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Biomedical subjects

B Wagner

Publications and source records attributed to B Wagner.

At least 109 records · Page 6Linked to original sources

[Demonstration of immunoglobulin isotypes in the vitreous body as a contribution to the etiology of recurrent equine uveitis].

The functional properties of different immunoglobulin isotypes in equine recurrent uveitis (ERU) has not been investigated yet. Here, we describe the quantitative determination of total immunoglobulin levels and isotype differentiation in the vitreous of four horses with ERU as compared to that of seven healthy horses. In contrast to almost equal amounts of total immunoglobulin in the vitreous of both groups, remarkable differences were found: All four of the horses with ERU had significantly higher IgA contents in their vitreous as compared to the control group. However, the other isotypes monitored (IgM, IgGa, IgGb, IgGc and IgG(T)) indicated no differences between both groups. Comparing the individual ratios of immunoglobulin isotypes in the vitreous and the autologous serum of two horses with ERU and two control animals provided informative results: IgM was only detected in serum but not at all in vitreous of all horses investigated. All four IgG isotypes monitored in the diseased animals as well as these IgG isotypes and the IgA in healthy animals were present in the same ratios in serum and in vitreous of the individual horses. In general, the content of such isotypes in the vitreous was about 1000 fold lower then the respective isotypes in the autologous serum. These results are compatible with a transfer of the IgG and IgA isotypes from the serum into the vitreous in healthy individuals. All four horses with ERU, however, had a selectively increased relative IgA content in the vitreous as compared to their serum. This argues for a preferential local IgA production within the framework of a local immunological reaction to antigens located within the eyes of horses with ERU.

Animals↗

Tyramine pressor sensitivity in healthy subjects during combined treatment with moclobemide and selegiline.

OBJECTIVE: The objectives of this double-blind study were to assess the tolerability and i.v. tyramine pressor response during combined treatment with moclobemide and selegiline. SUBJECTS: Two parallel groups of 12 healthy male and female subjects were treated with 200 mg moclobemide or 5 mg selegiline b.d. for 14 days. On Day 7, selegiline or moclobemide was added to the other treatment. IV tyramine pressor tests were conducted at baseline and at steady state during mono- and combined treatment. RESULTS: Treatment with moclobemide and selegiline alone was well tolerated, whereas combined treatment led to a slight increase in adverse events. Tyramine pressor sensitivity during moclobemide, selegiline and moclobemide + selegiline treatment was enhanced, on average, by 2.4-, 1.3- and 8.4-times, respectively. CONCLUSION: Although combined treatment with moclobemide and selegiline was well tolerated, the supra-additive potentiation of the tyramine pressor effects means that dietary restriction of tyramine intake will be necessary during such combination therapy.

Adrenergic Agents↗

Fetal ventral mesencephalon of human and rat origin maintained in vitro and transplanted to 6-hydroxydopamine-lesioned rats gives rise to grafts rich in dopaminergic neurons.

Free-floating roller tube cultures of human fetal (embryonic age 6-10 weeks post-conception) and rat fetal (embryonic day 13) ventral mesencephalon were prepared. After 7-15 days in vitro, the mesencephalic tissue cultures were transplanted into the striatum of adult rats that had received unilateral injections of 6-hydroxydopamine into the nigrostriatal bundle 3-5 weeks prior to transplantation. Graft survival was assessed in tyrosine hydroxylase (TH)-immunostained serial sections of the grafted brains up to post-transplantation week 4 for the human fetal xenografts and post-transplantation week 11 for the rat fetal allografts. D-amphetamine-induced rotation was monitored up to 10 weeks after transplantation in the allografted animals and compared with that of lesioned-only control animals. All transplanted animals showed large, viable grafts containing TH-immunoreactive (ir) neurons. The density of TH-ir neurons in the human fetal xenografts and in rat fetal allografts was similar. A significant amelioration of the amphetamine-induced rotation was observed in the animals that received cultured tissue allografts. These results promote the feasibility of in vitro maintenance of fetal human and rat nigral tissue prior to transplantation using the free-floating roller tube technique.

Animals↗

Staff security and work pressure: contrasting patterns of stability and change across five dialysis units.

Differences among clinical care units in social dynamics and social organization are associated with differences in the clinical course of patients with a range of chronic illness. These differences are also associated with well-being of staff members. Recent attention has focused on understanding these differences among units with an eye towards correcting deficiencies and enhancing strengths of clinical care units. The current study sought to delineate the effect of social and organizational dynamics unique to each unit on staff perceptions of the security of their relationships with other staff and their perceived work pressure. The unit as a major source of differences among staff subjects was compared with the impact of ethnic identity, of work in the morning shift vs other shifts, and of professional role. Results confirmed that unit membership was, by far, the most important correlate of staff perceptions of the unit, particularly those concerning security of relationships with others and perceived work pressure. Moreover, the results suggested that unit differences in perceived security were due to differences among units in long standing turmoil within the unit or long standing problematic ties between the unit and the larger institution which controls it. However, perceived work pressure seems more transient and may reflect the challenge of shorter-term fluctuations in the demands of patient care.

Adult↗

Preoperative evaluation of ovarian tumors in the premenopause by transvaginosonography.

OBJECTIVE: The aim of the study was to establish reproducible sonomorphologic criteria by use of transvaginosonography in the preoperative evaluation of ovarian tumors in the premenopause. STUDY DESIGN: In a prospective study from 1987 to 1993 we investigated 1072 ovarian tumors. All tumors > or = 3 cm were included in the study. To avoid unnecessary operations, all tumors we rescanned after 6 weeks. The sonomorphologic criteria were correlated with the histologic findings. RESULTS: A total of 4.3% of ovarian tumors in the premenopause were malignant. In the special group of sonographically simple ovarian cysts we found 0.8% malignancies. The incorporation of a control scan after 6 weeks in the management of ovarian cysts reduces the number of unnecessary operations on functional cysts. Only 5.5% of the functional tumors were operated on. The risk for malignancy in cystic-solid ovarian tumors is 17.0%, the highest of all sonomorphologic tumor types. CONCLUSIONS: The use of reproducible sonomorphologic criteria in combination with a control scan in premenopausal women with ovarian cysts proved to be efficient to reduce the number of unnecessary operations and to evaluate the risk for malignancy.

Adult↗

Permissiveness of human embryonal fibroblasts for coxsackieviruses B3. Investigations on virus genetic markers in vitro and localization of virus receptor distribution by immunogold replica technique.

In our previous paper (29) we could show, that the replication of four Coxsackie B3 virus strains in human fibroblast lines from different origin was dependent on both the virus strain and the cell line used. Although generally no cytopathic effect could be observed out of one virus strain more pathogenic virus variants could be selected able to destroy virus-sensitive as well as insensitive fibroblasts. The present study was designed to characterize these virus strains by using several in vitro genetic markers. Differences were found concerning plaque size and the temperature marker, whereas the other markers (d, DD, DEAE-D) remained constant. Furthermore, these models of persistent as well as lytic CVB3 infection were analysed by immunoelectron microscopy to study the interaction of viral ligands with cellular receptors. The qualitative and quantitative differences in adsorption of the CVB3 strains to two human fibroblast lines as well as to HeLa cells corresponded well with the virological results. They underline that even in vitro in human cell lines of different origin changes in distribution, quantity and quality of receptors were demonstrable forming the base for the various virus sensitivity.

Animals↗

Characterization of a chicken luteinizing hormone receptor (cLH-R) complementary deoxyribonucleic acid, and expression of cLH-R messenger ribonucleic acid in the ovary.

Studies were conducted to characterize the chicken ovarian LH receptor (cLH-R) cDNA and to evaluate expression of cLH-R mRNA in follicles at different stages of development. A total of 1.89 kb of nucleic acid sequence corresponding to the cLH-R (1.79 kb of the predicted coding region) was isolated by a combination of reverse transcription-polymerase chain reaction and cDNA library screening techniques. Also of interest was the finding that two of three positive clones isolated from the hen ovarian cDNA library contained an 86-bp insert located in the extracellular domain within 69 bp of the putative transmembrane domain. This insert contains an inframe TGA stop codon, suggesting that an alternatively spliced transcript results in translation of a truncated protein corresponding to the extracellular domain of the cLH-R. Considering all protein domains thus far characterized, the deduced amino acid sequence of the cLH-R shares 73.2% and 74.2% identity with the rat and porcine LH-R sequences, respectively, with highest homology occurring within the seven transmembrane spanning regions (86-88% identity vs. mammalian sequences). Northern blot analysis determined that cLH-R mRNA levels in the theca layer tend to increase through follicle development to the second largest (F2) preovulatory follicle (p = 0.084), and to decrease in the largest preovulatory (F1) follicle (p < 0.02 vs. F2). By comparison, cLH-R mRNA levels are nondetectable (by Northern blot analysis) in granulosa cells from prehierarchal (3-8-mm diameter) follicles. Constitutive expression of cLH-R mRNA in granulosa cells is first detectable at the 9-12-mm diameter stage of follicle development, and levels are further increased in cells from large preovulatory (F1, F2, and F3) follicles (p < 0.01 vs. 9-12-mm stage). Collectively, these results are consistent with previous observations that granulosa cells from prehierarchal follicles fail to produce cAMP or steroids in response to short-term incubation with ovine LH, in vitro, and that granulosa cells acquire LH responsiveness only subsequent to follicle selection into the rapid growth phase.

Alternative Splicing↗

Reduction of cytochrome-c oxidase copper precedes failing cerebral O2 utilization in fluorocarbon-perfused cats.

We determined the relationship of the low-potential copper (CuA) redox state of cytochrome-c oxidase to the brain tissue PO2 (PtiO2) and global cerebral O2 consumption (CMRO2) in vivo. The redox state of cytochrome-c oxidase copper was monitored in perfluorocarbon-exchanged cats under normoxic and graded hypoxic conditions with use of near-infrared spectroscopy. Continuous spectra ranging from 730 to 960 nm were acquired, and the change in copper redox state was assessed by the absorption changes at 830 nm. PtiO2 was measured with O2-sensitive electrodes implanted into the cortex, and CMRO2 was determined by sampling arterial and superior sagittal sinus perfusate and by measuring blood flow with radiolabeled microspheres. As PtiO2 decreased with hypoxia, the CuA of cytochrome-c oxidase became progressively reduced, whereas the CMRO2 was unchanged during the initial stages of hypoxia. Only with severe hypoxia, did CMRO2 and the amplitude of somatosensory evoked potentials decrease. We conclude that the CuA site of cytochrome-c oxidase is involved in a regulatory adjustment that helps maintain CMRO2 constant.

Animals↗

Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia.

We evaluated the methylation status of the X-linked gene phosphoglycerate kinase (PGK1) and the DXS 255 locus detected by probe M27 beta to study clonality in acquired aplastic anemia (AA). A total of 30 females were suitable for clonal analysis of peripheral blood polymorphonuclear cells (PMN) and mononuclear cells using a polymerase chain reaction-based procedure in 24 patients and Southern blotting in 9. Overall, 10 of 30 patients exhibited an imbalanced X-inactivation pattern. However, in 4 patients, analysis of constitutional DNA suggested a skewed methylation pattern and 2 further cases had to be excluded because of the lack of an appropriate control. A truly clonal pattern was thus established in 4 of 30 (13%) patients. In 7 patients who later developed clonal disorders of hematopoiesis, X-inactivation analysis did not predict this event in any case. In patients with a paroxysmal nocturnal hemoglobinuria phenotype, there was no correlation between the proportion of phosphatidylinositol glycan anchored protein (PIG-AP)-deficient blood cells and the corresponding X-inactivation pattern. X-inactivation analysis detected clonal hematopoiesis in only 3 of 10 patients with a deficiency in PIG-AP in the cell population under study, but sorting of nucleated cells on the basis of PIG-AP expression showed the clonal nature of PIG-AP-deficient cells. We conclude that the majority of patients with AA show polyclonal hematopoiesis using X-linked clonal analysis, but that minor clonal populations, such as PIG-AP-deficient cells, may not be detected unless sorted cell populations are separately analyzed.

Adolescent↗

Emergence of CD52-, phosphatidylinositolglycan-anchor-deficient T lymphocytes after in vivo application of Campath-1H for refractory B-cell non-Hodgkin lymphoma.

CD52 is a phosphatidylinositolglycan (PIG)-anchored glycoprotein (PIG-AP) expressed on normal T and B lymphocytes, monocytes, and the majority of B-cell non-Hodgkin lymphomas. We observed the emergence of CD52- T cells in 3 patients after intravenous treatment with the humanized anti-CD52 monoclonal antibody Campath-1H for refractory B-cell lymphoma and could identify the underlaying mechanism. In addition to the absence of CD52, the PIG-AP CD48 and CD59 were not detectable on the CD52- T cells in 2 patients. PIG-AP-deficient T-cell clones from both patients were established. Analysis of the mRNA of the PIG-A gene showed an abnormal size in the T-cell clones from 1 of these patients, suggesting that a mutation in the PIG-A gene was the cause of the expression defect of PIG-AP. An escape from an immune attack directed against PIG-AP+ hematopoiesis has been hypothesized as the cause of the occurrence of PIG-AP-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. Our results support the hypothesis that an attack against the PIG-AP CD52 might lead to the expansion of a PIG-anchor-deficient cell population with the phenotypic and molecular characteristics of PNH cells.

Antibodies, Monoclonal↗

[Predictive factors of minimally effective nCPAP ventilation in treatment of obstructive sleep apnea?].

BACKGROUND: Nasally applied continuous positive airways pressure (nCPAP) ventilation is an effective treatment of obstructive sleep apnoea syndrome (OSAS). As the lowest effective nCPAP-level (nCPAPmin) inter-individually is quite variable individual pressure titration under polysomnographic monitoring is necessary. AIM: To determine whether nCPAPmin can reliably be predicted on the basis of clinical and polysomnographic variables. PATIENTS AND METHODS: A set of 77 unselected OSAS-patients was investigated in the sleep laboratory. We used a standard sleep-related questionnaire, examined anthropometric variables, performed lung function tests and blood gas analyses, and measured nasal cross-sectional area as well as nasal flow resistance. In the night prior to the nCPAP titration a cardiorespiratory polygraphy was performed. Stepwise multiple regression analysis using the titrated nCPAPmin as dependent variable and the clinical and polygraphic data as independent variables revealed gender (GES), neck circumference (NCF), body mass index (BMI), and apnoea-/hypopnea index (AHI) as the optimal set of predictors of nCPAPmin in this model. RESULTS: Multiple regression analysis with these factors yielded the following equation: predicted nCPAPmin = 1.95 + 0.80 x GES + 0.09 x BMI + 0.01 x NCF + 0.03 x AHI (woman: GES = 1; man: GES = 2). The reliability of the equation was tested with a second set of 180 prospective OSAS-patients. In these patients the mean nCPAP-level as titrated in the sleep laboratory was 9.1 +/- 2.0 mbar, whereas the mean predicted nCPAP-level was 8.4 +/- 3.6 mbar (p = n.s.). In 51% of the patients the difference between nCPAPmin measured and predicted was greater than +/- 1 mbar. CONCLUSION: This equation is neither sufficient to reliably predict nCPAPmin nor to prescribe nCPAP without individual pressure titration. The calculated nCPAP-level might however contribute to choosing the most suitable flow generator prior to the titration night.

Adult↗

Monoclonal equine IgM and IgG immunoglobulins.

In order to define equine immunoglobulins (Igs) and to produce monoclonal reference Igs we fused equine peripheral blood mononuclear cells with X63-Ag8.653 non Ig producing murine myeloma cells. A total of 29 equine Ig producing equi-murine heterohybridomas were obtained, of which ten expressed equine Ig for more than 3 months. One of these heterohybridoma lines produced monoclonal IgM, an equine isotype which has not been available in monoclonal form before. Four lines secreted equine IgG of two distinct Ig heavy chain types as assessed by the molecular weight (MW), while the remaining five lines expressed only equine Ig light chains. A sixth Ig light chain expressing variant was obtained by cloning of one of the IgG producing heterohybridoma lines. These monoclonal IgGs were compared with previously described equine IgG monoclonal antibodies (mabs) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). According to their MW we identified five groups of gamma-chains and four groups of Ig light chains.

Animals↗

Controlled multicenter study with quinapril, hydrochlorothiazide, and combination in patients with moderate to severe hypertension.

In an 8-week, double-blind, randomized, active-controlled, multicenter study with three parallel treatment groups, we compared the efficacy and safety of once-daily 20 mg quinapril plus 12.5 mg hydrochlorothiazide (HCTZ) with each drug as monotherapy in patients with moderate to severe hypertension. Hypertensive out-patients with supine diastolic blood pressure (DBP) > or = 105 and < or = 120 mm Hg at the end of a 2- to 4-week placebo-baseline period were randomly assigned to one of the treatment groups. Of the 323 patients who were randomized to double-blind medication, 297 completed the study, but 6 patients were excluded for violations of protocol; therefore, statistical analysis was performed in 291 patients. Only 7 patients withdrew owing to lack of efficacy (2 receiving combination therapy). In all three treatment groups, clinically significant reductions in DBP were achieved. Combination therapy was statistically more effective than each component in both evaluable data and intent-to-treat analyses. The incidence of adverse events (AE) was 24% in the quinapril monotherapy group, 14% in the combination therapy group, and 11% in the HCTZ monotherapy group. Orthostatic hypotension with related symptoms was observed in 4 patients (2 receiving quinapril monotherapy, 1 receiving HCTZ monotherapy, and 1 receiving combination therapy). Once-daily quinapril plus HCTZ provided increased reduction of DBP as compared with the monotherapies and was well tolerated in patients with moderate to severe hypertension.

Adult↗

The pathology of hysterectomy specimens following trans-cervical resection of the endometrium.

The pathological findings in 29 hysterectomy specimens from a series of 175 patients undergoing trans-cervical resection of the endometrium are presented. In all but one case endometrium was present. Although all phases of the normal menstrual cycle were represented, in nine (28%) cases the endometrium appeared inactive, sometimes showing appearances similar to those in Asherman's syndrome. Adenomyosis was present in five (17%) cases and simple hyperplasia in one case. Haematocolpos was present in two cases. Inflammation was uncommon, usually mild in degree and present in the superficial myometrium. Four (14%) cases contained epithelioid or foreign body granulomas in the superficial myometrium. Deposits of haemosiderin and amorphous brown and/or particulate black pigment were seen in a total of 20 (69%) cases. A combination of transmission electronmicroscopy and energy dispersive analysis of X-rays showed these pigments to be a combination of charred organic material and metals, the latter corresponding to the composition of the diathermy cutting loop and electrocautery rollerball used in the ablative surgery.

Adult↗