Coding sequence, exon-intron structure and chromosomal localization of murine TNF-stimulated gene 6 that is specifically expressed by expanding cumulus cell-oocyte complexes

We hypothesized that the direct stimulus of the central chemoreceptor neurons is the CO2/H+-induced change in intracellular pH (pHi). If it is true, pHi responses during hypercapnic stimulation should be exhibited in the central chemoreceptor neurons in the ventral medullary surface (VMS) and some neurons in the CO2/H+ sensitive regions such as the nucleus tractus solitarii of the medial dorsal medulla (MDM). To test this hypothesis, the cultured VMS and MDM neurons (control) derived from one day-old neonate rats were labeled with H+-sensitive fluorescent indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF), and were exposed to perfusate of various pHs. The H+-sensitive neurons were determined by a rapid decrease in the intracellular BCECF fluorescence intensity. In almost all the MDM neurons (99.6%) and 94% of the VMS neurons, the intracellular BCECF fluorescence intensity remained unchanged when the extracellular pH (pHo) was decreased. In contrast, in 0.4% of the MDM neurons (8/1800) and in 6% of the VMS neurons (111/1800), the intracellular BCECF fluorescence intensity decreased when the pHo was decreased from 7.4 to 7.2. This subpopulation of MDM and VMS neurons were considered to be H+-sensitive neurons. The H+-sensitive neurons in the VMS showed positive immunoreactivity to glutamate (57%, 17/30) and glutamic acid decarboxylase (23%, 7/30), but no immunoreactivity to choline acetyltransferase, tyrosine hydroxylase, phenylethanolamine N-methyltransferase, somatostatin, serotonin and substance P. These results indicate that the H+-sensitive neurons are present specifically in the VMS, and are mainly glutamatergic and GABAergic.     

Russell's viper venom fractions and nephrotoxicity

Apparently healthy Wistar rats of body weight 250-300 g were chosen for the experiments. A group of 6 rats were assigned for each fraction. The dose of Russell's viper venom (RVV) fraction used for in vivo experiments was 0.75 microgram/g body weight. Of each batch of 6 rats 3 were sacrificed on the third day and the remaining 3 on the fifth day after the administration of test venom fractions. Daily urine output with proteinuria and serum creatinine were determined on the day they were sacrificed. Kidneys from the rats were also examined under light microscopy after hematoxylin and eosin staining. In the in vitro experiment, kidney slices (1 mm thickness) from normal rat was incubated with RVV fractions of 5 mg/ml concentration. The predominant renal lesions observed in both sets of animal experiments were tubular degeneration and necrosis. The changes were mostly confined to proximal tubules. Glomerular changes were mild. Similar tubulotoxic effects were produced by whole RVV as well as single fractions. Therefore, it is possible that RVV contains a common nephrotoxic (protein) component which is present in all fractions of the venom. The renal damage caused by RVV seemed to be due to both systemic effects (mainly DIC and renal ischemia) and direct tubulotoxic effects of the venom.     

CNS tumours in south-western Finland: high location, high incidence

The Department of Paediatrics at the University Central Hospital of Turku, Finland has 130,000 children under 17 y of age within its catchment area. We collected all 103 cases of newly diagnosed CNS tumours from the 15-y period of 1981-95. The incidence was 5.3:100,000, a figure twofold those usually presented. During the period 1981-85 the incidence was lower (4) than during the subsequent 5-y periods (5.7 and 6.2). There were no statistical differences between the incidences of the supra- vs infratentorial brain tumours. Optic glioma was unusually common (17%, CI 13.9-20%).     

Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors

This study examined whether the high sensitivity of plasma free metanephrines for diagnosis of pheochromocytoma may result from production of free metanephrines within tumors. Presence in pheochromocytomas of catechol-O-methyltransferase (COMT), the enzyme responsible for conversion of catecholamines to metanephrines, was confirmed by Western blot analysis, enzyme assay, and immunohistochemistry. Western blot analysis and enzyme assay indicated that membrane-bound and not soluble COMT was the predominant form of the enzyme in pheochromocytoma. Immunohistochemistry revealed colocalization of COMT in the same chromaffin cells where catecholamines are translocated into storage vesicles by the vesicular monoamine transporter. Levels of free metanephrines in pheochromocytoma over 10,000 times higher than plasma concentrations in the same patients before removal of tumors indicated production of metanephrines within tumors. Comparisons of the production of metanephrines in patients with pheochromocytoma with production from catecholamines released or infused into the circulation indicated that more than 93% of the consistently elevated levels of circulating free metanephrines in patients with pheochromocytoma are derived from metabolism before and not after release of catecholamines into the circulation. The data indicate that the elevated plasma levels of free metanephrines in patients with pheochromocytoma are derived from catecholamines produced and metabolized within tumors. Some tumors do not secrete catecholamines, but all appear to metabolize catecholamines to free metanephrines, thus explaining the better sensitivity of plasma free metanephrines over other tests for diagnosis of pheochromocytoma.