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Biomedical subjects

M Plante

Publications and source records attributed to M Plante.

At least 55 records · Page 3Linked to original sources
PubMed1993

Ontogenesis of the rabbit pituitary intermediate lobe. An ultrastructural and immunocytochemical study.

The development of the intermediate lobe of the rabbit pituitary was investigated by light and electron microscopy and by using immunocytological techniques. The first immunoreactive melanotrophic cells were detected at the fetal day 17 in the dorsal zone of Rathke's pouch epithelium facing the neural lobe; this coincided ultrastructurally with the appearance in this area of a few cells exhibiting secretory vesicles and granular condensations in the Golgi saccules. The differentiation of the gland probably required an infundibular inductive effect. Secretory cells increased in number following a dorsoventral gradient during the next fetal and neonatal stages until postnatal day 20, the stage at which the intermediate lobe exhibited its definitive organization. The gland innervation occurred during the first days after birth. The advent of these oxytocin- and neurophysin-immunoreactive fibres coincided with an obvious stimulation of the synthetic activity of the melanotrophic cells. The possible neurotrophic effect of these cells on their innervating system remains to be established.

Animals↗
PubMed1993

Prognostic significance of HER-2/neu expression in advanced epithelial ovarian cancer: a multivariate analysis.

OBJECTIVE: We tested the hypothesis that there is prognostic significance to the level of expression of the protooncogene HER-2/neu in advanced ovarian cancer, as prior studies have suggested. STUDY DESIGN: We determined expression of HER-2/neu by immunohistochemistry, with monoclonal antibody 9G6 and the indirect immunoperoxidase technique, on frozen tumor specimens from 105 patients with stage III or IV epithelial ovarian cancer. All patients were treated at Memorial Sloan-Kettering Cancer Center, and no patient was lost to follow-up. Median follow-up among surviving patients is 34 months. HER-2/neu expression was scored as negative, weak, 1+, 2+, or 3+. The staining pattern of normal ovarian epithelium was scored negative to 1+. Multivariate analysis was performed to evaluate the prognostic significance of HER-2/neu expression. RESULTS: Twenty-five of the 105 patients (24%) showed strong membrane staining (3+); the other tumor specimens showed weaker membrane staining or no immunoreactivity. There was no correlation of HER-2/neu expression with any of a variety of clinical factors, including stage, grade, cell type, and residual tumor. No significant survival difference was found between patients with levels of staining intensity similar to those of normal ovarian epithelium and those with increased expression (3+). Median survival times were 36 and 27 months, respectively, for the two groups (95% confidence intervals 29 to 45 and 18 to 39 months). Multivariate analysis of possible prognostic factors showed that HER-2/neu overexpression conferred a marginal worsening of survival (p = 0.09) for the subgroup of patients in whom a negative surgical reassessment was not achieved after chemotherapy. CONCLUSION: HER-2/neu expression does not appear to be an important prognostic factor in patients with advanced epithelial ovarian cancer.

Adult↗
PubMed1993

High IL-6 levels in ascitic fluid correlate with reactive thrombocytosis in patients with epithelial ovarian cancer.

Non-haematopoietic malignancies are commonly associated with thrombocytosis. The aetiology of tumour-associated thrombocytosis is still unclear but may be related to tumour-derived thrombopoietin-like factors. Epithelial ovarian tumour cells have been shown to release IL-6 in vitro and high IL-6 levels have been identified in ascites of patients with ovarian cancer. Since IL-6 is a potent stimulator of megakaryocytopoiesis we examined IL-6 production at the tumour site and its relationship to serum IL-6 levels and circulating platelet counts in patients with ovarian cancer. Forty patients undergoing exploratory laparotomy for epithelial ovarian cancer [stage I+II: 6 (15%); stage III: 25 (62.5%); stage IV: 9 (22.5%)] and 24 women with benign ovarian conditions were evaluated. Sera were available from 39 cases with ovarian cancer and from 19 cases with benign ovarian tumours. Ascites was obtained from 35 patients with ovarian cancer. IL-6 activity in serum and ascitic fluid was determined by the standard B9 proliferation assay (detection level: 1 pg/ml). IL-6 bioactivity was detectable in 22 (56%) sera from patients with ovarian cancer, but in only five (26%) of the serum samples obtained from benign cases (P < 0.001). Serum IL-6 levels in patients with ovarian cancer were significantly higher (median 3 pg/ml; range < 1 to 1221 pg/ml) than in patients with benign ovarian conditions (median 0 pg/ml; range < 1 to 4 pg/ml) (P < 0.001). However, much higher concentrations of IL-6 were measured in malignant ascites specimens (median 22,100 pg/ml; range < 1 to 182,600 pg/ml). IL-6 bioactivity in serum and ascites samples was completely inhibited by a neutralizing goat anti-human IL-6 antiserum. Thrombocytosis (platelet counts > 400 x 10(9)/l) occurred in 25 (62.5%) of the 40 patients with ovarian cancer, but in only two (8%) of the 24 cases with benign ovarian tumours. In eight (20%) cases with malignant disease platelet counts ranged between 600 x 10(9)/l and 1060 x 10(9)/l. IL-6 bioactivity in ascitic fluid correlated significantly with circulating platelet counts (r = 0.5916; P < 0.001). Maximum IL-6 bioactivity in ascites and highest platelet counts occurred in patients with undifferentiated ovarian adenocarcinoma or advanced disease. In conclusion, these observations strongly suggest a role for IL-6 in the development of tumour-associated thrombocytosis.

Adult↗
PubMed1993

Relationship between saliva and serum CA 125 in women with and without epithelial ovarian cancer.

OBJECTIVE: To determine the distribution of saliva CA 125 levels in women with and without ovarian cancer, and to determine whether there is a correlation between saliva and serum CA 125 levels in either group. METHODS: CA 125 levels were measured by immunoradiometric assay in the serum and saliva of 50 women with epithelial ovarian cancer known to have elevated serum CA 125 levels (above 35 U/mL) and in 50 women seen for benign gynecologic conditions. RESULTS: Serum and saliva CA 125 values followed a log-normal distribution in both groups. The medians for serum and saliva CA 125 levels in cancer patients were 578 and 1379 U/mL, respectively. In the benign group, the median CA 125 value was 11 U/mL in serum and 994 U/mL in saliva. The correlation between saliva and serum CA 125 levels was not statistically significant in either the cancer (r = 0.003) or the benign group (r = 0.025). CONCLUSION: There is no relationship between saliva and serum CA 125 levels in women with either epithelial ovarian cancer or benign gynecologic conditions.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Differentiation of the melanotrophic cells of rat pituitary primordium in organotypic culture in defined medium.

Organotypic cultures, in defined medium, of pituitary primordia obtained from 15-day-old rat fetuses were performed in order to study the in vitro differentiation of melanotrophic cells. The morphological and ultrastructural features of the transplants resembled those of the gland developing in vivo. In situ hybridization on semi-thin sections, using a 35S-labelled oligonucleotide probe, revealed pro-opiomelanocortin-mRNA-containing cells on the first day of culture in the anterior lobe and after 2-3 days in the intermediate lobe. Immunoperoxidase labelling of adjacent sections showed that the same cells reacted with antibodies against alpha-melanocyte-stimulating hormone (alpha MSH), gamma 3MSH and adrenocorticotropic hormone in both lobes. The pro-opiomelanocortin-mRNA-containing cells formed progressively conspicuous areas in the intermediate lobe, which was almost uniformly labelled after 6 days. In the anterior lobe, these cells remained scattered in small cell groups, and colloidal gold immunolabelling showed the progressive disappearance of alpha MSH labelling from the secretory vesicles in cells exhibiting morphological features of adult corticotrophic cells. Both the alpha MSH content of the explants and alpha MSH release into the culture medium increased with time. Treatment with the dopamine agonist bromocriptine induced a strong dose-dependent decrease in alpha MSH secretion, which was significant after 3 days in culture, indicating that dopamine D2 receptors are able to regulate hormonal release of melanotrophic cells at early stages. This system constitutes a suitable model for further studies of factors controlling cell differentiation and cellular interactions involved in histogenesis.

Adrenocorticotropic Hormone↗
PubMed1992

Biosynthesis of hepatic corticosteroid-binding globulin: ontogeny and effect of thyroid hormone.

The present study reports on the ontogeny and the effect of thyroid hormones on liver corticosteroid-binding globulin (CBG) biosynthesis, in relation to plasma CBG binding capacity in the rat. We show that mRNACBG contents were high in liver of 18-day-old fetuses and decreased with age to reach almost undetectable levels by postnatal day 1. Interestingly, at the latter time point plasma CBG concentration remained elevated and disappeared thereafter from the circulation with a half-life of about 3 days. The messenger was localized in parenchymatous cells and not in hematopoietic ones, although the latter constitute the major cell population in fetal liver. It is not until after 10 days of age that mRNACBG and plasma CBG levels increased in concert, with a sex-difference being noticed by postnatal day 30. Treatment of rats with 3,3',5-triiodo-L-thyronine (T3), but not reverse T3 (rT3) (the predominant form present in fetal serum), enhanced CBG biosynthesis. These findings show that liver mRNACBG contents undergo dramatic changes during ontogeny and suggest the existence of a differential regulation of the messenger in fetal and neonatal rats.

Animals↗
PubMed1990

Different molecular basis for fumarylacetoacetate hydrolase deficiency in the two clinical forms of hereditary tyrosinemia (type I).

Hereditary tyrosinemia is characterized by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH; E.C.3.7.1.2), the last enzyme in the catabolic pathway of tyrosine. FAH was purified from rat and human liver and was used to immunize rabbits. Specific antibodies were used to probe protein extracts of livers and other tissues of normal and tyrosinemic patients. No immunoreactive FAH band was observed on immunoblots of liver, kidneys, and lymphocytes from patients presenting with the acute form of hereditary tyrosinemia. Patients with the chronic form had immunoreactive FAH at a level approximately 20% of normal liver values, which was correlated with the measured enzymatic activity. Immunoblot analysis of aborted fetal tissues revealed normal FAH immunoreactivity in normal liver and kidneys. No FAH immunoreactivity was found in liver and kidneys of tyrosinemic fetuses. The presence of FAH immunoreactivity in normal fetal tissues suggests that deficient FAH activity in tyrosinemia is not simply related to a developmentally regulated expression of the enzyme. By this immunoblot assay, FAH was detected in most human tissues, with maximal immunoreactivity in liver and kidneys and with only trace amounts in chorionic villi and cultured amniocytes. These data confirm that the primary defect in the acute form of hereditary tyrosinemia is an absence of FAH. Moreover, these data suggest that both clinical forms of the disease have a different molecular basis.

Amino Acid Metabolism, Inborn Errors↗
PubMed1989

Renal vasodilatation and microvessel adenylate cyclase stimulation by synthetic parathyroid hormone-like protein fragments.

The hypercalcemia caused by malignancy factor, also called parathyroid hormone-related protein (PTHrP), exhibits most of the biological activities of parathyroid hormone (PTH) in kidney and bone. On the basis of the well-documented vascular action of PTH, we characterized the vasodilator action of human (h) PTHrP-(1-34) on a preparation of the isolated rat kidney, and its activity to stimulate adenylate cyclase in microvessels isolated from rabbit kidney cortex. Injection of sequential cumulative doses of hPTHrP-(1-34) into the isolated kidney preparation produced increasing vasodilatation up to 10(-8) M (EC50 of 3 x 10(-9) M) and decreasing responses thereafter. The maximal effect represented 26% of the reference relaxation induced by papaverine. Single injections of hPTHrP-(1-34) resulted in a greater (over 60%) vasodilatation. These results were reminiscent of the tachyphylaxis that occurs after repeated exposure to the peptide. The (3-34) PTH antagonist inhibited the hPTHrP-induced vasodilatation. Human PTHrP-(1-34) was equipotent with hPTH-(1-34) (EC50 values of 3 x 10(-9) M) but 5-fold less potent than rat (r) PTH-(1-34) in stimulating microvessel adenylate cyclase. GTP enhanced the enzyme responses to the peptides but reduced their potency. Both (3-34) and (7-34) PTH antagonists were inhibitors of hPTHrP- or PTH-stimulated microvascular adenylate cyclase. Synthetic hPTHrP-(1-16) had neither vasodilator nor adenylate cyclase-stimulating activity. This hPTHrP fragment exhibited some inhibitory effect on the hPTHrP-(1-34)-induced stimulation of microvessel adenylate cyclase. These results indicate that hPTHrP possesses PTH-like activity to cause vasorelaxation and to stimulate microvascular adenylate cyclase in the kidney.

Adenylyl Cyclases↗
PubMed1989

The vasodilator action of parathyroid hormone fragments on isolated perfused rat kidney.

The renal vasodilator responses to various fragments of PTH were quantified on a model of isolated perfused rat kidney (IPK), under non-filtering conditions. The 1-34 fragment of bovine PTH, its Nle analogue and rat PTH, injected in sequential cumulative doses, caused concentration-dependent vasodilatation in the vasculature of the IPK which was preconstricted with prostaglandin F2 alpha. The EC50 of PTH for renal vasodilatation ranged from 1 to 2 nM for all PTH fragments and maximum vasodilatation ranged from 33 to 41% of the maximum vasodilatation induced by papaverine. Renal vasodilation was not related to prostaglandin release since similar vasodilatation occurred after the inhibition of prostaglandin synthesis with indomethacin. When PTH was administered in single bolus injections, using a separate kidney for each hormone concentration, rather than repeated injections into the same kidney, higher maximum vasodilatations were obtained (64%). These results most likely reflected tachyphylaxis of the renal vasculature to PTH occurring after repeated exposure of a single kidney to the hormone. The antagonist analogue [Nle8,18, Tyr34]-bPTH-(3-34)A shifted the concentration-related response curve to the right, indicating that the renal vasodilator response to rPTH-(1-34) involved specific vascular receptors.

Animals↗
PubMed1989

Beta-adrenergic receptors in DMBA-induced rat mammary tumors: correlation with progesterone receptor and tumor growth.

In order to gain further knowledge about the potential role of catecholamines in mammary carcinoma, we have used the potent beta-adrenergic antagonist cyanopindolol (CYP) as iodinated ligand to characterize beta-adrenergic receptors in membranes prepared from mammary tumors induced by dimethylbenz(a)anthracene (DMBA) administration in the rat. The binding of [125I]CYP to membrane preparations of DMBA-induced rat mammary tumors is rapid at room temperature, reaching half maximal specific binding at 30 min of incubation. Scatchard analysis of the data indicates that [125I]CYP binds to a single class of high affinity sites (114 +/- 2.1 fmoles/mg protein) at an apparent KD value of 38.0 +/- 0.3 pM. The order of potency of a series of agonists to compete for [125I]CYP binding is consistent with interaction with a beta 2-subtype receptor: zinterol greater than (-)isoproterenol greater than (-)epinephrine much greater than (-)norepinephrine. In addition, the potency of a series of specific beta 1 and beta 2 synthetic compounds to displace [125I]CYP in mammary tumors is similar to their potency in typical beta 2-adrenergic tissues. The binding of [125I]CYP to DMBA-induced rat mammary tumors shows a marked stereoselectivity, the (-)isomers of isoproterenol and propranolol being 150 and 80 times more potent, respectively, than their respective enantiomers. The autoradiographic localization of [125I]CYP performed on frozen sections revealed the presence of specific beta-adrenergic receptors in all the malignant cells. Spontaneous mammary tumors of aging (18-22 months) female rats have high levels of beta-adrenergic receptors. Castration decreased the concentration of [125I]CYP binding sites in DMBA-induced mammary tumors. A close correlation was observed between progressing, static, and regressing tumors after ovariectomy and beta-adrenergic receptor concentration. The presence of beta-adrenergic receptors in mammary tumors as well as the modulation of their level by ovarian hormones provides a mechanism for catecholaminergic influence in mammary cancer tissue.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Stimulatory effect of synthetic progestins currently used for the treatment of prostate cancer on growth of the androgen-sensitive Shionogi tumor in mice.

In order to assess the androgenic activity of synthetic progestins currently used as "antiandrogens" for the treatment of prostate cancer in men, the effect of a series of these compounds has been studied in mice on the growth of the androgen-sensitive Shionogi tumor. Female mice (DD/S strain) were inoculated subcutaneously with 10(6) viable cells and divided into groups who received, respectively, the synthetic "progestins" medroxyprogesterone acetate (MPA), megestrol acetate (MEG), cyproterone acetate (CPA) or chlormadinone acetate (CMA), compared with the non-steroidal antiandrogen Flutamide (Flu), each administered at the twice-daily dose of 250 micrograms. Each synthetic "progestin" exerted a marked stimulatory effect on the growth of the tumor. The most impressive effect on growth was observed with MPA. In fact, in MPA-treated mice, tumor size was 17 times larger than control at 4.92 +/- 0.36 cm2/mouse 21 days after inoculation. CPA, CMA and MEG also stimulated the growth of this androgen-sensitive tumor, the percentages of stimulation of tumor size being 3.1-, 3.2- and 11.0-fold above control, respectively, on day 21, while Flu had no significant stimulatory effect. The present data clearly show that all the above-mentioned progestins have variable levels of stimulatory activity on the growth of the androgen-sensitive Shionogi tumor and indicate that such drugs are unlikely to be recommendable for the treatment of prostate cancer.

Androgens↗
PubMed1988

Castration levels of plasma testosterone have potent stimulatory effects on androgen-sensitive parameters in the rat prostate.

In order to assess the biological significance of low serum androgens comparable to those which remain after castration in men treated for prostate cancer. Silastic depots continuously releasing predetermined doses of testosterone (T) have been implanted into castrated adult male rats in the absence or presence of simultaneous treatment with the pure antiandrogen Flutamide. Quite remarkably, a 3- to 5-fold increase in prostate weight (P less than or equal to 0.001) was observed at plasma T concentrations comparable to those found in the serum of castrated men. Although of lower magnitude, castration levels of plasma T also caused a significant stimulation of seminal vesicle weight (P less than 0.01). This dramatic stimulatory influence of "castration" levels of plasma T on ventral prostate and seminal vesicle weight can be explained by the 13- to 15-fold higher intraprostatic level of the active androgen dihydrotestosterone (DHT) compared to the plasma T concentration. In fact, a near-maximal intraprostatic concentration of DHT is reached at concentrations of plasma T of 0.2-0.5 ng/ml and a positive correlation was found between prostatic DHT concentration and ventral prostate weight. Prostatic growth and DHT concentrations were also positively correlated with ornithine decarboxylase (ODC) activity, an enzyme highly sensitive to androgens in the rat ventral prostate. In fact, a dramatic (30-fold) increase in ODC activity was observed at plasma T values corresponding to those found in castrated men. The level of prostatic beta 2-adrenergic receptors fell within 10 days of castration and an increase in beta 2-adrenergic receptor concentration was observed with low doses of T, thus indicating that beta 2-adrenoreceptor levels are also a sensitive parameter of androgenic activity in the rat prostate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Occupational and residential 60-Hz electromagnetic fields and high-frequency electric transients: exposure assessment using a new dosimeter.

One problem that has limited past epidemiologic studies of cancer and exposure to extremely low-frequency (0-100 Hz) electric and magnetic fields has been the lack of adequate methods for assessing personal exposure to these fields. A new 60-Hz electromagnetic field dosimeter was tested to assess occupational and residential exposures of a group of electrical utility workers and a comparison background group over a 7-day period. Comparing work periods only, utility workers' exposures were significantly higher than background levels by a factor of about 10 for electric (E) and magnetic (B) fields and by a factor of 171 for high-frequency transient electric (HFTE) fields. When overall weekly time-weighted averages combining work and nonwork exposures were compared, ratios of the exposed to background groups were lower. B and HFTE exposure ratios remained statistically significant, with values of 3.5 and 58, respectively, whereas the electric field exposure ratio was no longer significant, with a value of 1.7. E-field exposures of the background group were the highest during the nonwork period, probably reflecting the use of electrical appliances at home. Residential E- and B-field exposures were in the same range as published results from other surveys, whereas occupational E-field exposures tended to be lower than exposures reported in other studies. The high variability associated with occupational exposures probably accounts for the latter discrepancy. Worker acceptance of wearing the dosimeter was good: 95% of participants found it to be of little or no inconvenience while at work. At home, 37% found the device to be inconvenient in its present form but would not object to wearing a slightly smaller and lighter dosimeter.

Electricity↗
PubMed1987

Analysis of the androgenic activity of synthetic "progestins" currently used for the treatment of prostate cancer.

In order to assess the androgenic activity of synthetic "progestins" currently used as "antiandrogens" for the treatment of prostate cancer in men, the effect of a series of these compounds has been measured following 14 days of treatment of adult castrated rats on specific and sensitive parameters of androgenic activity, namely ventral prostate weight and prostatic ornithine decarboxylase (ODC) activity. Medroxyprogesterone acetate (MPA) is almost equipotent with 5 alpha-dihydrotestosterone (DHT), a 49% increase in prostatic weight being observed at the low dose of 0.15 mg, twice daily (P less than 0.01). Megestrol acetate (Megace), chlormadinone acetate (CMA) and spironolactone were less potent but caused a 36-59% increase in prostatic weight at the highest dose used, namely 10 mg. At the 5 mg dose, cyproterone acetate (CPA) caused a 75% increase in prostatic weight. The androgenic activity of the compounds is even more clearly illustrated by their marked stimulatory effect on prostatic ornithine decarboxylase (ODC) activity. MPA, at the low dose of 0.15 mg, caused a 20-fold increase (relative to the effect of placebo) in the activity of the enzyme while the same dose of DHT caused a 15-fold stimulation of enzymatic activity. At the 10 mg dose, megestrol acetate, CMA and spironolactone caused 13.1, 11.8 and 8.6-fold stimulations of ODC activity, respectively. Flutamide, on the other hand, had no stimulatory effect on either ventral prostate weight or prostatic ODC activity. In agreement with glucocorticoid activity, MPA, megestrol acetate and CMA caused a marked inhibition (45-64%) of adrenal weight. The present data show that MPA is a highly potent androgen while megestrol acetate, CMA, CPA and spironolactone have lower but significant androgenic activity on all the parameters measured. It should be added that MPA, megestrol acetate and CMA are completely devoid of antiandrogenic activity while spironolactone shows weak antiandrogen action and CPA is a mixed agonist-antagonist. Flutamide, the compound used as reference, is the only compound devoid of any androgenic action and is thus acting as a pure antiandrogen on both ventral prostate weight and prostatic ODC activity. The present data have major implications for the choice of drug to be used for the treatment of androgen-sensitive diseases, especially prostate cancer. As shown by the present data, the synthetic "progestins" so-far available all possess variable levels of androgenic activity and are thus not recommended for the treatment of prostate cancer.

Adrenal Glands↗
PubMed1981

[Breast neoplasms: a 1980 dilemma].

For many reasons, breast cancer is still the most controversial topic in oncology. Questions raised many years ago in relation to diagnosis and treatment have not yet been answered. Clinical classification, such as the TNM system, is open to many pitfalls and the degree of error in axillary staging is still high, even in expert hands. The situation with regard to management is similar. The types of treatment are numerous and controversial, so that interpretations of results is unreliable. The fundamental questions will be answered only by clinical trials.

Breast Neoplasms↗