Biomedical subjects
Publications and source records attributed to T Török.
The expansion instability of a toroidal current ring in low-beta magnetized plasma is investigated. Qualitative agreement is obtained with experiments on spheromak expansion and with essential properties of solar coronal mass ejections, unifying the two apparently disparate classes of fast and slow coronal mass ejections.
The proliferation disrupter (prod) gene of Drosophila melanogaster encodes a novel protein associated with centromeric chromosomal regions that is required for chromatin condensation and cell viability. We have examined the binding of the Prod protein to DNA in vitro. Co-immunoprecipitation experiments demonstrate that Prod is a DNA-binding protein that specifically recognizes the 10 bp AGAATAACAT satellite repeat of D.melanogaster. Footprinting experiments show that the protein interacts with a 5-8 bp target sequence in each 10 bp repeat and suggest that it can mediate condensation of this satellite into a superhelix. Gel retardation experiments indicate that Prod does not have a well defined DNA-binding domain and it binds the satellite in a co-operative manner, probably forming Prod multimers. Since Prod localizes to both heterochromatin and euchromatin in vivo, we discuss the possibility that the ability of pre-existing euchromatic proteins to bind DNA in a co-operative manner, might be a prerequisite of satellite compaction and satellite amplification, thereby providing a basic factor in heterochromatin evolution.
OBJECTIVE: Signs of a parasympathetic dysfunction have been revealed in primary Sjögren's syndrome (SS). Its role in the pathogenesis and the clinical picture of the disease is not clear. To investigate the responsiveness of SS patients to a cholinergic agonist, a model was used involving examination of the cutaneous microcirculation. The microvascular response to the administration of carbachol was measured, a muscarinic cholinergic agonist. METHODS: Twenty two SS patients and 12 controls were examined. Carbachol and 0.9% saline solution were administered intracutaneously into the forearm skin at two distinct places. Skin blood flow (SBF) in the injected areas was measured continuously before and for 10 minutes after the injections by means of a laser Doppler perfusion monitor. The increase in SBF in response to carbachol (dSBF), reflecting vasodilatation, was calculated by a formula including the baseline and the maximum SBF values after the injections of carbachol and saline solution. RESULTS: The vasodilatation was significantly lower in SS patients than in the controls (mean dSBF: 2.1 (range: 1.0-4.5) versus 3.3 (range: 1.7-7.6), p=0.02). With non-responder patients defined as those in whom a smaller response was observed than in any of the controls, 11 of the 22 SS patients proved to be non-responders to carbachol. Comparisons of demographic, clinical and laboratory characteristics and HLA class II genotypes between responder and non-responder SS patients did not show any significant differences. CONCLUSIONS: A diminished or absent response to carbachol indicates a cholinergic dysfunction in SS patients. A disturbance in the neurotransmission at a receptorial or postreceptorial level is hypothesised. Unresponsiveness to cholinergic stimuli may contribute to exocrine insufficiency.
Low frequency (2 Hz) of electrical depolarisation induced [3H]noradrenaline ([3H]NA) release has been measured from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3x10(-5)M and corticosterone, 5x10(-5)M), with parallel measurements of post-junctional contractile responses. The K+ATP-channel opener pinacidil (10(-6)-10(-4)M), slightly potentiated the nerve-evoked release of [3H]NA which failed to show close concentration-dependency. Large concentration of pinacidil (10(-4)M) increased the ratio of [3H]NA release from 0.99 +/- 0.02 to 1.28 +/- 0.05 (P < 0.0005). On the other hand, pinacidil inhibited the nerve-evoked contractions in a concentration-dependent manner. 10(-4)M caused nearly 70% inhibition of contractile response. The pre- and post-junctional effects of pinacidil were studied under the following experimental conditions: 1) exogenously applied 1-NA; 2) excess K+; 3) 'L-type' Ca(2+)-channel activation (BAY K 8644); K(+)-channel inhibition (4-AP); and 5) Na(+)-pump inhibition/reactivation. Pinacidil (10(-4)M) retained its marginal NA-release stimulatory effect in all cases. However, pinacidil inhibited the contraction of smooth muscle, although to a different extent, in all of the experimental conditions used in our study.
Numerous recent observations have indicated autonomic reinnervation of transplanted human hearts. In order to assess autonomic regulation 5 patients were studied 1 to 5 years following cardiac transplantation. A series of tests were performed, including blood pressure and ECG recordings on rest, during 15/min patterned breathing, isometric handgrip exercise, and Valsalva manoeuvre. The time domain indices (SDRR, pNN50, rMSSD) and the frequency domain indices of heart rate variability were also studied. Among the five patients under study only one exhibited features compatible with both sympathetic and parasympathetic reinnervation. Traditional autonomic reflex tests and the analysis of time and frequency domain indices of HRV serve as simple tool in primary assessment of cardiac reinnervation.
Carotis sinus syncope is one of the leading indications for pacemaker implantation in Hungary. Although the role of the vasodepressor component is emphasized in our current guidelines, documentation of the vasodepression in technically difficult and therefore often abandoned. A case of a patient is presented who received a VVI pacemaker in spite of documented mixed carotid sinus syncope. Subsequent to the pacemaker implantation, patient's condition deteriorated, characterized by frequent syncopal episods. Replacing the VVI pacemaker by a DDD device resulted in prompt relief of symptoms. The importance of invasive or noninvasive hemodynamic monitoring in the diagnostic workup of these patients is emphasized.
Pacemaker syndrome is caused primarily by the lack of atrial kick and by neurocardiogenic reflex mechanisms due to simultaneous atrial and ventricular contractions. The most common clinical symptoms are dyspnoe, hypotension, dizziness and syncopal attacks. A case report of a patient with pacemaker syndrome is presented, in which the main clinical manifestation was a recurrent chest pain. A VVI demand pacemaker was implanted because of sick sinus syndrome ten years ago and shortly afterwards anginal attacks of rest developed. Coronary angiography revealed a non-significant (25%) narrowing of the right coronary artery (RCA). Casual and long-term ambulatory blood pressure (ABPM) measurements elucidated that the patient occasionally has extremely low diastolic blood pressure. This later phenomenon was confirmed and refined by a "beat-to-beat" blood pressure measuring technique. The elimination of the pronounced "beat-to-beat" variability of arterial blood pressure and transient coronary hypoperfusion due to implantation of an AV sequential bifocal pacemaker resulted in a full disappearance of angina pectoris.
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Homozygosity for a null mutation in the proliferation disrupter (prod) gene of Drosophila causes decreased mitotic index, defects of anaphase chromatid separation, and imperfect chromosome condensation in larval neuroblasts and other proliferating cell populations. The defective condensation is especially obvious near the centromeres. Mutant larvae show slow growth and massive cell death in proliferating cell populations, followed by late larval lethality. Loss of prod function in mitotic clones leads to the arrest of oogenesis in the ovary and defective cuticle formation in imaginal disc derivatives. The prod gene encodes a novel 301-amino-acid protein that is ubiquitously expressed and highly concentrated at the centric heterochromatin of the second and third mitotic chromosomes, as well as at > 400 euchromatic loci on polytene chromosomes. We propose that Prod is a nonhistone protein essential for chromosome condensation and that the chromosomal and developmental defects are caused by incomplete centromere condensation in prod mutants.
A case of syncope is reported, where hemodynamic responses compatible with pacemaker syndrome occurred during defecation. A 73 year old female received a VVI pacemaker for complete heart block. Subsequently she sustained repeated episodes of defecation syncope. Hemodynamic investigations revealed an abnormal blood pressure drop occurring at the overshoot phase of the Valsalva maneuver in association with alternation of sinus and pacemaker rhythm. This modified Valsalva response in the presence of contributing factors, such as hypovolemia and nitroglycerin therapy manifested as defecation syncope. The abnormal condition was treated by eliminating the contributing factors, and by programming a low pacemaker frequency, thus precluding sinus-pacemaker alterations.
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Mutations in a gene (Klp38B) encoding a novel kinesin-like protein in Drosophila melanogaster lead to the formation of polyploid cells in the larval central nervous system and in the follicle cells of adult egg chambers. Some homozygous mutants survive to adulthood and also exhibit morphological defects indicative of abnormal cell cycle progression, including rough eyes, missing bristles, and abnormal abdominal cuticles. In larval brains, there is no accumulation of mitotic cells and the frequency of anaphase figures is comparable to wild type, suggesting that nuclear division is not affected. Such brains contain polyploid cells with metaphase and anaphase chromosomes associated with bipolar spindles. Such spindles have a number of unseparated centrosomes at their poles reflecting the degree of polyploidy of the cell. Follicle cells frequently contain two nuclei of roughly equal size. Taken together, we conclude that these Klp38B mutations lead to a failure of cytokinesis resulting in polyploidy, and discuss whether or not this is a direct effect of the mutation.
The micturition syncope is a special manifestation of the so called "situational syncopes". These reflex syncopes share efferent mechanisms with the neurocardiogenic, or vasovagal syncope. A case of a patient is reported, who presented with micturition syncope. The patient's tendency for vasovagal syncope was documented by a positive tilt table test. The uniform premonitory symptoms preceding the two fainting attacks indicated the relation between the episodes. The authors review the literature of the micturition syncope, and discuss the potential pathomechanisms.
Adhesion molecules of the cadherin superfamily have an important role during vertebrate development. The DE-cadherin homolog DE-cadherin is the first classic cadherin isolated from invertebrates. We report here that DE-cadherin is encoded by the shotgun (shg) gene. shg is expressed in most embryonic epithelia and decreases in cells that undergo epithelial-mesenchymal transitions like the mesoderm or neural precursors. Removal of both maternal and zygotic shg function leads to severe defects in all epithelia expressing shg, suggesting that DE-cadherin, similar to vertebrate classic cadherins, has a crucial role for the formation and/or maintenance of epithelial tissues. Interestingly, the analysis of different shg alleles indicates that the requirement for shg in a given epithelium depends on the degree of its morphogenetic activity. Only epithelia involved in extensive morphogenetic movements require zygotic shg function in addition to maternal expression. In support of this view we find that suppression of morphogenetic movements rescues the zygotic shg phenotype. We find that in zygotic shg nulls the level of Dalpha-catenin and Armadillo at adherens junctions is dramatically reduced, surprisingly also in epithelia that differentiate normally and possess a zonula adherens.
This paper describes a fast and efficient approach to correlating cloned genes with mutant phenotypes in Drosophila. We make use of a large collection D. melanogaster lines with recessive lethal insertions of a P[lacW] transposon on their second chromosome. Within this collection there clearly must be many insertions corresponding to Drosophila genes that have been cloned and characterized, e.g., via homology with cloned mammalian genes, but for which mutant phenotypes have yet to be identified. We have made use of the fact that P[lacW] contains a plasmid replicon to establish a collection of rescued plasmids containing genomic DNA flanking the sites of transposon insertion. Plasmids representing a total of 1836 lines were independently rescued and pooled in batches of 10 and 100. Pools of 100 plasmids were screened by hybridization with cDNAs corresponding to cloned second chromosome loci. Hybridizing pools were then narrowed down to single plasmids by a process of subdivision and rehybridization, and corresponding mutant lines were obtained. The success rate was better than one in four. This rate would undoubtedly be improved by the use of genomic DNA probes.
The tumor suppressor gene overgrown hematopoietic organs-31 (oho31) of Drosophila encodes a protein with extensive homology to the Importin protein of Xenopus (50% identity), the related yeast SRP1 protein, and the mammalian hSRP1 and RCH1 proteins. A strong reduction in the expression of oho31 by a P element inserted in the 5' untranslated region of the oho31 transcript or a complete inactivation of oho31 by imprecise P element excision leads to malignant development of the hematopoietic organs and the genital disc, as shown by their growth autonomy in transplantation assays. We have cloned the oho31 gene of Drosophila melanogaster and determined its nucleotide sequence. The gene encodes a phosphoprotein of 522 amino acids made of three domains: a central hydrophobic domain of eight repeats of 42-44 amino acids each, displaying similarity to the arm motif found in junctional and nucleopore complex proteins, and flanked by two hydrophilic NH2- and COOH-terminal domains. Immunostaining revealed that the OHO31 protein is supplied maternally and rapidly degraded during the first 13 nuclear divisions. Thereafter, the OHO31 protein is predominantly expressed, albeit at reduced levels, in proliferating tissues. During the interphase of early embryonic cell cycles, the OHO31 protein is present in the cytoplasm and massively accumulates in the nucleus at the onset of mitosis in late interphase and prophase. The nuclear import of OHO31 is, however, less pronounced during later developmental stages. These results suggest that, similar to Importin, OHO31 may act as a cytosolic factor in nuclear transport. Moreover, the cell cycle-dependent accumulation of OHO31 in the nucleus indicates that this protein may be required for critical nuclear reactions occurring at the onset of mitosis.
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