HIV infection and AIDS among drug injectors at Rio de Janeiro: perspectives and unanswered questions

Determination of the presence and characterization of oestrogen receptors (ERs) in subcutaneous and internal fat depots were performed and compared with ERs in the uterus using ligand binding and immunological techniques. Successful and consistent measurement of ERs in ovine adipose tissue could only be accomplished in animals depleted of endogenous sex steroids by combined ovariectomy and adrenalectomy. Scatchard, sucrose gradient and Western blot analyses all confirmed the presence of ERs in the cytosolic fractions of various adipose and uterine tissues from ovariectomized-adrenalectomized ewes. The approximate Kd values of 0.1-0.4 nmol/l for oestradiol binding in cytosolic fractions of gluteal, omental and perirenal adipose tissues were similar to the expected high affinity binding of Kd 0.35 nmol/l observed in uterine tissue. The binding was specific for oestrogens, as unlabelled diethylstilboestrol and oestradiol effectively competed with labelled hormone for receptor sites and progesterone, R5020, testosterone and dexamethasone all failed to compete. Mean (+/- S.E.M.) concentrations of ERs, expressed as fmol specific binding sites per mg protein, were much lower (P < 0.05) in adipose tissues than in uterine tissue (975 +/- 33). However, the content of ERs was greater (P < 0.05) in subcutaneous gluteal fat (11.5 +/- 0.8) than in the internal omental or perirenal fat (5 +/- 0.6) depots. ERs from adipose and uterine tissues both migrated as moieties of 8S on 5-20% sucrose gradients. Western blot analysis of ERs from uterine and adipose tissues in the presence of protease inhibitors demonstrated an immunostaining band with a molecular mass of 67 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody

Although histologically benign, one-third of all pituitary tumors will be invasive of surrounding structures. In this study, the relationship between the proliferative activity in pituitary adenomas and their invasiveness was investigated. Invasion was defined as gross, operatively or radiologically apparent infiltration of dura or bone. Using the recently developed MIB-1 monoclonal antibody, which recognizes the Ki-67 cell cycle-specific nuclear antigen, the growth fractions of 37 noninvasive adenomas, 33 invasive adenomas, and 7 primary pituitary carcinomas were determined. All tumors were fully classified by histology, immunohistochemistry, and electron microscopy. The mean Ki-67 -derived growth fractions for noninvasive adenomas, invasive adenomas, and pituitary carcinomas were 1.37 +/- 0.15%, 4.66 +/- 0.57%, and 11.91 +/- 3.41%, respectively (mean +/- standard error of the mean). An analysis of variance and then individual pairwise comparisons confirmed significant differences in the mean Ki-67 labeling index between each of the three tumor groups (P < 0.01). The mean growth fraction of hormonally active pituitary adenomas (3.25 +/- 0.26%) was significantly higher than that for nonfunctioning adenomas (2.06 +/- 0.23%) (P = 0.03). Establishing a threshold labeling index of 3% served to distinguish invasive from noninvasive adenomas with 97% specificity and 73% sensitivity and was associated with positive and negative predictive values of 96 and 80%, respectively. Although invasive pituitary tumors exhibited significantly higher growth fractions than did noninvasive tumors, there were individual exceptions, indicating that in a subpopulation of invasive pituitary tumors, factors other than proliferative activity determine invasive potential.     

Modulation of intestinal estrogen receptor by ovariectomy, estrogen and growth hormone

Ovarian hormone deficiency decreases and estrogen (E2) and growth hormone (GH) administrations increase intestinal absorption of calcium (Ca++). However, the underlying mechanisms are uncertain. To examine whether alterations in the binding characteristics of intestinal estrogen receptors (ERs) are involved, we developed and validated methods for simultaneous measurement of intestinal ERs in cytosolic and nuclear fractions and applied these techniques to four groups of female rats: sham-operated, ovariectomized (Ovx), Ovx + 5 micrograms E2/kg b.wt./day and Ovx + 8 mg GH/kg. b.wt./day. All animals were killed on day 21, and mucosal cells harvested from the duodenum for ER determination. The cytosolic and nuclear ERs were 117.2 +/- 2.7 fmol/mg protein and 64.9 +/- 1.2 fmol/mg DNA, respectively, in sham-operated rats and decreased by 16.1% and 17.0% to 98.4 +/- 1.7 fmol/mg protein and 53.8 +/- 1.3 fmol/mg DNA, respectively in Ovx rats (P < .001). E2 therapy prevented completely the decrease in cytosolic and nuclear ERs that occurred in Ovx rat (126.1 +/- 2.9 fmol/mg protein and 68.0 +/- 3.0 fmol/mg DNA, respectively, in the E2-treated group). Similarly, GH administration prevented the decrease in cytosolic and nuclear ERs that resulted from ovariectomy (119.2 +/- 3.2 fmol/mg protein and 63.4 +/- 1.3 fmol/mg DNA, respectively, in the GH-treated group). The Kd of nuclear ER-ligand complex was 2.0 +/- 0.03 nM in sham-operated rats and was slightly modulated by Ovx, E2 and GH (3.3 +/- 0.02, 2.33 +/- 0.09 and 2.23 +/- 0.04 nM, respectively, P < .001), but the Kd of cytosolic ER-ligand complex was not altered by Ovx, E2 or GH. Our findings indicate that E2 deficiency down-regulates, whereas E2 and GH administrations up-regulate intestinal ERs and prevent ovariectomy-induced decrease in receptor binding affinity. We conclude that E2 deficiency, E2 and GH may modulate intestinal Ca++ absorption, in part, by altering the abundance and binding characteristics of intestinal ERs.     

Transgenic A1 adenosine receptor overexpression increases myocardial resistance to ischemia

Activation of myocardial A1 adenosine receptors (A1AR) protects the heart from ischemic injury. In this study transgenic mice were created using the cardiac-specific alpha-myosin heavy chain promoter and rat A1AR cDNA. Heart membranes from two transgene positive lines displayed approximately 1,000-fold overexpression of A1AR (6,574 +/- 965 and 10,691 +/- 1,002 fmol per mg of protein vs. 8 +/- 5 fmol per mg of protein in control hearts). Compared with control hearts, transgenic Langendorff-perfused hearts had a significantly lower intrinsic heart rate (248 beats per min vs. 318 beats per min, P < 0. 05), lower developed tension (1.2 g vs. 1.6 g, P < 0.05), and similar coronary resistance. The difference in developed tension was eliminated by pacing. Injury of control hearts during global ischemia, indexed by time-to-ischemic contracture, was accelerated by blocking adenosine receptors with 50 microM 8-(p-sulfophenyl) theophylline but was unaffected by addition of 20 nM N6-cyclopentyladenosine, an A1AR agonist. Thus A1ARs in ischemic myocardium are presumably saturated by endogenous adenosine. Overexpressing myocardial A1ARs increased time-to-ischemic contracture and improved functional recovery during reperfusion. The data indicate that A1AR activation by endogenous adenosine affords protection during ischemia, but that the response is limited by A1AR number in murine myocardium. Overexpression of A1AR affords additional protection. These data support the concept that genetic manipulation of A1AR expression may improve myocardial tolerance to ischemia.     

Constitutively active Gs alpha is associated with an increased phosphodiesterase activity in human growth hormone-secreting adenomas

Because phosphodiesterase (PDE) expression and activity are controlled by cAMP, we investigated whether activating mutations of Gs alpha gene that occur in human GH-secreting adenomas are associated with increased PDE activity. We studied 10 adenomas with wild-type Gs alpha (gsp-) and 8 with mutant Gs alpha (gsp+). Although, in the absence of PDE inhibitors, intracellular cAMP levels were similar in gsp+ e gsp- adenomas, the PDE blockade with 3-isobutyl-1-methylxanthine induced a marked increase in cAMP in all but one gsp+ adenoma (% increase: from 77 to 2900) and a slight rise in only 2 gsp-. Similar results were obtained with the PDE4 selective inhibitor 4-[3-(cyclopentyloxy)-4-methoxyphenyl)]-2-pyrrolidinone. In vitro GH release was significantly higher in gsp+ than in gsp- adenomas (315 +/- 158 vs. 82 +/- 53 micrograms/well; P < 0.01), and PDE blockade caused a further increase in 3 of 5 gsp+ adenomas but not in gsp- tumors. By direct measurement, PDE activity was about 7-fold higher in gsp+ than in gsp- adenomas (320 +/- 213 vs. 48 +/- 23 pmol/min.mg protein; P < 0.05) and was largely 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidinone sensitive. This study first demonstrates that activating mutations of the Gs alpha gene that naturally occur in pituitary adenomas is associated with an increased PDE activity that might, at least partially, counteract the constitutive activation of the cAMP-dependent pathway.     

Expression of adrenomedullin mRNA in adrenocortical tumors and secretion of adrenomedullin by cultured adrenocortical carcinoma cells

Immunoreactive-adrenomedullin concentrations and the expression of adrenomedullin mRNA were studied in the tumor tissues of adrenocortical tumors. Northern blot analysis showed the expression of adrenomedullin mRNA in tumor tissues of adrenocortical tumors, including aldosterone-producing adenomas, cortisol-producing adenomas, a non-functioning adenoma and adrenocortical carcinomas, as well as normal parts of adrenal glands and pheochromocytomas. On the other hand, immunoreactive-adrenomedullin was not detected in about 90% cases of adrenocortical tumors (<0.12 pmol/g wet weight (ww)). Immunoreactive-adrenomedullin concentrations ranged from 0.44 to 198.2 pmol/g ww in tumor tissues of pheochromocytomas and were 9.2 +/- 1.2 pmol/g ww (mean +/- SD, n = 4) in normal parts of adrenal glands. Adrenomedullin mRNA was expressed in an adrenocortical adenocarcinoma cell line, SW-13 and immunoreactive-adrenomedullin was detected in the culture medium of SW-13 (48.9 +/- 1.8 fmol/10(5) cells/24h, mean +/- SEM, n = 4). On the other hand, immunoreactive-adrenomedullin was not detectable in the extract of SW-13 cells (<0.09 fmol/10(5) cells), suggesting that adrenomedullin was actively secreted from SW-13 cells without long-term storage. These findings indicate that adrenomedullin is produced and secreted, not only by pheochromocytomas, but also by adrenocortical tumors. Undetectable or low levels of immunoreactive-adrenomedullin in the tumor tissues of adrenocortical tumors may be due to very rapid secretion of this peptide soon after the translation from these tumors.     

Coexpression and cross-regulation of the prolactin receptor and sex steroid hormone receptors in breast cancer

The sex steroid hormones and PRL interact synergistically to control the neoplastic growth of the mammary gland. The basis for this hormonal synergy is unknown, but may involve cellular coexpression of the sex steroid and PRL receptors, coupled with receptor cross-regulation. To examine this hypothesis the expression of the sex steroid and PRL receptors was examined in 20 human breast cancer cell lines and 123 primary breast cancers. Regulation of sex steroid receptors by PRL and of the PRL receptor by sex steroids was examined in T-47D and MCF-7 breast cancer cells. Northern analysis of the breast cancer cell lines and tumors indicated that the PRL receptor and the sex steroid receptors were coexpressed. The level of PRL receptor expression in the breast cancer cell lines was linearly related to that of the estrogen and progesterone receptors, but not to that of the androgen receptor. In MCF-7 and T-47D cells, acute treatment with progestins and androgens and long term treatment with estrogens increased PRL receptor levels. Analysis of sex steroid receptor messenger ribonucleic acid and binding activity showed that acute PRL treatment produced a time- and concentration-dependent increase in progesterone receptor and a decrease in androgen receptor. These results indicate that receptors for sex steroids and PRL are coexpressed and are cross-regulated, providing a potential mechanism for the observed synergy among estrogen, progesterone, and PRL in the control of tumor growth.     

Thyroid hormones in human tumoral and normal nervous tissues

We have studied T4 and T3 concentrations, DNA and protein concentrations and 5' and 5 deiodinases in samples of brain tumors obtained at surgery from 49 patients, and, in most cases, also from surrounding normal tissue. T4 concentrations in normal cortical tissue (6.19+/-0.45 ng/g) were lower than in white matter, but the difference disappeared when referred to the DNA content (2.26+/-0.27 ng/mg DNA). No other differences were found between cortical and white matter, or among cortical lobes. T4 in normal tissue was higher than previously reported, mostly from autopsy samples, whereas T3 (0.99+/-0.07 ng/g) was similar. 5'D-I activity was negligible as compared to 5'D-II (8.11+/-1.09 fmol/h/mg protein). When expressed in relation to the different DNA contents of normal vs. tumoral tissue, 5'D-II activities were the same for both. 5D activity was highly variable in the tumoral tissue, with negligible activities in meningiomas and pituitary adenomas. When referred to the DNA content, T4 and 5'D-II were the same, but T3 concentrations were lower in the tumor (0.24+/-0.03 ng/mg DNA) as compared to normal (0.35+/-0.04 ng/mg DNA) tissue samples. Whether or not this decrease of T3 affects the expression of T3-sensitive processes remains to be studied.     

Sixty adrenal masses of large dimensions: hormonal and morphologic evaluation

OBJECTIVES: To evaluate the nature and function of adrenal masses of large dimensions (macrotumors). METHODS: Sixty consecutive patients (31 women, 29 men, age range 15 to 84 years) with adrenal masses 4.0 cm in diameter or larger (range 4.0 to 15.0 cm) underwent morphologic study by computed tomography (CT); the majority also underwent 131-I-6beta-norcholesterol (131I-NC) or 131I-MIBG scintigraphy. Basal evaluation of glucocorticoids, mineralcorticoids, and catecholamines was performed in all patients, and in 38 cases determination of androgens was also made. In addition, on the basis of various clinical suspicions, a dynamic hormonal study was performed. RESULTS: Macrotumors were benign in 78.3% of cases and included pheochromocytomas (n = 17), nonfunctioning cortical adenomas (n = 12), and cortisol-secreting tumors (n = 7, Cushing's syndrome). Malignant forms were 21.7% of the total, including pheochromocytomas (n = 3), cortical carcinomas (n = 6), and metastases (n = 4). On CT, malignant masses were larger (8.4+/-0.9 cm) than benign ones (5.7+/-0.3 cm) (P < 0.0001) and the mass size was strictly related to malignancy (P < 0.03). CT did not offer other diagnostic criteria for malignancy, except irregular margins and regional lymph node enlargement, which were more frequently (P < 0.0001) found in malignant forms. 131I-MIBG scintigraphy showed tracer uptake in all pheochromocytomas, both benign and malignant. By contrast, on 131I-NC scintigraphy, cortical malignancies never accumulated the radiotracer, whereas uptake was observed in all cases of solid cortical benign adenomas. Patients with cortical carcinomas showed plasma sex steroids above the normal range, pheochromocytomas were asymptomatic in 15% of cases, and almost half of the patients with Cushing's syndrome did not show clinical features of the disease (pre-Cushing's syndrome). CONCLUSIONS: Adrenal macrotumors frequently show endocrine activity and the medulla seems to be involved more than the cortex. Pheochromocytomas and cortisol-secreting adenomas are sometimes asymptomatic. Malignancy is often found in macromasses and, at least for the cortical forms, size of the tumor on CT, 131I-NC uptake on scintigraphy, and determination of levels of sex steroids seem to be useful criteria for predicting the nature of the mass.     

The MEN-1 gene is rarely down-regulated in pituitary adenomas

The gene for multiple endocrine neoplasia type 1 (MEN-1) has recently been cloned and encodes a putative tumor suppressor protein named menin. We have previously reported inactivating MEN-1 gene mutations associated with loss of heterozygosity (LOH) of the normal allele in tumors of patients with MEN-1 and in some sporadic pituitary tumors. These genetic alterations, however, are noted in no more than 10% of sporadic adenomas. To investigate whether other mechanisms may result in down-regulation of menin gene expression in pituitary adenomas, we examined menin gene expression by semiquantitative RT-PCR in 60 sporadic pituitary adenomas. Ribonucleic acid (RNA) was extracted from surgically resected, morphologically characterized tumors. Primers were designed to amplify a 257-bp fragment spanning exons 4-6 of the MEN-1 gene. A product of the predicted size was amplified from normal pituitary samples as well as from adenomas. Competitive PCR was performed with the housekeeping gene PGK-1 to quantitate menin gene expression. A comparable ratio of menin/PGK-1 messenger RNA was identified in all but three samples; in two tumors with LOH, menin expression was weak, and in one tumor, menin messenger RNA was undetectable, associated with LOH and mutation of the other allele. Reduced expression of menin in some sporadic adenomas is consistent with a putative tumor suppressor role for this gene product. However, lack of menin down-regulation in the majority of these tumors, which exhibit LOH at 11q13 in up to 20% of cases, provides compelling evidence for an additional tumor suppressor gene at this locus, which is more commonly involved in the pathogenesis of pituitary neoplasms.     

Quantification of ethnic differences in facial profile

The effect of Tri-iodothyronine (T3) administration leading to the precocius differentiation of Sertoli cell in prepuberal rats has been previously shown. The functional maturation of Sertoli cells is associated with changes in androgen metabolism. We have recently demonstrated that T3 influences androgen metabolism in Sertoli cells by inhibiting aromatase activity and reduces drastically the ER contents in peripubertal hypothyroid rats. To better understand the role of T3 in modulating steroid action on Sertoli cells, we performed a time course study evaluating the in vitro effects of T3 and testosterone (T) on androgen (ARs) and estrogen (ERs) receptor content in Sertoli cells isolated from two weeks old Wistar rats. ARs and ERs basal levels did not change during the time course study indicating that the exposure to culture medium per se did not affect either receptor type. After 24 hrs of incubation with either T3 or T, a decrease of ERs in both nucleus and cytosol was observed. Such a decrease was augmented by the simultaneous administration of both hormones. ARs displayed a different temporal pattern in the two cellular compartments and exhibited an earlier rise in the cytosol induced by either T3 or T. At 36 hrs, ARs were significantly enhanced in both compartments in response to either T or T3 exposure while combined hormonal treatment caused an additive increase compared with the single treatment group. As a consequence of the opposite behaviour pattern displayed by ARs and ERs, the ratio between total ARs and ERs contents was increased after 24 hrs of exposure to hormonal treatment. To evaluate if treatments performed induced a functional maturation of Sertoli cells, transferrin levels in culture medium were measured. The increase of this protein paralleled that of ARs content as well as that of ARs/ERs ratio. This study demonstrates that thyroid hormone induces a progressive increase of (AR)/(ER) ratio in the differentiating Sertoli cells bringing them to a prevalent androgen dependency along their functional maturation.     

Differentiating lymphocytic adenohypophysitis from pituitary adenoma in the peripartum patient

Lymphocytic adenohypophysitis (LAH) is an autoimmune disorder of the pituitary gland with a predilection for the peripartum period and often mimics a pituitary adenoma. We sought to define the clinical, endocrinologic and radiographic characteristics differentiating peripartum LAH from pituitary adenoma to enable the use of noninvasive diagnosis and appropriate therapy. From published reports and our own case, the clinical histories and laboratory and radiographic studies of 45 patients fulfilling the diagnosis of peripartum LAH were reviewed. History of infertility or menstrual irregularity, symptomatology, endocrinologic evaluation, diagnostic imaging and associated medical conditions were analyzed. For comparison, 806 patients with pituitary adenoma and pregnancy from published series were evaluated. The spontaneous pregnancy rate in pituitary adenoma patients was 2.4% vs. 100% in LAH patients. Visual disturbances and headaches were significantly more frequent in patients with LAH. Prolactin levels were significantly lower in patients with LAH than in those with pituitary adenomas (34.6 +/- 46.3 [SD] vs. 393.0 +/- 300.4, P < .0001). Abnormalities in thyroid and/or adrenal function were also more common in patients with LAH (57.5% vs. 2.5%, P < .001). There were no distinguishing characteristics on radiographic studies. History and endocrinologic evaluation can differentiate between LAH and pituitary adenoma in the peripartum patient.     

In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide

The somatostatin analog, octreotide, is an inhibitor of growth hormone (GH) secretion that has been used to treat patients with GH-producing pituitary tumors. In this study we investigated the in vivo responsiveness to treatment with this analog in patients harboring different morphological types of GH-producing pituitary adenomas. Both GH and insulin-like growth factor I (IGF-I) plasma levels in 30 patients treated with octreotide (300 micrograms/day) for 4 months preoperatively were compared with those from 30 patients who did not receive treatment preoperatively. Tissue samples were studied using ultrastructural and immunohistochemical techniques. Amongst patients harboring densely granulated (DG) adenomas, mean GH levels were reduced to 32 +/- 9% by octreotide, to 30 +/- 7% by surgery and to 26 +/- 9% of baseline by both interventions. Surgery was equally as effective in lowering GH levels in patients with sparsely granulated (SG) adenomas as it was in those with DG adenomas; in patients with SG adenomas, GH levels were reduced by surgery alone to 37 +/- 16% and to 24 +/- 15% when performed following octreotide pretreatment. In contrast, treatment with octreotide alone in patients harbouring SG adenomas reduced GH levels to only 70 +/- 13% of baseline (p < 0.02 compared to surgery alone, or surgery and octreotide). We conclude that the GH inhibitory effects of octreotide are significantly better in patients harboring DG somatotroph adenomas compared with those harboring SG adenomas.     

Cleveland Clinic experience with adrenal Cushing's syndrome

PURPOSE: Cushing's syndrome due to adrenal adenoma or adrenocortical carcinoma is rare. To understand better the clinical and biochemical presentation of this disorder, as well as therapy efficacy and patient survival, we conducted a retrospective review. MATERIALS AND METHODS: Between August 1971 and April 1994, 40 patients presented to our institution with adrenal Cushing's syndrome (27 adenomas and 13 carcinomas). These groups were analyzed with respect to clinical signs and symptoms preoperatively and postoperatively, biochemical analysis, length of postoperative steroid replacement therapy, disease recurrence and patient survival. Followup was obtained by chart review and telephone interviews and averaged 59.6 +/- 66.4 and 47.6 +/- 56.2 months for adenoma and carcinoma patients, respectively. RESULTS: Women predominated in both groups (26 of 27 adenomas, 11 of 13 carcinomas), and tumors affected the left adrenal gland more frequently (19 of 27 adenomas, 9 of 13 carcinomas). Adenoma patients were younger than carcinoma patients (39.6 +/- 14.4 versus 51.5 +/- 16.6 years, p = 0.026) and presented with smaller tumors (3.3 +/- 1.0 versus 8.6 +/- 4.5 cm., p = 0.001). There was a trend toward increased incidence of glucose intolerance among carcinoma patients but no significant differences in clinical signs or symptoms between adenoma and carcinoma patients could be made. Similarly, while there was no significant difference in biochemical evaluation of adenoma versus carcinoma patients, 24-hour urinary free cortisol and serum lactate dehydrogenase levels tended to be higher among carcinoma patients. In addition 17-ketosteroid and dehydroepiandrosterone sulfate levels were more elevated in carcinoma than in adenoma patients, and several adenoma patients actually had subnormal levels. Among adenoma patients mean length of steroid replacement therapy was 16.8 +/- 9.1 months. However, 7 adenoma patients (25.9%) required greater than 24 months of exogenous steroids, and only 1 of these patients was subsequently weaned off steroid replacement. There were no recurrences among adenoma patients, although there was 1 perioperative death due to hypoglycemia. Ten (76.9%) carcinoma patients had recurrences at a mean followup of 33 months. The 3 and 5-year survival rates were 41.5 and 31.2%, respectively. CONCLUSIONS: While presenting signs and symptoms and hormonal analysis may suggest benign or malignant disease, only tumor size and patient age are reliable preoperative indicators of adrenal adenoma versus adrenocortical carcinoma among patients with adrenal Cushing's syndrome. Surgery is curative for adenoma patients, but lifelong steroid replacement may be required. Survival remains poor among carcinoma patients.     

Immunohistochemical analysis of progesterone receptor and Ki-67 labeling index in astrocytic tumors

BACKGROUND: Intracranial tumors such as meningiomas express steroid hormone receptors but little is known regarding progesterone receptor (PR) in astrocytic tumors. The authors evaluated expression of PR in 86 astrocytic tumors in relation to tumor proliferative potential. METHODS: Paraffin embedded tumor sections were stained with polyclonal antiprogesterone antibody by the peroxidase-antiperoxidase method and with monoclonal MIB-1-Ki-67 antibody by avidin-biotin complex immunohistochemistry. RESULTS: Sixty-three of the 86 astrocytic tumors (73%) showed positive PR immunoreactivity. PR expression was observed in 4 of 9 pilocytic astrocytomas, 13 of 24 Grade 2 astrocytomas, 15 of 20 anaplastic astrocytomas, and 31 of 33 glioblastomas. In addition to the tumor cells, cells of microvascular endothelial proliferation and the smooth muscle of tumor vessel walls were frequently PR positive. Glioblastomas had a significantly higher percentage of PR positive cells compared with anaplastic (P < 0.0008) and low grade (P < 0.0001) astrocytomas. Patients with PR positive astrocytomas were of an older age than patients with PR negative astrocytomas (48.71 +/- 21.95 years vs. 37.09 +/- 24.69 years; P < 0.04). The mean Ki-67 labeling index (LI) was significantly higher in the high grade (3-4) astrocytomas compared with low grade (1-2) astrocytomas (P < 0.0001). PR positive astrocytic tumors had higher Ki-67 LI than PR negative tumors. PR expression was not correlated with tumor recurrence and patient survival. CONCLUSIONS: The current study suggests that PR in the astrocytic tumors correlates with histologic grade and PR may participate in the growth of these tumors and tumor angiogenesis. The measurement of PR in these tumors may indirectly represent tumor growth potential.     

Modifications of platelet phospholipid fatty acid composition in streptozocin-induced diabetic rats

Mesulergine (N,N-dimethylsulphamide-N'-1,6-dimethyl-ergoline-8 alpha-yl) is an active semisynthetic ergot derivative with lower antiprolactin potency compared with bromocriptine or pergolide. Since no data are yet available on the effects of mesulergine on pituitary dopamine receptors, the present study has been designated to elucidate the influence of this drug on prolactin secretion in vivo and in vitro and 3H-spiperone binding by the anterior pituitary gland in female Wistar rats with experimentally induced hyperprolactinemia. Three weeks after bilateral ovariectomy and subcutaneous implantation of silastic tubes, containing 10 mg of diethylstilbestrol, a dramatic rise in serum prolactin levels was observed (1.67 +/- 0.23 vs. 80.82 +/- 3.80 ng/ml; P less than 0.001). Mesulergine attenuated the stimulatory effect of diethylstilbestrol on serum prolactin level in a time- and dose-dependent fashion. At concentration range between 10(-5) and 10(-7) M it also inhibited prolactin secretion from cultured rat pituitary cells to the medium during 180 min incubation in a dose-dependent manner. Scatchard analyses performed on the in vitro 3H-spiperone binding kinetics in a dispersed anterior pituitary cell culture, prepared from the pituitaries from rats treated for four weeks with diethylstilbestrol, showed that chronic mesulergine treatment (in dose of 3.0 mg/kg injected s.c. for 10 days) induced a significant decrease in the number of dopamine D2-binding sites (Bmax 28.00 +/- 4.20 vs. 42.80 +/- 4.76 fmol/10(6) cells; P less than 0.01) without any changes in D2-receptor affinity. Our results suggested that antiprolactin activity of mesulergine in vivo and in vitro is probably associated with agonistic effect of this drug on D2-dopamine receptors.     

Expression of androgen receptors in nasopharyngeal angiofibroma: an immunohistochemical study of 24 cases

Angiofibromas are uncommon benign tumors that typically occur in the lateral portion of the nasopharynx of adolescent boys. Numerous reports showed indirect evidence for the presence of sex-hormone receptors, i.e., androgen (AR), estrogen (ER), and progesterone (PR) receptors, in these tumors. The goal of the current study was to show direct evidence of sex hormone receptor expression in angiofibromas with use of sensitive immunocytochemical techniques and to document which cell populations express the receptor. Twenty-four nasopharyngeal angiofibromas were obtained from archived tissue, and immunocytochemical studies were performed with antibodies to AR, PR, and ER. Positive stromal and endothelial nuclear immunostaining, implying the presence of ARs, was seen in 18 (75%) of 24 cases, whereas 2 (8.3%) of 24 cases were positive with antibodies to PR. None of the 24 cases examined was positive with antibodies to ER. These results provide the first direct evidence for the presence of ARs in angiofibromas, which might help to explain the unique clinicopathologic features of these tumors.     

Isolation and characterization of brain-specific transglutaminases from rat

Angiotensin II (AT2) has been implicated in the growth and/or differentiation of its target tissues. In the present study, testicular AT2 receptor and its subtypes in hypophysectomized rats were examined using quantitative in vitro autoradiography and Northern blot analysis in an attempt to determine possible involvement of pituitary hormones in their expression. Prepubescent (3 weeks of age) male Sprague-Dawley rats underwent hypophysectomy or sham operation. From 10 days thereafter, they were treated with vehicle, growth hormone, human chorionic gonadotrophin or human menopausal gonadotrophin for 10 days. Testicular AT2 receptors were labelled with 125I-[Sar1,Ile8] AT2 and differentiated into its subtypes (AT1 and FAT2) according to their susceptibility to AT1 (losartan, 5 microM) and AT2 (CGP42112B, 1 microM) antagonists. Hypophysectomy led to a marked increase in AT2 receptor concentration (sham-operated rats: 0.7 +/- 0.2 fmol/mg protein, hypophysectomized rats: 2.5 +/- 0.6 fmol/mg protein, mean +/- SEM, n = 11-12, p < 0.01) with predominant occurrence of AT1 receptors. Both human chorionic gonadotrophin and human menopausal gonadotrophin decreased testicular AT2 receptor concentration, whereas growth hormone did not affect AT2 receptor expression. Northern blot analysis revealed both testicular AT1 and AT2 receptor mRNA expression to be significantly increased after hypophysectomy and reduced by gonadotrophin treatment. These results suggest that the expression of testicular AT2 receptors is regulated by pituitary gonadotrophins and that AT2 may play a role in testicular growth and/or differentiation.