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Biomedical subjects

I Weber

Publications and source records attributed to I Weber.

At least 19 recordsLinked to original sources

Adhesion complexes formed by OVCAR-4 cells on laminin 1 differ from those observed on fibronectin.

Cell adhesion to laminin 1 or to fibronectin is mediated by distinct sets of integrins and is differentially regulated by protein kinase C (PKC). It suggests that upon integrin ligation to laminin 1 or to fibronectin different intracellular signaling pathways could be activated. we have therefore investigated the formation of signaling complexes induced during cell adhesion to laminin 1 or to fibronectin. Following cell adhesion to laminin 1 the re-arrangement of the cytoskeleton was slower than that observed on fibronectin and it was activated by treating the cells with H-7, an inhibitor of PKC. Conversely, treatment of laminin-adhering cells with a PKC activator resulted in a rapid disorganization of the actin cyto skeleton while a similar treatment had no effect on fibronectin-adhering cells. These results suggested that the structural organization of the adhesion complexes might be substrate-specific and might correspond to a different arrangement of cytoskeletal and/or cytoplasmic proteins. Reflection interference contrast microscopy (RICM) images revealed that cell-substratum contacts formed on laminin 1 were not well differentiated in contrast to those developed on fibronectin. However, immunofluorescence staining revealed a similar organisation of actin microfilaments, talin and phosphotyrosyl-containing proteins on both substrates. In contrast, differences were observed for vinculin distribution within cells spread on fibronectin or on laminin 1. Following cell adhesion to fibronectin most of the vinculin appeared as thick patches at the tips of the actin stress fibers while in laminin-adhering cells vinculin was recruited into thin streaks localized at the end of only some actin stress fibers.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

[Methadone substitution in public health management--results of a random day study sample].

Subject of this paper is methadone-maintenance given by the office-based physicians in Germany within the framework of the statutory health insurance (SHI). Results of a survey of the associations of SHI-accredited physicians are presented, comprising the number of substituted patients, the distribution of indications and the number of physicians engaged in this field. The increasing trend in the number of substituted patients continues, although less steeply. Strongholds of methadone maintenance are still the cities of Hamburg, Berlin, and Bremen, where the highest rates of substituted patients were found in relation to the resident population. The method of data-gathering used trends to overestimate the number of substituted patients. Comparing the determined numbers with different data sources, the actual number of addicts who are substituted in the longer term at the cost of the SHI is estimated to be 10 000 patients.

Costs and Cost Analysis

Motility and substratum adhesion of Dictyostelium wild-type and cytoskeletal mutant cells: a study by RICM/bright-field double-view image analysis.

To investigate the dynamics of cell-substratum adhesion during locomotion, a double-view optical technique and computer-assisted image analysis has been developed which combines reflection interference contrast microscopy (RICM) with bright-field imaging. The simultaneous recording of cell-substratum contact and cell body contour has been applied to aggregation-competent cells of Dictyostelium discoideum. These cells are distinguished from cells at earlier stages of development by small areas of contact to a substratum. Three questions have been addressed in analysing the locomotion of aggregation-competent cells. (1) What is the relationship between changes in the shape of cells and their contact to a substratum during a chemotactic response? (2) What is the relationship between protrusion and retraction of the cell body, and between local attachment and detachment? (3) Are there differences between wild-type and mutant cells that lack certain cytoskeletal proteins? During a chemotactic response the front region of the amoeba can bend towards the gradient of attractant without being supported by its contact with a surface, which excludes the necessity for gradients of adhesion for the response. The finding that in locomoting cells protrusion of the leading edge often precedes retraction establishes a pioneer role for the front region. The finding that gain of contact area precedes loss provides evidence for the coordination of interactions between the cell surface and a substratum. For comparison with wild-type, aggregation-competent triple mutant cells have been used that lack two F-actin crosslinking proteins, alpha-actinin and 120 kDa gelation factor, and an actin filament fragmenting protein, severin. Disturbances in the spatial and temporal control of cytoskeletal activities have been unravelled in the mutant by RICM and quantified by cross-correlation analysis of attachment and detachment vectors. In order to detect these disturbances, it was essential to analyse cell locomotion on the weakly adhesive surface of freshly cleaved mica.

Animals

[The Mannheim long-term study of schizophrenia. Initial results of follow-up of the illness over 14 years after initial inpatient treatment].

A 14-year follow-up was accomplished on 56 out of a total of 70 patients first admitted to hospital with Schneiderian first-rank symptoms. Data collected during 5 years after index admission were also at our disposal. Three quarters of the probands are living alone, and barely one third are in regular employment. At the time of the 14-year follow-up about one third showed delusions or hallucinations. Almost the same number had psychological impairments and 64% were socially disabled. Comparison with the data collected at 1 year and 5 years reveals no difference in the rates of impairments and symptomatology, but a significant increase of social disability.

Adult

Fully-automated, nonradioactive solid-phase sequencing of genomic DNA obtained from PCR.

Nonradioactive sequencing in combination with solid-phase template purification is a powerful method for sequence analysis, especially of PCR-generated fragments. To perform DNA sequencing under optimal conditions, it is necessary to obtain a well-purified and single-stranded (ss) DNA template. The disadvantage of ssDNA sequencing is that additional steps are required to generate ssDNA templates before any sequencing reactions can be carried out and is thus more time-consuming. Here we describe an automated solid-phase system for direct sequencing of ssPCR products that incorporates magnetic beads coated with streptavidin as solid support and a computer-controlled device (PolySeq) with heating, magnetic and mixing functions, all of which are integrated into a robotic workstation (Biomek 1000). This solid-phase method is extremely useful for rapid template purification and strand separation of DNA obtained from PCR as well as for high-quality dideoxyribonucleotide chain termination sequencing with fluorescently labeled primers. The system allows the complete automation of the sequencing procedure starting with PCR amplicons. DNA sequencing results obtained with this system were reproducible and gave an excellent length of readable sequences with low background and an analysis capacity of 30,000-40,000 bp per week.

Base Sequence

[Methadone substitution in national public health care in Germany--patients, indications, physicians. Results of a survey of public health service facilities].

Subject of this paper is methadone-maintenance given by office-based physicians in Germany in the framework of the statutory health insurance (SHI). Results of a survey of the associations of SHI-accredited physicians are presented, comprising the number of substituted patients, the distribution of indications and the number of the physicians engaged in this field. The results are presented under regional aspects and discussed. It was ascertained that in respect of the number of substituted patients, the increasing trend continues.

Ambulatory Care

[Mortality of foreign and indigenous population in the German Federal Republic].

Comparative mortality studies with respect to nationality have not yet been published in a comprehensive way for the Federal Republic of Germany. A recent special analysis of causes of death for German mortality statistics of the year 1986 indicates a lower mortality risk among the migrant compared to the indigenous population. Apart from potential biases, such as underreporting of nationality of death cases or overestimation of the size of the non-indigenous population in Germany, from the perspective of socio-epidemiology the possibility arises that selection processes lastingly affect the mortality risk of migrants. The dependence of the length of stay from the quality of the state of health or rather a plausible increased likelihood of remigration in case of chronic disease may constitute important influences, which could explain the differences in mortality between indigenous and migrant population.

Adult

Site-directed mutational analysis of human tumor necrosis factor-alpha receptor binding site and structure-functional relationship.

In order to define the receptor binding site and the structure-functional relationship of tumor necrosis factor (TNF), single amino acid substitutions were made by site-directed mutagenesis at selected residues of human tumor necrosis factor, using a phagemid mutagenesis/expression vector. The recombinant TNF mutants were compared to the wild type TNF in assays using crude bacterial lysates, for protein yield, solubility, subunit trimerization, receptor binding inhibition activity, and in vitro cytotoxic activity. All mutants which did not form cross-linkable trimer also showed little cytotoxic activity or receptor binding inhibition activity, indicating that trimer formation is obligatory for TNF-alpha activity. Most mutations of internal residues yielded no cross-linkable trimer, while most mutations of surface residues yielded cross-linkable trimer. Mutations at surface residues Leu29, Arg31, and Ala35 yielded cross-linkable trimers with good activities, except proline substitutions which may cause conformational changes in the polypeptide chain. This suggested that these residues are near the receptor binding site. Mutations at other strictly conserved internal residues such as Ser60, His78, and Tyr119 form cross-linkable trimer with little activity. These mutations may indirectly affect the receptor binding site by forming trimers with undetectable abnormalities. Mutants of surface residues Tyr87, Ser95, Ser133, and Ser147 affect receptor binding and cytotoxic activity but not trimer formation, suggesting that these residues are involved directly in receptor binding. The fact that residues Arg31, Ala35, Tyr87, Ser95, and Ser147, located on the opposite sides of a monomer, are clustered at the intersubunit grooves of TNF trimer supports the current notion that TNF receptor binding sites are trivalent and are located at the three intersubunit grooves. However, our finding that Ser133, which is outside the groove, can also be involved directly in receptor binding suggested that the receptor binding sites of TNF may not be confined to the intersubunit grooves, but extended to include additional surface residues.

Amino Acid Sequence

[Obstacles to maintaining the elderly in their own homes].

Elderly people desire deeply to remain in their own homes even if age or illness should limit their independence. This observation leads the authors to examine the obstacles for maintaining them in their own homes, i.e.: health problems leading to what is termed "social hospitalization", architectural barriers, housing crisis, and financial difficulties. They propose a number of solutions designed to reduce the number of patients placed in hospitals and institutions. In addition to psychological benefits, such measures could yield substantial financial savings.

Activities of Daily Living

[Narcissism: origin and goal of the ego. Reflections of Lou Andreas-Salomé].

The author presents Andreas-Salomé's theoretically relevant, though largely neglected writings. She devoted special interest to narcissism. Her contributions to this topic are discussed in relation to Freud's corresponding texts, with whom she maintained an enduring friendship. General reference is made to the more recent psychoanalytic debate about narcissism.

Ego

Sociological concepts in the etiology of chronic disease: the case of ischemic heart disease.

This paper first gives a selective and critical review of conventional sociological variables included into epidemiologic and clinical studies of ischemic heart disease (IHD). In a second section, links between social and biological processes are discussed, and a conceptual sociological approach is developed which relates critical experiences of active distress to impaired long-term control of social status. This approach is elaborated to some extent in order to illustrate possible avenues of future research which strengthen cross-fertilization between medical and social sciences.

Adaptation, Psychological

The social context of active distress in patients with early myocardial infarction.

Data of a retrospective case control study on 380 male patients with clinically documented first myocardial infarction (MI) (age 30-55) as well as findings of a follow-up over 18 months of 70% of this sample are presented. Results show first, that specific work stressors, lack of social support, and acute life changes are each significantly more prevalent among subjects with MI than among healthy controls; second, that significantly greater parts of MI subjects can be classified as simultaneously exposed to several chronic and acute social risks; third, that social stressors are related to the recurrence of cardiac symptoms in a follow-up after rehabilitation. These findings are discussed with regard to possible methodological bias such as the role of denial and neuroticism in patients under study, influences caused by interviewers, and limited validity of subjective stress rating. After controlling for these biases, findings basically remain stable. It is argued that a certain class of critical socio-emotional experiences, labeled 'active distress' may be harmful to neurohormonal imbalance, and, consequently, to several precursors of cardiovascular diseases. This class of experiences is reinforced and sustained by social contexts as the ones investigated in this study.

Adult

Towards a cognition - performance model of coronary - prone behavior.

The extent of coronary-prone behavior (CPB) is partially dependent upon specific, contextual characteristics of the work setting. Specific work demands reinforce a style of unrealistic cognitive appraisal which is thought to form a significant part of CPB. In order to test this assumption in a first step, we developed a questionnaire measuring this notion more appropriately than the well known tests of CPB (JAS, Bortner). Preliminary results of an experimental psychophysiologic study on the basis of this instrument are presented.

Adult