Showing papers in "Experimental Biology and Medicine in 1959"
TL;DR: The small amounts of rat kidney proteins used, support the interpretation that an isoand autosensitization mechanism is at play, and help clarify the mechanism behind the severe nephrotic syndrome noted in 20 rats given Freund's adjuvants and a supernate of rat kidneys suspension by intraperitoneal injection.
Abstract: Summary1) A severe nephrotic syndrome was noted in 20 rats given Freund's adjuvants and a supernate of rat kidney suspension by intraperitoneal injection. When kidney tissue was replaced by liver, only 3 of 21 animals developed a much milder renal disease. Lung or muscle suspensions failed to induce proteinuria in 10 rats. 2) In large doses (0.5 ml) Freund's adjuvants alone produced a mild nephrotic disease in 3 of 10 rats. Even though the smaller amounts of the adjuvants usually used (0.25 ml) never produced proteinuria, slight histological alterations of the glomerular structure were frequently noted. 3) In contradistinction to other tissue suspensions addition of rat kidney supernate enhanced the effect of adjuvants markedly and regularly. 4) The small amounts of rat kidney proteins used, support the interpretation that an isoand autosensitization mechanism is at play.
533 citations
TL;DR: Radioautographs of early neural tube of chick embryos treated with thymidine-H3 for varying intervals of time give evidence substantiating the concept of inter-kinetic migration of nuclei, as well as confirming DNA synthesis in nuclei of peripheral part of wall.
Abstract: ConclusionRadioautographs of early neural tube of chick embryos treated with thymidine-H3 for varying intervals of time give evidence substantiating the concept of inter-kinetic migration of nuclei. Synthesis of DNA occurs only in nuclei of peripheral part of wall, and does not take place in those of juxta-luminal zone. The period of DNA synthesis continues for at least 4 hours, but does not extend much beyond this time.
235 citations
TL;DR: Monkey and guinea pig sera inhibit human C'1-esterase to about the same extent as human serum, while rabbit serum is about one-third as active.
Abstract: Discussion and SummaryAn assay is described for measurement of a serum inhibitor of an esterase derived from preparations of the first component of complement (C'1-esterase). Esterolysis of N-acetyl-L-tyrosine ethyl ester by C'1-esterase is inhibited instantaneously and stoichiometrically by fresh human serum. Units of C'1-esterase and of serum inhibitor are defined. The inhibitor in human serum is stable at 45 for at least 4 months, at 37° for at least 24 hr. and at 48° for at least 30 min. It is completely inactivated during 30 min. incubation at 60° and is labile at 0° at pH values below 6. The inhibitor is inactivated at —5 in the presence of methanol concentrations of 15° or greater but is recovered quantitatively in a 40° ammonium sulfate supernatant fraction. These data are being applied to purification of the inhibitor from human serum. Purification procedures and properties of the purified inhibitor will be reported elsewhere.Monkey and guinea pig sera inhibit human C'1-esterase to about the same...
191 citations
TL;DR: Taurine and glycine were given to human subjects and the bile acids studied and markedly increased the proportion of taurine conjugated bile acid, whereas glycine did not change the biles acid pattern of the normal subject.
Abstract: SummaryTaurine and glycine were given to human subjects and the bile acids studied. Taurine (0.5 g × 3 daily) markedly increased the proportion of taurine conjugated bile acids, whereas glycine (7 g × 3 daily) did not change the bile acid pattern of the normal subject. The findings have been discussed in relation to conjugation of bile acids under normal and pathological conditions.
157 citations
TL;DR: Non-precipitating antibodies to glucagon have been produced in rabbits and detected by both Berson-Yalow and Skom-Talmadge technics, and a basis for an immunoassay for glucagon appears to have been established.
Abstract: SummaryNon-precipitating antibodies to glucagon have been produced in rabbits and detected by both Berson-Yalow and Skom-Talmadge technics. A basis for an immunoassay for glucagon appears, thereby,...
157 citations
TL;DR: Findings support previous studies which suggested the occurrence of a rapid shift from carbohydrate to fat catabolism in the neonatal period.
Abstract: SummaryConcentration of UFA in blood plasma of fetal sheep and newborn man was consistently much lower than in plasma obtained simultaneously from their mothers. The levels were comparable to those found in man after administration of glucose or insulin. In both species the plasma level of UFA rose rapidly within 2 hr of birth with an associated hypoglycemia. These findings support previous studies which suggested the occurrence of a rapid shift from carbohydrate to fat catabolism in the neonatal period.
153 citations
TL;DR: It would appear that the effect of epinephrine on mobilization of free fatty acids is not mediated by a decrease in carbohydrate availability, but possibly by increased rate of glyceride breakdown.
Abstract: SummaryEpinephrine increases glucose uptake of adipose tissue incubated in vitro. This effect is common to both insulin and epinephrine. However, epinephrine increases and insulin decreases release of free fatty acids. It would appear that the effect of epinephrine on mobilization of free fatty acids is not mediated by a decrease in carbohydrate availability, but possibly by increased rate of glyceride breakdown.
151 citations
TL;DR: Nychthemeral variations in levels of plasma free corticosteroids in the rat have been observed, with highest concentrations of steroid between 4 p.m. and midnight.
Abstract: SummaryNychthemeral variations in levels of plasma free corticosteroids in the rat have been observed, with highest concentrations of steroid between 4 p.m. and midnight. The magnitude of these cyclic variations is such that they will have to be considered in measurement of “resting levels” of plasma corticosteroids in this species.
140 citations
TL;DR: Serum non-esterified fatty acids (NEFA) and triglyceride (TG) levels were measured in four normal individuals during difficult levels of emotional arousal, which were accompanied by rises in serum NEFA levels, but not of TG levels.
Abstract: Summary1. Serum non-esterified fatty acids (NEFA) and triglyceride (TG) levels were measured in four normal individuals during difficult levels of emotional arousal. 2. Periods of arousal in which feelings of anxiety and/or hostility were evoked were accompanied by rises in serum NEFA levels, but not of TG levels.
128 citations
TL;DR: When arginine was deleted, the typically rounded cell of Novikoff hepatoma was no longer apparent; but a predominance of fibroblasts remained attached to the surface of the flasks.
Abstract: SummaryNovikoff hepatoma requires 12 amino acids and glutamine for growth in vitro. When both glycine and serine were deleted from the medium, no growth occurred. In presence of serine some growth was apparent, but glycine was more effective in stimulating tumor cell proliferation. Glutamic acid and sodium thioglycolate could partially spare glutamine and cysteine requirements, respectively, and several sulfur-containing inorganic salts could partially replace cysteine. Arginine could be replaced by citrulline but ornithine was not active. When arginine was deleted, the typically rounded cell of Novikoff hepatoma was no longer apparent; but a predominance of fibroblasts remained attached to the surface of the flasks.
105 citations
TL;DR: A tentative hypothesis concerning the mechanism of complement fixation by antigen-antibody reaction is presented and it is shown that inactivation of C'3 by aggregated HGG is markedly dependent upon temperature.
Abstract: Summary1. Aggregated human gamma globulin, obtained by heating, gave immediate skin reactions in normal guinea pigs and inactivated complement, whereas aggregated bovine gamma globulin did not have either activity. 2. Aggregated human gamma globulin and antigen-antibody complexes are comparable on weight basis with respect to skin reactivity and complement inactivation. 3. Divalent cation(s) are required for inactivation of complement by aggregated HGG. Inactivation of C'3 by aggregated HGG is markedly dependent upon temperature. 4. A tentative hypothesis concerning the mechanism of complement fixation by antigen-antibody reaction is presented.
TL;DR: Repeated doses of ergotamine and hexamethonium had no effect on increase in plasma non-esterified fatty acid (NEFA) concentration which occurs during fasting, suggesting that the stimulus to increased NEFA mobilization during fasting may not be mediated by the adrenergic nervous system.
Abstract: SummaryRepeated doses of ergotamine and hexamethonium had no effect on increase in plasma non-esterified fatty acid (NEFA) concentration which occurs during fasting. Dibenzyline was similarly without effect on this response. These findings suggest that the stimulus to increased NEFA mobilization during fasting may not be mediated by the adrenergic nervous system.
TL;DR: In rats with radiation-induced hypoplasia, this fall in erythropoietine titer was modified, and it is suggested that the marrow utilizes erymorphine, and the clinical implications are discussed.
Abstract: SummaryData have been presented on rate of appearance and disappearance of erythropoietine. Plasma level of erythropoietine rises promptly in response to hypoxia but on continued exposure declines. In rats with radiation-induced hypoplasia, this fall in erythropoietine titer was modified. Accordingly, it is suggested that the marrow utilizes erythropoietine and the clinical implications are discussed.
TL;DR: It is suggested that ACTH may have a physiological role in fatty acid mobilization not mediated by adrenal cortical tissue and addition of small amounts of ACTH in vitro to adipose tissue increases release of NEFA.
Abstract: Summary1. Adrenalectomy decreases release of nonesterified fatty acids (NEFA) from rat epididymal adipose tissue. 2. Addition of small amounts of ACTH in vitro to adipose tissue increases release of NEFA. This effect is markedly diminished in adrenal-ectomized animals. 3. It is suggested that ACTH may have a physiological role in fatty acid mobilization not mediated by adrenal cortical tissue.
TL;DR: Inactivated (56°C 1/2 hr) rabbit and guinea pig serum, prepared with agent X filtrates, only partially neutralized passage A leukemic agent; passage A immune rabbit serum had a distinct, though not complete neutralization effect on the passage A agent.
Abstract: A filterable leukemic agent designated virus X'' recovered from a C3H female in which leukemia was induced by x irradiation was passed serially through 4 consecutive cell-free inoculations of suckling C3H mice. Of 40 mice inoculated, 26 developed leukemia at ages varying from 3 to 11 months. Inactivated rabbit and guinea pig serum, prepared with agent X filtrates, only partially neutralized passage A leukemic agent; passage A immune rabbit serum had a distinct, though not complete, neutralization effect on the passage A agent. (auth)
TL;DR: Preliminary results of administering a resin with bile acid sequestering properties with lower serum total cholesterol levels are reported, with no systemic side-effects observed.
Abstract: SummaryPreliminary results of administering a resin with bile acid sequestering properties are reported. The preparation was administered to 26 patients for periods of 2 to 34 weeks. Serum total cholesterol levels were lowered by more than 10% in 23 of 26 patients. Average decrease in serum total cholesterol for all subjects was 20% (p<0.001). No systemic side-effects were observed. Six subjects treated for 6 weeks or longer maintained lowered values of serum total cholesterol without escape.
TL;DR: There exists a striking correlation between the amount of juxtaglomerular granulation and the amountof extractable renin in a kidney, which does not prove that these granules are composed of renin but the observations are compatible with such a hypothesis.
Abstract: SummaryNormal rat kidneys and kidneys with a narrowed renal artery have abundant granules in the juxtaglomerular cells and large quantities of extractable renin. On the other hand, kidneys of rats with desoxycorticosterone hypertension and the “untouched' kidney of rats with unilateral renal hypertension (resulting from narrowing of the contralateral renal artery) both have a virtual absence of juxtaglomerular granules as well as absence of extractable renin. There is so little renin in these kidneys that the renal extracts usually produce a depressor response. Thus, there exists a striking correlation between the amount of juxtaglomerular granulation and the amount of extractable renin in a kidney. This does not prove that these granules are composed of renin but the observations are compatible with such a hypothesis.
TL;DR: It is concluded that optimal thyroid function is requisite for the NEFA mobilizing action of epinephrine in vivo.
Abstract: SummaryMobilization of NEFA by epinephrine in rhesus monkeys is abolished by hypophysectomy while the hyperglycemic response is retained. Pretreatment of hypophysectomized monkeys with cortisol acetate, ACTH, prolactin and growth hormone fails to restore response to epinephrine in terms of NEFA mobilization. Pretreatment with TSH or triiodothyronine, however, produced a restoration of the response. It is concluded that optimal thyroid function is requisite for the NEFA mobilizing action of epinephrine in vivo.
TL;DR: Evidence was cited that in Chinese hamsters, the disease is genetically determined and certain inferences were drawn as to the importance and significance of this observation for the future study of inheritance of diabetes, screening of hypoglycemic agents in the Chinese hamster, and metabolic studies.
Abstract: SummarySpontaneous diabetes mellitus, as observed in Chinese hamsters, has been described and compared with diabetes in human and experimental animals. Evidence was cited that in Chinese hamsters, ...
TL;DR: Zymosan renders mice highly susceptible to the lethal effect of endotoxin at a time when activity of the R.C.E.S.G. is greatly stimulated, and Pretreatment with cortisone abolishes nearly completely the increased toxicity to endotoxin caused by zymosAn or B.C.)G.
Abstract: SummaryZymosan renders mice highly susceptible to the lethal effect of endotoxin at a time when activity of the R.E.S. is greatly stimulated. This effect is similar to that following B.C.G. infection. Pretreatment with cortisone abolishes nearly completely the increased toxicity to endotoxin caused by zymosan or B.C.G. infection.
TL;DR: It is concluded that chimyl alcohol can be absorbed unchanged but that it is extensively metabolized already in the mucosa cells, whether it is fed as free chimylcohol or as an alkoxydiglyceride.
Abstract: Summary1. C14-labelled chimyl alcohol (α:-/1-C14/-hexadecylglyceryl ether) has been fed as free chimyl alcohol or as chimyl dioleate to rats. Intestinal contents and thoracic duct lymph lipids have been analyzed and expired CO2 has been collected. 2. Mixed ether-glycerides have been isolated from the intestinal contents after feeding free chimyl alcohol dissolved in olive oil, indicating a synthesis of new glyceride ester bonds. 3. Free labelled chimyl alcohol has been isolated from the intestinal contents after feeding labelled chimyl dioleate indicating an exchange and release of fatty acids in both 1-, and 2-position in the mixed ether-glyceride. 4. In lymph lipids more than half the radioactivity was associated with palmitic acid, indicating a splitting of the ether bond in mucosa cells. 5. It is concluded that chimyl alcohol can be absorbed unchanged but that it is extensively metabolized already in the mucosa cells, whether it is fed as free chimyl alcohol or as an alkoxydiglyceride.
TL;DR: Mesenteric arteries of rats with acute renal hypertension showed a significant rise in sodium, potassium, and chloride, as well as expansion of total water, but total cation concentration in tissue water was not significantly altered.
Abstract: An accurate and convenient method for determination of tritium water in body fluids by liquid scintillation spectrometry is described. The method is based on distillation of body fluids with benzene to provide an almost pure sample of H/sup 3/-water, and use of an effective solvent (dioxanenaphthalene) to transfer the excitation energy of tritium to the phosphors, 2,5-diphenyloxazole and 1,4-bis-2 (5-phenyloxazolyl)-benzene. When applied to determination of tritium water in urine and plasma, the method gave recoveries ranging from 98 to 104%. By the new method, metabolism of intravenously administered H/sup 3/- beta -sitosterol to H/sup 3/-water was demonstrated in the guinea pig. (auth)
TL;DR: 6-MP, a powerful metabolic antagonist to nucleic acid synthesis, prolongs survival time of skin homografts in rabbits when administered after grafting when given continuously, but toxicity of 6-MP limits the length of time treatment may be given.
Abstract: Summary6-MP, a powerful metabolic antagonist to nucleic acid synthesis, prolongs survival time of skin homografts in rabbits when administered after grafting. Treatment must be given continuously to maintain graft viability. However, toxicity of 6-MP limits the length of time treatment may be given.
TL;DR: Concentrations of nonesterified fatty acids and of glucose in plasma were determined before and after infusion of epinephrine and norepinephrine into dogs.
Abstract: SummaryConcentrations of nonesterified fatty acids and of glucose in plasma were determined before and after infusion of epinephrine and norepinephrine into dogs. At the same concentration and rate of infusion, norepinephrine produced a greater increase in nonesterified fatty acids.
TL;DR: A simple tissue culture chamber is described which permits phase microscopy at high magnifications and easy staining for permanent record and is useful for time lapse photography.
Abstract: SummaryA simple tissue culture chamber is described which permits phase microscopy at high magnifications and easy staining for permanent record. The chamber is also suited to perfusion studies, permits observation of cells over extended periods, and is useful for time lapse photography.
TL;DR: Thymectomy, either preceding, or following inoculation of leukemic passage A filtrate, inhibits development of leukemia in otherwise susceptible C3H mice.
Abstract: Summary1. Of 39 young and adult C3H mice, thymectomized, and a few days later inoculated intraperitoneally with passage A leukemic filtrate, none developed leukemia. Of 41 normal controls inoculated simultaneously with the same filtrate 18 (44%), developed leukemia at 7 months average age. 2. Of 55 suckling C3H mice inoculated with passage A leukemic filtrate when less than 9 days old, then 1 month later thymectomized, only 1 thus far developed a palpable spleen, and definite leukemia. Of 78 control litter mates inoculated simultaneously with the same filtrates, but not thymectomized, 68 (87%), developed leukemia at 2.7 months average age. 3. Thymectomy, either preceding, or following inoculation of leukemic passage A filtrate, inhibits development of leukemia in otherwise susceptible C3H mice.
TL;DR: It is revealed that intravenous injection of human growth hormone to both hypophysectomized and normal individuals cause an increase in plasma unesterified fatty acids 6 hours after injection.
Abstract: SummaryThese studies reveal that intravenous injection of human growth hormone to both hypophysectomized and normal individuals cause an increase in plasma unesterified fatty acids 6 hours after injection. Also that level of plasma alpha amino acid nitrogen drops 4–6 hours after injection of growth hormone. Both fat-liberating and “protein sparing'effects of human growth hormone in man are demonstrated.
TL;DR: An extra-adrenal action of corticotropin on fat mobilization in the intact animal similar to that induced by growth hormone is demonstrated, and inhibition of fat loss by hydrocortisone in adrenalectomized mice could be overcome by simultaneous administration of cortICotropin.
Abstract: SummaryPurified corticotropin and growth hormone both stimulate lipid mobilization from the epididymal fat depots of fasting mice. Hydrocortisone failed to induce lipid loss in intact mice and inhibited fat mobilization in adrenalectomized mice, indicating that the lipid mobilizing effect of corticotropin is not mediated by adrenal stimulation. Furthermore, inhibition of fat loss by hydrocortisone in adrenalectomized mice could be overcome by simultaneous administration of corticotropin. The results demonstrate an extra-adrenal action of corticotropin on fat mobilization in the intact animal similar to that induced by growth hormone.
TL;DR: Findings are taken as direct evidence for the concept that growth hormone treatment causes NEFA mobilization from fat stores.
Abstract: SummaryThe release of nonesterified fatty acids (NEFA) from epididymal fat bodies removed from normal, hypophysectomized and hypophysectomized growth hormone treated rats has been investigated. Hypophysectomy inhibits and growth hormone administration stimulates NEFA release from adipose tissue in vitro. These findings are taken as direct evidence for the concept that growth hormone treatment causes NEFA mobilization from fat stores.
TL;DR: Intraperitoneal injection of hydroxylamine resulted in elevation of levels of γ-aminobutyric acid in 8 brain areas of the rat, even after rats were pretreated with methylene blue to reduce methemoglobin formation.
Abstract: Summary1. Intraperitoneal injection of hydroxylamine resulted in elevation of levels of γ-aminobutyric acid in 8 brain areas of the rat. 2. These elevated levels of γ-aminobutyric acid were attained even after rats were pretreated with methylene blue to reduce methemoglobin formation. 3. The effect of a single injection of hydroxylamine persisted for at least 5 hours. 4. The potential value of this procedure for physiological study has been discussed.