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Biomedical subjects

H Köhler

Publications and source records attributed to H Köhler.

At least 253 records · Page 14Linked to original sources

Distribution of Goodpasture antigens within various human basement membranes.

Collagenase-digested basement-membrane preparations from human kidney glomeruli, kidney tubules, lung, choroid plexus, aorta, intestine, and placenta were analysed according to their reactivity to anti-glomerular basement membrane (anti-GBM) antibody-positive Goodpasture sera. Sodium dodecylsulphate polyacryl gel electrophoresis (SDS-PAGE), and immunoblotting were performed after antigen enrichment by passage of the collagenase digests through an anion-exchange column. Reactivity of anti-GBM antibodies with one to three monomers (24, 26 and 28 kD) and two dimers (44 and 50 kD) were demonstrated in basement membrane preparations of kidney glomeruli, kidney tubules, lung, placenta, and aorta. In basement membranes of choroid plexus reactivity with only the 28 kD monomer and the 50 kD dimer were identified. In intestinal basement membrane, reactivity was restricted to the 50 kD dimer. Analysis of the amounts of Goodpasture antigen by inhibition ELISA demonstrated that the highest concentration were in glomerular basement membrane, while the lowest were found in aortic basement membrane. The results indicate that Goodpasture antigens are common to all the basement membranes investigated. The differences in antigen concentration and in reactivity on immunoblotting may indicate different antigen amounts, a heterogeneity of collagen IV within the various basement membranes, or differences in antigen accessibility within the membranes. We conclude that the primary clinical restriction of the anti-GBM disease to lungs and kidneys is not explained by a preservation of the antigen to this basement membrane. Rather, the clinical pattern may be influenced by differences in the molecular composition of the basement membranes as well as by non-immunological mechanisms.

Anti-Glomerular Basement Membrane Disease↗

Urinary secretory immunoglobulin A in acute renal allograft rejection.

Periodical determinations of the urinary secretory immunoglobulin A (S-IgA) excretion rate were performed in 12 cadaveric graft recipients. In five patients with primary functioning grafts the S-IgA excretion on the first postoperative day was 4.2 +/- 2.6 mg/g creatinine, decreasing to 1.8 +/- 1.2 mg/g creatinine (P less than 0.05) at the day of discharge. Acute tubular necrosis developed in the seven remaining patients. In this group the initial S-IgA excretion was 12.6 +/- 7.5 mg/g creatinine (P less than 0.05 compared to the former group), decreasing to 2.0 +/- 0.9 mg/g creatinine (P less than 0.05) at discharge. An acute rejection episode was observed in six patients. The S-IgA excretion increased from 3.0 +/- 1.5 mg/g creatinine 3-4 days before rejection to 6.4 +/- 3.1 mg/g creatinine (P less than 0.05) 1-2 days before rejection, and peaked at 14.0 +/- 8.6 mg/g creatinine (P less than 0.05) when the diagnosis of rejection was established and anti-rejection treatment was started. In three patients the initial steroid pulse therapy was not successful and S-IgA excretion further increased to 29.0 +/- 15.6 mg/g creatinine. After successful anti-rejection treatment, using steroids and OKT3, the S-IgA excretion decreased to 3.4 +/- 2.6 mg/g creatinine. In acute graft rejection, the elevated globulin synthesis by infiltrating plasma cells. In the early phase of rejection, dimeric IgA is the only immunoglobulin able to penetrate into the urine by transepithelial transport after binding to secretory component expressed on tubular epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Preservation of the porcine pancreas with HTK and Euro-Collins solution: studies in a reperfusion system.

The present study compares the preservation of the porcine pancreas by the standard Euro-Collins solution or the cardioplegic histidine-tryptophan-ketoglutarate solution (HTK). The explanted pancreas was stored at 4 degrees C for 6 and 24 h respectively, following which organ quality was assessed in a reperfusion chamber measuring physiological and biomedical parameters. After 6 h ischaemia, the amount of lactate was significantly lower when HTK was used for protection. Other parameters like insulin release, amylase release, vascular resistance and oxygen consumption of the pancreas did not indicate a significant difference. Protection with HTK significantly improved pancreas preservation after 24 h ischaemia: lactate content in the reperfusate was lower (HTK: 64.0 +/- 7.2 mumol 50 ml-1 n = 8, v. EC: 114.2 +/- 1.7 mumol 50 ml-1, n = 6), the arteriovenous flow rate was higher (HTK: 5.7 +/- 0.91 ml min-1 v. EC: 3.0 +/- 0.26 ml min-1), and the pancreatic oxygen consumption was increased (HTK: 2.15 +/- 0.22 microliter O2 min-1 g-1 v. 0.47 +/- 0.08 microliter O2 min-1 g-1). We conclude that pancreas preservation can be improved in vitro by protection with HTK solution.

Amylases↗

Influence of thymopentin on antibody response, and monocyte and T cell function in hemodialysis patients who fail to respond to hepatitis B vaccination.

We investigated the influence of thymopentin as an adjuvant for hepatitis B vaccination on in vitro monocyte and T cell function and in vivo antibody response in a prospective, placebo-controlled double-blind trial in 20 low- and nonresponders to hepatitis B vaccination on chronic hemodialysis. 50 mg thymopentin was given subcutaneously twice per week for 3 weeks, followed by 1 intramuscular injection of 40 micrograms HB-Vax and 3 subsequent injections of thymopentin. After 1 month, the patients were boostered with 40 micrograms HB-Vax. There was no significant difference in T cell and monocyte function after administration of thymopentin, as determined in vitro. After 3 months, 3 patients in the placebo and 2 patients in the thymopentin group had antibody titers greater than 10 U/l. In both groups only patients with normal or slightly impaired monocyte function responded to vaccination. Thus, we were not able to demonstrate a beneficial effect of thymopentin on hepatitis B vaccination in nonresponders on chronic hemodialysis. Furthermore, functional tests were not able to identify a subpopulation of uremic nonresponders who would benefit from thymopentin.

Adjuvants, Immunologic↗

Uremic serum inhibits monocyte-dependent, but not interleukin-2-dependent steps of T cell proliferation.

We examined the influence of uremic serum on antigen receptor triggered T cell proliferation in dialysis patients with impaired immune function, i.e., 12 nonresponders to hepatitis B vaccination. The dialysis patients showed a monocyte dysfunction and an increased responsiveness to interleukin 2 (IL-2) according to our previous findings. In vitro the addition of IL-2 completely reconstituted the defect. Uremic serum inhibited monocyte-dependent T cell proliferation of patients and of healthy controls. Contrary, monocyte-independent steps of T cell proliferation were not impaired by uremic serum. When IL-2 was added to cultures, the T cell proliferation in the presence of uremic serum was even enhanced. We conclude that uremic immunodeficiency may be enhanced by soluble factors present in uremic serum which inhibit monocyte-dependent steps of T cell proliferation.

Adult↗

Contribution of neurotensin to the entero-pancreatic axis.

Plasma neurotensin concentrations are markedly elevated in patients with severe exocrine pancreatic insufficiency. We therefore investigated whether the exocrine pancreatic function could influence postprandial neurotensin plasma concentrations. Subsequently, we tested the hypothesis that this peptide hormone is involved in regulation of pancreatic secretion. When pancreatic juice is diverted from modified Herrera fistulas in dogs, a simultaneous application of physiological amounts of lipase reduces the elevated plasma neurotensin concentrations. On the other hand, immunoneutralisation of the circulating neurotensin inhibits pancreatic secretion. This suggests a physiological role of neurotensin in the regulation of the exocrine pancreas via an entero-pancreatic axis.

Animals↗

[Diaphragmatic injuries, classification and therapy].

Injuries of the diaphragm are caused either by direct or indirect violence. In all such ruptures various portions of the abdominal viscera may have ascended into the thoracic cavity. The clinical manifestations are unpredictable and of infinite variety, and especially in massively traumatized patient masked by other injuries. A presumptive preoperative diagnosis of diaphragmatic injury from chest x-ray findings is only possible in about 50% of the cases. In other cases the diagnosis can be confirmed by water.soluble contrast enema into the stomach or colon. Rupture of the diaphragm is a strong indication for operation. In cases of fresh rupture we attempt repair of the diaphragm through a laparotomy incision. In old diaphragmatic rupture we prefer a thoracotomy incision.

Diagnosis, Differential↗

[Pancreatico-pleural fistula. Clinical aspects and therapy of a rare disease entity].

We report of 2 patients with pancreatic-pleural fistulas in chronic pancreatitis. In both cases abdominal symptoms were missed, the primary clinical manifestation was a recurrent pleural effusion with a high content of amylase. Endoscopic retrograde cholangiopancreaticography is necessary for a precise evaluation of the fistula and is indispensable to the surgical therapy. Computed tomography and ultrasonography showed in both cases a pancreatic pseudocyst. Our recommendation is surgical therapy when the fistula is not closed spontaneously within 2 weeks. Both patients were successfully treated by a left pancreatectomy.

Adult↗

[Bacteriuria].

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Anti-Bacterial Agents↗

Antibodies to cytoskeletal components in patients undergoing long-term hemodialysis detected by a sensitive enzyme-linked immunosorbent assay (ELISA).

To date only a few contradictory reports concerning the incidence of autoantibodies in patients undergoing long-term hemodialysis exist. The aim of the present study was to investigate the sera drawn from 45 patients with chronic renal failure, 39 of them on chronic hemodialysis (duration 1-17 years). Serum samples were tested for 15 autoantibodies, no antinuclear antibodies or antibodies to extractable nuclear antigens could be detected; all sera were also negative for antibodies to dsDNA, mitochondria, gastric parietal cells and smooth muscle. In contrast a high incidence of antibodies to cytoskeletal components could be demonstrated using a sensitive enzyme-linked immunosorbent assay that employed purified antigens. Antibodies of IgG-type (IgM-type shown in brackets) were detected against cytokeratin in 51.3% (15.4%), actin in 17.9% (5.1%), desmin in 28.2% (17.9%), vimentin in 15.4% (5.1%) and tropomyosin in 12.8% (5.1%) of the sera of patients on chronic hemodialysis. No association with diagnosis, duration of hemodialysis, age or interdialytic changes of body weight and antibody titers could be found. In a control group of 82 healthy blood donors no antibodies were detected. Positive correlations of incidence of antibodies to actin, desmin, vimentin and keratin suggests polyclonal activation of immune system in patients with chronic renal failure undergoing long-term hemodialysis. The mechanism is unknown.

Autoantibodies↗

[Multiple osteoarticular complications (dialysis-associated spondyloarthropathy) and carpal tunnel syndrome in chronic hemodialysis].

During a nine-year treatment by haemodialysis for renal failure a now 57-year-old woman developed multiple complications of the skeletal system. Acute calcific periarthritis of the right shoulder became manifest one year after the start of the haemodialysis, followed the next years by progressive arthropathy with subchondral amyloid cysts of both shoulders, effusions in the knee-joint and destructive spondylarthropathy of the middle vertebrae. Carpal-tunnel syndrome also occurred, caused by a beta 2-microglobulin amyloidosis (beta 2-microglobulin concentration in serum 42.6 ng/l) and an aluminium osteopathy. These multiple complications, observed here in one patient, are each of them typical long-term complications of chronic haemodialysis.

Carpal Tunnel Syndrome↗

Tumor idiotype vaccines. VI. Synergistic anti-tumor effects with combined "internal image" anti-idiotypes and chemotherapy.

Anti-Id antibodies that have biologic activity as stimulators of specific immunity have been used in experimental vaccines and tumor protection models. However, very little is known about the therapeutic potential of anti-Id antibodies in animals and men. In this study we explored the combination of anti-Id and chemotherapy in a murine tumor system for which we had previously generated protective anti-Id mAb. First, we investigated various protocols by using a protective anti-Id in active immunization. Mice preimmunized before tumor transfer and challenged again after tumor survived significantly longer. Next, we explored the use of soluble anti-Id as immunostimulator in tumor-bearing mice. Although this treatment did not induce long-term survival, it significantly increased survival time. Interestingly, this anti-Id effect was dose dependent, whereby large and small doses had no effect. Finally, stimulatory anti-Id therapy and cyclophosphamide (Cy) treatment was combined. Tumor bearing mice were given a single dose of Cy followed by different doses of soluble anti-Id. The optimal effect on tumor growth and survival was achieved with 80 mg/kg Cy and 10 micrograms/mouse of anti-Id, where 80% of mice survived longer than 100 days. These results provide guidelines for developing clinical protocols for cancer patients by using combination therapy of anti-Id and chemotherapy.

Adjuvants, Immunologic↗

[In vivo effects of high density lipoprotein rich serum fractions (HDLF) in the human. 1. Modification of circulating thrombocyte aggregates, cardiovascular parameters and lipid metabolism by HDLF].

By means of the modified Cohn-method 6 Cohn-IV-1-fractions were prepared in the small pool technique as sterile, pyrogen-free and HDL-rich serum fractions (HDLF), the HDL-concentrations of which were 15-20 g/l. In in-vitro investigations they inhibited the spontaneous aggregation of erythrocytes as well as the ADP-induced aggregation of thrombocytes and activated the molar and fractional initial cholesterol estirification rates as well as the prostacyclin synthesis. From HDLF intravenously applied in people as immediate effects result significant decreases of the cardiac pre- and afterload, an increase of the cardiac ejection fraction as well as a complete dissolution of circulating aggregates of thrombocytes. In 35 patients with hyperlipidaemias after infusion of 100 ml HDLF up to the 5th day increasing and for 14 days remaining increases of concentration of biliary bile acids, total phospholipids and of cholesterol were observed in lithogenic indices remaining in the normal region. The plasmatic lipo- and apolipoproteins reacted with increases, decreases or constancy of concentration which might be based on the different ethryopathogeneses of the hyperlipoproteinaemias.

Cholesterol, HDL↗

[In vivo effects of high density lipoprotein rich serum fractions (HDLF) in the human. 2. Effect of repeated HDLF infusions on atherogenic risk factors and arteriosclerotic vascular changes in patients with and without hyperlipoproteinemia].

10 patients with hyperlipoproteinaemia and 4 normolipaemic smokers with angiographically proved arteriosclerosis of different degrees of severity were infused in 2-week intervals 100 ml HDL-rich Cohn-IV-1 fractions each. After the infusion for 5 days essential phospholipids were injected and a permanent medication with cholestyramin and a choleretic drug were prescribed. In the patients with HLP increases of concentration, decreases of concentration, constancy of the plasma lipids and apoproteins independent of the phaenotype of the HLP as well as an improvement of the state of the antioxidant state were observed. In 6 of 10 patients in reproducible vascular areas regressions of athero- und arteriosclerotic findings could be made evident. Progressions were not observed also in extremely changed arteries in contrast to the normolipaemic smokers and the patients of the control group.

Arteriosclerosis↗

[Surgical therapy of chronic pancreatitis].

From a series of 411 surgical operations in chronic pancreatitis patients, 142 were analyzed with respect to indication, early and late mortality, and results. Average follow-up time was 10 years. Resective procedures were used in 51 patients and drainage in 24. Late mortality was twice as high for drainage (19%) as for resection (7.5%). The subjective late results were best for resection, since in these cases relapse occurred only in 16% and improvement of symptoms in 79%; for drainage the improvement rate was only 65% and the recurrence rate 39%. Drainage was followed by latent or manifest diabetes in 21% of cases, and resection in 63%. Deterioration of exocrine pancreas function was observed in 29% of resections but in only 14% of drainages. These data indicate that prognosis of the disease depends on the surgical procedure as well a withdrawal of alcohol.

Drainage↗

Perturbation of the idiotypic network. I. Induction with multiple alloantigen stimulation.

The effect of hyperimmunization on the immune network with allostimulated syngeneic lymphocytes responding to different haplotypes was analyzed. Ten different haplotypes were used to stimulate syngeneic donor mice. Control mice were multiply immunized with incomplete Freund's adjuvant alone or with syngeneic mixed lymphocyte culture-generated lymphocytes. BALB/c mice were immunized consecutively with alloreactive blasts or allogeneically stimulated spleen cells at 10-day intervals. After a rest period of 2 months, the ratio of T helpers to T suppressors was determined by immunofluorescent staining. The functional network was probed by immunizing the mice with phosphorylcholine (PC) coupled to hemocyanin. The sera were analyzed for anti-PC antibodies and TEPC15 (T15) idiotypic expression. The results demonstrated (i) a decrease in the level of anti-PC antibody titer and T15 idiotypic expression; (ii) a decrease in the number of T helper cells and an increase in the number of T suppressor cells; (iii) a loss of PC epitope specificity; (iv) an increase of IgM antibodies expressing T15 without anti-PC specificity; and (v) an elevated level of preimmune lymphocyte proliferation and Ig secretion. These results reveal a functional network linkage in the regulation of alloreactivity and antigen response and show how repeated exposure to alloantigens can induce a perturbation of the idiotypic network controlling the response of a non-alloantigen-related BALB/c strain dominant idiotype (T15).

Animals↗