PubMed Health⌕ Search

Biomedical subjects

H Brand

Publications and source records attributed to H Brand.

At least 19 recordsLinked to original sources

[Genetics in health research and public health].

Public health practice has to date concerned itself mostly with environmental determinants of health and disease and has paid scant attention to genetic variations within the population. The advances brought about by genomics is changing these perceptions. Many predict that this knowledge will enable health promotion messages and disease prevention programmes to be specifically directed at susceptible individuals or at subgroups of the population, based on their genetic profile. Obviously, the integration of genomics into public health research, policy and practice will be one of the most important future challenges that our health care systems will face. In this context, Public Health Genomics (PHG), defined as the responsible and effective translation of genome-based knowledge and technologies into public policy and health services for the benefit of population health, will encounter these chances and challenges.

Forecasting↗

[Community knowledge about stroke. A survey in the District of Wesel, Germany (2002)].

Community knowledge of stroke signs and risk factors in Germany is poor, while lacking knowledge is an important cause for delays in hospital admission. In the Wesel district (North Rhine-Westphalia) the local health conference put this issue on its agenda and initiated a phone survey. The aim was to assess community knowledge of stroke symptoms and risk factors as well as self-reported prevalence of established risk factors; in addition, the role of information on stroke risk provided to patients by the general practitioner (GP) was to be estimated. The study population was defined as comprising all residents in the district of Wesel between 18 and 87 years of age (approx. 385,000 people). The sample of 1,089 persons was drawn randomly and the telephone survey was carried out by the CATI-Laboratory (Computer Assisted Telephone Interviews) at the Institute of Public Health (lögd, Bielefeld) between 18 February and 28 March 2002. A total of 1,089 people were interviewed, of whom 31.9% knew no symptom, 25.7% could name one symptom, 23.8% two symptoms and 18.6% knew three or more correct signs. Weakness/paralysis was named most frequently by 43.6% of the respondents. The majority of respondents named smoking as a risk factor (59.6%), while hypertension was mentioned by 39.4% of the participants. Among 555 respondents aged 45 years and older, 75.1% said they had never received a GP's advice on stroke risk, while 75.3% among these persons reported to have at least one risk factor. The present study shows a persistent lack of community knowledge about stroke. It is recommended that knowledge be improved especially with regard to (a) proper action: "stroke is a medical emergency-call the emergency telephone code 112", (b) symptoms and warning signs and (c) major stroke risk factors, especially high blood pressure. Moreover, information and advice on stroke should play a bigger part in the doctor's daily practice; patients should be made aware of their stroke risks and ways of prevention.

Adolescent↗

[Cross-border cooperation in Europe: what are Euregios?].

In cross-border cooperation, much importance has been attributed to the so-called "Euregios", synonymously also called "Euroregions". These are cross-border structures in which, above all, local and regional authorities have joined together across one or several national borders. As early as 1958, the first Euregio was established along the German-Dutch border. Meanwhile many other Euregios have been set up. Euregios provide the testing ground for pilot projects to examine practical solutions of cooperation. Euregios are therefore also called "laboratories of Europe" or "testing laboratories of European integration". Also in the health sector, several cross-border projects are being and have already been carried out. According to what has been found out so far, above all Euregios with long years of experience in cross-border cooperation seem to commit themselves to the health issue. A huge number of the projects is co-financed by the European Union. Compared to other thematic areas, in some border regions the health issue has, on the whole been, underrepresented in cross-border cooperation. In this respect, there is potential for development. Information on existing projects as well as their experiences can facilitate the successful implementation of health-relevant cross-border projects also in those regions which have up to now not carried out any or only a few projects of this kind. The EU-funded Euregio project, carried out by lögd NRW, is the first project in which a systematic inventory analysis of cross-border health care projects will be drawn up.

Community Networks↗

[Local coordination of health care in North Rhine-Westphalia Interim review of the North Rhine-Westphalian model].

In January 1998, the Public Health Service Act (OGDG) was put into force by North Rhine-Westphalia's state parliament as Article 3 of the Act on the Strengthening of the Efficiency of Districts, Cities and Municipalities. The objective of the Public Health Service Act is the performance of functions through the public health service in a way which corresponds to problems, ambitions and priorities at the local level. The effects of the Act have been documented over a period of 5 years. The authors describe the method of evaluation and the most important results. As well as describing traditional tasks, they focus in particular on process and structural data of the local health conferences. These have been introduced as a consequence of the Public Health Service Act in all 54 districts and self-administered cities in North Rhine-Westphalia. Another task which has become obligatory as a result of the Public Health Service Act is health reporting. Here, the authors report on the state of affairs with regard to implementation, major topics and differences in concept. Based on the state of development at the end of 2002, the authors describe present developments and prospects. They expect continuous need for support, particularly in the fields of health conferences and health reporting.

Adolescent↗

An anti-MUC1-antibody-interleukin-2 fusion protein that activates resting NK cells to lysis of MUC1-positive tumour cells.

MUC1 mucin is aberrantly glycosylated and overexpressed in a number of epithelial malignancies and is therefore a promising tumour-associated antigen for target-directed immunotherapy of a panel of malignant diseases. In MUC1-positive tumours, MHC class I expression is frequently downregulated and MUC1-specific cytotoxic T cells (CTLs) are either not available or in a state of anergy allowing tumour growth without limitation by CTL control. To activate lymphocytes and natural killer (NK) cells, we here generated an anti-MUC1-scFv-IL2 fusion protein (C595scFv-Fc-IL2) that contains the C595 single-chain antibody for MUC1 binding, the human IgG1 CH2CH3 domain for protein dimerisation, and interleukin-2 (IL2) for activation of immunological effector cells. The fusion protein binds to MUC1-derived peptides and to MUC1-positive tumour cells with the same specificity as does the C595 monoclonal antibody. Bound to MUC1, the C595scFv-Fc-IL2 fusion protein stimulates proliferation of human activated lymphocytes in vitro. Upon binding to MUC1-positive MCF7 breast carcinoma cells, moreover, the fusion protein activates resting NK cells to tumour cell lysis. These properties make the C595scFv-Fc-IL2 fusion protein a suitable candidate for the immunotherapy of MUC1-positive tumours.

Antibodies, Monoclonal↗

[Socio-economic differences in the utilisation of screening programmes and health promotion measures in North Rhine-Westphalia, Germany].

This paper examines the effect of socio-economic status on the utilisation of screening programmes and health promotion measures, based on data of a representative health survey in North Rhine-Westphalia (Germany), with a sample of 1,920 respondents. The analysis focuses especially on the utilisation of the cancer screening programme and the 'Health Check-Up' programme, which both have a high rank in German secondary prevention strategies. During the study year and the year before 29.2 % of the relevant male and 56.5 % of the female population took part in cancer screening programmes. At the same time 29.6 % of the males and 30.1 % of the females took part in the 'Health Check-Up' programme. In respect of socio-economic differences, the data confirmed the results of former studies in which non-participation of cancer screening programmes increased with decreasing social class. The social gradient was more pronounced with women than with men. While for the 'Health Check-Up' no socio-economic differences could be found, the participation rates in health promotion measures for women varied significantly with socio-economic status. For both screening programmes generally weaker statistical associations were found if the socio-economic status index was substituted by the educational level of the respondents. The findings suggest that strategies designed to increase participation of such programmes should concentrate more on lower social status persons to prevent the development of inequalities in health.

Adolescent↗

Tissue-specific expression of human ERalpha and ERbeta in the male.

The important role of estrogens in women in physiological and pathological processes is well accepted, but recently it has become evident that estrogens are also important in male physiology, in particular, within bone metabolism and reproduction. Consequently, it is necessary to identify and to characterize the molecular mechanisms of estrogen action in order to evaluate how the pleiotropic effects of estrogens are mediated in a variety of tissues. We have recently shown that human estrogen receptor alpha (ERalpha) mRNA is transcribed from at least six different promoters (1A-1F). Transcription of ERalpha in bone is exclusively dependent on the F-promoter. To study the regulation of ER expression in this tissue, we examined 1 kbp of the F-promoter region of human ERalpha, which is located more than 70 kbp upstream of the transcription start site of the ERalpha gene. Transient transfection experiments demonstrated a basal activity from the F-promoter, which was further increased when ERalpha was cotransfected. We have shown recently that the F-promoter can give rise to at least two ERalpha isoforms in bone. On the contrary, ERbeta expression in primary osteoblasts is extremely low, indicating that this ER isoform plays only a minor role in these cells. In contrast to bone, we have demonstrated that both ERalpha and ERbeta transcripts are readily detected in testis. Here, we report that besides ERalpha, ERbeta transcripts can give rise to two protein isoforms and that this complex situation could have important functional consequences for the signalling of estrogens and their analogs.

Alternative Splicing↗

Infectious diseases before and after German unification: trends in mortality and morbidity.

After the fall of the Berlin Wall in 1989 the former communist countries of central and eastern Europe underwent substantial social and economic changes that had a major impact on health. The situation of the former German Democratic Republic was unique in that its existing institutions were replaced rapidly and it was quickly integrated economically with the West. This study describes recent trends in morbidity and mortality from infectious diseases in East and West Germany before and after unification using routine data from 1980 onwards. Substantial differences in morbidity and mortality resulting from infectious diseases were observed between East and West Germany. These seem to be the complex result of societal and health system differences in both parts of Germany before unification, differing population dynamics and health behaviours, and an increasing westernisation in the eastern part of Germany during recent years.

Communicable Diseases↗

[Approaches to quality management in public health: current and future prospects].

All institutions in the health care sector are facing increasing competition. Therefore, new management concepts are considered. Current strategies are evaluated, and the efficiency of outputs is questioned. Quality management becomes a powerful instrument for achieving quality and ultimate aims. This development will also be the key to success for public health services.

Forecasting↗

ERalpha gene expression in human primary osteoblasts: evidence for the expression of two receptor proteins.

The beneficial influence of E2 in the maintenance of healthy bone is well recognized. However, the way in which the actions of this hormone are mediated is less clearly understood. Western blot analysis of ERalpha in osteoblasts clearly demonstrated that the well characterized 66-kDa ERalpha was only one of the ERalpha isoforms present. Here we describe a 46-kDa isoform of ERalpha, expressed at a level similar to the 66-kDa isoform, that is also present in human primary osteoblasts. This shorter isoform is generated by alternative splicing of an ERalpha gene product, which results in exon 1 being skipped with a start codon in exon 2 used to initiate translation of the protein. Consequently, the transactivation domain AF-1 of this ERalpha isoform is absent. Functional analysis revealed that human (h)ERalpha46 is able to heterodimerize with the full-length ERalpha and also with ERbeta. Further, a DNA-binding complex that corresponds to hERalpha46 is detectable in human osteoblasts. We have shown that hERalpha46 is a strong inhibitor of hERalpha66 when they are coexpressed in the human osteosarcoma cell line SaOs. As a functional consequence, proliferation of the transfected cells is inhibited when increasing amounts of hERalpha46 are cotransfected with hERalpha66. In addition to human bone, the expression of the alternatively spliced ERalpha mRNA variant is also detectable in bone of ERalpha knockout mice. These data suggest that, in osteoblasts, E2 can act in part through an ERalpha isoform that is markedly different from the 66-kDa receptor. The expression of two ERalpha protein isoforms may account, in part, for the differential action that estrogens and estrogen analogs have in different tissues. In particular, the current models of the action of estrogens should be reevaluated to take account of the presence of at least two ERalpha protein isoforms in bone and perhaps in other tissues.

Alternative Splicing↗

Synergistic activation of the Atlantic salmon hepatocyte nuclear factor (HNF) 1 promoter by the orphan nuclear receptors HNF4 and chicken ovalbumin upstream promoter transcription factor I (COUP-TFI).

Hepatocyte nuclear factor 1 (HNF1) is a liver-enriched transcription factor that plays an important role in transcriptional networks involved in liver function. The promoters of mammalian HNF1 genes contains a single binding site for another liver-enriched transcription factor, the nuclear hormone receptor HNF4. A transcriptional hierarchy involving HNF4-mediated activation of the HNF1 promoter has been proposed to be of crucial importance in maintaining the differentiated hepatocyte phenotype. Here we present evidence that the Atlantic salmon HNF1 promoter contains three nuclear-hormone-receptor-binding sequences. Gel-shift assays showed that these motifs are recognized with different affinities by HNF4 and the orphan nuclear receptors chicken ovalbumin upstream promoter transcription factors COUP-TFI and COUP-TFII. In hepatoma cells, the site showing highest affinity for HNF4 appears to be crucial for promoter activity. Transfection experiments in non-hepatic cells indicated that the salmon HNF1 promoter was activated by both HNF4 and COUP-TFs. We also identified a promoter fragment encompassing the two more distal nuclear-hormone-binding sites that was activated by HNF4, unaffected by COUP-TF and showed a strong synergistic activation by HNF4/COUP-TF. Results are presented detailing these interactions in relation to the salmon HNF1 promoter architecture.

Animals↗

Identification of a new isoform of the human estrogen receptor-alpha (hER-alpha) that is encoded by distinct transcripts and that is able to repress hER-alpha activation function 1.

A new isoform of the human estrogen receptor-alpha (hER-alpha) has been identified and characterized. This 46 kDa isoform (hERalpha46) lacks the N-terminal 173 amino acids present in the previously characterized 66 kDa isoform (hERalpha66). hERalpha46 is encoded by a new class of hER-alpha transcript that lacks the first coding exon (exon 1A) of the ER-alpha gene. We demonstrated that these Delta1A hER-alpha transcripts originate from the E and F hER-alpha promoters and are produced by the splicing of exon 1E directly to exon 2. Functional analysis of hERalpha46 showed that, in a cell context sensitive to the transactivation function AF-2, this receptor is an effective ligand-inducible transcription factor. In contrast, hERalpha46 is a powerful inhibitor of hERalpha66 in a cell context where the transactivating function of AF-1 predominates over AF-2. The mechanisms by which the AF-1 dominant-negative action is exerted may involve heterodimeri zation of the two receptor isoforms and/or direct competition for the ER-alpha DNA-binding site. hERalpha66/hERalpha46 ratios change with the cell growth status of the breast carcinoma cell line MCF7, suggesting a role of hERalpha46 in cellular proliferation.

Base Sequence↗

[Foundations--a means for implementing strategic goals and measures in public health].

Social innovations are happening in many critical areas. Foundations make an enduring contribution towards increasing access to innovations in public welfare based on the philosophy that believes state-run organizations are neither efficient nor responsive to the people's changing needs. In this sense, foundations help to close the gap by turning hitherto tolerated conditions into problems and claims to action. The effectiveness of voluntary bodies as advocates of change owes much to their informal nature. In Germany, voluntary actions in Public Health are still underrepresented. Therefore, donors should be more supported by state government through adequate regulations. In addition, funders need to concentrate their efforts on the limited number of areas where they can have the greatest impact.

Forecasting↗

The 3'-untranslated region of the human estrogen receptor alpha gene mediates rapid messenger ribonucleic acid turnover.

Human estrogen receptor-alpha messenger RNA (hERalpha mRNA) has a relatively short half-life, which was determined to be approximately 5 h in MCF-7 cell line after actinomycin D treatment. The 3'-untranslated region (3'UTR) of hERalpha mRNA was previously shown to completely down-regulate chloramphenicol acetyltransferase activity when present at the 3'-end of chloramphenicol acetyltransferase transcripts, suggesting a destabilizing function of the hERalpha 3'UTR sequence. Chimeric genes composed of a serum-inducible Fos promoter, GH-coding sequences, and different segments of the hERalpha complementary DNA 3'UTR sequence were used to confirm this hypothesis and to localize the RNA region responsible for the destabilizing effect. The presence of the complete hERalpha 3'UTR reduced the half-life of the reporter mRNA from more than 24 to 3 h. When the hERalpha 3'UTR was subdivided into four fragments (UTR1-4), one fragment, UTR2, retained the most ability to down-regulate the reporter mRNA (t1/2 = 4 h). A stretch of four AUUUA motifs within UTR2 was shown not to mediate mRNA destabilization. In contrast, further subdivision of the UTR2 into three parts (UTR2a-c) resulted in the loss of the destabilizing activity. Finally, recombination of two UTR2 subfragments (UTR2a and -b) partially restored this function, indicating a cooperative role among the three UTR2a-c subfragments in the process that leads to destabilization of the hERalpha transcript.

3' Untranslated Regions↗

Identification of differentially expressed 5'-end mRNA variants by an improved RACE technique (PEETA).

A rapid and efficient procedure is described for mapping and cloning the 5'-ends of mRNAs, including those generated from a unique gene by alternative splicing and promoter usage. This method involves reverse transcription of the targeted mRNAs from a long, highly labeled specific primer, resolution of the extension products on a DNA sequencing gel, elution and poly(dC) tailing of the single-stranded cDNAs of interest, amplification of these cDNAs by PCR using an oligo(dG) adapter-primer and a gene-specific primer and finally DNA sequencing of the subcloned PCR fragments. The overall method is called PEETA (primer extension, electrophoresis, elution, tailing and amplification).

Adolescent↗