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Biomedical subjects

F Buttgereit

Publications and source records attributed to F Buttgereit.

At least 73 records · Page 4Linked to original sources

Effects of the mitogen concanavalin A on pathways of thymocyte energy metabolism.

The lectin concanavalin A (Con A) acts as a mitogen that preferentially activates T-cells. It stimulates the energy metabolism of thymocytes within seconds of exposure. We studied short-term effects (<30 min) of Con A on a conceptually simplified model system of rat thymocyte energy metabolism in the concentration range of 0-2 microg Con A per 107 cells, using metabolic control analysis. The model system consisted of three blocks of reactions, linked by the common intermediate mitochondrial membrane potential (Delta[psi]m): the substrate oxidation reactions, which produce the linking intermediate, and the proton conductance (or leak) and ATP turnover pathways which consume Delta[psi]m. Firstly, we used top-down elasticity analysis to establish which subsystems are targeted by Con A. Secondly, we quantitatively analysed the steady-state regulation of the system variables by Con A: how do the subsystem fluxes respond to Con A individually and as a whole? Our results indicate that: (1) steady-state respiration and Delta[psi]m increase as Con A concentration is raised, but at higher concentrations the increase in respiration is less and Delta[psi]m falls; (2) Con A independently changes the kinetics of the reactions that produce and consume Delta[psi]m: the Delta[psi]m-producing reactions are inhibited, and the reactions involved in ATP turnover are stimulated; and (3) the overall effects of Con A are mostly mediated by effects on ATP turnover.

Adenosine Triphosphate↗

Anti-phospholipid antibodies and CD5+ B cells in HIV infection.

This cross-sectional study evaluates the correlation between anti-phospholipid antibodies and CD5+ B cells in 110 patients infected with HIV-1. There were 89.1% of the patients who had IgG antibodies against cardiolipin and phosphatidylserine. The prevalence of IgM and IgA antibodies was < 22%. AIDS was associated with lower frequencies of IgM antibodies against cardiolipin (P = 0.05) and IgG-antibodies against cardiolipin and phosphatidylserine (P = 0.011). Drug users had higher IgM antibodies against phospholipids than patients from other risk groups (P = 0.02). A history of thromboembolic events was not accompanied by higher levels of anti-phospholipid antibodies (P > 0.2). No correlation between anti-phospholipid antibodies and CD5+ B cells was detected. Percentage part of CD5+ B lymphocytes was elevated in all patients and absolute CD4+ T lymphocyte counts and HIV p24 antigen were inversely correlated. In advanced disease a significant reduction of anti-phospholipid antibodies was contrasted with persistent elevation of CD5+ B lymphocytes. These observations may reflect immunological dysfunction involving apoptosis and endothelial damage rather than polyclonal B cell hyperstimulation. A possible explanation would be that in HIV infection an increased rate of spontaneous apoptosis in peripheral blood lymphocytes is accompanied by functional and structural changes of mitochondria. Therefore, structurally altered mitochondrial phospholipids could serve as antigen to induce specific humoral immune responses.

Adolescent↗

[Pregnancy-induced algodystrophy].

Pregnancy-induced algodystrophy is per se a rare, possibly too rarely diagnosed disease, since patients with algodystrophy may be misdiagnosed as having unspecific backache, musculoskeletal problems, and ligament pain associated with pregnancy. However, when clinical signs of beginning algodystrophia are present, immediate investigations and therapy are necessary for relief of pain and in order to prevent complications. The aim of this paper is to summarize our current knowledge on this disease. Furthermore, the clinical course and diagnostic evaluation are described in two cases with pregnancy-induced algodystrophy. The authors question the common distinction between pregnancy-induced and post-pregnancy algodystrophy, which result in a disturbed bone and calcium metabolism, but discuss both entities similary.

Calcitonin↗

Intravenous injection of India ink with suicidal intent.

We describe the case of a 33-year-old man who injected 4 ml of India ink into one of the median cubital veins with suicidal intent. He was hospitalized in good general condition 10 h after the injection. Abnormal laboratory test results were a leukocytosis, an oximetrically determined methemoglobin level of 36.9% (normal range: 1.5%) and a free hemoglobin level of 74 mumol/L (normal range: < 25 mumol/L). Toxicological examination showed the presence of nitrobenzene in blood and urine. Intravenous administration of vitamin C and tolonium chloride plus forced diuresis led to an improvement in cyanosis and a fall in the methemoglobin concentration. Repeated increase in the concentration of aminobenzene were successfully treated by hemodialysis with a high-flux dialyzer.

Adult↗

Methylprednisolone inhibits uptake of Ca2+ and Na+ ions into concanavalin A-stimulated thymocytes.

The glucocorticoid drug methylprednisolone inhibits respiration in concanavalin A-stimulated rat thymocytes at concentrations that are relevant to its acute clinical efficacy against autoimmune diseases and spinal cord injury. Methylprednisolone affects several processes, including ion cycling, substrate oxidation reactions and RNA/DNA synthesis. The inhibition of respiration used to drive ATP-consuming cycles of Ca2+ and Na+ ions across the plasma membrane has been proposed to be either primary or secondary to restriction of cellular ATP supply. By comparing the effects of methylprednisolone with those of myxothiazol, an inhibitor of the mitochondrial electron transport chain, we show that the effects of methylprednisolone on Ca2+ and Na+ cycling are primary. We propose that methylprednisolone acts by affecting membrane properties to inhibit Ca2+ and Na+ uptake across the plasma membrane and to increase H+ uptake across the mitochondrial membrane, and that other effects are secondary.

Adenosine Triphosphate↗

Value of anticardiolipin antibodies for monitoring disease activity in systemic lupus erythematosus and other rheumatic diseases.

The prevalence of anticardiolipin antibodies in active systemic lupus erythematosus (SLE) was compared with that in inactive SLE and other rheumatic and non-rheumatic diseases to determine the value of these autoantibodies in monitoring rheumatic diseases. Pairs of IgG- and IgM-aCL were measured by ELISA in 173 consecutive hospitalised patients, including 141 with rheumatic diseases (18 active SLE, 21 inactive SLE, 19 rheumatoid arthritis, 13 reactive arthritis, 7 other spondyloarthropathies, 16 vasculitis, 47 other autoimmune diseases) and 32 non-rheumatic controls. A further 101 aCL pairs were determined during follow-up in 19 patients with SLE. Serum concentrations were analysed with respect to SLE activity and compared between the different patient groups. IgG- and IgM-aCL levels in excess of 10 GPL and 9 MPL respectively were considered positive. 30.6% of all patients (53/173) were found to be positive for IgG-aCL, as against only 9.8% (17/173) for IgM-aCL. IgG-aCL serum levels in active SLE differed significantly from all other groups, including inactive SLE (all p < 0.005). Median IgM-aCL levels were below the cut off point in all groups, although measurable values were obtained almost exclusively in active SLE and RA. In this study IgM-aCL measurement was of less value in monitoring rheumatic diseases. IgG-aCL positivity in SLE was associated with a significantly higher odds ratio (OR) for active disease (OR 16.0, 95% confidence interval: 2.8-90.0). The results show that disease activity in SLE was accompanied by significantly increased IgG-aCL, whereas no elevation was found in other diseases. This parameter may therefore be useful in monitoring SLE activity.

Adult↗

[Persistent facial swelling of unclear etiology. The differential diagnostic considerations].

A 54-year-old, obese woman suffered from massive symmetrical swelling of the face, especially of the upper and lower eyelids. Initially the swelling occurred intermittently, but after 2 years it was permanent and progressive markedly limiting her visual fields. Neither laboratory findings nor imaging procedures provided any firm evidence of an underlying cardiac, renal or endocrinological disease. There was no suggestion of a storage disease. Skin biopsy showed foam cells and granulomatous inflammation, so the patient was tentatively diagnosed as having a monosymptomatic Melkersson-Rosenthal Syndrome. Eyelid surgery was performed to improve her visual fields. Treatment with clofazimine 100 mg daily was initiated. Regular follow-up visits over 7 months revealed no evidence of recurrence. The patient died a sudden cardiac death a few months later. The relatives refused an autopsy. The definite cause of her facial swelling remains unclear as we discuss the differential diagnostic possibilities.

Biopsy↗

[Protracted course of polychondritis as the etiology of progressive nose deformity, subglottic tracheal stenosis and inner ear hearing loss].

BACKGROUND: Relapsing polychondritis is a rare recurring inflammatory disorder with variable clinical course. Its etiopathogenesis is unknown, but autoimmune mechanisms are likely to be involved. PATIENT: We present a case report of a 42-year-old woman with polychondritis manifested in very slowly progressing destruction of the nasal cartilage, additional subglottic tracheal stenosis, and increasing cochlear dysfunction. RESULT: We describe and document by a series of photographs the very protracted course of the disease in this patient from early youth until now. Clinical signs and differential diagnosis in polychondritis are discussed. CONCLUSION: An early diagnosis in slowly progressing cases like this has to be established in order to permit adequate use of glucocorticoids and/or immunosuppressive drugs, to check the progress of the disease and prevent potentially lethal complications.

Adult↗

A hierarchy of ATP-consuming processes in mammalian cells.

The rates of different ATP-consuming reactions were measured in concanavalin A-stimulated thymocytes, a model system in which more than 80% of the ATP consumption can be accounted for. There was a clear hierarchy of the responses of different energy-consuming reactions to changes in energy supply: pathways of macromolecule biosynthesis (protein synthesis and RNA/DNA synthesis) were most sensitive to energy supply, followed by sodium cycling and then calcium cycling across the plasma membrane. Mitochondrial proton leak was the least sensitive to energy supply. Control analysis was used to quantify the relative control over ATP production exerted by the individual groups of ATP-consuming reactions. Control was widely shared; no block of reactions had more than one-third of the control. A fuller control analysis showed that there appeared to be a hierarchy of control over the flux through ATP: protein synthesis > RNA/DNA synthesis and substrate oxidation > Na+ cycling and Ca2+ cycling > other ATP consumers and mitochondrial proton leak. Control analysis also indicated that there was significant control over the rates of individual ATP consumers by energy supply. Each ATP consumer had strong control over its own rate but very little control over the rates of the other ATP consumers.

Adenosine Triphosphate↗

Effects of methylprednisolone and 21-aminosteroids on mitogen-induced interleukin-6 and tumor necrosis factor-alpha production in human peripheral blood mononuclear cells.

The compounds U-74389G (16-desmethyl tirilazad) and U-74500A are two of the novel series of nonglucocorticoid 21-aminosteroids (or lazaroids) which mimic the high-dose neuroprotective pharmacology of the glucocorticoid methylprednisolone (MP) in the injured CNS. Despite structural analogies to MP, it has been shown previously for a variety of endpoints that lazaroids are devoid of classical glucocorticoid effects. Our objective here was to measure the immunosuppressive effects of these lazaroids directly. Specifically, we have compared the in vitro effects of MP, U-74389G, and U-74500A on the mitogen-induced cytokine production in human peripheral blood mononuclear cells, which is known to be very sensitive and perhaps the most clinically relevant parameter reflecting immunomodulation. We show that, in contrast to the glucocorticoid MP, both lazaroids at therapeutically relevant concentrations have no significant inhibitory effects on stimulated interleukin-6 and tumor necrosis factor-alpha production, neither via residual glucocorticoid receptor-mediated activities nor via direct physicochemical effects on cellular membranes. These results strongly support the view that lazaroids lack glucocorticoid activities, but rather exert their tissue protective effects via mechanisms that are independent of glucocorticoid-receptor binding.

Cells, Cultured↗

[Combination of rare anomalies of the cervical spine and peripheral skeleton].

This paper presents a case report on a 59-year old patient of small stature with moderate mental retardation, strabismus and several rare skeletal anomalies. We found an os odontoideum, a dysontogenetic 3fold fusion of cervical vertebrae, multiple double-sided wrist bone dysplasias and brachytelephalangical digiti pedis I, but no anomalies of the heart or genitals. Clinical signs, biochemical parameters and results of x-ray and ultrasonic examination are demonstrated in this complex malformation syndrome that combines different anomalies known from other syndromes.

Abnormalities, Multiple↗