bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF GROWTH HORMONE ON THE UTILIZATION OF 1-C14OCTANOIC ACID BY RAT LIVER SLICES
Authors: Perry W. F. , Friesen H. G.
Published: October 2017

Young ([Formula: see text] months), adult (4–5 months), and old (2(+) years) rats were injected with growth hormone intraperitoneally in doses of 4 mg./100 g. at various intervals of time before removal of the liver. Slices of liver were incubated with radioactive octanoic acid and the production of CO2and acetoacetic acid measured.In adult rats fed ad libitum, growth hormone injected 4 hours before the rats were killed had no consistent effect on acetoacetic acid or carbon dioxide production by the liver slices. In adult rats fasted 24 hours before they were killed, growth hormone was likewise found to have no effect on ketogenesis and CO2production irrespective of whether it was injected 4, 12, or 24 hours before the rats were killed. Young rats that were fasted 24 hours and to which growth hormone was administered at the 20th hour of fasting showed a slight ketogenesis but the values for the specific activity of the acetoacetic acid suggested the increased ketogenesis was not derived from the labelled fatty acid. No effect on CO2production was noted. In old rats that were fasted 24 hours and to which growth hormone was given at the 20th hour of fasting, a slight decrease in acetoacetic acid formation by the liver slices was observed which appeared to be due to an over-all reduction in fatty acid utilization. There was again no alteration in CO2production. Treatment of adult rats for 5 days with growth hormone, followed by incubation of the liver slices with octanoate, was found to influence neither ketogenesis nor CO2production.
FURTHER STUDIES ON THE ENDOCRINE CONDITIONING OF THE HEPARIN-INDUCED LIPEMIA CLEARING ACTIVITY (LCA) IN THE RAT
Authors: Constantinides P. , Cairns A. , So Y.
Published: October 2017

The effects of various endocrines and of stress on the "lipemia clearing activity" (LCA) which is elicited in rat plasma by intravenous heparin injection were studied.High dosage cortisone accelerated LCA, but low dosage cortisone did not affect it. Severe catabolic stress accelerated LCA. Application of a single mild stress was ineffective, but the combination of two mild stressors accelerated LCA. ACTH had no influence on LCA, but adrenalectomy accelerated it. Stilbestrol inhibited LCA at both a low and a high dosage level, but there was no difference in LCA production between males and females or between estrous and diestrous females. Estrous females, however, displayed less LCA than ovariectomized females. Anterior pituitary extract inhibited LCA in females and hypophysectomy accelerated it in both sexes. A synthetic oil emulsion yielded the same qualitative information as lipemic plasma wherever it was used as a substrate for the clearing activity of postheparin plasma.Thus, with the exception of the effects of sex difference and low dosage cortisone, most of the previously reported endocrine effects on the LCA that follows subcutaneous heparin were also obtained when heparin was injected intravenously. The physiological significance of these findings is discussed.
FACTORS INFLUENCING THE AMOUNT OF INSULIN EXTRACTABLE FROM BEEF PANCREAS: I. EFFECTS OF AGING FRESH PANCREAS AT ROOM TEMPERATURE
Authors: Wrenshall Gerald A. , Best Charles H. , Hartroft W. Stanley
Published: October 2017

Effects on the concentration of extractable insulin of aging fresh beef pancreas at temperatures in the 22–26 °C. range have been described. Two phases of change with time of aging have been observed, describable as a transient increase superimposed on a progressive fall toward zero in the concentration of insulin extractable from the pancreas. In two of the eight experiments reported only the second phase was detected.Various hypotheses concerning the cause of the first phase are considered. The available experimental evidence is considered to support the hypothesis that the early rise in extractable insulin resulted from the continuing new formation of insulin from structural components already present in the cytoplasm of the beta cells at time of exsanguination, or diffusing into it thereafter. The progressive fall in the extractable insulin during the second phase must have resulted from destruction or inactivation of insulin within the pancreas.The bearing of these recent findings on the usage of the term "The insulin content of the pancreas" has been discussed.
FACTORS INFLUENCING THE AMOUNT OF INSULIN EXTRACTABLE FROM BEEF PANCREAS: II. EFFECTS OF ALTERING THE EXTRACTION PROCEDURE ON THE CHANGES IN THE INSULIN EXTRACTABLE FROM AGING PANCREAS AND ON RECOVERY OF INSULIN
Authors: Labuschagne C. J. , Haessig B. K. , Wrenshall Gerald A.
Published: October 2017

Using variants of a hydrochloric acid – ethanol extraction procedure, which are described, only about one-tenth of the crude insulin extractable from beef pancreas was found to be extracted in the same way as crystallized Zinc-Insulin added to extraction fluid. An effective conjugation of most of the extractable crude insulin from beef pancreas with non-insulin factors thus appears to have occurred at least during the acid–alcohol phase of extraction. Nevertheless the mouse-convulsion method used for insulin assay proved effective in estimating the amount of this conjugated fraction of the extractable insulin following the addition either of the unconjugated Zinc-Insulin-Toronto or of the conjugated Protamine Zinc Insulin (Toronto) to the crude insulin in acid alcoholic extracts of pure beef pancreas. The phases of transient increase and progressive decrease in the insulin extractable from initially fresh beef pancreas during aging also occurred in the conjugated fraction of the extractable insulin. The proportion of this crude insulin which extracted as conjugated insulin did not change appreciably during the process of aging.The above findings support the view that the transient increase superimposed on a progressive decrease in the extractable insulin during aging of fresh pancreas are not caused by progressive changes in conjugation of insulin. The finding of similar changes with time of aging in the concentration of extractable insulin of beef pancreas when two different extraction procedures were employed, and again when two different extraction media were employed, suggests that these changes are not products of the method or materials employed for extraction.
FACTORS INFLUENCING THE AMOUNT OF INSULIN EXTRACTABLE FROM BEEF PANCREAS: III. EFFECTS OF TEMPERATURE AND OF FREEZING AND THAWING ON CHANGES ACCOMPANYING THE AGING OF FRESH PANCREAS
Authors: Wrenshall Gerald A. , Casselman W. G. Bruce , Best Charles H.
Published: October 2017

The early rise with time of aging in the amount of insulin extractable from fresh beef pancreas has been observed in two different extracts, both at 6 °C. and at 25 °C., in samples of the same mature beef pancreas. The same phenomenon has been seen to a lesser degree at 25 °C. in samples of fresh pancreas from immature animals. In the study with pancreas from the mature animal the rates of change in extractable insulin were 12 times as large at 25 °C. as at 6 °C. The early rise was observed in fresh pancreas but not in samples which had been frozen and thawed prior to aging.
THE PHYSIOLOGICAL ULTRASTRUCTURE OF CELL MEMBRANES
Authors: Burgen A. S. V.
Published: October 2017

Null
ELECTROLYTE METABOLISM IN THE RAT EXPOSED TO A LOW ENVIRONMENTAL TEMPERATURE
Authors: Baker D. G. , Sellers E. A.
Published: October 2017

Some aspects of electrolyte metabolism in the rat exposed to a low environmental temperature have been examined. The first day of exposure at 2 °C. was accompanied by a loss of chloride. Continued exposure to cold resulted in a retention of sodium, and to a lesser extent, of potassium. Exposure to cold for 45 days (at 2 °C.) caused a sustained elevation of concentration of sodium in the plasma, with a transient increase in potassium and no change in the chloride concentration. Prolonged exposure to cold resulted in an increased blood volume and total body water content. These observations suggest that the rats acclimatized to cold have a larger proportion of actively metabolizing tissues than do comparable animals at room temperature.
EFFECT OF HISTAMINE ON GASTRIC PEPSINOGEN, PEPSIN SECRETION, AND BLOOD PEPSINOGEN IN GUINEA PIGS
Authors: Kowalewski K.
Published: October 2017

The endocrine and exocrine activity of guinea pig stomach was measured by the determination of pepsinogen in gastric tissue and in plasma. Gastric juice pepsin was also studied.A significant increase of both pepsinogen and pepsin was found in animals treated with a dose of histamine (75 mg. per kg. of body weight). These results give further evidence that the zymogenic cells of gastric mucosa may be stimulated by histamine. The determination of pepsinogen in gastric tissue seems to permit a direct approach to the enzymatic function of zymogenic cells.
INHIBITION OF WALKER CARCINOMA 256 BY 6-AMINONICOTINAMIDE
Authors: McColl J. D. , Rice W. B. , Adamkiewicz V. W.
Published: October 2017

The nicotinamide antagonist, 6-aminonicotinamide, was administered for 2 days prior to, and for 10 days following, the transplant of a rapidly growing Walker carcinoma 256. At a dose which did not produce pronounced loss of body weight (0.5 mg./kg.), a significant inhibition of the tumor was observed. The degree of inhibition was similar to that obtained with the purine antagonist, 6-mercaptopurine, at a dose of 10 mg./kg.Splenomegalia was also significantly inhibited in those instances where there was an inhibition of tumor dimensions.
AEROBIC AND ANAEROBIC P32LABELLING OF PHOSPHOLIPIDS AND ADENOSINE PHOSPHATES IN HYPOTONIC HOMOGENATES OF RAT BRAIN
Authors: Berry J. F. , McMurray W. C.
Published: October 2017

Under aerobic conditions, a suitably 'reinforced' homogenate of rat brain prepared in distilled water was capable of labelling lipid P, ATP, ADP, and AMP from inorganic P32. The labelling was 'uncoupled' by the addition of DNP. The DNP decreased the specific activity of each of the above compounds and decreased the steady-state concentrations of ATP, with an increase in the concentrations of inorganic P, ADP, and AMP. Fluoride increased the specific activity of the lipid P and the steady-state concentration of ATP. Cyanide decreased the specific activity of lipid P and both the specific activity and the steady-state concentration of ATP.Under anaerobic conditions, the labelling of the lipid P and the adenosine phosphates was as good as that observed in the presence of oxygen. The anaerobic labelling of both lipid P and the adenosine phosphates was less sensitive to DNP or cyanide and more sensitive to iodoacetate than the aerobic labelling. In contrast to the aerobic labelling, the anaerobic labelling was inhibited by fluoride.In most instances, changes in the labelling of lipid P corresponded to those observed for the labelling of ATP. An exception was the labelling of lipid P that occurred under aerobic conditions in the presence of fluoride. Here the specific activity of the lipid P was related to the concentration rather than to the specific activity of ATP.
THE DISTRIBUTION OF RADIOACTIVE CARBON IN THE RAT AFTER THE ADMINISTRATION OF RANDOMLY LABELLED C14-β-CAROTENE
Authors: Willmer J. S. , Laughland D. H.
Published: October 2017

The distribution of C14 has been studied in rats following the oral administration of C14-β-carotene, which is known to be readily converted to vitamin A in the intestine. The rats were maintained in a respiration chamber and individuals removed at various time intervals up to 28 hours after dosing, and the concentration of C14 in tissues was determined. The counts per million per gram of tissue was higher in the adrenal glands and hypophysis than in the other organs examined. The pattern of C14 distribution in intestine, liver, kidneys, and blood appears consistent with current knowledge of the metabolism of vitamin A.
STUDIES ON THE PRESERVATION OF BLOOD: V. THE INFLUENCE OF THE HYDROGEN ION CONCENTRATION ON CERTAIN CHANGES IN BLOOD DURING STORAGE
Authors: Kashket Shelby , Rubinstein David , Denstedt Orville F.
Published: October 2017

The hexokinase of the erythrocyte has two optima of activity, a pronounced one at pH 7.8 and a lesser one at pH 6.0. Glycerate-2,3-diphosphatase of the red cell similarly has two sharp optima, at pH 7.0 and 8.1, respectively. From pH 7.2 to 7.8 the activity of the diphosphatase is very low. During storage of blood with the citrate–dextrose (CD) medium at 4 °C. the pH of the samples falls from about pH 7.4 to 6.9, by the end of the fourth week. When blood is preserved with the acidified citrate–dextrose (ACD) medium, the pH falls from about 7.1 to 6.5 in the same period. The content of 2,3-diphosphoglycerate and the diminution in the activity of the hexokinase of the red cells are related to the change in the pH of the blood during storage. The significance of these changes is discussed.
CHOLINE KINASE OF RAPESEED (BRASSIGA CAMPESTRIS L.)
Authors: Ramasarma T. , Wetter L. R.
Published: October 2017

Choline kinase from aqueous extracts of Polish rapeseed (Brassica campestris L.) has been purified 25-fold by fractionation with acetone and calcium phosphate gel. The purified enzyme was relatively stable when stored frozen at neutral pH, and was active over a broad range of pH, the optimum being at about pH 8.6 – 10.0. The enzyme required Mg++ and exhibited maximum activity only when the Mg++: ATP ratio was 1:1. Phosphorylcholine, ADP, and Mn++ inhibited the activity. In addition to choline, the enzyme preparation phosphorylated dimethyl- and diethyl-aminoethanol but not ethanolamine. The choline kinase from rapeseed is similar to that from yeast except that the former does not require sulphydryl groups for activation.
ENVIRONMENTAL INFLUENCES AFFECTING ARTERIAL PRESSURE IN MALES IN THE SEVENTH DECADE
Authors: Brown R. G. , McKeown Thomas , Whitfield A. G. W.
Published: October 2017

Measurements of arterial pressure in 1045 representative men in the seventh decade are used to examine its relation to age, social class (as indicated by occupation), physical and mental demands of occupation, and smoking habits. It is shown that both systolic and diastolic pressures tend to rise as economic and social circumstances become progressively less favorable; they are lower in smokers than in non-smokers. There is no evidence that arterial pressures are related to the physical or mental demands of employment.
STUDIES ON THE TRANSPLANTATION OF A RAT TUMOR TO MICE
Authors: Wallace A. Cameron , Davis Susan
Published: October 2017

The growth and survival of Walker 256 rat tumor grafted direct from rat into mouse thigh was compared with that of the same tumor after long continued residence in mouse brain, and also with that of tumors cultivated for a prolonged period in vitro. It was found that the pattern of growth and regression with tumor grown for 8 months in tissue culture was identical with that produced with tumor direct from rats. Tumor previously grown for 30 generations in mouse brain showed poorer growth and earlier regression. Since both prolonged growth in vitro and serial passage in mouse brain should have removed all the original rat stroma, it is concluded that loss of foreign stroma does not appreciably affect heterologous transplantation. Similarly, prolonged growth of this tumor in a foreign species under the conditions outlined apparently fails to produce any selective adaptation of the tumor to the host.
THE RATE OF DISCHARGE OF ADRENOCORTICOTROPHIC HORMONE AS DETERMINED BY TIMED HYPOPHYSECTOMY IN THE RAT
Authors: Long C. N. H. , Bonnycastle M. F. M.
Published: October 2017

The pattern of secretion of adrenocorticotrophic hormone (ACTH) has been studied by opening the pituitary fossa of rats 36 hours before unilateral adrenalectomy. At selected intervals afterwards, the pituitary gland was removed and the effect on the fall in the ascorbic acid content of the remaining adrenal gland was determined. It was found that ACTH discharge is initiated with great rapidity and that the secretory pattern is a biphasic one. The first phase continues for about 5 minutes and then declines. It is succeeded by a second period of secretion that is much more prolonged. It is suggested that these results support the view that both a neural or neural–humoral and a purely humoral mechanism participate in the regulation of ACTH secretion.
BIOSYNTHESIS OF LECITHIN IN. BRAIN AND DEGENERATING NERVE. PARTICIPATION OF CYTIDINE DIPHOSPHATE CHOLINE
Authors: Rossiter R. J. , McLeod I. M. , Strickland K. P.
Published: October 2017

The radioactivity of cytidine diphosphate choline labelled with P32(CMP-P32Ch) was incorporated in vitro into the phosphatides of both hypotonic homogenates of rat brain and mitochondria prepared from isotonic sucrose homogenates. With both preparations the incorporation was increased by addition of D-α,β-diglycerides prepared enzymatically from naturally-occurring lecithins.Hydrolysis of the labelled phosphatides, followed by separation of the hydrolysis products by two-dimensional paper chromatography, indicated that most of the radioactivity was in lecithin (phosphatidyl choline). Only traces of activity were present in phosphatidyl ethanolamine and phosphatidyl serine. There was also some radioactivity in an alkali-stable fraction that was designated 'sphingomyelin'.These findings are consistent with the view that the phosphatides of brain are formed in situ from smaller molecules and that the metabolic pathways for their formation are similar to those postulated by Kennedy and colleagues for the biosynthesis of phosphatides in chicken liver.The radioactivity of CMP-P32Ch also was incorporated into the phosphatides of homogenates of rat sciatic nerve. This incorporation was greater in homogenates prepared from nerves removed 13 days after previous section. It is suggested that these and other increases, found in the in vitro labelling of phosphatides in nerves degenerating after previous section, reported elsewhere, represent an increase in the potentiality of the nerve for remyelination. These increases are associated with the increase in the number of Schwann cells in the nerve.
A NEW CONCEPT OF THE METABOLISM OF THE PATHOLOGICAL PROTEINS IN MYELOMATOSIS
Authors: Neufeld A. H.
Published: October 2017

The principal features of myelomatosis are the presence of abnormal globulins in the blood and of pathological cells resembling plasma cells in the bone marrow. Disappearance studies with patients' own and with normal adults' I-131 labelled albumin and globulins showed that the time was shortened for the disappearance of the pathological globulins in the patients, whereas that of all other fractions in the controls and in the patients was normal. Incubation studies have shown that the bone marrow plays some part in the breakdown of these pathological proteins and in one experiment there is suggestion that, in the disease, the liver may be involved in the synthesis of these abnormal globulins.
FLUID, ELECTROLYTE, GASTROINTESTINAL, AND HAIR CHANGES IN ADRENALECTOMIZED-SYMPATHECTOMIZED DOGS
Authors: Cleghorn R. A. , Fowler J. L. A.
Published: October 2017

Five male dogs were adrenalectomized and sympathectomized and maintained by adrenocortical extract for periods of weeks to months. Their general behavior did not differ from those subject to adrenalectomy alone, but in three it was observed that the hair grew long and curly. In the other two a lesser change may have been missed. Following withdrawal of the hormone, death occurred rather suddenly in three, and adrenal insufficiency developed sooner in the other two than in dogs only adrenalectomized. Pathological changes in the gastrointestinal tract were qualitatively the same following death after hormone withdrawal in the adrenalectomized–sympathectomized animals and in dogs only adrenalectomized. Blood changes appeared to be no different in the two groups. The urinary changes with respect to water and electrolytes differed in that the sympathectomized group appeared to take in less water and excrete less urine, but to put out more sodium and chloride, in the few days following withdrawal of hormone. These findings are discussed in particular with respect to the relationship of adrenergic function of the sympathetic nervous system and hormones of the adrenal cortex.
THYROTROPHIN ASSAY BY PLASMA I131 MEASUREMENTS
Authors: Adams D. D. , Purves H. D.
Published: October 2017

The thyrotrophin assay, based on measurement of the effect of the hormone in causing a rise in the plasma I131 level of thyroxine-injected guinea pigs, has been studied further. The dose–response relationship from 0.0001 to 0.015 International Units of thyrotrophin is described. It is directly proportional from 0 to 0.0006 I.U., and closely approximates linearity over any threefold range of dosage from 0.0006 to 0.015 I.U. A modified design for the assay is suggested, embodying this knowledge of the dose–response relationship and the use of a Latin square arrangement to eliminate much of the unwanted variation. The proved limit of detection is 0.0001 I.U., the minimum concentration detectable being 0.00005 I.U. per ml., when 2 ml. of test material is injected. Accurate assays can be performed with small numbers of animals.
AMINO ACIDS IN THE BLOOD AND URINE OF NORMAL AND ARTHRITIC SUBJECTS BEFORE AND AFTER A GLYCINE LOAD GIVEN WITH AND WITHOUT ADRENOCORTICOTROPIN
Authors: Derrick J. B. , Hanley Audrey P.
Published: October 2017

Observations have been made on the specific free amino acids (chromatographic analysis) and other nitrogenous constituents in the serum and urine of normal and arthritic men under controlled dietary conditions, before and after a glycine load and adrenocorticotropin administered separately and together.Differences in the metabolism of amino acids between normal individuals and arthritics, particularly of alanine, proline, glutamic acid, taurine, and possibly tyrosine (and/or tryptophan) and cystine, were apparent. The differences were largely confined to the non-essential amino acids. Concomitant increases seen in the serum levels and in the excretion of several amino acids, in response to a load of a single amino acid, indicate that the increases in excretion are more than a matter of competition for reabsorption in the kidney. A prerenal phenomenon appears to be involved, possibly interconversion of amino acids. This concept is supported by the evidence that the increases in the serum levels were restricted to the non-essential amino acids.
ON THE ANTI-INFLAMMATORY ACTION OF AMINOACETONITRILE (AAN)
Authors: Selye Hans
Published: October 2017

Experiments on adrenalectomized rats maintained on small doses of cortisol acetate and desoxycorticosterone acetate indicate that aminoacetonitrile markedly inhibits the production of inflammatory exudate in the "granuloma pouch" test. It is concluded that this antiphlogistic effect is an inherent property of the lathyrogenic aminonitrile and not merely the consequence of an adrenal-mediated stressor action.
STEROIDS AND RELATED PRODUCTS: X. 17α-BROMOPROGESTERONE, A NEW POTENT GESTOGEN
Authors: Engel Ch. R. , Jahnke H.
Published: October 2017

The synthesis of a new derivative of progesterone, 17α-bromoprogesterone, from pregnenolone acetate, is reported. The product was found to be a potent gestogen in contradistinction to its isomer, 21-bromoprogesterone.
METABOLIC CHANGES ASSOCIATED WITH TRANSPLANTABLE ACTH-PRODUCING PITUITARY TUMORS OF THE MOUSE
Authors: Bahn Robert , Wilson Hildegard , Kedda Leonard , Furth Jacob , Anderson Evelyn
Published: October 2017

Following the implantation of adrenocorticotrophin-producing tumors into LAF1 mice, a reproducible syndrome was observed which was characterized by adrenal cortical hypertrophy, thymic atrophy, lymphopenia, ovarian atrophy, cessation of estrus cycles, obesity, polydipsia, and polyuria. These changes appeared after intervals of a few weeks or several months, depending on the secretory activity of the tumor. Metabolic balance studies indicated an increased excretion of nitrogen and potassium. In place of an intolerance to glucose in the tumor-bearing mice, there was an apparently increased tolerance, presumably due to the presence of the large tumor mass. Observations on intact, castrated, and hypophysectomized mice bearing ACTH tumors suggested that the C21 steroids of LAF1 mice possess moderate glucocorticoid as well as discernible mineralocorticoid activity; the C19 steroids apparently are either very weak or inactive androgens, but may be capable of directly affecting the anterior pituitary and the vagina.
A NONPROTEIN CONSTITUENT OF PARATHYROID GLAND EXTRACTS
Authors: Stewart G. S.
Published: October 2017

Dinitrophenylation of a commercial parathyroid gland extract under mild conditions yielded a water-insoluble protein derivative and a water-soluble nonprotein fraction that was nondialyzable and had a pH around 3.5 in dilute salt-free solution. The latter fraction was unstable and became partially dialyzable upon standing. It would appear that the original extract consists of a firm complex between a basic protein and a large, acidic, nonprotein molecule or aggregation of molecules. There is some evidence that this fraction contains sulphur in a covalent form.
SARIN AND PARAOXON ANTAGONISM IN DIFFERENT SPECIES
Authors: deCandole C. A. , McPhail M. K.
Published: October 2017

The intravenous LD50 of sarin, alone and in combination with antagonists, has been determined in mice by a procedure standardized to control certain variables, namely rate of injection, weight, and sex of animals, and volume of fluid injected, all of which are known to influence the test.Trial of the antagonistic potency of atropine sulphate against sarin and paraoxon was also made in anaesthetized animals belonging to four additional species—cat, dog, rabbit, and monkey. Relatively fewer animals were used and a graded response (effect on the respiratory volume) was used for assessment, as well as the quantal response of death or survival. Pentamethonium was studied for its adjuvant action as an antagonist in these species. Varying with the species, a wide difference is shown to exist in the protection afforded by atropine sulphate against intravenous sarin. Thus prior atropinization was found to increase resistance in the monkey one thousand times, in the dog about one hundred and fifty times, in the cat about ten times, in the rabbit about three times, and in the mouse less than twice. A parallel, but less extreme, species difference was found to exist in the protection afforded by atropine against intravenous paraoxon.A synergistic effect was obtained when pentamethonium bromide was given along with atropine, part at least of which is attributable to improved conduction at the neuromuscular junction. Its value as a synergist was greatest in those species where the antagonistic potency of atropine was least. To obtain the maximum benefit from the combination of atropine sulphate and pentamethonium bromide in mice it was necessary to give them aftercare in the form of warmth and oxygen.Three oximes, and one hydroxamic acid, were tested in mice in combination with the therapy described. None of the four conferred any added benefit, nor did they allow aftercare to be dispensed with.Prior administration of pentobarbital intravenously was not found to lessen the toxicity of sarin to mice.
INFLUENCE OF A DIETARY SUPPLEMENT OF ERUCIC ACID AND OTHER FATTY ACIDS ON FERTILITY IN THE RAT: STERILITY CAUSED BY ERUCIC ACID
Authors: Carroll K. K. , Noble R. L.
Published: October 2017

Male rats were raised on a diet of powdered Masters Meal with a supplement of 10% or more by weight of erucic acid. The animals suffered a progressive reduction in spermatogenesis and became completely sterile after about 5 months, despite their normal rate of growth and their apparently excellent state of health. Subsequent experiments have suggested that similar effects can be produced, though less readily, in adult rats on the same diet. Recovery of spermatogenesis apparently can take place provided testicular degeneration has not advanced too far. The impairment of spermatogenesis appears to be a specific effect of the erucic acid in the diet. The estrous cycles of female rats on the diet usually remained undisturbed but there was some interference with parturition. Few of the offspring survived for long because of deficient mammary development and lactation in the mother. The same impairment, occurred also when the animals were fed the diet with 15% by weight of oleic acid. The defects resemble those which occur in animals when fed a diet deficient in essential fatty acids. The suggestion is offered, therefore, that erucic acid may interfere with reproduction by interfering with the metabolism of the essential fatty acids. The administration of erucic acid in the diet may afford a new lead for the control of fertility.
THE DETECTION OF ESTROGENIC ACTIVITY IN TISSUES OF STEERS WHICH HAVE BEEN FED DIETHYLSTILBESTROL
Authors: Wiberg G. S. , Stephenson N. R.
Published: October 2017

The immature female rat was used to detect estrogenic residues in the tissues of cattle fed a ration containing diethylstilbestrol. The criterion of response to the estrogen was the increase in uterine weight which resulted from the ingestion of the beef tissues. The weanling rat was twice as sensitive as the ovariectomized mouse to oral diethylstilbestrol. Significant levels of the estrogen were found in lean meat, liver, and kidney 24 hours after the removal of the diethylstilbestrol from the steers' diet, but such residues could not be detected when this period was extended to 48 hours.
THE INTERRELATION OF THE GROWTH AND METABOLIC RESPONSES TO ANTERIOR PITUITARY GROWTH HORMONE ADMINISTRATION
Authors: Beaton George H. , Banky Hannah Z. , Haufschild Audrey M.
Published: October 2017

Doses of growth hormone which were minimal with respect to body weight increase were sufficient to produce significant alterations in liver alanine – glutamic transaminase and arginase activities and blood urea and amino nitrogen levels. The biochemical effects of the hormone appeared coincident with the body weight increase. Female rats showed a more pronounced response to growth hormone than did male rats. This sex difference was evident with respect to all of the metabolic alterations observed. Although it is not possible to state whether the metabolic alterations are direct effects of the hormone, they do take an integral part in bringing about the over-all biological effect.
BIOCHEMICAL STUDIES ON CHLORPROMAZINE: 1. THE EFFECT OF CHLORPROMAZINE ON RESPIRATORY ACTIVITY OF ISOLATED RAT BRAIN CORTEX
Authors: Lindan O. , Quastel J. H. , Sved S.
Published: October 2017

Chlorpromazine exerts a progressive inhibitory activity (at 0.3–0.6 mM) on the respiration of brain cortex in presence of either glucose, fructose, pyruvate, or L-glutamate. A similar progressive inhibition occurs with other phenothiazine derivatives such as methylene blue and phenergan. However, chlorpromazine does not inhibit oxygen uptake in the presence of succinate. Potassium-stimulated respiration is highly sensitive to chlorpromazine, as it is markedly diminished by 0.2 mM concentration of the drug, a concentration which does not affect the unstimulated respiration. The increased inhibition of potassium-stimulated respiration is only clearly seen during the early part of the experiment.Chlorpromazine is bound by tissue constituents. At a constant concentration of chlorpromazine (0.6 mM), its inhibitory effect on cortical respiration may be abolished by markedly increasing the amount of tissue present. The inhibitory effect of chlorpromazine may be diminished by addition of plasma proteins (αβ-globulin) or by addition of heated homogenized brain, liver, or kidney. No binding occurs with polyglutamic acid, ribonucleic, and deoxyribonucleic acids, but binding does occur with certain acid dyes such as trypan red. Trypan red may be used to immobilize free chlorpromazine. When the latter drug is absorbed, however, by the nervous tissue, the addition of trypan red has no effect on the metabolic inhibitions brought about by the absorbed chlorpromazine.It is concluded that chlorpromazine resembles a large variety of narcotics and anaesthetics in its marked inhibitory effects on potassium-stimulated respiration of the brain. Its action, in vitro, however, differs from that of the narcotics in bringing about progressive, apparently irreversible, inhibitions and in its high binding power with tissue proteins. Such apparently irreversible inhibition is consistent with the conclusion that the drug, after combination with the tissue, gradually diffuses into the cell bringing about metabolic inhibitions.
THE RELATION BETWEEN HEART RATE AND VAGAL STIMULATION FREQUENCY IN THE RAT AT DIFFERENT BODY TEMPERATURES
Authors: Mainwood G. W.
Published: October 2017

The peripheral end of the right vagus was stimulated in acutely vagotomized rats under anaesthesia at different body temperatures. A fairly abrupt increase in the R–R time on the electrocardiogram was observed when a critical stimulation frequency was reached. At a body temperature of 35 °C. the critical frequency is 10 per second or more. On lowering of the body temperature to 28 °C. the critical frequency is greatly reduced so that considerable slowing may be elicited at frequencies as low as one to five per second. Possible theoretical models to account for the critical frequency and its variation with temperature are considered. The temperature effect is too great to be accounted for either on the basis of the increased number of impulses which reach the heart per cardiac cycle, or the reduced rate of cholinesterase activity. The theory most consistent with the results is that each vagal impulse liberates or inactivates a substance, the concentration of which varies directly with heart rate. The interimpulse interval at the critical frequency would then represent the regeneration time of this substance. The temperature coefficient of the regeneration process appears to be about 3.3 per 10 °C.
THE PREPARATION OF LECITHIN FROM L-α-GLYCERYLPHOSPHORYLCHOLINE
Authors: Tattrie N. H. , McArthur C. S.
Published: October 2017

L-α-Lecithin (dipalmitoyl) has been prepared from L-α-glycerylphosphoryl-choline by acylation with palmitoyl chloride in anhydrous chloroform in a yield of about 31%. This reaction also gives rise to two by-products having hemolytic activity. One of these, although not yet completely characterized, is chromatographically comparable with lysolecithin formed from lecithin by the action of snake venom lecithinase. The second by-product possessing hemolytic activity but chromatographically different from common lysolecithin was shown to be a monoacyl derivative of L-α-glycerylphosphorylcholine.
THE EFFECT OF SULPHAEMOGLOBIN ON RED CELL VIABILITY
Authors: Israels L. G. , Chutorian A. , Delory G. E. , Israels Esther
Published: October 2017

Sulphaemoglobinaemia was produced in rabbits by the injection of para-aminopropriophenone and calcium sulphide. The disappearance of this pigment from the blood was used as an index of red cell survival. Sulphaemoglobin disappeared in an exponential fashion, indicating a mean red cell life span of 36 days. The red cells were also tagged with Cr51, and this method of measuring erythrocyte life span yielded values strongly suggesting that sulphaemoglobin in the red cell impairs its viability and leads to random cell destruction. Under these conditions it would seem that the disappearance rate of sulphaemoglobin is not a true measure of red cell survival.
CERTAIN METABOLIC EFFECTS OF CORTICOTROPIN, HYDROCORTISONE, PREDNISONE, AND ASPIRIN, IN NORMAL DOGS
Authors: Gaebler O. H. , Glovinsky Rachel , Lees Helen , Vitti Trieste
Published: October 2017

The losses of weight and nitrogen produced by daily doses of corticotropin (20 units), hydrocortisone acetate (15 mg.), and prednisone (10 mg.) were studied in normal bitches receiving a constant amount of food equal to that which before therapy had either maintained weight or permitted it to increase slowly. Loss of weight during therapy was accompanied by a decrease in the difference between water intake and urine volume, regardless of whether water intake rose or fell. Weight was restored fairly soon after cessation of therapy with prednisone, but not after corticotropin or hydrocortisone. The probability that calorigenic effects of these substances were involved is discussed. Aspirin (20 grains daily) increased nitrogen output, but weight, as well as the difference between water intake and urine volume, increased. The pattern of response to each of the compounds, was, in general, quite similar, but varied in detail in different animals or experiments. Effects of applying hydrocortisone ointment to affected areas in a bitch with dermatitis are also recorded. Prompt improvement was accompanied by losses of weight and nitrogen. Other instances in which the local and general effects of a hormone appear to be contradictory are cited.
ON THE INCORPORATION OF LABELLED ADENINE INTO THE PURINES OF THE NUCLEIC ACIDS IN THE RAT
Authors: Tomlinson R. V. , Zbarsky S. H.
Published: October 2017

Adenine labelled with C14in position 2 and with N15in positions 1 and 3 was injected intraperitoneally into rats, and the purines of the nucleic acids from the pooled viscera were isolated. The C14/N15ratios of the isolated adenine and guanine were considerably lower than that of the injected adenine, indicating that during the formation of the nucleic acid purines from the administered material there was a loss of C14relative to N15. This loss was larger for the guanine, which had a C14/N15ratio 52–67% lower than that of the injected adenine. Metabolic removal of carbon 2 of the adenine was shown further by the excretion of 22% of the injected radioactivity as respiratory carbon dioxide. Fifty-three per cent of the administered radioactivity was excreted in the urine and of this less than half was accounted for as allantoin, adenine, and urea. The C14/N15ratio of the urinary allantoin was intermediate in value between those of the adenine and guanine. The evidence obtained indicates that during the metabolic conversion of adenine to guanine the purine ring may undergo rupture at the 2 position. A possible mechanism for the reaction is presented.
TREATMENT OF HEMORRHAGIC SHOCK IN THE DOG WITH CHLORPROMAZINE AND/OR HYPOTHERMIA
Authors: Gowdey C. W. , Kilborn R. M. , Stevenson J. A. F.
Published: October 2017

Treatment of established hemorrhagic shock, produced in anesthetized dogs by a standardized technique, with chlorpromazine (2.5 mg./kg.) and/or hypothermia (immersion cooling: 25 °C.) did not increase the survival rate and tended to shorten the survival time. The cardiac output of all the treated animals, especially those subjected to chlorpromazine combined with hypothermia, failed to return to prehemorrhage levels even after reinfusion. The results suggest that once hemorrhagic shock has occurred, treatment with chlorpromazine or hypothermia is of no value and with the combination is deleterious.
THE EFFECT OF STRESS AND ADRENALECTOMY ON THE RESPONSE TO DICUMAROL IN RATS
Authors: Mogenson G. J. , Fisher L. M. , Jaques L. B.
Published: October 2017

The prothrombin time was followed in a large number of rats receiving daily doses of dicumarol. Prothrombin times, using the Schwager–Jaques method, were determined on blood samples obtained from the tail vein. It was found that rats, like rabbits, showed a wide variation in their response to dicumarol at dose levels of 10 and 20 mg./kg. body weight per day but, unlike rabbits, they seemed to develop a tolerance to the drug. This began after a peak prothrombin time was reached and occurred later in rats having a higher prothrombin time, or receiving the higher dose of the drug. Stress, in the form of electroshock or sound-induced seizures, increased the variability of the prothrombin time and significantly increased the mean values with 20 mg./kg. dicumarol. These changes persisted in some rats for at least 48 hours. They were prevented by ether anesthesia. Adrenalectomized rats fed dicumarol showed a marked increase in prothrombin time, did not develop tolerance to the drug after a few days, and died of hemorrhage. An analysis of blood samples obtained by cardiac puncture from adrenalectomized, sham-operated, and normal rats fed dicumarol at a dose level of 10 mg./kg. body weight for 5 days showed that values for the Quick one-stage prothrombin times of the adrenalectomized group were elevated significantly above those of the sham-operated and normal groups. No significant differences, however, were noted in the values for the two-stage tests for prothrombin, hematocrit, or plasma dicumarol levels of these animals.
THE PROPERTIES OF THROMBINOGEN
Authors: Ronwin Edward
Published: October 2017

Evidence is given which demonstrates the existence of an intermediate, designated thrombinogen, during the conversion of prothrombin to thrombin. The conversion of prothrombin to thrombinogen requires thromboplastin. The conversion of thrombinogen to thrombin requires thrombin, though other tryptic enzymes can replace thrombin. The properties of thrombinogen have been studied.
THE ACUTE ORAL TOXICITY OF SPIRAMYCIN
Authors: Boyd Eldon M.
Published: October 2017

Spiramycin was administered as a suspension by stomach tube in a range of doses to 46 young male albino rats, with 16 controls, and to 14 small mongrel bitches, with eight controls. The oral acute LD50 was found to be 9.4 ± 0.8 g. (mean ± S.D.) per kg. body weight in rats and 5.2 ± 1.6 g. per kg. body weight in dogs. From these values, the oral acute LD50 in man was estimated to be of the order of 1 to 2 g. per kg. body weight or 20 to 40 times the usual therapeutic dose. The clinical effects of these acutely toxic oral doses in rats and dogs were anorexia, vomiting (dogs only), diarrhea, and lassitude, progressing to prostration, pallor, a fall in body temperature, cessation of respiration, and death usually within 48 hours. At autopsy the stomach and intestines were distended with gas and liquid, the tunica propria and submucosa were acutely congested, and there was excessive necrosis and desquamation of the surface epithelium. Areas of acute necrosis were found in the hepatic cells and sinusoids of the liver, and in the (mostly distal) convoluted tubules of the kidney. The cause of death, therefore, was an acute fulminating gastroenteritis accompanied by acute regional necrosis of the liver and kidneys, produced by the orally administered lethal dose of spiramycin.
LIMITATIONS OF THE IN VITRO PITUITARY INCUBATION SYSTEM AS AN ASSAY FOR ACTH-RELEASING ACTIVITY
Authors: Fortier Claude , Ward Darrell N.
Published: October 2017

The applicability of Saffran and Schally's in vitro pituitary incubation technique to the detection of the ACTH-releasing activity of blood serum fractions, obtained from intact, stressed, adrenalectomized, and stressed–adrenalectomized donor rats, was investigated. The various fractions assayed in this system were found to be markedly active. The activity, which bore no apparent relationship to the physiological state of the donors, was related in part to inhibition of ACTH inactivation, in part to enhanced release of ACTH by the incubated pituitaries. In view of the non-specificity of the observed responses, it is suggested that the increased in vitro release of ACTH may reflect passive leakage of the hormone, as opposed to true secretory activity, and the physiological significance of findings obtained with this method is seriously questioned.
THE METABOLISM OF ANIMAL TISSUES CULTIVATED IN VITRO: II. AMINO ACID METABOLISM OF CHICK EMBRYONIC KIDNEY, CHICK EMBRYONIC LIVER, AND MONKEY KIDNEY CORTEX CULTURES
Authors: Pasieka Arthur E. , Morton Helen J. , Morgan Joseph F.
Published: October 2017

Freshly-explanted chick embryonic kidney, chick embryonic liver, and trypsinized monkey kidney cortex cells have been cultivated in vitro in completely synthetic medium M 150. The amino acid changes in the nutrient medium during cultivation of these tissues have been studied by paper chromatography. A characteristic pattern of amino acid uptake and accumulation in the used culture medium has been demonstrated with each type of tissue culture. It has also been shown that, while the amino acid changes in the medium are different with each type of tissue culture, all cultures examined removed adenine from the medium and liberated small amounts of material thought to be hypoxanthine.
A MODIFIED PROCEDURE FOR THE ESTIMATION OF VITAMIN B12 IN NATURAL MATERIALS OF LOW POTENCY
Authors: McLaughlan J. M. , Rogers C. G. , Middleton E. J. , Campbell J. A.
Published: October 2017

The isotope dilution assay for vitamin B12 depends on the extraction and removal of vitamin B12-like factors prior to the spectrophotometric measurement of vitamin B12. Since it is not suitable for low potency materials, modifications have been made in the method of extraction and purification. Vitamin B12 is measured with Lactobacillus leichmannii 313. The purification procedure was effective in removing pseudovitamin B12 and factor A, but was ineffective in the removal of vitamin B12III. A correction factor was used in place of Co60-labelled vitamin B12 to adjust for loss during purification. Statistical analysis showed this correction factor to be valid and reproducible. Purification did not affect the estimates of vitamin B12 activity of milk, blood plasma, chick mash, or fish meal. True vitamin B12 activity was apparently responsible for 50% of the total vitamin B12 activity of dried cattle faeces and for less than 10% of the total activity of yeast extract. The coefficient of variation of the modified method was 8.7% based on 20 potency estimates.
METABOLIC EFFECTS OF ALPHA-TOCOPHERYL ACETATE: I. INFLUENCE OF ALPHA-TOCOPHERYL ACETATE ON SOME LIPIDS AND NITROGEN COMPOUNDS OF PLASMA IN HUMAN SUBJECTS
Authors: Gray Doris E. , Loh Shiu-May
Published: October 2017

Significant increases in phospholipids, total cholesterol, and alpha-2 globulins and significant decreases in amino acids were found in the plasma of healthy medical students following daily ingestion of 100 mg. alpha-tocopheryl acetate (αTAc). The significance of these findings is discussed.
RETICULO-ENDOTHELIAL SYSTEM STIMULATING COMPOUNDS AND THEIR MECHANISM OF ACTION
Authors: Gözsy B. , Kátó L.
Published: October 2017

A series of compounds are described which exhibit therapeutic activity in experimental tuberculosis, acting exclusively on the host. The active compounds (citronellyl acetate, d-limonen, linalyl acetate) induce a local India ink and trypan blue accumulation and also stimulate the macrophages in vitro and in vivo to an increased phagocytic activity. Sera of the animals treated with therapeutically active compounds stimulate the macrophages of normal animals to an increased phagocytosis. A correlation between chemical structure of the reticulo-endothelial system stimulating compounds and the above effects is discussed.
THE EFFECT OF MUSCULAR EXERCISE ON PLASMA SODIUM AND POTASSIUM IN THE RAT
Authors: Sréter F. A. , Friedman Sydney M.
Published: October 2017

After running a distance of 100 meters in 7 minutes, untrained rats showed a rise in plasma potassium and a fall in plasma sodium as measured in tail vein samples. These changes are in accord with in vitro observations of the effects of exercise on isolated muscle preparations and similarly are taken to indicate a gain of sodium and a loss of potassium by the exercised muscles in the whole animal. Within 10 minutes of completion of the exercise, plasma sodium concentration was restored to normal while potassium was restored within 20 minutes. Exercise was accompanied by a fall in haematocrit, which remained low for up to 40 minutes. A period of 2 months of preliminary training modified the response to exercise. In these trained animals, a fall in sodium concentration occurred as before but the rise in potassium concentration was less in degree and the haematocrit did not change. It is suggested that the rate of increase of plasma potassium is an index of muscle efficiency while the height of plasma potassium is correlated with the fatigue limit of exercise.