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Biomedical subjects

W Haase

Publications and source records attributed to W Haase.

At least 109 records · Page 6Linked to original sources
PubMed1991

Differential diagnosis of histogenetically distinct human epithelial renal tumours with a monoclonal antibody against gamma-glutamyltransferase.

The localization of membrane-bound gamma-glutamyltransferase with monoclonal antibody (mAb) 138H11 proved to be of value for differential diagnosis of renal cancer, since it correlated with the histogenetic profile of human epithelial renal tumors. Immunoreactive gamma-glutamyltransferase was located in the proximal tubule in all normal human kidneys (15/15) examined thus far by both ultrastructural and immunohistochemical techniques. From 68 epithelial renal cancers tested 31/31 clear-cell carcinomas and 15/16 chromophilic carcinomas expressed the target epitope of mAb 138H11. In contrast, 0/11 oncytomas, 0/9 chromophobic carcinomas, and 0/1 Duct-Bellini carcinoma were immunoreactive. These results support a model of histogenesis and classification of epithelial renal tumours, according to which clear-cell and chromophilic renal carcinomas originate from transformed proximal tubule cells, whereas oncocytomas, chromophilic and Duct-Bellini carcinomas originate from cells of the collecting duct.

Antibodies, Monoclonal↗
PubMed1991

Analysis of Na+-D-glucose cotransporter and other renal brush border proteins in human urine.

A sensitive quantitative radioimmunoassay is described by which different antigens in the urine can be assayed simultaneously. Urinary excretion of three proteins from proximal tubules was compared: 1) the Na+-D-glucose cotransporter from brush border membranes and subapical vesicles; 2) a kidney-specific hydrophobic M(r) 400,000 polypeptide from intermicrovillar invaginations and subapical vesicles; and 3) villin from microvilli cores. In the normal urine about 50% of the excreted Na+-D-glucose cotransporter and villin, and about 25% of the M(r) 400,000 polypeptide was associated with brush border membrane vesicles, whereas the remaining fractions of the three proteins formed small sedimentable aggregates which contained some cholesterol and fatty acids but no phospholipids. The normal urinary excretion of the Na+-D-glucose cotransporter was correlated with that of villin and the M(r) 400,000 polypeptide. The data show that membrane proteins from the proximal tubule are excreted by the shedding of different brush border membrane areas. They suggest that some microvilli are released in total, and that a large fraction of the brush border membrane proteins is excreted without being associated with a phospholipid bilayer. In an attempt to define protein excretion patterns during kidney malfunctions, the excretion of brush border membrane proteins was analyzed after one intravenous injection of the X-ray contrast medium, iopamidol. No change in villin excretion was observed, but a reversible increase in the excretion of brush border membrane proteins was found in patients without diabetes. With diabetes a more pronounced iopamidol effect on the excretion of brush border membrane proteins and a significant increase in the excretion of villin was observed.

Adolescent↗
PubMed1991

[Statistical meta-analysis of multicenter clinical studies of ibuprofen with regard to cohort size].

The metaanalysis can be either understood as a confirmatory analysis, i.e., imposing a requirement for reproducibility, or it can be rated as a descriptive analysis. To derive confirmatory statements from the statistical metaanalysis of comparative studies, the same requirements prevail as for every individual clinical study: The statistical metaanalysis must be planned prospectively, operational target criteria must be specified ex ante, requirements for inclusion for the individual studies must be fulfilled (comparability of aim, design, inclusion and exclusion criteria, investigational methods of the individual studies). The statistical metaanalysis of comparative studies especially undergoes criticism then, when after inspection of the individual studies that show non-significant results, the summarization, i.e., the compilation of these individual studies leads to a significant overall result in the metaanalysis, which is possibly medically irrelevant. In addition to the metaanalysis, reviews or synopses of a preparation or a substance are also important, in which all available reports on a topic are taken into consideration for a summarizing medical assessment. The results of 28 comparative studies with ibuprofen in the treatment of osteoarthritis are classified in a synopsis. The results of these studies are classified as "ibuprofen better, ibuprofen worse, or ibuprofen equivalent to the respective reference substance". These results lead to the conclusion that ibuprofen at a daily dose of 1200 mg or more is superior to placebo, equivalent or superior to acetylsalicylic acid and, at an appropriate dosage, is comparable to other NSAIDs with regards to the efficacy. The tolerance of ibuprofen must be classified as excellent. The results of six non-comparative studies with ibuprofen carried out from 1985-1990, on a total of 45742 patients in 9115 study centers can be presented in a descriptive statistical metaanalysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cohort Studies↗
PubMed1991

[Discrimination difficulties--expression of disordered relative localization?].

Spatial uncertainty was examined according to a procedure suggested by Bedell and Flom (1981) ("triangle procedure") and additionally with a line-division test designed by Kundt. A horizontal line of a length of about 20 degrees and a shorter one of 4.3 degrees was divided into two equal parts. Strabismic amblyopes mark the middle of such a line with less precision and greater uncertainty than visually normal subjects do. Visual acuity was measured by single optotypes (Landolt rings), as well as by line optotypes with spaces of 2.6 min of arc between each other (C-test). Surprisingly, there was little correlation between visual acuity--even line acuity--and localization tasks.

Amblyopia↗
PubMed1990

Activation of protein kinase C by phorbol ester induces downregulation of the Na+/K(+)-ATPase in oocytes of Xenopus laevis.

Full-grown prophase-arrested oocytes of Xenopus laevis were treated with 50 nM phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, or with 50 nM 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD) that does not activate protein kinase C. The effect on membrane currents and capacitance, inulin uptake and ouabain binding, and on membrane morphology were analyzed. (i) During application of PMA, current generated by the Na+/K+ pump decreases; in addition, Cl- and K+ channels become inhibited. This general decrease in membrane conductance reaches steady state after about 60 min. 4 alpha PDD was ineffective. (ii) Ouabain binding experiments demonstrate that PMA (K1/2 = 7 nM), but not 4 alpha PPD, induces a reduction of the number of pump molecules in the surface membrane. Permeabilization of oocytes by digitonin plus 0.02% SDS renders all binding sites present prior to PMA treatment again accessible for ouabain. The KD value for ouabain binding is not influenced. 4 alpha PDD was ineffective. (iii) Exposure of oocytes to PMA reduces membrane capacitance and stimulates uptake of inulin suggesting an increase in endocytosis. Electron micrographs show that PMA reduces the number and length of microvilli, leading finally to a smooth membrane surface with a reduced surface area. From these results we conclude that stimulation of protein kinase C leads to downregulation of the sodium pump. A major portion of this inhibition is brought about by reduction in area of surface membrane with a concomitant internalization of pump molecules. In addition to this mode of downregulation, a direct effect of stimulation of protein kinase C on the pump molecule cannot be excluded.

Animals↗
PubMed1990

Flunarizine (10 and 20 mg) i.v. versus placebo in the treatment of acute migraine attacks: a multi-centre double-blind study.

In a multi-centre, randomized double-blind study, the effect and tolerance of 10 and 20 mg flunarizine i.v. versus placebo was tested on 102 migraineurs with acute migraine attacks with and/or without aura. Thirty-seven patients received 10 mg flunarizine, 32 received 20 mg and 33 received placebo. The groups were comparable. Response to treatment was defined as pain reduction of at least 50% within 60 min on a visual analogue scale after i.v. drug administration. This effect was noted on 59.4% with 20 mg flunarizine, on 24.3% with 10 mg flunarizine and on 30.3% with placebo. The tolerance of flunarizine i.v. was similar to placebo. Blood pressure and pulse rate were not affected by flunarizine. All in all, 20 mg flunarizine i.v. appeared to be a suitable alternative for treatment of acute migraine attacks.

Acute Disease↗
PubMed1990

[Post-concussion decrease in aniseikonia tolerance].

Besides loss of convergence and accommodation, head injuries can cause fusion deficiency. Part function of sensory fusion is tolerance to sphaerical and meridional aniseikonia. We will present a patient, whose aniseikonia tolerance decreased after a brain concussion.

Aniseikonia↗
PubMed1990

[Evaluation of instrument improvements in oculomotor muscle surgery].

Five improvements of surgical instruments for strabismus-surgery are introduced; these are a small muscle-hook, a broad, flat muscle-hook, two variants of a retractor and one instrument for the resection or tucking of a rectus-muscle. All instruments have proved to be less traumatic and seem much safer than others even in less experienced hands. Most of them have been used over a period of more than 10 years in a specialized department.

Humans↗
PubMed1990

Characterization and histochemical localization of the rat intestinal Na(+)-D-glucose cotransporter by monoclonal antibodies.

The localization of the Na(+)-D-glucose cotransporter in rat small intestine was investigated with four monoclonal antibodies which were raised against porcine renal brush-border membrane proteins. The antibodies alter high affinity phlorizin binding or Na+ gradient-dependent D-glucose uptake in kidney and intestine. In both organs, the antibodies react with polypeptides with apparent molecular weights of 75,000 and 47,000. In pig kidney, these polypeptides were identified as components of the Na(+)-D-glucose cotransporter (Koepsell, H., K. Korn, A. Raszeja-Specht, S. Bernotat-Danielowski, D. Ollig, J. Biol. Chem. 263, 18419-18429 (1988)). The electron microscopic localization of antibody binding was investigated by immunogold labeling of ultrathin plastic sections. In villi and crypts of duodenum, jejunum and ileum the antibodies bound specifically to brush-border membranes of enterocytes and did not react with the basolateral membranes. The density of antigenic sites in brush-border membranes was highest in jejunum, intermediate in ileum and lowest in duodenum. On the tip, the middle and the basis of the villi the density of antigenic sites was similar. The data demonstrate homologous Na(+)-D-glucose cotransporters in kidney and intestine. They suggest that during maturation of the enterocytes when the total area of brush-border membrane increases, the concentration of the Na(+)-D-glucose cotransporter in the brush-border membrane remains constant. However, we found that different segments of small intestine not only contain different surface areas of the transporter-containing brush-border membrane per intestinal length but also different densities of the transporter within the brush-border membrane.

Animals↗
PubMed1990

Immunological characterization and localization of the Na+/Ca2(+)-exchanger in bovine retina.

The sodium/calcium exchanger was purified from bovine retinal rod outer segment membranes and used for the immunization of New Zealand White rabbits. A polyclonal antibody was produced which was found to bind specifically to the 230 kDa Na+/Ca2(+)-exchanger protein as assessed by Western blotting. The antibody did not bind to the high-molecular-weight "rim protein," thereby demonstrating that this protein is distinct from the rod outer segment of Na+/Ca2(+)-exchanger. We used the polyclonal antibody for immunohistochemically localizing the exchange protein in bovine retina. Fluorescent light microscopy revealed intensive immunolabeling of the photoreceptor outer segments, whereas other retinal cell layers exhibited minimal binding. Using the electron microscopic immunogold method, we found specific antibody binding to the extracellular side of rod outer segment plasma membrane. Rod disk membranes, rod inner segments, and cone photoreceptors displayed no significant labeling. We therefore conclude that the Na+/Ca2(+)-exchanger is localized primarily in the rod outer segment plasma membrane, the most appropriate localization considering its proposed role in the process of vertebrate phototransduction.

Animals↗
PubMed1990

Electron beam therapy of primary tumors of the skin.

High energy electrons have, in comparison with 50-100 kV X rays, definitive advantages in treating large, thick or deeply infiltrating skin cancers. Moreover, a skillful therapeutic policy (fractionation, use of acrylic absorbers, shrinking field technique) often leads to excellent late results, with none or only insignificant side effects especially on bone and cartilage.

Aged↗
PubMed1990

[The association of strabismus and aphakia in children].

The frequency and polarity of secondary strabismus was related retrospectively to the onset of deprivation in 131 children with mono- and bilateral aphakia after congenital cataract or perforating injury. The frequency was highest in patients up to 2 years of age at the onset of deprivation. From the 3rd year on, it declined to 50% or less. Esotropia was predominant in the first 2 years of life. At the end of the first decade of life exotropia was up to 80%.

Aphakia↗
PubMed1989

Microtubules are involved in the secretion of proteins at the apical cell surface of the polarized epithelial cell, Madin-Darby canine kidney.

Microtubule-disrupting drugs (nocodazole, colchicine) and cytochalasin D, which inhibits the polymerization of the actin microfilaments, were used to study the role of the cytoskeleton in protein secretion in the polarized Madin-Darby canine kidney (MDCK) epithelial cells. Two proteins were analyzed. The gp 80 glycoprotein complex, which in untreated cells is sorted into the apical pathway and lysozyme, which is released randomly at both cell surfaces in transfected MDCK cells. Our results show that cytochalasin D has no influence on the transport of the gp 80 complex and lysozyme to either cell surface. However, in the presence of nocodazole or colchicine the secretion of both proteins at the apical cell surface is reduced by 50% with a concomitant increase in the basolateral release. These data suggest that microtubules are necessary for an efficient secretion of proteins at the apical cell surface of MDCK cells. In regard to the yet unresolved discrepancy concerning the involvement of microtubules in the transport of membrane proteins to the apical surface of MDCK cells, our results are consistent with the data of Rindler et al. (Rindler, M. J., Ivanov, I. E., and Sabatini, D. D. (1987) J. Cell. Biol. 104, 231-241) who observed a nonpolarized delivery of the influenza virus hemagglutinin in the presence of nocodazole or colchicine.

Animals↗
PubMed1989

[Human pharmacologic studies on transdermal administration of mepindolol. Pharmacodynamic and orienting pharmacokinetics].

The pharmacodynamic effects of acute and repeated application of a transdermal patch (BIO TSD) containing 20 mg of the beta-receptor blocking agent mepindolol were assessed in 13 normotensive male volunteers. Orienting measurements of mepindolol serum levels were performed additionally. At rest, the effects on blood pressure and heart rate were very limited. However, during submaximum ergometer exercise, significant systemic beta-blocking effects were observed, especially after 5 days treatment. Repeated administration did not induce tachyphylaxis but resulted in an enhanced efficacy. The mepindolol serum concentrations were markedly lower than those measured after oral application of the drug. No systemic or local adverse reactions nor any relevant changes in laboratory parameters were observed.

Administration, Cutaneous↗
PubMed1989

Electron microscopic immunohistochemical localization of components of Na+-cotransporters along the rat nephron.

The localization of Na+-cotransport proteins in cortex and outer medulla of rat kidney was investigated with five monoclonal antibodies. Recently, it was found that these antibodies altered Na+-D-glucose cotransport and/or Na+-dependent high affinity phlorizin binding in pig kidney cortex and that three of these antibodies interacted also with Na+-cotransporters for lactate, L-alanine and/or L-glutamate (Koepsell, H., K. Korn, A. Raszeja-Specht, S. Bernotat-Danielowski, D. Ollig, J. Biol. Chem. 263, 18,419-18,429 (1988]. In pig and rat the monoclonal antibodies bind to two brush-border membrane polypeptides with identical molecular weights and isoelectric points of 75,000 and pI 5.5, and 47,000 and pI 5.4. These polypeptides have been previously identified as components of the porcine renal Na+-D-glucose cotransporter (Neeb, M., U. Kunz, H. Koepsell, J. Biol. Chem. 262, 10,718-10,727 (1987] and may also be part of other Na+-cotransporters. The electron microscopic localization of antibody binding was demonstrated by protein A-gold labeling on ultrathin plastic sections. Three antibodies bound to brush-border membranes of proximal convoluted and straight tubules. In the proximal convoluted tubules all antibodies reacted with apical endocytic vacuoles, apical dense tubules and lysosomes. Since dense tubules are supposed to originate from endocytic vacuoles and to fuse with brush-border membranes the data suggest recycling of Na+-cotransporters in the proximal convoluted tubule. In the outer medulla two antibodies bound to apical membranes of descending thin limbs (DTL) of short loops of Henle and to apical and basal membranes of DTL of long loops of Henle. Three antibodies bound to apical membranes of collecting ducts. These data indicate that Na+-cotransporters or homologous proteins exist beyond the proximal tubule.

Animals↗
PubMed1988

Isolation of rat liver endocytic vesicles using the proton pump as a marker.

ATP-driven acidification visualized by the delta pH indicator acridine orange was used as marker for isolation of endocytic vesicles from rat liver. By differential and Percoll density gradient centrifugation, a vesicle fraction was obtained with an approx. 80-fold enriched H+-pump activity. The preparation contained vesicles that had taken up fluorescein isothiocyanate-labeled dextran or horseradish peroxidase injected into rats in vivo, proving the presence of endosomes. The H+-pump in these vesicles showed: (a) strict preference for ATP; (b) stimulation by Mg2+ and Mn2+, but not by monovalent cations; (c) stimulation by Cl-, I- and Br-; (d) electrogenicity; (e) insensitivity to vanadate, slight inhibition by oligomycin and strong inhibition by N-ethylmaleimide (NEM) and N,N'-dicyclohexylcarbodimide (DCCD). The vesicles exhibited an ouabain-, oligomycin- and levamisole-resistant ATPase activity, which was slightly stimulated by Cl-, unaffected by vanadate and inhibited by NEM and DCCD. Thus, a simple and efficient high-speed centrifugation method is available for isolation of endocytic vesicles from mammalian liver.

Acridine Orange↗