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Biomedical subjects

R Manz

Publications and source records attributed to R Manz.

At least 19 recordsLinked to original sources
PubMed2006

Induction of pathogenic anti-dsDNA antibodies is controlled on the level of B cells in a non-lupus prone mouse strain.

The SmD1(83-119) peptide is a main target of autoantibodies and T cells in human and murine lupus, but its role in autoimmunity induction remains elusive. Therefore, female Balb/c mice and (NZW x Balb/c)F1 [CWF1] mice with identical MHC haplotype as lupus prone NZB/W mice were immunized with SmD1(83-119). Immunizations of CWF1 mice with SmD1(83-119), but not with the controls (irrelevant peptide, HEL peptide, or saline), induced anti-SmD1(83-119) and anti-dsDNA antibodies and proteinuria not present in Balb/c mice. DsDNA-specific plasma cell induction after SmD1(83-119) immunizations was confirmed by ELISPOT assays showing that the generation of dsDNA-specific antibody forming cells (AFC) was mainly driven by increased T-cell help. T-cell help for the generation of dsDNA-specific AFC was also present in saline-treated CWF1 mice but was controlled on the levels of B cells preventing autoimmunity.

Animals↗
PubMed2001

Strong acceleration of murine lupus by injection of the SmD1(83-119) peptide.

OBJECTIVE: The mechanisms of IgG anti-double-stranded DNA (anti-dsDNA) antibody induction are incompletely understood. We recently demonstrated a high prevalence of autoantibodies to the C-terminus of SmD1 in patients with systemic lupus erythematosus (SLE) that was closely associated with anti-dsDNA reactivity. The aim of the present study was to analyze the influence of the SmD1 C-terminus on the generation of pathogenic anti-dsDNA antibodies in a murine model of SLE. METHODS: Female lupus-prone prenephritic (NZB x NZW)F1 mice (NZB/NZW mice) as well as female control BALB/c, NZW, and (BALB/c x NZW)F, mice (CWF1 mice) were subcutaneously injected with keyhole limpet hemocyanin (KLH)-coupled SmD1(83-119). Controls received injections of recombinant SmD1 (rSmD1), KLH-rSmD1, KLH-coupled randomized peptide of SmD1(83-119), ovalbumin, or saline. Animals were monitored for survival and proteinuria and for levels of plasma creatinine, urea, and autoantibodies. In addition, histologic examinations were performed and T cell responses against SmD1(83-119) peptide and rSmD1 protein were determined in SmD1(83-119)-treated and -untreated NZB/NZW mice. RESULTS: Immunization with KLH-SmD1(83-119), but not with control peptide, significantly accelerated the natural course of lupus in NZB/NZW mice, with premature renal failure and increased development of anti-dsDNA antibodies. Control strains of mice remained healthy, with no relevant anti-SmD1(83-119) antibodies detectable even after immunization. In contrast to findings in control mice, a T cell response against SmD1(83-119) was already present in unmanipulated NZB/NZW mice, and this response was further amplified after immunization. CONCLUSION: The SmD1(83-119) peptide can influence the pathogenic anti-dsDNA response in the NZB/NZW murine lupus model. The data suggest that an SmD1(83-119)-specific T cell response is critical. Therefore, modulation of these autoantigen-specific T cells by tolerance induction may provide a therapeutic approach to specific immunosuppression in lupus.

Animals↗
PubMed2001

Anxious and depressive symptoms in adolescents: epidemiological data of a large scale study in Dresden.

OBJECTIVES: The present large scale epidemiological study was designed to assess the prevalence of mental disorders in adolescents. METHODS: Two cross-sectional studies have been performed in adolescents in Dresden and the results of the examination of 627 high school and 485 secondary school students (mean age 15.5 years) are presented. Self rating procedures like the Beck Depression inventory (BDI) and clinical interviews have been used to enhance validity. RESULTS: The results underline the high prevalence rates of anxiety and depression in adolescents. Up to 30% of the 9th and 10th grades students suffer from mental disorders or are at risk for the development of mental disorders. CONCLUSIONS: Therefore primary prevention of mental disorders is desirable.

Adolescent↗
PubMed2000

[Anxiety and depression in students. A study in Dresden middle schools and high schools].

OBJECTIVES: Recent investigations by the WHO have shown once again the high prevalence of mental disorders in European countries. Mainly in the field of mental disorders considerable deficits exist particularly with regard to primary prevention. METHODS: Although there is no doubt as to the importance of primary prevention within the scope of Public Health, there are deficits in this branch in Germany. This is unfortunate, considering that the proof of successful interventions is evidence for causal risk models. The current investigation is part of a study focusing upon the development, implementation and evaluation of a prevention program for anxiety and depression in adolescents and young adults. RESULTS: Presented here are the prevalence rates of anxiety disorders and depression ascertained in the first cross-sectional study carried out in secondary schools and high schools. A total of 627 high school students and 485 secondary school students in grades nine and ten in Dresden were examined.

Adolescent↗
PubMed1999

Cerebral endothelial cells release TNF-alpha after stimulation with cell walls of Streptococcus pneumoniae and regulate inducible nitric oxide synthase and ICAM-1 expression via autocrine loops.

TNF-alpha, inducible NO synthase (iNOS), and ICAM-1 are considered to be key proteins in the inflammatory response of most tissues. We tested the hypothesis that cell walls of Streptococcus pneumoniae (PCW), the most common cause of adult bacterial meningitis, induce TNF-alpha, iNOS, and ICAM-1 expression in rat primary brain microvascular endothelial cell cultures. We detected TNF-alpha mRNA by RT-PCR already 1 h after stimulation with PCW, while TNF-alpha protein peaked at 4 h (9.4 +/- 3.6 vs 0.1 +/- 0.1 pg/microgram protein). PCW induced iNOS mRNA 2 h after stimulation, followed by an increase of the NO degradation product nitrite (18.1 +/- 4 vs 5.8 +/- 1.8 at 12 h; 18.1 +/- 4 vs 5.8 +/- 1.8 pmol/microgram protein at 72 h). The addition of TNF-alpha Ab significantly reduced nitrite production to 62.2 +/- 14.4% compared with PCW-stimulated brain microvascular endothelial cells (100%). PCW induced the expression of ICAM-1 (measured by FACS), which was completely blocked by TNF-alpha Ab (142 +/- 18.6 vs 97.5 +/- 12.4%; 100% unstimulated brain microvascular endothelial cells). Cerebral endothelial cells express TNF-alpha mRNA as well as iNOS mRNA and release the bioactive proteins in response to PCW. PCW-induced NO production is mediated in part by an autocrine pathway involving TNF-alpha, whereas ICAM-1 expression is completely mediated by this autocrine loop. By these mechanisms, cerebral endothelial cells may regulate critical steps in inflammatory blood-brain-barrier disruption of bacterial meningitis.

Animals↗
PubMed1998

Analysis and sorting of T cells according to cytokine expression.

Functional distinct populations of T helper cells can be defined according to the expression of cytokines. A remarkable diversity of cytokine expression has been demonstrated in single T cells even from clonal populations and up to now no stable surface markers have been described which on the single-cell level directly correlate with the secretion of a certain cytokine. Since cytokines are the major parameters of T cell effector function we have developed strategies which now allow to separate cells according to the specific cytokines they secrete. The "affinity matrix technology"--secreted molecules are relocated to the cell surface by an artificially created antibody matrix--allows to isolate cells according to a distinct secreted product. In addition to this universal, but laborious technology, we could demonstrate by high-sensitivity immunofluorescence that IFN-gamma and IL-10 but not IL-2 and IL-4 are specifically expressed in low copy number on the surface of cells secreting these cytokines. Surface IFN-gamma and IL-10 are the first unambiguous surface markers for pro-inflammatory IFN-gamma-secreting Th 0/1 cells and IL-10-producing anti-inflammatory Th2/3 cells. We have used purified cytokine-secreting T cells to study in individual T cells the sequential production of IL-2, IFN-gamma, and IL-10, the stability of IFN-gamma expression and the selective homing of IFN-gamma-producing cells into inflamed tissues.

Animals↗
PubMed1997

[Body image disturbances in patients with anorexia nervosa 12 years after clinical consultation].

Of 103 patients with anorexia nervosa, 50 women and 5 men were followed-up on the average 11.8 year after clinical presentation with a differentiated method for body awareness according to Askevold. A considerable number of women with body image disturbances, however, largely corresponded to those of a healthy female control group. Both the male anorexia nervosa patients and the healthy male controls had normal findings. Applying to touch-induced stimulus, the body assessment indices only increased in former male anorexia patients but remained the same in female anorexia patients, while they clearly normalized in the sense of a realistic assessment in the two healthy control groups. Surprisingly, there was only little correlation between the visually measured body perception disorder and the self (EDI) and expert assessment (Sianex) at the time of follow-up (exception: the EDI scale 3 [dissatisfaction with one's own body). The global expert rating of body image disturbances at clinical presentation was important as a predictor for the severity of anorexia nervosa after 12 years. The findings were discussed under methodological and clinical aspects.

Adult↗
PubMed1997

[Confounding effects in social science studies and their control. The examples of personality, social support, psychiatric disease].

Social scientific investigations on coping with illness, on the relevance of life events or social support for psychic disorders are concerned with a variety of constructs with interdependent structures. Hypotheses in interrelationships are set up and tested on the construct level. A problem quite often overlooked here is that almost all constructs overlap to a considerable extent both with regard to their content as well as operationally, i.e. they are confounded. Interrelations of constructs which are strongly content-related or operationally confounded are thus in danger of demonstrating artificial results. Data from an extensive epidemiological research project on the incidence and prevalence of psychic disorders in the general population are used applying structural equation models for latent variables to demonstrate confoundation effects for the constructs personality, social support and state of health. Appropriate control methods are described. The results show that partner support maintains a strong influence on the psychic and physical state of health even confoundation of content has been excluded. Application of this method of content confoundation control is discussed with regard to research on coping life event research etc.

Adaptation, Psychological↗
PubMed1996

Pneumococcal cell wall components induce nitric oxide synthase and TNF-alpha in astroglial-enriched cultures.

Astroglia and microglia, the most numerous cells in the central nervous system (CNS), have been shown to produce the inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) upon stimulation with the cytokines IFN-gamma, IL-1-beta, or bacterial lipopolysaccharides (LPS). However, it is not known whether gram-positive bacteria like Streptococcus pneumoniae cause astroglial cells to release nitric oxide (NO) and TNF-alpha. S. pneumoniae meningitis still has a high incidence and mortality in spite of antibiotic therapy. Cell wall components from S. pneumoniae (pneumococcal cell-wall components, PCW) and TNF-alpha have been shown to cause meningeal inflammation and cerebrovascular changes in experimental meningitis. Addition of PCW to cultured rat astroglial cells increased nitrite in the supernatant significantly after 24 h, from 17 +/- 21 to 133 +/- 62 nM/micrograms protein. Nitrite release was dose-dependent in a range shown to cause meningeal inflammation in vivo and was inhibited by the competitive NO synthase inhibitor NW-nitro-L-arginine (L-NA 10(-4 M)) and dexamethasone (10(-6 M)), with transcriptional and translational inhibition by actinomycin D and cycloheximide, respectively. PCW caused a significant increase in the release of TNF-alpha from astroglial cells after 4 h, from 2 +/- 3.5 pg/ml to 102 +/- 13.5 pg/ml, which was inhibited by dexamethasone (10(-6 M)). Our results suggest a role for astroglial-derived NO and TNF-alpha as mediators of vascular and inflammatory response in the early phase of experimental pneumococcal meningitis.

Animals↗
PubMed1995

Analysis and sorting of live cells according to secreted molecules, relocated to a cell-surface affinity matrix.

We have developed a technology for analysis and sorting of live cells according to secreted molecules. An artificial affinity matrix, specific for the secreted product of interest, is created on the cell surface, and the cells are allowed to secrete for a defined time period. The secreted molecules bind to the affinity matrix on the secreting cell and are subsequently labeled with specific fluorescent or magnetic staining reagents for cytometric analysis and cell sorting. Crossfeeding of the secreted products to other cells is prevented by decreasing the permeability of the incubation medium. This approach will have a wide range of applications in biotechnology and biomedical research. Here, we describe analysis and sorting of hybridoma cells, according to secreted antibodies, and of activated T lymphocytes, according to secreted cytokines.

Animals↗
PubMed1995

[Postoperative pulmonary function after lung surgery. Total intravenous anesthesia with propofol in comparison to balanced anesthesia with isoflurane].

After lung resection, early extubation and the rapid return of the patients ability to cooperate is the predominant goal. Propofol anaesthesia is characterised by rapid awakening and recovery of cognitive and psychomotor functions and is consequently desirable for such operations. Experience so far in lung surgery, however, is limited. Besides the level of consciousness we investigated various spirometric parameters after lung resection. Total intravenous anaesthesia was performed with propofol, while balanced anaesthesia was performed with isoflurane. METHODS. A total of 93 patients evaluated electively for wedge excision or lobectomy were enrolled in an open, prospective, randomised, interindividual comparative study. Sixty-three patients could be evaluated with complete data sets. In the evening and the morning before the operation the patients were premedicated orally with clorazepate 0.5-0.7 mg/kg. Anaesthesia was induced in group 1 with propofol (1.0-2.5 mg/kg) and maintained with propofol (4-12 mg/kg) in 50% O2/air. The patients in group 2 received methohexital (1-2 mg/kg) for induction and isoflurane (0.4-2.0 vol%) in 50% O2/air for the maintenance of general anaesthesia. In both groups analgesia was achieved by using fentanyl (up to 10 micrograms/kg) and muscle relaxation by using atracurium. Psychomotor tests (minimal mental state, reaction time) were performed the day before the operation (t1), immediately prior to induction of anaesthesia (t2) and 5 min, 30 min, 60 min, 90 min, 24 h, and 7 days after extubation (t3-t8). Spirometry (forced expiratory volume in 1 s, FEV1; forced vital capacity, FVC; peak expiratory flow, PEF) was carried out at times t1, t2 and t5-t8. RESULTS. The two groups were comparable regarding preoperative status (age, sex, preoperative risk score, psychomotor tests, and spirometric values) and the operation performed (wedge excision/lobectomy, duration of anaesthesia). The extubation time was slightly shorter in the propofol group (18 +/- 8 min) than in the isoflurane group (20 +/- 6 min). Also, the results of the psychomotor tests were somewhat better in the propofol group than those in the isoflurane group. The clearest differences were found in the early postoperative period, but not all differences were significant. Statistically highly significant differences between the two groups were found for the three spirometric parameters. Based on the FEV1 value of the 7th postoperative day, FEV1 taken 60 min after extubation declined by 27.9% in the propofol group vs. 51.7% in the isoflurane group (P = 0.01). At 90 min after extubation the corresponding decline in the propofol group was 26.6%, in the isoflurane group 51.1% (P = 0.003). In addition, the decline of FVC and PEF measured 60 min and 90 min after extubation was significantly smaller in the propofol group than in the isoflurane group. CONCLUSION. The postoperative impairment of lung function after lung resection under propofol anaesthesia is statistically significantly smaller than under isoflurane anaesthesia. Total intravenous anaesthesia with propofol is particularly suitable for this kind of operation.

Adult↗
PubMed1995

[The course of immunologic parameters in inpatient psychotherapy exemplified by 2 single case studies].

Psycho-neuroimmunology depicts a conceptual frame in which possible interactions between psychic and physical processes can be examined. It could be very significant in the field of psychosomatics when the courses of psychic and somatic processes are examined. However, the research results from this field of study are varied and only for a few parameters of immunity is it possible to prove correlations with psychic variables. Many of the studies that have been conducted up to date were construed as cross-section studies and possibly therefore are not very suitable for depicting the probably very complicated forms of interactions between psychic and somatic levels in an adequate manner. In the framework of stationary psychosomatic psychotherapy two single case studies were carried out in order to examine temporal connections between psychic and immunological course parameters. Both single case studies are to be viewed as explorative attempts of examining questions of examination design and organization which are highly resolved regarding time. Furthermore we report several interesting individual results which emphasize in general the correlation between psychic and somatic parameters also in the course of time. However the limits of such studies regarding the significance of the individual immunological parameters, using time serial analytical methods as well as constructing models in the field of psycho-neuroimmunology are discussed.

Adult↗
PubMed1995

[What modifies the course of Crohn disease?].

This paper presents empirical results concerning the interdependency of somatic and psychological factors in the course of Crohn's disease. Data derived from the Heidelberg psychosomatic study on Crohn's disease are explored with the help of canonical correlation analysis. Somatic data recorded in the acute stage of Crohn's disease were not empirically found to be predictive of the psychological status after convalescence empirically. On the other hand, we did find psychological data that allowed prediction of the somatic status when the patients were in remission. Of these psychological data, coping resources are the most important predictors of the course of the disease. In particular, depressive forms of coping are correlated with personality factors, whereas active coping forms are not. The results have implications for scientific theory as well as for clinical practice.

Adaptation, Psychological↗
PubMed1995

[Methodological and statistical aspects of therapy evaluation exemplified by the Berlin psychotherapy study].

The answer to the question concerning the efficacy of psychotherapy is increasingly sought metaanalytically. For this purpose almost exclusively investigations are taken into consideration which have at least one control group. Using realistic data, the present paper refers to some basic considerations for the investigation and evaluation of therapeutic changes, which are however not always satisfyingly solved in metaanalytical studies. Investigations, therefore, especially of naturalistic samples, such as may be found in the context of outpatient or inpatient routine care, have a high clinical relevance for the evaluation of therapeutic changes even if they do not satisfy experimental requirements/standards. However, they do supplement experimental studies where the important aspect of external validity is concerned.

Germany↗
PubMed1994

[Do patients with anorexia nervosa return to psychological health? results of a 12-year follow-up of 103 patients].

In a long-term follow-up study over 12.7% (range 9-19) years, 16 of 103 patients with anorexia nervosa died. 92% of the survivors were followed up personally, 7% only indirectly. The paper presents the psychological changes assessed by means of the Anorexia Nervosa Symptom Score in the course of the disorder. At the time of catamnesis, the psychic condition of the patients was furthermore evaluated in more detail by procedures of independent assessment (DSM III-R, Impairment-Score (IS), Confidant Rating) as well as by using different instruments of self-assessment (Eating Attitude Test, Eating Disorder Inventory, Social Network Questionnaire). In a case conference taking into account all relevant findings, 40.1% of the patients were found to be healthy, 30.4% were considered to still show severe psychic disorders, and 29.4% were rated as desolate. These results suggest that part of the patients become psychicalls healthy again. Altogether, however, the long-term prognosis of anorexia has to be regarded as rather poor.

Adaptation, Psychological↗
PubMed1994

[Results of psychoanalytic therapy].

Within a naturalistic design 44 psychoanalytic treated patients are examined with regard to qualitative and quantitative outcome. The results are compared to 56 dynamic and 164 inpatient therapies. A comparison of symptoms, diagnoses and motivation before therapy leads to the conclusion that there are very different patient groups treated within this different settings. Therefore randomization seems to be an inadequate strategy to compare groups in different therapeutic settings. Using different criteria of outcome it can be demonstrated that psychoanalytic treated patients improve very well and to a larger extent than psychodynamically treated patients or inpatients. Different criteria of outcome and different observing perspectives (patient/therapist) lead to interesting results. Patients report primarily improvements in somatic, anxiety and depressive complaints. Therapists moreover report substantial improvements in interactional symptoms and behaviour. The different results in using several criteria are presented and discussed with regard to the methodology of outcome measurement. Finally recommendations for further studies in the psychoanalytic context are presented.

Ambulatory Care↗
PubMed1993

[The prognostic significance of the therapeutic working alliance from the perspective of the patient and therapist].

In general, the prognostic relevance of a working alliance for both the course and the outcome of psychotherapy is no longer a matter of dispute. Since a working alliance is conceived as an interactional variable, the results must be interpreted on the basis of several important dimensions: the perspective of the investigator and the time structure during the course of therapy. Using the data available from the Berlin Psychotherapy Study (Rudolf 1991), we investigated for the 238 patients (inpatients and outpatients who received psychoanalytically oriented therapy in the study) the prognostic relevance of diagnostic and therapy-related working alliance variables for the various outcomes investigated. A complex correlation-statistical method (latent-trait-model) was used to consider the investigator perspective with regard to the working alliance and the outcome as well as the time structure and the diagnostic variables. Our results emphasize the relevance of the therapist's perspective beginning with the diagnostic indication, the working alliance and finally the outcome. The patient's perspective, however, seems to be less relevant. The results are presented and discussed in relation to the relevant literature. One result we have found as a further important dimension is that the kind of therapy carried out must be taken into consideration. This implies that as in our study for all phases of the investigation therapy specific instruments must be applied. In this regard our results also contribute to the validation of the instrument used to measure the working alliance TAB.

Adult↗