremic" inhibitor was tested in both the isolated toad bladder and rat bioassay systems. The fraction from dogs maintained on 258 meq qodium plus 0.2 mg fludrocortisone/day consistently inhibited SCC in the toad bladder and induced a natriuresis in the rat (P less than 0.001). The fraction from dogs on the same sodium intake without fludrocortisone was also natriuretic (P less than 0.01) but did not inhibit SCC significantly. In contrast, the fraction from dogs fed 3 meq sodium with fludrocortisone or 91 meq sodium without fludrocortisone had no significant effect in either assay system. Thus, an inhibitor of sodium transport has been found in the urine of nonuremic dogs. Both the degree of natriuresis in the rat and the degree of inhibition of SCC in the toad bladder correlated with the state of sodium balance which ensued in the dog.


Free radicals and inflammation. Protection of phagocytosine leukocytes by superoxide dismutase. Isolated human polymorphonuclear leukocytes engaged in phagocytosis liberate superoxide radical and hydrogen peroxide into the surrounding medium. These two chemical species react to produce the hydroxyl radical, which attacks the leukocyte and leads to premature death of the cell. The hydroxyl radical may be scavenged by mannitol, or its formation can be prevented by the addition of superoxide dismutase or catalase to the medium, thereby eliminating the premature death of the cells. This phenomenon may partially explain the observed anti-inflammatory activity of superoxide dismutase.


Human lymphocytes: 5'-nucleotidase-positive and -negative subpopulations. The enzyme, 5'-nucleotidase (5'N) (E.C.-3.1.3.5) is present in lymphocytes isolated from the blood of normal subjects. This activity is markedly decreased or not detectable in the cells from three-quarters of patients with chronic lymphocytic leukemia (CLL), while supranormal levels are found in less than 10% of the cases. To determine whether the decreased 5'N value in CLL represents a lower activity per cell or fewer enzyme-containing cells than in the normal, conditions were established for the histochemical measurement of 5'N in human lymphocytes. It was found that the cells isolated from the blood of normal subjects or patients with CLL consist of 5'N-positive and 5'N-negative subpopulations. Normal subjects who had high 5'N specific activity were shown to have a greater percentage of 5'N-positive cells than individuals with low 5'N activity. Patients with CLL who had no activity by standard chemical assay had no 5'N-positive cells, while the exceptional patient with CLL with a higher than normal specific activity showed an percentage of 5'N-positive cells. It is suggested that the selective proliferation of 5'N-positive and 5'N-negative populations may account for the heterogeneity of 5'N in CLL.


Radioimmunoassay of myoglobin in human serum. Results in patients with acute myocardial infarction. A radioimmunoassay has been developed for the measurement of serum myoglobin in order to evaluate the time-course and frequency of myoglobinemia in patients with acute myocardial infarction. The method can detect as little as 0.5 ng of myoglobin and is not affected by hemolysis or storage of serum at -- 20 degrees C. Myoglobin was detected in all of 92 sera from normal adults and ranged between 6 and 85 ng/ml. Levels were markedly elevated in sera from 18 of 20 patients with acute myocardial infarction when samples were obtained within 12 h after hospital admission, the mean concentration being 380+/-53 ng/ml. Wehn the initial sample was drawn between 12 and 24 h after admission in another group of 20 patients with acute myocardial infarcts, the mean serum myoglobin concentration was 195+/-47 ng/ml, and 11 of these individuals had normal levels. Serial determinations performed on nine patients with acute infarction demonstrated that maximum myoglobin levels occurred within the first 8-12 h after admission and fell rapidly toward normal thereafter. The serum concentration of myoglobin in 21 additional patients admitted with chest pain but without acute myocardial infarction was 41+/-6 ng/ml. Radioimmunoassay of serum myoglobin appears to be useful and sensitive test for the early detection of myocardial infarction.


Glucagon regulation of plasma ketone body concentration in human diabetes. The present study was designed to test the hypothesis that physiological concentrations of glucagon may increase plasma ketone body concentration when sufficient free fatty acid substrate is available to support hepatic ketogenesis. Physiological elevations of plasma glucagon concentration were produced by a constant infusion of hormone, and increased plasma-free fatty acid availability was produced by simultaneous heparin injection to induce intravascular lipolysis. In the five insulin-dependent subjects studied, when plasma glucagon concentration remained at the normal basal level of 72+/-14 pg/ml during control saline infusion, the heparin-induced increase in free fatty acid availability resulted in approximately a 20% increase in plasma ketone body concentration. In contrast, when plasma glucagon concentration was elevated by hormone infusion to the physiological level of 215+/-35 pg/ml, the heparin-induced increases in free fatty acid availability resulted in approximately an 80% increase in plasma ketone body concentration. These results suggest that physiological elevations in plasma glucagon concentration may augment ketonemia in diabetic man when simultaneous elevations in plasma-free fatty acid arepresent.


Effects of cholera toxin on adenylate cyclase. Studies with guanylylimidodiphosphate. Similarities exist between the properties of adenylate cyclase after stimulation by cholera toxin and after stimulation by guanylylimidodiphosphate (Gpp-(NH)p). Thus a strong stimulation is achieved by both agents, the stimulation is essentially irreversible, the action of certain hormones is enhanced and the enzyme can be solublized with Lubrol PX in the activated state. Because of these similarities the interaction of cholera toxin and Gpp(NH)p on adenylate cyclase was examined. It was found that prior activation of rat liver adenylate cyclase by cholera toxin in vivo, or by cholera toxin and NAD in homogenates, blocked the stimulatory effect of Gpp(NH)p. Furthermore under conditions in which the effect of Gpp(NH)p was less than that of cholera toxin, inhibition of stimulation by cholera toxin was seen. Stimulation of adenylate cyclase by maximal concentrations of Gpp(NH)p, but not by submaximal concentrations, blocked the stimulatory effect of cholera toxin. The mutant interference of the actions of these two agents suggests a common target in the regulatory mechanism of the adenylate cyclase complex.


Adenylate cyclase of human fat cells. Expression of epinephrrine-sensitive activation revealed by 5'guanylyl-imidodiphosphate. Although catecholamines stimulate lipolysis in human fat cells, activation by epinephrine of adenylate cyclase in human fat cell membranes is not readily observed. The possible role of guanine nucleotides in this reaction has now been examined with human material. Fat cell ghosts were prepared from subcutaneous fat obtained from patients undergoing elective surgery. Adenylate cyclase was assayed with [alpha-32P]ATP as substrate. Fluoride ion stimulated the enzyme 8.3-fold relative to basal levels, but epinephrine activation of cyclase was not statistically significant. GTP did not allow expression of an epinephrine effect. However, the addition of the GTP analogue, 5'-guanylyl-imidodiphosphate [GMP-P(NH)P], along with epinephrine produced 5.7-fold activation of the enzyme (P less than 0.001). GMP-P(NH)P alone was without stimulatory effect. Comparable augmentation by GMP-P (NH) P of adenylate cyclase activity was seen with isoproterenol, norepinephrine, and epinephrine. Propranolol blocked catecholamine-GMP-P (NH) P stimulation of the enzyme, suggesting that the nucleotide-dependent activation of catecholamine-sensitive adenylate cyclase is mediated by beta-receptors. GMP-P(NH)P may prove useful in allowing in vitro demonstration of additional hormone-sensitive adenylate cyclase systems.


Differentiation of porphyria cutanea tarda symptomatica from other types of porphyria by measurement of isocoproporphyrin in faeces. The faecal porphyrin patterns of 24 patients with porphyria cutanea tarda symptomatica (PCTS), eight patients with variegate porphyria, three patients with other types of porphyria, and 20 non-porphyrics subjects have been compared using a two-demensional thin layer chromatographic technique that separates porphyrins of the isocoproporphyrin series from other faecal porphyrins. The 'isocoproporphyrin': coproporphyrin ratio ranged from 0-1 to 5-6 for patients with PCTS, whereas in other types of porphyria and non-porphyric subjects it was 0-05 or less.


A comparative study of serum total thyroxine estimation on unextracted serum by radioimmunoassay and by competitive protein binding. A rapid and precise radioimmunoassay (RIA) for serum total thyroxine (T4) on as little as 1-10 mul of unextracted serum is described. Results in hypothyroidism (overt and borderline), in euthyroid subjects in pregnant and oestrogen-medicated subjects, and in hyperthyroidism (overt and borderline) are compared with the results on the same sera by an established competitive protein binding technique (Ames' Tetralute) on unextracted serum from a different laboratory. The correlation between the two methods was excellent (r= 0.94) and no significant difference between overall appeared to measure total T4 Reliaby in sera containing only 1-3 or 2-6 nmol/1. Both methods predicted the clinical outcome in borderline hypothyroidism and borderline hyperthyroidism equally well and both gave normal results in T3-toxicosis. It is concluded that both techniques reliably measure total T4- RIA appears to have advantages of sensitivity and precision (especially in the hypothroid range), of simplicity, and of low cost.


Asymptomatic liver disease in haemophiliacs. The incidence of jaundice and of abnormal liver function tests has been assessed in 91 multitransfused patients with severe haemophilia A and B. Tests of hepatocyte function were within the normal range in the majority of patients. On the contrary, tests of biliary cell function, liver cell damage, and bromsulphthalein retention gave high rates of abnormal values, which tended to increase with age. Hepatitis B surface antigen was present in 8% and the corresponding antibody in 66% of the cases; 18% had a history of jaundice. All patients were asymptomatic and only a minority showed clinical signs of liver involvement. These data suggest that in haemophilacs repeated and prolonged contact with the agent(s) responsible for post-transfusion hepatitis may cause chronic liver damage not associated with overt illness.


Measurement of plasma renin activity by semi-micro radioimmunoassay of generated angiotensin I. A semi-micro method for determination of plasma renin activity (PRA) by radioimmunoassay of generated angiotensin I (AI) is described. The method permits measurement of PRA on 250 mul of plasma without loss of specificity, sensitivity, accuracy or preision. The small sample size has considerable application in terms of investigation of infants and young children. A reference range was established for healthy children on free diets. There was a 15-fold decline in PRA with age from a mean value of 1404pgAI/ml h-1 (ngAI/1. h-1) in infancy to a mean of 85 pgAI/ml h-1 (ngAI/1. h-1) in adult life.


Ultrastructure of cell migration throught the gastric epithelium and its relationship to bacteria. The migration of polymorphonuclear leucocytes and lymphocytes through the gastric mucosa has been studied with the electron microscope. Bacteria have been found related to the gastric epithelium. Arguments in favour of these bacteria not being contaminants at the time that the biopsies were taken are presented. The relationship between polymorphonuclear leucocyte migration and the occurrence of bacteria is discussed.


The cytocentrifuge NBT test.

The cytocentrifuge NBT test. The NBT test is a non-specific test of neutrophil membrane stimulation which has application to the study of neutrophil function, particularly in the septicaemic patient. An improved cytochemical test which eliminates potential sources of laboratory error has been developed. Venous or capillary blood samples may be studied and the technique can be applied to the neutropenic patient since available neutrophils are concentrated by cytocentrifugation. Clinical evaluation in 443 patients is described.


Muscle fibre type changes in hypothyroid myopathy. Changes in muscle fibre type in hypothyroid myopathy were studied by serial percutaneous needle biopsy of vastus lateralis before and during treatment with L-thyroxine. A type II fibre atrophy and loss was found, which correlated with the clinical and biochemical evidence of a myopathy. The type II fibre atrophy was corrected by L-thyroxine but type II fibre loss was still apparent in severely myopathic patients up to two years after starting treatment. The pathogenesis and significance of type II fibre atrophy and loss are discussed in relation to prognosis.


Some observations on cooling in laboratory autoclaves. Cooling times for various autoclave loads were recorded using thermocouples. Loads which may be encountered during normal laboratory working require between 17 and 174 minutes to cool to 100 degrees, C and up to 260 minutes to cool to 95 degrees C. Such long cooling times had an adverse effect on nutritive properties of bacteriological culture medium. Observations are made on some factors which influenced the cooling times, and the need for artificially assisted cooling is stressed. Recommendations are given for the safe operation of laboratory autoclaves.


Elution patterns of rubella IgM, IgA, and IgG antibodies from a dextran and an agarose gel. The elution pattern of serum proteins and the distribution of rubella HAI activity in 95 sera from 65 cases were determined after gel filtration with (a) Sephadex G-200 and (b) Bio-Gel A-5M. Rubella HAI antibody in peak 1 after Sephadex G-200 fractionation of early convalescent sera consists of both IgM and high molecular weight IgA. However, these two classes of antibody can be distinguished by gel filtration with Bio-Gel A-5M. Bearing these differences in mind, the results of fractionation with the two gels correlate very well although the use of Bio-Gel A-5M gives a slightly less sensitive technique for the diagnosis of recent infection.


Determination of cefalexin pharmacokinetics and dosage adjustments in relation to renal function. Following oral administration of a single 500-mg dose of cefalexin, serum and urine levels of the antibiotic were determined comparatively in ten normal subjects, ten patients with renal impairment, and ten patients with chronic nephritis on maintenance hemodialysis. In normal subjects, mean serum peak levels (12.0 +/- 0.8 mcg/ml) were observed 2 hours after drug administration. Absorption half-time (Ta1/2) averaged 0.82 hour and mean serum half-life (T 1/2) was 1.03 hours. Urinary recovery of cefalexin over a 6-hour period amounted to 64 per cent of the ingested dose. The renal clearance of the drug was 214 ml/min. In patients with renal impairment and in patients on maintenance hemodialysis, total elimination rate constant (Ke) was markedly lower (CrCl=0; Ke=Km=0.0766), whereas serum half-life (T 1/2) was significantly increased, reaching theoretically 8.47 hours in patinets with creatinine clearance of 0 ml/min. A correlation was established between Ke values and the creatinine clearances of the patients under study (Ke=0.0766 + 0.0060 CrCl). Initial loading doses, maintenance doses, and intervals adjusted to creatinine clearances were calculated from these data; accurate dosage schedules well adjusted to the renal status of each individual patient were derived from the calculated values.


Interhemispheric neocortical connections of the corpus callosum in the normal mouse: a study based on anterograde and retrograde methods. Interhemispheric neocortical connections are widely distributed through the corpus callosum in the mouse. Callosal connections are present in all cytoarchitectonic fields except field 25. The distal extemity representations of SmI, and MsI the representation of the mystacial vibrissae in SmI, and the more peripheral field representation of VI are relatively acallosal. Dense projections lie in the midline or truncal representations of SmI, MsI, SmII, at the vertical meridian representations bordering field 17, and medial to the AI representation. The radial distribution of terminals is bimodal in most cytoarchitectonic fields. It is unimodal in the supracallosal segment of field 29b and fields 49 and 27, trimodal in fields 13 and 35. The cells of origin of callosal fibers appear to have the same topographic pattern of distribution as the callosal terminals, observing the same steep and gradual density gradients. No cells giving rise to callosal axons are identified in the acallosal regions of fields 2 and 17. Further, superficial focal lesions in cortical areas which receive callosal connections give rise only to homotopic contralateral degeneration. Acallosal areas of 17 and 2 give rise to no callosal connections. The cells of origin of callosal connections are located at all laminar levels of the cortex and include pyramidal and polymorphic cells but not the granule cells of layer IV.


Architectonic map of neocortex of the normal mouse. The neocortex of the normal mouse has been subdivided into architectonic fields on the basis of its cellular and fiber patterns. The map of medial, retrohippocampal, frontal and insular regions is little different from that of Brodmann as modified in minor ways by Krieg. The map of parietal, occipital and temporal regions follows closely the major rearrangements introduced to Brodmann's map by Krieg. Krieg's map has been modified to give individual status to the barrel fields and to disignate occipital fields around the full circumference of field 17, and temporal fields circumferentially around field 41.


Immunocytochemical localization of glutamate decarboxylase in rat spinal cord. The GABA synthesizing enzyme, glutamate decarboxylase (GAD), has been localized by light and electron microscopy in the rat lumbosacral spinal cord using a peroxidase-labeling antibody technique. The light microscopic localization shows heavy, punctate reaction product for GAD in the dorsal horn laminae I-III. Moderately heavy reaction product is also seen in the deeper dorsal horn laminae IV-VI, the medial aspect of the intermediate gray (lamina VII) and the region around the central canal (lamina X). A moderately light concentration of GAD reaction product is observed in the ventral horn, and punctate deposits of reaction product also are seen on motoneuron cell bodies. The punctate distribution of reaction product for GAD in both ventral and dorsal horns, as visualized by light microscopy, corresponds to GAD-containing synaptic terminals seen by electron microscopy in comparable regions of the spinal gray. Many more GAD-positive terminals are observed in dorsal horn laminae I-III than in deeper laminae IV-VI. GAD-containing terminals in the dorsal horn are presynpatic to dendrites and cell bodies. Gad-containing terminals presynaptic to other axon terminals are observed also, and they are more numerous in laminae II and III. In the ventral horn motor nuclei, GAD-positive knobs are presynaptic to large and small dendrites and motoneuror cell bodies. In addition, small GAD-containing terminals also are presynaptic to larger axonal terminals which are in turn presynaptic to motoneuron somata. The observation of GAD-containing terminals presynaptic to dendrites and cell bodies in both dorsal and ventral horns is compatible with the evidence suggesting that GABA terminals may mediate postsynaptic inhibition of spinal interneurons and motoneurons. The additional finding of GAD-positive terminals presynaptic to other axonal terminals in the dorsal horn and motor nuclei is consistent with the growing evidence that GABA also may be the transmises mediating presynaptic inhibition via axo-axond synapses in the spinal cord.


Anatomical identification of a telencephalic visual area in crocodiles: ascending connections of nucleus rotundus in Caiman crocodilus. Nucleus rotundus receives a major input from the optic tectum in crocodiles, Caiman crocodilus. Telencephalic projections of nucleus rotundus were studied in Caiman by means by the Fink-Heimer procedure after anodal, stereotaxic lesions. Efferent axons of nucleus rotundus assemble on the ventromedial aspect of this nucleus and swing ventrolaterally to enter the dorsal peduncle of the lateral forebrain bundle. These ascending fibers continue rostrally in the dorsal peduncle of the lateral forebrain bundle to enter the telencephalon where they remain restricted to a lateral portion of the lateral forebrain bundle. At more anterior levels, these fascicles turn dorsally, pass through the ventrolateral area, and terminate massively in a lateral part of the rostral dorsolateral area. The results of this experiment are compared with similar studies on thalamotelencephalic connections of diencephalic visual areas in other amniotes. Parallels in fiber connections of thalamic auditory and visual areas and the segregation of these modalities in the telencephalon of Caiman are discussed. These similarities in neural circuitry and synaptic elements of auditory and visual systems that synapse in the midbrain of Caiman form the basis for a different interpretation of sensory system organization in amniotes.


Catecholamine distribution in feline hypothalamus. Catecholamine distribution was examined in cat hypothalamus using the histochemical fluorescence technique of Falck and Hillarp. The heaviest accumulations of catecholamine-containing varicosities were seen within the: anterior periventricular nucleus; dorsal hypothalamic area; bed nucleus of the inferior thalamic peduncle; doral component of the paraventricular nucleus; dorsomedial nucleus; infundibular nucleus; bed nucleus of the stria terminalis-medial division; and supraoptic nucelus. Catecholaminergic perikarya were observed within periventricular, dorsal, and caudal hypothalamic areas as well as within the supramamillary nucleus and caudal diencephalon. Catecholamine distribution in cat hypothalamus possesses both similarities and dissimilarities in relation to distributions reported in other mammals.


Distribution and properties of commissural and other neurons in cat sensorimotor cortex. Commissural, cortico-cortical and cortico-caudate neurons have been investigated in the primary sensorimotor cortex of the cat, using antidromic stimulation techniques, and histological identification of recording sites. These neurons are to be found in all cortical laminae except the first; commissural and cortico-cortical neurons were found to be commonest in laminae III and VI, whilst cortico-caudate neurons were most abundant on the border between laminae III and V, in motor areas. In sensory areas topographically identified as representing distal parts of limbs, commissural neurons are very rare, confirming neuroanatomical studies on the origin and termination of callosal fibres. The intracerebral neuronal projections investigated in this study had slow conduction velocities (less than 1 m/sec, up to about 10 m/sec). It was found that projections from area 6, whether commissural, cortico-caudate, or cortico-peduncular have slower conduction velocities than their counterparts from area 4. It is suggested that this is related to the type of motor control in which these two areas are involved (slowly-responding postural movements, as opposed to more rapid distal limb movements). No neurons were found which had both commissural (or cortico-cortical), and cortico-fugal projections.


Corticoseptal projections in the snakes Natrix sipedon and Thamnophis sirtalis. The projections of the cerebral cortex upon the septum in water snakes (Natrix sipedon) and garter snakes. (Thamnophis sirtalis) were studied with the Fink-Heimer degeneration techniques. Two cortical areas send major projections to the septum. Medial cortex projects bilaterally to the dorsal portion of the precommissural septum along its full rostrocaudal extent. The ipsilateral projection is more massive than the contralateral one. Dorsal cortex projects ipsilaterally to a column within the septum which is present dorsally, caudal to the level of the anterior commissure, but shifts ventrally as the septum is followed rostrally. Lateral cortex may send a sparse projection to the ipsilateral ventral septum.


Trigeminal deafferentation and hunger in the pigeon (Columbia livia). The location and distribution of the pigeon's trigeminal nerve permit deafferentation of the oral region without affecting motor functions. Although trigeminal deafferentation does not affect drinking, it reduces the efficiency of the consummatory response of eating and disrupts motivational processes underlying hunger and weight regulation. Although the two types of deficit may be experimentally dissociated, trigeminal deafferentation invariably affects both sensorimotor and motivational mechanisms. The deficits in food intake and weight regulation seen after trigeminal deafferentation in the pigeon resemble some components of the "lateral hypothalamic syndrome" in the rat. The results are related to recent studies of the contribution of peripheral and central oropharyngeal factors to the neural control of food intake in both rat and pigeon.


Trigeminal nerve and eating in the pigeon (Columba livia): neurosensory control of the consummatory responses. Electrophysiological, neurobehavioral, and cinematographic techniques were used to study the role of the trigeminal nerve in the neurosensory control of eating. Analaysis of single-unit data recorded in the pigeon's trigeminal ganglion indicates that the trigeminal nerve provides somatosensory inputs from the oral region that signal the location and movement of food and monitor the extent of mouth opening. Trigeminal deafferentation, although it does not affect pecking or swallowing, severly impairs the efficiency of eating. Cinematographic analysis shows that the impairment is due to disruption of the neurosensory control of mandibulation-the process by which grain is grasped at the beak tip and moved to the back of the mouth.


Septal lesions and behavior: effects of presurgical rearing and strain of mouse. Male mice (C57BL/10J or SJL/J strains) were reared in either enriched social cages or restricted individual cages from 25 days of age until they underwent septal or control surgery 1 mo later. Enrichment differentially altered septal or control behavior as measured by: fluid consumption of water, saccharin, and quinine; performance on a rotorod; and the acquisition of an active avoidance task. The interactions of presurgical history with brain damage were manifested differently in the two strains of mice. The importance of attending more to genetic and presurgical history in attempts to define the effects of brain damage on behavior and to determine the function of brain structures is discussed.


Sparing of function after infant lesions of selected limbic structures in the rat. The effects, in adult animals, of limbic lesions produced in infancy were studied in 273 male Wistar rats using weight gain and conditioned emotional response (CER) and conditioned avoidance response (CAR) acquisition as the critical measures. Subjects received bilateral lesions of the amygdala, septum, posteroventral hippocampus (PH), anterodorsal hippocampus (AH), or frontal cortex either as infants (at 10 days of age) or as adults (at 60 days). Normal and anesthetized control groups were also used. Frontal cortical lesions, AH lesions, and anesthetization had no effect on weights or on CER and CAR acquisition. Both infant and adult amygdala and septal lesions significantly disrupted normal weight gain. Adult-accrued amydala and PH lesions significantly retarded CER acquisition, and adult septal and PH lesions significantly facilitated CAR acquisition. Infant-accrued amygdala lesions significantly retarded CER acquisition but had no effect on CAR acquisition. Infant septal lesions significantly facilitated CAR acquisition, and infant PH lesions had no effect on either task. The results were interpreted to mean that the observed task-specific recovery in early-operated animals may have been due to some form of functional reorganization.


Sensorimotor responsiveness in rats with unilateral superior collicular and amygdaloid lesions. Large unilateral lesions of superior colliculus, but not amygdala, result in strong ipsiversive progression tendencies and permanent neglects of visual, auditory, and whisker-touch stimuli presented on the contralateral side of the body. Combined collicular-amygdaloid lesions also yield circling behaviors and multimodal neglects that are completely independent of the order or laterality of the amygdaloid lesion. Rats with colliculectomy either neglect or else turn away from pinches of the contralateral ear and forepaw. Subjects with combined lesions display more crossed orientations, and this tendency is greatly potentiated by ipsilateral lesion placement. The nature and time course of the crossed response in rats with sensory neglects is reminiscent of the clinical syndrome described as alloaesthesia or as contralateral sensory displacement.


Differential effects of environmental enrichment on the open-field behavior of wild and domestic Norway rats. Early postweaning experience in an enriched environment had a greater influence on the open-field behavior and body weight of wild Norway rats than of their domestic counterparts. Genetic changes accompanying the domestication process may have reduced the relative impact of postweaning experience on the development of the domestic rat's response to changes in its environment.


Development of species identification in ducklings: III. Maturational rectification of perceptual deficit caused by auditory deprivation. Mute ducklings, devocalized as embryos and maintained in auditory isolation, manifest a selective high-frequency perceptual deficit vis-à-vis the maternal call of their species at 24 hr after hatching. Since it takes a rather specific auditory experiential input to rectify this high-frequency insensitivity at 24 hr, it was predicted that, in the absence of auditory experience, devocal-isolated ducklings would fail to show sufficient endogenously mediated improvement to bring them up to the level of perceptual competence of vocal-communal ducklings at any age. This hypothesis proved wrong in that the proportion of devocalized ducklings showing a preference for the normal maternal call over the greater than 825-Hz attenuated one became equivalent to the vocal ducklings at 48 hr after hatching, as did their ability to discriminate the normal maternal call from greater than 1,800-Hz attenuated maternal call. At 65 hr, however, the devocalized ducklings' performance deteriorated back to the level observed at 24 hr. Embryonic exposure to the (sibling) contact-contentment call prevents the perceptual deficit at 24 hr and the deterioration at 65 hr.


Free-operant comparisons of wild and domestic Norway rats. Wild and domestic rats (Rattus norvegicus) were compared on nondifferential appetitive variable interval responding, discrimination, and discrimination reversal procedures. The effects of strain, sex, deprivation, preexperimental handling, and sessions on response rate were examined. Performances during the 60 days of variable interval training showed prolonged increases over that period for all strain-sex groupings, with domestic subjects responding at higher rates than wild. Males also tended to respond at higher rates than females. During the discrimination procedure wild subjects showed more resistance to extinction than did the domestic subjects, although these differences generally diminished after the 30 days of training. During the discrimination reversal procedure domestic subjects reversed their responding pattern more readily than did the wild subjects, and domestic females reached criterion significantly sooner than domestic males. The effects of deprivation and handling were not significant during the experimental procedures.


Cephalic mechanism for social control of fissioning in planarians: III. Central nervous system centers of facilitation and inhibition. Previous studies have indicated that asexual reproduction (fissioning) in the planarian Dugesia dorotocephala is socially controlled through a cephalic mechanism: Isolation releases fissioning; grouping inhibits it; decapitation, at the level of the auricles, releases it even in grouped subjects. The brain is not necessary for programming the actual events of fissioning; these are orchestrated by the segmental plexus fissioning (SPF) system. Various surgical cuts were made to ablate selected portions of the central nervous system of isolated and grouped planarians in order to ascertain the inhibitory or facilitatory effects of these in the physiological mediation of such control on the SPF system. These results were synthesized into a model of this control system; the anterior lobes and optic regions of the brain inhibit the SPF system, and the anterior and caudal segmental plexuses facilitate it. These influences are partially tonic and partially contingent upon social stimulation.


Orogastric, hydrational, and behavioral controls of drinking following water deprivation in rats. Drinking and its associated behaviors were studied in rats deprived of fluid for 8,24, or 48 hr. The behavior of rats drinking water could be divided into three successive stages: (a) an initial intense burst of drinking that could not be easily disrupted; (b) intermittent drinking, often distinguished by the brief appearance of conflict behavior directed at the drinking spout; and (c) termination of drinking. Drinking stopped well before the fluid loss, reflected in a sizable extracellular deficit, was restored. Intake of water was terminated when serum hyponatremia and hypoosmolality (and presumably cellular overhydration) developed in temporal continguity with drinking. These and other considerations suggest that the cellular fluid phase exerts significant inhibitory as well as excitatory control over drinking.


Intestinal satiety in rats.

Intestinal satiety in rats. Infusion of liquid food into the duodenum inhibited sham feeding. The inhibition of sham feeding reflected satiety because the duodenal infusion elicited the complete behavioral sequence characteristic of satiety. The chemical and/or colligative load that the infusion imposed on the intestine appeared to be the adequate stimulus for satiety. Duodenal infusions that inhibit sham feeding and elicit satiety are not aversive because they will not function as the unconditioned stimulus for the formation of a conditioned taste aversion for saccharin. We call the satiety elicited by the infusion of food into the duodenum "intestinal satiety." This emphasizes our belief that satiety is a reflex that can be elicited by the activation of receptors in the wall of the intestine. It is known that the activation of some intestinal receptors releases the hormone cholecystokinin (CCK). Since CCK mimics a duodenal infusion by inhibiting sham feeding and eliciting the complete behavioral sequence of satiety, we suggest, but do not prove, that CCK mediates intestinal satiety in  the rat.


Ingestive responses of human newborns to salty, sour, and bitter stimuli. Human newborns (1-4 days old) were offered two fluids differing in taste for 3 min each. The volumes ingested were measured. Infants offered water and bitter or sour solutions did not ingest them differentially, which corroborated earlier observations with weaker solutions. A sucrose solution was used to raise baseline ingestion above that of water. Infants offered the sucrose solution with and without urea, citric acid, or sodium chloride consumed less of it when citric acid was added. They were indiffferent to  the addition of urea or sodium chloride. The failure to observe intakes lower than that of water suggests that newborns maximally inhibit their ingestion of water. The effects of sex, age, birth weight, and individual consistency on intake were assessed.


Taste rejection of nonnutritive sweeteners in cats. Cats reject saccharin and cyclamate and are indifferent to dulcin, although they, like other mammals, prefer sucrose. The rejection threshold for saccharin found in this experiments, .0001 M, is about 2 log steps lower than a previously reported rejection threshold for sodium saccharin. Water produces a taste in cats adapted to their own saliva. The high sodium saccharin threshold may have resulted because the taste of the sodium saccharin was masked by the taste of the water solvent; however, saccharin may also be somewhat more aversive to the cat than sodium saccharin. Saccharin may produce an aversive taste because it stimulates receptor sites sensitive to substances bitter to man as well as those sensitive to sugars. In addition, saccharin may not be an effective stimulus for all sugar-sensitive sites.


Task complexity as a factor in eliciting heterosis in mice: aversively motivated behaviors. Three inbred strains of mice (A/J, DBA/2J, and C57BL/6J) and their six reciprocal F1 hybrids were tested in activity levels before and after shock, inhibitory avoidance, one-way avoidance, and shuttle avoidance. In the activity and inhibitory situations the hybrids generally exhibited an intermediate pattern of inheritance. In the one-way avoidance task complete dominance was the rule, whereas in the shuttle task overdominance was apparent in all the hybrid strains. Overdominance was found to be more evident in tasks requiring increased versatility of associative processes. It is suggested that when the task involves relatively simple contingencies or reflexive behaviors, increased versatility is not necessary and consequently the hybrid advantage is not apparent. When the task involves integrative capacities, the hybrid advantage emerges.


Composition of cottontail rabbit milk from stomachs of young and directly from gland. Milk samples were from stomachs of 27 nursing cottontail rabbits (Sylvilagus floridanus) within 5 min after cessation of nursing. Four milk samples were directly from mammary glands by hand milking aided by tranquilizer and oxytocin. Means and standard errors for 27 stomach samples for total solids, fat, protein, lactose, and ash were 33.6 +/- .8%, 13.9 +/- 1.7%, 14.6 +/- .5%, 2.22 +/- .05%, and 2.06 +/- .07%. Those values of 4 samples directly from the gland were 35.2 +/- .4%, 14.4 +/- .4%, 15.8 +/- .6%, 2.67 +/- .26%, and 2.07 +/- .06%. Fatty acid compositions were similar for the groups, except linoleic acid was 30.0% of fatty acids from stomach milk and 24.7% in milk obtained directly. Differences between sampling methods in palmitoleate, stearate, and oleate may have been from differences in season of sampling. Minerals were more concentrated in milk obtained directly, except potassium. Differences between milks of domesticated and cottontail rabbits are discussed.


External form and internal anatomy of Holsteins and Jerseys. Body weights, external dimensions, and postmortem measures of internal body dimensions or weights of organs and glands of Holsteins and Jerseys were used to establish norms, interrelationships of traits, and effects of sire and inbreeding on changes in external form. Sires differed in nearly all measures of external body form. Sire effects increased with advancing age whereas effects of inbreeding (greater than 12.5, 3.0 to 12.4, or less than 3.0% of inbreeding) declined. Skeletal dimensions were smallest in the greater than 12.5% inbred group. Differences due to inbreeding were largest at 3 and 6 mo of age and in first lactation. Body heights and head dimensions were nearer to mature size at 3 and 6 mo than other measures. In both breeds, most rapid development was between 3 and 6 mo, but Jersey matured 1 to 2% faster. Age (2 to 3, 4 to 5, 6 to 10, greater than 10 yr) was significant for most postmortem measurements. Correlations among measures of external form were .30 to .93. Correlations between external form and internal features or between internal dimensions and organs were lower. External and internal features were positively correlated, but few external features showed strong enough association with internal features for use as predictors of size of organs, glands, or digestive capacity.


Assay and use of magnesium ferrite as a reference in absorption trials with cattle. Magnesium ferrite, an inert ferrimagnetic material, was introduced as reference substances in absorption trials with ruminants. A method for assaying magnesium ferrite was based upon the difference between the weight of the test material on an analytic balance and that of the same material weighed below a permanent magnet. Four heifers in two pairs were in a feeding experiment lasting for 6 wk divided into two 3-wk periods. Each animal received once daily 12 g magnesium ferrite and, as control, 12 g shredded paper impregnated with 4.2 g chromium oxide. The rations were composed of chopped wheat straw and concentrates, given twice daily, with a different straw-concentrate ratio for each group. The treatments were reversed after the first experimental period. Mean recoveries of magnesium ferrite and chromic oxide in total collection of feces were 103 and 90.2%. Mean absorption coefficients of organic matter calculated by total collection and by the ratios of magnesium ferrite and chromic oxide in feces taken from the rectum were 68.1, 70.1, and 65.7%. The method is simple and accurate and may replace methods involving time consuming chemical determinations.


Fungal cellulase and hemicellulase prediction of forage digestibility. An enzymatic procedure using Trichoderma viride carbohydrases, a fungal hemicellulase, and pepsin was developed to provide a laboratory method for predicting forage digestibility. The amount of forage dry matter solubilized by enzymes and incubation buffer was less than that in vivo or by in vitro fermentation by rumen microorganisms. Total forage dry matter solubilized by the enzymatic procedure was correlated (.92) with in vitro digestibility. Simple correlation coefficients between in vivo true digestibility of 18 forages and total dry matter solubilized by enzymes and buffer was .87; that soluble in the buffer only, .65; and that solubilized by the enzymes, .82. Correlation coefficients with in vivo true digestible amount of cell-wall and protein were greater when the forage species were considered separately than when pooled together. With this restriction, the enzymatic procedure can be a useful method for predicting forage digestibility. Fermentations with rumen inoculum however, provided more accurate predictions of in vivo digestibility in a variety of forage species.


Iodine absorption, excretion, recycling, and tissue distribution in the dairy cow. Research on iodine metabolism was reviewed with special reference to cattle and milk secretion. Iodine metabolism in the fetus and thyroid activity as related to milk secretion and iodine feeding have also been considered. Between 70 and 90% of dietary iodine is absorbed directly from the bovine rumen, reticulum, and omasum. In the abomasum, rate of iodide secretion is approximately 18 times the rate of absorption. Circulating thyroxine is not secreted into the abomasum but enters the small intestine in the bile. Most of the iodide secreted into the abomasum is reabsorbed from the small and large intestines; absorption of thyroxine averages less than 10%. The thyroid usually contains an amount of iodine equal to the daily dietary intake; extrathyroidal tissues concentrate only .006 to .04% as much radioiodine per unit weight as the thyroid. At normal iodine intake (less than 10 mug/kg body weight daily), iodine losses average 30% of the daily intake in feces, 40% in urine, and 8% in milk. Milk iodine is influenced by amount and chemical form of dietary iodine, stage of lactation or milk yield, seasonal effects, goitrogens, and thyroid status. Cows secrete less iodine into milk than most other species and have an efficient iodine recycling system via the gastrointestinal tract which conserves iodine and can protect them against low dietary iodine.


Phospholipids and fat secretion by cows on normal and low fiber diets: lactational trends. Daily yields of milk, milk fat, phospholipids, and fatty acids were measured weekly during lactations of two groups of cows on a normal and restricted roughage diet. Milk yield was higher in normal cows during the initial 15 wk of lactation. Fat production decreased and was consistently lower in milk from cows on restricted roughage (from 1.2 to .4 in normal and from .8 to .3 kg/day for restricted). Phospholipid secretion decreased from an average 7 g to 3 g/day in both groups. The concentration of phospholipid in both milks fluctuated during lactation (20 to 30 mg/100 ml milk), but in milks from restricted cows it tended to increase with progress of lactation. Milk lipids from cows on restricted diets had higher phospholipid to fat ratio, (1.0 to 1.5 compared to .5 to .6 g phospholipid/100 g fat for milk from normal cows). Composition of the phospholipid classes changed slightly during lactation. Phosplatidylinositol changed most, increasing from 4 to 10 and 6 to 8% in normal and restricted milks, respectively. Fatty acids of short and medium chain lengths (C6 to C14) followed a typical quadratic regression in normal milks increasing from 10 to 30% of the total fatty acids during the first 25 wk of lactation. In restricted milk these fatty acids were already high (25%) within 2 wk and followed a linear regression with lactation. Both palmitic and stearic acid were lower in milk from restricted cows while oleic and linoleic acid were higher particularly after 10 wk of lactation.


Volatile fatty acid metabolism by rumen mucosa from cattle fed hay or grain. Effects of an all-grain versus an all-hay diet on metabolic activity of rumen mucosa of cattle were investigated. After diets had been fed for 3 to 4 mo, rumen papillae were collected at slaughter from the dorsal rumen sac and incubated with one of various volatile fatty acids. Rates of substrate utilization were in the order: n-butyrate greater than n-valerate approximately propionate greater than iso-butyrate approximately iso-valerate. Over-all, papillae from hay-fed steers utilized greater amounts of volatile fatty acids. Dietary treatment did not significantly affect extent of conversion of volatile fatty acids to lactate and to ketone bodies. Lactate was the major metabolite from propionate and n-valerate. Ketone body formation accounted for more than 90% of n-butyrate uptake by papillae. Ketone formation from n-valerate was restricted to beta-hydroxybutyrate while that from iso-valerate was essentially acetoacetate plus acetone. Metabolic systems in rumen mucosa of physiologically mature ruminants seem to adapt little to varying individual volatile fatty acids available for absorption in vivo.


Influence of dry matter and nitrogen intakes on fecal nitrogen losses in cattle. Dietary factors influencing loss of fecal nitrogen in Holstein steers have been examined in data on metabolism from forage diets. Two factors- total nitrogen and dry matter intake, accounted for a large part of the variation in fecal nitrogen. Nitrogen intak expressed as grams per kilogram dry matter intake more accurately accounted for variability in total fecal nitrogen than did nitrogen intake expressed as grams per animal per day. Data were from trials on 68 forages covering a range of nitrogen intakes and of nitrogen concentration in dry matter of forage. Correlations were .93 between total fecal nitrogen and dry matter intake, .90 between total fecal nitrogen and total nitrogen intake, and .95 between total fecal nitrogen and total fecal dry matter. However, at high and low nitrogen intake there was evidence of departure from a linear relationship. The relative usefulness of three regression analyses to estimate metabolic fecal nitrogen is discussed.


Effects of silage diets on health, reproduction, and blood metabolites of dairy cattle. Forty-eight Hostein dairy cows were assigned uniformly by parity and calving date to three forage treatments for three lactations. Forage treatments were corn silage (F-I), corn silage plus Hay-crop silage (-f-II), and corn silage plus hay (F-III). Records of health and reproductive data were kept to evaluate dietary effects. During the third lactation six animals in each treatment were blood-sampled on a 4-day interval from 24 days prepartum to 60 days postpartum to determine metabolites. Reproductive traits were similar among the treatment groups as were occurrences of mastitis. Corn silage and hay-crop silage cows had more ketosis than hay cows. Corn silage cows had more parturient paresis than the other two groups, and abomasal displacement occurred only in the corn silage group. There were differences in concentrations of plasma metabolites among treatments; however, they appeared to be within normal ranges, and no pathological implications were obvious. Blood pH, blood packed cell volume, blood alkaline reserve, and pH values were similar among treatment groups. Histological evaluation of hepatic and endocrine tissues revealed no treatment effects.


Effect of 1,2-propanediol on the rumen mucosal growth of kids. Intra-abomasally administered 1,2-propanediol, 150 to 160 g per Japanese meat-type kid in 3 to 4 wk, increased the ratio of rumen to body weight, of rumen to total stomach, and of rumen mucosa to muscle over the control which received only water. Intra-abomasal administration of glycerol, glucose, fructose, 1.3-butanediol, xylitol, lactic acid, sodium propionate, or sodium butyrate showed no increases over the control. Only propanediol chemically stimulated rumen mucosal growth. Intraruminal administration of propanediol showed the same stimulation as intra-abomasal. Intraruminal administration of minerals or of polyethylene glycol (Carbowax 4,000) and intraruminal insertion of plastic cubes were not effective, but the latter showed a cooperative effect to accelerate rumen growth with propanediol stimulation. Average fresh tissue weights of rumen mucosa in kids of 2.7 kg body weight of control, of propanediol-treatment, and of plastic cube plus propanediol-treatment were 6.4, 10.4, and 14.8 g, and those of rumen muscle were 7.9, 8.3, and 11.1 g. Propanediol may be involved directly in the local control of rumen epithelial growth.


Body length, head circumference, and weight of bovine fetuses: prediction of gestational age. Ninety fetuses from 92 pregnant uteri from Red Danish and Holstein cows were collected at a slaughterhouse. Fetal weights, body length, and head circumference were measured. Correlations were linear between log weight and log length, log weight and log head circumference, and log body length and log head circumference. From these relationships a method of calculating fetal age was derived.


Routine postpartum treatment of dairy cattle with intrauterine neomycin sulfate boluses. Within location, 119 dairy cattle from two experiment station herds, which had no problems associated with parturition, were randomly either treated by insertion of two intrauterine boluses containing a total of 1000 mg neomycin sulfate 24 h postpartum or maintained as a control. Uteri and ovaries of all cows were palpated 17 to 24 days postpartum and at 14 day intervals thereafter until inovulation of the uterus was judged complete and an estrus had been observed. All cows were inseminated at the first estrus after 60 days postpartum and at each estrus thereafter until conception. Cows treated with neomycin sulfate required more services per conception (1.7 to 1.4) and were open more days before conception (100.5 to 88.5) than the controls. The probable cause of the lowered reproductive efficiency is discussed. Treatment did not later significantly days to ovulation, estrus, involution, or first service. Three treated and five control animals needed additional uterine treatment. Routine intrauterine treatment of all cows with neomycin sulfate boluses should not be recommended.


Multiple comparisons: comparisonwise versus experimentwise Type I error rates and their relationship to power. Some statisticians contend that the experimentwise Type I error rate is the most important attribute of multiple comparison procedures to be used for making all possible pairwise comparisons among treatment means after an analysis of variance. That contention is challenged here. The importance of Type I errors is discussed as well as the occurrence of Type I errors in biological experiments. Also considered is the effect of Type I error protection on power. The two methods of measuring Type I error rate, comparisonwise and experimentwise, are explained, and the reader may decide which kind he wishes to control. Several references cited support Fisher's least significant difference and Duncan's new multiple range test despite their higher-than-nominal experimentwise Type I error rates. These procedures control the comparisonwise Type I error rates and are considerably more powerful in finding differences among treatments than procedures that control the experimentwise Type I error rates.


The A.D.A. registration examination. Development and operation. The registration examination is the means by which The American Dietetic Association seeks to determine whether candidates throughout the country have attained a basic level of competence in terms of significant and appropriate areas of basic knowledge. The goal of every registration program is the passing, and thus, the registration of every candidate. If the examination reflects what the Association believes a registered dietitian must know, then candidates who answer correctly the questions on the registration examination will have shown that they are qualified to be registered representatives of the profession.


Functions of dietetic personnel in ambulatory care. By observation in ten ambulatory care settings and a literature review, the author found that dietetic service is being delivered by a variety of personnel--trained lay aides, nurses, and physicians, as well as professional dietitians. Employers in such settings agree that nutrition is an important component of total health care but question whether it must necessarily be delivered by dietetic personnel. The dietitian, to survive, must justify on a cost-benefit basis the unique value of her competency to the outcome of patient care. Sixty-eight nutritional care functions, appropriate for dietitians and/or dietetic technicians working in ambulatory care organizations, are identified and listed. In contrast to hospital-based, in-patient care, the author concludes that performance of these functions requires greater interest in helping others and greater flexibility, and she sees such service as the wave of the future.


Chilled food systems. Effects of chilled holding on quality of beef loaves. Following storage at 32 degrees or 42 degrees +/- 1 degrees F. for zero (4 hr.), and one, two, four, seven, and nine days, beef loaves which had either been cooked; cooked and pasteurized; or cooked, frozen, and thawed prior to storage were compared with a freshly prepared, freshly cooked loaf. Loaves were initially cooked to an internal temperature of 165 degrees F. and reheated to the same temperature prior to testing. A freshly prepared loaf cooked immediately prior to evaluation statistically had a shorter heating time, less cooking losses, higher moisture content, lower thiobarbituric acid (TBA) scores, and higher taste panel scores for odor, juiciness, flavor, and appearance. In all quality-related properties evaluated, the reference loaf rated higher. Pasteurized loaves were not significantly different from refrigerated loaves. Frozen, thawed loaves had significantly different values for TBA scores for all taste panel evaluations; these differences were indicative of reduced quality. Taste panel scores decreased and TBA scores increased significantly over nine-day storage. The hypothesis that changes over time were linear was not rejected. The only significant difference noted for the two storage temperatures of 32 degrees and 42 degrees F. was for total heating time. Standard plate counts for aerobic bacteria were extremely low when samples were taken after storage and after reheating. Only two loaves sampled had counts per gram above 100. The absence of microbial growth pattern indicated that increases in TBA scores and decreases in odor and flavor scores were produced by autoxidation of lipids.


Protein value of two imitation milks. Chemical and biologic assays. Two imitation powdered milk products were compared with whole milk for both quantity and quality of protein. One product had comparable quantity of protein, but inferior quality, while the other had comparable quality but inferior quantity. Therefore, neither was equivalent to whole milk when a reconstituted serving of the product was calculated in terms of the U.S. RDA. However, a single serving of either product would constitute 10 per cent of the U.S. RDA for protein. Calcium contribution in terms of U.S. RDA would also be significant, but would not equal whole milk for these particular products. Thus ingredient composition varies widely for imitation milk products. These products were not evaluated for other nutrients, such as fats and vitamins.


Rat brain fatty acid composition: effect of dietary fat and age. The polyunsaturated fatty acid composition of human brain changes, as well as progressively decreases, with age. To determine if whole brain rat lipid shows similar changes with age, rats born to mothers fed semi-synthetic diets were raised on the same diet as their mothers for varying periods prior to sacrifice. Whole brain lipid composition was determined for female offspring, fed diets containing 20% w (by weight) of either lard or safflower oil, from age 6 days to 730 days. The percentage of 20:4omega6 and 22:6omega6 decreased with age; as in man these changes were compensated for largely by increases in 18:1omega9. In contrast, 22:6omega3 rose gradually from 6 to 730 days of age. Varying the degree of unsaturation and/or the amount of dietary fat, with the exception of lard, did not influence the fatty acid composition of whole brain lipid or of the two major phospholipids, phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC). Lard was found to contain trace amounts of 22:5omega3; this acid was avidly retained in the brain accompanied by corresponding decreases in 22:5omega6. The functional significance of the observed age-related brain lipid changes is unknown; it is likely that the lipid changes are in some way related to the deterioration of the central nervous system with time.


Unrecognized psychiatric illness in elderly medical-surgical patients. Research diagnostic criteria were used in a structured interview to evaluate the presence of unrecognized psychiatric illness in 50 acute medical and surgical patients over the age of 65 at the La Jolla Veterans Administration Hospital; 24% of the subjects had unrecognized major mental disorders -- predominantly depression or alcoholism. The geriatric patients most likely to have unrecognized illness were older, widowed or divorced, had past jail and/or psychiatric hospital experiences, and gave histories of vascular disorders. The results are consistent with past literature on the elderly.


Aging and postural sway in women.

Aging and postural sway in women. The effects of aging on postural sway in upright and forward lean stance were investigated. Postural sway was measured on a center of gravity apparatus using two age groups of female subjects 20 to 30 years old and 70 to 80 years old. The older adults demonstrated significantly larger sway areas than the young adults in both stance positions. The patterning of the center of gravity projections on the base of support tended to be similar under all conditions except in the young adults/upright position where the antero-postero excursion was larger than the medial-lateral. The mean locations of the center of gravity projections were often posterior and to the left of the geometric center of the base of support. The distance between the two points was least in the older adults/forward lean position, i.e., the experimental unit which demonstrated the largest area of sway.


Gerontological research in psychology published in the Journal of Gerontology 1963-1974: Perspectives and progress. Psychological research on human subjects published in the Journal of Gerontology from 1963 through 1974 was summarized along a variety of dimensions, including subject selection procedures, sample characteristics, data analysis techniques, research design, author characteristics, and area of psychological research. Comparison of 1963-1968 with 1969-1974 showed a dramatic increase in the number of studies analyzing data for sex differences and a lessened concern for the health status of subjects. Studies of intellectual/cognitive functioning clearly dominated, while those measuring a physiological variable increased the most over the 12-year span. Discussion focused on variations among studies on definitions of age, concerns with sample description with respect to health, and sex differences.


Age differences in the speed of a spatial cognitive process. Older subjects responded slower than younger subjects on a spatial task which required them to rotate mentally a perspectively drawn figure in order to judge whether it was congruent with a second figure. Decision time was partitioned into two components: (1) the time taken for the "mental rotation" process, (2) the time taken for the remaining processes such as stimulus encoding and motor output. Both components required more time in the elderly group. The increase with age in the component of decision time representing rotational processes was similar to those increases seen by other investigators examining age-dependent differences in time required for memory-scanning processes using verbal stimuli.


The relationship of impulse control to cognition and adjustment among institutionalized aged women. Several dimensions of impulse control (i.e., delay of gratification, reflectivity, and motor control) were related to intelligence, mental status, and adjustment among 91 institutionalized aged women. Four different types of impulse control measures were used: Self reports of impulse control, staff ratings, interviewer's ratings, and tests of impulse control. Impulse control measures yielded statistically significant multiple correlations with all outcome measures except life satisfaction. The findings suggest that impulse control in its various forms has a consistent and significant relationship with indices of adaptation. Utilizing stepwise regression analyses, the best predictors of outcome among impulse control measures are presented.


Modernization, modernity, and perceptions of aging: A cross-cultural study. Data from a comparative study of 5,450 young males in six developing nations were used to investigate the association between modernization or modernity and negative attitudes toward aging. The findings question the frequent assertion that "modernity" (the exposure of individuals in developing nations to industrial technology and urban social experience) results in negative perceptions of aging and diminished value attributed to the aged. The data do provide support for the hypothesis that "modernization" (societal development) is related to negative perceptions of aging. Results suggest the necessity of differentiating between "modernization" and "modernity" as levels of analysis and of avoiding value-laden assumptions concerning advantages of either traditional or industrial social settings with respect to the position of elders.


Age and fearfulness: Personal and situational factors. Recent research in the quality of life has identified a sense of security as a significant component. Taking its negative, fear, the personal and structural factors associated with fear of walking around one's neighborhood were assessed in a secondary analysis using data from a 1973 representative national sample collected from the National Opinion Research Center. Although the direct effect of age on fear was minimal, clear and significant age differentials on fear were found by income, size of city of residence, and the presence or absence of others in the household.


Happiness and social participation in aging. This paper reports on a 4-year longitudinal study of 60 elderly women. Data about their happiness and social activities were collected using the Affect Balance Scale and nine measures of socially relevant activities, including three measures of media use, three of interpersonal interaction, and three of activities in voluntary associations. Direct relationships between happiness and social activity among elderly people were found in analysis of these data. This finding was not spurious according to longitudinal data: activity increments were associated with happiness and decrements with unhappiness. Although these findings describe the over-all picture, changes in activities may be more important to happiness among the most elderly persons interviewed than others.


Ego-defense or cognitive consistency effects on environmental evaluations. Numerous investigators have commented upon the sanguine evaluations of their living environments which are given by elderly people. The discrepancy between residents' and observers' evaluations suggests the involvement of ego defense or dissonance reduction. Insofar as this is true, old people's evaluations should become more negative when their efforts to move to a more desirable setting meet with sucess. This hypothesis was tested with the original group of applicants to one housing project for the elderly and cross-validated 9 years later with the original group of applicants to a different project. In both cases the hypothesis was supported. Applicants who were selected to move to new housing became more negative in their evaluations of housing than applicants who were not selected to move.


Clinico-pathological studies on naturally-occurring bovine fascioliasis in the Sudan. An investigation was made of the pathological, haematological and biochemical aspects of naturally-occurring bovine fascioliasis in the Sudan. 228 animals infected with Fasciola gigantica and 25 non-infected controls were used in the study. The infected cattle revealed emaciation, typical liver pathology, and, occasionally, lesions in the lung and the pancreas. Analysis of their sera also showed reduced albumin values, increased globulin concentrations and decrease albumin/globulin ratio, in addition to increased arginase activity. The serum iron concentration, on the other hand, was decreased, while the total iron binding capacity increased and the resultant iron saturation values reduced. Haematological findings in the infected animals included reduced erythrocyte counts, decreased haematocrit values, increased mean corpuscular volumes, eosinophilia and decreased neutrophil, lymphocyte and monocyte counts. Other parameters were similar in infected and control cattle.


Motheaten, an immunodeficient mutant of the mouse. I. Genetics and pathology. A new recessive mutation, motheaten (me), is on chromosome 6, 21.9 +/- 4.3 recombination units distal to white (Miwh). Mice homozygous for the new mutation have neutrophilic lesions of the skin beginning as early as day 1, and pneumonitis with many macrophages in the alveoli as early as day 3. They suffer high mortality from birth onward and none has survived longer than 8 weeks. The lymph nodes may be enlarged, but the thymus, Reyer's patches, and lymphatic tissue of the spleen are much reduced in size. Lymph nodes, spleen, and Peyer's patches lack lymphatic nodules. The lymph nodes and spleen contain many plasma cells. There are increased numbers of neutrophils and monocytes in the peripheral blood, and increased numbers of neutrophils in bone marrow at the expense of red cell precursors. Hematopoietic tissue in the spleen is increased and appears more active than normal. Motheaten mice appear to have an immune deficiency beginning very shortly after birth.


Hereditary chondrodystrophy in the rabbit. Genetics and pathology of a new mutant, a model for metatropic dwarfism. Thirty-one cases of a new hereditary chondrodystrophy in the rabbit have been shown to be associated with a fully penetrant autosomal recessive gene symbolized cd. The mutant is viable prenatally but does not survive after birth. It differs from the two other inherited chondrodystrophies, dachs and achondroplasia, but is very similar to the metatropic dwarf reported in man.


Sensitivity of rat testes to inhibitors of nucleic acid synthesis. III. The inheritance of mitomycin C-induced structural rearrangements of chromosomes. The inheritance of mitomycin C-induced aberrations was studied. Examination of spermatogonia showed statistically significant differences between the progeny of the untreated and treated rats in terms of total aberrant cells and chromosomal structural rearrangements. With the exception of gaps, breaks and fragments, which showed no significant differences between the progeny of the two treatment groups, the rest of the aberrations scored revealed significant increases in their frequencies with an increase in daily doses of mitomycin C (MC). The profile of the aberrations demonstrated a high incidence of X and Y chromosome dissociations, multiple autosomal associations, hypodiploidy, and translocation. Translocations consisted of autosome-autoome, autosome-X chromosome, autosome-X-Y chromosome, and autosome-Y chromosome. It is suggested that the reduced number of offspring per female in the F1 was the consequence of inherited MC-induced chromosomal errors.


The genetics of two new eye color mutants in Culex tarsalis. Two mutants are described the affect eye pigment in the Culex tarsalis mosquito. The data indicate that carmine eye car, and black eye ble, are each linked to one of the two autosomes. The expression of the two pigment in individuals homozygous for both mutants is unique in that larvae and pupae have car eyes and young adults show both the car and ble phenotypes.


[Quantitative architectonic variations in the visual cortex of mice following varying light exposure of the visual organ]. Quantitative - architectural investigations were carried through with two experimental groups of white mice. One group was expsed to a source of light day and night, the other group lived under normal light variations. The animals of both groups were already born under the mentioned conditions and killed in etherization after 51 days. After the determination of the brain-weights, which showed smaller quantities for the group living under light day and night, sections of 10 mum were stained according to the NISSL method and the thickness of the cortex was measured. The layers in the area striata were examined with regard to possible differences. But in this connection no differences between the two groups were to be found. According to the point - method the different coefficients of the cortical layers were determined. The mathematical - statistical analysis with the help of t-test showed significantly bigger coefficients with the latter group (living under light day and night). These coefficients correspond to a smaller part of volume of neurons or their components in a defined volume. This way it was proved that changed light conditions result in changes of the microscopical structure of the area striata. At the same time significant changes occur in the nucleus-plasma-relation of the various layers. These make us recognize the functional adaptations to the changed environmental influences.


Genes associated with leukocyte production in mice. We have investigated the genes influencing leukocyte production in mice by selective breeding for differences in leukocyte count and developed two major lines differing about 8-fold. In these lines we have made counter selective breeding, crossbreeding between them, and developed methods of using marker genes to search for individual genes distributed on different chromosomes. We have revealed an overall dominance of genes for low leukocyte count over those for high counts, and effects of genes at the agouti locus, certain mutant genes, and a gene or genes in the XVI linkage group. We have commented on the application and approach of quantitative genetic experimentation from both a theoretical and practical point of view and, on the basis of present results, discussed the nature of polygenes in relation to genes causing polymorphisms.


[The ontogenetic development of pyramidal neurons in the hippocampus (CA1) of the rat]. 1. The development of pyramidal neurons of the hippocampus (CA1) of the albino rat was investigated by means of light-microscopy with GOLGI impregnation methods. The stages of age of the animals covered the period from the 15th prenatal to the 30th prematal day. Three and six months old rats were used for comparison. In addition some histological series were made by staining with hemalaun-eosine. 2. The formation of the apical, basal and side dendrites, the existence of common signs of growth (swellings, growth cones, sprouts) and the amount of spines were used for the estimation of neuronal changes. The development of the typical structure of the hippocampal region and of the pyramidal layer in the CA1-field was described. 3. The migration of neuronal elements to the pyramidal layer is finished around the time of birth, but lasts in the area dentata at least to the 8th postnatal day. The hippocampus shows a nearly mature figure in its hitology 15 days after birth. 4. Until the 19th embryonal day bipolare spongioblasts can be seen, but already one day before postmigratory neuroblasts are existent. During this period the division of matrix cells occurs and the migration of the neuroblasts is beginning. (early prenatal developmental period) 5. Since the 19th prenatal day the neuroblasts show long apical dendrites, growing axons with first sprouts of collaterals, but also sprouts of basal and side dendrites. Until the time of birth a further formation of dendrites and a narrowing of the perikarya in the pyramidal layer follow. (late prenatal developmental period) 6. The intermediate neuroblasts grow continuously in the first postnatal time and let perceive an increase in the number of dendritic stems and branches. Postsynaptic structures (spines) appear in a little increasing number. The initial segment of the apical dendrite remains free of spines. (early postnatal developmental period).


Linkage of white band and long hair in the Syrian hamster. The mutant genes Ba and l display autosomal linkage of 20.2 +/- 2.3. The available evidence indicates that the linkage is independent of two others previously reported. Thus, three linkage groups are now known for the Syrian hamster.


[Development of the telencephalon of Salmo irideus Gib]. A developmental study of the Telencephalon of the trout (Salmo irideus) has been done. The stages of fixation were 18 days after fecondation, hatching; 5 days, 1, 2, and 3 months, and 1 year after hatching. The different cell-masses are summarized in table 1. In the young trout, eversion is not important. Just, 2 olfactory bulbs are evaginated. In front of the commissura anterior, we can see: the Nucleus ventroventralis and the Nucleus ventrodorsalis, on the one hand; a voluminous dorsal area which includes: the Nucleus dorsolateralis, the Nucleus dorsomedialis, the Nucleus dorsocentralis and the dorso and ventro-lateral groups, on the other hand. The different Nuclei of the dorsal area are differentiated from a primordial territory which is the area intermedius at the hatching stage. On the hemispheric wall at the level of the tela, we can see the Nucleus teniae. Behind the plan of the commissura anterior, the Nucleus posterior is already seeing at the end of the first month after the hatching. A Golgi-Cox study showed some aspects of different kinds of neurons, and an important neuropil at the level of the Nucleus dorsocentralis too.


[Chronoarchitectonic analysis of the rat brain using radioautography. I. Histogenesis of the telencephalon]. 1) Isocortex We find a centrifugal type chronoarchitectonic gradient with, however, a considerable overlap between the various generations of neurons. Thus in the older, deep layers (13.5 days) of the lateral neocortex 35% of the cells are chromologically incongruous (certain are very recent: 17.5 days and more). Cell production is a continuous process and has its peak towards 15.5 days of gestation. This refutes the existence of successive waves of cells. It is not possible to give even an approximate date to the isocortical layers, for the cortical laminations and the isochrones are nor concentric. What finally characterizes this structure from a chronoarchitectonic point of view is the considerable duration of the sequence of neuron production going from 13,5 days to birth. 2) Allocortex We find a centrifugal gradient in the paleocortex. In several of the structures of which it is composed a chronoarchitectonic incongruity can be attributed to the microneurons. It is the case with the islands of CALLEJA (in the olfactive tubercule) which separate very late on. In the archicortex the dominant gradient is again centrifugal. Here we find horizontal variations of the chronoarchitectonic patterns which are discussed with reference to the conception of a possibly fragmented cortex. 3) Striatum the chronoarchitectonic results largely confirm the diencephalic origin of the paleostriatum (STRASSER 1920, SPATZ 1921). In the archistriatum we find a steep rostrocaudal gradient, while the chronoarchitectonic heterogeneity of the structure tends to confirm the conception of a mixed origin (striatum and paleopallium). 4) Claustrum there is a real chronoarchitectonic incongruity between this structure and the isocortex. On one hand the sequence of the anterior part of the claustrum is of the paleostriate type. The posterior part is more probably archistriate. These findings suggest that the formation of the claustrum is of hybrid origin. 5) Septum The characteristic gradient of this formation is caudorostral. This gradient is practically common to all the structures except the telencephalon. We also find a centrifugal gradient related to the presence of a recent "cortex" which could be the counterpart of the cortical septal nuclei in superior mammals.


Niridazole, a potent long-acting suppressant of cellular hypersensitivity. III. Minimal suppression of antibody responses. Niridazole, an anthelminthic drug, has been shown to be a potent long-acting suppressant of cell-mediated immune responses both in man and in experimental animals. In the present study the effect of niridazole on the magnitude and kinetics of the primary and secondary antibody responses of mice to sheep erythrocytes, human serum albumin, and keyhold limpet hemocyanin was investigated. The therapeutic dose of niridazole for murine schistosomiasis moderately and transiently inhibited the primary antibody response to these antigens, but had no effect on ongoing antibody production against keyhole limpet hemocyanin or on secondary responses to any of the antigens. Single doses of niridazole (which suppress cell-mediated immune responses) had no effect whatsoever on the most strongly inhibited of the primary antibody responses, that to alum-precipitated polymerized human serum albumin.


Specifically cytotoxic human and mouse lymphoid cells induced with antibody or antigen-antibody complexes. Human or mouse lymphoid cells could be "armed" with anti-NIP antibodies to become cytotoxic to NNP-conjugated fowl erythrocytes (NNP and NIP are closely related haptens). The arming factor was neutralized by a sufficient concentration of NIP-BSA (twice the concentration causing maximal precipitation) but low concentrations (e.g., 7% of the maximal precipitation concentration) increased the arming capacity.