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Biomedical subjects

C Bieber

Publications and source records attributed to C Bieber.

18 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed2006

High survival in poor years: life history tactics adapted to mast seeding in the edible dormouse.

Edible dormice (Glis glis) reproduce in years with beech mast seeding, but entire populations may skip reproduction in years when tree seeds, a major food resource of this small hibernator, are absent. We tested the hypothesis that the year-to-year variability in reproductive effort caused by this breeding strategy should lead to detectable differences in yearly survival rates. Therefore, we analyzed capture-recapture data from animals occupying nest boxes, collected over nine years at two study sites in Germany. Among fully grown adults (aged two years or older), survival probabilities were significantly lower (0.32 +/- 0.04) after reproductive years (n = 5) compared to years (n = 4) with absent or below-average reproduction (0.58 +/- 0.07) on both study sites. This trade-off between reproduction and subsequent survival was observed in both females and males and appears to be a relatively rare case in which costs of reproduction in terms of longevity are detectable at the population level. Effects of reproduction on survival were less pronounced when yearlings (with a generally lower reproductive effort) were included and were more distinct in a suboptimal habitat. Of those females breeding in nest boxes, 96.5% had only one or two litters within the study period. Considering these and previously published results, including a report of extremely high mean longevities (9-12 years) of dormice in a habitat with infrequent mast seeding, we conclude that edible dormice flexibly adjust life history tactics to local mast patterns. Long stretches of mast failures can in fact lead to relative semelparity, i.e., a strategy in which dormice "sit tight" for several years until environmental conditions are favorable for reproduction.

Animals↗
PubMed2005

[Stress and autonomic dysregulation in patients with fibromyalgia syndrome].

AIM: The aim of the present study was to evaluate to what extent the orthostatic dysregulation of FMS patients can be attributed primarily to reduced baroreceptor-mediated activation of the sympathetic nervous system and whether a hyporeactive sympathetic nervous system can also be confirmed for mental stress. PATIENTS AND METHODS: A total of 28 patients with primary FMS were examined and compared with 15 healthy subjects. Diagnostic investigations of the autonomic nervous system were based on measuring HRV in frequency range and assessing spontaneous baroreflex sensitivity (sBRS) under mental stress and passive orthostatism. RESULTS: Both under orthostatic and mental stress FMS patients exhibited reduced activation of the sympathetic nervous system as measured by the spectral power of HRV in the low-frequency range and the mean arterial blood pressure or heart rate. The present study provided no indications for dysregulation of sBRS. CONCLUSION: The results obtained confirm the hypothesis of a hyporeactive stress system in FMS patients for both peripherally and centrally mediated stimulation of the sympathetic nervous system.

Adult↗
PubMed2004

[Development and validation of assessment instruments for shared decision making].

The German Ministry for Health and Social Security is funding ten projects to introduce shared decision making into clinical practice. The medical problems the projects are focussing on were chosen from among various diseases (e. g. depression, multiple sclerosis, cancer). The ten projects achieved consensus on a core set of instruments for the measurement of process and outcome of the shared decision making. Instruments developed in German-speaking countries are currently not available. Thus, linguistic and cultural validation had to be performed for the core set instruments. The results of the data analysis as well as patient interviews demonstrate the need for improving these instruments. Therefore, the members of the methodological working group concentrated on the integration of these results in a new instrument. In a first step the construct of "shared decision making" was defined, followed by a definition of the process elements characterising shared decision making. Thereafter, items were developed on the basis of the process elements. The new instrument will now be validated for different diseases.

Decision Making↗
PubMed2004

[Shared decision making (SDM) with chronic pain patients. The patient as a partner in the medical decision making process].

Fibromyalgia syndrome (FMS) is an exemplary condition of chronic widespread pain that is difficult to control and often leads to frustration and resignation on the part of both the patient and the doctor. Shared decision making (SDM) could be a means to facilitate doctor-patient interaction and might therefore influence therapeutic decisions taken. We conducted a prospective study to evaluate the effects of SDM with FMS patients. We developed a communication train-ing program for physicians and a computer-based information tool on FMS for patients. The study included 133 FMS patients. Intervention group I (IG I) was treated by communication-trained doctors and had access to a computer-based information tool on FMS,intervention group II (IG II) was treated by standard doctors and received the information tool, and the control group (CG) was treated by standard doctors and got no additional information. All three groups we-re offered the same evidence-based treatment options for FMS. Patients of the IGs were more willing to become involved in exercise, to enroll in integrated group therapy for FMS patients (IGTF), and to take analgesics. Patients of the CG preferred anti-depressants. More patients from IG II and CG opted for relaxation techniques. Patients in IG I and IG II choose significantly more therapeutic options than patients in the CG. SDM is one means to increase FMS patients' readiness for treatment. Especially the element of providing sufficient medical information seems to account for this effect. The readiness to enroll in physical activities, to take analgesics, and to participate in psychotherapeutic elements was most likely to be raised through SDM.

Adult↗
PubMed2004

[Psychosomatics in rheumatology].

Psychosocial factors influence the course and the outcome of chronic somatic diseases. This is also valid for rheumatic diseases like rheumatoid arthritis, spondyloarthropathies, systemic collagen vascular diseases, and fibromyalgia syndrome. The article summarises the evidence-based findings and it illustrates possibilities of psychosomatic treatment in rheumatic diseases by means of three case reports.

Adult↗
PubMed2003

[Psychosocial factors in a fibromyalgia syndrome patient. Assessment by means of electron pain diaries--casuistics and multivariate time series analysis].

OBJECTIVE: Fibromyalgia syndrome (FMS) is a condition of chronic widespread pain. In its process of chronification psychosocial factors play an important role. A multimodal treatment including integrated group therapy has been proved to be effective. Yet little attention has been paid so far to the exact sequence of changes and interrelation between psychosocial factors, functional capacity, and level of pain under integrated group therapy for FMS patients. METHODS: One FMS patient was exemplarily monitored with an electronic diary over 13 weeks while undergoing integrated group therapy. On a daily basis we assessed the level of pain, functional capacity, and other disease-related variables (anxiety, depression, quality of sleep, self-efficacy) via visual analog scales. By the means of multivariate time series analysis the timing of changes in psychosocial factors and their effects on perceived functional capacity was identified. RESULTS: Under integrated group therapy all assessed variables gradually changed in the predicted way. Pain, depression, anxiety could be reduced, whereas self-efficacy, quality of sleep, and functional capacity improved. 71% of the variance could be explained by the multiple regression model. Self-efficacy was, beside pain intensity and depression, an important predictor for functional capacity on the same day. High self-efficacy correlated negatively with the level of functional capacity 3 days later. CONCLUSION: Integrated group therapy proved to be effective. Self-efficacy played an important role regarding the improvement of functional capacity. Depicting the exact timing of changes in the assessed variables helped to detect patterns of influence and indicate directions for further treatment.

Electronics↗
PubMed1989

Tryptophan and 8-anilino-1-naphthalenesulfonate compete for binding to trp repressor.

Anilinonaphthalenesulfonate (ANS) and tryptophan compete for binding to the trp repressor protein; thus, the fluorescence decrease associated with ANS dissociation can be used as a fluorometric marker for tryptophan binding to the protein. Using this approach, the tryptophan equilibrium dissociation constant was measured at 25 degrees C to be 3.7 (+/- 1.2) X 10(-5) M, a value which compares favorably with that obtained by other methods for determining the affinity of this ligand. The presence of nonspecific DNA had no effect on the binding affinity, whereas addition of trp operator DNA yielded a 6-fold increase in affinity of tryptophan binding. The kinetics of tryptophan binding to the aporepressor were monitored directly and by ANS displacement at 4 degrees C. The association rate constant was approximately 4 X 10(6) M-1 s-1, and the dissociation rate constant was approximately 60 s-1. The ratio of these values agrees with the binding constant determined by equilibrium dialysis at this temperature. Using the gel retardation method (Carey, J. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 975-979), the dissociation rate constant for the 40-base pair operator fragment was estimated to be 2 X 10(-2) s-1, which combines with the measured Kd of 0.3 nM to yield an association rate constant comparable to other DNA binding proteins (approximately 10(8) M-1 s-1).

Anilino Naphthalenesulfonates↗
PubMed1985

Treatment of cadaveric renal transplant recipients with total lymphoid irradiation, antithymocyte globulin, and low-dose prednisone.

The ability of preoperative total lymphoid irradiation (TLI) to reduce the need for chronic immunosuppression after cadaveric renal transplantation was examined in 25 recipients who were given a brief course of antithymocyte globulin (ATG) postoperatively with daily low-dose prednisone (0.1-0.2 mg/kg) as the sole maintenance immunosuppressive drug. Patients were selected for the study on the basis of their low levels of cytotoxic antibodies. Grafts were not HLA-matched, and the mean interval between completion of TLI and transplantation was 9 days. During an observation period of up to 25 months, 2 grafts were lost because of rejection. There were two deaths due to disseminated viral infections and two to late cardiovascular complications. At the last observation point, the mean serum creatinine of the 19 patients with functioning grafts was 1.5 mg/dl, and the mean dose of prednisone was 10.2 mg/day. 10 of these patients did not have a rejection episode. Comparison of patients given TLI with a group given cyclosporin at the same institution showed similar graft survival but better graft function in the TLI group.

Adult↗
PubMed1983

Activation of antigen-specific suppressor T cells in the presence of cyclosporin requires interactions between T cells of inducer and suppressor lineage.

To probe the mechanism of suppressor T cell generation in man, we have carried out mixed leukocyte reactions (MLR) in the presence of cyclosporin (CsA), a fungal metabolite which prevents the generation of cytotoxic lymphocytes while permitting activation of suppressor cells. After a 12-d MLR in the presence of 1 microgram/ml CsA, T cells were fractionated into subsets with monoclonal antibodies, and each subset was tested for the ability to inhibit a second fresh MLR that is devoid of CsA. The results show that Leu 2+ T cells derived from the first culture suppress the second MLR in an HLA-DR antigen-specific manner and in the absence of detectable lysis of stimulator cells. However, Leu 2+ cells do not develop into suppressor cells unless acted upon by alloantigen-primed Leu 3+ inducer cells. Furthermore, only those Leu 3+ cells that also express the Leu 8 marker (Leu 3+, 8+) are capable of inducing suppressor cells. Thus, antigen-specific feedback inhibition of an immune response in man results from an ordered series of interactions between T cells of distinct phenotype.

Antibodies, Monoclonal↗
PubMed1979

T-lymphocyte rosette inhibition titering of antisera by direct microassay.

A 60-sample micro-rosette inhibition assay for determining the 100% rosette inhibitory titers of heterologous antisera is described. The assay is performed in histocompatibility trays, under oil, using frozen-thawed thymocytes or peripheral blood lymphocytes for an appropriate period, either with or without added complement; SRBC are inoculated into each well, and rosettes formed by centrifugation of the trays at 200 x g. following centrifugation, glutaraldehyde is added to each well to fix rosettes to the well bottom and the plates inverted to allow unbound SRBC to fall away. One hundred percent rosette inhibition is determined by low power microscopic examination of the inverted wells. Highly reproducible in-assay (+/-4% average standard error) and between-assay (+/-9%) inhibition values are obtained which correlated well (r = 0.99) with values calculated by more conventional methodology.

Animals↗