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Biomedical subjects

M Gerber

Publications and source records attributed to M Gerber.

At least 91 records · Page 5Linked to original sources

Zinc and copper in breast cancer. A joint study in northern Italy and southern France.

The relationship between breast cancer and two trace elements, zinc (Zn) and copper (Cu), was investigated by means of an hospital based case-control study at Milan (Italy) and Montpellier (France). Variables concerning dietary intake of Zn and Cu (in Milan) and their blood levels (both in Milan and Montpellier) were measured. Dietary intake, evaluated through a questionnaire of the dietary history type, and blood levels of Zn and Cu were measured in 261 cases and 261 controls. Cu blood level showed a contradictory tendency in the two samples (higher in controls in Milan, higher in cases in Montpellier), which tended to lessen after adjustment for related variables. No odds ratios (OR) in the different quantiles, nor X2 for trend reached statistical significance. A sharp difference was evidenced on the opposite with regard to Zn blood values in cases and controls. In both samples Zn mean values are significantly higher in cases than in controls, and the difference remains significant in the two samples even after adjustment for related variables. The pooled OR computed from the two samples, after adjustment for known risk factors and related variables, reaches in the fourth quartile a value of 9.5 (CI: 4.9-18.2). Dietary intake of the two minerals (measured only in Milan sample) showed no difference between cases and controls, but a stronger relationship between dietary and blood Zn was evidenced in cases with respect to controls. The authors suggest that the higher Zn level in cases might be related with an higher incorporation of Zn in cancer cases and that the same mineral might play a possible role in tumor growth promotion.

Adult↗

The pattern of risk factors for breast cancer in a southern France population. Interest for a stratified analysis by age at diagnosis.

A hospital-based case-control study was conducted over 4 years in Southern France to assess the pattern of established risk factors for breast cancer and to examine its variation according to age at diagnosis. Cases studied (450) were women admitted to the Montpellier Cancer Institute, with histologically confirmed primary breast carcinoma. Controls (576) were patients from a nearby hospital admitted in the early stages of a neurological or mild psychological diseases and from a clinic for general surgery. Any patient with malignant tumours, chronic and cardiovascular diseases were excluded. The total population globally showed the commonly reported pattern for these risk factors. When stratified by age, the reproductive factors occurring early in life (menarche, first full term pregnancy) were shown to be significant risk factors only in the youngest group of patients and do not seem to influence risk in older women, for whom risk factors are those occurring later in life (menopause, obesity). This suggests a complex involvement of the reproductive and sociodemographic features with the various stages of the 'natural history' of breast cancer.

Adult↗

Geographical and temporal distribution of babesial infection in Connecticut.

Human babesiosis was first recognized in Connecticut in 1989, nearly 15 years after Lyme disease, a similarly transmitted spirochetosis, was detected in the state. To determine the seroprevalence for the babesial pathogen and whether it was recently introduced, we used an indirect immunofluorescence assay to test for Babesia microti antibody in 1,285 Connecticut residents. Four groups were studied: I, people seropositive for Lyme disease, tested from 1986 to 1989; II, randomly selected outpatients tested in 1989; III, college students residing in Connecticut, tested from 1959 to 1989; and IV, healthy people without tick exposure or Lyme disease, tested in 1989. Babesia seropositivity was significantly higher in group I (9.5%; n = 735) than in groups II (2.6%; n = 304, P less than 0.0001) and III (1.0%; n = 206, P less than 0.0001) but not group IV (2.5%, n = 40). Babesia seropositivity for group I ranged from 9.2 to 10.2% between 1986 and 1989, and Babesia seropositivity for group III ranged from 0% between 1959 and 1985 to 2.9% between 1986 and 1989. There is a considerable risk of babesial infection among residents of the Connecticut mainland who are seropositive for Lyme disease, a risk that appears to have remained constant over the past 5 years.

Animals↗

Antioxidants in female breast cancer patients.

Blood levels of selenium, zinc, copper, and vitamins E and C were measured in 48 cases and 50 controls from a hospital-based case-control study bearing on breast cancer risk factors in Montpellier (France). Cellular levels of selenium and vitamins E and C were also evaluated in most of the subjects. We found that the blood and cellular levels of these antioxidants were overall higher in cases than in controls, significantly for serum zinc, plasma, and leukocyte vitamin E. The statistical significance of the difference between case and control serum Cu crude levels disappeared after adjustment for metabolically related variables. The difference was borderline significant for leukocyte vitamin C. These results were slightly modified when vitamin pill users were excluded from case and control samples. The serum zinc odds ratios computed after adjustment for related variables were significantly elevated (2.53, confidence interval: 1.34-4.78, for the highest tertile) as were those computed previously for pooled plasma vitamin E levels in a joint study.

Adult↗

Phase II study of oral idarubicin in favorable histology non-Hodgkin's lymphoma.

Idarubicin, a new analogue of daunorubicin, was administered p.o. for 3 consecutive days every 3 weeks at a dose of 45 mg/m2 in 46 patients (45 eligible and evaluable) with previously treated, favorable histology, non-Hodgkin's lymphoma. Median clinical characteristics included an age of 66 years, a performance status of 1, and one prior chemotherapeutic regimen. Forty-one patients were relapsing from prior therapy, and 37 had stage IV disease. Patients with prior anthracycline therapy were excluded. Responses were observed in 58% of patients (10 complete and 16 partial), with a median duration of 6+ months (2-41+ months). Idarubicin was well tolerated. Nonhematological toxicities (nausea/vomiting, mucositis/diarrhea, alopecia, and anorexia) were observed in less than or equal to 50% of patients. Median hematological values during the first cycle include a WBC of 4100/mm3 and a platelet count of 147,000/mm3. With dose escalation, hematological toxicity was the dose-limiting toxicity. Symptomatic cardiac toxicity was not observed. Median values for the resting left ventricular ejection fraction during the course of therapy were 0.65 (initial) and 0.63 (final). Idarubicin in oral form is an active drug in previously treated patients with favorable histology non-Hodgkin's lymphoma.

Administration, Oral↗

The role of diet history and biologic assays in the study of "diet and breast cancer".

Nutritional factors related to breast cancer were investigated by means of a hospital-based case-control study in Milan (Italy) and Montpellier (France). Liposoluble vitamins, cholesterol and triglycerides were measured in blood samples taken from interviewed subjects (319 cases and 344 controls). In addition serum zinc and copper was assessed in the Italian samples and serum fatty acids and malonyl-di-aldehyde in the French samples. A significant difference was found between cases and controls in total fat and cholesterol intake in both populations, and in saturated fatty acid and mono-unsaturated fatty acid consumption in the French samples. No difference emerged in liposoluble vitamin consumption in both populations nor in zinc and copper consumption in the Italian samples. A statistically significant higher serum level of cholesterol and plasma level of vitamin E was observed in cases compared to controls in both populations. The difference in plasma vitamin E was confirmed after adjustment on total cholesterol and triglycerides. Similarly, zinc serum level was higher in Italian cases than in Italian controls, while malonyl-di-aldehyde was lower in French cases than French controls. A multivariate analysis was performed after classification of cases and controls according to quantile distribution of controls. Nutrient consumption and relevant blood markers were directly or partially correlated in both populations. All known risk factors plus age, serum total cholesterol and triglycerides were used as covariates. The odds ratio values for the highest quantiles are: Dietary cholesterol, OR = 1.9 (1.1-3.4); total dietary lipids, OR = 1.9 (1.0-3.4); plasma vitamin E, OR = 4.2 (1.9-9.0); serum zinc, OR = 12.2 (5.4-27.7); serum malonyl-di-aldehyde, OR = 0.56 (0.33-0.97).

Breast Neoplasms↗

Relationship between vitamin E and polyunsaturated fatty acids in breast cancer. Nutritional and metabolic aspects.

Intake of vitamin E, total lipids, total cholesterol, and fatty acids were analyzed with the blood levels of vitamin E, total cholesterol, triglycerides, and the serum distribution of fatty acids in a hospital-based population of 120 patients and 109 controls. In regard to nutritional intake, the only significant differences involve saturated and monounsaturated fatty acid consumption, which is more elevated in postmenopausal patients than in postmenopausal controls. Vitamin E and total cholesterol blood levels are significantly higher in patients than in controls, where the difference is that vitamin E is independent from cholesterol level in premenopausal women only. Fatty acid serum distribution is comparable in both samples, with the exception of arachidonic acid, which is significantly lower in premenopausal patients than in premenopausal controls. Two multivariate regression analyses of the plasma vitamin E levels of patients and controls were done with menopausal status and nutrients as independent variables for the first analysis, and with menopausal status and all blood analytes for the second one. The regression coefficients for total cholesterol and triglycerides are statistically significant for both samples, whereas a positive association between vitamin E plasma level and sunflower oil consumption and between vitamin E plasma level and serum linoleic acid distribution is significant for patients only. Furthermore, the multiple regression shows that, when adjusted for analyte variables, plasma vitamin E levels are higher in premenopausal than in postmenopausal patients. In addition, plasma lipid peroxidation, evaluated by malondialdehyde measurement, is shown to be significantly lower in patients than in controls. Malondialdehyde level is associated with a significant lower odds ratio (OR) after multivariate tertile analysis (OR for the highest tertile: 0.51; 95% CI: 0.29-0.89). Together, these findings are consistent with a picture of lower lipid peroxidation in patients than in controls.

Adult↗

Alcohol consumption in a case-control study of breast cancer in southern France.

The effect of alcohol consumption on breast cancer risk was investigated in a hospital-based, case-control study of 808 patients (349 cases and 459 controls) in Montpellier (France). Semi-quantified diet history including beverage consumption as well as relevant medical and personal characteristics were assessed by interview. A dose-rate relationship for total alcohol consumption was found with unadjusted odds ratios ranging from 1.8 (95% CI 1.2-2.8) for 1 to 2 drinks per week to 3.5 (95% CI 2.0-6.1) for more than 17 drinks per week, in comparison with less than 1 drink per week. Confounding by known or suspected determinants of breast cancer, smoking, use of oral contraceptives, lipid and vitamin consumption was looked into. Significant interactions were found with level of education and lipid consumption, with a higher risk for alcohol in women having had less schooling or consuming less fat. Adjustment with respect to the other risk factors did not modify the relationship. There was a significant risk increase both for wine and stronger drinks. Along with several other studies, our results give support to the hypothesis that alcohol is a risk factor in breast carcinogenesis.

Alcohol Drinking↗

Evaluation of a new assay for pancreatic amylase: performance characteristics and estimation of reference intervals.

We have evaluated a new assay for the specific determination of pancreatic (P) isoamylase, the principle being based on a synergistic inhibitory effect of two monoclonal antibodies directed towards salivary (S) amylase. After 3 min incubation, activities were determined with maltoheptaoside-PNP as substrate on a Hitachi 705 analyzer at 25, 30 and 37 degrees C, respectively. Coefficients of variation ranged from 0.6 to 5.4% for within-run and 2.1 to 9.9% for day-to-day precision. Linearity held up to 1200 U/L (25 degrees C) and 2300 U/L (37 degrees C). Comparison of the new method with the wheat germ inhibitor technique showed an excellent correlation, with coefficients ranging from 0.990 to 1.00. Using purified P- and S-amylase we observed no inhibiting cross-reactivity of the antibodies with the P-isoenzyme, but an incomplete blockage of S-amylase: residual activity was approximately 2% at 25 and 30 degrees C, and 2.5% at 37 degrees C. The distribution pattern of P-, S- and total amylase activity in serum of healthy subjects was only slightly skewed to the right. We found neither an influence of sex nor of age on the reference ranges. In random urine samples, distribution of activities was strongly skewed. However, if the activity was related to the urinary creatinine concentration, an approximately normal distribution was obtained, allowing, as in serum, the establishment of upper and lower reference values.

Adolescent↗

Inhibition of murine T-cell responses by anti-oxidants: the targets of lipo-oxygenase pathway inhibitors.

We have previously established that oxidative phenomena are involved in human T-cell activation (Sekkat, Dornand & Gerber, 1988). In the present work we have studied the effect of different anti-oxidants (scavengers of O2-, .OH and lipo-oxygenase inhibitors) on the stimulation of murine T cells. We report here that all the anti-oxidants used suppressed T-lymphocyte proliferation and IL-2 synthesis, the former effect resulting very likely from the latter. This inhibition was concomitant with the triggering of activation. We also demonstrate that the various anti-oxidants have different biochemical targets. Unlike the other compounds, the phenolic drugs nordihydroguaiaretic acid (NDGA) and butylated hydroxyanisole (BHA), which block lipid peroxidation, affect both signals triggered by the binding of lectin to its receptors: they suppress the rise of intracellular free calcium concentration and inhibit some of the events, depending on the sole protein kinase C activation, namely IL-2 receptor expression and phorbol myristate acetate (PMA)-induced pH change. Our results are discussed within the framework of a possible involvement of reactive oxygen species and of arachidonic acid derivative(s) in T-cell activation and IL-2 production.

Animals↗

The influence of interleukin-2, feeder cells, and timing of irradiation on the radiosensitivity of human T lymphocytes assessed by the colony-forming assay.

The radiosensitivity of human lymphocytes was investigated by the method of colony formation in the absence of interleukin-2 (IL2) and feeder cells, both of which enhance growth of T-cell colonies. The shape of the survival curve and the radiosensitivity was shown to depend upon the ability of lymphocytes to produce IL2: the survival curve for lymphocytes that were the most competent producers of IL2 is the closest to linearity; the lymphocytes that were poor producers show biphasic survival curves. The radiosensitivity of the lymphocytes from the first group is less than that of the latter, when the comparison is based on the first part of the biphasic survival curve. This is more easily seen when cultures are irradiated 24 h after stimulation by phytohemagglutinin (the time of the peak IL2 production) than when cultures are irradiated 2 h before stimulation. This study demonstrates that growth conditions influence the response of lymphocytes to irradiation and that optimal growth conditions result in a linear survival curve.

Adult↗

Liposoluble vitamins and lipid parameters in breast cancer. A joint study in northern Italy and southern France.

The relationship between breast cancer, liposoluble vitamins, cholesterol and triglycerides was investigated by means of a hospital-based case-control study conducted at Milan (Italy) and Montpellier (France). These parameters were measured in blood samples taken from 319 cases and 344 controls. The interview included an evaluation of dietary intake of liposoluble vitamins. No difference emerged in liposoluble vitamin consumption, whereas a statistically significantly higher serum level of cholesterol and plasma level of vitamin E existed in cases compared to controls. The difference in plasma vitamin E was confirmed after adjustment for total cholesterol and triglycerides. In contrast, vitamin A variations appear to follow triglyceride trends. A multivariate analysis of the vitamin E plasma level was performed after classification of cases and controls according to quintile distribution of controls. All known risk factors plus age, serum total cholesterol and triglycerides were used as covariates. The odds ratio value for the highest quintile of plasma vitamin E is: 4.2 (1.9-9.0).

Adult↗

Localization of human ERBA2 to the 3p22----3p24.1 region of chromosome 3 and variable deletion in small cell lung cancer.

Human genes homologous to the v-erbA oncogene of avian erythroblastosis virus have been mapped to at least two human chromosomes. Recently, the ERBA2 gene was shown to encode a thyroid hormone receptor and localized to chromosome 3 by using flow-sorted chromosomes. We now demonstrate that this gene is located at 3p22----3p24.1, using both somatic cell hybrids and in situ hybridization studies. Since this localization is close to the distal border of the small cell lung cancer (SCLC) 3p14----3p23 deletion, we undertook additional studies to examine the ERBA2 gene in SCLC. Using somatic cell hybrids constructed from the SCLC line NCI-H182 as well as matched patient tumor and control tissue samples, we found that ERBA2 is variably deleted. Therefore, ERBA2 defines at the molecular level the distal border of the SCLC deletion and further implies that the putative suppressor gene is located centromeric of this locus. We also determined that, at least in NCI-H182, the 3p14 breakpoint is proximal to the constitutive 3p14.2 fragile site. These studies would indicate that the mechanism or initiation site of chromosomal rearrangement in SCLC is different from that which occurs during induction of the 3p14 fragile site by aphidicolin.

Carcinoma, Small Cell↗