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Biomedical subjects

H W Birk

Publications and source records attributed to H W Birk.

12 recordsLinked to original sources
PubMed1997

Renal disease in lymphatic filariasis: evidence for tubular and glomerular disorders at various stages of the infection.

Brugia malayi-infected patients, endemic normals with high levels of specific antibodies and European controls were investigated for kidney disorders by noninvasive techniques. Groups of patients with filarial infections included asymptomatic, microfilaraemic cases (group 1), patients with filarial fever (group 2) and with obstructive filariasis (group 3). Several patients underwent a treatment course with diethylcarbamazine (DEC) when blood and urine samples were collected. Urine samples were investigated for proteinuria and analysed by SDS-PAGE to discriminate between proteinurias caused by tubular and glomerular disorders. In addition, urine levels of alpha-1 microglobulin, of the brush border antigen gp400 and of N-acetyl-beta-glucosaminidase (NAG) activity were determined as indicators of tubular disorders, the albumin content of the urines served as indicator of glomerular alterations. IgG rheuma factors were also determined in the serum as possible reasons for glomerulonephritis. Neither in the endemic normals nor in the European controls there was evidence for kidney disorders. Infected patients had significantly increased proteinuria compared to controls. There were no significant differences between the 3 groups of infected persons, although the mean protein levels were highest in cases with chronic disease and lowest in asymptomatic patients. Quantitative urine analyses and results of accompanying tests suggest predominantly tubular but generally relatively weak disorders in asymptomatic infections; abundant involvement of the kidney which involves both compartments of the organ in the course of filarial fever; and partly severe and probably chronically progredient kidney alterations, which predominantly affect the glomerula in symptomatic cases. IgG rheuma factors do not seem to play a role in filarial infection associated renal disease. DEC-treatment indeed did not significantly alter degree and character of the proteinuria, but relatively high albumin levels in the urine of treated persons yet suggest increased glomerular disorders in these cases. In conclusion, renal disease appears to be a common event in Brugia filariasis; involving both the tubular and glomerular compartment of the organ its pathogenesis is obviously complex and not only immune complex-mediated.

Acetylglucosaminidase↗
PubMed1995

Protein adsorption by artificial membrane materials under filtration conditions.

Elevated plasma levels of numerous low molecular weight proteins (LMWP) in renal insufficiency are likely to contribute to the uremic syndrome. Dialysis-related amyloidosis, caused by the accumulation of beta 2-microglobulin (beta 2M), has highlighted the need for a renal replacement therapy that allows the elimination of LMWP in addition to small solutes. Synthetic membrane materials employed under hemofiltration conditions proved to be most effective in lowering elevated beta 2M plasma levels. In addition to convection, protein adsorption to artificial membrane materials is an important mechanism for beta 2M removal. Using an in vitro setup, 12 commercially available hemofilters representing 11 different membrane materials were perfused with human blood containing 125I-labeled plasma proteins. Under filtration conditions, total protein adsorption ranged from 338-2,098 mg/m2 of membrane surface, and the fraction of adsorbed LMWP varied between 14-70% of total protein adsorption and was negatively correlated to total protein adsorption. beta 2M adsorption showed up to an 8-fold difference between membranes, and was negatively correlated with total protein adsorption and positively correlated with the adsorption of LMWPs.

Adsorption↗
PubMed1993

Monoclonal antibodies against luminal membranes of renal proximal tubules which are kidney-specific.

After immunization with porcine brush-border membrane proteins, 11 monoclonal antibodies were generated which react with proximal tubules. Their antigenic polypeptides were characterized with respect to apparent molecular weight, histochemical localization in porcine and human kidney, and tissue distribution in pig. In porcine kidney, six antibodies bind selectively to the proximal tubule whereas the others also react with other nephron segments. With the exception of one antibody which reacts with the luminal and the basolateral membrane of the porcine proximal tubule, the other antibodies specific for the proximal tubule only stain the brush-border membrane. Four of them react along the entire length of the porcine proximal tubule, whereas one (R1A2) binds to the S3-segment in pig and to the entire length of the proximal tubule in man. This indicates that segment-specific expression may be species-dependent. Testing the antibodies in 21 different extrarenal tissues it was found that three of the antibodies, specific for the brush-border membrane in renal proximal tubules, only react in kidney. Two of these are specific for pig kidney whereas one also reacts with human kidney. This antibody (N4A4) is directed against a polypeptide with an apparent molecular weight of 400,000. Electron microscopic immunohistochemistry showed that N4A4 binds to the intervillus region of the brush-border membrane and to subapical vesicles.

Animals↗
PubMed1991

Analysis of Na+-D-glucose cotransporter and other renal brush border proteins in human urine.

A sensitive quantitative radioimmunoassay is described by which different antigens in the urine can be assayed simultaneously. Urinary excretion of three proteins from proximal tubules was compared: 1) the Na+-D-glucose cotransporter from brush border membranes and subapical vesicles; 2) a kidney-specific hydrophobic M(r) 400,000 polypeptide from intermicrovillar invaginations and subapical vesicles; and 3) villin from microvilli cores. In the normal urine about 50% of the excreted Na+-D-glucose cotransporter and villin, and about 25% of the M(r) 400,000 polypeptide was associated with brush border membrane vesicles, whereas the remaining fractions of the three proteins formed small sedimentable aggregates which contained some cholesterol and fatty acids but no phospholipids. The normal urinary excretion of the Na+-D-glucose cotransporter was correlated with that of villin and the M(r) 400,000 polypeptide. The data show that membrane proteins from the proximal tubule are excreted by the shedding of different brush border membrane areas. They suggest that some microvilli are released in total, and that a large fraction of the brush border membrane proteins is excreted without being associated with a phospholipid bilayer. In an attempt to define protein excretion patterns during kidney malfunctions, the excretion of brush border membrane proteins was analyzed after one intravenous injection of the X-ray contrast medium, iopamidol. No change in villin excretion was observed, but a reversible increase in the excretion of brush border membrane proteins was found in patients without diabetes. With diabetes a more pronounced iopamidol effect on the excretion of brush border membrane proteins and a significant increase in the excretion of villin was observed.

Adolescent↗
PubMed1990

Effects of a modified hemodiafiltration method on low-molecular-weight protein composition in plasma.

To assess the biochemical effects of a hemodiafiltration procedure where low-molecular-weight proteins can be removed from the plasma, 7 patients with end-stage renal disease were studied during a 6-month period of high-flux dialysis as well as during a succeeding 6-month period of hemodiafiltration. Distinct changes in the plasma protein composition occurred during the hemodiafiltration period, which cannot be explained solely as a result of molecular-weight-dependent filtration. Low-molecular-weight proteins in the plasma were reduced but losses of larger proteins occurred simultaneously. It is concluded that by increasing the dose of diffusive and convective transport in hemodiafiltration the renal tubular function in the catabolism of low-molecular-weight proteins cannot be replaced. The main obstacle to achieve such a goal appears to be the low selectivity of current high-flux membranes for low-molecular-weight proteins.

Adult↗
PubMed1990

Tubule-derived membrane glycoproteins in the urine of patients (including those with AIDS) as analysed by radioimmunoblotting.

As a contribution to the noninvasive diagnosis of kidney damage, polyclonal antisera specifically directed against brush border surface glycoproteins of the proximal tubule of the human kidney were used in radioimmunoblotting studies for the assessment of kidney-tissue proteinuria. Urine specimens from healthy controls, from patients (n = 41) with various forms of renal involvement and from those suffering from symptomatic HIV-infection (AIDS) but having normal kidney function, were investigated for the excretion of kidney-derived membrane proteins. After SDS-polyacrylamide gel electrophoresis of urine samples and electroblotting of protein bands on nitrocellulose sheets, followed by incubation with the antibody and subsequently with 125I-labelled protein A, 3 major tubular glycoproteins (Mr 240 000, 160 000, 120 000) were revealed by autoradiography. The results indicate and increased shedding of epithelial membrane glycoproteins in the urine of patients with kidney lesions, and they also demonstrate the suitability of radioimmunoblotting for the determination of such tissue-antigens ("brush border-histuria").

Acquired Immunodeficiency Syndrome↗
PubMed1988

Search for optimizing dialysis therapy. I. Acute effects of hemodiafiltration with a highly permeable membrane and a large dose of convection and diffusion.

Based on the concept that an optimisation of dialysis therapy might be achieved by increasing the removal of small metabolic substances as well as low molecular weight proteins, hemodialfiltration (HDF) was modified. In 9 ESRD patients, HDF was performed acutely for 4 h, where 60 liters of substitution fluid were infused per patient. Two polysulphone F60 membranes in line were used as hemodialfilters. As compared to conventional hemodialysis (HD), performed with a cuprophane dialyser, HDF resulted in higher extraction indices for small solutes assessed by HPLC. Due to the large amount of convection applied, HDF was followed by significant decreases of low molecular weight proteins ranging from 9.5 kdaltons (iPTH, p less than 0.01) to 17 kdaltons (myoglobin, p less than 0.01). Analysis of the protein pattern of the serum revealed a nonlinear function in the decrease of plasma proteins after HDF. It is concluded that even though the detoxification efficacy of the described HDF method is by far superior to conventional HD in quality and quantity, the efficacy is still far from that of excretory renal function. Thus, to further improve efficacy with respect to the catabolic renal function for low molecular weight proteins, membranes for HDF or hemofiltration barriers but should surpass the sieving properties of the glomerulus in the low molecular protein range.

Adult↗
PubMed1987

Reaction of monoclonal antibodies with plasma membrane proteins after binding on nitrocellulose: renaturation of antigenic sites and reduction of nonspecific antibody binding.

The immunochemical reaction of monoclonal antibodies directed against native membrane proteins was investigated after their separation in sodium dodecyl sulfate polyacrylamide gels and electrotransfer to nitrocellulose. Nonspecific binding of antibodies to membrane proteins, which was increased by beta-mercaptoethanol treatment or heat denaturation of the antibodies, could be significantly reduced if 1 M D-glucose plus 10% (v/v) glycerol was added during the incubation with the antibodies. It was found that specific antibody binding was drastically reduced by SDS treatment of the membrane proteins. During the electrotransfer to nitrocellulose and the simultaneous removal of SDS, some increase in antibody binding was observed. Considerable renaturation of antigenic sites in the blotted proteins could be induced if the nitrocellulose blots were incubated for 16 h at 37 degrees C in phosphate-buffered saline. With the introduction of both modifications, the renaturation step, and the addition of D-glucose and glycerol to reduce nonspecific antibody binding, the immunoblot technique may be successfully applied to detect conformational antibodies against membrane proteins.

Animals↗