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Biomedical subjects

C Winkler

Publications and source records attributed to C Winkler.

At least 91 records · Page 5Linked to original sources
PubMed1996

Pluripotency and differentiation of embryonic stem cell lines from the medakafish (Oryzias latipes).

Small aquarium fish, like the medaka and zebrafish, offer an excellent opportunity to combine embryological, genetic and molecular analyses of vertebrate development. Pluripotent embryonic stem (ES) cells have enormous potential to study the totipotency and differentiation of cells and provide s bridge linking in vitro manipulations of the genome. In this report we describe the establishment, pluripotency and differentiation of medaka ES-like cell lines (MES). The MES cells exhibit stable growth over 18 months of culture with 100 passages using defined culture conditions in the absence of feeder layer cells. They have a normal karyotype and form colonies of densely packed, alkaline phosphatase-positive cells resembling undifferentiated mouse ES cells. In suspension culture they form embryoid bodies, and under appropriate conditions, differentiate into a variety of cell types.

Alkaline Phosphatase↗
PubMed1996

Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection.

Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human immunodeficiency virus type 1 (HIV-1). Comprehensive statistical analysis produced an HLA profile that predicted time from HIV-1 infection to the onset of AIDS. The profile was developed in a cohort of 139 men and evaluated in a second unrelated cohort of 102 men. In the evaluation cohort, the profile discriminated a sixfold difference between groups with the shortest and longest times to AIDS (P = 0.001). These findings support current theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV-1 and other infections.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[The efficacy of radiotherapy in vertebral hemangiomas].

AIM: Assessment of the efficacy of radiation therapy for symptomatic vertebral hemangiomas. PATIENTS AND METHODS: Records of 19 patients who were treated from 1969 to 1988 were retrospectively analyzed. Radiation treatment was given at 2 Gy per fraction to 20 Gy (n = 2), 30 Gy (n = 11), or 40 Gy (n = 6). Improvement of symptoms was chosen to determine the efficacy of the treatment. In addition the lesions were controlled radiographically. RESULTS: Symptomatic improvement was achieved in 17 of 19 patients, remission was complete in 7 patients. No dose-response relationship was observed. The median time to improvement of symptoms was 3 months. The radiographic controls did not correlate with the clinical course. CONCLUSIONS: Radiation therapy is an effective treatment for symptomatic vertebral hemangiomas. The aim of the treatment is to ameliorate clinical symptoms, radiographic improvement is of minor importance.

Adult↗
PubMed1996

Who should be screened to reduce the endoscopy workload in Mulago Hospital?

A retrospective study of 330 patients who had been endoscoped in Mulago hospital was done. It was found that of these 119 (36.1%) were normal endoscopically. Normal endoscopy was significantly associated with patients presenting with dyspepsia. Dyspepsia was commoner in the age group 13-45 years compared to the age group 46-85 years. The older age group, 46-85 years, had a significantly higher prevalence of serious disease. It is concluded that it is the younger patients with dyspepsia who should be screened to reduce the endoscopy workload. Published guidelines should be used to assist in the screening process.

Adolescent↗
PubMed1995

Telepathology: frozen section diagnosis at a distance.

Telepathology may be used to provide a frozen section service to hospitals without a department or institute of pathology. We have developed a telepathology system using the commercially available Integrated Services Digital Network (ISDN). The main software and hardware elements of our system are: Apple Macintosh workstations, a program for simultaneous transfer of image, voice and data, and a data bank for storage of patients' data and microscopic images. A picture instrument manager (PIM) makes remote control of microscopes or other instruments possible. The system connects the Department of Pathology of the University of Basel with the Regional Hospital of Samedan, 250 km away, and the Regional Hospital of Burgdorf, 100 km away. During a period of 20 months, frozen sections with the hospitals in Samedan and Burgdorf were performed in 53 patients. Between 54 and 58 s were required for the transfer of a diagnostic 8-bit grey level image containing 341 +/- 26.1 (standard error) kbytes (n = 13) or a diagnostic 24-bit colour image containing 165 +/- 16.9 kbytes (n = 40). Frozen section diagnosis was completed in 20-40 min. True-positive diagnoses of malignant tumours were achieved in 85.7% of cases (sensitivity = 0.857). No false-positive diagnosis was made. In 3 of the 53 cases telepathological diagnosis was not possible for technical reasons.

Frozen Sections↗
PubMed1995

Influence of propionibacterium avidum KP-40 on the proliferation, maturation, emigration and activity of thymocytes and monocytes.

Inactivated cells of Propionibacterium avidum KP-40 could be shown to induce thymocyte proliferation and maturation in BALB/c-mice after intraperitoneal administration of the optimal immunomodulating dosage (1 mg per mouse). The increase in thymus weight and thymocyte numbers per mg organ weight was most pronounced and statistically significant 10 days after P. avidum KP-40 administration. Determinations of lymphatic subsets revealed a considerable up-regulation of mature cells expressing helper/inducer (L3T4+) or cytotoxic/suppressor (Lyt-2+) phenotypes and immature cells presenting both L3T4+/Lyt-2+ antigens. Obviously, P. avidum KP-40 administration accelerated murine thymocyte proliferation and maturation. Counts of BALB/c-mouse peripheral blood lymphocytes (PBL) and monocytes (PBM) revealed statistically significant increases after P. avidum KP-40 administration with peak values after 6-10 days. The determination of activated PBL (expressing interleukin-2 receptors) or PBM (expressing MAC-3 antigens) proved that P. avidum KP-40 induced a potent immunostimulation since counts of these cells were significantly enhanced after P. avidum KP-40 treatment.

Animals↗
PubMed1994

Neurotrophin-6 is a new member of the nerve growth factor family.

During vertebrate development, many neurons depend for survival and differentiation on their target cells. The best documented mediator of such a retrograde trophic action is the neurotrophin nerve growth factor (NGF). NGF and the other known members of the neurotrophin family, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) are conserved as distinct genes over large evolutionary distances. Here we report the cloning of neurotrophin-6 (NT-6), a new member of this family from the teleost fish Xiphophorus. NT-6 distinguishes itself from the other known neurotrophins in that it is not found as a soluble protein in the medium of producing cells. The addition of heparin (but not chondroitin) effects the release of NT-6 from cell surface and extracellular matrix molecules. Recombinant purified NT-6 has a spectrum of actions similar to NGF on chick sympathetic and sensory neurons, albeit with a lower potency. NT-6 is expressed in the embryonic valvulla cerebelli; expression persists in some adult tissues. The interaction of NT-6 with heparin-binding molecules may modulate its action in the nervous system.

Amino Acid Sequence↗
PubMed1994

Polymorphic admixture typing in human ethnic populations.

A panel of 257 RFLP loci was selected on the basis of high heterozygosity in Caucasian DNA surveys and equivalent spacing throughout the human genome. Probes from each locus were used in a Southern blot survey of allele frequency distribution for four human ethnic groups: Caucasian, African American, Asian (Chinese), and American Indian (Cheyenne). Nearly all RFLP loci were polymorphic in each group, albeit with a broad range of differing allele frequencies (delta). The distribution of frequency differences (delta values) was used for three purposes: (1) to provide estimates for genetic distance (differentiation) among these ethnic groups, (2) to revisit with a large data set the proportion of human genetic variation attributable to differentiation within ethnic groups, and (3) to identify loci with high delta values between recently admixed populations of use in mapping by admixture linkage disequilibrium (MALD). Although most markers display significant allele frequency differences between ethnic groups, the overall genetic distances between ethnic groups were small (.066-.098), and < 10% of the measured overall molecular genetic diversity in these human samples can be attributed to "racial" differentiation. The median delta values for pairwise comparisons between groups fell between .15 and .20, permitting identification of highly informative RFLP loci for MALD disease association studies.

Alleles↗
PubMed1994

Ligand-dependent tumor induction in medakafish embryos by a Xmrk receptor tyrosine kinase transgene.

Xmrk encodes a subclass I receptor tyrosine kinase (RTK) which has been cloned from the melanoma-inducing locus Tu of the poeciliid fish Xiphophorus. To demonstrate a high oncogenic potential in vivo we transferred the gene into early embryos of the closely related medakafish. Ectopic expression of the Xmrk oncogene under the control of a strong, constitutive promoter (CMVTk) led to the induction of embryonic tumors with high incidence, after short latency periods, and with a specific pattern of affected tissues. We demonstrate ligand-dependent transformation in vivo using a chimeric receptor consisting of the extracellular and transmembrane domains of the human EGF receptor (HER) and the cytoplasmatic domain of Xmrk. Expression of the chimeric receptor alone does not lead to kinase activation or induction of tumors. Coexpression of the chimera with its corresponding ligand, human transforming growth factor alpha (hTGF alpha), however, results in the activation of the chimeric RTK. In injected fish embryos the induction of the neoplastic growth is observed with similar incidence and tissue distribution as in embryos carrying the native Xmrk oncogene suggesting that the ligand as well as factors downstream of the RTK are required for tumor formation. In this study we show single-step induction of tumors by ectopic expression of RTKs in vivo substantiating the significance of autocrine stimulation in RTK induced tumors in vertebrates.

Animals↗
PubMed1993

Telepathology with an integrated services digital network--a new tool for image transfer in surgical pathology: a preliminary report.

We describe a low-cost telepathology system working via a commercial integrated services digital network (ISDN) and consisting of modular software and hardware elements. The main elements are Apple Macintosh workstations; a software program for the simultaneous transfer of pictures, voice, and data; and procedures for image processing and general administration of all the information generated. Additionally, the system allows remote control of any peripheral instruments by a "picture-instrument manager." The transfer rate is currently 64 kbit/s; it will be extended to 128 kbit/s (ISDN basic rate) in the near future and to 2 Mbit/s (ISDN primary rate) in the next 2 years. The system was tested by the regional hospital in Samedan, Switzerland, and the Department of Pathology, University of Basel, Basel, Switzerland, a distance of 250 km, by offering a remote frozen section service to the regional hospital in 16 cases. Fifty-four to 58 seconds were needed for the transfer of a diagnostic 8-bit grey-level image containing 341 (median value) +/- 26.1 (standard error) kbytes (n = 13) or a diagnostic 24-bit color image containing 165 (median value) +/- 16.9 (standard error) kbytes (n = 3). The time required for a diagnostic session was between 25 and 35 minutes.

Adult↗
PubMed1992

Tophi as the initial manifestation of gout. Report of six cases and review of the literature.

The development of tophi in the absence of prior episodes of gouty arthritis is unusual. We present six such cases and review 26 previously published cases. These patients differ from those with typical gout in that they were older, more likely to be women, and usually had predominant or exclusive finger involvement. Most had renal insufficiency and many were receiving an anti-inflammatory or diuretic. Although several possibilities for the lack of gouty arthritis in the presence of tophi exist, usually no clear explanation is found.

Adult↗
PubMed1991

Transient expression of foreign DNA during embryonic and larval development of the medaka fish (Oryzias latipes).

Species of small fish are becoming useful tools for studies on vertebrate development. We have investigated the developing embryo of the Japanese medaka for its application as a transient expression system for the in vivo analysis of gene regulation and function. The temporal and spatial expression patterns of bacterial chloramphenicol acetyltransferase and galactosidase reporter genes injected in supercoiled plasmid form into the cytoplasm of one cell of the two-cell stage embryo was promoter-specific. The transient expression was found to be mosaic within the tissue and organs reflecting the unequal distribution of extrachromosomal foreign DNA and the intensive cell mixing movements that occur in fish embryogenesis. The expression data are consistent with data on DNA fate. Foreign DNA persisted during embryogenesis and was still detectable in some 3- and 9-month-old adult fish; it was found in high molecular weight form as well as in circular plasmid conformations. The DNA was replicated during early and late embryogenesis. Our data indicate that the developing medaka embryo is a powerful in vivo assay system for studies of gene regulation and function.

Animals↗
PubMed1990

Oncofetal antigen in Xiphophorus detected by monoclonal antibodies directed against melanoma-associated antigens.

Monoclonal antibodies (MAbs) directed against Xiphophorus melanoma cells were developed and tested by indirect immunofluorescence and immunoperoxidase staining for reactivity with a panel of 15 allogeneic tissues and 12 allogeneic cell lines. The reactivity of such MAbs was restricted to melanoma cells from tumor biopsies and melanoma-derived cell lines. In addition, all embryonic cells of all histiotypes from developmental stages later than mid-organogenesis and from corresponding short term in vitro cultures reacted with these MAbs. In contrast, normal tissues and organs from adult fish displayed no reactivity, thus implying that the melanoma-associated antigens detected by the MAbs described are oncofetal antigens.

Animals↗
PubMed1990

[Afterloading contact therapy in childhood tumors].

Two examples are presented to apply high dose rate afterloading therapy in treatment of tumors in childhood. The AL-therapy can be indicated in tumors in natural or artificial openings of the body that are limited locoregionally or were operated in sano. Applying brachytherapy radiogenic late-effects can be prevented in normal tissue like gonads and skeleton predominantly. On the other hand a tumor dimension greater than the target volume attainable by contact therapy has to be excluded certainly to avoid local recurrences.

Bone Neoplasms↗
PubMed1990

[Radiogenic pneumopathy in irradiated breast cancer--a follow-up assessment based on chest radiographs].

In 232 surgically treated and irradiated patients with breast carcinoma 27 cases of radiogeneous pneumopathia were found and analyzed in the chest radiograph. Special attention was given to the evaluation of the stage and the course of the radiation pneumonitis. No correlation between clinical results and x-ray symptoms was seen. Not every roentgenologically diagnosed pneumonitis is seen in the late follow-up as a fibrosis. The reasons for this are discussed. For the improved detectability of pneumonitic changes in the p.a. or lateral image no significant differences were found and no general rules. Additional CT-investigations of the chest demonstrated the radiogeneous lung changes more clearly and more exactly in its depths. Therefore an exact use of CT in the diagnostics of pneumonitis can be useful, but must be seen under the aspects of relevant therapy the availability of methods and economy.

Adult↗
PubMed1990

[Results of an epidemiological study with subsequent specialized diagnostic studies in dust exposure].

Preparing a special occupational health follow-up a cross sectional study in 304 dust exposed workers was performed. According to these screening results 23% of the workers examined revealed as fit only under special conditions. Clinical examinations confirmed these judgements except a small group of 2.9%. In confirmed cases hygienic measures in regard of the working places and/or medical treatments were started. Effectivity will be studied in a longitudinal manner.

Adult↗
PubMed1989

Genetic characterization of FLA, the cat major histocompatibility complex.

The major histocompatibility complex (MHC) of the domestic cat (termed FLA) has been refractile to genetic and serological definition largely because of repeated failure to detect cytotoxic antibodies in multiparous cats or to elicit antibody following allogeneic lymphocyte immunization. We have developed a protocol for producing cytotoxic alloantisera in the cat following rejection of multiple surgical skin grafts. Of 59 cats subjected to grafting, 13 produced lymphocytotoxic antisera which had varying specificities among a panel of outbred cat cells. A population cluster analysis of the 13 alloantisera permitted the identification of six clusters of overlapping FLA specificities. Serological analysis of cells from 12 cat kindreds led to the definition of 24 allogeneic haplotypes, which segregate as a single Mendelian complex. Feline FLA antisera were characterized as class I or class II specific by immunoprecipitation of FLA gene products on lymphocyte cell surfaces. Abundant antigenic polymorphisms for both class I and class II MHC determinants were discovered, a result consistent with precedence in other species and the common expectation of the adaptive value of MHC variation. Development of feline MHC typing reagents and the definition of haplotypes for the cat hold promise for experimental analysis of valuable feline models for virus-induced immune deficiencies.

Animals↗