Biomedical subjects
Publications and source records attributed to H Köhler.
By means of an exact nephrologic examination 6 weeks post partum of 128 patients with hypertension in pregnancy an exact classification in preeclampsia (46 per cent), chronic hypertension (34%) and superimposed preeclampsia (13 per cent) is possible. In cases of essential hypertension a hypotensive therapy is necessary.
The existence of soluble forms of MHC class II molecules is well established. To quantify soluble HLA-DR antigens (sHLA-DR) in human serum and other body fluids, we developed an enzyme immunoassay using two non-overlapping HLA-DR-specific monoclonal antibodies (RoDR, BL-la/5) and an immunoaffinity chromatography-purified sHLA-DR standard. In serum of healthy individuals, sHLA-DR levels were found in the range between 0.6 and 3 ng/ml (median 0.85 ng/ml) whereas EDTA plasma samples showed concentrations about 20 times higher (median 21 ng/ml). In tears, saliva, sweat, urine, amniotic fluid, cerebrospinal fluid, and bronchoalveolar lavage, sHLA-DR could also be detected. No association was found between sHLA-DR serum levels and distinct HLA specificities. In the sera of patients with autoimmune diseases, slightly enhanced sHLA-DR values were found (juvenile rheumatoid arthritis: median 2.0 ng/ml, lupus erythematosus: 1.5 ng/ml, diabetes mellitus: 2.1 ng/ml).
In 78 patients (47 men, 31 women; mean age 53 [22-78] years) 174 dialyses were undertaken within one week of a bleeding episode or a diagnostic or therapeutic procedure which may cause bleeding. Minimal anticoagulation with low molecular weight heparin (LMWH) was the aim, using a biocompatible dialyser. During the dialysis coagulation was controlled by global tests (Quick value/international normalized ratio [INR], partial thromboplastin time, thrombin time, antifactor Xa activity), by molecular markers of clotting activity (thrombin-antithrombin III complex [TAT], D-dimers), as well as measurement of elastase (elastase-alpha 1-protein inhibitor complex). The LMWH dosage averaged 932 units as an initial bolus and 234 units/h as a continuous infusion. In the group of chronic dialysis patients (n = 72) this meant (standard heparin units = 2/3 LMWH units) a reduction to 45 +/- 11% from the previously used routine heparin dosage for a 4-hour dialysis. All dialyses were completed without bleeding complications. Considerable clotting formation in the extracorporeal circulation occurred in 11 dialyses (6.3%). TAT, D-dimer and elastase values proved to be suitable for determining individual clotting activity and for reducing anticoagulation to the minimum.
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A potential physiological function of the regulatory gastrointestinal peptide neurotensin (NT) is the stimulation of exocrine pancreatic secretion. We investigated therefore whether immunoneutralization of the postprandially circulating peptide, intravenous application of either atropine or the highly specific CCK receptor antagonist, L-364,718, could influence neurotensin-mediated pancreatic secretion in dogs. The use of CCK receptor antagonist (0.1 mg kg-1 intraduodenally) inhibited postprandial and NT-mediated exocrine pancreatic secretion. The integrated postprandial protein secretion fell from 31 +/- 1.6 to 23 +/- 2.1 g 180 min-1 while the corresponding values in response to i.v.-NT (postprandial neurotensin concentration course was imitated by the infusion of 50 pmol kg h-1 NT) fell from 22 +/- 1.9 to 7.5 +/- 0.8 g 180 min-1. Immunoneutralization of postprandial NT led to a simultaneous significant reduction in postprandial pancreatic secretion (integrated protein release 31 +/- 1.6 and 15.5 +/- 1.4 g 180 min-1 respectively). The i.v. application of atropine lowered NT-mediated pancreatic secretion (e.g., protein output) from 22 +/- 1.9 to 7.1 +/- 7.1 +/- 0.9 g 180 min-1. We conclude that NT plays an important role in the endocrine regulation of exocrine pancreatic secretion. This influence could be mediated by a CCK-dependent cholinergic mechanism.
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The aim of the following study was to gain some insight into the functional characteristics of different portions of the small intestine after either partial resection or syngeneic and allogeneic transplantation 3 months postoperatively. Nutritional parameters (serum albumin levels, serum triglyceride levels, maltose absorption, excretion of fecal fat) and fat-stimulated neurotensin release were determined in Lewis rats that underwent small-bowel resection (n = 21), syngeneic (Lewis-->Lewis, n = 21), or allogeneic transplantation (Brown Norway-->Lewis, n = 24). The length of the remnant, isograft, or allograft was 27 cm (i.e., one-third of the rat small intestine) and consisted of the proximal (n = 7), middle (n = 7), or distal (n = 7) portion. Three postoperative deaths were due to ileus or pneumonia. After allotransplantation cyclosporine (15 mg/kg body wt. s.c.) was administered for graft acceptance. The control group was not operated upon, but was composed of weight- and age-matched Lewis rats (n = 7). We found that resection of two-thirds of the small intestine led to significantly lower levels of albumin and triglycerides in all three portions investigated (P < 0.01), but did not affect maltose absorption. Excretion of fecal fat was elevated significantly only after distal resection (P < 0.05). When compared to resected animals, syngeneic transplantation did not affect the nutritional parameters, but caused a significantly higher hormone release (P < 0.05) in all three different intestinal grafts. Allogeneic transplantation was successful when the middle or distal portion was grafted. All recipients of proximal allografts showed a severe loss of body weight and died between day 8 and 10 after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of hydroxyethyl starch on pancreas preservation with cardioplegic histidine-tryptophan-ketoglutarate solution (HTK) was investigated. The study was performed using an in vitro reperfusion system of the porcine pancreas. During organ preservation pancreatic weight, arterial pressure, volume flow, and washout of amylase and lactate were quantified. Addition of hydroxyethyl starch did not affect arteriovenous volume flow or washout of amylase and lactate during protective perfusion after pancreas preparation. However, hydroxyethyl starch in HTK prevented an increase in pancreatic weight at the end of the protective perfusion (102.2 +/- 4.55% vs 127.8 +/- 4.62% in controls; p < 0.005) and after 24 h cold ischemia (72.9 +/- 3.91% vs. 83.5 +/- 3.49% in controls; p < 0.05). Hydroxyethyl starch did not affect postischemic organ quality assessed during reperfusion in a perfusion chamber by pancreatic vascular resistance, amylase and lactate release, insulin secretion, and oxygen consumption. We conclude that hydroxyethyl starch does not bring about any further improvement in immediate postischemic organ quality assessed in an in vitro reperfusion system.
Besides vagal cholinergic mechanisms, pancreatic polypeptide (PP) secretion is thought to be mediated by hormones. This study was performed to delineate the role of extrinsic pancreatic innervation and cholecystokinin (CCK) in amino acid- and fat-stimulated PP secretion. In ten mongrel dogs, pancreatic denervation was performed by the method of Debas et al. [3]. Total denervation of the pancreas did not alter PP response to intraduodenal application of amino acids (integrated output 24,434 +/- 3260 pmol/1 x 120 min before vs 22,797 +/- 2470 pmol/1 x 120 min after operation) and to intraduodenal fat solution (19,595 +/- 2121 pmol/1 x 120 min vs 19,983 +/- 2031 pmol/1 x 120 min). Also, no significant differences were measured in CCK release (491 +/- 71 pmol/1 x 120 min vs 430 +/- 57 pmol/1 x 120 min for amino acids, 571 = 63 pmol/1 x 120 min vs 563 +/- 89 pmol/1 x 120 min for fat solution). Plasma PP and CCK levels were compared by linear regression analysis. Correlations between PP and CCK were high in the intact pancreas (amino acids, r = 0.92; fat, r = 0.99) as well as in the denervated pancreas (r = 0.93 amino acids and r = 0.98 fat). These results show that extrinsic pancreatic innervation does not influence PP and CCK release after intraduodenal amino acids or fat solution and that PP secretion seems to be mediated to some extent through the release of CCK.
Organ harvesting from a living donor or spatial constraints in the recipient's abdominal cavity are the main factors to be considered in the segmental transplantation of the small intestine. It was the aim of the following study to gain insight into the functional characteristics of different portions of the small intestine either after partial resection or syngeneic and allogeneic transplantation during the early postoperative period. Nutritional parameters (serum albumin levels, serum triglyceride levels, maltose absorption, excretion of fecal fat) and fat-stimulated neurotensin release were determined in Lewis rats that underwent small bowel resection (n = 21), syngeneic (Lewis-->Lewis, n = 21), or allogeneic transplantation (Brown Norway-->Lewis, n = 24). The length of the remnant, isograft, or allograft was 27 cm (i.e. one third of the rat small intestine) and consisted of the proximal (n = 7), middle (n = 7), or distal (n = 7) portion. Three postoperative deaths were due to ileus or pneumonia. After allotransplantation, cyclosporine (15 mg/kg BW s.c.) was administered for graft acceptance. Controls were unoperated, weight- and age-matched Lewis rats (n = 7). We found that resection of two-thirds of the small intestine led to significantly lower levels of albumin and triglycerides in all the three portions investigated (P < 0.01) but did not affect maltose absorption. Excretion of fecal fat was elevated after distal resection (P < 0.05). When compared to resected animals, syngeneic transplantation did not affect the nutritional parameters, but caused a significantly higher hormone release (P < 0.05) in all three different intestinal grafts. Allogeneic transplantation was successful when the middle or distal portion was grafted. All recipients of proximal allografts showed a severe loss of body weight and died between day 8 and 10 after transplantation. Postmortem examination revealed no signs of acute rejection. When transplantation of short intestinal segments is considered, it is of vital importance to take into account the functional differences and the influence of immunosuppressive drug therapy in the regulatory bowel function.
This study presents data on the fat-stimulated release of cholecystokinin (CCK) in conscious rats 11 and 84 days after one-stage transplantation of the entire small bowel, or of jejunal, jejunoileal, or ileal segments, under syngeneic and allogenic conditions. After allotransplantation, ciclosporin (CsA) was administered for graft acceptance. The results were compared with those in unoperated controls and in animals that had undergone small-bowel resections leaving jejunal, jejunoileal, or ileal remnants. When the entire small bowel was grafted under syngeneic (92.5 +/- 8.3; 106.6 +/- 7.5) or allogeneic (110.5 +/- 5.5; 101.2 +/- 6.9) conditions, CCK release (pg/ml per 60 min) was similar (P > 0.05) to that of the controls (110.3 +/- 9.0; 94.7 +/- 6.8) at both measurement points. Recipients of jejunal or ileal segmental isografts showed a significantly elevated (P < 0.05) output of CCK (jejunal graft: 176.4 +/- 18.5; 125.5 +/- 10.1 -ileal graft: 55.9 +/- 9.0; 30.1 +/- 5.4) compared with corresponding small-bowel resections (jejunal remnant: 69.0 +/- 7.9; 93.5 +/- 3.9-ileal remnant: 16.7 +/- 3.7; 6.6 +/- 1.3). In contrast, the difference was not significant (P > 0.05) when jejunoileal segments were grafted (jejunoileal graft: 74.4 +/- 19.6; 47.0 +/- 10.4-jejunoileal remnant: 50.7 +/- 11.0; 47.0 +/- 11.9). All recipients of jejunal allografts died between day 8 and day 10 after transplantation, due to functional impairment. Two-stage segmental jejunal allotransplantation, with insertion of the graft into the continuation of the gastrointestinal tract in an accessory, non-functional position after 28 days was successful. Due to this technique, we could gather data on day 84. Recipients of jejunal (118.2 +/- 7.6), jejunoileal (87.1 +/- 19.7; 48.6 +/- 9.3), or ileal (48.1 +/- 6.7; 21.6 +/- 4.6) allografts showed no significant (P < 0.05) differences in CCK output compared with isografts, either on day 11 or on day 84. Our data indicate that transplantation of the entire small bowel affects the fat-stimulated CCK release neither in the early postoperative period nor 3 months after transplantation. In contrast, transplantation of jejunal or ileal segmental isografts caused a significantly elevated output of CCK compared with corresponding resection remnants. Immunosuppression with CsA did not affect CCK release after transplantation, but led to functional impairment with fatal outcome when a short jejunal segment was grafted. This could be prevented by applying the two-stage technique.
The influence of the intestinal bile acid content on the secretion of the exocrine pancreas and on the plasma concentrations of the relevant peptides (NT), and CCK is the subject of continuing controversy. Thus the alterations of pancreatic secretion and both hormones during variations of intestinal bile acid content were investigated. Modified Herrera fistulas were implanted in six dogs for analysis of the pancreatic secretions. Intraduodenal application of taurocholate (1.8, 3.6, or 7.2 mM) led to a marked reduction of the pancreatic secretion as well as to a simultaneous decrease of NT and CCK release after stimulation by the intraduodenal instillation of a 20% lipid emulsion. (The integrated protein secretion decreased from 20.1 +/- 1.9 g to 15.2 +/- 1.6 g, NT release dropped from 4970 to 3050 pg/180 min, and CCK from min.) cholestyramine together with the lipid emulsion had the opposite effect. The pancreatic protein as well as NT and CCK release increased. It therefore appears that there is a negative feedback relationship between the postprandial intestinal bile acid content on the one hand, and the secretion of the exocrine pancreas and the regulatory peptides NT and CCK on the other hand. This relationship is independent of any interaction between pancreatic proteases and bile acids.
The immunosuppressive effect of chronic renal failure is correlated with an impaired proliferation of peripheral blood leukocytes in vitro. This is mainly due to an impaired function of the accessory cells rather than the T cells. Here we tried to define a missing accessory signal for T cell activation in hemodialysis patients. We substituted cell surface bound molecules by adding tumor cell lines to the in vitro assays that express different patterns of accessory molecules. Cell lines that express the costimulatory B7 molecule reconstituted the activation of patients' cells whereas B7 negative cells did not. The reconstitution was also achieved using mouse fibroblasts transfected with human B7 or by monoclonal antibodies that stimulate the B7 ligand CD28 on T cells. These data further emphasize that impaired leukocyte function in renal failure is due to an accessory cell defect, and that T cells of these patients have normal functional capacities when they get the costimulatory signals required. We demonstrate that it is the B7/CD28 pathway that reconstitutes cellular functions in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
The 1F7 idiotype previously defined (J Immunol 147:933;1991 and Eur J Immunol 22:1749;1992) is expressed on antibodies reactive to different proteins of HIV (gp41, p24, gp120). Since serum levels of 1F7 (IgM or IgG) are significantly higher in patients with HIV lymphoma as opposed to HIV-infected individuals, normal controls and non-HIV lymphoma patients, we hypothesized the B-cell neoplasms were the source of the idiotype. However, immunohistochemistry on cryostat sections revealed no 1F7 idiotype signal on neoplastic B-cells nor tumor infiltrative T-cells (n = 8). Interestingly, reactive lymphocytosis adjacent to tumor masses and reactive follicular hyperplastic controls (n = 5) exhibited significant 1F7 reactivity. The reactivity appeared in paracortical and perifollicular lymphoid regions, predominantly regions of B, T and antigen presenting cells in lymph nodes or tonsils. A survey of electrophoretically defined paraproteins with anti-HIV specificities derived from HIV-infected patients showed no Western blot reactivity with the 1F7 anti-idiotypic antibody. Therefore, the idiotype does not appear to be a direct product of B-cell neoplasia or abnormal B-cell proliferation, but is produced by B cell clones responding to HIV infection. This high level of serum 1F7 reactivity could be an important clue in the pathogenesis of HIV lymphomas and confers a highly predictive serological test for HIV lymphoma.
Important basic physiological mechanisms of exocrine pancreas secretion were delineated in a canine model. However, dogs have been considered unsuitable for the study of the controversial feedback regulation of exocrine pancreas secretion. The present study reveals a marked modification of pancreas secretion following the intraduodenal instillation of lipase: The postprandial lipase secretion decreases from 2,421 U x 180 min-1 to 1,490 U x 180 min-1, but simultaneously determined cholecystokinin (CCK) concentrations in plasma do not increase under these circumstances. The intraduodenal application of a protease inhibitor (800 mg camostate) significantly stimulates the secretion of the exocrine pancreas in the fasting dog: After 15 min the protein release increased to 133 +/- 30 mg. Intravenous atropine blocks this increase. The plasma concentrations of CCK are not significantly influenced. These results in our canine model show that the secretory activity of the exocrine pancreas depends on the intraduodenal enzyme content. CCK is irrelevant in this context.
The present study compares the effect of organ preservation with Euro-Collins solution, cardioplegic histidine-tryptophan-ketoglutarate solution, and University of Wisconsin solution on immediate pancreatic function after cold storage at 4 degrees C for 24 hr. Postischemic organ quality of a porcine pancreas preparation was tested by quantification of physiological and biomedical parameters in a one-line reperfusion system. During reperfusion with a constant arterial pressure the arteriovenous flow rate was significantly higher for HTK (5.7 +/- 0.91 ml/min, n = 8; P < 0.05 vs. EC) and UW (7.4 +/- 0.81 ml/min, n = 8; P < 0.05 vs. EC) than for EC (3.0 +/- 0.26 ml/min, n = 6). The lowest lactate content in the reperfusate was found after HTK protection (HTK, 64.0 +/- 7.2 mumol/50 ml, n = 8; versus EC, 114.2 +/- 1.7 mumol/50 ml, n = 6, P < 0.001; versus UW, 148.0 +/- 28.6 mumol/50 ml, n = 8, P < 0.05). Amylase in the venous effluent was significantly lower (P < 0.05) for HTK or UW protection than for EC (HTK, 189 +/- 72.6 U/ml; UW, 188 +/- 39.4 U/ml; EC, 416 +/- 71.7 U/ml). Oxygen consumption during reperfusion was significantly higher for HTK (2.15 +/- 0.22 microliters/g/min, P < 0.001) and UW (1.80 +/- 0.52 microliters/g/min, P < 0.05) than for EC (0.47 +/- 0.13 microliters/g/min). We conclude that immediate postischemic organ quality and pancreatic function after protection with HTK is not inferior to preservation with UW.
Antibodies in sera of HIV-1 infected individuals against the HIV-1 core protein (p24), HIV-1 envelope glycoprotein (gp120) and reverse transcriptase (RT) are characterized by a skewed light chain isotype expression. The kappa/lambda ratios of antibodies to p24 and gp120 in infected individuals were found to be unique in each individual, but constant over several years independently from disease progression. The oligoclonal nature of the anti-HIV-1 antibodies suggested by skewed kappa/lambda expression was confirmed with isoelectric focusing of affinity purified antibodies to p24 and gp120. Analysis of the utilization of V gene families in purified anti-p24 and anti-gp120 antibodies revealed a restricted and biased VH gene family usage. In contrast, the utilization of VK gene families appeared to be random. The finding of stable and restricted antibody responses in infected individuals could be one of the causes for the failure to produce antibodies to HIV-1 that are effective against escape virus variants.