Two sibs with Wiedemann-Rautenstrauch syndrome: possibilities of prenatal diagnosis by ultrasound.

A girl with Wiedemann-Rautenstrauch syndrome was born to a non-consanguineous couple. During the pregnancy, growth retardation particularly in the biparietal and abdominal diameters but not the femoral length was detected through serial ultrasound scans. When the woman became pregnant again, in spite of having been assessed as having a 25% risk of recurrence, the prenatal findings seen in her previous pregnancy led us to suggest sequential echography and a similar pattern of growth retardation was shown. After termination, the male fetus was found to be affected by Wiedemann-Rautenstrauch syndrome. This case shows that ultrasound examination can be a useful tool in the prenatal diagnosis of this rare, autosomal recessive syndrome.     

Cardiomyopathy associated with Leigh's disease

Summary Clinical and postmortem findings in a female infant, suffering from Leigh's disease and cardiomegaly are described. The cardiac enlargement was due to symmetrical thickening of both ventricular walls and the septum. On light microscopy a widespread fibre disarray with a slight predilection for the ventricular septum was observed. Ultrastructural changes included an extreme reduction in the number of myofibrils and an excess of mitochondria. Abnormalities of the mitochondrial structure with tubular and myelinic transformation of the cristae suggested that a mitochondriopathy is responsible for the cardiomegaly in Leigh's disease.Dedicated to Prof. Dr. Waldemar Hort on the occasion to his 60th birthday     

Comparative study ofin vitro inhibition of activation of the classical and alternative pathways of human complement by the magnesium and sodium salts of the anti-inflammatory peptide N-acetyl-aspartyl-glutamic acid (NAAGA)

The inhibitory activity of the sodium salt of the anti-inflammatory peptide N-acetyl-aspartyl-glutamic acid (NAAGA) on activation of the classical and alternative pathways of human complement was compared with that of the clinically used magnesium salt of NAAGA (NAAGA-Mg). Sodium salt of NAAGA (NAAGA-Na) inhibited both pathways of activation in a dose-dependent manner at concentration ranging from 1 to 10 mM by acting on formation and/or function of the C3 convertases as shown by the inhibitory capacity of the peptide on the release of the C3 cleavage fragment C3b and C3a. NAAGA-Na was as effective as NAAGA-Mg in inhibiting classical pathway activation at concentration above 10 mM. NAAGA-Na was more effective than NAAGA-Mg in inhibiting the alternative pathway since the sodium salt did not interfere with Mg-dependent formation of the alternative pathway C3 convertase.     

Activated type II collagen reactive T cells are not eliminated by in vivo anti-CD4 treatment. Implications for therapeutic approaches on autoimmune arthritis.

Activation of CD4+ T cells plays an important role in type II collagen (CII) induced arthritis (CIA). The CD4+ T cell dependency is demonstrated by anti-CD4 antibody treatment which suppresses CIA in mice if injected before CII immunization. The same anti-CD4 treatment at a later stage does not suppress CIA, despite extensive elimination of peripheral CD4+ T cells. A possible explanation for this discrepancy is that activated T cells might not be as easily influenced by the anti-CD4 antibodies as resting T cells. To address this question, the proliferative capacity of CII reactive CD4+ lymph node (LN) T cells, in mice treated with anti-CD4 antibodies before or after the CII immunization, was analyzed. In mice treated before immunization the capacity of LN cells to proliferate in vitro was markedly suppressed while in mice receiving anti-CD4 treatment after immunization it was retained. Flow cytometric analysis revealed that the anti-CD4 treatment before and after immunization reduced the number of CD4+ LN T cells to the same level. The small population of CD4+ LN cells which were left after anti-CD4 treatment of naive mice all expressed CD44, a marker for previously activated T cells in mice. We propose that activation render CII reactive T cells more resistant to anti-CD4 treatment than virgin T cells are and suggest that the lack of therapeutic effect of late anti-CD4 treatment in CIA does not necessarily implicate that CD4+ T cells are unimportant in that stage of the disease.     

The inflammatory lesion of T cell line transferred experimental autoimmune encephalomyelitis of the Lewis rat: distinct nature of parenchymal and perivascular infiltrates

We have investigated the T cell receptor (TCR) repertoire in the inflammatory infiltrates of T line-transferred experimental autoimmune encephalomyelitis (EAE) of the Lewis rats. Using a panel of TCR V-specific monoclonal antibodies (mAbs) and immunocytochemistry, we studied the nature of the T cells entering the central nervous system (CNS) after transfer of either myelin basic protein (MBP)-reactive, or MBP-reactive but non-encephalitogenic T cell lines. All the MBP-specific T cell lines predominantely used the V8.2 TCR chain. T cell lines specific for the tuberculin purified protein derivative (PPD), using TCR V genes different from V8.2, served as controls. We first studied the time course of T cells entering the CNS. In all recipient rats, small, but significant numbers of -TCR-expressing infiltrate cells appeared in the CNS within the first 24 h after T cell transfer. In animals injected with either type of MBP-reactive T cells, the early infiltrate cells were preferentially located within the parenchyma of the spinal cord, while in PPD T lineinjected rats, the lymphocytes were mostly found in the meninges. TCR V gene usage was examined on the peak of clinical disease. Six days after T cell transfer, the TCR repertoire used by infiltrating lymphocytes in general seemed to be highly diverse. None of the V isotypes examined (i.e. V8.2, V8.5 or V10) was used by a major population of the -TCR-positive T cells. A more detailed, quantitative analysis of individual infiltrate compartments revealed, however, a preferential accumulation of V8.2-positive T cells within the parenchyma. In contrast, perivascular infiltrating cells used V genes randomly. Our results confirm first that activated T lymphocytes enter the brain rapidly irrespective of their antigen specificity. Second, the data show that most of the perivascular infiltrate T cells in the acute EAE lesion are host-derived, recruited presumably from the recirculating T cell pool, while the encephalitogenic, V8.2-positive T cells preferentially persist within the parenchyma.Abbreviations EAE experimental autoimmune encephalomyelitis - MBP myelin basic protein - TCL T cell line Supported by the Brazilian Research Council (CNPq)     

Ranolazine: A New Anti-Ischemic Drug Which Affects Myocardial Energetics

Ranolazine is a new, orally active pharmacologic agent that experimentally has been shown to favorably affect myocardial metabolism during myocardial ischemia. It has no direct action on myocardial hemodynamics but appers to improve ventricular functioning by blocking uptake of free fatty acids by the heart while shifting metabolism to anaerobic glycolysis during myocardial ischemia. Preliminary clinical studies suggest a dose-dependent antianginal, and anti-ischemic effect and an excellent safety profile for this unique drug. However, the results of a recent double-blind efficacy and safety study showed no antianginal effect of ranolazine (30--120 mg thrice daily) when compared to placebo.     

Noise-Induced Endocrine Effects and Cardiovascular Risk

Noise has the potential to cause stress reactions. Chronic noise-induced stress accelerates the ageing of the myocardium and thus increase the risk of myocardial infarction. The involved pathomechanisms include acute increase of catecholamines or cortisol under acute noise exposure and an interaction between endocrine reactions and intracellular Ca/Mg shifts. Chronic noise exposure of animals on a diet with suboptimal magnesium content led to increase of connective tissue and calcium, and decrease of magnesium in the myocardium. These changes were correlated to noradrenaline and normal ageing. Post mortem studies of hearts from victims of ischemic heart diseases confirmed the importance of Ca/Mg shifts in humans. Recent epidemiological studies support the importance of noise as a risk factor in circulatory and heart diseases, especially in myocardial infarction.     

Value of conjunctival biopsy in the diagnosis of sarcoidosis

PURPOSE: Retrospective study concerning the value of conjunctival biopsy in the diagnosis of sarcoidosis. PATIENTS AND METHODS: Between 1990 and 1996 we performed conjunctival biopsy in 11 patients (mean age 42.7 +/- 16.4 years) with suspect of sarcoidosis. RESULTS: In 8 of the 11 patients the diagnosis of sarcoidosis was established during the clinical course. In four of these eight patients conjunctival biopsy was positive. Five of the eight were under systemic steroids at the time of biopsy. Of the four patients with clinically established sarcoidosis and negative biopsy, three were under systemic steroids at the time of biopsy. In two patients diagnosis of sarcoidosis was established primarily by conjunctival biopsy. CONCLUSION: Conjunctival biopsy is a simple tool in the diagnostic of sarcoidosis. If possible, biopsy should be undertaken before systemic steroid treatment. We consider conjunctival biopsy to be useful as the first diagnostic tool before other invasive methods.     

Virusacanthome und besondere Formen von Keratinosomen “Membrane Coating Granules”

Zusammenfassung Bei Virusacanthomen können in den ballonierten Zellen des Stratum spinosum und granulosum alle Übergänge von multivesiculären Körpern (MVK) zu Keratinosomen beobachtet werden. Eine Besonderheit stellen die Rad-Körper bei Condylomata acuminata dar. Diese Gebilde sind als typisch für nicht verhornende Plattenepithelien beschrieben worden. Eine Beteiligung intercellulär ausgeschleuster Rad-Körper, MVK und atypischer Keratinosomen an einer nicht regelhaften basoapikalen Diffusionsbarriere in der Epidermis bei Virusacanthomen wird diskutiert. Auf Grund der Beziehungen von MVK zum Golgi-Apparat, ihrer Umwandlung zu teilweise atypischen Keratinosomen bei Virssacanthomen und Ausschleusung in den Intercellularraum könnte dafür sprechen, daß die enzymatisch gesteuerte Rückkopplung zwischen Zelloberfläche und Synthesefähigkeit der Keratinocyten virusbedingt verändert ist. Die Störung scheint sich am Golgi-Apparat zu manifestieren und durch das Terrain spezifiziert zu werden.Mit Unterstützung durch die Deutsche Forschungsgemeinschaft