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Biomedical subjects

H Köhler

Publications and source records attributed to H Köhler.

At least 199 records · Page 11Linked to original sources
PubMed1993

Coexpression of extracellular matrix glycoproteins undulin and tenascin in human autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common entity of cystic diseases of the kidney leading to end-stage renal insufficiency. Changes in extracellular matrix (ECM) are regarded to be an important pathogenic factor connected with the genes assumed to be responsible for human ADPKD. In order to assess the biological significance of altered expression and deposition of ECM glycoproteins for human ADPKD at molecular levels fresh-frozen tissue from ADPKD kidneys, fetal kidneys and normal adult kidneys were comparatively tested by immunohistochemistry for the presence of multifunctional ECM glycoproteins undulin, tenascin and fibronectin, interstitial collagen types I, III and VI and intrinsic basement membrane components laminin and collagen type IV using monoclonal antibodies and polyclonal antisera. Studies were especially focused on ECM glycoproteins undulin and tenascin which in connection with interstitial collagens and fibronectin have specific structural and functional roles in tissue development and differentiation. Cultures of cyst-lining epithelial cells from two polycystic kidneys and autologous fibroblasts were investigated in vitro. By Northern blot analysis mRNA levels of undulin, tenascin and the ECM-regulating growth factor transforming growth factor-beta 1 (TGF-beta 1) were investigated. A strong increase of fibrogenesis was demonstrated in tissue architecture of polycystic kidneys. Immunohistochemically subepithelial fibrous tissue of cyst walls in ADPKD kidneys showed strong coexpression of both undulin and tenascin with marked intensity adjacent to cyst-lining epithelium. In contrast the normal adult human kidney and developmental stages of the fetal kidney showed expression patterns of undulin and tenascin which were significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion Molecules, Neuronal↗
PubMed1993

Gastrin-releasing peptide and cholecystokinin in the regulation of exocrine pancreatic secretion in dogs.

Exocrine pancreatic secretion in conscious dogs is significantly stimulated by the intravenous application of small doses of gastrin-releasing peptide (GRP; 30 pmol x kg-1 x h-1). There is no increase of the GRP concentrations in peripheral blood which is also the case under physiological postprandial conditions. There is also no increase in the peripheral cholecystokinin (CCK) concentrations, in contrast to previous reports. Nevertheless other CCK-related mechanisms may play an important role, since the administration of the highly specific CCK receptor antagonist MK-329 causes a marked reduction of the GRP-induced exocrine pancreatic secretion.

Animals↗
PubMed1993

Pituitary adenylate cyclase-activating peptide is a potent modulator of human colonic motility.

Pituitary adenylate cyclase-activating peptide (PACAP) represents a novel brain-gut peptide with high sequence homology to vasoactive intestinal polypeptide (VIP). Since PACAP has been identified in the human gut, the effect of the two molecular forms PACAP-(1-38) and PACAP-(1-27), the hybrid PACAP-(1-23)VIP-(24-28), and VIP on the contractility of the longitudinal muscle of human sigmoid colon was tested in vitro. All peptides inhibited the spontaneous phasic contractions and relaxed concentration-dependently carbachol-precontracted preparations. The effects of the peptides remained unaffected by tetrodotoxin, by inhibition of phosphodiesterase activity, and by inhibition of nitric oxide synthesis. Apamin reduced only the effects of the PACAP peptides, whereas tetraethylammonium blocked only the effect of VIP. In conclusion, PACAP peptides and VIP mediate their relaxant effects via activation of specific PACAP and VIP receptors coupled to different potassium channels.

4-Aminopyridine↗
PubMed1993

[Aerogenous immunostimulation of weaner swine against experimentally induced respiratory infections with Pasteurella multocida].

The clearance of Pasteurella, Bordetella and Haemophilus from the lung of weaners was increased by aerogenous immunostimulations using a lysate mixture consisting of 12 strains of 8 bacterial species, as well as live and inactivated temperature sensitive mutants of Pasteurella multocida. The severity of experimental pneumonias caused by Pasteurella has also been decreased by this treatment. The effect of the lysate was shown to be unspecific and short, as antibody production against Pasteurella was not induced and no booster effect of subsequent aerogenous immunizations with Pasteurella antigens could be detected.

Animals↗
PubMed1993

Intracavernosal kinetics of eicosanoids and endothelin during erection. Data from human and animal studies on intrapenile and systemic prostaglandins.

The release of mediator substances of the arachidonic acid cascade is closely related to the functional state of the endothelium. A significant lower prostacyclin/thromboxane A2 ratio in penile plasma of organogenic impotent patients in comparison to patients with psychogenic erectile dysfunction has been described in the literature. We observed the time-related liberation of prostacyclin, thromboxane A2 and the vasoactive peptide endothelin for 16 minutes of a drug-induced erection. We compared kinetics of patients with penile deviation and transsexualism, to patients suffering from severe organogenic impotence. We assessed the usefulness of the prostacyclin-to-thromboxane A2 ratio as a possible indicator of corporal degeneration. An animal model has been created to observe differences between rabbits under 100 days of standard diet alimentation, rabbits under cholesterol enriched diet and rabbits with hereditary hyperlipidemia type II A. Hyperlipidemia is suspected to be one possible factor causing organogenic impotence. Enzyme-immuno-assays were used for the determination of all substances. The systemic prostacyclin-to-thromboxane A2 ratio differed significantly between control rabbits and rabbits with hyperlipidemia. Prostacyclin, thromboxane A2 and endothelin in corpus cavernosum plasma showed a typical profile during spontaneous and drug-induced erection. A significant difference between groups of patients suffering from organogenic or psychogenic impotence could not be found. The value of the determination of the studied substances in differential diagnosis seems to be dubious.

Alprostadil↗
PubMed1992

Two major groups of neutralizing anti-gp120 antibodies exist in HIV-infected individuals. Evidence for epitope diversity around the CD4 attachment site.

The aim of this study was to dissect neutralizing anti-gp120 antibody populations in seropositive asymptomatic individuals. Murine anti-Id mAb were raised against polyclonal affinity-purified human anti-gp120 antibodies. These anti-Id mAb were used to fractionate anti-gp120 antibodies from a pool of HIV-positive sera into idiotypically distinct anti-gp120 antibody (Id+Ab) preparations. Immunochemical and neutralization studies indicated that all Id+Ab that neutralized HIV-1 in vitro interacted with either the V3 loop or the CD4 attachment site of gp120. The V3-specific Id+Ab neutralized HIV-1 in a strain-restricted manner. Id+Ab specific for the CD4 attachment site exhibited different spectra of neutralizing activities against multiple strains of HIV-1. This finding indicates that multiple, antigenically diverse epitopes reside around the CD4 attachment site of gp120. Significantly, depletion of the Id+Ab from affinity-purified total anti-gp120 antibodies abrogated most of the neutralizing activities of these antibodies, suggesting that neutralizing anti-gp120 antibodies consist of two major specificities, either to the V3 region or to the CD4 attachment site. The understanding of specificities and neutralizing activities of different anti-gp120 antibodies in seropositive healthy individuals will be helpful for designing effective vaccines and immunotherapeutic strategies for AIDS.

Animals↗
PubMed1992

[Baclofen intoxication in chronic hemodialysis and kidney transplantation].

Fourteen days after renal transplantation, at first gave with good transplant function, a 36-year-old woman developed neurogenic dysfunction of bladder emptying. This was treated with baclofen, 5 mg three times daily by mouth. Between the 7th and 10th treatment day she progressively developed an organic psychotic syndrome and increasing respiratory paralysis after the onset of renal failure, associated with rejection of the transplanted kidney which required dialysis. Plasma concentration of baclofen was 565 ng/ml (therapeutic range 80-400 ng/ml). After discontinuing the drug and renewed haemodialysis the baclofen level rapidly fell and the symptoms receded. In a second case, a 57-year-old man on dialysis developed a thalamic pain syndrome after an intracerebral haemorrhage in the region of the basal ganglia. He was given four times 10 mg baclofen by mouth over 24 hours. 24 hours after the first dose he became deeply unconscious with respiratory failure. Plasma concentration of baclofen after the first haemodialysis period was 480 ng/ml. After 48 hours of artificial ventilation it was possible to extubate; a symptomatic transitory psychotic syndrome disappeared within 4 days. Both patients had pre-existing cerebral damage in addition to the chronic renal failure (in the first patient, meningoencephalitis 30 years previously with persisting focal lesions in the computed tomogram CT]; in the second one, residual lesions in the CT after intracerebral haemorrhage). It is emphasized that in patients who are in renal failure baclofen treatment should be undertaken cautiously: toxic signs can quickly develop especially if there is pre-existing cerebral damage.

Adult↗
PubMed1992

Anti-idiotype monoclonal antibody elicits broadly neutralizing anti-gp120 antibodies in monkeys.

Murine monoclonal antibodies (mAbs) were raised against human, polyclonal, anti-gp120 antibodies (Ab1) and were selected for binding to broadly neutralizing anti-gp120 antibodies in sera positive for human immunodeficiency virus (HIV). One anti-idiotype mAb (Ab2), 3C9, was found to be specific for human anti-gp120 antibodies directed against an epitope around the conserved CD4 attachment site of gp120. The 3C9 reactive human anti-gp120 antibodies (3C9+ Ab) neutralized MN, IIIB, RF, and four primary isolates of HIV type 1 (HIV-1). Cynomolgus monkeys were immunized with 3C9 in adjuvant to test whether this anti-idiotype mAb could induce neutralizing anti-gp120 antibodies. The results show that purified anti-anti-idiotype antibodies (Ab3) from 3C9 immune sera bind to an epitope around the CD4 attachment site of gp120SF and gp120IIIB. Furthermore, purified gp120-specific Ab3 neutralize MN, IIIB, and RF isolates. These results demonstrate that primates immunized with an anti-idiotype mAb produce broadly neutralizing anti-HIV-1 antibodies. Since this anti-idiotype mAb was selected by identifying a clonotypic marker, its biological activity can be explained as the results of clonotypic B-cell stimulation.

Animals↗
PubMed1992

Human monoclonal and polyclonal anti-human immunodeficiency virus-1 antibodies share a common clonotypic specificity.

Human monoclonal and purified polyclonal anti-human immunodeficiency virus (HIV)-1 antibodies were tested for binding to a murine monoclonal anti-idiotypic antibody (1F7, IgM, kappa). Four human monoclonal anti-p24 and three human monoclonal anti-gp120 antibodies express the 1F7 clonotype, while one human monoclonal anti-gp41 antibody does not bind to 1F7. Affinity-purified anti-p24 and anti-gp120 antibodies from HIV-1-infected individuals also react with 1F7. Western blot analysis and enzyme-linked immunosorbent assay confirmed that 1F7 reacts with human antibodies of different HIV-1 antigen specificities. A survey of sera from 329 HIV-1-infected individuals showed binding to 1F7 in 239 sera (72.6%) while 1F7 was not reacting with 109 HIV-1-negative sera. These results show that 1F7 idiotype is an HIV-1 infection-associated clonotypic marker shared by anti-HIV-1 antibodies with different epitope specificites.

Antibodies, Anti-Idiotypic↗
PubMed1992

[Effect of pancreatic innervation on exocrine secretory performance of the pancreas].

In the present study we examined the influence of extrinsic pancreatic innervation on exocrine pancreatic response to secretin, caerulein, tryptophan and fat, and furthermore the amino acid- and fat-stimulated release of neurotensin and CCK in dogs. Denervation of the pancreas did not alter secretory response to secretin and caerulein, whereas transsection of the extrinsic nerves significantly diminished the protein response to tryptophan and fat. Release of CCK was not altered by pancreatic denervation. However, fat-evoked neurotensin plasma levels were significantly increased after denervation of the pancreas.

Animals↗
PubMed1992

Influence of different methods of vagotomies on the secretion of cholecystokinin in dogs.

In six dogs, a selective proximal vagotomy, gastric vagotomy, and truncal vagotomy were performed successively. Basal and postprandial cholecystokinin (CCK) concentrations in the peripheral blood were measured by radioimmunoassay. After all the different types of vagotomy, especially after truncal vagotomy, an increased postprandial secretion of CCK was found compared with the healthy animal. Possible causes discussed are the cutting of vagal fibers, which might inhibit the secretion of CCK cells, and the changed gastric and pancreatic secretion.

Animals↗
PubMed1992

Endocrine response to intragastric and intravenous glucose challenge in the denervated dog pancreas.

The functional connection between the gut and the islet cells comprises nerves and gastrointestinal hormones. In this study, we quantified the incretin effect and the glucose tolerance (KG value) before and after denervation of the pancreas in dogs in order to find out whether the incretin effect is mediated by nerves. The participation of nerves was estimated by comparing metabolic tests before and after total extrinsic pancreatic denervation in 10 dogs. Fifty-nine percent of the insulin response after intragastric glucose was calculated preoperatively to be the result of incretin factors, a value similar to the 62% found in the postoperative series (with denervated pancreas). The response of GIP to intragastric glucose was not significantly different between pre- and postoperative tests. The KG values pre- and postoperative were in the same range. From our data, we conclude that extrinsic nerves of the pancreas do not seem to play an important role in mediating glucose homeostasis in dogs.

Animals↗
PubMed1992

Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma.

Cellular differentiation and mRNA levels of genes involved in kidney growth were investigated in normal kidney cells, cyst-lining epithelial cells of polycystic kidney disease, and renal carcinoma cells (RCC). All cells comparatively studied exhibited an antigenic phenotype of proximal tubular cells as shown by the expression of a panel of brush border membrane enzymes and kidney-associated cell surface antigens. The epithelial developmental antigen Exo-1 was expressed in 50% to 80% of cyst-lining epithelia in polycystic kidney tissue and in 20% to 30% of polycystic kidney cells cultured in vitro. Normal kidney cells and RCC were negative under identical culture conditions. The expression of antigen Exo-1 is associated with hyperproliferation in an epithelial tissue compartment composed of cells which have not yet reached their terminal differentiation state. Increased amounts of mRNA of the growth factor receptor system of epidermal growth factor (EGF) receptor and its ligand transforming growth factor (TGF)-alpha were associated with the malignant phenotype of RCC. Increased expression of EGF receptor and TGF-alpha, although less prominent, were also observed in polycystic kidney cells compared with normal kidney cells. In conclusion, the expression of Exo-1 in cyst-lining epithelial cells of autosomal dominant polycystic kidney disease (ADPKD) and the altered regulation of TGF-alpha and EGF receptor in these cells contribute to the hypothesis that hyperproliferation is an underlying pathogenic mechanism of ADPKD.

Antibodies, Monoclonal↗
PubMed1992

Effect of total extrinsic denervation and atropine on HCl-stimulated pancreatic exocrine secretion and CCK release in conscious dogs.

In 10 dogs with pancreatic fistulas, we studied the effect of extrinsic pancreatic innervation and atropine on protein and bicarbonate secretion and cholecystokinin (CCK) release after intraduodenal perfusion with HCl. Before and after extrinsic denervation of the pancreas, the dogs were given 0.05 M HCl in increasing doses (1.5-48 mmol/h). Tests were repeated with atropine. Increasing doses of HCl resulted in a dose-dependent release of protein and bicarbonate output in both the intact and the denervated pancreas. However, pancreatic denervation significantly decreased pancreatic secretion in response to low loads but not to high loads of HCl. HCl-stimulated CCK release was not altered by pancreatic denervation. In the intact pancreas, atropine significantly reduced bicarbonate and protein response to low loads but not to high doses of HCl. In the denervated gland, atropine had no further inhibitory effect on exocrine pancreatic secretion. Furthermore, atropine showed no influence on HCl-stimulated CCK release under either condition.

Animals↗