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Biomedical subjects

K M Koch

Publications and source records attributed to K M Koch.

At least 91 records · Page 5Linked to original sources
PubMed1996

Interleukin-1 beta stimulates glucose uptake of human peritoneal mesothelial cells in vitro.

To investigate whether the glucose uptake (GU) of human peritoneal mesothelial cells (HPMC) is mediated by glucose transporters and whether this uptake is influenced by interleukin 1-beta (IL-1 beta), we measured 2-deoxy-(3H)-GU of HPMC in vitro, after exposing the cells for different times (two and 12 hours) to increasing concentrations (0.1, 1.0, and 2.0 ng/mL) of IL-1 beta. To exclude a noncarrier-mediated transport, GU was also tested in the presence of cytochalasin B. All experiments were performed in triplicate in the cells of two donors. Cytochalasin B inhibits GU of HPMC almost completely. GU of HPMC is not stimulated by insulin. GU is stimulated by IL-1 beta in a dose-dependent manner. These data indicate a GU of HPMC, which is mediated by a glucose transporter and stimulated by IL-1 beta. The increased uptake of glucose from the dialysate in patients with peritonitis may be mediated by a (cytokine-induced) increased activity of HPMC glucose transporters.

Blood Glucose↗
PubMed1995

Angiotensin-converting-enzyme inhibitors suppress synthesis of tumour necrosis factor and interleukin 1 by human peripheral blood mononuclear cells.

Administration of angiotensin-converting-enzyme (ACE) inhibitors reduce vascular proliferation following endothelial injury as well as progression of renal disease in various animal models. These effects might be due to interference with cytokines such as interleukin 1 (IL-1) or tumour necrosis factor alpha (TNF) since they have been implicated in regulating the effects of vascular cell growth factors such as fibroblast- and platelet-derived growth factors. We investigated the in vitro synthesis of IL-1 and TNF from human peripheral blood mononuclear cells (PBMC) in the presence of various ACE-inhibitors. Captopril dose-dependently suppressed the IL-1 beta-induced synthesis of TNF by 74% (P < 0.01) and the IL-1 beta-induced synthesis of IL-1 alpha by 60% (P < 0.01). Cytokine synthesis induced by lipopolysaccharide was less affected. At concentrations suppressing TNF and IL-1, captopril did not reduce the synthesis of complement C3 in the same cells. Enalapril and cilazapril also suppressed cytokine-induced cytokine synthesis. Ramipril, lisinopril, perindopril and spirapril had no significant effect on TNF synthesis suggesting that the effect was not related specifically to the inhibition of ACE. Accumulation of mRNA for IL-1 and TNF were not affected by captopril, suggesting a posttranscriptional effect. We conclude that certain ACE-inhibitors suppress IL-1 and TNF synthesis at a posttranscriptional level and might therefore influence cytokine-mediated cell growth.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Cytokines in human renal interstitial fibrosis. I. Interleukin-1 is a paracrine growth factor for cultured fibrosis-derived kidney fibroblasts.

We studied the role of interleukin-1 beta (IL-1 beta) and basic fibroblast growth factor (bFGF) in the proliferative response of transformed human renal interstitial fibroblast cell lines established from either a kidney with glomerulonephritis and interstitial fibrosis or a normal kidney in comparison to primary human foreskin fibroblasts. Growth of fibrosis-derived renal fibroblasts was inhibited in the presence of IL-1 receptor antagonist (IL-1Ra) by 35% (P < 0.005), suggesting that these cells produce IL-1 and possess IL-1 receptors as part of paracrine growth. In contrast, spontaneous proliferation of fibroblasts derived from a normal kidney or normal skin were not inhibited by IL-1Ra. In fibrosis-derived but not in normal renal cells, fibronectin synthesis was increased 2.2-fold (P < 0.01) in the presence of IL-1Ra. Addition of exogenous IL-1 beta or bFGF stimulated proliferation of skin fibroblasts. In contrast, growth of fibrosis-derived renal fibroblasts was stimulated by IL-1 beta and unchanged by bFGF. Growth of normal kidney fibroblasts was unaffected by bFGF and inhibited by IL-1 beta. We conclude that compared to normal fibroblasts, fibrosis-derived renal fibroblasts have a different cytokine-response profile, are IL-1-dependent, produce IL-1 as a paracrine growth factor and do not proliferate to bFGF, a classical fibroblast growth factor.

Cell Count↗
PubMed1995

Cytokines in human renal interstitial fibrosis. II. Intrinsic interleukin (IL)-1 synthesis and IL-1-dependent production of IL-6 and IL-8 by cultured kidney fibroblasts.

We compared cytokine production from transformed human fibroblast cell lines derived from either a kidney with interstitial fibrosis or a normal kidney to that from primary human foreskin fibroblasts. Fibrosis-derived as well as normal renal fibroblasts, but not skin fibroblasts, spontaneously produced the chemokine, IL-8, and the growth promoting cytokine, IL-6. Spontaneous IL-8 and IL-6 synthesis by renal fibroblasts was dependent on the intrinsic release of IL-1, since blocking IL-1 receptors with IL-1 receptor antagonist (IL-1Ra) partially inhibited the constitutive production of these cytokines. Both kidney cell lines had detectable mRNA and protein for IL-1 alpha and IL-1 beta. Renal and skin fibroblasts stimulated by picomolar concentrations of exogenous IL-1 or TNF-alpha produced large amounts of IL-6 and IL-8, whereas nanomolar concentrations of basic fibroblast growth factor did not. Fibrosis-derived cells expressed less high affinity IL-1 receptors (600 receptors/cell; KD = 0.6 pM) compared to normal renal fibroblasts (1000 receptors/cell). However, fibrosis-derived renal fibroblasts produce three- to fourfold more IL-8 and IL-6 in response to picomolar concentrations of IL-1 beta compared to cells derived from a normal kidney. As this enhanced production is not due to increased numbers of IL-1 receptors, we speculate that post-receptor responsiveness to either endogenous or exogenous IL-1 is greater in fibrosis-derived renal fibroblasts than in cells from normal kidneys.

Cell Line↗
PubMed1995

Impaired endotoxin-induced interleukin-1 beta secretion, not total production, of mononuclear cells from ESRD patients.

Lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) production and secretion from peripheral blood mononuclear cells (PBMC) were determined in a longitudinal study with repeated measurements in PBMC from patients with chronic uremia not on hemodialysis (N = 8), end-stage renal disease (ESRD) patients (N = 8), and healthy controls (N = 7). ESRD patients were studied while using low-flux Cuprophan dialyzers and again using high-flux AN 69 dialyzers. Total (cell-associated plus secreted) LPS-induced IL-1 beta production was enhanced in uremic patients, but similar to controls in ESRD patients on Cuprophan. In contrast, LPS-induced IL-1 beta secretion (secreted amounts in % of total production) was similar to controls in uremic patients, but significantly reduced in ESRD patients on Cuprophan (P < 0.01). During AN 69 hemodialysis, LPS-induced total IL-1 beta production remained unchanged but IL-1 beta secretion increased significantly (P < 0.05) compared to Cuprophan dialysis. Increased IL-1 beta secretion coincided with a suppression in PGE2 synthesis (P < 0.02). Similarly, blockade of endogenous PGE2 by indomethacin increased LPS-induced IL-1 beta secretion (P < 0.01) but did not enhance total IL-1 beta production in PBMC from controls and patients on Cuprophan hemodialysis. Neither total production nor secretion of TNF alpha was different comparing the three study groups. We conclude that LPS-induced IL-1 beta secretion, but not total production, is impaired in PBMC from ESRD patients on long-term Cuprophan hemodialysis. This functional change in the PBMC response is specific for IL-1 beta, not due to uremia per se but hemodialysis-dependent and reversible. Hemodialysis with AN 69 suppresses endogenous PGE2 synthesis in PBMC which is associated with increased LPS-induced IL-1 beta secretion in the presence of unchanged total IL-1 beta production. We speculate that PGE2 could inactivate the IL-1 beta converting enzyme which is essential for processing and secretion of mature IL-1 beta.

Adult↗
PubMed1995

Minimally invasive diagnosis of renal artery stenosis by spiral computed tomography angiography.

We prospectively compared in a blinded fashion spiral computed tomography angiography (CTA) with arteriography in 62 consecutive patients with suspected renal artery stenosis (RAS). For CTA 150 ml of contrast material were injected intravenously. Arteriography was performed by DSA technique with selective catheterization of renal arteries. Of the 157 visualized renal arteries 155 could be evaluated with DSA and a total of 157 with CTA. Sensitivity of CTA for RAS > or = 50% was 98% and the specificity was 94%. Comparison of the grade of stenosis as evaluated by DSA versus CTA showed: identical gradation in 59 arteries (DSA > or = 50%/CTA > or = 50%), underestimation by CTA in one artery (DSA 50 to 75%/CTA < 50%), and overestimation by CTA in six arteries (DSA < 50%/CTA 50 to 75%). Factors that may contribute to these differences include impaired renal function and possibly "underestimation" of ostial RAS by arteriography. One artery not evaluable by arteriography showed a 70% stenosis by CTA. CTA showed no major side effects. We conclude that CTA has the same accuracy for the diagnosis of RAS > or = 50% as arteriography. However, CTA is only minimally invasive, safe, and causes less discomfort to patients.

Adult↗
PubMed1995

Pathogenetic and diagnostic aspects of dialysis-related amyloidosis.

Dialysis-related amyloidosis (DRA) is a major cause of morbidity in end-stage renal disease patients. While retention of the precursor protein beta 2-microglobulin (beta 2-m) forms the essential basis for DRA, pathogenetic concepts include: qualitative and quantitative alterations in beta 2-m metabolism; local and systemic inflammatory changes, partly related to different treatment modes; general predisposing factors such as age at the onset of dialysis treatment. Clinical and radiological signs, as well as synovial thickening on sonography, suggest the presence of DRA, but histomorphological demonstration of beta 2m-amyloid is required for definitive proof. Scintigraphic imaging of DRA represents an additional, sensitive non-invasive diagnostic tool. Successful kidney transplantation stops the progression of DRA.

Amyloidosis↗
PubMed1995

Biocompatibility in hemodialysis: clinical relevance in 1995.

Hemodialysis therapy for end-stage renal disease is still empirical even after more than 30 years of experience. Although long-term survival can now be assured in selected patients, clinical results tend to be disappointing. Hemodialysis therapy needs to be improved. Zealots of the biocompatibility school believe that this improvement will come from reducing undesirable consequences of blood membrane interaction, particularly complement activation. However, there is controversy over the clinical meaningfulness of biocompatibility when exclusively related to blood membrane interactions. Another dimension needs to be added, namely ultrapure dialysate to avoid subclinical chronic effects of activation of the cytokine cascade by bacterial fragments present in dialysate. While the pathogenesis of acute anaphylactoid reactions are understood and largely preventable, the relation of the chronic syndromes such as amyloidosis to the use of a particular membrane remain unproven. Prospective studies that will occupy at least a decade will be necessary to decide these issues.

Bacterial Toxins↗
PubMed1995

Prevention of glomerular hypertrophy and glomerulosclerosis in Milan normotensive rats by low-protein diet, but not by low-dose captopril treatment.

Milan normotensive rats, which spontaneously develop marked proteinuria (PU) and glomerulosclerosis (GS), were either kept on a normal-protein diet, a normal-protein diet with additional low-dose captopril (CAP), which did not affect blood pressure, or on a low-protein diet. After 8 months PU (79 +/- 25 mg/day) GS (3 +/- 2%) and total glomerular volume (TGV; 27.9 +/- 2.9 mm3/kidney) were significantly lower (p < 0.05) in the low-protein diet group than in both the normal-protein group (PU 583 +/- 210 mg/day, GS 12 +/- 5%, TGV 34.6 +/- 8 mm3/kidney) and the low-CAP group (PU 611 +/- 224 mg/day, GS 16 +/- 6%, TGV 41.8 +/- 8.6 mm3/kidney). In conclusion, the development of glomerular hypertrophy and GS in Milan normotensive rats was reduced by the low-protein diet, but not by low-CAP treatment.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Basic fibroblast growth factor augments podocyte injury and induces glomerulosclerosis in rats with experimental membranous nephropathy.

Podocyte injury is believed to contribute to glomerulosclerosis in membranous nephropathy. To identify the factors involved, we investigated the effects of basic fibroblast growth factor (bFGF), a cytokine produced by podocytes, on rats with membranous nephropathy (passive Heymann nephritis [PHN]). All rats received a daily i.v. bolus of 10 microg bFGF or vehicle from days 3-8 after PHN induction. In proteinuric PHN rats on day 8, bFGF injections further increased proteinuria. Podocytes of bFGF-injected PHN rats showed dramatic increases in mitoses, pseudocyst formation, foot process retraction, focal detachment from the glomerular basement membrane, and desmin expression. bFGF injections in PHN rats did not alter antibody or complement deposition or glomerular leukocyte influx. bFGF-injected PHN rats developed increased glomerulosclerosis when compared with control PHN rats. Also, bFGF induced proteinuria and podocyte damage in rats injected with 10% of the regular PHN-serum dose. None of these changes occurred in bFGF-injected normal rats, complement-depleted PHN rats or rats injected with 5% of the regular PHN serum dose. These divergent bFGF effects were explained in part by upregulated glomerular bFGF receptor expression, induced by PHN serum. Thus, bFGF can augment podocyte damage, resulting in increased glomerular protein permeability and accelerated glomerulosclerosis. This bFGF action is confined to previously injured podocytes. Release of bFGF from glomerular sources (including podocytes themselves) during injury may represent an important mechanism by which podocyte damage is enhanced or becomes self sustained.

Animals↗
PubMed1995

Pre-transplant hypertension: a major risk factor for chronic progressive renal allograft dysfunction?

Despite of advances in 1-year survival rates of renal allografts, no comparable achievements have been made in long-term graft survival. To identify risk factors for chronic progressive renal allograft dysfunction we conducted a retrospective study in 639 patients transplanted between 1983 and 1990. Graft function was assessed by the slope of individual 1/creatinine regression lines and chronic progressive graft dysfunction was defined as a slope of the 1/creatinine line of > 0.1 dl/mg/year, indicating a loss of glomerular filtration rate of > 10 ml/min/year regardless of the initial serum creatinine value. A number of possible risk factors were determined and analysed by linear regression analysis. One hundred and six patients (16.6%) showed chronic progressive graft dysfunction. No correlation was found between the rate of functional deterioration and the age and gender of the donor or the recipient, the blood group, the prevalence of hepatitis B or C, the number of blood transfusions, the total ischaemia time, or the number of kidneys from female donors grafted into male recipients. Chronic progressive graft dysfunction was associated with the number of HLA-B/DR mismatches (P = 0.04) and with a first acute rejection episode later than 60 days after transplantation (P < 0.001). Chronic progressive graft dysfunction also occurred in the absence of an acute rejection episode. Significantly (P < 0.001) more patients with chronic progressive graft dysfunction were hypertensive not only 12 months after transplantation, but also at the time of transplantation, indicating that hypertension may not only be secondary to deteriorating graft function, but that hypertension per se leads to graft damage and initiates chronic progressive graft dysfunction. All efforts should be made to control blood pressure adequately to improve long-term survival of renal allografts.

Adult↗
PubMed1995

The role of plasma coating on the permeation of cytokine-inducing substances through dialyser membranes.

We studied the effects of coating of dialyser membranes with plasma proteins on the permeation of bacteria-derived cytokine-inducing substances (CIS). An in vitro dialysis circuit using polysulphone (PS) or modified cellulose triacetate (mCT) dialysers was used. Precoating of the dialysers was performed by recirculation of 10% normal human plasma for 30 min in the blood compartment and subsequent rinse with pyrogen-free saline. Samples from the blood compartment were tested for induction of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF alpha) at various time points after challenging the dialysate with sterile culture supernatants from Pseudomonas aeruginosa. Contamination of the dialysate resulted in the appearance of CIS in the blood compartment of both polysuphone modified cellulose triacetate (IL-1 alpha: PS, time 0: 81 +/- 11 pg/ml, time 60 min: 4747 +/- 1822 pg/ml, P < 0.05; mCT, time 0: 235 +/- 141 pg/ml, time 60 min: 1632 +/- 531 pg/ml, P < 0.05). The plasma protein layer reduced the penetration of CIS significantly only for polysulphone (IL-1 alpha: PS, time 60: 4747 +/- 1822 versus 880 +/- 525 pg/ml, P < 0.05; modified cellulose triacetate, time 60 min: 1632 +/- 531 pg/ml versus 930 +/- 326 pg/ml). Samples from the blood compartment contained < 6 pg/ml LAL-reactive material at all time points. We conclude that plasma coating of polysulphone dialysers reduces the permeability for CIS derived from Pseudomonas, either by reducing the effective pore size or by adsorption of proteins that bind CIS.(ABSTRACT TRUNCATED AT 250 WORDS)

ADP Ribose Transferases↗
PubMed1995

The use of epoetin beta in anemic predialysis patients with chronic renal failure.

UNLABELLED: Two clinical studies were conducted to investigate the efficacy and safety of epoetin beta in 266 [corrected] anemic predialysis patients. Epoetin beta was administered subcutaneously either daily or thrice weekly. Mean duration of treatment was 211 days (interquartile range: 105 to 350 days). RESULTS: Renal anemia could be corrected and the regular transfusion need could be eliminated in all patients. There was no difference in the dose requirement per week between daily and thrice weekly administration of epoetin beta. Regarding the entire study population, there was no acceleration of the progression of renal failure during epoetin beta treatment nor were there any notable changes in laboratory values other than retention values. Epoetin beta was safe and well tolerated; the most important adverse event was the development or aggravation of hypertension.

Adult↗