DUCTAL CARCINOMA IN-SITU OF THE BREAST - HISTOLOGIC CATEGORIZATION AND ITS RELATIONSHIP TO PLOIDY AND IMMUNOHISTOCHEMICAL EXPRESSION OF HORMONE RECEPTORS, P53, AND C-ERBB-2 PROTEIN

Background. Ductal carcinoma in situ (DCIS) of the breast has been diagnosed increasingly since the advent of mammography. However, the natural history of these lesions remains uncertain. Ductal carcinoma in situ of the breast does not represent a single entity but a heterogeneous group with histologic and clinical differences. The histologic subtype of DCIS seems to have an influence on its biologic behavior, but there are few studies correlating subtype with biologic markers.Methods. The authors studied a consecutive series of 40 cases of DCIS and after its histologic categorization verified its relationship with ploidy using image analysis and analyzing estrogen receptor (ER), progesterone receptor (PR), p53 and c-erbB-2 expression using immunohistochemistry.Results. The three groups proposed according to the grade of malignancy were correlated significantly with some of the additional parameters studied, including aneuploidy and c-erB-2 expression. Aneuploidy was detected in 77.5% of cases of DCIS mainly in high and intermediate grade subtypes (100% and 80% vs. 35.7% in low grade) whereas immunoreactivity for c-erbB-2 was detected in 45% of cases of DCIS mainly in the high grade group. Expression of ER and PR were observed frequently in this study (63.9% and 65.7% respectively), but without correlation with the histologic subtype of DCIS, although we found a somewhat significant association between high grade DCIS and lack of ER. p53 protein expression was detected in 36.8% of these cases, but no relationship between this expression and histologic subtype or grading of DCIS was found.Conclusions. These results provide further evidence for the morphologic and biologic heterogeneity of DCIS. Besides histologic classification and nuclear grading, some biologic markers such as aneuploidy and c-erbB-2 expression constitute additional criteria of high grade of malignancy.

Thermogenic activity of growth hormone transgenic mice

The objective was to determine the effect of a mouse metallothionein/bovine growth hormone transgene on resting metabolic rate (RMR), cold-induced thermogenesis, and beta-agonist stimulated nonshivering thermogenesis in mice. Non-transgenic littermates were used as controls. Open-circuit indirect calorimetry was used to assess RMR and cold-induced thermogenesis in 64 mice. Air temperature in the chamber was set at 31 degrees C for RMR and was decreased to 28, 25, 21, or 17 degrees C to determine cold-induced thermogenesis. Response to the beta-agonist isoproterenol was evaluated by monitoring changes in colonic temperature of 34 mice upon injection of the drug or saline. Despite the fact that RMR tended to be lower in transgenics than in nontransgenics, at 31 degrees C transgenic mice were able to regulate colonic temperature at the same level as nontransgenics, but colonic temperature decreased in transgenics relative to nontransgenics as air temperature was reduced. For each degree decrease in air temperature between 31 and 17 degrees C, nontransgenic mice increased heat production by 1.03 +/- .10 watt/kg, whereas transgenic mice increased it by only .56 +/- .08 watt/kg, indicating that the thermogenic response of transgenics to cold was inferior. The magnitude of the maximal increase in colonic temperature after isoproterenol injection was similar for both groups, but the response was slower in transgenics. We suggest that lean body mass and substrate availability for shivering thermogenesis are reduced in transgenics relative to total body weight, and that they allow colonic temperature to decrease to conserve energy.

SEX DETERMINATION IN BEES .30. EFFECTS OF JUVENILE-HORMONE ON THE DEVELOPMENT OF TERGAL GLANDS IN MELIPONA

Worker larvae of Melipona rufiventris, M. quadrifasciata and M. compressipes were treated topically with juvenile hormone (JH) during the cocoon-spinning phase. Examination of the tergites of the queens obtained following JH application showed induced differentiation into adults with full female (queen) traits. Melipona workers had tergal glands only in tergite II, whereas natural and JH-induced queens had tergal glands in tergite II plus additional glands in at least one other of tergites Ill to VII.

Effects of central alpha-adrenergic agonists on hormone-induced 3% NaCl and water intake

Male rats received intracerebroventricular (ICV) renin (600 ng) or daily subcutaneous injections of deoxycorticosterone (5 mg) to induce 3% NaCl and water intake. Noradrenaline (NOR; 40-160 nmol) and clonidine (CLO; 5-20 nmol) injected ICV. induced 70 to 100% inhibition of the intakes. Phenylephrine (PHE; 40-160 nmol) injected ICV induced 60 to 95% inhibition of the intakes. NOR and PHE induced a stronger inhibition on the 3% NaCl intake induced by renin than on the intake induced by deoxycorticosterone (DOC), and CLO did the opposite. CLO was always more effective than PHE to induce inhibition of the intakes. The results suggest that NOR inhibits hormone (angiotensin II, aldosterone)-induced NaCl intake by acting mainly on alpha(2)-adrenergic receptors.

Non-ventilation during early incubation in combination with dexamethasone administration during late incubation: 1. Effects on physiological hormone levels, incubation duration and hatching events

This study investigated the effect of non-ventilation of the incubator during the first 10 days of incubation and its combination with dexamethasone administration at day 16 or 18 of incubation on hatching parameters and embryo and post-hatch chick juvenile physiology. A total of 2400 hatching eggs produced by Cobb broiler breeders were used for the study. Blood samples were collected at day 18 of incubation, at internal pipping stage (IP), at the end of hatch (day-old chick) and at 7-daypost-hatch for T-3, T-4 and corticosterone levels determination. From 448 to 506 h of incubation, the eggs were checked individually in the hatcher every 2 h for pipping and hatching. The results indicate that non-ventilation during the first 10-day shortened incubation duration up to IP, external pipping (EP) and hatch, had no effect on hatchability and led to higher T-3 levels at IP but lower corticosterone levels at 7-day-post-hatch. The injection of dexamethasone at days 16 and 18 of incubation affected hatching and blood parameters in both the ventilated and non-ventilated embryos differentially and the effect was dependent on the age of the embryo. Dexamethasone increased T-3 levels and T-3/T-4 ratios but the effect was greater with early non-ventilation of eggs. Dexamethasone decreased hatchability but the effect was greater when injected at day 16 and especially in ventilated embryos. The effects of incubation protocols and dexamethasone treatments during incubation were still apparent in the hatched chicks until 7 days of age. The changes in T-3, T-4 and corticosterone levels observed in response to the early incubation conditions and late dexamethasone treatments in this study suggest that incubator ventilation or non-ventilation may influence the hypothalamic-pituitary-adrenal axis (HPA) regulation of stress levels (in terms of plasma corticosterone levels) and thyroid function in the embryo with impact on incubation duration, hatching events and early post-hatch life of the chick. Our results also suggest that some stages of development are more sensitive to dexamethasone administration as effects can be influenced by early incubation protocols. (c) 2006 Elsevier B.V. All rights reserved.

Effect of zinc administration on thyrotropin releasing hormone-stimulated prolactinemia in healthy men

Previous in vitro studies have demonstrated zinc (Zn++) inhibition of basal and of potassium (K+) or thyrotropin-releasing hormone (TRH)-stimulated prolactin (PRL) secretion, in a selective, reversible, and dose-dependent manner. Thus, Zn++ may regulate physiologically pituitary PRL secretion. Furthermore, studies with patients with uremia, cirrhosis or prolactinoma, have shown the coexistence of hypozincemia and hyperprolactinemia and zinc supplementation did not correct hyperprolactinemia in these patients. In normal individuals Zn++ administration produced controversial results on PRL secretion. Here, we investigated whether zinc administration affects TRH-stimulated PRL in healthy men. We found that Zn++ administration does not change the TRH-stimulated PRL. Therefore, in normal conditions, Zn++ does not inhibit TRH-stimulated prolactinemia. In addition, we found that acute increases of blood PRL and TRH do not alter blood Zn++ levels.

Mispatterning in the ommatidia of Apis mellifera pupae treated with a juvenile hormone analogue

To further understand the function of morphogenetic hormones in honeybee eye differentiation, the alterations in ommatidial patterning induced by pyriproxyfen, a juvenile hormone (JH) analogue, were studied by scanning and transmission electron microscopy. Prepupae of prospective honeybee workers were treated with pyriproxyfen and the effects on ommatidial differentiation were described at the end of the pupal development. The results show that the entire ommatidia, i.e., the dioptric as well as the receptor systems, were affected by the JH analogue. The wave of ommatidial differentiation, which progresses from the posterior to the anterior region of the pupal eyes, was arrested. In treated pupae, the rhabdomeres only differentiated at the apical axis of the retinula, the secondary and tertiary pigment cells did not develop their cytoplasm protrusions, and the cone cell quartet did not pattern correctly. Simultaneously, an intense vacuolization was observed in cells forming ommatidia. In a previous study we showed that pyriproxyfen exerts an inhibition on pupal ecdysteroid secretion. In this sense, the arrested ommatidial differentiation in pyriproxyfen-treated pupae could be due to a secondary effect resulting from an alteration in pupal ecdysteroid titers. J. Morphol. 249:89-99, 2001. (C) 2001 Wiley-Liss, Inc.

Clinical features and genetic analysis of four Brazilian kindreds with resistance to thyroid hormone

Objective Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of reduced tissue responsiveness to thyroid hormone usually due to mutations located in the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor beta (TR beta). In the present report we describe the clinical and laboratory characteristics and the genetic analysis of patients with this rare disorder from a Brazilian population.Patients Four unrelated Brazilian families with diagnosis of RTH were studied. Age at diagnosis varied from 14 months to 29 years.Results All affected individuals were clinically euthyroid, except for one patient who presented immediately after birth with hyperthyroidism. All individuals had tachycardia and goitre, elevated concentrations of free thyroid hormones and reduced sensitivity to thyroid hormone. Direct sequencing analysis of the TR beta gene revealed four previously reported mutations: c.949G -> A, c.1313G -> A, c.1357C -> A and c.1358dupC in families A, B, C and D, respectively.Conclusion the present report shows that the frequent mutations described in the thyroid hormone receptor worldwide are also present in the Brazilian population, which is characterized by a variable ethnic background.

Granulocyte colony-stimulating factor expression from transduced vascular smooth muscle cells provides sustained neutrophil increases in rats

Granulocyte colony-stimulating factor (G-CSF) regulates granulocyte precursor cell proliferation, neutrophil survival, and activation. Cyclic hematopoiesis, a disease that occurs both in humans and grey collie dogs is characterized by cyclical variations in blood neutrophils. Although the underlying molecular defect is not known, long-term daily administration of recombinant G-CSF eliminates the severe recurrent neutropenia, indicating that expression of G-CSF by gene therapy would be beneficial. As a prelude to preclinical studies in affected collie dogs, we monitored hematopoiesis in rats receiving vascular smooth muscle cells transduced to express G-CSF. Cells transduced with LrGSN, a retrovirus expressing rat G-CSF, were implanted in the carotid artery and control animals received cells transduced with LASN, a retrovirus expressing human adenosine deaminase (ADA). Test animals showed significant increases in neutrophil counts for at least 7 weeks, with mean values of 3,670 +/- 740 cells/mu l in comparison to 1,870 +/- 460 cells/mu l in controls (p < 0.001). Thus, in rats G-CSF gene transfer targeted at vascular smooth muscle cells initiated sustained production of 1,800 neutrophils/mu l, a cell number that would provide clinical benefit to patients. Lymphocytes, red cells and platelets were not different between control and test animals (p > 0.05). These studies indicate that retrovirally transduced vascular smooth muscle cells can provide sustained clinically useful levels of neutrophils in vivo.