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Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 235 records · Page 13Linked to original sources
PubMed1996

Association of T cell dysfunction with the presence of IgG autoantibodies on CD4+ lymphocytes in haemophilia patients; results of a 10-year study.

HIV induces progressive dysfunction followed by numerical depletion of CD4+ lymphocytes. IgG autoantibodies and gp 120-containing immune complexes have been implicated in the pathogenesis of AIDS. We carried out a longitudinal study in 19 HIV- and 72 HIV+ haemophilia patients over a 10-year period in order to investigate a possible relationship between the occurrence of autoantibodies and CD4+ lymphocyte changes. IgM, IgG, C3d and gp120 on the surface of CD4+ lymphocytes were determined in heparinized whole blood with flow cytometry and double-fluorescence. The in vitro response of autoantibody-coated cells was tested in cell cultures with concanavalin A (Con A), phytohaemagglutinin (PHA), pokeweed mitogen (PWM) anti-CD3 MoAb or pooled allogeneic stimulator cells (MLC). After a 10-year follow up, 12 of 71 HIV+ and 16 of 19 HIV- haemophilia patients showed no evidence of immunoglobulins on circulating CD4+ lymphocytes. HIV- haemophilia patients without autoantibodies had CD4+ and CD8+ cell counts in the normal range (957+/-642/microliters and 636+/-405/microliters) and normal T cell responses in vitro (mean relative response (RR) > or = 0.7). In contrast, HIV+ haemophilia patients showed immunological abnormalities which were associated with the autoantibody and immune complex load of CD4+ blood lymphocytes. HIV+ patients without autoantibodies had a mean CD4+ lymphocyte count of 372+/-274/microliter, a mean CD8+ lymphocyte count of 737+/-435 microliter, and normal T lymphocyte stimulation in vitro (mean RR > or = 0.7). HIV+ patients with complement-fixing IgM on CD4+ lymphocytes had somewhat lower CD4+ (255+/-246/microliters, P = NS) and CD8+ (706 +/- 468/microliters, P = NS) lymphocyte numbers, and also normal T lymphocyte stimulation (mean RR > or = 0.7) in vitro. However, patients with complement-fixing IgG autoantibodies showed a strong decrease of CD4+ (150 +/- 146/microliters, P< 0.02) and CD8+ (360 +/- 300 microliters, (P<0.02) lymphocytes and impaired CD4+ lymphocyte stimulation in vitro with a mean RR of 0.5+/-0.5 for Con A (P = NS), 0.7 +/- 0.8 for PHA (P<0.03), 0.4 +/- 0.4 for PWM (P = NS), 0.8 +/- 1.2 for anti-CD3 MoAb (P<0.04) and 0.7 +/- 1.0 for pooled allogeneic stimulator cells (P=0.05). Patients with gp120-containing immune complexes on CD4+ blood lymphocytes demonstrated strongly decreased CD4+ (25+/-35/microliters, P<0.0001) and CD8+ (213+/-212/microliters, P<0.006) lymphocyte counts as well as strongly impaired T lymphocyte responses in vitro upon stimulation with PHA (RR 0.2+/-0.1, P<0.02), PWM (RR 0.2+/_0.2, P=0.05), anti-CD3 MoAb(RR 0.1+/-0.1, P<0.04), and allogeneic stimulator cells (RR 0.2+/-0.1, P<0.02). These data led us to speculate that autoantibody formation against CD4+ lymphocytes is an important mechanism in the pathogenesis of AIDS. We hypothesize that autoantibodies against circulating CD4+ lymphocytes inhibit CD4+ cell function, especially the release of cytokines, and induce CD4+ cell depletion. The reduction and dysfunction of CD4+ lymphocytes may be responsible for the CD8+ cell depletion observed in HIV+ patients.

Antigen-Antibody Complex↗
PubMed1996

Use of recombinant human erythropoietin in combination with parenteral iron in the treatment of postpartum anaemia.

The authors compared the effect of recombinant human erythropoietin (rhEPO) in combination with iron with that of iron therapy only in the treatment of postpartum anaemia. Ninety patients (30 patients/group) received either rhEPO (300 U kg-1, i.v. or s.c., once) and iron (parenteral and oral), or iron therapy only. Erythropoiesis was assessed by haemoglobin and haematocrit increase, absolute reticulocyte counting and reticulocyte flow cytometry. Ferrokinetics was assessed by serum ferritin, transferrin and transferrin saturation measurements. There was no difference before therapy for baseline haematological values or iron status. Patients with endogenous EPO levels below 145 mU mL-1 had a significant benefit from intravenous rhEPO administration with highest haematocrit and haemoglobin levels 4 and 14 days after therapy. rhEPO-treated groups showed a higher absolute reticulocyte count 1 and 4 days after therapy and an elevated percentage of high fluorescent reticulocytes (HFRs). Parenteral iron therapy caused a significant increase of ferritin and transferrin saturation, while transferrin concentration decreased. Ferritin and transferrin levels were lowest after i.v. administration of rhEPO, 1 and 4 days after therapy. C-reactive protein concentration was highest in patients who underwent caesarean section until the end of the observation period. A single dose of rhEPO in combination with iron was more effective in treating postpartum anaemia than iron therapy only, in patients who had low EPO levels despite peripartal blood loss. Postpartum low endogenous EPO levels might be a consequence of inhibiting inflammatory cytokines that are released after spontaneous or operative deliveries.

Anemia↗
PubMed1996

Bilateral brachial amelia, facial clefts, encephalocele, orbital cyst and omphalocele: a recurrent fetal malformation pattern coming into focus.

Ultrasonographic and pathoanatomical features of a fetus displaying bilateral brachial amelia, complex facial clefting, encephalocele and omphalocele are described. The findings are compared with the few previously published cases. Bilateral brachial amelia with complex other organ malformations in previable fetuses may be more frequently diagnosed with improving prenatal ultrasonography.

Abnormalities, Multiple↗
PubMed1996

CD8+ lymphocyte decrease in HIV disease: association with anti-CD4+ but not with anti-CD8+ lymphocyte autoantibodies.

HIV+ patients form autoantibodies against CD4+ and CD8+ lymphocytes. It was shown that anti-CD4+ lymphocyte autoantibodies are associated with the depletion of CD4+ cells. In the present study we analyzed the relationship of anti-CD4+ and anti-CD8+ autoantibodies with the CD8+ lymphocyte decrease commonly observed during HIV disease. IgM and IgG antibodies as well as complement fragments were determined on the surface of CD4+ and CD8+ lymphocytes using double fluorescence flow cytometry. Anti-CD8+ lymphocyte autoantibodies were found more often in HIV + hemophilia patients (75/105 = 71%) than HIV- hemophilia patients (13/37 = 35%; p < 0.0001), patients with pharyngeal carcinoma (20/44 = 45%; P = 0.002), habitual abortions (3/13 = 23%; p = 0.0009) or healthy individuals (93-223 = 42%; p < 0.0001). Anti-CD8+ antibodies, mostly of the IgM type, occurred significantly more frequently than anti-CD4+ antibodies in healthy controls (p < 0.0001), patients with pharyngeal carcinoma (p = 0.0001), or HIV- patients (p = 0.01). In HIV+ patients, however, anti-CD4+ autoantibodies were found more often than anti-CD8+ antibodies (85 vs 71%; p = 0.02). 70 of 104 (67%) HIV+ patients had autoantibodies on both CD4+ and CD8+ lymphocytes and the IgG/IgM/C3d autoantibody pattern was identical in 31 (44%) of the patients. Interestingly, peripheral blood CD8+ cell counts were significantly associated with anti-CD4+ (p = 0.01) but not with anti-CD8+ lymphocyte autoantibodies. It is hypothesized that the inhibition and depletion of CD4+ cells by anti-CD4+ autoantibodies is associated with a loss of regulatory functions that leads to a depletion of antiviral cytotoxic CD8+ lymphocytes.

Autoantibodies↗
PubMed1996

Serum parameters and nuchal translucency in first trimester screening for fetal chromosomal abnormalities.

OBJECTIVE: To assess the relation between serum parameters and nuchal translucency in pregnancies affected by fetal aneuploidy in the first trimester. DESIGN: Retrospective study of different serum parameters collected prior to chorionic villus sampling and measurement of nuchal translucency in relation to fetal aneuploidy. SETTING: Switzerland (German and Italian sector) and Bregenz, Austria. POPULATION: One thousand one hundred and fifty-one women aged 25 to 44 years at 10 to 13 weeks of gestation undergoing chorionic villus sampling, mostly for advanced maternal age. Fetal aneuploidy was found in 23 pregnancies including four cases of trisomy 21, five of trisomy 18 and one case of trisomy 13. MAIN OUTCOME MEASURE: Fetal karyotype, serum levels of free beta-hCG, pregnancy-associated plasma protein A (PAPP-A) and alpha-fetoprotein and the measurement of nuchal translucency. RESULTS: Serum PAPP-A was decreased in all common chromosomal abnormalities. Free beta-hCG levels were increased in trisomy 21 but decreased in trisomy 18, whereas alpha-fetoprotein was low in trisomy 21, 18 and other chromosomal abnormalities. Nine of twenty-three abnormal embryos had evidence of an increased nuchal translucency. Nuchal translucency, however, did not seem to be associated with any alteration in the levels of the biochemical parameters in either chromosomally normal or abnormal embryos. A low serum PAPP-A or an increased nuchal translucency was seen in two-thirds of all pregnancies with chromosomal abnormalities. CONCLUSION: A nuchal translucency > or = 3 mm and depressed serum PAPP-A levels have a good predictive value in the detection of fetal aneuploidy at 10 to 13 weeks of pregnancy. Serum free beta-hCG and alpha-fetoprotein levels may give additional information. An increased nuchal translucency was not associated with altered serum parameters. This would allow these different markers to be used in combination.

Adult↗
PubMed1996

Does labor start too late?

To determine the optimal time of delivery, in terms of lowest risk of peripartum complications, the relative incidences of the parameters. Abnormal cardiotocogram (CTG), operative vaginal delivery, Apgar < 7 at 1 and 5 min, artery cord blood pH < 7.20, blood loss > 500 ml, epidural anesthesia, and Cesarean section, were retrospectively analysed with regard to mode of labor onset (spontaneous, induced) and gestational age in all deliveries between gestational weeks (GW) 35 + 0/7 and 42 + 6/7 from 1986 through 1993 at Zurich University Hospital (n = 11,834) and additionally with regard to birth weight in the same population from 1987 through 1993 (n = 10,346). The distribution of most parameters was parabolic with nadirs at GW 37-38; the incidence of low Apgar scores and Cesarean sections, however, was lowest nearer term (GW 39-40). Mode of labor onset had little effect (< or = 1 week) on the time of lowest incidence. The birth weight associated with the fewest complications was 3000 g, with the optimal time of delivery being GW 37-38, assuming a birth weight normal for gestational age.

Anesthesia, Epidural↗
PubMed1996

Stem cell separation in paediatric patients.

We performed 28 separations in 11 children weighing from 14 to 72 kg (median: 27 kg) using either the Cobe Spectra or the Fresenius AS 104 cell separator. For children under 20 kg, human albumin solution was used for the last 200 mL of the priming procedure instead of NaCl. Blood flow was reduced to 30-50 mL min-1 depending on the children's size and weight to prevent citrate reactions. Within 149-337 min we processed three times the patients' total blood volume and collected 309.7 x 10(6) (102.9-1140.0) mononuclear cells (MNC) and 2.01 x 10(6) (1.90-6.50) CD34+ cells per kg body weight. These results were comparable to the results we previously obtained in adults. We conclude from these initial results that peripherae blood stem cells (PBSC) separations, with both devices, can be adapted successfully to the needs of paediatric patients.

Antigens, CD34↗
PubMed1996

Separation of peripheral blood derived stem cells in children.

We performed 28 separations in 10 children from 14 to 44 kg (median: 24 kg) using either the Cobe Spectra or the Fresenius AS 104 cell separator. For children below 20 kg, human albumin solution was used for the last 200 ml of the priming procedure instead of NaCl. Blood flow was reduced to 30 - 50 ml/min depending on the childrens' size and weight to prevent citrate reactions. Within 149 - 337 minutes we processed 3 x the patients' total blood volume and collected 326.9 x 10(6) (76.5-1, 140.0) MNC and 2.03 x 10(6) (0.14-10.12) CD34+ cells per kg body weight. These results were comparable to the results we previously obtained in adults. We conclude from these initial results that PBSC separations with both devices can be adapted successfully to the needs for paediatric patients.

Adolescent↗
PubMed1996

[Expanded serologic infection testing of autologous blood donors: a report of experiences].

PURPOSE: The transmission of hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV-1/2) may cause serious disease in the recipient in cases of inadvertant homologous transfusion of autologous blood. Therefore data on the incidence of these infections in autologous blood donors are necessary. METHODS: We tested 7,438 autologous donations from 3,030 patients for anti-HIV, anti-HCV, and HBsAG. In addition, we tested all patients for antibodies to Treponema pallidum and hepatitis B virus core antigen (anti-HBc) and for elevated serum ALT levels. Confirmation tests were performed only for positive anti-HIV-EIAs. RESULTS: The frequencies of anti-HIV, anti-HCV, and HBsAG were 0.05, 2.8 and 0.6% of all units. The rate of anti-HCV decreased from 4.0 to 3.4% after introduction of a 2nd generation EIA but was only 0.6% using a 3rd generation EIA. Anti-HBc was positive in 9.4%, the TPHA test in 0.5%. ALT was above 45 U/I in 1.2%, but outside the sex related normal range in 8.4% of all units. 23.7% of all donations positive for anti-HIV, anti-HCV, or HBsAG showed at least one pathologic surrogate test; 7.5% of all surrogate marker positive units contained anti-HIV, anti-HCV, or HBsAG. DISCUSSION: The overall frequency of anti-HIV, anti-HCV, and HBsAG was only 3.45% of all autologous donations and was reduced further after introduction of 2nd and 3rd generation anti-HCV-EIAs. However, the rate of surrogate marker positive units was 10.9%. The overlap between both groups was remarkable. We conclude from our data that procedures to minimize the risk of inadvertant homologous transfusion of autologous blood are necessary despite the implementation of screening tests in autologous donation programs.

Adolescent↗
PubMed1996

[Functional treatment of the interphalangeal joints in palmar ligament rupture].

Palmar plate injuries of the interphalangeal joints are very common, yet they require careful treatment until full functional recovery is attained. This paper presents the results of follow-up examinations of 76 patients who underwent early functional treatment with a special dynamic splint. All had sustained an injury of the palmar plate of the PIP-joint (Type 1 or 2 according to Hintringer and Leixnering). After a velcro strip is released, the splint enables daily active exercise of the PIP joint with the joint being protected laterally and protected against hyperextension. This splint was worn for four weeks. After removal of the splint, 71% of all patients indicated that they did not have any problems, while 26% achieved the same mobility as the unaffected joint of the other hand after two more weeks of dynamic splinting. In only one case motion was inhibited for several further weeks.

Exercise Therapy↗
PubMed1995

Protein disulphide isomerase and a lumenal cyclophilin-type peptidyl prolyl cis-trans isomerase are in transient contact with secretory proteins during late stages of translocation.

The transport of a presecretory protein into the mammalian endoplasmic reticulum can be divided into early translocation events which include specific targeting of the presecretory protein to and insertion into the endoplasmic reticulum membrane and late translocation events, comprising signal sequence cleavage, completion of translocation and folding of the secretory protein into a functional conformation. The microsomal membrane proteins Sec61 alpha p and translocating-chain-associating membrane protein were previously identified as being in close contact with a nascent presecretory protein at an early step of translocation. Here, we investigated whether additional microsomal proteins are in contact with translocating chains during or immediately after transit. This was addressed by crosslinking after release of the nascent chain from Sec61 alpha p. We observed two additional membrane proteins interacting with the nascent precursor in the early stages of translocation and three lumenal proteins interacting with the processed polypeptide chain in the late stages of translocation. One of the lumenal proteins was identified as protein disulphide isomerase by immunoprecipitation. Another of the lumenal proteins was suggested to be a lumenal cyclophilin-type peptidyl prolyl cis-trans isomerase by the effect of cyclosporin A. We propose that molecular chaperones, such as protein disulphide isomerase and cyclophilin may represent two of the lumenal proteins which are involved in completion of translocation.

Amino Acid Isomerases↗
PubMed1995

Stable photobleaching of P840 in Chlorobium reaction center preparations: presence of the 42-kDa bacteriochlorophyll a protein and a 17-kDa polypeptide.

Simple procedures for the anaerobic preparation of photoactive and stable P840 reaction centers from Chlorobium tepidum and Chlorobium limicola in good yield are presented and quantitated. The subunit composition was tested by cosedimentation in sucrose density gradients. For C. limicola, it minimally comprises four subunits: the P840 reaction center protein PscA, the BChla antenna protein FMO, the FeS protein PscB with centers A and B, and a positively charged 17-kDa protein denoted PscD. The preparation from Chlorobium tepidum additionally contained PscC, a cytochrome c-551. The BChla absorption peak of the purified complexes was at 810 nm, with a shoulder at 835 nm. The ratio of the shoulder to the peak was 0.25, which corresponds to 1 reaction center per 70 BChla molecules if a uniform extinction coefficient of BChla is assumed. However, bleaching at 610 nm in continuous light corresponded up to 1 photoactive reaction center per 50 BChla molecules. Therefore, either the extinction coefficient of BChla in the reaction center is overestimated or the one for photobleaching is underestimated. In any case, the major portion of the reaction center was photoactive in the preparations. A P840 reaction center subcomplex, lacking PscD and deficient in FMO and PscB, but retaining the cytochrome c subunit, was obtained as a side product. It was photoinactive and had an absorption peak at 814 nm and a 835/814 absorbance ratio of 0.42. FMO and PscB show the tendency to form a complementary subcomplex. FMO and PscD are apparently required to stabilize the photoactive reaction center, while the cytochrome c subunit is not.

Algorithms↗
PubMed1995

[Trisomy-21 screening using AFPplus in the eastern part of Switzerland].

Two years after introduction of maternal serum screening for Down's syndrome in German-speaking Switzerland, based on measurements of alpha-fetoprotein, unconjugated estriol and total beta-HCG, results were analyzed of the two cytogenetic laboratories in Zurich and of a separate collective of the Department of Obstetrics at the University of Zurich. In a total of 489 cases with increased risk for Down's syndrome (> or = 1:380 at term) 19 (1:26; approximately 4%) had an abnormal fetal karyotype from which 16 had a trisomy 21. 13 out of these 16 mothers were aged below 35 years. Thus, after ultrasound, maternal serum screening detects the highest percentage of fetuses with chromosomal abnormalities. At the Department of Obstetrics 2962 serum screening tests were performed during a period of 2 1/2 years. 14.6% of the women were > or = 35 years old, 7.6% showed increased risk and 14 fetuses had an abnormal karyotype including 10 with Down's syndrome. 7 of these 10 were detected by the serum test. Nevertheless, the limited sensitivity of serum screening, its limitation predominantly to detection of fetuses with Down's syndrome and the rather late stage of screening, make effective first trimester screening mandatory.

Adult↗