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Biomedical subjects

J Weinberg

Publications and source records attributed to J Weinberg.

At least 19 recordsLinked to original sources

Endocrine mediation of psychosocial stressor effects on mouse mammary tumor growth.

We have demonstrated that differential housing alters the growth rate of the androgen-responsive Shionogi mouse mammary carcinoma (SC115). In the present study we wished to determine if changes in plasma levels of hormones or a shift in the responsiveness of the tumor cells to hormones was responsible for the differential tumor growth rates observed. Plasma testosterone and corticosterone levels were assayed 24 h, 3 days and 1 week post tumor cell/vehicle injection. Also 3 weeks post injection androgen and glucocorticoid receptor binding capacity (Bmax) and binding affinity (Kd) and the in vitro responsiveness of tumor cells to dihydrotestosterone and hydrocortisone were measured. At 24 h post injection, plasma testosterone levels were significantly increased in mice with large tumors, but remained low in mice with small tumors. Plasma corticosterone levels were significantly elevated in mice with small tumors compared to those of mice with large tumors at all time points measured. Androgen and glucocorticoid receptor binding capacity and binding affinity of tumor cells did not differ among groups. Further, all groups tested had the ability to respond to dihydrotestosterone and hydrocortisone in vitro. These data indicate that an effect of housing condition on plasma levels of steroid hormones may, in part, mediate the differential tumor growth rates observed in this model.

Analysis of Variance

The effect of anoxic submergence and recovery on circulating levels of catecholamines and corticosterone in the turtle, Chrysemys picta.

The ability of some freshwater turtles to tolerate prolonged anoxia is well known. The role of hormones in the regulation of the metabolic adjustments that occur during anoxia, however, is unknown. This study examined the changes in plasma glucose, lactate, catecholamine, and corticosterone levels during submergence anoxia and recovery at 22 degrees C in the painted turtle, Chrysemys picta. Plasma catecholamine levels increased greatly during anoxia, while corticosterone levels decreased. During recovery from anoxia, plasma catecholamine levels fell rapidly while corticosterone levels increased 10-fold over controls. The results are consistent with a role for the catecholamines and corticosterone in the regulation of glucose metabolism in the turtle during anoxia and recovery, respectively. We hypothesize that the catecholamines function to stimulate hepatic glycogenolysis during anoxia and thereby increase plasma glucose levels. Corticosterone may function in the recovery from anoxia by enhancing the resynthesis of liver glycogen from lactate.

Analysis of Variance

The influence of HIV status on single and multiple drug reactions to antituberculous therapy in Africa.

OBJECTIVE: To document the influence of HIV status on drug reactions occurring in patients on antituberculous therapy in Harare, Zimbabwe. DESIGN: Retrospective cohort study. SETTING: City of Harare Tuberculosis Unit. PATIENTS: Records of 906 patients with tuberculosis, of whom 162 reacted to antituberculous therapy, were analysed. RESULTS: Reactions to antituberculous drugs were more frequent in HIV-positive (98 out of 363) than in HIV-negative (64 out of 543; P less than 0.0001) patients. The most common drug reaction was cutaneous hypersensitivity, occurring in 139 patients, 89 (64%) of whom were HIV-positive. Thiacetazone was implicated in 115 (82.7%) of the 139 cutaneous reactions and streptomycin in 10 (7.2%). Almost all cutaneous reactions occurred within 8 weeks of beginning treatment. Severe cutaneous reactions occurred more often in HIV-positive patients (P less than 0.001) and the only two deaths occurred in this group. Reactions to multiple drugs occurred in 18 HIV-positive and three HIV-negative patients (P = 0.017). CONCLUSIONS: The use of thiacetazone and streptomycin in antituberculous drug regimens should be reassessed in those countries where coinfection with HIV and tuberculosis is common.

Adult

Roles of catecholamines and corticosterone during anoxia and recovery at 5 degrees C in turtles.

The roles of the catecholamines and corticosterone in glucose regulation during 28 days of submergence anoxia and air-breathing recovery at 5 degrees C in the turtle Chrysemys picta were examined. Anoxia resulted in an increase in mean plasma epinephrine and norepinephrine levels (from 42 and 49 to 966 and 3,826 pg/ml, respectively) and a decrease in hepatic glycogen levels. Despite the increase in plasma catecholamine levels, plasma glucose levels did not change, and the percent of the alpha form of hepatic glycogen phosphorylase was decreased compared with normoxic controls. Plasma levels of lactate increased from 1.5 to 95 mM, and corticosterone decreased during anoxia. During recovery in air, corticosterone returned to control levels within 1 day, and plasma lactate levels slowly decreased. In contrast to a previous study on anoxic turtles at 22 degrees C, at 5 degrees C the catecholamines do not stimulate hepatic glycogenolysis by increasing the level of glycogen phosphorylase alpha. The results do not support the hypothesis that corticosterone enhances lactate clearance from turtle plasma during recovery from anoxia.

Air

Criteria for audit of annual reports on the public health: do they exist?

Production of an annual report is a statutory duty of the Director of Public Health; its production uses significant resources. Audit of reports may help in the effective use of these resources. For audit to be performed criteria need to be agreed upon which to set standards. The present study investigated whether Directors of Public Health agree on suitable criteria for the audit of annual health reports. Districts within North East Thames Regional Health Authority were paired; Directors of Public Health, who had produced the most recent report, interviewed each other using a semi-structured questionnaire. Reports were examined for the presence of the 'key indicators' from the common data set. The results show that there was little agreement on what were suitable criteria to evaluate reports. The criteria in the Toolbox produced by the Faculty of Public Health Medicine were thought to be unsuitable because of the diversity of Districts. Effective audit requires agreed criteria and standards but these were not identified. The Faculty criteria were not considered suitable. Directors of Public Health may develop criteria that they consider suitable for audit of their annual report in discussion, focusing upon their objectives in producing an annual report. This should be the first step in the audit process and an integral part of producing an annual report.

Annual Reports as Topic

The febrile response to mild infections in elderly hospital inpatients.

We studied 74 patients whose temperature was normal according to nurses' temperature charts and who were not on antibiotic treatment. The subjects were inpatients whose condition had deteriorated on the ward, or patients admitted the previous day in whom no diagnosis had been established. One simultaneous set of measurements was made of sublingual, rectal, axillary and proximal auditory canal temperatures. A fever was recorded in 63 of 74 patients (85%); 54 febrile patients had a raised rectal temperature, and 54 had a raised proximal auditory canal temperature; 60 patients were febrile at one or both of these sites. A further three patients had raised sublingual temperatures alone. All patients who were regarded as being definitely or probably infected were febrile at one or more sites. Eighty-one per cent of those considered to be possibly infected, and 71% of those with no clinical evidence of infection were also febrile. Rectal and proximal auditory canal temperatures can each detect fever in approximately 86% of febrile patients, sublingual temperature in 66%, and axillary temperature in 32%. Rectal temperature is clinically the most useful temperature measurement in elderly patients. We conclude that significant infections in patients in a warm environment result in a fever which often remains undetected when only sublingual temperature is measured.

Age Factors

Suppression of immune responsiveness: sex differences in prenatal ethanol effects.

Exposure to ethanol in utero results in changes in the offspring's developing immune system, including thymus lymphocyte subpopulation shifts and functional lymphocyte changes that persist in adult animals. The present study was designed to define further the extent of changes in the immune system that result from fetal ethanol exposure and to compare effects in male and female offspring. In adulthood, male and female offspring from Sprague-Dawley dams fed an ethanol-containing liquid diet (alcohol, A), an isocaloric liquid control diet (pair-fed, PF), or laboratory chow and water (control, C) during pregnancy were tested for several measures of immune competency. Prenatal ethanol exposure differentially affected male and female offspring. Fetal ethanol-exposed males exhibited a decrease in thymocyte number as well as a decreased splenic lymphocyte proliferative response to the T-cell mitogen, concanavalin A (Con A), with a concomitant decrease in recoverable blast cells, when compared with PF and C males. Further, the defect in T-cell proliferation of A males was not due to an inability to produce the critical growth factor, interleukin-2 (IL-2), but to an inability of lymphoblasts to utilize exogenous IL-2. Fetal ethanol-exposed females showed some suggestion of lower thymocyte counts and decreased splenic T-cell proliferative responses to Con A compared to PF and C females. For most of the immune measures, however, no significant differences occurred among A, PF, and C females. In utero ethanol exposure did not significantly alter spleen cell counts or IL-2 production, splenic B-cell proliferation to bacterial lipopolysaccharide (LPS), or thymocyte response to IL-2 in animals of either sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of prenatal ethanol exposure on glucocorticoid receptors in rat hippocampus.

Animals exposed to ethanol in utero are typically hyperresponsive to stressors in adulthood as indicated by increased adrenocortical activation and/or deficits in response inhibition or recovery following stress. In the present study we reasoned that a deficit in feedback control of pituitary-adrenal activity might underlie this hyperresponsiveness in fetal ethanol-exposed (FEE) animals. Further, we hypothesized that a long-term decrease in hippocampal glucocorticoid receptor concentration, induced by prenatal ethanol exposure, might mediate such a deficit in pituitary-adrenal feedback regulation. Male and female Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF), and control (C) treatment groups were tested in adulthood for determination of cytosolic hippocampal glucocorticoid receptor binding. No significant differences in specific binding (Bmax) or binding affinity (Kd) of either type I or type II glucocorticoid receptors were found among animals from E, PF, and C conditions. There were, however, significant sex differences in receptor concentration and binding affinity; females showed significantly greater maximal binding and significantly lower binding affinity than males. These data do not support the hypothesis that prenatal ethanol exposure induces a long-term decrease in hippocampal glucocorticoid receptors in animals tested under basal nonstressed conditions. However, these data do not preclude the possibility that receptor binding capacity may be differentially affected in E, PF, and C animals during stress.

Analysis of Variance

Alterations in splenic natural killer cell activity induced by the Shionogi mouse mammary tumor.

We have previously demonstrated that differential housing conditions alter the growth rate of the Shionogi mouse mammary carcinoma (SC115). The present study was undertaken to determine if natural killer (NK) cells are involved in mediating the effects of differential housing on SC115 tumour growth rate. Splenic NK cell activity was assayed at 24 h, 3 days and 1 week post-injection in both tumour- and vehicle-injected animals. Significant stimulation of splenic NK cell activity occurred 3 days post-injection of SC115 cells. However, no correlation was observed between the level of splenic NK cell activity and tumour growth rate induced by housing condition. We conclude that either splenic NK cell activity does not accurately reflect NK cell activity at the tumour site or that NK cells are not a significant regulator of the differential tumour growth rates seen in this model.

Analysis of Variance

Adrenocortical activity during conditions of brief social separation in preweaning rats.

Rat pups (18 days of age) placed into a novel test cage for 30 min exhibited greater concentrations of plasma corticosterone if alone than if with the biological mother regardless of whether she was conscious or anesthetized. Pups tested with a conscious nonlactating female had higher corticosterone levels than did pups tested with their own conscious mother. Anesthetizing the adult stimulus females eliminated this differential effect. Further, pups isolated in the home cage for 30 min exhibited corticosterone elevations as great as those of pups placed into a novel environment. However, pups left in the home cage with the mother for 30 min displayed corticosterone elevations similar to those of pups isolated in the home cage. In contrast, if pups were left in the home cage with both the mother and the littermates corticosteroid levels were reduced. These results indicate that, under certain conditions, brief separation from the mother can elevate plasma corticosterone levels in the 18-day-old rat. The differential effect of the biological mother and the nonlactating female appears attributable to differences in the behavior of the adult females. Finally, brief isolation from all littermates was also found to evoke a plasma corticosterone response.

Animals

A simple transnasal procedure for treating choanal atresia.

Bilateral choanal atresia is a rare but life-threatening disorder. Prompt diagnosis and emergency treatment are necessary. Various transnasal tools as well as other techniques have been tried in the past: they have all been associated with complications. The authors report a treatment of a newborn with a simple and previously unreported procedure for dealing with bilateral choanal atresia. As described, the use of a simple hand-powered drill and bit offers an approach which is straightforward and free of complications. Efficacy of this procedure is documented by a 6-year follow-up period.

Choanal Atresia

Biochemical evaluation of calcium stone patients: how soon can it be done after stone surgery/passage?

Biochemical evaluations were done two times for 29 outpatients with calcium stone disease, the first time within one month after surgical extraction or passage of stones and the second time two months or more later. Classification of the etiologic basis for the stone disease was the same after both tests in 27 patients. In the other 2 patients the diagnosis was changed from renal to absorptive hypercalciuria. Both of these patients had creatinine clearance rates less than 60 percent of normal during the first test. One also had multiple residual stones during both evaluations, and the second had a urinary tract infection during the first test that resolved with a normal creatinine clearance by the second test period. When nephrogenous cyclic adenosine monophosphate (cAMPn) assays were done on fasting specimens in these patients, the results were consistent with absorptive hypercalciuria. Almost all patients can be evaluated and placed in management programs within a few weeks after surgery. If cAMPn assays are not done, patients with decreased renal function secondary to residual stones or infection can be tested at a later time.

Adolescent

A histological study of the Shionogi adenocarcinoma 115 grown in male and female mice.

We have previously demonstrated that growth rate and morphology differ between androgen-responsive Shionogi mouse mammary tumours maintained in male and female mice. Furthermore, we can modulate the growth rate of these tumours in male mice by exposing the mice to psychosocial stressors. In the present study, we were interested in determining if tumours in male mice with a comparable growth rate to that in females, also had a morphology similar to that in females. SC115 tumours were examined using histochemical and immunohistochemical techniques. Tumours in male mice were easily distinguishable from tumours in female mice regardless of growth rate. Tumours maintained in female mice contained osteoid-like regions which stained positive for sialic acid and sulphate moieties. No such regions were observed in any of the tumours from male mice. In addition, although all tumours contained MSA (muscle specific actin)-positive and S100 protein-positive cells, these regions were more extensive in the tumours of female mice. This study suggests that tumour growth rate and morphology are independently regulated by the host environment.

Actins

Effects of psychosocial stressors on mouse mammary tumor growth.

We describe a sensitive and replicable animal model which demonstrates that psychosocial variables both increase and decrease tumor growth rate. The effects of social housing condition and daily exposure to novel environments were investigated in mice bearing the transplantable androgen-responsive Shionogi mouse mammary carcinoma (SC115). Being reared individually housed and remaining individually housed or being reared in a sibling group and then singly housed following tumor cell injection markedly increased tumor growth compared to that in mice remaining in their standard sibling rearing groups (n = 2-3 per group), if animals were also exposed to acute daily novelty stress. In contrast, being reared individually and then moved to a larger social group (n = 4-5 nonsiblings per group) markedly reduced tumor growth, both in the presence and absence of acute daily novelty stress.

Animals

Prenatal ethanol exposure alters adrenocortical development of offspring.

Interactive effects of prenatal ethanol and maternal nutritional status on reproductive outcome and maternal and offspring adrenocortical activity were examined. Ethanol was administered to pregnant females in liquid diets (36% ethanol-derived calories) which were marginal or optimal in terms of requirements for pregnancy. Both pair-fed and ad libitum fed control groups were included. Females consuming ethanol from gestation Day 1 through parturition gained less weight, were delayed in parturition, and had fewer and smaller live born young than pair-fed or control females, regardless of whether they consumed marginal or optimal diets. Withdrawing ethanol on Day 21 of gestation attenuated many of ethanol's adverse effects on reproductive outcome. However, prenatal maternal ethanol intake altered adrenocortical activity/responsiveness of the mother, the fetus, and the preweaning offspring, regardless of maternal nutritional status. Relative adrenal weights and basal corticosterone levels were increased in the dam both prenatally and at parturition. Ethanol-exposed fetuses (A) had increased relative adrenal weights but lower basal corticosterone levels than pair-fed (PF) and control (C) fetuses on gestation Day 21. At birth, plasma and adrenal corticosterone levels were increased, while absolute adrenal weights and corticosterone binding globulin (CBG) binding capacity were decreased in A neonates. At 5 days of age, A pups showed reduced plasma corticoid responses to ether at 15 min poststress and to novelty or saline injection at 90-min post stress compared to PF and C pups. CBG binding capacity was also reduced in A pups. At 10 days of age, plasma corticosterone levels were lower overall in A and PF than in C pups following exposure to a number of different acute stressors while at 18 days plasma corticoids were decreased and adrenal corticosterone was increased in A compared to PF and/or C pups. These data support and extend previous studies indicating that in utero ethanol exposure alters postnatal adrenocortical development. This effect is specific to ethanol and unaltered by maternal nutritional status.

Adrenal Cortex