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Biomedical subjects

P A Miescher

Publications and source records attributed to P A Miescher.

At least 19 recordsLinked to original sources
PubMed1996

Renal biopsy findings and followup of renal function in rheumatoid arthritis patients treated with cyclosporin A. An update from the International Kidney Biopsy Registry.

OBJECTIVE: To review data from the International Kidney Biopsy Registry, which describes the occurrence of cyclosporin A (CSA)-induced nephropathy, and to discuss the potential risk factors for its development. METHODS: The report examines data on a total of 60 first and 14 second renal biopsies performed in rheumatoid arthritis (RA) patients treated with CSA for up to 87 months. RESULTS: Five of the 60 patients with RA included in the Biopsy Registry had findings consistent with CSA-induced nephropathy at first biopsy. One further patient had such findings at second biopsy. Of the 22 patients who started CSA at dosages < 4 mg/kg/day and subsequently received dosages no higher than 5 mg/kg/ day, none developed CSA-induced nephropathy. Continuous assessment of renal function did not show any evidence of deterioration over time in patients maintained on low-dose CSA. CONCLUSION: The data indicate that in RA patients being treated according to current dosing recommendations, the risk of developing CSA-induced nephropathy is low.

Adolescent↗
PubMed1995

Polyclonal hypergammaglobulinaemia in a case of B-cell chronic lymphocytic leukaemia: the result of IL-2 production by the proliferating monoclonal B cells?

SEQ DATA who developed polyclonal hypergammaglobulinaemia: 38.3 milligrams polyclonal IgG, 0.97 milligram IgA and 0.33 milligram IgM. Immunophenotyping showed a monoclonal lymphocytic population CD19+ CD5+ CD40+ CD23+, low sIg+ (95%), kappa type in the great majority (96%). RT-PCR of immunoglobulin genes gave evidence of monoclonal rearrangement of the IgM type. Our tests showed that IL-2 was produced when leukaemic B cells were stimulated with phorbol myristate acetate, ionomycin and lipopolysaccharide. In addition, transfections with the full IL-2 promoter or elements thereof revealed that IL-2 expression is inducible and mediated through the NF-kB-promoter element. Finally, the amount of IL-2 secreted by these cells is about 39 ng/ml/10(6) cells, which is remarkably high for non-T cells. These results suggest that the large amounts of polyclonal IgG seen in this case of B-CLL are secreted by normal B cells which are in turn stimulated by IL-2 produced by proliferating monoclonal (leukaemic) B cells. Under cyclosporin A treatment, immunoglobulin secretion and B cell count remained low.

Adult↗
PubMed1995

Association of anticardiolipin antibodies and abnormal nailfold capillaroscopy in patients with systemic lupus erythematosus.

Anticardiolipin antibodies (aCL) are found in about 40-50% of patients suffering from systemic lupus erythematosus (SLE) and their presence carries an increased risk of thromboembolism. Since there is a high prevalence of nailfold capillary abnormalities in patients with SLE, we studied the relationship between aCL and skin microcirculatory changes or vascular symptoms in 51 consecutive patients with SLE (49 women, 2 men, 34.8 +/- 13.7 years). Twenty-two patients (43.1%) had positive aCL (IgG 22 (5-60) GPL; IgM 5 (3-16.5) MPL; median titre and range) and 12 (54.5%) of them had abnormal capilloscopic findings. By contrast, among the 29 patients without aCL, only six (20.7%) had an abnormal capillaroscopy (P = 0.027). There was no correlation between either aCL or capillaroscopy and Raynaud's phenomenon. These results show a relationship between aCL and nailfold capillary changes in patients with SLE, suggesting a direct damage of the vascular endothelium by aCL.

Adult↗
PubMed1994

[Cyclosporin in autoimmune diseases].

At a symposium held in Zurich in November 1993, a series of presentations covered the optimal use of cyclosporin A (CsA) in autoimmune diseases. Besides its immunosuppressive effects in organ transplantation, CsA appears to be active in a variety of autoimmune disorders. Its most pronounced and beneficial clinical effects are seen in patients with severe rheumatoid arthritis. New clinical studies include the nephrotic syndrome in children and patients with systemic lupus erythematodes. The main concern remains CsA induced nephrotoxicity. For the treatment of autoimmune disorders CsA can be used at lower doses (< or = 5 mg/kg per day) than in transplantation medicine. Thus, monitoring of CsA blood concentrations is not usually necessary. The galenics of CsA has been optimized recently, an achievement which will further improve the clinical use of CsA. Due to increased knowledge of intracellular CsA binding proteins and of effects of CsA on T-lymphocytes and cytokine production, it can be expected that novel immunosuppressive compounds will be developed.

Adult↗
PubMed1993

De novo initiation codon mutation (ATG-->ACG) of the beta-globin gene causing beta-thalassemia in a Swiss family.

Investigation of microcytic anemia with normal ferrous status in two members (father and daughter) of a Swiss family originating from Bern revealed high levels of HbA2 (4%, 7.3%) and HbF (3.2%, 3.1%). Direct sequence analysis of asymmetrically amplified DNA showed the ATG-->ACG mutation in the intiation codon of the beta-globin gene. Heterozygous beta-thalassemia was not found in either of the propositus's parents or in any of his brothers and sisters. Extended restriction fragment length polymorphism haplotyping of the beta chromosomes led us to the conclusion of a recent spontaneous mutation in the paternal germ cell. The results of routine HLA and blood group testing supported the stated paternity. We also found that the intragenic sequence polymorphisms (frameworks) are not always in linkage disequilibrium with the Bam HI polymorphism downstream from the beta-globin gene as previously observed. This is the second family found to carry this initiation codon mutation in the beta-globin gene. Unlike the first reported family, of Yugoslavian origin, our patients have high HbF levels and this in the absence of a C-->T substitution at -158 site 5' to G gamma.

Base Sequence↗
PubMed1993

Recombinant human erythropoietin as adjuvant treatment for autologous blood donation. A prospective study.

In a prospective randomized study we investigated the potential of subcutaneous recombinant human erythropoietin (rhEpo) as adjuvant treatment for autologous blood transfusions (3 units) in elective surgery. Four and 2 weeks before surgery, 49 patients received 6 x 10,000 U of rhEpo. delta Hb values (days -28 and 0) of the rhEpo group were compared to delta Hb values of 52 controls (no rhEpo). Reticulocytes were measured at days -21, -14, -7 and 0. Peri- and postoperative supplementary homologous blood requirements were compared in the two randomized groups. delta Hb of rhEpo group was 0.96 g/dl (mean value) and 2.38 for controls. Reticulocyte count increased earlier and to higher levels in rhEpo-treated patients. Except in 1 case, Epo was well tolerated. These results indicate that autologous predonation (3 x 400 ml) does not create anemia if adjuvant Epo treatment is given. However, homologous blood requirements were not significantly different, which is probably due to the fact that 96 of the 101 treated patients underwent elective orthopedic surgery requiring limited blood replacement. Significant benefit of the Epo regimen can be expected in elective cardiovascular and hepatic surgery where larger amounts of blood (5-6 units) are needed.

Adult↗
PubMed1992

Trisomy 8 detection in granulomonocytic, erythrocytic and megakaryocytic lineages by chromosomal in situ suppression hybridization in a case of refractory anaemia with ringed sideroblasts complicating the course of paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) was diagnosed in a 20-year-old male patient who suffered from anaemia since the age of 11. Eighteen years after diagnosis, PNH transformed into refractory anaemia with ringed sideroblasts (RARS). Trisomy 8 was observed in 27%, 45% and 53% of the bone marrow metaphase cells analysed in 1987, 1988 and 1990 respectively. In order to determine which bone marrow cell lineages were affected by trisomy 8 and at which stage of stem cell differentiation, MAC (Morphology, Antibody, Chromosomes) and CISS (Chromosomal In Situ Suppression) hybridization techniques were combined. The MAC technique enables karyotypic analysis of morphologically and immunologically classified mitotic cells. CISS hybridization makes it possible to detect individual chromosomes and chromosome aberrations using recombinant DNA libraries from sorted human chromosomes. Trisomy 8 was detected in granulomonocytic (50.6%), erythrocytic (67.2%) and megakaryocytic (one megakaryocyte with trisomy 8, one normal) lineages, providing evidence for the occurrence of trisomy 8 in early haematopoietic cell precursors, at the GEMM or pluripotent level. Cytogenetic and clinical data suggest that the sideroblastic clone originated from a mutation affecting a cell of the PNH clone, progressively replaced by the PNH/RARS clone, due to proliferative advantage.

Adult↗
PubMed1992

Frequencies of HIV-reactive B cells in seropositive and seronegative individuals.

Peripheral blood mononuclear cells (PBMC) from HIV-infected seropositive (HIV+) but not from normal, seronegative (HIV-) individuals are known to produce anti-HIV antibodies in vitro, in the absence or presence of pokeweed mitogen (PWM). Previous studies showed that up to 20-40% of spontaneously immunoglobulin-secreting B cells from HIV+ individuals are HIV-specific. To analyse the frequency of anti-HIV B cells among 'total' peripheral blood B cells in the present study, we used a limiting dilution assay in which EL-4 thymoma cells induce clones of immunoglobulin-secreting cells in activated as well as resting B cells. Anti-HIV B cells were detected not only in 11/12 HIV+ individuals (with frequencies from 1/910 to 1/21,500 B cells cultured; one negative test was from a person undergoing seroconversion), but also in 4/9 HIV- normal blood donors (1/16,200 to 1/49,000 B cells cultured) and in 3/6 newborns from HIV- mothers (1/11,800 to 1/26,600 B cells cultured). The mean frequency was nine times higher in the HIV+ individuals than in the normal donors. As in previous studies, only the cells from HIV+ individuals generated anti-HIV antibodies in PBMC bulk cultures with or without PWM. The relative proportion of specific anti-HIV antibody/total immunoglobulin in PBMC bulk cultures was 800 times higher by the mean than in EL-4 B cell cultures from HIV+ individuals (whereby the total immunoglobulin secretion for equal numbers of B cells cultured was 500 times lower for PBMC). These different results obtained with different assays suggest that in seropositives most anti-HIV B cells belong to an activated B compartment which is quite small, even in a disease with B cell hyperactivity. Therefore, the specific B cells are strongly diluted among the EL-4 cell-responsive, total B cells. On the other hand, the EL-4 assay can detect HIV-reactive B cells in the B cell repertoire of normal, non-infected individuals.

B-Lymphocytes↗
PubMed1990

[Role of T lymphocytes in systemic lupus erythematosus].

In very active systemic lupus erythematosus (SLE), the serum levels of interleukin-2 (IL-2) are increased, indicating activation of T lymphocytes in the organism. The peripheral blood, however, contains T cells with a strongly reduced functional capacity, which results from a post-activation/refractory state; this hypofunction is reversible. Thus, the activity of the T lymphocytes in the circulating pool is the "mirror image" of the activity of these cells at the level of the whole organism. The B lymphocyte hyperactivity in SLE is T-dependent. A highly specific mechanism is involved in the activation of the B cells producing anti-native DNA antibodies. The investigation of lymphocyte functions enables one to follow the effect of immunosuppressive therapy.

B-Lymphocytes↗