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Biomedical subjects

O Vogel

Publications and source records attributed to O Vogel.

At least 19 recordsLinked to original sources

Expression of the conjugate export pump encoded by the mrp2 gene in the apical membrane of kidney proximal tubules.

A novel ATP-dependent export pump for amphiphilic anionic conjugates, which has been cloned recently from liver, was identified in rat kidney and localized to the apical membrane domain of proximal tubule epithelia. This 190-kD membrane glycoprotein (Mrp2) has been described previously as the hepatocyte canalicular isoform of the multidrug resistance protein and as the canalicular multispecific organic anion transporter. Mrp2 was identified in kidney by reverse transcription PCR followed by sequencing of the amplified 786-bp fragment and by immunoblotting, using an antibody specifically reacting with the carboxy terminus of rat Mrp2. Double immunofluorescence and confocal laser-scanning microscopy showed the presence of Mrp2 in the brush-border membrane domain of segments S1, S2, and S3 of proximal tubule epithelia. Mrp2 was not detectable in other segments of the nephron. The onset of Mrp2 expression during development occurred in a very early stage of nephron development. Mrp2 represents the first cloned ATP-dependent export pump for amphiphilic organic anions identified in kidney and localized to the apical membrane domain of proximal tubule epithelia. Mrp2 may contribute to cellular detoxification and to the secretion of endogenous and xenobiotic anionic substances, most of which are conjugates, from the blood into urine.

Adenosine Triphosphate↗

Determination of urinary glutathione S-transferase and lactate dehydrogenase for differentiation between proximal and distal nephron damage.

Cytosolic glutathione S-transferase (GST) activity is confined to the proximal convoluted and straight tubules. Damage to these parts of the nephron should result in leakage of GST into the urinary space. Lactate dehydrogenase (LDH), in contrast, is more generally distributed along the nephron. Measurement of both enzyme activities could therefore be expected to discriminate between different localizations of nephrotoxicity. To test this hypothesis, we determined both enzyme activities in 24 h urine samples from 10-12 female Sprague-Dawley rats, each treated with single i.p. injections of puromycin aminonucleoside (PAN, 130 mg/kg), Na2 CrO4 10, 20, 30 mg/kg), mercuric chloride (HgCl2, 0.5, 0.75, 1.0 mg/kg), folic acid (125, 350, 375 mg/kg), ethyleneimine (0.5, 2.0, 5.0 microliters/kg). Bovine serum albumin (BSA) was injected by the same method, twice daily on 3 consecutive days (2.5, 7.14 g/kg). The results obtained indicate a characteristic dose- and time-dependent pattern of excreted enzyme activities for each of the tested compounds. In both models with primarily glomerular damage, proximal tubular parts were also affected, as could be demonstrated by increased urinary GST and histopathological changes. Damage, mainly to the S1/S2 segment by 20 or 30 mg Na2 CrO4/kg, resulted in moderate to marked increases in LDH excretion, while GST was only moderately elevated at 30 mg/kg. Extreme increases in GST and LDH output were measured after predominant S3 segment damage after 0.75 and 1.0 mg HgCl2/kg. The distally active compounds, folic acid and ethyleneimine, did not increase GST excretion at lower doses. At the high doses, a small rise in GST excretion indicated some, probably secondary, proximal tubular involvement, which correlated with the histopathological findings in these groups.

Animals↗

Chronic effects on single and multiple oral and subcutaneous cadmium administrations on the testes of Wistar rats.

Thirty mature male Wistar rats were administered cadmium as CdCl2 X 1H2O in single doses of 50 mg/kg p.o. or 2.5 mg/kg i.p. or 10 weekly doses of 5 mg/kg p.o. or 0.25 mg/kg i.p., respectively. Ten males, each treated correspondingly with the vehicle, served as control groups. Some of the animals were necropsied after 12 and 18 months, respectively, the remainder were kept for up to 30 months. In a supplementary study 25 males were each treated once with 200 mg/kg p.o. or 2 mg/kg s.c. and 35 males with 100 mg/kg p.o. This experiment was terminated after 6 months. Animals having received 1 X 100 or 1 X 200 mg/kg p.o. or 1 X 2.0 or 1 X 2.5 mg/kg s.c. showed severe lesions of the whole testicular parenchyma with massive calcification of the necrotic tubuli and pronounced fibrosis of the interstitium. All animals receiving 2.5 mg/kg s.c. had a Leydig cell tumor in at least one of the testes. In 5 out of 15 animals surviving 18 months these tumors were classified as malignant (mean time of induction: 858 +/- 77 days). All the other tumors detected were not regarded as causally related to treatment. The results of the supplementary study indicate that with very high oral cadmium dosages Leydig cell tumors may be induceable. Since the massive lesion of the testes appears to be the prerequisite for the occurrence of induced Leydig cell tumors, a non-genetic mechanism is to be assumed in respect to the formation of these tumors.

Administration, Oral↗

In vivo activity of proteases of Pseudomonas aeruginosa in a rat model.

The granuloma pouch technique was used to study the in vivo characteristics of four strains of Pseudomonas aeruginosa that differed in levels of alkaline protease and elastase production. Bacterial counts, alkaline protease and elastase concentrations, and IgG levels of pouch exudates were determined quantitatively; total protein levels were determined semiquantitatively. In vivo protease concentrations were in the nanogram range; during the investigated period individual strains either increased enzyme production or remained negative. In vitro alkaline protease:elastase ratios correlated with in vivo ratios in three of the four strains. Proteolytic strains caused a decrease in IgG and alpha 2-fraction proteins. Purified rat IgG was cleaved rapidly by elastase and slowly by alkaline protease; both cleaved IgG at the hinge region. The study determines the concentration of P aeruginosa alkaline protease and elastase after infection in a rat model, shows cleavage of rat IgG and other proteins due to alkaline protease and elastase, and suggests that enzymes other than proteases are involved in the pathogenesis of P aeruginosa infections.

Animals↗

Pattern formation by interaction of three cytoplasmic factors in the egg of the leafhopper Euscelis plebejus.

Developmental capacities of different parts of the Euscelis plebejus egg were tested by translocating posterior pole material and subsequent transverse constriction of the egg posterior to the translocated material. The results support the hypothesis that at least three cytoplasmic factors of maternal origin are necessary to form a complete germ band. Those factors do not act autonomously. The anterior and posterior factors require interaction with the middle factor in order to cause formation of head and abdomen, respectively. The middle factor, on the other hand, forms a complete thorax only if it is in contact with the posterior factor.

Animals↗

Pathomorphologic findings in short-tailed voles (Microtus agrestis) experimentally-infected with Frenkelia microti.

Following oral infection of Microtus agrestis with sporocysts of Frenkelia microti, transient focal necrosis and cellular infiltrations in the liver, hyperplasia of lymphoid organs, and inflammatory infiltrations in the heart, pulmonary veins, skeletal muscles and brain occurred during the first asexual multiplication period of the parasite in the liver. Frenkelia cysts were first observed in the brain 23 days after infection.

Animals↗