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Biomedical subjects

T Abel

Publications and source records attributed to T Abel.

At least 55 records · Page 3Linked to original sources

Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice.

Brain-derived neurotrophic factor (BDNF) is expressed at high levels in hippocampal neurons, and its expression is modulated by neural activity. Knockout mice can be used to study the roles of molecules like BDNF in synaptic plasticity with more molecular specificity than is possible using pharmacological approaches. Because in conventional knockouts the disrupted gene product is absent in all tissues throughout the life of the animal, developmental effects may complicate the interpretation of deficits in the adult. Rescue experiments can help to distinguish between developmental and acute requirements for the missing gene product. We here demonstrate that treatment of hippocampal slices from BDNF knockout mice with recombinant BDNF completely reverses deficits in long-term potentiation and significantly improves deficits in basal synaptic transmission at the Schaffer collateral-CA1 synapse. Thus, BDNF has an acute role in hippocampal synaptic function.

Animals↗

Studies on 13C-phenacetin metabolism. II. A combination of breath test and urine test of in vivo metabolites in the diagnosis of liver disease.

We determined the optimum 13C-labeling position in phenacetin for use in a breath test to diagnose liver disease based on infrared spectroscopy detection of 13CO2 in exhaled air. ([1-13C]Ethoxy)phenacetin gave the best result. This compound was also employed in a urine test using 13C-NMR spectroscopy. In the urine test, healthy subjects gave a higher signal of phenacetin than of its metabolite, phenetidine, whereas in patients with liver disease the situation was the reverse. The combination of the breath and urine tests may be a valuable new tool for the diagnosis of liver disease.

Acute Disease↗

[Molecular genetic markers of Alzheimer dementia].

Alzheimer's dementia (AD) is a progressive neurodegenerative disease which is one of the most common forms of dementia in the above 65 years old age group. Diagnosis is based upon evaluation of cognitive skills, elimination of other dementia associated diseases and on cranial CT examination. However, definitive diagnosis is proved only by neurohistological findings. The etiology of the disease is unknown and effective treatment is not available. Intensive research into the pathomechanism of the disease revealed a connection between increased frequency of apolipoprotein E4 allele and later onset of AD. The aim of the author's research was to characterize apolipoprotein E polymorphisms in AD patients and to examine immunological factors which could play an important role in the development of the disease such as the polymorphism of complement and lipoprotein(a) [Lp(a)] alleles previously had not been investigated. 35 AD patients (26 female, 9 male) were examined (mean age 66.4 years +/- 8.7 SD). 18 of these patients showed late onset of the disease. The E4 allele was significantly more frequent in both early and late onset groups compared to controls (0.29 vs. 0.14 and 0.33 vs 0.09). The high frequency of apo E4 found in the early onset group in this study differs from other international data. Serum lipid, lipoproteins, Lp(a) concentrations and Lp(a) phenotype distribution showed no significant difference compared to controls. Furthermore, it was found that the frequency of complement C4AQ0 (null) and Bf F alleles was higher in the late onset AD group compared to controls (0.35 vs 0.139 and 0.305 vs. 0.225) suggesting an active involvement of the complement system in the pathogenesis of this disease.

Age Factors↗

Transgenic approaches to cognition.

Reverse genetic techniques, including gene 'knockouts' and transgenesis, allow defined mutations to be introduced into the mouse genome. The application of these techniques to neurobiology is beginning to provide a bridge between genes and cognition. Specifically, genetically altered mice make it possible to explore molecular mechanisms underlying implicit and explicit forms of learning, short-term and long-term memory, and emotional behaviors. The analysis of these mutant mice has begun to link specific behavioral deficits to defined changes in synaptic physiology.

Animals↗

Requirement of a critical period of transcription for induction of a late phase of LTP.

Repeated high-frequency trains of stimuli induce long-term potentiation (LTP) in the CA1 region that persists for up to 8 hours in hippocampal slices and for days in intact animals. This long time course has made LTP an attractive model for certain forms of long-term memory in the mammalian brain. A hallmark of long-term memory in the intact animal is a requirement for transcription, and thus whether the late phase of LTP (L-LTP) requires transcription was investigated here. With the use of different inhibitors, it was found in rat hippocampal slices that the induction of L-LTP [produced either by tetanic stimulation or by application of the cyclic adenosine monophosphate (cAMP) analog Sp-cAMPS (Sp-cyclic adenosine 3',5'-monophosphorothioate)] was selectively prevented when transcription was blocked immediately after tetanization or during application of cAMP. As with behavioral memory, this requirement for transcription had a critical time window. Thus, the late phase of LTP in the CA1 region requires transcription during a critical period, perhaps because cAMP-inducible genes must be expressed during this period.

Animals↗

A Drosophila GATA family member that binds to Adh regulatory sequences is expressed in the developing fat body.

We have identified a Drosophila transcription factor that binds a sequence element found in the larval promoters of all known alcohol dehydrogenase (Adh) genes. DNA sequence analysis of cDNA clones encoding this protein, box A-binding factor (ABF), reveals that it is a member of the GATA family of transcriptional regulatory factors. ABF-binding sites within the D. mulleri and D. melanogaster larval Adh promoters function as positive regulatory elements and in cotransfection experiments, ABF functions as a transcriptional activator. In further support of a role for ABF in the regulation of Adh expression, ABF mRNA is expressed in the embryonic fat body, a tissue that contains high levels of Adh mRNA. Our studies demonstrate that the fat body develops from segmentally repeated clusters of mesodermal cells, which later expand and coalesce to form the mature fat body. These observations establish ABF as the earliest known fat body precursor marker in the Drosophila embryo. Together with the established role of GATA factors during mammalian development, these results suggest that ABF may play a key role in the organogenesis of the fat body.

Alcohol Dehydrogenase↗

A GATA family transcription factor is expressed along the embryonic dorsoventral axis in Drosophila melanogaster.

The GATA transcription factors are a family of C4 zinc finger-motif DNA-binding proteins that play defined roles in hematopoiesis as well as presumptive roles in other tissues where they are expressed (e.g., testis, neuronal and placental trophoblast cells) during vertebrate development. To investigate the possibility that GATA proteins may also be involved in Drosophila development, we have isolated and characterized a gene (dGATAa) encoding a factor that is quite similar to mammalian GATA factors. The dGATAa protein sequence contains the two zinc finger DNA-binding domain of the GATA class but bears no additional sequence similarity to any of the vertebrate GATA factors. Analysis of dGATAa gene transcription during Drosophila development revealed that its mRNA is expressed at high levels during early embryogenesis, with transcripts first appearing in the dorsal portion of the embryo just after cellularization. As development progresses, dGATAa mRNA is present at high levels in the dorsal epidermis, suggesting that dGATAa may be involved in determining dorsal cell fate. The pattern of expression in a variety of dorsoventral polarity mutants indicates that dGATAa lies downstream of the zygotic patterning genes decapentaplegic and zerknüllt.

Amino Acid Sequence↗

[Health behavior of young adults: empirical analysis of complex behavior patterns and their determinants].

Complex associations between alcohol consumption, cigarette smoking, eating habits and physical exercise are explored. Data from the 1985 German Cardiovascular Prevention Study are used to explore associations between these behaviours, separate for young men (n = 561) and young women (n = 509) between 25 to 34 years of age. Analyses concern three forms of associations: 1. associations between different categories of single health behaviours; 2. associations between various health behaviours, and 3. associations between health behaviours, and their social determinants. Contingency tables, cluster analyses and logistic regression analyses are applied. Cluster analyses identified subgroups with particular health behaviour patterns. One distinct pattern, similarly among men and women, was typified by increased physical exercise, less smoking and increased beer consumption. For young men, results from regression analyses showed significant effects of higher income and positive health attitudes on belonging to this distinct cluster. For young women cluster membership was significantly correlated with higher education and positive health attitudes. Results of the statistical analyses demonstrate the usefulness of a multi-methods approach in studying complex behaviour patterns. Finally the relevance of the present findings for future studies and applications is indicated.

Adult↗

A Drosophila CREB/ATF transcriptional activator binds to both fat body- and liver-specific regulatory elements.

We have identified a Drosophila transcription factor that binds to fat body-specific enhancers of alcohol dehydrogenase (Adh) and yolk protein genes. DNA sequence analysis of cDNA clones encoding this protein, box B-binding factor-2 (BBF-2), indicates that it is a member of the CREB/ATF family of transcriptional regulatory proteins. A number of observations suggest that BBF-2 is involved in fat body-specific expression: Mutations that disrupt BBF-2 binding to two different Adh fat body enhancers in vitro decrease the activity of these enhancers in transgenic flies. BBF-2 mRNA is present in all cell types examined, and the protein is present in cells that express ADH. Finally, BBF-2 is a transcriptional activator in Drosophila tissue culture cells. Remarkably, BBF-2 also binds specifically to regulatory elements required for liver-specific expression of the human Adh and rat tyrosine aminotransferase genes. Thus, BBF-2 and the DNA sequence to which it binds may be important components of a tissue-specific regulatory mechanism conserved between Drosophila and man.

Activating Transcription Factors↗

Patterns of unhealthy eating behaviours in a middle aged Scottish population.

This paper examines unhealthy eating in a middle aged Scottish population. Data from a 1989 survey of 500 Scottish men and women aged 45 to 59 years are used to explore inter-relations among five items of unhealthy eating, smoking and alcohol consumption. The results show that unhealthy eating behaviours are highly correlated, indicating strong links among certain nutrition habits. The findings also reveal that such patterns of unhealthy eating vary considerably between males and females. Finally, unhealthy eating behaviours were also found to be significantly associated with smoking and alcohol consumption. Implications of these findings for future research in epidemiology and health promotion are considered.

Aged↗

Stratification, competition and risk distribution: health insurance in Germany and the United States.

Issues of unequal risk distribution among sickness funds are given increasing attention in the current discussions on the reform of the statutory health insurance system in Germany. This paper examines the structural determinants of risk distribution and points toward the links between social stratification, competition, health risk and insurance status. A model showing the links between basic structural determinants is presented. Using health survey data from Germany and the U.S., statistical analyses are conducted. The results support the model and indicate its applicability for both health care systems. The paper concludes by indicating the relevance of such findings for health policy and future research.

Economic Competition↗

[Social status, health risk and sickness insurance: a comparative analysis between the FRD and the USA].

Issues of unequal risk distribution among sickness funds are given increasing attention in the current discussions on the reform of the statutory health insurance system in Germany. This paper raises the question on the structural determinants of risk segregation and points towards the links between social stratification, health risk and insurance status. A model showing the links between basic structural determinants is presented. Using health survey data from Germany and the U.S. statistical analyses are conducted. The results support the model and indicate its applicability for both health care systems. The paper concludes by indicating the relevance of such findings for health policy and future research.

Adolescent↗

Measuring health lifestyles in a comparative analysis: theoretical issues and empirical findings.

The concept of lifestyle bears great potential for research in medical sociology. Yet, weaknesses in current methods have restrained lifestyle research from realizing its full potentials. The present focus is on the links between theoretical conceptions and their empirical application. The paper divides into two parts. The first part provides a discussion of basic theoretical and methodological issues. In particular selected lines of thought from Max Weber are presented and their usefulness in providing a theoretical frame of reference for health lifestyle research is outlined. Next, a theory guided definition of the subject matter is introduced and basic problems in empirical applications of theoretical lifestyle concepts are discussed. In its second part the paper presents findings from comparative lifestyle analyses. Data from the U.S. and West Germany are utilized to explore issues of measurement equivalence and theoretical validity. Factor analyses indicate high conceptual equivalence for new measures of health lifestyle dimensions in both the U.S. and West Germany. Divisive cluster analyses detect three distinct lifestyle groups in both nations. Implications for future lifestyle research are discussed.

Health Behavior↗

Universal health insurance and high-risk groups in West Germany: implications for U.S. health policy.

Access to West Germany's broad-based health-insurance system is geared to the country's occupational structure. People who qualify, however, may seek coverage from alternative sources, including local "sickness funds." The changing nature of the German job market is leading to concentration of high-risk groups in the local funds, some of which could in turn face serious financial problems. Proponents of a universal health-insurance program for the United States need to take account of the growing segmentation of risk groups in the current German experience, which may ultimately threaten the concept of solidarity on which the system is founded.

Economic Competition↗