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Biomedical subjects

K Bucher

Publications and source records attributed to K Bucher.

At least 19 recordsLinked to original sources

[Does weather modify headaches? An empirical evaluation of bio-weather categorization].

BACKGROUND: Headache patients frequently refer to the weather as a triggering factor for their headaches. Apart from a literature review, we tested empirically the generally used classification of weather epochs into a so called bio-weather categorization. METHOD: Headache diary data (frequency, duration, intensity) of 98 patients in a headache trial were correlated with the concurrent bio-weather classification. RESULTS: Correlations were small and significant only for the summer-half of the year (contingency coefficients between 0.04 and 0.06). The classification of certain types of weather as headache prone as used in the current bio-weather classification could only partly be verified. CONCLUSION: There is a clear but small correlation between headache and weather. More, and more fine-grained, studies are warranted, especially for identifying those patients at risk for weather prone headaches. Clinically more important is the weather as a source of causal attributions.

Data Interpretation, Statistical↗

The T cell oncogene Tal2 is necessary for normal development of the mouse brain.

Transcription factors are commonly involved in leukemia by activation through chromosomal translocations and normally function in cell type(s) that differ from that of the tumor. TAL2 is a member of a basic helix-loop-helix gene family specifically involved in T cell leukemogenesis. Null mutations of Tal2 have been made in mice to determine its function during development. Tal2 null mutant mice show no obvious defects of hematopoiesis. During embryogenesis, Tal2 expression is restricted to the developing midbrain, dorsal diencephalon, and rostroventral diencephalic/telencephalic boundary, partly along presumptive developing fiber tracts. The null mutant mice are viable at birth but growth become progressively retarded and they do not survive to reproductive age. Tal2-deficient mice show a distinct dysgenesis of the midbrain tectum. Due to loss of superficial gray and optical layers, the superior colliculus is reduced in size and the inferior colliculus is abnormally rounded and protruding. Death is most likely due to progressive hydrocephalus which appears to be caused by obstruction of the foramen of Monro (the connection between the ventricles of the forebrain). Thus, in addition to its oncogenicity when ectopically expressed, Tal2 normally plays a pivotal role in brain development and without this gene, mice cannot survive to maturity.

Animals↗

Winter mortality in relation to climate.

We report further details of the Eurowinter survey of cold related mortalities and protective measures against cold in seven regions of Europe, and review these with other evidence on the relationship of winter mortality to climate. Data for the oldest subject group studied, aged 65-74, showed that in this vulnerable group, high levels of protection against indoor and outdoor cold at given outdoor temperatures were found mainly in countries with cold winters, and were associated with low levels of excess mortality at a given level of outdoor cold. Regions such as London that had poor protection against cold and/or high baseline mortalities had higher levels of winter excess mortality than expected for the coldness of their winters.

Aged↗

Atmospheric heat exchange of the human being, bioclimate assessments, mortality and thermal stress.

In epidemiological investigations of the impact of the atmospheric environment on mortality usually only air temperature, in addition to sometimes relative humidity, are used, although it is generally known that the heat exchange conditions of the human body also depend on water vapour pressure, wind velocity, and short- and long-wave radiation. The state-of-the-art approach to this problem is the application of complete heat budget models which allow thermophysiologically significant assessments of the above-mentioned meteorological variables taking metabolic rate and isolation of clothing into account. The application of such a model to 30-year mortality data of Baden-Württemberg (SW-Germany) shows, in winter, increasing daily mortality rate with decreasing "perceived temperature." (a term which relates temperature to a fixed standard condition). A sudden warming during a cold period also results in an increase in mortality, a certain contradiction which has not yet been able to be explained. During cold spells a marked increase in mortality with a delay of 3 days can be observed. Above normal values last for about 4 weeks and will then be partially compensated by an "undershot". Generally the explanation of variance in winter is distinctly lower than in summer, probably because in winter there is rarely direct exposure to outdoor conditions. The degree of cold stress is likely to serve only as an indicator for indoor conditions which promote infectious diseases.

Body Temperature Regulation↗

The effect of chromosomal translocations in acute leukemias: the LMO2 paradigm in transcription and development.

Two general features have emerged about genes that are activated after chromosomal translocations in acute forms of cancer. The protein products of these genes are transcription regulators and are involved in developmental processes, and it seems that the subversion of these normal functions accounts for their role in tumorigenesis. The features of the LMO family of genes, which encode LIM-domain proteins involved in T-cell acute leukemia through chromosomal translocations, typify these abnormal functions in tumorigenesis. For example, the LMO2 protein is involved in the formation of multimeric DNA-binding complexes, which may vary in composition at different stages of hematopoiesis and function to control differentiation of specific lineages. In T cells, enforced expression of Lmo2 causes aberrant protein complex formation that primarily seems to hinder the T-cell differentiation program. These observations underscore the conclusion that protein-protein interaction (in this case, through the LIM domain) is a key determinant in tumorigenesis. Furthermore, the study of chromosomal translocations as naturally occurring mutations has been informative about mechanisms in hematopoiesis as well as in tumor etiology.

Acute Disease↗

The oncogenic T cell LIM-protein Lmo2 forms part of a DNA-binding complex specifically in immature T cells.

The LIM-only protein LMO2 is expressed aberrantly in acute T-cell leukaemias as a result of the chromosomal translocations t(11;14) (p13;q11) or t(7;11) (q35;p13). In a transgenic model of tumorigenesis by Lmo2, T-cell acute leukaemias arise after an asymptomatic phase in which an accumulation of immature CD4(-) CD8(-) double negative thymocytes occurs. Possible molecular mechanisms underlying these effects have been investigated in T cells from Lmo2 transgenic mice. Isolation of DNA-binding sites by CASTing and band shift assays demonstrates the presence of an oligomeric complex involving Lmo2 which can bind to a bipartite DNA motif comprising two E-box sequences approximately 10 bp apart, which is distinct from that found in erythroid cells. This complex occurs in T-cell tumours and it is restricted to the immature CD4(- )CD8(-) thymocyte subset in asymptomatic transgenic mice. Thus, ectopic expression of Lmo2 by transgenesis, or by chromosomal translocations in humans, may result in the aberrant protein interactions causing abnormal regulation of gene expression, resulting in a blockage of T-cell differentiation and providing precursor cells for overt tumour formation.

Adaptor Proteins, Signal Transducing↗

Winter mortality and cold stress in Yekaterinburg, Russia: interview survey.

OBJECTIVES: To evaluate how mortality and protective measures against exposure to cold change as temperatures fall between October and March in a region of Russia with a mean winter temperature below -6 degrees C. DESIGN: Interview to assess factors associated with cold stress both indoors and outdoors, to measure temperatures in living room, and to survey unheated rooms. SETTING: Sverdlovsk Oblast (district), Yekaterinburg, Russia. SUBJECTS: Residents aged 50-59 and 65-74 living within approximately 140 km of Yekaterinburg in Sverdlovsk Oblast. Survey of sample of 1000 residents equally distributed by sex and age groups. MAIN OUTCOME MEASURES: Regression analysis was used to relate data on indoor heating and temperatures, the amount of clothing worn, the amount of physical activity, and shivering while outside, to outdoor temperature; results were compared with mortality patterns for ischaemic heart disease, cerebrovascular disease, respiratory disease, and mortality from all causes. RESULTS: As mean daily temperatures fell to 0 degree C the amount of clothing worn outdoors increased, physical activity while outdoors became more continuous, and only 11 (6.6%) of the 167 people surveyed who went outdoors at temperatures above 0 degree C reported shivering. The mean temperature in living rooms in the evening remained above 21.9 degrees C. Mortality from ischaemic heart disease, cerebrovascular disease, respiratory disease, and all causes did not change. As the temperature fell below 0 degree C the number of items of clothing worn plateaued at 16.0 and the number of layers at 3.7. With regression analysis, shivering outdoors was found to increase progressively to 34.6% (P < 0.001) of excursions at -25 degrees C, and mortality (after declining slightly) rose progressively (all cause mortality rose by 1.15% for each 1 degree C drop in temperature from 0 degree C to -29.6 degrees C, 95% confidence interval 0.97% to 1.32%). 94.2% of bedrooms were directly heated, and evening temperatures in the living room averaged 19.8 degrees C even when outside temperatures reached -25 degrees C. CONCLUSIONS: Outdoor cold stress and mortality in Yekaterinburg increased only when the mean daily temperature dropped below 0 degree C. At temperatures down to 0 degree C cold stress and excess mortality were prevented by increasing the number of items of clothing worn and the amount of physical activity outdoors in combination with maintaining warmth in houses.

Activities of Daily Living↗

[Correlation of odontogenic soft tissue infection and thermal effects with special reference to temperature sense. Statistical analysis of 2,111 patients].

A possible correlation between the thermal effects of the weather and the frequency of odontogenic soft-tissue infections was investigated with special regard to the so-called felt temperature (gT). Clinical data of 2111 patients of the years 1992-1996 in whom an incision was made because of an odontogenic soft-tissue infection were evaluated retrospectively and correlated to meteorological data for Aachen, collected or calculated by the "Deutsche Wetterdienst". In order to describe the thermal exchange between the human organism and the surroundings in a satisfactory way, the gT was chosen. The gT is a complexly calculated meteorological parameter which allows physiologically adequate estimation of the thermic surroundings of humans. Over the whole study time there was no impressive correlation between course and changing of the gT and the frequency of odontogenic soft-tissue infections. This result agrees with our finding that there was no seasonal accumulation of odontogenic soft-tissue infections over the year in Aachen. Nevertheless, there was a statistically significant negative correlation between values or weighted changes of the gT and the frequency of abscess and/or infiltration in the winter and less in springtime. A similar statistically significant correlation could not be found for summer or autumn.

Adolescent↗

Growth-inhibitory activity and downregulation of the class II tumor-suppressor gene H-rev107 in tumor cell lines and experimental tumors.

The H-rev107 gene is a new class II tumor suppressor, as defined by its reversible downregulation and growth-inhibiting capacity in HRAS transformed cell lines. Overexpression of the H-rev107 cDNA in HRAS-transformed ANR4 hepatoma cells or in FE-8 fibroblasts resulted in 75% reduction of colony formation. Cell populations of H-rev107 transfectants showed an attenuated tumor formation in nude mice. Cells explanted from tumors or maintained in cell culture for an extended period of time no longer exhibited detectable levels of the H-rev107 protein, suggesting strong selection against H-rev107 expression in vitro and in vivo. Expression of the truncated form of H-rev107 lacking the COOH-terminal membrane associated domain of 25 amino acids, had a weaker inhibitory effect on proliferation in vitro and was unable to attenuate tumor growth in nude mice. The H-rev107 mRNA is expressed in most adult rat tissues, and immunohistochemical analysis showed expression of the protein in differentiated epithelial cells of stomach, of colon and small intestine, in kidney, bladder, esophagus, and in tracheal and bronchial epithelium. H-rev107 gene transcription is downregulated in rat cell lines derived from liver, kidney, and pancreatic tumors and also in experimental mammary tumors expressing a RAS transgene. In colon carcinoma cell lines only minute amounts of protein were detectable. Thus, downregulation of H-rev107 expression may occur at the level of mRNA or protein.

Animals↗

Tumour suppressor gene p53 in the horse: identification, cloning, sequencing and a possible role in the pathogenesis of equine sarcoid.

The tumour suppressor protein p53 enhances the genetic stability of the cell and plays a critical role in tumour suppression. Equine p53 was analysed by sequencing exons 5 to 9, a region which includes most known mutations and all the mutational hotspots in the species that have been investigated. The fragment was amplified, cloned and sequenced from genomic and complementary DNA. A comparison of the predicted amino acid sequences between the horse and other species resulted in identities between 66 per cent with the clawed frog and 92 per cent with the cat. Using the single strand conformation polymorphism technique, exons 5 to 8 amplified from sarcoid tissue and peripheral leucocytes of 28 sarcoid-affected and 11 healthy horses were screened for mutations. No mutations were identified, suggesting that the frequency of p53 mutations in equine sarcoid might be low. However, the high incidence of bovine papillomavirus (BPV) infection in equine sarcoid may indicate the functional inactivation of p53 by BPV-encoded E6 protein.

Amino Acid Sequence↗

Partial sequence of the equine immunoglobulin epsilon heavy chain cDNA.

In order to isolate a part of the immunoglobulin E (IgE) heavy chain cDNA of the horse, primers have been designed based upon well conserved sequences in humans, sheep and rats. The PCR resulted in a 500 bp fragment which hybridised with a human IgE constant region probe. The fragment was cloned and sequenced and its derived protein sequence compared with the corresponding sequences in humans, sheep and mice. Most amino acids common to these three species are also shared by the horse.

Amino Acid Sequence↗

[Are degenerative joint diseases chronic compartment syndromes?].

An increase of the intraosseous pressure is observed in the epiphyses of bones involved in degenerative joint disease. The increase of pressure may be caused by an accumulation of osmotically active substances in the interstitium as it has been described in case of the Compartment Syndrome. Based on the postulated pathophysiological mechanism a causative therapy of the degenerative joint disease is proposed.

Animals↗

[Are degenerative joint diseases chronic compartment syndromes?].

An increase of the intraosseous pressure is observed in the epiphyses of bones involved in degenerative joint disease. The increase of pressure may be caused by an accumulation of osmotically active substances in the interstitium, as it has been described in case of the compartment syndrome. Based on the postulated pathophysiological mechanism, a causative therapy of degenerative joint disease is proposed.

Algorithms↗

Meteorotropy and medical-meteorological forecasts.

The meteorotropic reaction of the human organism is a function of different factors, such as the type and intensity of the effects of the physical environment as well as individual conditions like adaptive capacity and state of health. Many medical-meteorological studies show causal correlations between conditions in the lower atmosphere and reactions of the human organism, but also combined or synergistic effects of different weather situations, which can only be proved stochastically. These effects are described and the methodology of the investigations, as well as the results, critically discussed. Furthermore, application of the results in the areas of medical-meteorological consultation, with the goal of improving living conditions, is considered.

Climate↗

Sorting of endogenous plasma membrane proteins occurs from two sites in cultured human intestinal epithelial cells (Caco-2).

We studied the postsynthetic sorting of endogenous plasma membrane proteins in a polarized epithelial cell line, Caco-2. Pulse-chase radiolabeling was combined with domain-specific cell surface assays to monitor the arrival of three apical and one basolateral protein at the apical and basolateral cell surface. Apical proteins were inserted simultaneously into both membrane domains. The fraction targeted to the basolateral domain was different for the three apical proteins and was subsequently sorted to the apical domain by transcytosis at different rates. In contrast, a basolateral protein was found in the basolateral membrane only. Thus, sorting of plasma membrane proteins occurred from two sites: the Golgi apparatus and the basolateral membrane. These data explain apparently conflicting results of earlier studies.

Adenocarcinoma↗

Microtubule perturbation retards both the direct and the indirect apical pathway but does not affect sorting of plasma membrane proteins in intestinal epithelial cells (Caco-2).

Endogenous plasma membrane proteins are sorted from two sites in the human intestinal epithelial cell line Caco-2. Apical proteins are transported from the Golgi apparatus to the apical domain along a direct pathway and an indirect pathway via the basolateral membrane. In contrast, basolateral proteins never appear in the apical plasma membrane. Here we report on the effect of the microtubule-active drug nocodazole on the post-synthetic transport and sorting of plasma membrane proteins. Pulse-chase radiolabeling was combined with domain-specific cell surface assays to monitor the appearance of three apical and one basolateral protein in plasma membrane domains. Nocodazole was found to drastically retard both the direct transport of apical proteins from the Golgi apparatus and the indirect transport (transcytosis) from the basolateral membrane to the apical cell surface. In contrast, neither the transport rates of the basolateral membrane nor the sorting itself were significantly affected by the nocodazole treatment. We conclude that an intact microtubular network facilitates, but is not necessarily required for, the transport of apical membrane proteins along the two post-Golgi pathways to the brush border.

Adenocarcinoma↗

Dissection of the asynchronous transport of intestinal microvillar hydrolases to the cell surface.

Novel subcellular fractionation procedures and pulse-chase techniques were used to study the intracellular transport of the microvillar membrane hydrolases sucrase-isomaltase and dipeptidylpeptidase IV in the differentiated colon adenocarcinoma cell line Caco-2. The overall rate of transport to the cell surface was two fold faster for dipeptidylpeptidase IV than for sucrase-isomaltase, while no significant differences were observed in transport rates from the site of complex glycosylation to the brush border. The delayed arrival of sucrase-isomaltase in the compartment where complex glycosylation occurs was only in part due to exit from the endoplasmic reticulum. A major slow-down could be ascribed to maturation in and transit of this enzyme through the Golgi apparatus. These results suggest that the observed asynchronism is due to more than one rate-limiting step along the rough endoplasmic reticulum to trans-Golgi pathway.

Biological Transport↗