Biomedical subjects
Publications and source records attributed to A Krause.
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CD2R is an activation-associated epitope unmasked by a conformational change of the CD2 cell-surface glycoprotein. In spite of elaborate studies on the role of CD2 and CD2R in adhesion and stimulation of T cells in vitro, no instances of CD2R expression in vivo were known to date. We report high levels of CD2R observed on blood and synovial fluid T cells in rheumatoid arthritis and on peripheral blood T cells in juvenile rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and Lyme disease. In vivo, expression of CD2R was restricted to T cells, not limited to a particular T-cell subset and not correlated with the expression of p55 interleukin 2R (IL-2R) (CD25) or major histocompatibility complex (MHC) class II molecules. When stimulated to proliferation via CD2 or CD3, ex vivo CD2R+ T cells showed the same basic activation requirements as CD2R-T cells.
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It is postulated that chondrocytes may be actively involved in the pathogenesis of inflammatory joint diseases, presumably by providing tissue specific antigens that may initiate or sustain autoimmune reactions. To investigate whether chondrocytes may also function as accessory cells in ongoing immune processes, mixed leukocyte-chondrocyte cultures and antigen presentation assays were studied. Freshly isolated and short term cultured HLA class II antigen (Ia) negative as well as gamma-interferon treated Ia positive chondrocytes were weakly or not stimulatory to allogeneic or autologous resting lymphocytes derived from either normal donors or patients with rheumatoid arthritis. In an antigen presenting system using tetanus toxoid, the majority of chondrocyte preparations tested induced an antigen driven response in HLA matched allogeneic or autologous resting T cells which, however, was much less when compared to blood monocytes. In contrast, using activated T cells derived from tetanus toxoid specific T cell lines, an efficient antigen presenting capacity could be demonstrated in both Ia positive and initially Ia negative chondrocytes. Interestingly, the latter population had acquired Ia antigens upon incubation with the T cell line.
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Central pontine myelinolysis is a process of demyelinisation with variable neurological symptoms related to the localization. Predisposing factors are alcoholism and malnutrition. Rapid correction of severe hyponatremia is suspected to be a primary cause for central pontine myelinolysis. We report a 43 year old chronic alcoholic and polytoxicomanic female patient, who was admitted comatose with a serum sodium level of 94 mmol/l, caused by a syndrome of inappropriate ADH secretion. After initial improvement under careful sodium correction, the patients neurologic condition degraded progressively and within 4 weeks she developed a "locked-in"-syndrome. Only then the suspected central pontine myelinolysis could be demonstrated in nuclear magnetic resonance and computer tomography. We presume that, although sodium correction was done relatively slowly in this patient, it probably contributed to her development of central pontine myelinolysis all the same. Due to this case we review the literature on correction of hyponatremia, which shows growing evidence that it should start early but be continued very slowly (rise in serum-Na: max. 0.6 mmol/l/h) and requires frequent laboratory controls.
To determine the efficacy of the new immunosuppressive agent ciamexon in patients with rheumatoid arthritis (RA), we conducted a 6-month, prospective, double-blind, placebo-controlled study. The study included 21 outpatients with confirmed RA, who were randomized into 3 treatment groups of 7 patients each. Group 1 received 400 mg/day of ciamexon, group 2 received 100 mg/day of ciamexon, and group 3 received placebo. We investigated the influence of ciamexon on the clinical course, the systemic inflammatory activity, and the lymphocyte subsets in the peripheral blood. Significant, dose-dependent improvement was seen in both the clinical and the biochemical activity indexes at the end of the treatment period (P = 0.02 to P = 0.05). The proportion of activated T lymphocytes was significantly decreased (P = 0.05), and the proportion of CD8-positive lymphocytes was significantly increased (P = 0.03) in patients taking ciamexon. The major adverse effects were hepatotoxicity (2 patients) and rash (2 patients). This study documents the clinical efficacy of ciamexon therapy in RA patients and identifies the agent's potential toxicity.
Application of computerized equipment in psychodiagnosis and cognitive training entails novel methodical aspects which relate to design of operator and response controls as well as to the test configuration. Some of these aspects are discussed.
Ciamexone, a 2-cyanoaziridine derivative, had been shown previously in animal studies to inhibit the proliferation of autoreactive lymphocytes dose dependently, without affecting the reaction against foreign antigens. To extend the experimental models of ciamexone's in vitro effects to the clinical level, we performed a pilot study to evaluate the clinical efficacy of ciamexone therapy. We further studied its influence on the systemic inflammatory activity and T-lymphocyte subsets in the peripheral blood of 10 patients with active rheumatoid arthritis (RA). Following 6 months' treatment with ciamexone all patients showed a significant decrease of both the clinical and biochemical scores. Concerning the T-lymphocyte subsets analysis, a relatively decreased rate of the activated T-lymphocytes was observed concurrently. Minor side effects included rash (n = 1), hepatotoxicity (n = 1) and diarrhea (n = 1). The study thus documents the clinical efficacy of ciamexone in patients with RA, but also indicates the agent's potential toxicity.
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According to recent investigations neopterin (a pyrazinopyrimidine derivative) is a biochemical marker that reflects the activity of the proinflammatory immunocellular system of the synovial tissue in rheumatoid arthritis (RA). Interferon gamma, derived from antigen activated T lymphocytes, stimulates macrophages to synthesise and release neopterin into the culture supernatant in vitro. To extend this in vitro model to a clinical level a sensitive new radioimmunoassay technique was used to measure neopterin concentrations in the synovial fluid (SF) of 17 patients with active RA, nine with osteoarthritis, and six with acute gout, and in that of 12 controls undergoing meniscectomy. The SF neopterin concentrations were significantly higher in patients with RA than in the other groups of patients, particularly the controls. Multivariant analysis showed that SF neopterin concentrations correspond better with the systemic inflammatory activity of RA than with the local disease activity of the knee joints. Thus the study strengthens the hypothesis that neopterin reflects the essential role of the activated immunocellular reaction in the pathogenesis of RA.
Concentration-dependent relaxation (6-70%) of segments of human saphenous veins under isometric conditions could be demonstrated with cumulative concentrations of isosorbide dinitrate (ISDN) and Glycerol trinitrate GTN (10(-9)-10(-5) M). Vein segments were obtained during coronary by-pass surgery. Nitrate (GTN)-induced relaxation was accompanied by a 2- to 3-fold increase of cyclic GMP content in the vessel walls. However, no change of concentrations in the vessel walls could be determined for the metabolites of prostaglandines: (PG E2, PG F2 alpha, TX B2, 6-keto-PGF1 alpha). Pretreatment of patients with 40 mg ISDN (standard release formulation) 4 times daily for 1 week prior to surgery with the last dose 1 hour before harvesting the vein segments did not influence relaxation. by ISDN. Immersion of vein segments for 1 hour in buffer solution containing 10(-6) M ISDN (= therapeutic concentration) prior to relaxation with cumulative concentrations of ISDN did not influence relaxation either. Induction of in vitro tolerance required ISDN concentrations which exceeded the range achieved under therapeutic conditions: 4.4 x 10(-4) M. This in vitro tolerance could be widely reversed by 10 mM N-Acetylcysteine (NAC) suggesting involvement of sulfhydril (SH) groups. Since tolerance in this experimental model was not seen under concentrations achieved in patients it seems likely that clinical tolerance is caused by activation of counterregulatory forces.
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It is well established that plasma phosphate (Pp) is largely determined by the renal phosphate threshold, which is best described by the maximal rate of tubular phosphate reabsorption divided by the glomerular filtration rate (Tmp/GFR). For its clinical assessment either direct phosphate loading with simultaneous measurement of GFR is performed, or the nomogram described by Walton and Bijvoet is used. In order to test the validity of the two methods, we compared in 20 infants and 31 children the fasting values of phosphate reabsorption [endogenous phosphate reabsorption/inulin clearance (Tp/Cin) and Tp] with those obtained after phosphate loading [maximal phosphate reabsorption (Tmp) and Tmp/Cin], and both with those derived from the nomogram. In addition the fasting Tp/Cin of 50 infants and 143 children could be compared with the nomogram. The results demonstrate that the directly measured Tp/Cin was the same as the directly measured Tmp/Cin and that the measured Tmp/Cin was correctly estimated by the nomogram. However, the comparison of fasting Tp/Cin with nomogram-derived values showed a systematic error, by which the latter values were higher than those measured. The discrepancy was due to the splay of the phosphate titration curve, which was found by Bijvoet when the ratio of phosphate clearance (Cp) corrected for GFR (Cp/GFR) fell below 0.2. The incorporation of this splay in the nomogram could not be confirmed by data measured in our children. It is concluded that fasting Tp is already "maximal" and that, therefore, no phosphate loading is necessary to estimate Tmp. Furthermore, there is no evidence of a major splay, which makes the nomogram incompatible below a Cp/GFR ratio of 0.2.(ABSTRACT TRUNCATED AT 250 WORDS)
On stimulation by green flashes, the isolated, aspartate-treated bovine retina exhibits transient changes in the scattering of near-infrared (880 nm) light. A single component, termed the "ATR" (a flash-induced scattering signal, where ATR designates amplified transient-retina), dominates the amplitude and rising-phase kinetics of the initial peak of the light-scattering response. Superfusion with physiological solution containing low Na+ concentration reversibly abolishes the photoreceptor electroretinographic response but preserves the ATR signal, indicating a receptoral origin for the ATR. The increase of ATR amplitude (A/Amax) with flash intensity (R*/R, where R indicates rhodopsin) is described by A/Amax = (1- e-kR*/R), with R*/R = k-1 occurring on generation of approximately two photoactivated rhodopsins (R*s) per disc surface in the rod outer segment. Weak background light and bright flashes reversibly depress the ATR. Kinetic and sensitivity data suggest a basis of the ATR in stochastic, unit activation events, each initiated by a single R*. They further suggest an essential invariance of the unit event under differing conditions of illumination. A delay, apparently governed by the lifetime of a light-activated substance regulating ATR generation, precedes ATR recovery after a bright flash. The flash dependence of the delay period indicates an upper limit of 3 s for the lifetime of R* in the ATR-generating process. The unit event appears to be an R*-catalyzed and disc-localized reaction of phototransduction.
A South African Afrikaans speaking family is reported in which a new high activity plasma cholinesterase variant was found to occur in the mother and son. The variant has the same electrophoretic mobility as the "usual' enzyme, but greater heat stability. Its higher specific activity is associated with a normal number of enzyme molecules. The variant may be inherited as a dominant trait, though its locus is uncertain.
Lyme spirochaetal disease (LSD) is a complex multisystem disorder which has been recognized as a separate entity due to its close geographic clustering of affected patients. The study aimed at evaluating the clinical and immunological features of LSD with chronic symptoms of meningoradiculitis, carditis and pauciarticular arthritis. Six patients with LSD and erosive arthritis who developed an increase of serum IgM rheumatoid factor (RF) which correlated with the inflammatory activity of the disease are described in detail. Besides raised IgG antibody titers to Borrelia burgdorferi (B. burgd.) antigen measured by ELISA technique, circulating immune complexes, antinuclear antibodies (ANA) and RF measured by laser nephelometric immunoassay were detected. Increased ANA and RF antibody rates suggest that LSD may closely be linked with transient autoimmune phenomena. Thus, in some cases, B. burgd. antigens might be able to produce a strong polyclonal B-cell stimulation, hence leading to an unspecific autoimmune reaction. But the question remains if transient unspecific autoimmune reactions actually take part in the pathogenesis of LSD.
Some test procedures of the computer assisted instrumentation system COMBITEST 2 were examined in order to evaluate the strength of diagnostical differentiation. For this purpose tests for evaluating the concentration capacity and the psychomotor performance, especially tapping, were used in a sample of 92 neurological patients (60 patients with and 32 without cerebral impairment). It became evident, that performance differentiations between patients with cerebral impairment and others are predominantly characterized by speed parameters (reaction time, duration of test), scarcely by parameters of accuracy (number of errors). Configuration - frequency - analyses emphasize deceleration of psychic/psychomotoric speed as diagnostic indicator in cerebral impaired patients: the best pattern was the "configuration" of reduced speed in concentration test and in tapping.