Effect of hypercholesterolemia on blood cell production and leukemia progression in the chick.
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Biomedical subjects
Publications and source records attributed to J Lewis.
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To examine the effect of an aging environment on sister chromatid exchange (SCE) induction, Ehrlich ascites tumor (EAT) cells were introduced into young and old C57BL/6J mice. Background SCE levels were not significantly different in either EAT cell or normal bone marrow cell populations between young and old animals. Despite a decline in SCE induction in EAT cells was not significantly affected by the age of the animal. These findings suggest that the aging environment may not play a major role in the diminished SCE induction observed in old cell populations.
Six subjects with exercise-induced anaphylactoid symptoms were evaluated by exercise challenge. Five of the six patients developed symptoms during free running. One subject developed only periorbital angioedema; another developed giant urticaria, wheeze, and hypotension; and three subjects developed cholinergic urticaria. One of the subjects with cholinergic urticaria also became hypotensive. Both of the subjects who developed hypotension also exhibited elevations in plasma histamine (11.2 and 23.2 ng/ml). Subjects who exhibited only cutaneous or subcutaneous manifestations failed to develop elevated levels of plasma histamine. Serum complement determinations (C'3, C'4) remained normal in all subjects at all time intervals. Thus exercise-induced anaphylactoid reactions can appear with a variety of cutaneous manifestations, including angioedema only, giant urticaria, and cholinergic urticaria. Elevated levels of plasma histamine are found only when systemic symptoms such as hypotension occur concomitantly.
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Levels of endogenous somatostatin, gastric inhibitory polypeptide (GIP), glucagon and insulin were measured during gastric (abomasal) emptying in the conscious calf. Isotonic NaHCO3 infused into the duodenum increased rates of emptying of a saline test meal and of gastric acid secretion, but had no effect on basal levels of blood glucose, somatostatin, GIP, insulin or glucagon. By contrast, intraduodenal infusion of 60 mM-HCl caused complete inhibition of gastric emptying, reduction of acid secretion, and an immediate increase in plasma somatostatin from 121.3 +/- 9.4 (S.E.M.) to 286.3 +/- 16.3 pg/ml (P less 0.01) but levels of GIP, insulin, glucagon and glucose were unaltered. Intravenous injection of somatostatin (0.5 microgram/kg) suppressed the antral electromyographic recording and gastri efflux so long as plasma somatostatin levels remained above approx. 200pg/ml. This suggest that somatostatin can be released by intraduodenal acidification and that it inhibits gastric function by an endocrine effect. Since somatostatin retards gastric emptying it may therefore have an indirect role in nutrient homeostasis by limiting discharge of gastric chyme to the duodenum.
Toxemia of pregnancy is characterized by a combination of at least two of the following clinical symptoms: hypertension, edema, and proteinuria. In three successive trials over three consecutive years, the dietary intakes of a selected number of young pregnant women attending a Maternal and Infant Care Clinic at Tuskegee Institute were evaluated for protein, amino acids, and total calories. Women with toxemia were identified, and women without toxemia served as controls. The toxemic group generally consumed more protein than the controls, but values were statistically significant only in the first trial. However, all essential amino acids were consumed in significantly greater amounts by the toxemic group. Protein and essential amino acids were consumed in adequate amounts (at least two-thirds of the RDA) by both groups but in amounts smaller than the national average. Non-essential amino acids were also consumed in adequate amounts, with the toxemic group consuming larger quantities than the controls. Caloric intakes were adequate for young pregnant women. The relationships of glucosuria and of toxemia to protein and amino acid intake were similar and were opposite to the relationship of anemia to protein and amino acid intake. Meats and grains contributed the greatest quantity of protein and amino acids to the diet in all groups. Data seem to imply that any relationship of protein and amino acids with toxemia of pregnancy is a complex one involving several possibly interrelated nutritional parameters.
The bromodeoxyuridine differential chromatid labeling techniques were applied to the simultaneous in vivo examination of cell cycle kinetics and sister chromatid exchange (SCE) induction by various cancer chemotherapeutic agents in normal and Ehrlich ascites tumor cell populations. Compounds which yielded high ratios of SCE (in tumor cells):SCE (in normal cells) also produced greater inhibition of cellular replication in tumor cells when compared to normal cells. Thus, this approach permits in vivo assessment of induction of DNA damage by SCE analysis as well as inhibition of cellular replication by specific cancer chemotherapeutic agents in tumor and normal cell populations.
If the somitic mesoderm of a 2-day chick embryo is destroyed by X-irradiation, the adjacent limb develops with a normal pattern of connective tissues, but is devoid of muscle. The innervation of muscleless wings produced in this way was examined in silver-stained whole mounts, fixed 3 to 8 days later. The main nerve trunks and their cutaneous branches developed normally; but the nerve branches which in a normal limb would lead to individual muscles were generally absent. In almost all those exceptional cases where muscle nerve branches were present, muscle was found to be present also, despite the X-irradiation. Where there was no muscle, the muscle nerve branches apparently did not even begin to form. As a control for side effects of the X-irradiation, wing buds were grafted from normal to irradiated embryos and vice-versa, and again analysed for their innervation. The results confirmed that the absence of muscle nerve branches was due to the absence of muscle cells in the limb. Thus (1) the routes taken through a limb by the main mixed nerve trunks and by their cutaneous branches are determined by the connective tissues, and not by any mechanisms requiring muscle cells; but (2) muscle cells are necessary to provoke the formation of the side branches leading to the sites of individual muscles.
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The effects of prolactin (PRL) on fetoplacental function were studied by measuring the beta subunit of human chorionic gonadotropin (hCG-beta), estradiol (E2), progesterone (P), and PRL concentrations throughout seven pregnancies in a control group (N = 6 women) and in three pregnant women with prolactinomas, who were receiving bromocriptine. In one of the latter, estriol (E3) was also assayed. Long-term suppression of PRL was associated with augmentation of hCG-beta at the first-treimester peak and in late pregnancy. Concomitant augmentation of E3 (in late gestation) and possibly E2, but not P, levels was also observed. This effect on hCG appeared dependent on PRL rather than the dopaminergic effect of bromocriptine. Short-term drug induced alterations in PRL (over 3 hours) during early pregnancy did not result in significant changes in hCG-beta or steroid concentrations. In each control pregnancy, a significant negative correlation (p less than 0.05) was observed between hCG-beta and PRL, while a significant positive correlation between the latter and E2 concentrations in these women was also demonstrated. Apart from its effect on lactation, osmoregulation, and gonadal and adrenal function, a further role for PRL during reproduction appears to be in the control of hCG and estrogen secretion in the fetoplacental unit.
Sclerotherapy of esophageal varices is being reevaluated by many surgeons because of increasing dissatisfaction with shunting procedures. A new technique of sclerotherapy using the flexible fiberoptic endoscope with balloon tamponade of variceal channels is being evaluated. To date, 18 patients have been treated by us with this method. Nine patients with active bleeding had control of their hemorrhage. Two patients experienced three episodes of rebleeding. Of patients not actively bleeding at the time of injection, one patient experienced rebleeding and subsequently died. Four other deaths not related to varices have occurred in this series. All surviving patients underwent repeated sclerotherapy until eradication of varices was achieved. This report demonstrates the feasibility of sclerotherapy of esophageal varices using the flexible fiberoptic endoscope.
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Studies in both patients and mice have been carried out using heterologous antibody directed at secreted products of tumors. In preliminary therapeutic studies in patients with drug-resistant choriocarcinoma and malignant teratoma, heterologous anti-human chorionic gonadotrophin (HCG) and anti-alpha-fetoprotein have been combined with continued cytotoxic chemotherapy. The results to date, although interesting, are inconclusive. In nude mice, anti-HCG administration at the time of inoculation with choriocarcinoma cells failed to inhibit tumor growth. 131I-Labeled anti-HCG and anti-carcinoembryonic antigen have been used in localization studies. Specific:nonspecific ratios of up to 2:1 were obtained in human and murine studies with HCG- and carcinoembryonic antigen-producing tumors.
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