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J Floege

Publications and source records attributed to J Floege.

134 records · Page 8Linked to original sources
PubMed1988

Detection of endotoxin-like interleukin-1-inducing activity during in vitro dialysis.

In order to study the integrity of dialysis membranes to pyrogens, the dialysate side of a closed loop hemodialysis (HD) circuit was challenged with E. coli microfiltrate containing 500 ng/ml endotoxin. Three solutions, a) tissue culture medium/saline, b) 5% human serum albumin, and c) 10% fresh human plasma, were circulated in the blood loop for five hours. Samples drawn from the blood side were assayed for interleukin-1 (IL-1)-inducing activity on human mononuclear cells (MNC) in vitro. No IL-1-inducing substances were detected when saline or culture medium was circulated in the blood loop. Circulating 5% human serum albumin revealed IL-1-inducing activity in the samples drawn only after five hours of HD. However, the addition of 10% fresh human plasma to the blood side resulted in the appearance of an IL-1-inducing substance(s) after 15 minutes of HD. After 30 minutes, maximum IL-1-inducing activity was observed (control stimulation index, 3.30 +/- 0.67 SEM vs. 7.59 +/- 1.50, P less than 0.02). The IL-1-inducing activity of the samples was completely inhibited by polymyxin B, a cationic antibiotic which blocks the IL-1-inducing activity of endotoxin. Additional experiments demonstrated that in vitro MNC IL-1-production induced by the same E. coli microfiltrate is enhanced in the presence of 10% plasma. These studies demonstrate that: (a) in the presence of plasma, IL-1-inducing factors pass into the blood compartment of a dialysis system challenged with bacterial pyrogen; and (b) MNC production of IL-1 is enhanced in the presence of plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Endotoxins↗
PubMed1988

Beta 2-microglobulin kinetics during haemofiltration.

To study the kinetics of beta 2-microglobulin during haemofiltration, seven patients with end-stage renal failure were treated with the AN 69 (acrylonitrile), Duo-Flux (cellulose acetate) and F 60 (polysulphone) haemofilter. Low beta 2-microglobulin sieving coefficients and a highly negative filter mass balance error were observed during the initial phase of treatment with AN 69 but not with Duo-Flux or F 60, indicating a high degree of beta 2-microglobulin adsorption by AN 69. Total removal of beta 2-microglobulin was calculated by addition of the total amount adsorbed by the membrane and the total amount recovered in the collected ultrafiltrate. With AN 69 and F 60, total removal of beta 2-microglobulin amounted to 393 +/- 135 (SD) and 316 +/- 35 mg per treatment, while total removal with Duo-Flux was 242 +/- 79 mg per treatment. Thus, highly permeable membranes such as AN 69 or F 60 used in a haemofiltration mode may nearly balance the presumed generation of beta 2-microglobulin in uraemic patients. During treatment, an increase of the calculated beta 2-microglobulin distribution volume occurred with all three membranes, probably representing extra-to-intracellular water shifts. The water shifts occurring during haemofiltration reduce the value of precision of beta 2-microglobulin kinetics and limit the value of the plasma level decrease as an index of beta 2-microglobulin removal.

Acrylonitrile↗
PubMedDate not supplied

Imaging techniques in the diagnosis of dialysis-related amyloidosis.

beta(2)-microglobulin amyloidosis (A beta(2)M) is a major determinant of morbidity in patients on dialysis treatment. Symptoms of A beta(2)M amyloid are mainly related to (peri-)articular amyloid deposition. Imaging techniques [i.e., joint ultrasonography, X-ray, computed tomography (CT), or magnetic resonance imaging (MRI) findings], as well as conventional bone scans, are helpful in the screening of local lesions but are relatively nonspecific and/or not sensitive enough. Scintigraphic techniques using radiolabeled serum amyloid P component (SAP) or the radiolabeled A beta(2)M precursor protein, beta(2)M, generate more specific results. A beta(2)M deposits have been visualized in several long-term hemodialysis patients by using (123)I-labeled SAP. However, this scan did not show tracer accumulation in some frequently involved sites such as hips or shoulders, and frequently labeled the spleen, which is usually spared from A beta(2)M deposits. Improvements in technical sensitivity and specificity could be achieved by scanning with (131)I-labeled beta(2)M: this technique detected tracer accumulations corresponding to the typical distribution pattern of A beta(2)M. Further, both the radiation exposure and the optical resolution of this latter scan have been refined by substituting (111)In for (131)I. In a final step we generated recombinant human beta(2)M (rh beta(2)M). While (111)In rh beta(2)M again failed to show significant tracer accumulation over joint regions in patients on short-term hemodialysis without evidence of A beta(2)M, local tracer accumulations similar to those observed with natural, (111)In-labeled beta(2)M could be demonstrated in long-term hemodialysis patients with evidence of A beta(2)M. In conclusion, scintigraphy for A beta(2)M with (111)In-labeled rh beta(2)M provides a homogeneous and safe recombinant protein source and represents a suitable detection method of beta(2)M amyloid deposits in dialysis patients.

Amyloidosis↗
PubMedDate not supplied

Rodent models of nephropathy associated with type II diabetes.

End-stage renal disease from diabetic nephropathy, mainly due to type II diabetes, is an increasing problem in Western countries. The pathogenesis of diabetic nephropathy is still incompletely understood and much of the experimental insight has been obtained from insulinopenic animal models, resembling type I diabetes. This review therefore aims to describe available rodent models of nephropathy associated with type II diabetes. The review focusses on the metabolic as well as renal functional and structural changes. The usefulness of these rodent models to study renal involvement in type II diabetes is discussed with particular emphasis on confounding factors such as hyperlipidemia, hypertension, immunologic abnormalities, urogenital structural abnormalities and other associated pathological conditions. In addition recent observations on two rat strains, the obese Zucker (fatty) and Goto Kakizaki (GK) rat, are discussed in detail.

Animals↗
PubMedDate not supplied

Present and future therapy options in IgA-nephropathy.

Over the last 5 years the evidence base for therapeutic approaches in patients at risk for progressive IgA-nephropathy (IgAN) has markedly improved. In addition to several studies with low power, two randomized controlled trials suggest that in patients with preserved renal function, i.e. a GFR above 70 ml/min, corticosteroid-therapy can effectively prevent the development of progressive renal failure, whereas in patients with already impaired renal function, combination therapy consisting of cyclophosphamide, azathioprine and corticosteroids was effective. However, so far no study has firmly established that such immunosuppressive therapy is indeed superior to aggressive supportive therapy as it is available nowadays, i.e. high dose ACE-inhibitors and/or angiotensin-II receptor blockers, smoking cessation etc. It therefore appears prudent to first institute such supportive therapy and to limit immunosuppressive therapy to those patients, who maintain a proteinuria above 1 g/day or exhibit a progressive decline of GFR despite optimal supportive measures. Based on pathogenetic insights derived from experimental studies, antagonism of platelet-derived growth factor-B or -D provides an attractive and possibly more specific therapeutical alternative to immunosuppression. While clinical studies testing this new approach are about to start, the development of other novel therapeutic approaches is greatly hampered by the lack of sufficient animal models of IgAN. In this respect a recently described primate model of IgAN offers some hope for the future.

Animals↗
PubMedDate not supplied

PDGF-BB, but not PDGF-AA, stimulates calcium mobilization, activation of calcium channels and cell proliferation in cultured rat mesangial cells.

The effects of different isoforms of platelet-derived growth factor (PDGF) on cellular growth and on cytoplasmic Ca2+ levels in mesangial cells using a microfluorometric system and the calcium indicator FURA-2 were investigated. A rapid increase of cytoplasmic calcium in response to PDGF-BB was found and in the presence of 1.25 mM extracellular calcium, the resting level of cytoplasmic calcium following the initial peak was significantly increased compared with a calcium-free medium, but was completely attenuated with the calcium channel blocker verapamil (50 microM). PDGF-AA did not cause any increase in cytoplasmic calcium. In growth arrested MC PDGF-BB, but not PDGF-AA, also enhanced cell growth. It is concluded that cultured rat mesangial cells react to PDGF-BB but not to PDGF-AA with a rapid mobilization of intracellular calcium followed by subsequent activation of calcium channels and a stimulation of cell growth. A PDGF-BB driven mechanism for MC proliferation in inflammatory and metabolic glomerular diseases is suggested.

Animals↗