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Biomedical subjects

A Hecht

Publications and source records attributed to A Hecht.

At least 37 records · Page 2Linked to original sources
PubMed1996

Spreading of transcriptional repressor SIR3 from telomeric heterochromatin.

Telomeric genes and the HM loci in saccharomyces cerevisiae are transcriptionally repressed and adopt a heterochromatin-like structure. The trans-acting factors RAP1, SIR3 and SIR4 are required for telomeric and HM silencing, and are thought to be chromosomal, but how they contribute to histone-dependent repression of adjacent chromatin is unclear. SIR3 suppresses silencing defects in histones, is limiting for silencing adjacent to telomeres, and interacts with the H3 and H4 amino termini in vitro. Here we show that SIR3 co-immunoprecipitates SIR4, RAP1 and histones from cellular extracts, suggesting the presence of large chromatin-associated protein complexes. Crosslinking experiments show that SIR3 is present at HMRa, HMLalpha and telomeres in vivo, and that is spreads from telomeric regions into adjacent chromatin when overexpressed. Thus SIR3 is a structural component of yeast heterochromatin, repressing adjacent genes as it spreads along the chromosome.

Chromosomes, Fungal↗
PubMed1995

Usefulness of increased myocardial cyclic adenosine 3',5'-monophosphate content as a sign of rejection after cardiac transplantation.

Cardiac allograft rejection represents a series of cellular and molecular events triggered by the recognition of the graft by the host immune system. One of the second messenger systems involved in mitogenic mechanisms is the cyclic adenosine 3',5'-monophosphate (cAMP)-coupled signaling system. The aim of this preliminary study was to evaluate whether rejection after cardiac transplantation is accompanied by changes in the expression of cAMP. Myocardial cAMP content was determined by radioimmunoassay in endomyocardial biopsy specimens taken during routine follow-up after cardiac transplantation with or without cellular and/or vascular (i.e., coronary vasculopathy) rejection, respectively. Analysis of the different subgroups of patients showed that patients without any signs of rejection (no vasculopathy, no cellular rejection) had the lowest myocardial cAMP content (1.41 +/- 0.12 pmol/mg wet weight). Patients with either cellular or vascular rejection had significantly higher myocardial cAMP levels (2.25 +/- 0.29 and 2.24 +/- 0.59 pmol/mg wet weight, respectively, p < 0.05). Patients with both cellular rejection and coronary vasculopathy had the highest cAMP levels (5.95 +/- 1.6 pmol/mg wet weight; p < 0.001). We speculate that cAMP may play a functional role in mediating rejection induced by mitogenic factors activated after cardiac transplantation, suggesting a possible "cross-talk" between different cellular signaling pathways.

Adult↗
PubMed1995

Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast.

The silent mating loci and chromosomal regions adjacent to telomeres of S. cerevisiae have features similar to heterochromatin of more complex eukaryotes. Transcriptional repression at these sites depends on the silent information regulators SIR3 and SIR4 as well as histones H3 and H4. We show here that the SIR3 and SIR4 proteins interact with specific silencing domains of the H3 and H4 N-termini in vitro. Certain mutations in these factors, which affect their silencing functions in vivo, also disrupt their interactions in vitro. Immunofluorescence studies with antibodies against RAP1 and SIR3 demonstrate that the H3 and H4 N-termini are required for the association of SIR3 with telomeric chromatin and the perinuclear positioning of yeast telomeres. Based on these interactions, we propose a model for heterochromatin-mediated transcriptional silencing in yeast, which may serve as a paradigm for other eukaryotic organisms as well.

Amino Acid Sequence↗
PubMed1995

Diagnosis and treatment of pneumonia in the nursing home.

Risk factors, diagnosis, ethical considerations, and treatment of pneumonia in a nursing home setting are summarized. Risk factors for pneumonia include age-associated changes, co-morbid conditions, declining general health, and iatrogenic factors. Diagnosis can be challenging in geriatric residents because of atypical presentations and complex underlying diseases. Key features of presentation include rhonchi and confusion. An increased respiratory rate can be a sensitive indicator for pneumonia. Ethical dilemmas include identifying a resident's wishes for treatment in the event of an acute illness and the decision on whether to relocate the resident to an acute care facility. Decisions are based on available resources, medical stability of the resident, unimpeded access to a hospital, and the resident's well-informed decision. The common etiologic pathogen(s) of nursing-home-acquired pneumonia reflect a mixture between community-acquired and hospital-acquired pathogens. Multiple pharmacologic interventions are available, as well as supportive measures including oxygen therapy and hydration. Preventive measures are utilized to decrease the incidence of further infection.

Aged↗
PubMed1995

The regulation of euchromatin and heterochromatin by histones in yeast.

Yeast chromosomes may lack the linker histone H1 (normally required to compact 10 nm beads-on-a-string fiber into the 30 nm fiber) and there is no cytological evidence for higher order fiber structure but they do contain regions which correspond to euchromatin and heterochromatin of higher eukaryotes. Both euchromatin and heterochromatin contain nucleosomal particles (composed of two molecules each of H2A, H2B, H3 and H4), however histones have been shown to regulate genes in these regions in quite different ways. The mechanisms by which such regulation occurs are the topic of this paper.

Amino Acid Sequence↗
PubMed1993

[Chance occurrence in illness].

The chance as an objective existing category is responsible for the fact that the processes in the nature and in the society seem to be chaotic although they are running of determinated. The chance is of special significance for the behaviour of complex organized living systems. It is an essential factor for the evolution and the development of the variety of the species. Disease represents a being of the life and in this context the chance is of great importance, too. This is concerning life and death, the process of the pathogenesis of the disease and its cause as well the individuality in relation to the group, the population and the species. In all these processes the chance is of different significance, so one can speak from the dialectic of the chance. The chance also determines the borderline of our scientific cognition.

Biological Evolution↗
PubMed1993

[Discourse on the onto-epistemologic aspects of medical diagnosis].

Medical diagnosis represents an essential condition of a successful therapy. It is the result of a complicated subject-object-relation. Depending on the recognition of pathological phenomenons it requires an epistemological view too, e.g. on the ontoepistemology founded by Sandkühler. Significant categories in making a diagnosis are the pattern, the "Gestalt" and the whole. They represent the result of an association process which assigns a signification to the pattern. Whereas a young doctor perceives or describes the pattern only it is digested cognitively by the older well versed doctor.

Clinical Competence↗
PubMed1992

Changes in cardiac beta 1- and beta 2-adrenoceptor densities after human cardiac transplantation: relation to transplant coronary vasculopathy and pretransplantation disease.

In 100 patients 12 to 60 months after cardiac transplantation, the influence of transplant coronary vasculopathy and of the pretransplantation disease (end-stage heart failure caused by coronary artery disease or dilated cardiomyopathy) on the beta-adrenergic receptor (AR) numbers and beta 1/beta 2-AR ratio of right ventricular biopsies was determined. Patients with coronary vasculopathy (CVP) after cardiac transplantation had lower absolute numbers of beta 1-AR compared with patients without CVP. Since patients with CVP had increased left ventricular (LV) end-diastolic pressure and LV muscle mass, it is suggested that decreased beta 1-AR may be the result of an altered hemodynamic situation of the transplanted heart after development of CVP. Patients with dilated cardiomyopathy (DCM) before cardiac transplantation showed a decrease in total beta-AR and of the beta 1/beta 2-AR ratio as a result of an increase in beta 2-AR and a decrease in beta 1-AR numbers. The decreased beta 1/beta 2-AR ratio in patients with previous DCM may indicate that the beta-AR system of the transplanted heart might be influenced (at least in part) by pathophysiologic factors that are characteristic of the pretransplantation disease ultimately leading to cardiac transplantation and persisting after cardiac transplantation.

Adult↗
PubMed1992

Decrease in beta 1- and increase in beta 2-adrenoceptors in long-term follow-up after orthotopic cardiac transplantation.

Total beta 1- and beta 2- subtype distribution were examined in right ventricular biopsies taken from 100 patients 1-60 months after orthotopic cardiac transplantation and from eight prospective transplant donor hearts serving as controls. The patients were classified into eight groups depending on the time after transplantation that the biopsies were taken: 1-3 (n = 15), 4-7 (n = 15), 8-11 (n = 6), 12 (n = 15), 24 (n = 15), 36 (n = 12), 48 (n = 12) and 60 months (n = 10). The non-selective beta-adrenoceptor antagonist (-)-[125I]-iodocyanopindolol (ICYP) was used as a radioligand to assess total beta-adrenoceptor density. The beta 1- and beta 2-subtype distribution was determined with a beta 1-adrenoceptor saturating concentration of the selective beta 1-adrenoceptor antagonist CGP 20712A (300 nmol/l). In transplant donor hearts the total beta-adrenoceptor density was found to be 70.8 +/- 7.1 fmol/mg protein including a beta 1:beta 2-adrenoceptor ratio of about 80:20%. Until 36 months after cardiac transplantation the total number of beta-adrenoceptors showed no significant change. A slight but insignificant decrease was observed after 48 (16.2%) and 60 (21.2%) months. In contrast, from 12 to 60 months after cardiac transplantation the beta 1:beta 2-adrenoceptor ratio was shifted significantly (66:33% to 61:39%) as compared with transplant donor hearts which was due to an increase in beta 2- and a decrease in beta 1-adrenoceptor number. Thus, the surgically denervated, transplanted human heart exhibits a beta 2-adrenoceptor up-regulation during long-term follow-up. It is suggested that this up-regulation of the beta 2-adrenoceptor subtype could be owing to an increased importance of circulating catecholamines in modulating positive chronotropic and inotropic effects.

Adult↗
PubMed1992

The -6.1-kilobase chicken lysozyme enhancer is a multifactorial complex containing several cell-type-specific elements.

In the chromatin domain of the chicken lysozyme gene of myeloid and oviduct cells, which both have the potential to activate the gene, a developmentally stable DNase I-hypersensitive site is formed around 6.1 kb upstream of the gene. This implies that this DNA region, which has previously been demonstrated to function as a transcriptional enhancer element in myeloid cells, is intimately involved in the cell-type-specific activation of the lysozyme gene locus. Deletion analysis identifies a 157-bp minimal fragment that confers the same promacrophage-specific enhancer activity as the originally described 562-bp -6.1-kb enhancer fragment. By introducing specific point mutations, we demonstrate in transient gene transfer experiments that the minimal fragment consists of at least six adjacent elements, each substantially contributing to enhancer function. The compact multifactorial enhancer complex includes a nuclear factor I (NF-I)/TGGCA binding site, homologies to AP1, and octanucleotide or enhancer core consensus motifs. Point mutation of the NF-I binding site results in the loss of NF-I binding in vitro and enhancer activity in vivo after gene transfer. Surprisingly, four overlapping oligonucleotides, each consisting of at least two elements of the -6.1-kb enhancer, confer myeloid-cell-specific enhancer activity. We found several myeloid-cell-specific DNA-binding proteins interacting with the -6.1-kb enhancer, a result consistent with that described above. Therefore, we suggest that more than a single trans-acting factor mediates the cell type specificity of the -6.1-kb enhancer.

Animals↗
PubMed1992

[Causality and disease].

The interpretation of the causal relations in the beginning of a disease offers a central problem in medicine. It obtains a special interest with the increasing significance of the chronic diseases. The handling of this problem cannot depend on the experience of the every day life. It must take in consideration the general aspects of the causality as they are the topic of modern physics and biology as well as of philosophy. In the principle acknowledgement of the principle of causality a change from a deterministic monocausal to a more complex thinking takes place considering a complex of conditions followed by a field of possibilities of effects. Special interest needs the differentiation between the description and the interpretation of causal relations that means between ontological and epistemological thinking. The causal relation in medicine depends on the same principles as in physics and in biology.

Chronic Disease↗