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Biomedical subjects

M Zoller

Publications and source records attributed to M Zoller.

At least 19 recordsLinked to original sources
PubMed2006

[Research interest by general practitioners: a survey].

BACKGROUND: For doing research on topics in primary care medicine participation of primary care physicians is necessary. Research in this field of medicine is only marginally established in Switzerland. OBJECTIVE: In a postal survey we evaluate the general attitudes of physicians towards research in the field of primary care. In particular we were interested in their willingness to participate in research projects and the facilitating and impeding factors to take part in such projects. METHODS: A purpose designed questionnaire was sent by post to 3044 primary care physicians in the central and eastern parts of Switzerland. RESULTS: The return rate was 52%. A majority of 94% of the responding physicians revealed interest in primary care research and 60% of all responders are willing to participate actively in such projects. They are prepared to spend about 15 min a day for data acquisition. Their willingness to participate depends on the conditions that, first, the research topic is relevant for daily practice and, second, boards odder Continuous Medical Education credits for time spent for research. Time constraints, additional administrative work and lack of relevance of research topics to daily practice are the main barriers. CONCLUSION: This survey demonstrates the general interest of primary care physicians to participate in relevant research projects. Therefore the structure to set up such research should be established.

Attitude of Health Personnel↗
PubMed2003

[Anticoagulatin in atrial fibrillation--status of therapy in a network of physicians].

Despite of sound evidence, that oral anticoagulation reduces substantially the incidence of stroke-events in patients with atrial fibrillation and concomitant risk factors, in daily practice only a part of these patients is in fact treated with anticoagulation. The aim of this cross-sectional study was to evaluate to which extent existing guidelines for the treatment of patients with atrial fibrillation are transformed in the "real world" context of a Swiss urban network of primary care providers. The greatest part (88.4%) of the included patients with atrial fibrillation had a high risk for thromboembolism and herewith the indication for anticoagulation was given. For a primary care collective the amount of patients with anticoagulation was high: 74.1% did receive this kind of preventive therapy. 89% had robust International normalized ratio (INR) values within the recommended range (INR 2.5-3.5). The most common reasons not to prescribe oral anticoagulation were: old age (17.5%; mostly in combination with other reasons), risk of falls (16.5%), medical indication not given (16.5%). Thus the recommendations of the guidelines have been transformed into practice for a bigger part of the included patients. Given these results a broadly implemented quality-improvement-project to bring up the anticoagulation rate even higher hardly seems to be efficacious and is presently not of top priority in this network of primary care providers.

Adult↗
PubMed2003

[Differential diagnosis of acute appendicitis and ileus. Invagination due to polypoid heterotopic gastric mucosa in the ileum without Meckel diverticulum].

A 13-year-old female presented with recurrent, right-sided abdominal pain since the age of 2 years. Examination showed a tender, cylindric mass in the right lower quadrant. Ultrasound and MRI revealed an ileocolic intussusception. On laparotomy, there was an ileo-ileal intussusception due to a 3.8-cm polypoid tumor about 40 cm proximal to the ileocoecal valve. Histology showed polypoid heterotopic gastric mucosa with no Meckel's diverticulum. To our knowledge, only 12 cases of intussusception of heterotopic gastric mucosa in the ileum without Meckel's diverticulum have been reported in literature. This case adds to this small list and represents a possible cause of intussusception.

Abdomen, Acute↗
PubMed2001

Relationship between cellular radiosensitivity and DNA damage measured by comet assay in human normal, NBS and AT fibroblasts.

PURPOSE: To study the relationship between cellular radiosensitivity and DNA damage measured by the comet assay. MATERIALS AND METHODS: Experiments were performed with nine human fibroblast lines (six normal, one NBS, and two AT). Cellular radiosensitivity was determined by colony assay and DNA damage was assessed by the comet assay. RESULTS: The cellular radiosensitivity of the fibroblast lines used covered a broad range with SF2 values varying between 1.3% and 53%. The comets analysed immediately after irradiation with doses up to 5 Gy showed marked differences among the cell lines; the relative initial tail moment at a dose of 5 Gy, ITM5, varied from 2.7+/-0.2 to 5.0+/-0.3. This variation was considered not to result from different numbers of DNA strand breaks induced but from differences in chromatin structure. There was an inverse correlation between SF2 and ITM5, i.e. radiosensitive cell lines exhibited a higher initial tail moment than radioresistant cell lines. In contrast, the repair kinetics measured with the comet assay for a dose of 2Gy followed by an incubation of up to 2h showed little variation and were found not to correlate with SF2. Repair kinetics as well as the amount of residual damage measured by this version of the comet assay were fairly similar to those measured by the alkaline unwinding technique and unlike that measured by neutral gel electrophoresis, indicating that this comet assay detects primarily single-strand breaks and alkali-labile sites, not double-strand breaks. CONCLUSIONS: The correlation between SF2 and the initial tail moment at 5 Gy found here suggests that the cellular radiosensitivity of human fibroblasts also depends on the chromatin structure.

Ataxia Telangiectasia↗
PubMed2000

Vaccination: a future modality of cancer therapy.

With an expanding list of known tumor antigens and increasing knowledge of the requirements for activation of immune effector functions, immunotherapy of cancer is about to become the fourth weapon in the fight against cancer, together with surgery, radiation and chemotherapy. Although our knowledge has come mostly from experimental models, the mechanistic premises observed in these models will provide a reasonable basis for immunotherapeutic protocols in cancer patients.

Journal Article↗
PubMed1999

Antitumor and immunotherapeutic effects of activated invasive T lymphoma cells that display short-term interleukin 1alpha expression.

Expression of cytokines in malignant cells represents a novel approach for therapeutic treatment of tumors. Previously, we demonstrated the immunostimulatory effectiveness of interleukin 1alpha (IL-1alpha) gene transfer in experimental fibrosarcoma tumors. Here, we report the antitumor and immunotherapeutic effects of short-term expression of IL-1alpha by malignant T lymphoma cells. Activation in culture of T lymphoma cells with lipopolysaccharide-stimulated macrophages induces the expression of IL-1alpha. The short-term expression of IL-1alpha persists in the malignant T cells for a few days (approximately 3-6 days) after termination of the in vitro activation procedure and, thus, has the potential to stimulate antitumor immune responses in vivo. As an experimental tumor model, we used the RO1 invasive T lymphoma cell line. Upon i.v. inoculation, these cells invade the vertebral column and compress the spinal cord, resulting in hind leg paralysis and death of the mice. Activated RO1 cells, induced to express IL-1alpha in a short-term manner, manifested reduced tumorigenicity: approximately 75% of the mice injected with activated RO1 cells remained tumor free. IL-1 was shown to be essential for the eradication of activated T lymphoma cells because injection of activated RO1 cells together with IL-1-specific inhibitors, i.e., the IL-1 receptor antagonist or the M 20 IL-1 inhibitor, reversed reduced tumorigenicity patterns and led to progressive tumor growth and death of the mice. Furthermore, activated RO1 cells could serve as a treatment by intervening in the growth of violent RO1 cells after tumor take. Thus, when activated RO1 cells were injected 6 or 9 days after the inoculation of violent cells, mortality was significantly reduced. IL-1alpha, in its unique membrane-associated form, in addition to its cytosolic and secreted forms, may represent a focused adjuvant for potentiating antitumor immune responses at low levels of expression, below those that are toxic to the host. Further assessment of the immunotherapeutic potential of short-term expression of IL-1alpha in activated tumor cells may allow its improved application in the treatment of malignancies.

Animals↗
PubMed1996

Membrane-bound ezrin is involved in B-cell receptor-mediated signaling: potential role of an ITAM-like ezrin motif.

Ezrin is a cytoskeleton-plasma membrane linker molecule which is implicated in the T-cell antigen receptor signaling as one of the major tyrosine phosphorylated components. Its function in B-lymphocyte activation has not yet been clarified. Here we studied the potential involvement of ezrin in the B-cell receptor (BCR) signaling in BL41 Burkitt lymphoma cells. Our data demonstrate that ezrin, which shows predominantly cytosolic distribution in unstimulated cells, undergoes only a moderate tyrosine phosphorylation in response to BCR triggering, with no concomitant translocation of the protein from the cytosol to the plasma membrane. Instead, BCR-independent stimulants like oxidant stress induced by phenylarsine oxide, resulted in rapid redistribution of ezrin to the plasma membrane. When BCR triggering was preceded by membrane recruitment of ezrin, it became one of the main and earliest substrates of tyrosine kinases activated by BCR. No detectable influence on distribution or phosphorylation of ezrin was triggered by the tyrosine phosphatase inhibition by orthovanadate, suggesting that these effects of phenylarsine oxide are not attributable to its tyrosine phosphatase inhibitory capacity. The notion that BCR-mediated phosphorylation of ezrin negatively correlates with activation events such as phosphorylation of tyrosine kinase, syk and induction of calcium mobilization response, suggests that ezrin might be implicated in the regulation of transmembrane signaling and cellular responsiveness. As will be discussed, the regulatory function of ezrin may be due to an immunoreceptor tyrosine-based activation motif (ITAM)-like sequence.

Actins↗
PubMed1994

Involvement of immune responses in the eradication of IL-1 alpha gene-transduced tumour cells: mechanisms of tumour rejection and immunotherapeutical implications.

We detected a strong correlation between the constitutive expression of IL-1 alpha and reduced tumorigenicity, using fibrosarcomas which produce the cytokine spontaneously (as an aberration of the transformation process) or upon gene transfer. In fibroblasts intracellular or membrane-associated IL-1 alpha is expressed, whereas the secreted form of the cytokine (IL-1 beta) is absent. Studies on the mechanisms of tumour regression of the IL-1 alpha producing fibroblastoid cell lines indicated that IL-1 alpha potentiates the development of tumour cell-specific CTLs, which are of importance for tumour eradication. It also appears that IL-1 alpha-induced enhanced helper T-cell activity provides auxiliary signals for the growth/development of CTLs. In addition, we observed a massive lymphocytic infiltrate in IL-1 alpha producing regressing tumours which ultimately replaces the tumour's mass. Non-adaptive effector cells, activated locally by IL-1 alpha expressing fibrosarcoma cells, were also shown to contribute, to some extent, to the eradication of IL-1 alpha expressing fibrosarcomas. Local IL-1 alpha expression potentiated antigen presentation, by the malignant fibroblasts as well as by tissue-resident antigen-presenting cells, and by this anti-tumour immune responses were further potentiated. Mice, in which IL-1 alpha producing tumours regressed, developed systemic immunity and rejected a challenge with a non IL-1 producing violent tumour cell line. It appears that endogenous IL-1 alpha, being a strong inducer of cytokine production, operates a whole cytokine cascade (such as IL-6, CSFs and prostaglandins). However, studies using clonal populations have indicated that IL-1 alpha is essential for fibrosarcoma eradication, whereas the other cytokines possibly amplify and sustain its action. We assume that most naturally occurring tumours are not constitutive IL-1 alpha producers, as it would be disadvantageous for the tumour to express a cytokine which increases its immunogenicity. However, IL-1 non-producing fibrosarcomas can be induced easily to express IL-1 transiently, by treatment with cytokines/LPS, and upon the induction of the cytokine they shift from progressor to regressor tumours. We also obtained positive immunotherapeutical effects when treating mice bearing IL-1 non-producing fibrosarcomas with cells from the same line induced in vitro to express IL-1 alpha. The results may shed light on a novel parameter affecting tumour-host interactions, namely cytokine expression by the tumorous cells, and may provide the basis for new immunotherapy protocols for fibrosarcoma management.

3T3 Cells↗
PubMed1994

Thyroglossal duct carcinoma.

The thyroid gland originates from the foramen cecum, and by 7 weeks gestation, descends ventrally in the midline of the neck. During its descent, a patent diverticulum, the thyroglossal duct, connects the gland to the base of the tongue. While the duct normally closes by the tenth gestational week, it is not uncommon to have all or a portion of the duct remain patent as a thyroglossal duct cyst or sinus. While these cysts are relatively common, thyroglossal duct carcinomas are very uncommon. They are generally of two types: squamous cell carcinoma arising from metaplastic columnar cells, and thyrogenic carcinoma arising from thyroembryonic rests in the duct or cyst. We report one case of each. The squamous cell carcinoma was resected via the Sistrunk procedure with no evidence of recurrence over a 10-year follow-up. The thyrogenic carcinoma (papillary type) was resected via the Sistrunk procedure with subsequent total thyroidectomy.

Adenocarcinoma, Papillary↗
PubMed1993

Cytokine-induced tumor immunogenicity: endogenous interleukin-1 alpha expressed by fibrosarcoma cells confers reduced tumorigenicity.

A direct correlation between the constitutive expression of IL-1 alpha and reduced tumorigenicity of fibrosarcomas was observed. This was established in fibrosarcoma cell lines which produce IL-1 alpha 'spontaneously', possibly as an aberration of oncogene-mediated transformation or upon IL-1 alpha gene transfer. In fibroblasts intracellular or membrane-associated IL-1 alpha is expressed, whereas the secreted form of the cytokine (IL-1 beta) is absent. Studies on the mechanisms of tumor regression of the IL-1 alpha-positive fibroblastoid cell lines indicated that IL-1 alpha potentiates the development of tumor cell-specific CTLs, which are of importance for tumor eradication. Thus, IL-1 alpha induces enhanced helper T cell activity which provides auxiliary signals for the growth/development of CTLs. Non-adaptive effector cells, activated locally by IL-1 alpha-expressing fibrosarcoma cells, also contribute to the eradication of IL-1 alpha-expressing fibrosarcomas. Local IL-1 alpha expression potentiated antigen presentation, by the malignant fibroblasts as well as by tissue-resident antigen-presenting cells, thus further potentiating anti-tumor immune responses. Mice, in which IL-1 alpha-producing tumors were regressed, developed an immune memory and rejected a challenge with an IL-1 non-producing violent tumor cell line. Endogenous IL-1 alpha activates a cytokine cascade (i.e., IL-6, CSF), produced by the malignant cells and possibly also by stromal cells. However, IL-1 alpha expression is essential for fibrosarcoma eradication, while other cytokines possibly amplify and sustain its action.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1988

cAMP-independent control of sporulation, glycogen metabolism, and heat shock resistance in S. cerevisiae.

Genes encoding the regulatory (BCY1) and catalytic (TPK1, TPK2, and TPK3) subunits of the cAMP-dependent protein kinase (cAPK) are found in S. cerevisiae. bcy1- yeast strains do not respond properly to nutrient conditions. Unlike wild type, bcy1- strains do not accumulate glycogen, form spores, or become resistant to heat shock when nutrient limited. We have isolated mutant TPK genes that suppress all of the bcy1- defects. The mutant TPK genes appear to encode functionally attenuated catalytic subunits of the cAPK. bcy1- yeast strains containing the mutant TPK genes respond appropriately to nutrient conditions, even in the absence of CDC25, both RAS genes, or CYR1. Together, these genes encode the known components of the cAMP-generating machinery. The results indicate that cAMP-independent mechanisms must exist for regulating glycogen accumulation, sporulation, and the acquisition of thermotolerance in S. cerevisiae.

Alleles↗
PubMed1987

Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase.

We have isolated three genes (TPK1, TPK2, and TPK3) from the yeast S. cerevisiae that encode the catalytic subunits of the cAMP-dependent protein kinase. Gene disruption experiments demonstrated that no two of the three genes are essential by themselves but at least one TPK gene is required for a cell to grow normally. Comparison of the predicted amino acid sequences of the TPK genes indicates conserved and variable domains. The carboxy-terminal 320 amino acid residues have more than 75% homology to each other and more than 50% homology to the bovine catalytic subunit. The amino-terminal regions show no homology to each other and are heterogeneous in length. The TPK1 gene carried on a multicopy plasmid can suppress both a temperature-sensitive ras2 gene and adenylate cyclase gene.

Amino Acid Sequence↗
PubMed1987

The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway.

The gene corresponding to the S. cerevisiae cell division cycle mutant cdc25 has been cloned and sequenced, revealing an open reading frame encoding a protein of 1589 amino acids that contains no significant homologies with other known proteins. Cells lacking CDC25 have low levels of cyclic AMP and decreased levels of Mg2+-dependent adenylate cyclase activity. The lethality resulting from disruption of the CDC25 gene can be suppressed by the presence of the activated RAS2val19 gene, but not by high copy plasmids expressing a normal RAS2 or RAS1 gene. These results suggest that normal RAS is dependent on CDC25 function. Furthermore, mutationally activated alleles of CDC25 are capable of inducing a set of phenotypes similar to those observed in strains containing a genetically activated RAS/adenylate cyclase pathway, suggesting that CDC25 encodes a regulatory protein. We propose that CDC25 regulates adenylate cyclase by regulating the guanine nucleotide bound to RAS proteins.

Adenylyl Cyclases↗
PubMed1987

Paradoxic vocal cord syndrome with surgical cure.

Paradoxic vocal cord motion (PVCM) can cause wheezing, stridor, weak or absent voice, and ineffective cough. We have described a patient who had a posterior fossa arachnoid cyst, which was thought to be causing PVCM by compressing the brain stem. The PVCM and all symptoms resolved after surgical treatment of the arachnoid cyst.

Brain Diseases↗
PubMed1987

Cloning and characterization of BCY1, a locus encoding a regulatory subunit of the cyclic AMP-dependent protein kinase in Saccharomyces cerevisiae.

We have cloned a gene (BCY1) from the yeast Saccharomyces cerevisiae that encodes a regulatory subunit of the cyclic AMP-dependent protein kinase. The encoded protein has a structural organization similar to that of the RI and RII regulatory subunits of the mammalian cyclic AMP-dependent protein kinase. Strains of S. cerevisiae with disrupted BCY1 genes do not display a cyclic AMP-dependent protein kinase in vitro, fail to grow on many carbon sources, and are exquisitely sensitive to heat shock and starvation.

Amino Acid Sequence↗