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Biomedical subjects

C Zimmermann

Publications and source records attributed to C Zimmermann.

At least 73 records · Page 4Linked to original sources

SV40 T1-mRNA trans-splicing and translation requires that the in vitro synthesized cRNA is capped before microinjection.

The purpose of this investigation was to study the effect on cap structure for trans-splicing in mammalian cells. The early SV40 Bst/Bam pre-mRNA (cRNA) was synthesized in vitro in both capped (cap-Bst/Bam-cRNA) and non-capped (Bst/Bam-cRNA) versions and microinjected into the nuclei of TC7 cells. Trans-splicing was monitored by immunofluorescence staining (T1-antigen) and by RT-PCR analysis. Cap-Bst/Bam-cRNA was trans-spliced with high efficiency, but not the Bst/Bam-cRNA molecules. Northern blot analysis revealed that both the capped and uncapped cRNA molecules had similar stability in the microinjected cells. The coinjected m7G(5')ppp(5')G cap analog did not inhibit the trans-splicing reaction in vivo and did not prevent nuclear export of the mRNA.

Animals↗

SV40 T-antigen induces breast cancer formation with a high efficiency in lactating and virgin WAP-SV-T transgenic animals but with a low efficiency in ovariectomized animals.

The whey acid protein (WAP) is a major mouse milk protein and its gene expression is induced by various lactotrophic hormones (eg, estrogen, progesterone). Transgenic animals harboring the early SV40 coding region (T/t-antigen) under the transcriptional control of the WAP promoter develop breast cancer after the first lactation period. The tumor cells synthesize the SV40 T-antigen with a high efficiency indicating that WAP-SV-T expression escapes down-regulation after the lactation period. However about 5-10% of the tumors became T-antigen negative during tumor progression and WAP-SV-T expression was only demonstrable by PCR analysis. Both T-antigen positive and negative tumor cells expressed the estrogen and progesterone receptor at a comparable rate, indicating that hormone receptor levels do not determine expression of the WAP-SV-T transgene. Furthermore, WAP and WAP-SV-T gene expression are not restricted to the pregnancy-lactation period. Virgin animals also express both genes with a low efficiency and about 70% of these animals also developed T-antigen positive breast tumors. The tumor rate however was strongly reduced in ovariectomized animals, indicating that the ovary hormones play a critical role in breast cancer formation.

Animals↗

Homeostatic regulation of CD8+ T cells after antigen challenge in the absence of Fas (CD95).

The role of Fas in the homeostatic regulation of CD8+ T cells after antigen challenge was analyzed in the murine model of lymphocytic choriomeningitis virus (LCMV) infection. Mice homozygous for the lpr mutation and carrying T cell receptor (TCR) alphabeta transgenes specific for the LCMV glycoprotein peptide aa 33-41 in the context of H-2Db were used. Five main results emerged: first, development of lymphadenopathy and of CD4- CD8- double-negative B220+ T cells in lpr mice was not inhibited by the alphabeta TCR transgenes; second, tolerance induction and peripheral deletion of CD8+ T cells induced by LCMV glycoprotein peptide injection was independent of Fas expression; third, clonal down-regulation of Fas-deficient TCR-transgenic CD8+ T cells after acute LCM virus infection was identical to the decline of transgenic T cells expressing Fas; fourth, in vivo activated CD8+ effector T cells from TCR transgenic and TCR-lpr/lpr mice were equally susceptible to activation-induced cell death in vitro; and fifth, transgenic effector T cells from lpr/lpr mice were cleared in the declining phase of the immune response in vivo without giving rise to CD4- CD8- double-negative T cells. Taken together, these data suggest that the homeostatic regulation of CD8+ T cells after antigen challenge in vivo is regulated by mechanisms that do not require Fas.

Animals↗

[Risk factors in self-injurious behavior in a Swiss prison].

Suicide is reported to be one of the leading causes of death in prison (25-45% of deaths), and attempted suicide is observed more frequently in prison than in the general population. The purpose of this study is to identify the risk factors of the suicidal gestures (including wrist slashing) in the Geneva prison, and their impact; with a view to elaborating possible preventive measures. A case-control study (172 cases and 169 controls) was conducted retrospectively on the basis of medical records. Demographic and medical data for cases were compared to similar data for non-suicidal inmates. A multivariate analysis of the data revealed that the risk of suicidal inmates. A multivariate analysis of the data revealed that the risk of suicidal gestures increased for the following characteristics: age less than 25 years (RR = 4.4), previous suicide attempts (RR = 4.7), a past history of psychiatric treatment (RR = 2.5), and finally, opiate drug dependence (RR = 2.8).

Adolescent↗

[Umbilical reconstruction after excision of melanomas in the area of the umbilicus].

Reconstruction of the navel after tumour excision with subsequent navel resection is of great aesthetic importance for the patient. Methods of navel reconstruction are found in the literature but do not provide an elegant solution to the problem. Our method permits reconstruction of the navel during wound closure, by creation of two opposing trapezoidal skin flaps at the excision margin in the midline of the body; the umbilical fossa is then restored by jointly anchoring these flaps to the linea alba. Reconstruction has been successfully carried out in this way after melanoma excision in 7 patients.

Abdominal Neoplasms↗

["Thunder clap headache": an independent form of headache?].

Acute severe headache indicative of subarachnoid haemorrhage (SAH), but without the requisite proof, is defined as thunderclap. A special pathophysiological mechanism for the development of this headache is not known as yet. This retrospective study comprised 84 patients. All had the typical clinical signs of a SAH, but cranial computer tomography and lumbar puncture excluded this diagnosis. In 82% of these patients the headache was classified according to aetiologically defined symptomatic groups. One patient with headache of vascular aetiology had an angiographically proven, but not ruptured aneurysm. No definite cause for the headache was found in 18% of cases. None of the patients followed up over a period of between 12 months and 6 years developed SAH or any other severe neurological disorder. 9% reported repeat of the headache event. Thunderclap headache seems to be only a descriptive term for patients with symptoms typical of a SAH without signs of bleeding. Thunderclap headache has no diagnostic or prognostic specificity and therefore we recommend use of this term only as a description of the headache characteristic. Thunderclap headache is not a predictor of a future SAH. Cerebral angiography should be restricted to cases with neurological deficits.

Adolescent↗

Fine specificity of anti-Ro(SSA) autoantibodies and clinical manifestations in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the fine specificity of the anti-Ro(SSA) autoimmune response in patients with systemic lupus erythematosus (SLE), and to correlate it with clinical and serological manifestations. METHODS: The frequency of anti-Ro and anti-La autoantibodies was determined by double immunodiffusion (DID), ELISA, and immunoblotting (IB) in 69 patients with SLE and 39 controls. Protein and RNA immunoprecipitation were used to further characterize anti-Ro positive sera. RESULTS: Anti-Ro antibodies were detected in 37 (54%) patients: 33 (48%) were positive by DID, 35 (51%) by ELISA, and 25 (35%) by IB; 32 sera were reactive in at least 2 of these 3 assay systems. By IB, 12 patients had antibodies to both the 60 kDa Ro (Ro60) and the 52 kDa Ro (Ro52), 11 patients were anti-Ro60 positive, 2 patients were anti-Ro52 positive, and 12 patients were not reactive with blotted Ro antigens. However, in immunoprecipitation assays all but one anti-Ro positive sera precipitated both Ro proteins. Anti-La reactivities were found in 15 anti-Ro positive patients: 13 sera were positive by IB, 11 by ELISA, and 9 by DID. Significant associations of anti-Ro antibodies with clinical symptoms were found for sicca syndrome, which was increased in anti-Ro positive patients (p < 0.05 vs anti-Ro negative patients), and for nephritis, for which an inverse correlation was found, since it was less frequently diagnosed in anti-Ro positive patients (p < 0.01). However, this association was seen only for those anti-Ro positive patients who were not reactive with Ro52 by IB. No difference was observed between anti-Ro/La and anti-Ro positive patients. CONCLUSION: DID and ELISA were of comparable sensitivity for detection of anti-Ro, IB was the most sensitive method for detection of anti-La. Moreover, our data indicate that IB may help to characterize clinically distinct subgroups of anti-Ro positive patients with SLE. Thus, determination of anti-Ro by IB may increase the prognostic value of this autoantibody.

Adolescent↗

[Cryoglobulinemia in chronic hepatitis C. Improvement by alpha-interferon is independent of virus elimination].

BACKGROUND: During the last few years, the association of mixed cryoglobulinemia with chronic viral infections has gained increasing interest. Chronic hepatitis C seems to play a major role. As alpha-interferon is an established therapy for chronic hepatitis C, it was also tried successfully in cryoglobulinemia type II, associated with chronic hepatitis C virus infection. PATIENTS: The course of 3 patients with cryoglobulinemia type II and chronic hepatitis C is presented. RESULTS: Two patients received immunosuppressive therapy prior to alpha-interferon without success. In all cases, remission or improvement of the cryoglobulinemia was noticed with alpha-interferon, but none of the patients cleared the hepatitis C virus. Although the treatment was well tolerated, two patients developed neurologic resp. psychiatric side effects, probably due to alpha-interferon. CONCLUSION: From our results and from data reported previously, immunomodulating treatment with alpha-interferon can be recommended for therapy of virus-associated cryoglobulinemia rather than the "classical" treatment with immunosuppressive agents. The specific side effects of alpha-interferon have to be monitored carefully.

Adult↗

Selection procedures for nonmatured phage antibodies: a quantitative comparison and optimization strategies.

Libraries of peptides and proteins can be displayed on the surface of filamentous bacteriophage. The efficient capturing of phage recognizing a defined target molecule remains a serious obstacle, in particular when the phage are present at a low frequency or have a reduced affinity like nonmatured phage antibodies and when the availability of target molecules is limited. We present theoretical considerations and experimental data which allowed us to substantially improve microselection under these conditions. We used a model phage displaying an anti-(2-phenyl-5-oxazolone) single-chain Fv antibody fragment. Following standard protocols and aiming at a low nonspecific binding, only 3.6 x 10(-3)% of the phage input could be recovered from a single round of selection performed in the wells of a microtiter plate. Our results explain why this often employed panning in wells is not efficient, especially with high-molecular-weight target molecules. We devised a procedure which increased the probability of microselection by a factor of 34. An alternative capturing method using immunotubes with a new protocol decreased the amount of required work by a factor of 30. In the case of a nonlimited supply of target molecules, column-affinity chromatography is recommended.

Antibodies, Viral↗

Plaque surface area after rinsing with a low-level fluoride-containing Darjeeling tea.

Plaque surface area after rinsing with a tea, containing low levels of fluoride, was evaluated in 30 human volunteers with a single-blind, one-operator, three-period, three-treatment cross-over study. The mouthwashes employed were: (1) tea (Darjeeling first flush:< 0.2 ppm F-), (2) Meridol(R), (3) control (tap water:< 0.2 ppm F-). During the experiment the participants refrained from oral hygiene procedures and rinsed their mouth three times a day after each meal with 20 ml of the respective rinse. After 3 d standardized photographs were taken of the upper canines and premolars and the plaque areas were measured planimetrically. Statistical analysis showed a marked decrease in plaque surface area after rinsing with Meridol, whereas no difference in plaque surface area was observed after mouthrinsing with tea and tap water, respectively.

Adolescent↗

[First treatment demands for drug abuse: and indicator of developmental trends].

The county of Geneva, Switzerland, is part of an international multi-city survey under the auspices of the Council of Europe. This survey is designed to use common indicators for assessing and comparing drug misuse and its evolution in participating cities and regions. Its aim is to improve the strategies for controlling drug misuse. The first indicator under study is the "first treatment demand". Its objectives are to evaluate the treatment demand as well as the evolution of drug misuse in terms of patient characteristics, so as to optimise prevention and treatment policies. All treatment demands for drug misuse that meet the study's entry criteria are recorded in a permanent and centralized data bank, through an anonymous encoded form filled in by the treatment centers at the time of the demand. Later demands by the same patient are merged with the precedent ones. In this way, both the totality of treatment demands and the subset of first demands can be analyzed and information about individual trajectories can be collected. The introduction of this indicator is subjected to various problems due first of all to the illicit character of drug misuse. In particular, the necessary measures to guarantee strict confidentiality make it more difficult to obtain reliable data, especially for the merging of different treatment demands by the same patient. This paper reports on the introduction of the indicator in Geneva and its anticipated results.

Confidentiality↗