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Biomedical subjects

A Belanger

Publications and source records attributed to A Belanger.

At least 37 records · Page 2Linked to original sources
PubMed1995

Localisation of 15-hydroxy prostaglandin dehydrogenase (PGDH) and steroidogenic enzymes in the equine placenta.

15-hydroxy prostaglandin dehydrogenase (PGDH) is the critical enzyme that determines metabolism of primary prostaglandins. Its expression is determined in part by steroid hormones, particularly progesterone, formed from delta(5) steroids through 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity. To assess whether the regulation of PGDH might occur in a paracrine, autocrine or intracrine fashion, we used immunohistochemistry (IHC) to determine the localisation of key steroidogenic enzymes in the equine placenta and compared these patterns to the distribution of immunoreactive (IR-) PGDH. Placental tissue was obtained from pony or Thoroughbred mares at about Days 150, 250-280 and >300 of pregnancy (term 320 to 360 days; n=5-8 each group). IR-PGDH, 3beta-HSD, cholesterol side chain cleavage enzyme (P450(scc)) and 17-hydroxylase/lyase (P450(C17)) were localised using specific antibodies and the avidin-biotin peroxidase technique and visualised using diaminobenzidine as substrate. IR-P450(scc) was present in trophoblast cells, but not in maternal tissues of the microcotyledons. In contrast, at Days 150 and 280, IR-PGDH was present in maternal epithelial and interstitial cells in the microcotyledons, but was not detected in trophoblast epithelium, chorioallantois or endometrial glands. After Day 300, IR-PGDH was present in the maternal epithelium and interstitial cells of the placenta and it was also present in trophoblast cells in some specimens.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Effect of oral isotretinoin treatment on skin androgen receptor levels in male acneic patients.

An oral daily dose (mean +/- SD, 0.75 +/- 0.05 mg/kg) of isotretinoin was administered for 3 months to six male patients with acne (scores of 4 and 5 according to Rosenfield). The therapy resulted in complete resolution of acne in four patients and improved acne significantly (score 1) in two patients. In accordance with recent findings, no change in serum testosterone and significant decreases in 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol glucosiduronate, and androsterone glucosiduronate levels were observed after treatment. Androgen receptor status was investigated in back skin biopsies obtained in acne areas before and after 3 months of isotretinoin treatment. The treatment did not modify the binding affinity constant of skin androgen receptor (0.44 vs. 0.32 nmol/L), but it did induce a 2.6-fold decrease in its binding capacity constant (62 vs. 24 fmol/mg cytosolic protein), as assessed by Scatchard plot and confirmed immunologically by Western blot analysis. These data clearly showed that skin androgen receptor was sensitive to oral isotretinoin administration in acneic patients. The decrease in skin androgen receptor levels (this study) and the recently reported suppression of skin 5 alpha-dihydrotestosterone production by isotretinoin treatment appeared consistent with the involvement of androgen receptor and 5 alpha-dihydrotestosterone in the pathogenesis of acne. Indeed, sebum production is under androgen control, and an abnormal response of the pilosebaceous unit to androgens appears to be implicated in the pathogenesis of acne. These observations were consistent with the absence of sebum in complete androgen-insensitive patients and normal sebum production in male pseudohermaphrodites.

Acne Vulgaris↗
PubMed1995

[Mortality due to bronchopulmonary cancers in workers of 2 foundries].

A mortality study was carried out in two factories producing stainless steel in order to assess lung cancer risk among workers employed in coke oven, blast and open hearth furnaces, foundry, electric furnace, hot and cold rolling mills and pickling areas. Occupational exposures of interest were chromium compounds, nickel compounds, polycyclic aromatic hydrocarbons (PAH), silica and asbestos. All male workers having at least one year of employment between 01.01.1960 and 31.12.1990 were followed up for mortality. The vital status was assessed from birth place registries. Complete job histories since date of first employment were abstracted from the company files. The smoking habits of 50% of the cohort members were known from medical records. The observed number of deaths (obs) were compared with the expected ones based on regional rates with adjustment for age, sex and calendar time (Standardized Mortality Ratio, SMR). The cohorts included 6324 (factory 1) and 5270 (factory 2) workers. The overall mortality did not differ markedly from that expected in both factories: SMR = 0.95 (obs = 1540, p = 0.05) in factory 1 and SMR = 1.06 (obs = 916, non-significant) in factory 2. SMRs for lung cancer did not differ from unity, respectively 0.99 (obs = 105) and 1.00 (obs = 54), in whole cohorts. Non-significant lung cancer excesses were observed among workers of some workshops where exposures of interest might have occurred: coke oven (SMR = 2.04), blast furnace (SMR = 1.36), open hearth furnace (SMR = 1.75), hot rolling mills (SMR = 1.29). These processes, however, are no longer involved in the study factories. Furthermore, no lung cancer excess was observed among workers employed in current workshops: electric furnaces and cold rolling mills.

Adult↗
PubMed1994

Evidence for decreased androgen 5 alpha-reduction in skin and liver of men with severe acne after 13-cis-retinoic acid treatment.

To investigate the effect of 13-cis-retinoic acid (13-cis-RA) treatment on androgen metabolism in men with severe nodulocystic acne, eight men with severe acne received an oral daily dose of 0.7 mg/kg 13-cis-RA over 3 months. Exploration of androgen metabolism in serum samples, 24-h urine collections, and skin biopsies obtained before and at the end of the treatment revealed no significant alterations in serum levels of either adrenal or gonadal androgens. However, the treatment did induce significant decreases in serum levels of the 5 alpha-reduced androgens: 5 alpha-dihydrotestosterone (P < 0.02), androsterone glucosiduronate (P < 0.04), and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate (P < 0.004). Unlike serum, the urinary 5 alpha-reduced metabolites 5 alpha-androstan-3 alpha, 17 beta-diol and androsterone did not vary significantly despite a decrease in the excretion of the latter. Moreover, a marginally significant increase in urinary excretion of etiocholanolone, very similar to the decrease in androsterone excretion, was observed. The ratio of androsterone to etiocholanolone decreased significantly (P < 0.004) after 13-cis-RA therapy and suggested a metabolic deviation from the androgen 5 alpha- to 5 beta-reduction pathway in the liver. The most pronounced effect was observed in skin biopsies, which lost 80% of their ability to form 5 alpha-dihydrotestosterone (P < 0.001). It is concluded that 13-cis-RA therapy in men with severe nodulocystic acne did not alter gonadal or adrenal functions, but it did induce 1) a highly significant decrease in 5 alpha-dihydrotestosterone formation by skin biopsies; 2) significant decreases in serum 5 alpha-dihydrotestosterone, androsterone glucosiduronate, and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate; and, finally, 3) deviation of the liver androgen 5 alpha- to 5 beta-reduction pathway. The effect of 13-cis-RA treatment on severe acne is consistent with the dramatic decrease in androgen 5 alpha-reduction observed mainly in the skin.

Acne Vulgaris↗
PubMed1994

Hirsutism and acne in women: coordinated radioimmunoassays for eight relevant plasma steroids.

We developed and validated a coordinated set of RIAs for the following eight steroids in single small aliquots (< or = 1 mL) of plasma: androstenedione, dehydroepiandrosterone, 11-deoxycortisol, 21-deoxycortisol (21-DF), 11 beta-hydroxyandrostenedione, 17 alpha-hydroxypregnenolone (17-Hpreg), 17 alpha-hydroxyprogesterone, and testosterone. Samples were extracted and then chromatographed on celite microcolumns. Radioiodinated tracers were used for two of the assays (17-Hpreg and 21-DF). Tritiated tracers and scintillation proximity assay counting were used to give separation-free procedures for the other six assays, which considerably improved their practicability and reproducibility. The basal and postadrenocorticotropic hormone plasma values for these steroids in normal women sampled in the follicular phase are presented. Finally, the measurement of the eight steroids as a diagnostic method is evaluated with reference to data from 203 patients with hirsutism and (or) acne.

17-alpha-Hydroxypregnenolone↗
PubMed1993

Combination therapy for prostate cancer. Endocrine and biologic basis of its choice as new standard first-line therapy.

RESULTS. All double-blind randomized and prospective clinical trials in advanced prostate cancer have shown that combination therapy using a nonsteroidal antiandrogen in association with a luteinizing hormone-releasing hormone (LHRH) agonist or orchiectomy has significant benefits according to all the subjective and objective parameters used, the most important being a prolongation of survival ranging from 5.4-15.0 months compared with LHRH agonists or orchiectomy alone (standard therapy). The benefits observed are probably the result of the blockade by the antiandrogenic agents of the androgens of adrenal origin, which represent, on average, 40% of the total androgens in men and which, otherwise, are left free to continue to stimulate prostate cancer after castration. These data are supported well by the demonstration of the expression of the genes encoding all enzymes required for the formation of active androgens in prostatic tissue from the inactive adrenal steroid precursors; this new specialty is called intracrinology. Both fundamental and clinical data indicate that low androgen levels cause changes in the cancer cells that lead to no or a poor response to antihormonal therapy. CONCLUSIONS. It is thus imperative that combination therapy be used as first treatment in all patients in whom endocrine therapy is indicated. Prior exposure to monotherapy shortens the patient's life by many months and produces a poor quality of life.

Adrenal Cortex Hormones↗
PubMed1993

Influence of heart rate on mortality among persons with hypertension: the Framingham Study.

Previous studies have shown positive associations between heart rate and both all-cause and cardiovascular mortality. These relationships, however, have not been investigated in persons with hypertension. Using 36-year follow-up data from the Framingham Study, we evaluated from 4530 subjects, aged 35 to 74, whose blood pressures were > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic and who were not treated with antihypertensive medication. We used pooled logistic regression to calculate biennial mortality rates. Odds ratios and 95% confidence intervals for each increment in heart rate of 40 beats/min, adjusted for age and systolic blood pressure level, were: for all-cause mortality, 2.18 (1.68, 2.83) for men and 2.14 (1.59, 2.88) for women; and for cardiovascular mortality, 1.68 (1.19, 2.37) for men and 1.70 (1.08, 2.67) for women. Exclusion of outcomes in the first 2 or 4 years after measurement of heart rate did not materially change the results, which suggests that rapid heart is not merely an indicator of preexisting illness. Therefore heart rate may be an independent risk factor for cardiovascular death in persons with hypertension.

Adult↗
PubMed1993

[Interprovincial migration among foreign-born Canadians, 1981-1986].

"This article analyzes the spatial distribution as well as interprovincial migration of foreign-born persons living in Canada, using data from the 1986 census. The focus is placed on differences observed in migratory behaviour between native-born Canadians and those born abroad. Net migration patterns as well as the propensity to migrate by place of origin and destination are presented for different population groups according to birthplace. Finally, multiregional life tables are used to evaluate the effect of these migratory differentials on the retentive force exerted by the various regions." (SUMMARY IN ENG AND SPA)

Americas↗
PubMed1992

Effect of ACTH on steroidogenic enzymes in guinea pig fasciculata-glomerulosa cells: changes in activity and mRNA levels.

Adrenocorticotropin (ACTH) is known to exert an acute effect on adrenal steroidogenesis as well as long-term effects by regulation of gene expression. In order to further study the long-term action of ACTH, guinea pig fasciculata-glomerulosa (FG) cells in primary culture were treated for up to 72 h with ACTH. The effects of this treatment on steroid secretion, enzyme activity and mRNA levels for steroid enzymes were measured. While the rate of 17-deoxy C-21 steroid secretion decreased over the 72-h period of incubation with ACTH, the 17-hydroxy C-21 steroid secretion rate remained constant for the first 24 h of incubation and declined thereafter; the rate of 4-ene C-19 steroid secretion increased over the 72-h incubation period. ACTH treatment increased 17-hydroxylase and 17,20-lyase activities and the maximal stimulation was reached after 48 h. In contrast, the activity of 21-hydroxylase (P450c21) steadily declined over the 72-h incubation period. ACTH also caused an increase in mRNA levels for P450c21, 17-hydroxylase and 17,20-lyase (P450c17), 3 beta-hydroxysteroid dehydrogenase 4-ene-5-ene-isomerase (3 beta-HSD) and cholesterol side-chain cleavage enzyme (P450scc). The maximal stimulation for the four mRNAs was observed after 18 h of incubation with ACTH, decreasing afterwards except for P450c17 mRNA levels which remained elevated over the 72-h incubation period. Despite the increase in mRNA levels for 3 beta-HSD and P450c21, no increase in their respective enzyme activities was observed and 21-hydroxylase activity even declined over the 72-h incubation period with ACTH, thus suggesting that mechanism(s) other than gene expression alone regulate steroid secretion in FG cells. In conclusion ACTH caused major changes in steroid distribution due to increased 17-hydroxylase and 17,20-lyase activities and decreased 21-hydroxylase activity in FG cells in culture. Moreover, our data revealed major differences in the induction of mRNAs for steroidogenic enzymes and their activities following ACTH treatment.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Effect of chronic ACTH treatment on guinea-pig adrenal steroidogenesis: steroid plasma levels, steroid adrenal levels, activity of steroidogenic enzymes and their steady-state mRNA levels.

We report here the effects of a 7-day treatment of guinea-pigs with ACTH on adrenal mRNA levels for steroid-transforming enzymes. Adrenal 3 beta-hydroxysteroid dehydrogenase 4-ene-5-ene-isomerase (3 beta-HSD), 17-hydroxylase, 17,20-lyase, 21-hydroxylase and 11-hydroxylase activities were also examined as well as plasma and adrenal steroid levels. Our data reveal that chronic ACTH-treatment stimulated all post-pregnenolone enzyme activities in glomerulosa-fasciculata cells. Plasma steroid levels increased 8 h after the last injection of ACTH and returned to the control levels 24 h later whereas, in the adrenal, the content in steroids in the group sacrificed 8 h after the last injection of ACTH were similar to the values of the control group and decreased markedly 24 h later. It is suggested that the steroid turn-over in the adrenal may be affected by the chronic ACTH-treatment. On the other hand, despite the significant stimulation in steroid-transforming enzyme activities, our data reveal that chronic ACTH administration caused a decrease in mRNA levels for P450c21 and P450c17 while P450scc, 3 beta-HSD and P450c11 remained unchanged. Taken together, these results suggest that in vivo chronic ACTH-treatment of guinea-pigs increases adrenal steroidogenic capacity by increasing steroid secretion and steroid enzyme activity. Moreover, the chronic treatment with ACTH may have a post-transcriptional effect on steroidogenic enzymes gene expression by affecting the half-life of their mRNAs.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Estrogen-stimulated glucuronidation of dihydrotestosterone in MCF-7 human breast cancer cells.

The non-aromatizable androgen dihydrotestosterone (DHT) has been shown to exert a potent inhibitory effect on the proliferation of some human breast cancer cell lines. DHT, however, has little or no significant inhibition on MCF-7 cell proliferation in either the presence or absence of estradiol (E2). Since the metabolism of DHT into non-active compounds may be responsible for the observed lack of androgenic effect in this cell line, we have investigated the metabolic fate of labeled DHT in MCF-7 cells. A time course incubation was performed with 1 nM [3H]DHT and analysis of the various metabolites formed revealed a time-dependent increase in glucuronidated steroids which was stimulated more than 4-fold by 0.1 nM E2. The major glucuronidated steroid was androstane-3 alpha, 17 beta-diol in both control and E2-stimulated cells, comprising 22 +/- 1.2% and 30 +/- 0.6% of the total radioactivity in the medium, respectively. Other steroid glucuronides observed included DHT, androstane-3 beta,17 beta-diol, and androsterone, all of which were elevated in the E2-treated cells relative to control values. The present data show that E2 exerts a stimulatory effect on the glucuronidation of androgens and their metabolites in the estrogen-dependent breast cancer cell line MCF-7. Since glucuronidation is an effective means of cellular elimination of active steroids, such a pathway may be considered as a possible site of regulation of breast cancer cell growth by hormones.

Breast Neoplasms↗
PubMed1992

Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study.

We determined the prevalence of dementia and probable senile dementia of the Alzheimer type (SDAT) for biennial Exam 17 of the Framingham cohort (1982/1983). The prevalence of dementia was 30.5/1,000 for men and 48.2/1,000 for women and increased with advancing age. Cases of probable SDAT constituted 55.6% of all dementia cases. THe prevalence of SDAT was 11.7/1,000 for men and 30.1/1,000 for women and also increased with advancing age. Prevalence of dementia and probable SDAT were greater for women than men. The female:male ratio of prevalence for cohort members 75 years of age and older was 1.8 for all cases of dementia and 2.8 for cases of probable SDAT.

Adult↗
PubMed1992

The internal migration and spatial redistribution of the foreign-born population in the United States: 1965-70 and 1975-80.

"This article examines the importance of place of birth [for] the internal migration and spatial redistribution patterns of the foreign-born population in the United States during the 1965-70 and the 1975-80 periods, relying principally on the Public Use Microdata Sample (PUMS) files for our input data. The diverse nationalities are aggregated into eight different regions of origin: Mexico, Puerto Rico, Rest of South and Central America, Europe, Asia, Africa and Oceania, Canada and the Rest of the World. First, the regional distribution of these eight groups at the 1970 and 1980 censuses are examined. Next, the spatial redistribution of the foreign-born population and its changes over time are studied...." This paper was originally presented at the 1990 Annual Meeting of the Population Association of America.

Age Factors↗
PubMed1992

Online bibliographic information: integration into an emerging IAIMS environment.

The Medical Library at Yale University has developed an online free-text database containing Current Contents citations. The database was designed to be integrated into an emerging campus-wide information environment. To this end Current Contents at Yale was designed with a user interface familiar to the Yale community, an alerting service based on electronic mail, and search expansion using the National Library of Medicine's Meta-1 metathesaurus.

Consumer Behavior↗
PubMed1991

Predicting reading problems in at-risk children.

This study was designed to determine early predictors of reading problems in children at risk for such problems. Three groups of children participated in the study: those with a specific language impairment; those who presumably had a language delay or disorder early in life and had no or a mild disorder at present; and a group of premature children. The data collected were standard speech and language test measures, given as the children entered the study, measures of language meta-processing abilities on an experimental battery, given 6 months after they entered the study; and standard measures of reading, given when the children were aged 80 to 96 months. Many significant relations were found between measures of oral language ability and meta-processing ability at an earlier age and reading ability in first and second grade. The language processing battery scores accounted for a somewhat greater amount of variance on the reading tests than did the scores on the standard language tests. Three ability groups, comparatively high, middle, and low, were found in the population as a result of cluster analysis. Some premature children and some children with early language disorder or mild language disorder at entry into the study, as well as most SLI children, were members of the low language-ability group. These data were then examined to see if membership in the low language-ability group, as measured by either standard speech and language tests or the language meta-processing battery predicted at-risk reading performance on the WRAT. Forty-six children were found to be at risk by this test. Twenty-one of the children were identified by either set of measures, an additional 10 were identified by the language meta-processing measures alone, an additional 3 by the intake measures alone, and 12 of the children were not identified by either set of measures as potential problem readers. The results indicate that early measures of language awareness are good predictors of later reading performance but that different measures of this awareness are good predictors for different children.

Child↗
PubMed1990

Multistate life table with duration dependence: an application to Hungarian female marital history.

"Building on recent developments in multistate demography, and using data from the 1984 Hungarian microcensus, this paper analyzes the impact that the introduction of duration-specific transitions has on the results of a multistate life table analysis of marital dissolution. The results show that the inclusion of duration has its greatest impact on the distribution of the stationary population between ages 25 and 35." (SUMMARY IN FRE)

Age Factors↗