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Biomedical subjects

B E Walker

Publications and source records attributed to B E Walker.

At least 19 recordsLinked to original sources
PubMed1992

Evidence of hypothalamic involvement in the mechanism of transplacental carcinogenesis by diethylstilbestrol.

Disruption of hypothalamic sex differentiation in the fetus is one hypothesis to explain female reproductive system anomalies and cancer arising from prenatal exposure to diethylstilbestrol (DES). To further test this hypothesis, breeding performance and behavior were monitored in a colony of mice exposed prenatally to DES, using a schedule previously shown to produce anomalies and cancer of the female reproductive system. Fertility decreased with age more rapidly in DES-exposed females than in control females. DES-exposed females were less accepting of the male than control females. These observations support the hypothesis of abnormal hypothalamic sex differentiation as a basic mechanism in DES transplacental carcinogenesis.

Animals↗
PubMed1992

Vitamin C depletion and pressure sores in elderly patients with femoral neck fracture.

OBJECTIVE: To evaluate the contribution of specific nutritional deficiencies (as indicated by zinc; vitamin A, C, and E; albumin; and haemoglobin concentrations) to the risk of pressure sores. DESIGN: Observational cohort study. SETTING: St James's University Hospital, Leeds. SUBJECTS: 21 elderly patients presenting consecutively to the orthopaedic unit with femoral neck fracture. MAIN OUTCOME MEASURE: Full thickness epidermal break over a pressure bearing surface. RESULTS: 10 patients (48%) developed a pressure sore during their hospital stay. Indices of zinc status and concentrations of albumin, haemoglobin, and vitamins A and E were similar in patients who developed a pressure sore and those who did not. Mean leucocyte vitamin C concentration, however, was 6.3 (SD 2.2) micrograms/10(8) cells in patients who developed a pressure sore as compared with 12.8 (4.6) micrograms/10(8) cells in patients who did not. CONCLUSIONS: Low concentrations of leucocyte vitamin C appear to be associated with subsequent development of pressure sores in elderly patients with femoral neck fractures.

Aged↗
PubMed1992

No effect of adult dietary fat on tumors induced prenatally by diethylstilbestrol.

Strain CD-1 female mice exposed prenatally to diethylstilbestrol (DES) or vehicle were placed on semipurified diets containing 2.6%, 10%, 20%, or 29% fat by weight at four weeks of age. These mice were used as a breeding colony for a few weeks and then maintained to terminal illness on the semipurified diets. Females exposed prenatally to DES developed mammary tumors, pituitary tumors, and glandular tumors of the reproductive tract. There was no significant difference in tumor frequency between low- and high-fat dietary groups. Fewer tumors appeared in the vehicle-exposed mice, as expected, and their frequency did not differ between the dietary groups. Pregnancy reduced tumor frequency in DES-exposed mice, but the incidence of pregnancy was not significantly different between low- and high-fat dietary groups. In the adult the failure of a high-fat diet to increase the frequency of reproductive system tumors induced prenatally is in marked contrast to the effectiveness of high-fat diets in promoting mammary tumors induced by carcinogens given to rats postnatally. This difference is critical in the interpretation of epidemiological studies. The relationship of dietary fat to reproductive system cancer in human populations was reviewed in comparison with these two animal models. The epidemiological literature was found to be more consistent with the animal model, showing high sensitivity to dietary fat prenatally but no significant sensitivity at the adult stage of life.

Animals↗
PubMed1992

Symptomatic zinc deficiency in experimental zinc deprivation.

An evaluation of indices of poor zinc status was undertaken in five male subjects in whom dietary zinc intake was reduced from 85 mumol d-1 in an initial phase of the study to 14 mumol d-1. One of the subjects developed features consistent with zinc deficiency after receiving the low zinc diet for 12 days. These features included retroauricular acneform macullo-papular lesions on the face, neck, and shoulders and reductions in plasma zinc, red blood cell zinc, neutrophil zinc and plasma alkaline phosphatase activity. Alcohol induced hepatitis, which was suspected in this subject, may have caused a predisposition to altered zinc metabolism and possible zinc deficiency which was exacerbated by subsequent zinc deprivation. The report supports the value of neutrophil zinc concentration as an indicator of poor zinc status.

Adult↗
PubMed1991

Monocyte zinc and in vitro prostaglandin E2 and interleukin-1 beta production by cultured peripheral blood monocytes in patients with Crohn's disease.

This study investigated the relationship between zinc status and prostaglandin E2 and interleukin-1 beta production by cultured monocytes in patients with Crohn's disease. Monocyte zinc was significantly decreased in both 12 inpatients and 22 outpatients compared with controls (P less than 0.001) but lymphocyte and polymorphonuclear cell zinc were normal. When cultured monocytes from 10 outpatients with Crohn's disease were stimulated with lipopolysaccharide, prostaglandin E2 production increased markedly, coupled with a fall in monocyte zinc. In matched controls, prostaglandin E2 production was significantly less and monocyte zinc remained stable. No difference in interleukin-1 release was noted between patients and controls. The addition of prednisolone to cell cultures suppressed prostaglandin E2, interleukin-1 synthesis, and monocyte zinc did not change. Zinc chloride augmented prostaglandin E2 production in patients, but not controls, and interleukin-1 remained stable. These results demonstrate a link between low monocyte zinc concentration and excessive prostaglandin production in patients with Crohn's disease.

Cells, Cultured↗
PubMed1991

Evidence of cellular zinc depletion in hospitalized but not in healthy elderly subjects.

Cellular immune function declines with age and is implicated in the increased incidence of cancer, and morbidity and mortality associated with infections in elderly people. Elderly people are at risk of nutritional depletion, including of zinc, and zinc is known to influence immunity. The present study assessed zinc status in both healthy elderly subjects and elderly inpatients. Polymorphonuclear-cell zinc was decreased in the hospitalized subjects and 27% had values below the reference range for healthy elderly and young subjects. Since PMNC zinc is decreased in experimental zinc depletion and correlates with muscle zinc, we suggest that 27% of the patients studied may be zinc depleted and may benefit from zinc supplementation.

Aged↗
PubMed1991

Effect of fasting, self-selected and isocaloric glucose and fat meals and intravenous feeding on plasma zinc concentrations.

This study investigated the effect of fasting, self-selected meals and isocaloric oral glucose and fat meals and intravenous (i.v.) feeding on plasma zinc concentrations in men. Plasma zinc remained stable when volunteers fasted all day, but self-selected meals and 600 kCal of dextrose or fat emulsion caused significantly reduced plasma zinc concentrations [mean (SD) 12.1 (1.4), 12.3 (0.6) and 12.2 (0.7) mumol/L at 1400 h, respectively, compared with a fasting level of 13.9 (1.6) mumol/L at 0800 h, P less than 0.05]. In patients undergoing intravenous hyperalimentation, plasma zinc decreased from 12.0 (1.4) mumol/L at 0800 h to 10.0 (1.1) mumol/L at 1400 h [mean (SD), P less than 0.01]. These data show that both enteral and i.v. feeding cause a decline in plasma zinc and that glucose alone is not responsible for this post-prandial fall since ingestion of isocaloric amounts of glucose or fat have a similar effect.

Circadian Rhythm↗
PubMed1990

Tumors in female offspring of control and diethylstilbestrol-exposed mice fed high-fat diets.

Strong correlations have been established internationally between female reproductive system cancer rates and dietary fat. To test the hypothesis that the prenatal period is a critical time for exposure to high dietary fat, we placed adult female strain CD-1 mice with or without prenatal exposure to diethylstilbestrol (DES) on diets with low or high levels of fat and mated them. After delivery of the litters, these mice were given the commercial diet on which they had been raised. Their female offspring were raised on this commercial diet until terminal illness occurred. Of the 47 offspring of control mice on low-fat diets, only five had reproductive system tumors, whereas tumors developed in 39 of 78 offspring of mice on high-fat diets. For DES-exposed mice, tumors developed in 18 of 64 offspring of mice on low-fat diets and 38 of 70 offspring of mice on high-fat diets. Nine mice with metastatic mammary tumors and seven with pituitary tumors were offspring of mice on high-fat diets.

Animals↗
PubMed1990

Cellular and muscle zinc in surgical patients with and without gastrointestinal cancer.

1. The zinc status of surgical patients with and without gastrointestinal cancer was studied. 2. Plasma zinc was lowest in patients with cancer concurrent with depressed plasma albumin concentrations. 3. Polymorphonuclear cell zinc was decreased in both patient groups and correlated strongly with abdominal muscle zinc (r = 0.89, P less than 0.001). 4. Mononuclear cell and total leucocyte zinc were similar to control values in both groups of patients. Total leucocyte, but not mononuclear cell, zinc correlated weakly with muscle zinc (r = 0.48, P less than 0.05). 5. The results suggest that polymorphonuclear cell zinc may be better than leucocyte zinc in assessing zinc status and that some surgical patients may be zinc-depleted. The presence of gastrointestinal cancer did not influence the zinc status.

Adult↗
PubMed1990

Relation between zinc status and hepatic functional reserve in patients with liver disease.

Patients with liver disease may be at risk of zinc depletion. We measured polymorphonuclear cell, mononuclear cell, plasma, and erythrocyte zinc values, and erythrocyte carbonic anhydrase activity to assess zinc status in 17 patients with non-alcoholic liver disease (primary biliary cirrhosis and chronic active hepatitis) and 13 patients with alcoholic liver disease. The plasma zinc concentration was reduced in both patient groups and correlated strongly with the plasma albumin concentration. The mean polymorphonuclear cell zinc value in both groups was similar to that of controls but when results were combined and grouped according to hepatic functional reserve, patients with more severe liver damage (grade C) had a lower polymorphonuclear cell zinc value (mean (SD) 0.86 (0.24) nmol/mg protein) than patients with grade A (1.44 (0.43) nmol/mg protein, p less than 0.01) or grade B liver damage (1.08 (0.30) nmol/mg protein, p less than 0.05), or control subjects (1.26 (0.28) nmol/mg protein, p less than 0.001). The polymorphonuclear cell zinc value did not correlate with other indices of zinc status. The mononuclear cell zinc value was normal in all patients and was unrelated to hepatic damage. The erythrocyte zinc value and carbonic anhydrase activity were raised in alcoholic patients only. Since the polymorphonuclear cell zinc concentration is low in human experimental zinc deficiency and also correlates with tissue zinc, we suggest that our results provide evidence of progressive leucocyte zinc depletion in patients with liver disease.

Adult↗
PubMed1989

Zinc concentrations in pure populations of peripheral blood neutrophils, lymphocytes and monocytes.

It is doubtful if the measurement of plasma or serum zinc is of value in assessing zinc status. Leucocyte zinc has been suggested as an alternative since it may be representative of tissue zinc stores; but in many studies poorly defined cell populations make interpretation difficult. This paper describes detailed techniques for the isolation and analysis of pure populations of neutrophils, lymphocytes and monocytes. Zinc concentrations (+/- 1SD) in normal subjects were 1.26 +/- 0.27 nmol/mg protein, 1.85 +/- 0.32 nmol/mg protein and 2.58 +/- 0.65 nmol/mg protein in neutrophils, lymphocytes and monocytes respectively. Fasting caused a significant decrease in neutrophil and lymphocyte zinc, and an increase in monocyte zinc. Supplementation of zinc-replete subjects with 135 mg zinc/day for 3 weeks had no significant effect on cellular zinc concentrations.

Cell Separation↗
PubMed1989

Animal models of prenatal exposure to diethylstilboestrol.

Animals of several species exposed perinatally to diethylstilboestrol (DES) have been evaluated for anomalies and tumours. In male offspring, anomalies of the testis and epididymis have been reported, but evidence for tumours has been very limited. Many anomalies and tumours have been recorded in female offspring, and some of these duplicate the anomalies and tumours reported in DES-exposed women, whereas others either have not yet been discovered or else do not occur in the human species. A variety of abnormal physiological responses has been identified in animals exposed perinatally to DES. There were altered levels of hormones and receptors; responses to postnatal injection of hormones were often modified; and an increased susceptibility to other carcinogens has been established. Several mechanisms have been postulated to explain tumour production later in life after perinatal exposure to DES. Deficiencies in immune function indicate a mechanism of impaired immune surveillance. The presence of DES and its metabolites in the fetus and neonate raise the issue of somatic mutation. Evidence for sister chromatid exchange, cell transformation in tissue culture and other toxic effects on chromosomes support the somatic mutation hypothesis. A third hypothesis is involvement of abnormal differentiation of the hypothalamus. Structural, hormonal and behavioural changes support this idea. Possible additional problems in humans after exposure to DES, on the basis of animal model studies, are increased tumour frequency with ageing and transmission of cancer risk to the third generation. The multigeneration effect of DES provides a model to test the mechanism of transmission of cancer risk from one generation to the next. The outcome of such experiments could have considerable impact on the understanding of the association between DES and cancer specifically and transplacental cancer generally.

Aging↗
PubMed1988

Vaginal tumors in mice from methylcholanthrene and prenatal exposure to diethylstilbestrol.

To test the hypothesis that mice exposed prenatally to diethylstilbestrol (DES) develop adenocarcinomas due to sensitivity of vaginal and cervical adenosis to carcinogens, sponges impregnated with methylcholanthrene (MCA) were lodged against the cervix and vaginal fornices of 6-month-old strain CD-1 mice exposed prenatally to DES. Only squamous cell carcinomas developed in these mice, but at a significantly higher rate than in MCA-treated mice not exposed prenatally to DES. An adenosquamous carcinoma and a precursor of adenocarcinoma developed in DES-exposed mice with control sponges.

Adenocarcinoma↗
PubMed1988

Leucocyte zinc in non-Hodgkin's lymphoma and Hodgkin's disease.

Zinc status and the effect of zinc supplementation were assessed in groups of patients with non-Hodgkin's lymphoma and Hodgkin's disease; patients were either untreated or in remission. In the patients in remission, plasma zinc was normal; and whereas 30% of untreated patients had low plasma zinc, the group as a whole did not differ from normal. For mononuclear cell zinc, the range of values in the disease group was far wider than in controls, but there was no significant difference between the means of the groups. Granulocyte zinc was significantly lower in both the groups of patients in remission from non-Hodgkin's lymphoma and Hodgkin's disease compared with the control group. Significant increases were found in the plasma copper, ceruloplasmin, and the copper-to-zinc ratio in several of the patient groups. Plasma zinc increased by 23% with zinc supplementation (50 mg elemental Zn/day), but there was no effect on mononuclear cell or granulocyte zinc. Apart from granulocyte zinc, there is little evidence of zinc deficiency in non-Hodgkin's lymphoma or Hodgkin's disease. However, the presence of depleted granulocyte zinc levels could modify the immune function of this cell population.

Adult↗
PubMed1987

Ovariectomy of adult mice exposed prenatally to diethylstilbestrol.

Mice exposed prenatally to diethylstilbestrol (DES) were ovariectomized at 5-10 weeks of age, or at 15 months of age. They were maintained to old age and studied for incidence of DES-related pathologic changes. Uterine metaplasia and adenomyosis were not seen after early ovariectomy, but adenomyosis persisted after late ovariectomy. No adenocarcinomas of the genital tract were found in 30 mice ovariectomized early, or in 18 mice ovariectomized at 15 months of age. This result is significantly different from the 14% frequency of genital tract adenocarcinomas reported previously in non-ovariectomized mice of this strain exposed prenatally to DES.

Age Factors↗