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Biomedical subjects

J Hirsch

Publications and source records attributed to J Hirsch.

At least 37 records · Page 2Linked to original sources

Treatment of P388 leukemia in vivo with perfluoroctylbromide and radiation: a preliminary study.

Perfluorinated hydrocarbon compounds (PFHC) possess unique physical properties suggesting possible usefulness in man. Their low surface tension allows free flow into tiny folds and crevices, facilitating dispersion along peritoneal surfaces affected by a tumor. These substances are also oxygen solvents. BDF1 female mice injected intraperitoneally (IP) with 10(6) P388 mouse leukemia cells were studied following treatment with preoxygenated compound 1913 and increasing doses of radiation. Preliminary results suggest increased life span compared to radiation treatment alone. Radioenhancement at high sublethal doses of whole-body radiation cannot be excluded.

Animals

Brain cholecystokinin and nutritional status in rats and mice.

Under certain conditions, exogenously administered cholecystokinin (CCK) or its COOH-terminal octapeptide can terminate feeding and cause behavioral satiety in animals. Furthermore, high concentrations of CCK are normally found in the brains of vertebrate species. It has thus been hypothesized that brain CCK plays a role in the control of appetite. To explore this possibility, a COOH-terminal radioimmunoassay was used to measure concentrations of CCK in the cerebral cortex, hypothalamus, and brain stem of rats and mice after a variety of nutritional manipulations. CCK, mainly in the form of its COOH-terminal octapeptide, was found to appear in rat brain shortly before birth and to increase rapidly in cortex and brain stem throughout the first 5 wk of life. Severe early undernutrition had no effect on the normal pattern of CCK development in rat brain. Adult rats deprived of food for up to 72 h and rats made hyperphagic with highly palatable diets showed no alterations in brain CCK concentrations or distribution of molecular forms of CCK as determined by Sephadex gel filtration of brain extracts. Normal CCK concentrations were also found in the brains of four strains of genetically obese rodents and in the brains of six animals made hyperphagic and obese by surgical or chemical lesioning of the ventromedial hypothalamus. It is concluded that despite extreme variations in the nutritional status of rats and mice, CCK concentrations in major structures of the brain are maintained with remarkable constancy.

Aging

Isotopic labeling of DNA in rat adipose tissue: evidence for proliferating cells associated with mature adipocytes.

The intraperitoneal administration of [3H]thymidine to adult rats resulted in the rapid appearance of label in the adipocyte fraction of collagenase digests of adipose tissue. Low-speed centrifugation followed by freezing and slicing showed the label to be uniformly distributed in the adipocyte fraction. The presence of label in DNA was confirmed by hydrolysis with deoxyribonuclease and by inhibition of incorporation with hydroxyurea. Organelle fractionation revealed that the label was predominantly in nuclei, and radioautography showed that only a few adipocyte nuclei were labeled. The label in the adipocyte fraction could not be reduced by increased collagenase digestion or by trypsin treatment. Mixing of labeled adipocytes with unlabeled stroma did not result in decrease of label and addition of labeled stroma to unlabeled adipocytes did not cause significant transfer of radioactivity. Addition of [3H]thymidine to the collagenase digestion medium of unlabeled adipose tissue resulted in more incorporation by adipocytes than by stroma, suggesting the presence of a very rapidly proliferating cell type associated more with adipocytes than with stroma. In vivo turnover studies of labeled DNA indicated that there are two components in both adipocytes and stroma, a rapidly labeled component with a half-life of only several days and another with a half-life of several months. These experiments suggest that there is a rapidly proliferating cell type in adipose tissue, closely associated with mature adipocytes, that may be an adipocyte progenitor or may have some other unknown function.

Adipose Tissue

Increased cellular proliferation in adipose tissue of adult rats fed a high-fat diet.

The feeding of a high-fat diet to adult rats was shown to increase the incorporation of [3H]thymidine into DNA of the adipocyte and stromal fractions. After only 2 days on a high-fat diet there was a marked increase in the incorporation of label. When a 2-week period was interposed between [3H]thymidine administration and determination of DNA specific activity, the greatest increase in incorporation of label was found after 1 week on the diet, when incorporation increased 6-fold or more in both adipocytes and stroma and subsequently decreased to stabilize at a level two or three times that of chow-fed rats in the adipocyte fraction. Rats labeled when young and later placed on a high-fat diet showed a decrease in DNA specific activity in both adipocytes and stroma, confirming that cellular proliferation had occurred in both fractions. The specific activities of both stromal and adipocyte DNA were very similar at all time points studied. An attempt to increase the difference in specific activities by waiting many weeks after [3H]thymidine injection before isolating DNA was not successful. This may be because the total amount of DNA in the stromal and adipocyte fractions increases in parallel on the diet. The significance of these findings in terms of the normal turnover of adipose tissue DNA and the responsiveness to diet is discussed.

Adipose Tissue

Decreased platelet thrombogenecity in association with increased platelet turnover and vascular damage.

Platelet turnover is increased when platelets interact with prosthetic surfaces and damaged vessel wall. To determine whether the resulting increase in young platelets is associated with an increased tendency to thrombosis, we induced a state of increased platelet turnover in rabbits by inserting a sterile cannula into the abdominal aorta and tested for platelet thrombogenecity by measuring the deposition of circulating platelets onto a second injury site in the carotid arteries. Platelet half-life was decreased and platelet turnover was increased after the aortic cannulation, although the circulating platelet count remained unchanged. Platelet thrombogenecity determined 20 hr after cannulation was significantly decreased when compared to sham-operated animals. Ear bleeding studies demonstrated that the platelets circulating in cannulated animals were hemostatically less effective than those in sham-operated animals. This effect was intrinsic to the platelet and was associated with a platelet function defect. These data suggest that platelets exposed to a damaged or foreign surface interact with the surface and then circulate in a less reactive state.

Animals

Purification and properties of a nuclear protein kinase associated with ribonucleic acid polymerase I.

A cyclic AMP-dependent nuclear protein kinase was found to be closely associated with rat liver nucleolar RNA polymerase I throughout most of its purification. This protein kinase was purified to near homogeneity. It exhibits a number of unusual catalytic properties, including the inability to utilize Mn2+ when RNA polymerase is the substrate and the ability to phosphorylate both acidic and basic substrates. Phosphorylation of RNA polymerase I by this protein kinase results in the formation of phosphoester bonds characteristic of phosphoserine and phosphothreonine. Radioautography of polyacrylamide-gel electrophoretograms of the phosphorylated RNA polymerase I revealed that the 32P was located primarily on enzyme subunits SA1, SA3, SA5, and SA6 [nomenclature of Kedinger, Gissinger & Chambon (1974) Eur. J. Biochem, 44, 421-436].

Animals

Mass spectrometry of uronic acid derivatives. XI--Structure elucidation by mass spectrometry of aldobiouronic and pseudoaldobiouronic acids and their beta-elimination products as per-o-methyl derivatives.

Electron impact mass spectra of a series of aldobiouronic and pseudoaldobiouronic acid per-O-methyl derivatives and of the corresponding 4,5-unsaturated analogues, found normally among the products of methylation of uronic acid containing disaccharides as a result of methylation accompanying beta-elimination, have been studied. Using labelling experiments, metastable transition measurements and high resolution mass spectrometry, the fragmentation mechanisms of substances of this class have been deduced. Application of the information to the structure elucidation of this type of compound is discussed. It is concluded that from the mass spectra alone it is possible to determine the molecular weight, the cycle masses as well as the mode of linkage between the monomeric units. The appearance potentials of ions formed by cleavage of the glycosidic linkages have also been determined and the energetic differences encountered in the fission of the glycosidic linkages of various types of uronic acid containing oligosaccharides are discussed.

Hexuronic Acids

Adipose tissue hyperplasia and hyperinsulinemia on Zucker obese female rats: a developmental study.

Obese female Zucker rats show persistent increases in fat cell number compared to lean female Zucker rats from 5 to 52 wk of age. The hyperplastic obesity of the Zucker rat is also accompanied by fat cell hypertrophy and elevated plasma immunoreactive insulin (IRI). Average adipocyte size reaches a peak value at 14 wk of age in the subcutaneous, retroperitoneal and parametrial depots of the female obese rat. Plasma IRI also shows a peak at 14 wk of age. In addition, at this age thymidine kinase activity, a measure of proliferative capacity in tissue, is elevated in obese compared to lean rats, and at 15 1/2 wk of age a bimodal distribution of adipocytes is present in obese rat adipose tissue. The data suggest that attainment of a critical adipocyte size accompanied by maximum levels of plasma IRI may act in concert to potentiate fat cell hyperplasia in Zucker obese rats.

Adipose Tissue

Diet-induced adipocyte number increase in adult rats: a new model of obesity.

Adult rats of various strains became obese when they were fed a highly palatable diet for several months. Analysis of their adipose tissue morphology revealed increases in both adipocyte size and number in most depots. Reintroduction of an ordinary chow diet to such animals precipitated a period of weight loss during which only mean adipocyte size returned to normal. Adipocyte number remained at the elevated level achieved during the period of weight gain. Thus, transient dietary obesity in rats results in a persistent obesity of a purely hyperplastic, nonhypertrophic form. Furthermore, the persistence of the cell number increase suggests that it is the result of proliferation or differentiation rather than of only an increase in the lipid content of a pool of very small and normally undetected adipocytes. An analysis of adipose tissue morphology changes during the course of diet-induced weight gain suggests that the achievement of some specific mean adipocyte size triggers the events that culminate in adipocyte number increase. What mechanisms may link adipocyte size to the formation of new adipocytes remains unknown.

Adipose Tissue

Volume, flow, and timing of each breath during positive-pressure breathing in man.

This study is a breath-by-breath analysis of the effects of 5, 10, and 15 cmH2O positive-pressure breathing (PPB) on man's steady-state breathing pattern. Inspiratory (TI), expiratory (TE), and cycle (TT) durations, tidal volumes (VT), minute ventilation (VE), mean inspiratory flow rate (VT/TI), and mean expiratory flow rate (VT/TE) were determined from pneumotachograph and Wedge spirometer recordings before and during steady states on PPB. End-tidal CO2 was continuously recorded. Seventeen adults, seated in a full body-box, breathed quietly for 8 min through a mouthpiece on a bag-in-box. Pressure in the body-box was lowered to the desired level prior to 4 min of stress. On all pressure levels, end-expiratory volume, VT, VE, VT/TI, and VT/TE increased; end-tidal CO2, TE, and TT decreased with no consistent change in TI. Calculated alveolar ventilations indicated that the increases in VE were true hyperventilations. Each individual increased VE by using a unique combination of VT, TI, and TE. End-expiratory volume increased less and expiratory flow increased more than would occur passively. Hence, it is concluded that active reflexes account for the resistance of the systems to the passive distention, the facilitation of expiratory flow, and the shortening of TE.

Adult

Effect of lithium chloride on electrically stimulated guinea-pig longitudinal muscle-myenteric plexus.

Lithium chloride, in the concentration range of 10(-4)M to 10(-2)M, increases the height of electrically induced contractions of guinea-pig longitudinal muscle-myenteric plexus preparation. Higher concentrations of the salt cause a progressive block of contractions. Sodium chloride shows no augmentation of contraction height, but concentrations above 10(-2)M only cause block of contractions. Inhibition of contractions by LiCl exactly parallels inhibition of responses of the tissue to exogenous acetylcholine (ACh); thus, the site of action is considered to be directly on the muscle. Sodium chloride causes insignificant inhibition of responses to exogenous ACh. Guinea-pigs injected chronically with high doses of LiCl (2 months, 5 mEq/kg show no stimulatory effect on LiCl in vitro, only inhibition. This finding suggests that tolerance to at least some of the actions of LiCl may occur upon chronic administration, particularly if the dose used is very high.

Acetylcholine

Adipose tissue regeneration following lipectomy.

Surgical removal of subcutaneous fat depots in weanling rats leads to a regenerative response. If the rats are fed a diet high in fat, adipose mass and adipocyte number are precisely restored within 7 months of surgery. Thus, under appropriate experimental circumstances, compensatory hyperplasia will occur in adipose tissues of the rat.

Adipose Tissue