Biomedical subjects

A Keil

Publications and source records attributed to A Keil.

34 records · Page 2Linked to original sources

PubMed1999

Regulation of CD95 expression and CD95-mediated cell death by interferon-gamma in acute lymphoblastic leukemia with chromosomal translocation t(4;11).

The regulatory effects of IFNgamma on CD95 expression and CD95-mediated cell death were investigated in three high-risk pro-B acute lymphoblastic leukemia (ALL) lines that carry the chromosomal translocation t(4;11)(q21;q23). These leukemias are characteristically refractory to conventional chemotherapeutic treatments operating through the induction of apoptosis. However, the mechanisms leading to increased cell survival and resistance to cell death in these leukemias are largely unknown. Interferon-gamma (IFNgamma), a potent inhibitor of hematopoiesis, acts in part by upregulating CD95 and sensitizing cells to CD95-induced apoptosis. The t(4;11) lines SEM, RS4;11, and MV4;11 expressed low levels of CD95, but were completely resistant to CD95-mediated death. Addition of IFNgamma markedly upregulated CD95 expression in SEM (8-9-fold), RS4;11 (2-3-fold), and MV4;11 (2-3-fold) lines. However, after treatment with IFNgamma, only an 11% increase in sensitivity to CD95-mediated cell death was observed in SEM cells, whereas RS4;11 and MV4;11 cells remained resistant. Cycloheximide, but not actinomycin D or brefeldin A, increased CD95-specific cell death only in IFNgamma-treated RS4;11 cells by approximately 12%. Abundant levels of Bcl-2 and Bcl-XL, known to inhibit CD95-signaling in some cells, were present suggesting a possible role for both molecules in the resistance to CD95-mediated cell death. Resistance of the leukemic blasts to CD95-mediated cell death and the failure of IFNgamma to substantially sensitize the CD95-signaling pathway may contribute to the highly malignant phenotype of pro-B ALL with translocation t(4;11).

Antigens, Surface↗

PubMed1999

TGF-beta1 in liver fibrosis: an inducible transgenic mouse model to study liver fibrogenesis.

Transforming growth factor-beta1 (TGF-beta1) is a powerful stimulus for collagen formation in vitro. To determine the in vivo effects of TGF-beta1 on liver fibrogenesis, we generated transgenic mice overexpressing a fusion gene [C-reactive protein (CRP)/TGF-beta1] consisting of the cDNA coding for an activated form of TGF-beta1 under the control of the regulatory elements of the inducible human CRP gene promoter. Two transgenic lines were generated with liver-specific overexpression of mature TGF-beta1. After induction of the acute phase response (15 h) with lipopolysaccharide (100 microgram ip), plasma TGF-beta1 levels reached >600 ng/ml in transgenic animals, which is >100 times above normal plasma levels. Basal plasma levels of uninduced transgenic animals were about two to five times above normal. As a consequence of hepatic TGF-beta1 expression, we could demonstrate marked transient upregulation of procollagen I and procollagen III mRNA in the liver 15 h after the peak of TGF-beta1 expression. Liver histology after repeated induction of transgene expression showed an activation of hepatic stellate cells in both transgenic lines. The fibrotic process was characterized by perisinusoidal deposition of collagen in a linear pattern. This transgenic mouse model gives in vivo evidence for the important role of TGF-beta1 in stellate cell activation and liver fibrogenesis. Due to the ability to control the level of TGF-beta1 expression, this model allows the study of the regulation and kinetics of collagen synthesis and fibrolysis as well as the degree of reversibility of liver fibrosis. The CRP/TGF-beta1 transgenic mouse model may finally serve as a model for the testing of antifibrogenic agents.

Animals↗

PubMed1998

Dynamical aspects of motor and perceptual processes in schizophrenic patients and healthy controls.

The present study examined the temporal stationarity of the performance of 16 schizophrenic patients and 16 controls matched for age and sex in a bimanual coordination task and a perceptual task. In the motor task, rhythmic finger oscillations (alternating activity of homologue muscle groups) at increasing speed levels resulted in two measures, the preferred oscillation frequency and the critical frequency at which phase transitions (change towards simultaneous activity of homologue muscle groups) occurred. A measure of local dimensional complexity (pointwise D2 or PD2), which is a measure of non-linear dynamics, was determined for the acceleration profiles of the subjects' movements. Schizophrenics exhibited less stable movement dynamics than controls in horizontal finger cycling, indicated by a lower ratio critical/preferred frequency (critical ratio) and by higher means and standard deviations of the pointwise D2. In vertical cycling, the critical ratio did not differentiate between groups, while PD2 means and standard deviations did. Groups also differed specifically in perception of two ambiguous figures (Schroeder stairs and Rubin vase). Schizophrenics showed significantly higher reversal rates for the Rubin vase and a differential perceptive in comparison to controls in the perception of the Schroeder stairs. Measures of perceptual and motor stability were unrelated, which suggests that perceptual and motor processes are not influenced by a common underlying mechanism.

Adult↗

PubMed1998

[Radiotherapy in surgical and nonsurgical patients. Therapy expectations, quality of life and physician assessment].

The present study investigates patients' expectations toward radiotherapy and their associations to quality of life and physician judgements. Fifty-five patients with tumors of different sites (30 with previous tumor-related surgery, 25 without surgery) admitted to the department of radiotherapy filled out a standardized questionnaire (EORTC QLQ-C30, PLC by Siegrist et al., therapy-related expectations and success) before and after inpatient radiotherapy. The corresponding physician ratings were collected. Fifty-eight percent of the patients expected the therapeutic goal "healing", whereas from the physician's standpoint this was realistic in only 7% of cases. The specific radiotherapy-related expectations "tumor control" and "pain relief" reached almost the same levels in patients and physician (71% vs 71% and 40% vs 44%). Patients with healing expectancy reported higher quality of life at the beginning of the therapy (53.4% vs 39.9%); patients expecting pain relief reported lower quality of life (37.1% vs 54.5%). Surgical patients who had been operated on within the past year (n = 18) showed a particularly high healing expectancy (83%), whereas patients whose operation dated back more than 1 year focused on pain relief as therapeutic goal (83%). The surgeon, as the primary contact person for patients, can influence patients' therapy-related expectations. In explaining the overall therapeutic strategy, surgeons should also mention the scope and limits of adjuvant therapies.

Adult↗

PubMed1991

Murray Valley encephalitis acquired in Western Australia.

OBJECTIVE: To report a recent fatal case of encephalitis associated with evidence of Murray Valley encephalitis virus infection, only the second fatality from this infection in Western Australia. CLINICAL FEATURES: An 18-month-old Aboriginal boy was admitted to hospital in northwest Western Australia with proven Haemophilus influenzae type b meningitis. INTERVENTION AND OUTCOME: After an initial good response to antibiotics (amoxycillin and cefotaxime) he relapsed and died with evidence of encephalitis. Analysis of serum showed a high titre of antibody to Murray Valley encephalitis (MVE) virus with the presence of specific IgM. No evidence was found for other infective agents. CONCLUSION: It is likely that this child died from MVE which followed his bacterial meningitis. Of the strains of mosquitoes trapped in the area of suspected infection 77.8% were Culex annulirostris, the major vector species for MVE. No MVE virus was isolated from these mosquitoes, but serum from one of the sentinel chickens contained MVE virus antibodies, indicating the presence of the virus in that region.

Encephalitis↗

PubMed1989

Binding of divalent and trivalent cations with crotoxin and with its phospholipase and its non-catalytic subunits: effects on enzymatic activity and on the interaction of phospholipase component with phospholipids.

We have studied the interaction of divalent and trivalent with a potent phospholipase A(2) neurotoxin, crotoxin, from Crotalus durissus terrificus venom. The pharmacological action of crotoxin requires dissociation of its catalytic subunit (component B) and of its non-enzymatic chaperone subunit (component A), then the binding of the phospholipase subunit to target sites on cellular membranes and finally phospholipid hydrolysis. In this report, we show that the phospholipase A(2) activity of crotoxin and of component B required Ca2+ and that other divalent cations (Sr2+, Cd2+ and Ba2+) and trivalent lanthanide ions are inhibitors. The lowest phospholipase A(2) activity was observed in the presence of Ba2+, which proved to be a competitive inhibitor of Ca2+. The binding of divalent cations and trivalent lanthanide ions to crotoxin and to its subunits has been examined by equilibrium dialysis and by spectrofluorimetric methods. We found that crotoxin binds two divalent cations per mole with different affinities; the site presenting the highest affinity (K(d) in the mM range) in involved in the activation (or inhibition) of the phospholipase A(2) activity and must therefore be located on component B, the other site (K(d) higher than 10 mM) is probably localized on component A and does not play any role in the catalytic activity of crotoxin. We also observed that crotoxin component B binds to vesicular and micellar phospholipids, even in the absence of divalent cations. The affinity of this interaction either does not change or else increases by an order of magnitude in the presence of divalent cations.

Cations, Divalent↗

PubMed1987

The role of childhood sexual abuse in the development of alcoholism in women.

The effects of childhood sexual abuse on the development of alcoholism in women were examined by comparing a sample of 45 alcoholic women selected from local treatment agencies and Alcoholics Anonymous groups with a group of 40 nonalcoholic women selected randomly from a household population. Face-to-face interview schedules were administered to both samples. Sexual abuse was defined as any unwanted sexual contact with a person at least five years older than the respondent, or with any family relative, regardless of age difference. Types of sexual contact included both nonphysical contact (e.g., invitations, exposure) and physical contact (e.g., fondling, intercourse). Results showed that alcoholic women were more likely to have experienced sexual abuse, had a greater number of different types of sexual abuse experiences, and endured sexual abuse over a longer period than the comparison group. The presence of any childhood sexual abuse experience was sufficient to discriminate between the alcoholic women and the comparison group, even controlling for demographic variables and the presence of a parent with alcohol-related problems. Although alcoholic women were more likely to report that a parent had alcohol-related problems, relatively few of the sexual abuse incidents were perpetrated by a parent. The data suggest that vulnerabilities to sexual abuse were attributable to environmental or psychological factors in homes in which a parent was reported as having alcohol-related problems.

Adolescent↗

PubMed1975

[Report of case of opalescent dentin. A polariation optic and microradiographic study on a pulpless tooth].

Ground sections prepared from a molar (-7) with opalescent dentine were investigated by the means of polarizing microscopy and microradiography. Histological and clinical findings are discussed. Unfortunately, heredity could not be surely determined. But in all experience we are shure, that a hereditary mutation, recently or earlier in a generation occured, was the cause also in this case.

Adult↗

PubMed1975