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Biomedical subjects

R Kinne

Publications and source records attributed to R Kinne.

At least 19 recordsLinked to original sources
PubMed1993

Renal proximal and distal tubular function is attenuated in diabetes mellitus type 1 as determined by the renal excretion of alpha 1-microglobulin and Tamm-Horsfall protein.

Diabetic nephropathy is usually characterized by glomerular dysfunction; the view that tubular damage occurs as a consequence, however, has been disputed. To verify this hypothesis we compared glomerular with proximal and distal tubular parameters in 62 patients with diabetes mellitus type I. The duration of disease ranged between 0 and 39 years and the glomerular, proximal tubular, and distal tubular parameters were investigated in 24-h urine samples. Excretion of albumin as a marker of the glomerulum, alpha 1-microglobulin and N-acetyl-beta-D-glucosaminidase as parameters of proximal tubule, and Tamm-Horsfall protein as parameter of distal tubule were determined by sensitive enzyme-linked immunosorbent assays. Patients were divided into five groups (D1-D5) according to the duration of diabetes as follows: D1, less than 1 year; D2, 1-4 years; D3, 5-9 years; D4, 10-14 years; D5, longer than 14 years. Healthy individuals (n = 61) aged 3-42 years served as controls. Significantly increased excretion of proximal tubular parameters were found in early course while albumin excretion was still in the normal range. In addition, proximal tubular alpha 1-microglobulin showed an increase during the course of diabetes duration, probably indicating an early proximal tubular impairment. Distal tubular Tamm-Horsfall protein showed increasing excretion in D1-D4, which may reflect disturbance of the thick ascending loop of Henle. Our results therefore stress the importance of tubular parameters such as alpha 1-microglobulin during early diabetes mellitus type I since they may serve as early markers of renal dysfunction and may precede albumin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1992

The serine-protease inhibitor of cartilage matrix is not a chondrocytic gene product.

Human articular cartilage contains significant amounts of antileukoprotease, a cationic low-molecular-mass serine-protease inhibitor, which was originally purified from mucous secretions (synonym: secretory leukocyte proteinase inhibitor). As it was not known whether the inhibitor molecule is also synthesized locally, we investigated antileukoprotease gene expression in chondrocytes. No antileukoprotease-specific mRNA was detected in adult or foetal human chondrocytes by in situ hybridization, Northern-blot analysis or polymerase chain reaction. Concurrently, the chondrocytes remained unstained on immunohistology, whereas immunoreactive antileukoprotease was demonstrated in the cartilage matrix. By Northern-blot analysis, the antileukoprotease message was detected in the promyelocytic cell line HL60, the myelomonocytic cell line U937 and even in mature polymorphonuclear leukocytes from the peripheral blood of healthy donors. Immunoperoxidase staining of polymorphonuclear leukocytes for the antileukoprotease protein indicated that this cell is likely to be the physiological source of the inhibitor in serum. The results further suggest an accumulation of the inhibitor in the cartilage matrix.

Base Sequence↗
PubMed1991

Uptake of bilirubin glucuronides by isolated rat hepatocytes.

The uptake of bilirubin diglucuronide (BDG) into isolated rat hepatocytes was investigated in order to characterize the mechanism by which bile pigments are transported by the liver. The BDG uptake by hepatocytes was saturable. The uptake was inhibited by bilirubin, sulfobromophthalein, and bilirubin monoglucuronide, but not by taurocholate. The uptake was not affected by replacement of sodium with other cations except for choline. Only when sodium was replaced with choline, was significant decrease in uptake observed. When chloride was replaced with nitrate, BDG uptake decreased, but it was not changed by replacement with sulfate. Metabolic inhibitors did not affect BDG uptake significantly. Thus bile pigments share a common sodium-independent and electrogenic potential-dependent transporter in liver cell membranes. A high concentration of albumin interferes with BDG uptake.

Animals↗
PubMed1990

Suppression and prevention of adjuvant arthritis in rats by a monoclonal antibody to the alpha/beta T cell receptor.

Adjuvant arthritis (AA) in rats is an experimentally induced autoimmune disease mediated by T lymphocytes specific for Mycobacterium tuberculosis. We raised the question whether T cells carrying the gamma/delta T cell receptor (TcR), reactive or not to mycobacterial antigens, are involved in the pathogenesis of AA. For this purpose, T cells bearing the TcR alpha/beta were depleted from circulation by treatment with a monoclonal antibody against the rat TcR alpha/beta (R73). This treatment efficiently suppressed existing disease. Even more efficient was pretreatment with R73 from birth, which prevented AA induction completely. In these alpha/beta+ T cell-depleted animals an elevated level of alpha/beta- T cells (about 15% vs. 1% in normal rats) was evident, which was not significantly increased by Mycobacterium tuberculosis injection. We found no positive evidence that gamma/delta + T cells do contribute to AA induction. Moreover, treatment with an anti-TcR alpha/beta monoclonal antibody may be very efficient treatment of T cell-mediated autoimmune diseases.

Animals↗
PubMed1990

Hepatic uptake of bilirubin diglucuronide: analysis by using sinusoidal plasma membrane vesicles.

In order to characterize the mechanism for bilirubin transport in the liver, the uptake of bilirubin diglucuronide (BDG) into purified sinusoidal plasma membrane vesicles was investigated. BDG uptake was saturable, and was inhibited by sulfobromophthalein and unconjugated bilirubin, but was not affected by sodium taurocholate. BDG uptake was sodium-independent and was stimulated by intravesicular bilirubin or BDG (trans-stimulation). BDG transport showed strong potential sensitivity; vesicle inside-negative membrane potential created by different anion gradients inhibited BDG uptake whereas vesicle inside-positive membrane potential generated by potassium gradients and valinomycin markedly stimulated BDG transport. These data suggest that BDG, sulfobromophthalein, and probably unconjugated bilirubin share a common transporter in liver cells which is sodium independent, membrane-potential-dependent and capable of exchange. The direction of transport in vivo may be governed by the intracellular concentration of BDG and of other yet unidentified organic anions sharing this transporter.

Animals↗
PubMed1990

Expression of activation antigens on T cells in rheumatoid arthritis patients.

The aim of our study was to identify differences in cell surface marker expression between T cells taken from the peripheral blood (PB) of healthy individuals and T cells recovered from inflamed joints of rheumatoid arthritis (RA) patients. Out of 118 monoclonal antibodies (MoAbs) directed against activation antigens on haematopoietic cells, 12 MoAbs recognizing nine distinct surface molecules were selected after a screening procedure to study the expression of the corresponding antigens on T cells from the PB, synovial fluid and synovial tissue of RA patients, and also on T cells from PB and spleens of controls. Using two-colour flow cytometry and immunohistology we found the molecules B-C5, CD39, CD40, CD45 R0, CD54, CD76 and potentially 1D11 to be substantially up-regulated on T cells from various body compartments in RA patients. We thus could determine that the cell surface of T cells in RA patients not only differs in MHC class II expression, but also in a number of other activation-associated cell surface molecules from T cells in healthy individuals.

Adult↗
PubMed1990

The suppressive effect of an antibody to the alpha beta cell receptor in rat adjuvant arthritis: studies on optimal treatment protocols.

An antibody (R73) to the alpha beta T cell receptor (TCR) was able to dramatically suppress adjuvant arthritis (AA) in rats. The efficacy of R73 treatment was investigated with regard to antibody dosage, injection route and timing of injections. R73 was equally effective in reducing joint swelling throughout a wide dose range (80 to 2000 microgram/dose) when given on day 15, 18, and 21 after arthritis induction. Both i.p. and i.v. injection were able to suppress the pre-existing joint swelling to the same extent. However, R73 was only effective when given before or at the peak of joint swelling which occurred between day 18 to 24. Synovial membrane hyperplasia, mononuclear cell infiltration as well as cartilage and bone destruction were markedly reduced after therapy. The effect of R73 was associated with depletion of alpha beta+ T cells from the circulation even at low antibody doses. Only few alpha beta+ T cells were found in the pannus tissue. Late treatment on day 27, 30 and 33 after arthritis induction did not influence clinical scoring of the disease and histological examination thereafter did not show any difference between treated animals and controls. We conclude that antibody therapy directed at the TCR seems to be very effective even in pre-existing autoimmune diseases if the relevant T cell population is affected. However, inflammation and joint destruction may reach a state at which anti-TCR treatment is no longer effective.

Animals↗
PubMed1989

A Na/H exchange mechanism in apical membrane vesicles of the retinal pigment epithelium.

The retinal pigment epithelium (RPE) interposed between the vascular system of the choroid and the neural retina performs a variety of functions essential for vision. In order to further elucidate the transport functions of the RPE, apical membranes were isolated from the RPE of the dogfish (Squalus acanthias) by differential precipitation with calcium. Na-K-ATPase, an apical marker enzyme in this tissue, was enriched 15-fold in the final membrane fraction. About 50% of the membranes form right-side-out vesicles in which the membrane has retained its in vivo orientation. Sodium uptake into these vesicles as determined by a rapid filtration method was stimulated 37% by the presence of a proton gradient across the membrane (pHi = 6.1, pHo = 8.1). The stimulation was also observed in membrane vesicles "short-circuited" with valinomycin and K. The pH gradient-dependent sodium uptake but not the uptake in the absence of a pH gradient was completely inhibited by 5 X 10(-4) M amiloride, and 56% inhibition was found at 10(-5) M amiloride. The uptake of 22Na was also strongly decreased in the presence of nonradioactively labelled sodium and lithium; potassium was without effect. pH gradient dependence, amiloride sensitivity, saturability and cation specificity of the sodium flux indicate the presence of a Na/H exchanger in the apical membrane of the retinal pigment epithelium. The presence of the Na/H exchange process might have important implications for the control of pH in the subretinal space, optimum intracellular pH of the RPE and the triggering of other functions of the RPE.

Amiloride↗
PubMed1988

Purification of a putative Na+/D-glucose cotransporter from pig kidney brush border membranes on a phlorizin affinity column.

Phlorizin, a potent inhibitor of the Na+/D-glucose cotransporter, was derivatised to 3-aminophlorizin and subsequently coupled to Affi-Gel 15. Affinity chromatography of pig kidney brush border membranes solubilised in Triton X-100 allowed the purification of a 60 kDa protein on this resin. We consider this protein to be the Na+/D-glucose cotransporter, or part of it, for the following reasons: (i) binding of this protein to Affi-Gel 15 specifically requires phlorizin covalently attached to the resin and is lowered when phlorizin is replaced by phloretin; (ii) binding of the 60 kDa protein to a phlorizin affinity column requires the presence of Na+; (iii) polyclonal as well as monoclonal antibodies against the 60 kDa protein inhibit binding of phlorizin to brush border membranes from rabbit and pig kidney.

Animals↗
PubMed1988

Taurine transport by rabbit kidney brush-border membranes: coupling to sodium, chloride, and the membrane potential.

Ion dependence and electrogenicity of taurine uptake were studied in rabbit renal outer cortical brush-border membrane vesicles isolated by differential precipitation. Na+-D-glucose cotransport was followed in parallel to monitor changes in the membrane potential. Concentrative taurine flux was dependent on a chemical and/or an electrical Na+ gradient (K+ diffusion potential) and could be completely inhibited by other beta-amino acids. It displayed a specific anion requirement (Cl- greater than or equal to Br- much greater than SCN- greater than I- greater than NO-3). At chemical Na+ equilibrium, Cl- gradients, depending on their orientation, stimulated or inhibited taurine uptake more than could be attributed solely to electrical anion effects, although a Cl- gradient alone could not energize an overshoot. Furthermore, taurine tracer exchange was significantly stimulated by Cl- as well as Br-. The Cl- stoichiometry was found to be one, whereas taurine transport, in the presence of Cl-, was sigmoidally related to the Na+ concentration, resulting in a coupling ratio of 2 to 3 Na+: 1 taurine. Upon Cl- replacement with gluconate, taurine uptake showed a reduced potential sensitivity and was no longer detectably affected by the Na+ concentration (up to 150 mM). These results suggest a 2 to 3 Na+ :1 Cl- :1 taurine cotransport mechanism driven mainly by the Na+ gradient, which is sensitive to the membrane potential due to a negatively charged empty carrier. Cl- appears to stimulate taurine flux primarily by facilitating the formation of the translocated solute-carrier complex.

Animals↗
PubMed1988

Modulation of sodium-cotransport systems by other ions.

After a brief review of Na+-cotransport systems which also accept other ions as co-ions or modifiers, modulation of the Na+-L-glutamate transport system in rabbit renal brush border membranes by K+ and H+ is discussed in more detail. Intravesicular K+ increases the initial uptake rate and electrogenicity of the cotransport. This effect of K+ is attributed to the formation of a K+-carrier complex that moves much more rapidly than do the other complexes. The resulting shift in rate limitancy (relative increase in overall rate over the relative increase in rate of step under consideration) from an electroneutral towards a charge-translocating pathway unmasks the electrogenicity of the initial L-glutamate uptake. A positive correlation between relative rate limitancy of the electrogenic pathway and electrogenicity is demonstrated supporting this model. Protons, in addition to acting as co-ions, modify Na+-glutamate cotransport by increasing both the initial rate and the electrogenicity of uptake. This phenomenon is assumed to represent a transition of the transport system from a carrier-like to an open channel-like translocation mode. Thus, the intrinsic properties of Na+-cotransport systems may vary under the influence of other ions. This holds true in particular for the electrogenicity of the initial transport rate which may change independently of alterations in charge stoichiometry.

Algorithms↗
PubMed1987

Dibutyryl cyclic AMP inhibits transport dependent QO2 in cells isolated from the rabbit medullary ascending limb.

Because the medullary thick ascending limb of the loop of Henle is the target of several polypeptide hormones that stimulate adenyl cyclase in this nephron segment, we examined the effects of cyclic AMP on thick ascending limb of the loop of Henle cells isolated by enzymatic digestion and density gradient centrifugation from the outer medulla of the rabbit kidney. The functional parameter that was measured was transport dependent oxygen consumption. Oxygen consumption was measured using a polarographic oxygen electrode in a constant temperature chamber. We found that dibutyryl cyclic AMP inhibited oxygen consumption in a dose dependent way. Maximal inhibition was observed at a concentration of 10(-5) M. The effect of dibutyryl cyclic AMP was not present in the absence of either sodium, chloride or both implying that its effect is restricted to the sodium and chloride dependent oxygen consumption. The effect of dibutyryl cyclic AMP was additive to that of furosemide 10(-4) M while that of furosemide was not additive to that of cyclic AMP suggesting that the site of action of cyclic AMP is distal to that of furosemide. The effect of dibutyryl cyclic AMP was not additive to that of ouabain and was absent in cells where oxygen consumption was stimulated with amphotericin B in the absence of chloride indicating that it has no effect on Na-K-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Renal handling of taurine, L-alanine, L-glutamate and D-glucose in Opsanus tau: studies on isolated brush border membrane vesicles.

Renal brush border membrane vesicles (bbmv) from the aglomerular toadfish (Opsanus tau), isolated by differential precipitation, were tested for their ability to actively translocate (i) taurine, known to be secreted by the kidney of several marine teleosts, and (ii) L-alanine, L-glutamic acid, and D-glucose, solutes that are normally reabsorbed in the filtering nephron. Vesicular taurine uptake displayed a Na+ dependence. Transport was greatest under conditions of an inward-directed Na+ gradient, but a significant stimulation by Na+ over K+ could also be observed in the absence of a salt gradient. At high extravesicular K+, the addition of valinomycin reduced taurine uptake. Na+-dependent 3H-taurine flux was almost completely inhibited by non-labeled taurine (tracer replacement) or beta-alanine, but was unaffected by L-alanine. Replacement of medium chloride by SCN- or NO3- in the presence of Na+ resulted in significantly lower uptake rates under both anion gradient and anion equilibrium conditions, whereas Br- could almost fully substitute for the stimulatory Cl- action. These results indicate the presence of an electrogenic Na+-cotransport mechanism with specificity for beta-amino acids in the toadfish renal brush border. Whether the system under physiological conditions mediates reabsorption or secretion of taurine remains to be determined. Toadfish bbmv also translocated L-alanine and L-glutamic acid in a Na+-dependent manner. Possible roles for these most likely reabsorptive transport systems in a non-filtering kidney are discussed. D-glucose uptake, however, appeared to occur via Na+-independent pathways, since it was not affected by phlorizin in the presence of Na+, or by Na+ replacement.

Alanine↗
PubMed1987

Ischemia induces surface membrane dysfunction. Mechanism of altered Na+-dependent glucose transport.

Reversible ischemia reduced renal cortical brush border membrane (BBM) Na+-dependent D-glucose uptake (336 +/- 31 vs. 138 +/- 30 pmol/mg per 2 s, P less than 0.01) but had no effect on Na+-independent glucose or Na+-dependent L-alanine uptake. The effect on D-glucose uptake was present after only 15 min of ischemia and was due to a reduction in maximum velocity (1913 +/- 251 vs. 999 +/- 130 pmol/mg per 2 s; P less than 0.01). This reduction was not due to more rapid dissipation of the Na+ gradient, altered sidedness of the vesicles, or an alteration in membrane potential. Ischemia did, however, reduce the BBM sphingomyelin-to-phosphatidylcholine (SPH/PC) and cholesterol-to-phospholipid ratios and the number of specific high-affinity Na+-dependent phlorizin binding sites (390 +/- 43 vs. 146 +/- 24 pmol/mg; P less than 0.01) without altering the binding dissociation constant (Kd). 20 mM benzyl alcohol also reduced the number of Na+-dependent phlorizin binding sites (418 +/- 65 vs. 117 +/- 46; P less than 0.01) without altering Kd. The reduction in Na+-dependent D-glucose transport correlated with ischemic-induced changes in the BBM SPH/PC and cholesterol-to-phospholipid ratios and membrane fluidity. Taken together these data indicate the cellular site responsible for ischemic-induced reduction in renal cortical transcellular glucose transport is the BBM. We propose the mechanism involves marked alterations in BBM lipids leading to large increases in BBM fluidity which reduces the binding capacity of Na+-dependent glucose carriers. These data indicate that reversible ischemia has profound effects on the surface membrane function of epithelial cells.

Animals↗
PubMed1987

Localization of Tamm-Horsfall protein in chloride transporting epithelia: lack of correlation with the Na, K, Cl cotransporter.

In order to test the hypothesis that Tamm-Horsfall protein (THP) and the Na, K, Cl cotransporter in chloride transporting epithelia are functionally related, the presence of THP in various rat epithelia was investigated by indirect immunocytochemical procedures. Positive staining was found in the apical cytoplasmic portion of the renal thick ascending limb, in apical large secretory granules of the pancreatic acinar cells, in the cytoplasm of the serous acinar cells of the salivary gland, and in the apical cytoplasm of mucosal cells in the jejunum. No staining was observed in the tracheal epithelial cells. These studies show that THP, or antigenically related substances, can be found in a variety of extrarenal organs. Only in the renal thick ascending limb the intracellular distribution of THP coincides partly with the distribution of the Na, K, Cl cotransporter. In all other epithelia investigated no correlation between THP staining and presence of the cotransporter was found. Thus, it seems very unlikely that Tamm-Horsfall protein and the Na, K, Cl cotransporter are functionally related.

Animals↗
PubMed1986

The anion specificity of the sodium-potassium-chloride cotransporter in rabbit kidney outer medulla: studies on medullary plasma membranes.

Plasma membrane vesicles were isolated from rabbit kidney outer medulla and employed in sodium, rubidium, and chloride flux studies. Chloride dependence and bumetanide sensitivity of (part of) the sodium and rubidium flux indicate that this plasma membrane fraction can be used to study the properties of Na-K-2Cl cotransport system present in the luminal membrane of the medullary thick ascending limb. The anion specificity of the cotransporter was investigated by determining the effect of anion replacement on sodium fluxes. When chloride was completely replaced by bromide, iodide, nitrate, or thiocyanate only bromide could effectively substitute for chloride (90% activity), whereas sodium uptake in the presence of iodide, nitrate, and thiocyanate amounted to only 25% of the sodium uptake observed in the presence of chloride. When similar replacement experiments were performed in the presence of 10 mmol/l chloride, bromide could substitute for chloride by 110%, iodide and nitrate by 60%, and thiocyanate by 70%. In the presence of 10 mmol/l bromide iodide, nitrate, and thiocyanate were similarly effective. The effect of nitrate and chloride on sodium flux was additive. Bumetanide-sensitive chloride uptake was inhibited by nitrate, the inhibition was however only partly, amounting to 60%. The results obtained are compatible with the view that the two anion binding sites of the Na-K-2Cl cotransporter can exhibit a different substrate specificity and that the transporter in addition to a 2Cl mode can also operate in a 2Br, Cl-, A- and Br-, A- mode, A- representing iodide, nitrate, or thiocyanate.

Animals↗