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Biomedical subjects

K Schindhelm

Publications and source records attributed to K Schindhelm.

At least 55 records · Page 3Linked to original sources
PubMed1988

Induction of endothelial cell migration by proline analogs and its relevance to angiogenesis.

The proline analogs cis-4-hydroxy-L-proline, 3,4-dehydro-L-proline, and 2-azetidinecarboxylic acid induced increases in the migration rate of retinal capillary endothelial cells, aortal endothelial cells, corneal endothelial cells, aortal smooth muscle cells, and retinal pericytes. cis-4-hydroxy-D-proline did not. The optimal concentration for migration induction by any of the active agents was approximately 10(-5) M. At higher concentrations (5 x 10(-4) M) migration was not induced or was inhibited. When tested by subcutaneous implant assays in rabbits, cis-4-hydroxy-L-proline and 2-azetidinecarboxylic acid consistently elicited a marked angiogenic response. Whereas these compounds are known to modulate collagen synthesis and secretion, the concentrations at which they are effective inducers of migration suggest that they may have a more specific target than general collagen synthesis.

Animals↗
PubMed1988

Membrane plasma exchange in experimental allergic neuritis: effect on antibody levels and clinical course.

The effect of membrane plasma exchange on the course of chronic experimental allergic neuritis in rabbits is described. Using miniature membrane plasma separators conscious animals were treated with 4 exchanges over 5 days removing one plasma volume per procedure and using a non-immunogenic gelatin plasma solution as replacement. Comparisons of clinical scores between control and treated groups indicated that treated animals received significant benefit from plasma exchange (day 1 post-treatment P less than 0.002; day 3 post-treatment P less than 0.01). However, relapse was observed in all plasma exchanged animals such that by day 8 post-treatment there was no significant difference in clinical scores between the two groups. Quantitation of anti-myelin IgG and IgM by ELISA assay showed that 55-60% of circulating antibody was removed per exchange. Rapid post-exchange antibody rebound was observed for both IgG and IgM so that pre-exchange levels were re-established within 24-48 h. However, no significant overshoot in circulating levels of anti-myelin IgG nor IgM could be observed. It is probable that long-term remission as a result of therapeutic plasma exchange is a function of effective circulating plasma removal and if present, the suppression of ongoing antigenic stimuli.

Animals↗
PubMed1988

A comparison of the effects of plasma exchange and immunoadsorption on anti-insulin antibody synthesis in rabbits.

Plasma exchange (PE) and ex vivo immunoadsorption (IA) may be applicable to the removal of anti-insulin antibodies (AI-Ab) from diabetic patients. However, the removal of antibodies may prompt an increase in their rate of synthesis and an overshoot of antibody levels which may be deleterious to the patient. The effects of both PE and IA on AI-Ab synthesis were studied in a rabbit model. Rabbits were immunized with insulin and the resulting AI-Abs removed by both plasma exchange and specific immunoadsorption. Following AI-Ab removal by PE no increase in AI-Ab synthesis or antibody overshoot occurred. However a large increase in AI-Ab synthesis and overshoot occurred following specific AI-Ab removal by immunoadsorption. Despite similar reductions in AI-Ab levels by PE and IA, no increase in antibody synthesis occurred due solely to antibody removal. It is likely that antigen released from the immunoadsorbent stimulated the increase in antibody synthesis following immunoadsorption. These findings are relevant to the clinical application of both PE and IA.

Animals↗
PubMed1987

Chronic experimental allergic neuritis. An electrophysiological and histological study in the rabbit.

Ten adult outbred New Zealand white rabbits were inoculated with a single multiportal dose of purified bovine peripheral nerve myelin and Freund's adjuvant containing 500 mg of nerve antigen. Seven animals developed chronic relapsing or progressive disease which was followed by clinical examination for 14 months. Electrophysiological studies showed marked slowing of motor conduction velocity, dispersion of the evoked muscle action potential (MAP) and reduction in amplitude of the MAP derived from distal stimulation. Histological examination of the peripheral nervous system showed at 12 months a marked hypertrophic neuropathy in the nerve roots with well developed onion bulbs, active demyelination and a moderate nerve fibre loss. It is suggested that these animals provide a reliable and predictable model for human chronic inflammatory demyelinating polyneuropathy (CIDP) which should prove valuable for therapeutic trials and studies of pathogenetic mechanisms.

Animals↗
PubMed1987

Linear response curves from an ELISA assay: measurement of anti-myelin IgG and IgM during experimental allergic neuritis.

An ELISA method for generating linear dose-response curves for measuring anti-myelin IgG and IgM is described. Linearity is achieved without logarithmic transformations. This test is used to measure plasma levels of anti-myelin antibodies in rabbits with EAN. Results are expressed as relative concentrations of antibody in arbitary mass units with 95% confidence limits fitted by inverse prediction. In the 8 animals studied, appearance of anti-myelin antibody always preceded onset of clinical signs and neither anti-myelin IgG nor IgM could be detected in any animal pre-inoculation. Five out of 8 animals displayed steady and progressive increases in anti-myelin IgG with the remaining 3 animals showing plateaus in IgG levels 21-30 days post-inoculation. Increases in anti-myelin IgG were generally parallelled by increases in disease severity. However, 2 animals showed recovery and relapse from EAN with no change in plasma levels of anti-myelin IgG. Patterns of production of anti-myelin IgM varied with some animals displaying early peaks while others showed gradual increases.

Animals↗
PubMed1985

Vascular access for extracorporeal therapy in the rabbit.

A technique allowing short-term blood access for extracorporeal therapy in rabbits is described. The technique utilizes silicone rubber cannulae and teflon vessel tips to construct an externalized carotid-jugular arteriovenous shunt. The insertion procedure takes 1 h and extracorporeal blood flows in excess of 10 ml/min are obtainable for up to 7 days. Blood flow may still be obtained following shunt clotting by insertion of smaller diameter catheters through the arterial cannula. This technique has been successfully used for extracorporeal therapy in rabbit disease models.

Animals↗
PubMed1985

The effect of extracorporeal antibody removal on antibody synthesis and catabolism in immunized rabbits.

Plasma exchange therapy is currently used to remove antibody from the circulation in a number of autoimmune diseases. It has been suggested that the decrease in antibody level may affect synthesis rate by the removal of inhibitory feedback. This would then cause a rapid rise in antibody levels to or beyond those prior to depletion. Based on this supposition immunosuppression is nearly always used concomitantly with plasma exchange to prevent the expected increase in synthesis rates. An assessment of the effect of specific antibody removal by immunoadsorption on synthesis and catabolic rates was undertaken to clarify the nature of the response. Rabbits were immunized to bovine serum albumin (BSA) injected with 125I-anti-BSA IgG and later underwent extracorporeal immunoadsorption with BSA-Sepharose. At least 60% of circulating anti-BSA-IgG was removed. Mathematical analysis of 125I-anti-BSA IgG and anti-BSA-IgG levels demonstrated a reduction in catabolic clearance following immunoadsorption. Conversely synthesis rate was not altered. No significant overshoot of anti-BSA-IgG beyond pre-removal levels occurred. Based on these findings it is postulated that an increase in antibody synthesis does not generally occur following plasma exchange. The rise in antibody levels seen following plasma exchange probably reflect a reduction of catabolism combined with an unchanged rate of synthesis.

Animals↗
PubMed1985

Analysis of immunoglobulin G kinetics in the non-steady state.

The effect of specific intravascular IgG depletion on IgG catabolism, generation, and intrabody transfer has been studied in rabbits. In contrast to previous studies, the radiolabeled IgG kinetics were analyzed in the non-steady state. A two-pool model was used to determine IgG distribution, catabolism, generation, and intrabody mass transfer after intravenous injection of 125I-IgG. Circulating IgG was then specifically removed by plasma perfusion through a Protein-A Sepharose column in an extracorporeal circuit. Based on the two-pool analysis, IgG catabolic clearance fell after IgG removal (1.0 ml/hr vs. 0.7 ml/hr), and mean generation rate was unchanged. Plasma levels rose 20 hours after IgG removal as a result equally of contributions from intrabody transfer and of generation. Model parameters from plasma 125I decay analysis overestimated plasma 125I levels in the first 24 hours after removal, although predicted endogenous levels corresponded well with experimental results over a 7-day period. Rapid intravenous infusion of a 7% body weight volume of saline solution during IgG removal resulted in 50% greater plasma levels of 125I-IgG 24 hours after removal. This indicated that an increased lymphatic flow had occurred, resulting in increased IgG transfer from the extravascular to the intravascular space. The two-pool model adequately describes circulating IgG levels after specific IgG removal. Catabolic clearance was found to be a function of IgG level, whereas generation does not appear to be similarly dependent. Both the two-pool model and saline infusion procedure may be applied directly to the planning and optimization of plasma exchange therapy regimens in human autoimmune disease.

Animals↗
PubMed1984

Kinetics of intravenous saline infusion and selective IgG removal in rabbits.

Selective removal of approximately 60% of the plasma immunoglobulin G (IgG) mass in conscious rabbits was studied and compared with similar procedures combined with intravenous saline infusions equal to 7.5% body weight. Plasma concentrations of 125I-IgG and endogenous IgG were employed in model analysis to examine if saline infusions could be used to shift IgG from extra- to intravascular pool, thereby making more protein available for removal by extracorporeal plasma treatment. After IgG removal, the fractional metabolic clearance and the extra- to intravascular transfer coefficient were 40-50% lower than before IgG removal, and model simulations indicated that this may be caused by IgG binding. Saline infusion resulted in 40% more IgG mass in plasma 24 h after treatment compared with procedures without saline. Model analysis indicated that the increased IgG mass in plasma after saline procedures could be explained by a three- to fourfold increase in lymphatic clearance. Crystalloid infusions may be a method to increase the efficacy of repeated plasma exchange treatment.

Animals↗
PubMed1982

Renal handling of uremic middle molecules. a study with the isolated perfused rat kidney.

Little is known of the normal renal handling of potential uremic toxins in the middle molecular weight (MMW) range (300-2,000 daltons). In this study the isolated rat kidney has been used as a model to investigate renal clearance and possible renal metabolic effects on uremic MMW species. Isolated rat kidneys were perfused with hemofiltrate from chronic renal failure patients containing 5% bovine albumin. Middle molecules (MM) were isolated from perfusates and urines by high-speed gel filtration (peak 7) and further separated by gradient elution chromatography to give 7-8 definable uremic MMW species (7a, b, c, etc.). Species 7b, d, e and f were tubularly reabsorbed by 15, 25, 23 and 34%, respectively, as indicated by simultaneous inulin clearances. 7a was freely filtered with negligible reabsorption. 1 MM (7c1) was found to be secreted by up to 220% at low perfusate concentrations, secretion being masked at high perfusate levels. No MMs were catabolized by the kidney, although one species (7c2) appeared to be synthesized. The results suggest that uremic MMs have differing biological or physicochemical activities as indicated by the selectivity of renal handling.

Animals↗
PubMed1982

Middle molecules in patients with pre-dialysis chronic renal failure: a comparative clearance study.

Residual renal function is an important parameter int he design of dialysis regimens. In this study residual renal clearance of potential uremic toxins in the middle molecular weight range (originally thought to be 300-2000 daltons, but now considered close to 300-700 daltons) was investigated in patients with predialysis chronic renal failure. Middle molecules were isolated from uremic sera and urines by gel filtration and further separated by gradient elution chromatography to give 7 to 8 definable uremic middle molecular weight species. The renal clearances of middle molecule fractions were compared with simultaneously measured endogenous creatinine, urinary inulin and single short inulin clearance. The four middle molecule fractions which were quantitated (7a, b, c and d) were found to be freely filtered and to have renal clearances in end stage renal failure approximately equal to the endogenous creatinine clearance. Thus, renal handling of middle molecules is strikingly different from that of other peptides of peptide hormones in that the species do not appear to be catabolized, secreted or reabsorbed by the renal tubules to any significant degree.

Aged↗
PubMed1981

Renal handling of middle molecules in uremic patients and in the isolated rat kidney.

Renal handling of uremic middle molecules (MW 300-2000 daltons) was investigated (1) in the diseased kidney in nine patients suffering from chronic renal failure in the pre-dialysis phase, and (2) in the isolated perfused rat kidney using hemofiltrate and albumin (5 gm/100 ml) containing perfusate. Middle molecules clearances are compared to the simultaneously measured inulin and creatinine clearances. Four middle molecule fractions (peak 7a, 7b, 7c, and 7d) were quantitated after high-speed gel filtration and gradient elution chromatography and found to be freely filtered (= middle molecules clearances not differing from inulin and creatinine clearances) in uremia in man. In the "intact" (isolated perfused) rat kidney, elimination also takes place by glomerular filtration (peak 7a, 7c at high perfusate levels). Peaks 7b and 7d are slightly reabsorbed (15% and 25%, respectively, of filtered load), whereas 7c1 is secreted up to 220% of inulin clearance at low perfusate levels. No renal catabolism and high urinary excretion of middle molecules clearly indicate different renal handling of this species in comparison to other peptides or peptide hormones of the same molecular weight range.

Aged↗