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Biomedical subjects

A Hecht

Publications and source records attributed to A Hecht.

At least 19 recordsLinked to original sources
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↗
PubMed1992

[Classification of causes of death in humans].

The cause of death of 2631 deceased persons (2418 adults, 213 children) was determined. Classification is proposed by monocausative, relatively monocausative, competitive and complex causes of death. This classification would be in accordance with types of dying, as suggested by Thieke and Nizze [17]. A comparison of results has revealed far-reaching agreement between the two principles of classification with regard to frequency distribution of causes, except for the category of complex causes which, however, was of minor importance in our investigations. This was attributed to the fact that classification was facilitated by consideration of epistemological approaches. Differences among categories of causes were attributable also to age and sex of the cases studied, both adults and children.

Adolescent↗
PubMed1991

Dynamic chromatin: the regulatory domain organization of eukaryotic gene loci.

It is hypothesized that nuclear DNA is organized in topologically constrained loop domains defining basic units of higher order chromatin structure. Our studies are performed in order to investigate the functional relevance of this structural subdivision of eukaryotic chromatin for the control of gene expression. We used the chicken lysozyme gene locus as a model to examine the relation between chromatin structure and gene function. Several structural features of the lysozyme locus are known: the extension of the region of general DNAasel sensitivity of the active gene, the location of DNA-sequences with high affinity for the nuclear matrix in vitro, and the position of DNAasel hypersensitive chromatin sites (DHSs). The pattern of DHSs changes depending on the transcriptional status of the gene. Functional studies demonstrated that DHSs mark the position of cis-acting regulatory elements. Additionally, we discovered a novel cis-activity of the border regions of the DNAasel sensitive domain (A-elements). By eliminating the position effect on gene expression usually observed when genes are randomly integrated into the genome after transfection, A-elements possibly serve as punctuation marks for a regulatory chromatin domain. Experiments using transgenic mice confirmed that the complete structurally defined lysozyme gene domain behaves as an independent regulatory unit, expressing the gene in a tissue specific and position independent manner. These expression features were lost in transgenic mice carrying a construct, in which the A-elements as well as an upstream enhancer region were deleted, indicating the lack of a locus activation function on this construct. Experiments are designed in order to uncover possible hierarchical relationships between the different cis-acting regulatory elements for stepwise gene activation during cell differentiation. We are aiming at the definition of the basic structural and functional requirements for position independent and high level gene expression. The result of these experiments will have important consequences for random gene transfer with predictable and reproducible expression of transgenes.

Animals↗
PubMed1991

Unusual volar dislocation of the lunate into the distal forearm: case report.

A case of a severe wrist injury (fractures of the scaphoid, capitate, hamate, and ulnar styloid process) with volar dislocation of the lunate into the soft tissues of the forearm is presented. This degree of displacement of the lunate is exceedingly rare, and we believe has not been previously reported. Possible mechanisms, hyperextension injury forcing the lunate forward out of the carpus, or contact between the volar wrist skin surface and another object or surface propelling the dislocated lunate into the forearm, are discussed.

Adult↗
PubMed1991

[Synergetics--a possible hypothetical approach to better understanding of pathologic processes].

Modern understanding of the human disease cannot be reduced only on the disturbed biological processes of the living organism. Disease as the consequence of the disorders of a complex system needs in the same sense a complex view. It is necessary to take in consideration the theory of systems, the concept of layers and the idea of the deterministic chaos. A helpful clamp to coordinate these different views seems to be the synergetics, the teaching of the cooperation in complex systems. Synergetics investigate the mechanisms of the self-organization, too. The self-organization is of great significance in the phylogenetic and ontogenetic morphogenesis. Especially all diseases which are characterized by the disorders in the differentiation the processes forming "Gestalten" are to understand as processes of the disturbed self-organization. These refers the malformations, the malignant tumours and the chronic diseases. Self-organization being a system-internal mechanism is to understand as a process which determines the behaviour of complex organized living systems in confrontation with their environment.

Biological Evolution↗
PubMed1991

[The contribution of modern biology to a better understanding of disease].

The human disease in its biological foundation must be congruent with the normal processes of the life and explicable by these. The simplified view on disease in the past with the reduction on its biological and physico-chemical course seems to become more and more insufficient and limiting to a comprehensive understanding. The discussion of the concept of disease from the standpoint of the epistomology needs in consequence of the so called new thinking the integrated inclusion of the systems theory, the theory of chaos and the concept of layers by Riedl. Taking this in the consideration a comprehensive understanding of disease is given. This allows to take into account as well its evolutionary conditionality, its human being as its individual, group, population and species specific characteristics. This kind of view emphasizes the necessity to complete the pragmatic reductionism by a comprehensive sight. In the consequence of such a thinking it seems easier to recognize the with the increasing complexity of the living beings emergent laws.

Adaptation, Physiological↗