Ovarian hyperstimulation caused by gonadotroph cell adenoma: a case report and review of the literature.

OBJECTIVE: We present a case of spontaneous ovarian hyperstimulation caused by pituitary gonadotroph macroadenoma, and include a review of the literature. CASE REPORT: A 27-year-old woman presented with irregular menstruation and bilateral multicystic enlargement of the ovaries. Serum estradiol (E(2)) levels were marginally elevated for the follicular phase but within the physiological range. Serum luteinizing hormone (LH) was extremely low, follicle-stimulating hormone (FSH) was normal, and prolactin (PRL) was high. Magnetic resonance imaging disclosed a pituitary macroadenoma. Immunohistochemical examination of the surgically removed adenoma showed intense reactivity for FSH and LH. After the operation, E(2), LH and PRL levels were normalized, the ovaries returned to a normal morphology, and regular menstrual cycles were resumed. CONCLUSION: A review of the literature showed that ovarian hyperstimulation caused by pituitary gonadotroph adenoma is not always accompanied by elevated FSH levels. High PRL and E(2) and low LH were reported in the majority of the cases, but E(2) may stay within the range observed in normal menstrual cycles.     

Mucin expression profile in pancreatic cancer and the precursor lesions

In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary–mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.     

Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.     

Amelioration by topical bunazosin hydrochloride of the impairment in ocular blood flow caused by nitric oxide synthase inhibition in rabbits.

We investigated whether topical instillation of an alpha(1)-adrenergic blocker would improve an insufficient blood supply in the optic nerve head (ONH) and visual function, in rabbits. The effect of systemic NOS inhibition on visual-evoked potentials (VEPs) and hemodynamics in ONH were determined. VEPs were recorded before and every 15 min during a 120-min observation period after an intravenous injection of 50 mg/kg N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. Capillary blood flow in ONH was evaluated by the laser speckle method throughout the same period. Then, we investigated the effect of topical instillation of a recently developed alpha(1) adrenergic blocker, bunazosin hydrochloride (0.01%), 60 min prior to the intravenous L-NAME (50 mg/kg) on the changes by NOS inhibition. The VEP amplitudes were reduced by L-NAME (10, 20, and 50 mg/kg) in a dose-dependent manner, while the VEP implicit time was unchanged, and no significant changes were detected in the electroretinogram. The reductions in ONH capillary blood flow and VEP amplitudes caused by L-NAME (50 mg/kg) were significantly suppressed by an instillation of bunazosin hydrochloride. These results indicate that blocking alpha(1)-adrenergic receptors may ameliorate the impairments in blood flow and retinal function caused by NOS inhibition. The enhancement of basal vascular tone due to deprivation of continuous NO production may be diminished by this alpha(1)-adrenergic blocker.     

Nonuniform blood flow in the canine left ventricle

In order to investigate the relationship between coronary perfusion pressure and blood flow distribution in the left ventricle (LV), we measured myocardial blood flow in small regions using radioactive microspheres in six anesthetized, open-chest dogs. Mean coronary perfusion pressure (CPP) was controlled with a femoral artery to left main coronary artery shunt which included a pressurized, servo-controlled blood reservoir. In each dog, we measured flow in 192 regions of the LV free wall (mean weight per region = 206 +/- 38 mg) at different perfusion pressures. At CPP = 80 mm Hg, blood flow to individual regions varied fourfold (0.30 to 1.18 ml/min/g; relative dispersion (RD) = 21.8 +/- 2.3%). At CPP = 50 mm Hg, flow varied over sevenfold (0.08 to 0.60 ml/min/g; RD = 42.8 +/- 10%; P less than 0.01 vs 80 mm Hg). This relationship between flow variability and CPP was present within individual LV layers as well between layers and is much higher than the error associated with the microsphere technique. We conclude that blood flow to small regions of the LV is markedly nonuniform. This heterogeneity becomes more profound at lower CPP. These findings suggest that (1) global measurements of coronary flow must be interpreted with caution, and (2) even in hearts with normal coronary arteries some regions of the LV are more susceptible to ischemia than others. In addition, these findings may help explain the patchy nature of myocardial damage that occurs following periods of low coronary pressure or inadequate myocardial protection during cardiopulmonary bypass.     

An immunocytochemical demonstration of calcineurin in human nerve cell tumors. A comparison with neuron-specific enolase and glial fibrillary acidic protein

Human central and peripheral nerve cell tumors were examined in detail using antibodies to calcineurin, glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE). Forty-eight formalin-fixed and paraffin-embedded specimens of human neuronal tumors, including 27 medulloblastomas, were examined. Calcineurin-positive cells were found in all peripheral nerve cell tumors and the two gangliogliomas, whereas 20 of the 27 medulloblastomas and one of the two cerebral neuroblastomas did not contain calcineurin-positive cells. Differentiation of cells along the neuronal lines was positively correlated with calcineurin immunoreactivity. NSE-positive cells were found in all of the tumors with the exception of the one cerebral neuroblastoma. NSE immunoreactivity was not invariably consistent with calcineurin immunoreactivity and non-neuronal cells were often positive. Calcineurin-positive cells were all devoid of GFAP, but NSE-positive cells expressed GFAP in some tumors. GFAP-immunoreactive cells were found only in central nerve cell tumors, and not in peripheral tumors. In addition, GFAP-positive cells in some tumors such as retinoblastoma and medulloblastoma morphologically revealed not only neoplastic but also reactive astrocytic features.     

Application of in vivo microdialysis to pineal research in birds: Measurement of circadian rhythms of melatonin

Circadian rhythms of pineal melatonin release were measured in free-moving pigeons, Japanese quails, and chickens under light-dark cycles followed by constant dim light. Although melatonin levels differed among individual birds, circadian rhythms of melatonin were observed in all of them. Using this technique, we could examine phase shifts of melatonin rhythms and suppression of melatonin release by photic stimulation in pigeons. We could also examine effects of norepinephrine infusion on melatonin release. These results indicate that microdialysis is useful for the study of pineal melatonin rhythms in birds.     

Dysferlin mutation analysis in a group of Italian patients with limb-girdle muscular dystrophy and Miyoshi myopathy

Mutations in the dysferlin gene (DYSF) on chromosome 2p13 cause distinct phenotypes of muscular dystrophy: limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy (MM), and distal anterior compartment myopathy, which are known by the term 'dysferlinopathy'. We performed mutation analyses of DYSF in 14 Italian patients from 10 unrelated families with a deficiency of dysferlin protein below 20% of the value in normal controls by immunoblotting analysis. We identified 11 different mutations, including eight missense and three deletion mutations. Nine of them were novel mutations. We also identified a unique 6-bp insertion polymorphism within the coding region of DYSF in 15% of Italian population, which was not observed in East Asian populations. The correlation between clinical phenotype and the gene mutations was unclear, which suggested the role of additional genetic and epigenetic factors in modifying clinical symptoms.