PubMed Health⌕ Search

Biomedical subjects

H Köhler

Publications and source records attributed to H Köhler.

At least 163 records · Page 9Linked to original sources
PubMed1994

In vitro effects of solubilized HLA-DR--role in immunoregulation?

To test the hypothesis that soluble HLA-DR antigens (sHLA-DR), binding to the T-cell receptor (TCR) and/or CD4 structures, compete with and abrogate functions of their cell-bound counterparts, we studied effects of detergent-solubilized, affinity-purified HLA-DR molecules on the DNA synthesis, IL-2, and IL-1 secretion by human peripheral blood mononuclear cells (PBMC). While resting T cells did not show any response, there was a dose-dependent suppression of T-cell responses induced by mitogen (phytohemagglutinin, PHA), recall antigen (purified protein derivative of tuberculin, PPD), or HLA class II alloantigens (Daudi cells). In the PHA system, sHLA-DR affected DR-identical and DR-disparate PBMC with equal efficiency, suggesting a nonspecific interference with accessory functions of cell-bound HLA class II molecules. A competitive ligation of lymphocyte (rather than of monocyte) CD4 is suggested based on the failure of sHLA-DR (i) to potentiate inhibitory effects of anti-CD4 mAb, (ii) to suppress mitogen responses after depletion of CD4+ lymphocytes and also following separate monocyte (vs lymphocyte) pretreatment, and (iii) to induce a reproducible IL-1 secretion inhibition. In the PPD system, suppressive sHLA-DR effects on autologous or DR-identical PBMC significantly exceeded that on DR-disparate PBMC, and in the MLR, third party allogeneic sHLA-DR was exceeded in its suppressive potency both by sHLA-DA pertinent to responder cells and by sHLA-DR pertinent to stimulator cells. These additional specific effects may result from competition (with cell-bound class II restriction and recognition determinants) at the TCR level rather than from peptide competition at the antigen-presenting cell level. Interference by sHLA-DR with the primary and/or accessory signaling may offer new therapeutic strategies in allotransplantation and autoimmunity.

Dose-Response Relationship, Drug↗
PubMed1994

Long-term manometry of tubular esophagus in progressive systemic sclerosis.

Long-term manometry of the tubular esophagus was performed in 20 consecutive patients (18 females, 2 males; median age 56.5 years) with progressive systemic sclerosis (PSS) and a control group of 20 healthy subjects (18 females, 2 males; median age 56.5 years). The measurements were performed via a data logger of 1 MByte memory capacity with the help of two pressure sensors placed 8 and 18 cm above the lower esophageal sphincter. Esophageal contractions were analyzed with respect to pressure amplitudes in the esophagus distal and proximal, quotient of pressure amplitudes distal/proximal, number of contraction waves in a 24-h period, and kind of spreading (propulsive, simultaneous). In the PSS group there was a significant decrease in pressure amplitudes in the distal sensor (median 31.5 versus 39.5 mbar in controls, P < 0.02), in the quotient of pressure amplitudes distal/proximal (median 0.885 versus 1.25 in controls, P < 0.001), in the number of waves in 24 h (median 939.5 versus 1656 in controls, P < 0.01), and in the occurrence of propulsive waves (median 34% versus 57% in controls, P < 0.01). Fifteen patients (75%) had hypomotility disorders as compared to the control group, in which the lower limit of normal values was defined by the 5th percentile of descriptive analysis. These first data of long-term manometry in patients with PSS indicate that long-term manometry may be an effective method for identifying esophageal involvement in PSS.

Adult↗
PubMed1994

Gastrin-releasing peptide and CCK after intraduodenal inhibition of proteases in dogs.

The intraduodenal application of a potent protease inhibitor (camostate, 600 mg) causes a significant increase in basal pancreatic secretion in the manner of a negative-feedback mechanism. The integrated protein secretion during the entire study period was 9.9 +/- 1.8 g in 120 min. The iv application of anti-GRP immunoglobulin caused a significant reduction to 5.0 +/- g in 120 min. No significant changes in the plasma concentrations of GRP and CCK were detectable. The increased secretion occurring after the administration of the protease inhibitor could be mediated by neural GRP-dependent mechanisms. These may also be relevant for CCK-dependent factors, which are only briefly mentioned.

Animals↗
PubMed1994

Deceptive imprinting in the immune response against HIV-1.

The clonal profile of anti-HIV-1 antibodies is established at the time of infection as part of a vigorous immune response against HIV-1, and remains stable during the infection process. This bias towards antibodies specific for the initially infecting clonal virus population, termed imprinting, is inappropriate for attempts of the infected host to control viral variants that subsequently emerge. Here, Heinz Köhler, Sybille Müller and Peter Nara argue that immunodominant epitopes on viral variants or recombinant proteins are selected that induce and maintain this deceptive state, and thereby remain unrecognized through a functional and cross-reactive hole in the B-cell repertoire.

Animals↗
PubMed1994

The immunosuppressive effects of verapamil upon mitogen activated and allo-antigen inducible human cytotoxic T-lymphocytes.

In this study, the effect of verapamil, a phenylalkylamine-type Ca2+ antagonist, upon the activation of human mononuclear cells was investigated and a detailed analysis of the kinetics and dose related effects of verapamil upon alloreactive cytotoxic T-cells (CTL) was undertaken. Verapamil suppressed the release of interleukin-2, proliferation and generation of CTL activity in mitogen and alloantigen stimulated human T-lymphocytes in a dose related fashion. Verapamil suppressed the steady state levels of several T-cell activation-associated gene transcripts, i.e. the mRNA encoding for interleukin-2, and a cytotoxic T-cell specific serine esterase. Verapamil exerted a novel immune-suppressive effect, i.e. the inhibition of mature alloantigen-inducible cytolytic T-cells, thus rendering verapamil a progenitor of potent and clinically useful immunosuppressive drugs.

Cytotoxicity Tests, Immunologic↗
PubMed1994

Laboratory control of minimal heparinization during haemodialysis in patients with a risk of haemorrhage.

For patients undergoing dialysis with a high risk of haemorrhage there is no standardized procedure for anticoagulation during extracorporeal circulation. Minimal heparinization with a dose equivalent to half that used for chronic haemodialysis was employed in 49 patients (125 haemodialyses) performed after operative interventions (83.3%), after haemorrhagic events (5.2%) and after invasive investigations (11.5%). Using a biocompatible membrane and a low molecular weight heparin (bolus dose 500-1300 U; continuous infusion 100-400 U) it was possible to complete haemodialysis in 74 cases (Group 0) without clots appearing in the venous bubble trap of the tubing system. In 30 cases (Group 1) only small clots were detected at the end of haemodialysis, and in 13 cases (Group 2) larger clots (exceeding a diameter of 1 cm) were found. In eight cases (Group 3) partial or complete clot formation occurred in the tubing. No haemorrhagic complications were observed. Anti-Xa activity, thrombin-antithrombin III complex (TAT) and D-dimer were determined before haemodialysis, 2 h after the start of haemodialysis and on completion of the procedure. The anti-Xa activities ranged between < 0.2 and 0.56 U/ml. In contrast, at 2 h there were significant differences (P < 0.05) in the TAT concentrations between Group 0 and the other groups, as well as between Group 1 and Group 2 and 3. Significant differences (P < 0.05) in D-dimer levels occurred only at the end of haemodialysis. Minimal heparinization in haemodialysis is a practicable alternative in patients with a high risk of haemorrhage and extended coagulation monitoring is helpful in adjusting heparin dosage.

Adult↗
PubMed1994

Increased adhesion and activation of polymorphonuclear neutrophil granulocytes to endothelial cells under heavy metal exposure in vitro.

Heavy metals have been implicated in the mechanisms of endothelial damage. Influences of heavy metal ions on diverse cell types have been studied using a variety of in vitro and in vivo methods. Polymorphonuclear neutrophil granulocytes (PMNs) have physiological and pathological functions, including the modulation of adhesion to and destruction of endothelial cells (ECs). PMNs were studied during interaction with human umbilical vein ECs under exposure to zinc, nickel and cobalt using an in vitro model. We studied adhesion processes with the help of a computer-controlled image-analyzing system and examined the activation of PMNs by quantification of leukotriene B4 (LTB4) release. The biphasic effects of the evaluated heavy metals on PMN-EC adhesion, with stimulation at very high and very low molar concentrations, were observed. The release of LTB4 by PMNs increased during exposure to very low metal concentrations. The initiation of these important pathogenetic mechanisms of inflammation at very low metal ion concentrations, which give no morphological changes, must be regarded as potentially significant with respect to the toxic effects of heavy metals.

Cell Adhesion↗
PubMed1994

Comparative studies on vascular endothelium in vitro. I. Cytokine effects on the expression of adhesion molecules by human umbilical vein, saphenous vein and femoral artery endothelial cells.

Endothelial cells (ECs) are very responsive to proinflammatory cytokines. ECs are stimulated by these substances to increase expression of cell surface adhesion molecules, leading to dramatically altered interactions with leukocytes. In these interactions, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are suggested to play the most important role. Recent evidence has suggested diversity in the responses of ECs from different regions of the vascular system. Human umbilical vein ECs (HUVECs) are the most often used EC culture model, although there are few studies comparing their response with other human EC types from the adult organism. In this study the expression of E-selectin, ICAM-1 and VCAM-1 on cultured human adult ECs from the saphenous vein (HSVECs) and from the femoral artery (HAFECs), as well as HUVECs was studied. Using a cell enzyme immunoassay as well as immunoelectron microscopical methods, we found that both HSVECs and HAFECs respond in a similar way to HUVECs to exogenous stimulation by IL-1 beta, TNF alpha or LPS. IL-1 beta and TNF alpha increased the expression of E-selectin on the cytoplasmic membranes of HUVECs, HSVECs and HAFECs and elicited even similar absolute quantities of this molecule, comparing the different cell types. ICAM-1 and VCAM-1 appeared to be regulated dose dependently by IL-1 beta, independent of the EC type. HUVECs as well as HSVECs and HAFECs gave a reproducible constitutive ICAM-1 expression, whereas E-selectin and VCAM-1 were absent on nonstimulated ECs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[The Chang mesocaval side-to-side shunt, an alternative shunt form after previous operations and portal vein thrombosis].

Over the time period from July 01, 1983 to June 01, 1993, 15 patients with portal hypertension and relapsing bleedings from esophageal varicosis were treated with Chang's mesocaval side-to-side shunt at the Department of General Surgery, University Hospital of Göttingen. All patients were pre-operated in the upper abdomen or exhibited thrombosis of the portal vein. While five cases revealed a prehepatic block, ten patients had an intrahepatic block, based on cirrhosis of the liver (Child classification A or B). The time required for operations was 180 +/- 32 minutes; the pressure in the portal circulation decreased by 56%. In three cases, patients suffered relapsing bleedings despite of regular shunt conditions. Complications which were due to the procedure were seen in two patients (one revealed intraabdominal posthemorrhage, followed by therapy-resistant coagulopathy; the other patient exhibited stenosis of the anastomosis). One patient developed encephalopathy. Given a rigid indication, we regard the procedure described herein an alternative to the mesocaval interposition shunt, and we consider the low rate of thrombosis (so far < 10%) without continued postoperative anticoagulant therapy as well as the avoidance of an interposition as important advantages of this technique.

Adolescent↗
PubMed1994

[Hypertension in pregnancy--dietary aspects].

Dietary recommendations about prophylaxis and treatment of hypertension in pregnancy are manifold and controversial. Only a few studies of evidence are published till now. Recommendations may be derivable from physiology and pathophysiology of hypertension in pregnancy. A normal protein intake of 70-80 g is to be recommendable, neither protein restriction nor increased protein supply. Protein restriction may be sensible only for blocking a progression of a chronic renal insufficiency. The value of caloric restriction is not secured, but an increasing body fat is not recommendable. Neither restriction nor increased supply of sodium can generally be recommended. The same is valit with respect to liquid supply, which is to be restricted in cases with hyponatriemy and hypoosmolality. Substitution of potassium and magnesium is not necessary, of linoleic acid and water-soluble vitamins not sufficiently verified. The efficacy of calcium substitution on hypertension in pregnancy has to evaluated by further studies.

Feeding Behavior↗