[Isolated immunoglobulin G (IgG) deficiency in dystrophia myotonica (Curschmann-Steinert)].
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Biomedical subjects
Publications and source records attributed to P Vaith.
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Clinical and biopsy findings in six patients (aged 29-64 years), suspected of having Wegener's granulomatosis, were not diagnostic. Cardinal signs were skin necroses, isolated deficits of cranial nerves, sudden amaurosis, renal failure with shunt sepsis and lung opacities suspicious of tumour. Only positive tests for anti-cytoplasmatic antibodies (ACPA) in serum made the diagnosis and led to appropriate treatment. This simple yet highly specific immunofluorescence test should be performed in every case of vasculitis of uncertain cause, even if typical clinical signs of Wegener's granulomatosis are at first absent.
We reviewed retrospectively the clinical records of 28 patients with AIDS staged group IV according to CDC-criteria. Among these, 19 had pulmonary disease: most of them (n = 17) had pneumocystis carinii pneumonia (Pcp). 12/17 patients with proven Pcp displayed typical x-ray findings with diffuse perihilar interstitial infiltration sparing lung periphery. 3/17 had atypical features and 2 normal chest x-ray findings. These data are important to identify patients with pulmonary complications of AIDS.
An immunoglobulin-independent deposition of the complement (C) components C4 and C3 occurs on rat kidney medullary structures, when sera of patients with various inflammatory diseases are studied by indirect immunofluorescence. The diagnostic value of this new test (C4-C3-IFT) for polymyalgia rheumatica (PMR) is stressed, since all sera from patients with active disease yielded positive reactions. Though highly sensitive with respect to PMR, C4/C3-IFT is not specific for this syndrome. Examples of positive reactions in systemic inflammatory diseases other than PMR are documented. Besides the clinical studies, C4/C3-IFT reactivity was analyzed with regard to the mechanisms of the reaction. Experimental data are presented which suggest that C-reactive protein (CRP) binds to rat kidney structures, thereby activating the classical C cascade. As a result of CRP-C interaction, C4 and C3 components are fixed to distinct renal medullary structures. Because of its technical simplicity, C4/C3-IFT can routinely be used to screen patients' sera for CRP-mediated C activation. This ex vivo test system may contribute to a better understanding of pathophysiological functions of serum CRP in various inflammatory diseases.
The case of a 84-year old woman is presented who developed a polymyalgia rheumatica/giant cell arteritis (PMR/GCA)-syndrome following a tick bite. Elevated titers of IgG-antibodies (indirect immunofluorescence and ELISA) as well as IgM (Immunoblot) against Borrelia burgdorferi antigens were found in her serum. When a total of 19 patients with PMR/GCA-syndrome was tested serologically, elevated or borderline IgG-titers against Borrelia antigens were detected in 12 of them (= 63%). Hence, Borrelia infection may be viewed as a potential trigger mechanism of a PMR/GCA-syndrome.
Endothelial cells from human umbilical cord veins proliferate in vitro up to 35-fold over control values when incubated for prolonged periods of time (up to 144 hrs) in the presence of sera from patients with SLE or PSS. The proliferation inducing capacity of patients' sera was high during remission and low during relapses. Similarly, induction of endothelial cell proliferation increased significantly following plasma separation; however, this effect did only last for a few hours. The in vitro stimulation of endothelial cells observed may be correlated to histological findings of hyperplasia and neoproliferation of vascular intima cells in SLE and PSS.
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Using indirect immunofluorescence deposition of complement C4 and C3 components to rat kidney medullary structures was demonstrated. This serological reaction (C4/C3-IFT) is regularly obtained with fresh sera of patients suffering from active polymyalgia rheumatica (PMR) and/or giant cell (temporal) arteritis (GCA). Sera of normal controls and of steroid-treated PMR and/or GCA patients in clinical remission have a negative C4/C3-IFT reaction. A positive conversion of the test in steroid-treated patients indicates enhanced disease activity. Because of its technical simplicity, C4/C3-IFT can be routinely used first, as a reliable serological marker in the primary diagnosis of PMR and/or GCA and second, as a sensitive criterion of disease activity in these patients. C4/C3-IFT reactivity is, however, not specific for GCA and/or PMR. Various systemic inflammatory diseases may have a positive reaction as well (e.g., certain viral and bacterial infections, malignant tumors, vasculitides, inflammatory joint diseases of different etiology). Recent experimental findings suggest that C-reactive protein (CRP) in patients' sera mediates an activation of the classical complement pathway resulting in a deposition of C4 and C3 complement components to certain rat kidney structures.
Fresh sera from patients with active polymyalgia rheumatica and/or giant cell arteritis are fixing the complement components C4 and C3 to structures of the medulla of rat kidney tissue as demonstrated by the indirect immunofluorescent technique. This PMR-associated reaction is also a useful tool in monitoring disease activity, as it becomes negative under effective treatment with steroids.
We report on a lethal course of an acquired immunodeficiency syndrome (AIDS) in a young female patient. She had spent her vacancies six years before diagnosis in Haiti, where a sexual intercourse with a Haitian man had occurred. Leading clinical symptoms consisted of recurrent Herpes simplex infections of the genital and perianal region as well as unexplained high temperatures. There were some typical laboratory and immunologic features of this disease with leukopenia, hypergammaglobulinemia, cutaneous anergy, a reduction of peripheral T-lymphocytes (OKT 3) and an almost complete loss of OKT 4 (helper cells) positive lymphocytes. The mitogenic response upon stimulation with allogeneic cells (MLC) or with the mitogens PHA, Con A and PWM was significantly reduced. There was no measurable interleukin-2 (IL-2) secretion of peripheral blood lymphocytes. Several immunostimulators (thymopentin, inosiplex, bestatin) were tested in lymphocyte proliferation assays in vitro. The mitogenic response could not be enhanced by neither of these substances. A clinical trial with Delimmun (inosiplex) for 14 days did not show any clinical or immunologic improvement in this patient. The intravenous application of high dose immunoglobulin G was without any observable effect. The proliferation inducing capacity of a highly purified IL-2 preparation on the AIDS cells in vitro led us to a clinical trial with this substance. We applied 100 Bödeker units of IL-2 per kg body weight and day subcutaneously for 16 days. A therapeutical effect, however, could not be observed. Cell marker analyses did not show significant changes in lymphocyte subpopulation composition under IL-2 therapy. There was an increase in the spontaneous cell proliferation 14 days after start of IL-2 therapy. The PHA- and IL-2 response of the AIDS cells, however, was unchanged. It cannot be excluded that an administration of IL-2 in earlier stages of AIDS may have beneficial effects.
We report on our experience with intravenous serum immunoglobulin therapy in five patients with common variable hypogammaglobulinemia. Our results support earlier observations that the immunoglobulin preparations used by us, namely Sandoglobulin and Polyglobin, are both effective in preventing severe infections and free of severe side effects. Essential clinical and laboratory findings of our patients are shown. We also point to the pathogenetic heterogeneity of these diseases as demonstrated by cell marker studies of lymphocyte subpopulations (anti immunoglobulin antisera and monoclonal OKT-antibodies). Finally we show in preliminary kinetic studies that the reduction of serum IgG-levels varies after administration of the same dose of IgG intraindividually in long-term follow-up. Further studies are required to demonstrate whether this variability is due to variable immunoglobulin synthesis and/or variable catabolism or elimination of administered immunoglobulin.
Bestatin was found to be a competitive inhibitor (with respect to the Leu-NA substrate) not only of the isolated microsomal and cytosolic leucine aminopeptidases (Leu-APm and Leu-APc) but also of the aminopeptidases (APs) present in membrane preparations (from mouse liver) and on the cell surface of L5178Y cells. Kinetic parameters indicate that cellular AP is identical to Leu-APm. To rule out the possibility that AP-B is involved in the inhibition reactions, comparable studies with amastatin were performed. Electrophoretical studies revealed the solubilized cell membrane bound AP to co-migrate with Leu-APm in polyacrylamide gels. The activity of the separated membrane AP was inhibited by bestatin in situ. The cell membrane bound AP activity was found to be lowest in lymphocytes, higher in tumor cells and highest in bone marrow cells and macrophages. Using synchronized L5178Y cells, the AP activity changes during the cell division cycle; the lowest activity was determined during the G1-phase and 35% higher values were measured during the S/G2-phase. The fluctuation of the cell surface associated AP activity parallels with changes in the number of binding sites for bestatin.
In 16 fo 20 patients with treatment-resistant hypertension endralazine, combined with beta-receptor blockers and diuretics, significantly lowered mean arterial blood pressure from 198/112 mmHg to 148/88 mmHg. The initial dose of endralazine was 2.5 mg three times daily. After this the dosage was increased, at the three to six-day intervals according to antihypertensive action and side effects, to a maximum of 50 mg daily in steps of 5.0--7.5 mg per dose. - In a second series of eleven additional patients with treatment-resistant renal hypertension the blood-pressure lowering effect of hydralazine and minoxidil was compared in an open cross-over trial. The result was in favour of hydralazine. Sodium and water retention was slightly less marked with endralazine. Sleep disorders, increased frequency of feeling cold, moderately severe flushing with red checks and feeling hot occurred but rarely with endralazine and regressed during the period of observation.
A D-galactose-specific lectin, purified from the marine sponge Geodia cydonium, is present on the cell surface of mucoid cells, free choanocytes and choanocyte clusters, as revealed first, by the adhesion assay which is based on the formation of "rosettes" with erythrocytes, and second, by immunofluorescence studies. Using the same techniques no lectin could be identified on the surface of archaeocytes. Rosette formation was inhibited in the presence of 20 mM D-lactose as well as after preincubation of erythrocytes with purified lectin. Titration experiments in a hemagglutination assay showed that the highest level of extractable lectin (5% of the total protein) is found in mucoid cells, lower concentrations are determined in choanocyte clusters (0.07%), free choanocytes (0.05%) and archaeocytes (0.01%). Only the mucoid cells were found to synthesize lectin which is secreted and subsequently transferred to the cell surface of other cell types. As one consequence of the binding of the lectin to the cell surface of aggregation-deficient choanocytes or archaeocytes, the conversion of these cells to aggregation-susceptible ones is observed. These results support previous evidence that the lectin is involved in the reaggregation process of single cells in the homologous biological system.
For the first time, the biological role of a lectin in the process of reaggregation of single cells from the same species (marine sponge: Geodia cydonium Jam.) is described. The galactose-specific lectin does not promote aggregation, but prevents the antiaggregation receptor from disaggregating cell clumps. Competition experiments showed that the lectin inactivates the antiaggregation receptor by binding to it, most likely via its terminal galactose residues. The lectin converts reversibly aggregation-deficient cells (carrying functional cell membrane-bound antiaggregation receptor molecules) to aggregation-susceptible cells.
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