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Biomedical subjects

J R Klinenberg

Publications and source records attributed to J R Klinenberg.

At least 55 records · Page 3Linked to original sources
PubMed1981

Current status of therapeutic apheresis in rheumatoid arthritis.

Evidence developed over the years has suggested that lymphocyte depletion and removal of plasma factors can ameliorate rheumatoid arthritis. In our studies of 40 patients, a subset of patients that respond best to 20 therapeutic lymphoplasmapheresis over 11 weeks has emerged. These are functional Class III patients with seropositive, erosive progressive disease who have little deformity. They must be on long-acting agents or cytotoxic drugs during pheresis to prevent antibody rebound. Other studies have since confirmed our work. The major side effects of pheresis are elucidated. Technologic developments will enable selective pheresis procedures to be in widespread use within a few years.

Arthritis, Rheumatoid↗
PubMed1980

Specificity of the transport system for tricarboxylic acid cycle intermediates in renal brush borders.

Uptake studies employing renal brush border membranes were used to examine the structural specificity of the TCA cycle intermediate transport system. The kinetics of reciprocal inhibition between succinate and citrate revealed these compounds to be transported by a common mechanism. The Michaelis constant for succinate (0.11 mM) was significantly lower than that of citrate (0.28 mM), indicating that the system has a higher affinity for succinate than for citrate. The specificity of the transport system was determined from the relative inhibitory constants of 40 organic acids on the transport of succinate. The results established that the system is highly specific for 4-carbon, terminal dicarboxylic acids in the trans-configuration, including the major intermediates of the TCA cycle. The system is comparatively insensitive to monocarboxylates. Substitution of one of several polar, non-charged residues on the alpha-carbon of succinate permitted interaction of the substrate with the transport system, but substitutions on both the alpha and beta-carbons did not. The structural specificity of the system is fundamentally different from that of the dicarboxylate and tricarboxylate exchange systems of mitochondria. The role of this transport system in the reabsorption of TCA cycle intermediates from the proximal tubule is discussed.

Animals↗
PubMed1980

Advances in the use of therapeutic pheresis for the management of rheumatic diseases.

Twenty-two patients with rheumatoid arthritis, 3 with seronegative juvenile rheumatoid arthritis, 4 with systemic lupus erythematosus, and 4 with psoriatic arthritis have undergone therapeutic pheresis at our institution over the last 3 yr. Lymphoplasmapheresis appears to be the most effective form of pheresis in treating rheumatoid arthritis. After achieving a remission with 20 treatments performed in 11 wk, a flare may be preventable by pheresing patients 3 times a week every 6 wk provided the patient is on a concomitant, long-acting agent. Therapeutic pheresis has been disappointing in seronegative juvenile rheumatoid arthritis. Life-threatening complications of systemic lupus erythematosus may respond dramatically to pheresis. In treating less severe disease on a long-term basis, pheresis has demonstrated excellent steroid sparing properties. Nonspondylytic psoriatic arthritis responds slowly to pheresis, but arthritic remissions may be prolonged, even though skin response is variable. Experience in the use of pheresis for treating these diseases has allowed for the development of criteria for deciding whether to institute such therapy as an adjunct to more standard modes of treatment for individual patients. Also, a variety of "technical" factors can influence the outcome of therapy, and these must be managed appropriately. Therapeutic pheresis is a promising tool for investigating and treating rheumatic diseases.

Adolescent↗
PubMed1980

Effects of metabolic intermediates on sugar and amino acid uptake in rabbit renal tubules and brush border membranes.

1. The effects of tricarboxylic acid cycle intermediates on the renal transport of alpha-methyl-D-glucoside and alpha-amino-isobutyric acid were examined using separated renal tubules of the rabbit. 2. The effect of citrate on alpha-methyl-D-glucoside and alpha-amino-isobutyric acid uptake was markedly biphasic with maximum stimulation of transport occurring at a citrate concentration of 0.64 mM. Biphasic effects were also apparent for L-malate, succinate, fumarate, alpha-ketoglutarate and oxaloacetate. 3. The route of uptake of alpha-methyl-D-glucoside into separated renal tubules is primarily across the brush border (luminal) membrane. 4. Tricarboxylic acid cycle intermediates produced significant stimulation of renal O2 consumption; however, the effects on O2 consumption were not biphasic suggesting that reduced stimulation of transport at high substrate concentration was not caused by a reduction in the supply of metabolic energy. 5. In purified renal cortical brush border membrane vesicles, citrate and alpha-ketoglutarate inhibited the uptake of alpha-methyl-D-glucoside and alpha-amino-isobutyric acid indicating that inhibition of their transport in respiring renal tubules by high concentrations of tricarboxylic acid cycle intermediates occurs via an effect at the membrane level.

Aminoisobutyric Acids↗
PubMed1979

Effects of dibutyryl cyclic AMP on the transport of alpha-methyl-D-glucoside and alpha-aminoisobutyric acid in separated tubules and brush border membranes from rabbit kidney.

The effect of dibutyryl cyclic AMP on the transport of alpha-methyl-D-glucoside and alpha-aminoisobutyric acid in separated tubules and purified brush border membranes from rabbit kidney was investigated using a rapid filtration procedure. Dibutyryl cyclic AMP stimulated the uptake of alpha-methyl-D-glucoside and alpha-aminoisobutyric acid by separated renal tubules in agreement iwth prior studies utilizing renal slices (Rea, C. and Segal, S. (1973) Biochim. Biophys. Acta 311, 615--624; Weiss, I.W., Morgan, K. and Phang, J.M. (1972) J. Biol. Chem. 247, 760--764). However, in contrast to previous reports, no preincubation of the tissue with dibutyryl cyclic AMP was required for stimulation of transport to be manifest. Dibutyryl cyclic AMP stimulated oxygen consumption by separated tubules suggesting that stimulation of transport may occur by a linkage with renal oxidative metabolism. Dibutyryl cyclic AMP increased the uptake of alpha-aminoisobutyric acid into purified renal brush border membranes. However the uptakes of alpha-methyl-D-glucoside, proline, leucine and phosphate into brush border membranes were significantly inhibited.

Aminoisobutyric Acids↗
PubMed1979

Transport of p-aminohippuric acid, uric acid and glucose in highly purified rabbit renal brush border membranes.

A procedure for preparing highly purified brush border membranes from rabbit kidney cortex using differential and density gradient centrifugation is described. Brush border membranes prepared by this procedure were substantially free of basal-lateral membranes, mitochondria, endoplasmic reticulum and nuclear material as evidenced by an enrichment factor of less than 0.3 for (Na+ + K+)-ATPase, succinate dehydrogenase, NADPH-cytochrome c reductase and DNA. Alkaline phosphatase was enriched ten fold indicating that the membranes were enriched at least 30 fold with respect to other cellular organelles. The yield of brush border membranes was 20%. Transport of D-glucose by the membranes was identical to that previously reported except that the Arrhenius plot for temperature dependence of transport was curvilinear (EA = 11.3--37.6 kcal/mol) rather than biphasic. Transport of p-aminohippuric acid and uric acid were increased by the presence of NaCl, either gradient or preequilibrated. However, no overshoot was obtained in the presence of a NaCl gradient, and KCl and LiCl also produced equivalent stimulation of transport suggesting a nonspecific ionic strength effect. Uptakes of p-aminohippuric acid and uric acid were not saturable, and were increased markedly by reducing the pH from 7.5 to 5.6. Probenecid (1 mM) reduced p-aminohippuric acid and uric acid (50 muM) uptake by 49% and 21%, respectively. We conclude that the uptake of uric acid and p-aminohippuric acid by renal brush border membranes of the rabbit occurs primarily by a simple solubility-diffusion mechanism.

Aminohippuric Acids↗
PubMed1979

Coexistent gout and rheumatoid arthritis. Case report and literature review.

A 73-year-old woman with Felty's syndrome and arthritis mutilans of long duration presented with tophaceous gout. The 7 previously reported cases of coexistent gout and rheumatoid arthritis (RA) are critically reviewed. Possible explanations for the rare coexistence of RA and gout are discussed: if uric acid is an inhibitor of the immune response, then hyperuricemia and gout could protect against development of RA. Conversely, crystalline protein binding may be a critical factor in the pathogenesis of gout, and the presence of abnormal proteins in RA could protect against gout.

Aged↗
PubMed1979

Plasmapheresis and lymphoplasmapheresis in the management of rheumatoid arthritis.

We have demonstrated the efficacy of therapeutic pheresis in a number of rheumatic diseases, especially rheumatoid arthritis (RA). Ten of 12 patients with RA went into remissions averaging 4 months. These patients were pheresed 20 times over 11 weeks in a tapering fashion on a Haemonetics Model 30 Blood Processor. Clinical remissions were sustained even though serologies, immunoglobulins, immune functions, sedimentation rates, and circulating immune complexes returned to their pre-pheresis baseline by pheresis number 20. All these patients were taking gold or D-penicillamine concurrently, but neither of the 2 patients who failed to respond was on these agents. Plasmapheresis was just as effective as lymphoplasmapheresis. It is theorized that removal of a plasma factor that modulates lymphocyte or neutrophil function produces remissions in RA and that long-acting drugs (e.g., gold or penicillamine) are able to prevent its continued production and produce a sustained remission.

Adult↗
PubMed1979

Transport of tricarboxylic acid cycle intermediates by membrane vesicles from renal brush border.

The uptake of citrate and alpha-ketoglutarate by membrane vesicles from rabbit renal brush border was studied by a rapid filtration technique. Both compounds exhibited transport characteristics similar to those seen for the sodium-dependent cotransport systems previously described for sugars and amino acids in brush border membranes. The estimated sodium-dependent Vmax and Km were 17 nmol per mg of protein per min and 0.18 mM for citrate and 17 nmol per mg of protein per min and 1.0 mM for alpha-ketoglutarate. The initial rate of citrate transport was 5 times that of sugars and amino acids under comparable conditions. Uptake rates of 0.1 mM citrate and alpha-ketoglutarate were inhibited by greater than 90% by 10 mM succinate, malate, fumarate, or oxaloacetate, indicating the presence in the brush border membrane of a transport system highly specialized for the renal conservation of intermediates of the tricarboxylic acid cycle.

Animals↗
PubMed1978

Effects of renal fuels on uptake of PAH and uric acid by separated renal tubules of the rabbit.

A rapid-filtration procedure was used to examine the effects of a wide variety of renal fuels on the uptake of p-aminohippuric acid (PAH) and uric acid (UA) by separated rabbit renal tubules. PAH and UA uptakes in 15 min over a range of substrate concentrations of 0.01-10.2 mM were determined. All tricarboxylic acid cycle intermediates and pyruvate showed biphasic stimulation of PAH and UA uptake. alpha-Ketoglutarate produced a 320 +/- 54% increase in PAH uptake and a 192 +/- 60% increase in UA uptake at 0.16 mM, the concentration at which uptake was maximal, while causing 20 +/- 3 (PAH) and 35 +/- 7% (UA) inhibition at 10.2 mM. Citrate produced a 373 +/- 19% increase in PAH uptake and a 246 +/- 41% increase in UA uptake at 0.64 mM. PAH and UA uptake were also stimulated by acetate, glucose frutose, phosphoenolypyruvate and L-glutamic acid. The data indicate a direct relationship between stimulation of PAH and uric acid transport and stimulation of renal cortical oxidative metabolism.

Aminohippuric Acids↗