Mechanisms of TGFß3 Action as a Therapeutic Agent for Promoting the Synthesis of Extracellular Matrix Proteins in Hyaline Cartilage.

Hyaline cartilage is a nonvascular connective tissue covering the joint surface. It consists mostly of the extracellular matrix proteins and a small number of highly differentiated chondrocytes. At present, various techniques for repairing joint surfaces damage, for example, the use of modified cell cultures and biodegradable scaffolds, are under investigation. Molecular mechanisms of cartilage tissue proliferation have been also actively studied in recent years. TGFß3, which plays a critical role in the proliferation of normal cartilage tissue, is one of the most important protein among cytokines and growth factors affecting chondrogenesis. By interacting directly with receptors on the cell membrane surface, TGFß3 triggers a cascade of molecular interactions involving transcription factor Sox9. In this review, we describe the effects of TGFß3 on the receptor complex activation and subsequent intracellular trafficking of Smad proteins and analyze the relation between these processes and upregulation of expression of major extracellular matrix genes, such as col2a1 and acan.

[Yeast chaperone Hspl04 regulates gene expression on the posttranscriptional level].

Yeast chaperon Hsp104 is known as a protein which is able to dissociate aggregates of the heat damaged proteins and prion aggregates into smaller pieces or monomers. In our work the effects of Hsp104 on the PrP-GFP and GFP proteins have been analyzed. The PrP-GFP protein forms the high molecular weight aggregates, whereas GFP is unable to aggregate in yeast cell. We have shown that Hsp104 regulates the amount of PrP-GFP and GFP in yeast cells and direction of chaperone action depends on promoter controlling production of these proteins. The overproduction of Hsp104 increases the amount of PrP-GFP and GFP proteins when the corresponding genes are under control of CUP1 promoter. In contrast, the overproduction of Hsp104 decreases the amount of PrP-GFP and GFP is case of their expression under control of GPD promoter. The effects of Hspl04 are not related with any changes in mRNA content of the genes under investigation and with ability of the proteins to form aggregates. Thus, the functions of this chaperon are not restricted by dissociation of the protein aggregates. Our data show that Hsp104 regulates the gene expression on the posttranscriptional level.

Climate change and landscape development in post-closure safety assessment of solid radioactive waste disposal: Results of an initiative of the IAEA.

The International Atomic Energy Agency has coordinated an international project addressing climate change and landscape development in post-closure safety assessments of solid radioactive waste disposal. The work has been supported by results of parallel on-going research that has been published in a variety of reports and peer reviewed journal articles. The project is due to be described in detail in a forthcoming IAEA report. Noting the multi-disciplinary nature of post-closure safety assessments, here, an overview of the work is given to provide researchers in the broader fields of radioecology and radiological safety assessment with a review of the work that has been undertaken. It is hoped that such dissemination will support and promote integrated understanding and coherent treatment of climate change and landscape development within an overall assessment process. The key activities undertaken in the project were: identification of the key processes that drive environmental change (mainly those associated with climate and climate change), and description of how a relevant future may develop on a global scale; development of a methodology for characterising environmental change that is valid on a global scale, showing how modelled global changes in climate can be downscaled to provide information that may be needed for characterising environmental change in site-specific assessments, and illustrating different aspects of the methodology in a number of case studies that show the evolution of site characteristics and the implications for the dose assessment models. Overall, the study has shown that quantitative climate and landscape modelling has now developed to the stage that it can be used to define an envelope of climate and landscape change scenarios at specific sites and under specific greenhouse-gas emissions assumptions that is suitable for use in quantitative post-closure performance assessments. These scenarios are not predictions of the future, but are projections based on a well-established understanding of the important processes involved and their impacts on different types of landscape. Such projections support the understanding of, and selection of, plausible ranges of scenarios for use in post-closure safety assessments.

The differential effects of exposure to tobacco smoke on the secretion of luteinizing hormone and prolactin in the proestrous rat.

The acute effects of tobacco smoke inhalation on the spontaneous proestrous rise in serum luteinizing hormone and prolactin have been investigated in the female Wistar rat. It was found that the surge of LH normally seen throughout the afternoon of proestrus was delayed by inhalation of tobacco smoke and that the delay was dose-related to the nicotine content of the cigarettes used in the experiment. In the case of prolactin neither the timing nor the magnitude of the surge was altered when compared with controls. These results suggest that under certain well-defined conditions inhalation of tobacco smoke of known nicotine content is capable of exerting profound influences on the hypothalamic-pituitary-gonadal axis.

Social and cultural factors in the successful control of tuberculosis.

The burden of tuberculosis on the public health is staggering. Worldwide, annual incidence of new cases is estimated to be about 8 million. Almost 3 million deaths occur yearly. Early case identification and adherence to treatment regimens are the remaining barriers to successful control. In many nations, however, fewer than half those with active disease receive a diagnosis, and fewer than half those beginning treatment complete it. The twin problems of delay in seeking treatment and abandonment of a prescribed regimen derive from complex factors. People's confusion as to the implications of the tuberculosis symptoms, costs of transportation to clinic services, the social stigma that attaches to tuberculosis, the high cost of medication, organizational problems in providing adequate followup services, and patients' perception of clinic facilities as inhospitable all contribute to the complexity. Sociocultural factors are emphasized in this report because hitherto they have not been adequately explored. Salient among those sociocultural factors is the health culture of the patients. That is, the understanding and information people have from family, friends, and neighbors as to the nature of a health problem, its cause, and its implications. A knowledge of the health culture of their patients has become a critical tool if tuberculosis control programs are to be successful. Several anthropological procedures are recommended to help uncover the health culture of people served by tuberculosis clinics.

Disseminated skeletal lesions associated with pathogenic actinomycetes in a Pygmy hog (Sus salvanius).

The clinical and pathological features of an unusual crippling bone disease in an adult male Pygmy Hog, Sus salvanius, born the smallest in a litter of five and representing the rarest of the known living Suidae, are described. Radiological studies revealed severe spondylosis deformans and focal sharply demarcated radiolucencies in virtually the whole skeleton, but particularly in the bones of the skull, the processes of multiple vertebrae, the ribs, scapulae and parts of the humeri and femora. The clinical chemistry measurements were indicative of pathological lytic processes in the skeleton. The focal bone lesions consisted of caseous necrosis, dystrophic calcification and peripheral fibroblastic demarcation. They contained colonies of filamentous bacteria identified as members of the Order Actinomycetales. Case history evidence suggests that the infection may have resulted from repeated skin trauma inflicted by litter-mates.

The process of faculty-mentored student research in family medicine: motives and lessons.

BACKGROUND AND OBJECTIVES: Research suggests that the strongest predictor of postgraduate research activity is medical student research involvement. Yet many medical students still regard family medicine as a "nonresearch" specialty. The purposes of this study were to discover what motivated a group of first-year medical students (and their faculty mentors) to participate in a summer research assistantship and how both groups evaluated the challenges and satisfactions of the experience. METHODS: The study used a grounded theory qualitative methodology that emphasizes an in-depth, inductive approach to evaluation research. Over a 2-year period, 11 first-year medical students who participated in a summer research assistantship and their 10 faculty mentors completed written questionnaires and were interviewed by our research team. Various categories of analysis were constructed and refined over the course of the study to explain the raw data collected through interviews, written questionnaires, and field notes. RESULTS: Findings included identification of a core theme or meaning that motivated participation in the project for students and faculty. This theme was expressed in terms of professional, personal, relational, and societal goals. The study also identified three interrelated mechanisms (socialization, relationship, and technical skill transmission) used in varying degrees by students and faculty to achieve these goals. CONCLUSION: In addition to technical mastery and knowledge, students were actively seeking professional relationships with faculty mentors, greater understanding of other peoples and cultures, and increased self-understanding and self-esteem. Junior and senior faculty reflected differing and multilevel motivations for participating in a research assistantship program.

Serological evidence of herpesvirus infection in captive Asian elephants (Elephas maximus).

In mid 1988 a 3-yr-old Asian elephant (Elephas maximus) from a circus in Switzerland died following generalized manifestation of a herpesvirus infection. In an effort to determine prevalence of infection with the herpesvirus, and due to lack of a corresponding virus isolate, it was decided to evaluate contact animals and elephants from a second herd for antibody to bovine herpesvirus 1 (BHV1) and bovine herpesvirus 2 (BHV2). Of 15 sera tested four displayed low neutralizing antibody titers to BHV2. None of the sera neutralized BHV1. However, as evidenced by protein A-mediated immunoprecipitation of metabolically radio-labeled virus-infected and mock-infected cell antigens, followed by separation of precipitation products in SDS-polyacrylamide gels, the 15 sera precipitated multiple antigens from both viruses. Similar results were obtained when using BHV4 antigens. The extent of reaction was most distinct with respect to BHV2 antigens, less prominent with BHV1 antigens, and least with BHV4 antigens. The respective protein patterns, although less marked, matched well with those obtained with bovine reference sera. Additional evaluation of sera from six elephants from two zoos in the Federal Republic of Germany gave essentially identical results. It was concluded that at least one herpesvirus, immunologically related to BHV2, may be widely distributed among captive Asian elephants, and that this virus apparently does not cause overt disease in the majority of animals.

The contribution of medical anthropology to a comparative study of culture: susto and tuberculosis.

Results of studies of the popular illness susto and the biomedical entity pulmonary tuberculosis are offered to illustrate how comparisons of sick and well people can elucidate societal processes in cultural anthropology.

[Animal welfare aspects relevant to the design of the spectacled bear facility in the Zürich Zoo]. / Tierschutzrelevante Aspekte bei der Gestaltung der Brillenbärenanlage im Zoo Zürich.

The Swiss animal welfare law and animal welfare regulations determine the conditions how wild animals have to be kept in captivity. The zoo animal working group of the Swiss Veterinary Association for Animal Welfare has analysed the respective definitions in relation to keeping bears. During the planning and construction of the new clouded forest exhibit for spectacled bears, the Zürich Zoo has put the conclusions of this analysis into practice. Beside the safety precautions for health the realisation of species-related requirements is the basis for the well-being of the animals. The shaping, the arrangement, the furniture and the management of the enclosure for spectacled bears in regard to these demands are described.

Observations on the female reproductive cycle of captive giant tortoises (Geochelone spp.) using ultrasound scanning.

The reproductive activities of one adult female Galápagos tortoise (Geochelone nigra) and three adult female Aldabra tortoises (Geochelone gigantea) were monitored over 2 yr using ultrasound scanning. A nonrestraining technique of tactile stimulation was used for all examinations. Developing, preovulatory, and atretic ovarian follicles, as well as eggs at various stages of shell deposition, were identified and measured. In G. nigra, follicles became preovulatory at a diameter of 40-42 mm and eggs were laid 34-84 days (mean = 55.6, n = 5) after the thin-shelled eggs were first detected in the oviducts. Geochelone nigra was capable of retaining eggs, with the shell already formed, until the next breeding season. No eggs have been produced by G. gigantea during their stay in Zürich Zoo although follicles of 38-40 mm have been observed frequently in two animals.