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Biomedical subjects

A Tóth

Publications and source records attributed to A Tóth.

At least 55 records · Page 3Linked to original sources
PubMed2000

Recent advances in biohydrogen research.

A fundamental and principal difficulty of the future energy supply is that the formation of fossil fuels is much slower than the rate of their exploitation. Therefore the reserves which can be recovered in an energetically feasible manner are shrinking parallel with an increasing world-wide energy demand. Among the alternative energy carriers, hydrogen is preferred because it is easy to transport and store and it burns to environmentally friendly water vapour when utilized. Hydrogen can be produced in biological systems, however, our understanding of the molecular details is just emerging.

Biotechnology↗
PubMed1999

Genes involved in hydrogen and sulfur metabolism in phototrophic sulfur bacteria.

The dsr genes and the hydSL operon are present as separate entities in phototrophic sulfur oxidizers of the genera Allochromatium, Marichromatium, Thiocapsa and Thiocystis and are organized similarly as in Allochromatium vinosum and Thiocapsa roseopersicina, respectively. The dsrA gene, encoding the alpha subunit of 'reverse' siroheme sulfite reductase, is also present in two species of green sulfur bacteria pointing to an important and universal role of this enzyme and probably other proteins encoded in the dsr locus in the oxidation of stored sulfur by phototrophic bacteria. The hupSL genes are uniformly present in the members of the Chromatiaceae family tested. The two genes between hydS and hydL encode a membrane-bound b-type cytochrome and a soluble iron-sulfur protein, respectively, resembling subunits of heterodisulfide reductase from methanogenic archaea. These genes are similar but not identical to dsrM and dsrK, indicating that the derived proteins have distinct functions, the former in hydrogen metabolism and the latter in oxidative sulfur metabolism.

Bacteria↗
PubMed1999

APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5.

Ubiquitin-mediated proteolysis due to the anaphase-promoting complex/cyclosome (APC/C) is essential for separation of sister chromatids, requiring degradation of the anaphase inhibitor Pds1, and for exit from mitosis, requiring inactivation of cyclin B Cdk1 kinases. Exit from mitosis in yeast involves accumulation of the cyclin kinase inhibitor Sic1 as well as cyclin proteolysis mediated by APC/C bound by the activating subunit Cdh1/Hct1 (APC(Cdh1)). Both processes require the Cdc14 phosphatase, whose release from the nucleolus during anaphase causes dephosphorylation and thereby activation of Cdh1 and accumulation of another protein, Sic1 (refs 4-7). We do not know what determines the release of Cdc14 and enables it to promote Cdk1 inactivation, but it is known to be dependent on APC/C bound by Cdc20 (APC(Cdc20)) (ref. 4). Here we show that APC(Cdc20) allows activation of Cdc14 and promotes exit from mitosis by mediating proteolysis of Pds1 and the S phase cyclin Clb5 in the yeast Saccharomyces cerevisiae. Degradation of Pds1 is necessary for release of Cdc14 from the nucleolus, whereas degradation of Clb5 is crucial if Cdc14 is to overwhelm Cdk1 and activate its foes (Cdh1 and Sic1). Remarkably, cells lacking both Pds1 and Clb5 can proliferate in the complete absence of Cdc20.

Anaphase↗
PubMed1999

Finishing the cell cycle.

The eukaryotic cell division cycle consists of two characteristic states: G1, when replication origins of chromosomes are in a pre-replicative state, and S/G2/M, when they are in a post-replicative state (Nasmyth, 1995). Using straightforward biochemical kinetics, we show that these two states can be created by antagonistic interactions between cyclin-dependent kinases (Cdk) and their foes: the cyclin-degradation machinery (APC) and a stoichiometric inhibitor (CKI). Irreversible transitions between these two self-maintaining steady states drive progress through the cell cycle: at "Start" a cell leaves the G1 state and commences chromosome replication, and at "Finish" the cell separates the products of replication to the incipient daughter cells and re-enters G1. We propose that a protein-phosphatase, by up-regulating the APC and by stabilizing the CKI, plays an essential role at Finish. The phosphatase acts in parallel pathways; hence, cells can leave mitosis in the absence of cyclin degradation or in the absence of the CKI.

Animals↗
PubMed1999

Yeast cohesin complex requires a conserved protein, Eco1p(Ctf7), to establish cohesion between sister chromatids during DNA replication.

Sister chromatid cohesion is crucial for chromosome segregation during mitosis. Loss of cohesion very possibly triggers sister separation at the metaphase --> anaphase transition. This process depends on the destruction of anaphase inhibitory proteins like Pds1p (Cut2p), which is thought to liberate a sister-separating protein Esp1p (Cut1p). By looking for mutants that separate sister centromeres in the presence of Pds1p, this and a previous study have identified six proteins essential for establishing or maintaining sister chromatid cohesion. Four of these proteins, Scc1p, Scc3p, Smc1p, and Smc3p, are subunits of a 'Cohesin' complex that binds chromosomes from late G1 until the onset of anaphase. The fifth protein, Scc2p, is not a stoichiometric Cohesin subunit but it is required for Cohesin's association with chromosomes. The sixth protein, Eco1p(Ctf7p), is not a Cohesin subunit. It is necessary for the establishment of cohesion during DNA replication but not for its maintenance during G2 and M phases.

Amino Acid Sequence↗
PubMed1999

An in vivo model for studying the dynamics of intracellular free calcium changes in slow- and fast-twitch muscle fibres.

The understanding of the regulation of the free cytosolic [Ca2+] ([Ca2+]i) in skeletal muscle is hampered by the lack of techniques for quantifying free [Ca2+]i in muscle fibres in situ. We describe a model for studying the dynamics of free [Ca2+]i in the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus (SOL) muscles of the rat in vivo using caffeine superfusion to induce changes in free [Ca2+]i. We assumed that differences in sensitivity between the two muscle types for this substance reflect differences in intracellular Ca2+ handling in the fibres of which these muscles consist. The Indo-1 ratiometric method, using intravital microscopy with incident light, was adapted to measure free [Ca2+]i in vivo. Fluorescence images were collected by means of a digital camera. Caffeine superfusion at 37 degrees C for 2 min, at concentrations of 1, 2, 5, 10 or 20 mmol/l, induced a concentration-dependent increase in free [Ca2+]i and revealed differences in caffeine sensitivity between the muscle types, with the SOL being more sensitive. In a separate set of experiments the contracture threshold, as assessed by topical application of caffeine, was determined in both muscle types. EDL had a higher threshold for developing contracture than SOL. These finding are in agreement with previous in vitro studies. We may conclude that the dynamics of free [Ca2+]i can be assessed reliably in intact mammalian muscle in vivo.

Animals↗
PubMed1999

Electronystagmographic analysis of optokinetic nystagmus for the evaluation of ocular symptoms in myasthenia gravis.

Ocular symptoms of 17 myasthenia gravis (MG) patients were examined by electronystagmographic registration of optokinetic nystagmus. The aim of this study was to replace the subjective methods used previously with a more reliable quantitative technique and thus assess ophthalmoplegia and diplopia, important initial symptoms in MG. Slow phase angular speed values of foveolar type optokinetic nystagmus in the horizontal plane at 10, 20 and 30 degrees/s target speed were determined. Measurements were performed before and after administration of Mestinon, a reversible cholinesterase inhibitor. Twelve healthy volunteers were examined as controls under standard conditions. Results showed significant differences between MG patients and control group. Slow-phase angular speed was significantly larger after Mestinon administration (p < 0.001). It is concluded, that the exhaustion of external ocular muscles in MG can be well characterized by the determination of the slow phase angular speed values of optokinetic nystagmus (OKN). The examination of OKN was also recommended for the evaluation of ocular symptoms in other neurological disorders.

Adult↗
PubMed1998

Attenuation of diabetic retinopathy by the molecular chaperone-inducer amino acid analogue canavanine in streptozotocin-diabetic rats.

The effect of canavanine treatment on the electroretinograms of healthy and streptozotocin-diabetic rats was studied. The characteristic amplitudes of the a-wave, W2 and W3 oscillatory potentials were markedly diminished in the 2-week streptozotocin-diabetic rats compared with those of the control rats. In contrast, the amplitudes of all the responses of the canavanine-pretreated streptozotocin-diabetic rats were practically indistinguishable from those of the control animals. Our results prompt further investigations for the use of amino acid analogues and other inducers of molecular chaperones in easing the chronic consequences of diabetes such as retinopathy.

Animals↗
PubMed1998

High-dose phosphate treatment leads to hypokalemia in hypophosphatemic osteomalacia.

The mechanism of the decrease in plasma potassium induced by phosphate treatment was investigated in a 24-year-old hypertensive patient with hypophosphatemic osteomalacia, who was the youngest of four patients, belonging to a 23 number kindred of five generations. Parameters of potassium, sodium, calcium, and phosphate metabolism as well as specific renal functions have been studied in the basal state and during administration of graded doses of phosphate (500-6000 mg). Progressive hypokalemia developed during phosphate treatment. An inverse correlation was found between plasma potassium and doses of phosphate (plasma potassium = -0.2 g phosphate + 3.9 r = -0.49; p < 0.05; N = 21). A renal route of potassium loss was suspected, but could not be confirmed as potassium excretion did not increase although sodium excretion was augmented [basal sodium output: 56.7 mmol/24 h; phosphate treatment: 153 mmol/24 h (p < 0.05)]. Transtubular potassium gradient (TTKG) also decreased and an inverse correlation was found between TTKG and doses of phosphate (r = -0.37; p < 0.02; N = 38). Decrease of TTKG was possibly the result of suppressed K+ secretion. It was concluded that potassium loss occurred by a non-renal (intestinal) route in phosphate-induced hypokalemia. Although major hazards of treatment of hypophosphatemic osteomalacia with phosphate and calcitriol are secondary hyperparathyroidism and vitamin D intoxication, potassium loss also should be kept in mind.

Adult↗
PubMed1998

Capillary blood flow and tissue metabolism in skeletal muscle during sympathetic trunk stimulation.

NADH fluorescence at tissue sites 15-20 microns in diameter and red blood cell velocity in adjacent capillaries were measured in resting sartorius muscle of the anesthetized cat during a 3-min period of sympathetic trunk stimulation. At stimulation frequencies of 2 and 4 Hz, red blood cell velocity fell briefly to 30-40% of control and then returned to approximately 75% of control values (vascular escape). No change in NADH fluorescence was observed. With stimulus frequencies of 6-12 Hz, flow reduction was greater and led to an increase in fluorescence when the flow reduction was > 50% and was sustained for > 30 s. NADH changes were more pronounced at tissue sites near venous capillaries than at sites near arterial capillaries. Hyperemia ensued after the end of sympathetic stimulation only when NADH fluorescence rose during stimulation. Resting blood flow in this muscle appears to be well above the minimum required to support oxidative metabolism. A shift to anaerobic metabolism does not appear to cause vascular escape during sympathetic stimulation but appears to be required for poststimulation hyperemia. These observations suggest that two separate oxygen-dependent mechanisms elicit vasodilation during and after sympathetic trunk stimulation.

Animals↗
PubMed1998

Quantitative assessment of [Ca2+]i levels in rat skeletal muscle in vivo.

Intracellular free Ca2+ concentration ([Ca2+]i) plays an essential role in physiological regulatory processes and common pathological conditions. Better understanding of these phenomena is still hampered by problems encountered in the quantitative assessment of [Ca2+]i changes, especially in blood-perfused organs. This study demonstrates that the ratiometric fluorescence technique can be adapted for quantitative in vivo [Ca2+]i determinations. The rat spinotrapezius muscle was topically loaded with indo 1-AM and imaged by a cooled digital camera. Ratio images were calculated in small regions (100 micrometers x 100 micrometers) practically devoid of large vessels in the resting state, after 30 min of ischemia, 20 min of reperfusion, or ionomycin or manganate treatments. When we assumed an average [Ca2+]i of 100 nM in the resting blood-perfused muscle, ischemia increased [Ca2+]i to approximately 200 nM. During reperfusion [Ca2+]i decreased to approximately 140 nM. Ionomycin induced an increase in [Ca2+]i to well above 750 nM. Manganate reduced Ca2+-dependent fluorescence to virtually zero. Our main conclusion is that changes in [Ca2+]i can be monitored and quantitatively determined in vivo.

Animals↗
PubMed1997

[Role of aldosterone in potassium secretion in chronic renal failure associated with hypertension (transtubular potassium gradient)].

Aldosterone protects against hyperkalemia in disorders with reduced number of over-working nephrons. It is not clear however, whether diminished aldosterone production or aldosterone resistance is responsible for the hyperkalemia in chronic renal failure. The importance of this question is underlined by the fact that antihypertensive drugs often reduce aldosterone level. Therefore we investigated the distal tubular potassium "driving force" (transtubular potassium gradient) in 9 patients with chronic renal failure accompanied by hypertension and compared it to the results obtained in 10 healthy persons. Glomerular filtration rate was 15.77 +/- 4.88 ml/min in the chronic renal patients. Serum potassium was normal in 3 of 9 patients, the average 4.88 +/- 0.16 mmol/l, higher than in healthy persons 4.27 +/- 0.09 mmol/l (p < 0.001). Nevertheless the transtubular potassium gradient was lower in patients (3.52 +/- 0.32) comparing to healthy persons (7.25 +/- 0.57, p < 0.001). The patients' plasma aldosterone was much higher than normal. The reduced tubular potassium secretion-decreased "driving force" --suggested to aldosterone resistance. We conclude that the renal tubules' aldosterone resistance is not an exceptional but rather frequent feature in chronic renal failure which should be considered when administering antihypertensive drugs.

Aldosterone↗
PubMed1997

[Reproducibility of malignancy grading in prostatic cancers using the Gleason-Böckling system].

Histologic slides from 50 cases of prostatic adenocarcinoma were evaluated by 5 pathologists, in order to test the reproducibility of grading in two systems. Twenty-five needle core biopsies and 25 surgical (adenomectomy) specimens were graded in two sessions, according to the histomorphologic criteria of Gleason and Böcking. The results were analyzed by the kappa statistics. In surgical specimens, there were no significant differences in the interobserver reproducibility of microscopically assessed categories. In needle biopsies, however, Gleason's primary pattern (62%, kappa = 0.42), and Böcking's histological pattern (63%, kappa = 0.37) showed the highest level of agreement. Among the computed (derivated) classification terms, those consisting of only 3 groups (Gleason grouping, kappa = 0.39; Böcking grade, kappa = 0.39) proved to be better reproducible than the corresponding score values (p < 0.05). When compressing both systems into two grades (high and "non-high"), reproducibility was improved (kappa = 0.52). For a substantial improvement of grading results, more accurate grade definitions, continuing training and regular consultation of pathologists are necessary. Based on the results obtained by intraobserver analysis we conclude that kappa statistics is of limited value when analyzing the role of individual experience at grading reproducibility.

Adenocarcinoma↗
PubMed1997

Prenatal exclusion of segmental trisomy in familial chromosome 21 pericentric inversion by fluorescence in situ hybridization.

We report the prenatal exclusion of partial trisomy in a family with maternal pericentric inversion of chromosome 21 by fluorescence in situ hybridization (FISH). After determining the structural rearrangement in the mother and her affected son with 46,XY,rec(21)dup(21q)inv(21)(p11q22) resulting in Down syndrome (DS), a chorionic villus sample from the current pregnancy was analysed for the copy number of the DS critical region with a cosmid contig. The signal distribution was normal and the cytogenetic analysis revealed that the fetus had inherited the inverted chromosome 21 in a balanced form. FISH probes specific for the DS region are of great value in supporting cytogenetic results, regardless of the structural status of chromosome 21.

Adult↗
PubMed1997

Prognosis of untreated liver metastasis from rectal cancer.

UNLABELLED: Majority of studies based of treatment of liver metastases from colorectal cancer compare their results to historical controls that include patients having untreated secondary liver tumours. The aim of this study was to show the natural history of patients with liver metastasis from rectal cancer. Data of 303 patients underwent laparotomy between 1984 and 1992 were reviewed. 47 of 57 patients who had liver metastasis at the time of surgery fulfilled the criteria of the study. The mean survival time was 8.5 (1-27) months for all patients, 11 months for patients with solitary hepatic tumour (n = 13) and 7.5 months for those with multiple tumours (n = 34). Patients who had liver and other distant metastases simultaneously (n = 9) survived a shorter time than those with hepatic secondaries only (4 and 9 months respectively). The mean survival time for patients in whom the primary tumour was resected (n = 17) was 11 months contrary to 7 months for those who underwent colostomy or exploratory laparotomy, but comparison of survival curves didn't revealed significant difference between the two groups. CONCLUSIONS: The incidence of liver metastases from rectal cancer at the time of laparotomy was 19%. The prognosis was very poor in case of synchronous secondary tumours. Palliative resection of the primary tumour is recommended for selected patients only to control local symptoms.

Carcinoma↗
PubMed1997

Clinicopathologic aspects of 8 Kaposi's sarcomas among 1009 renal transplant patients.

In 8 of 1009 patients receiving renal grafts and consecutive immunosuppressive therapy during the last 20 years in Budapest, Hungary, Kaposi's sarcoma developed 6.5 months (average) after transplantation. Of 8 cutaneous cases of this disease, 5 also presented visceral manifestations. Seven patients died. Those with visceral tumors died because of the tumor itself. One patient affected by cutaneous tumor has survived for 5 years post-treatment. The relatively high incidence of Kaposi's sarcoma may be explained by a high infection rate with Herpes virus 8, which was shown to be positive in all three cases investigated.

Adult↗
PubMed1996

[Molecular biologic study and the factor VIII gene in hemophilia A].

Results of inversion in the intron 22 region of the VIII factor gene studied by Southern blot are presented. Inversion was found in 20 of 46 patients. In 14 cases (70%) distal and in 6 cases (30%) proximal type of inversion was detected. The significance of the positive result in genetic counseling and in presymptomatic diagnosis of Haemophilia A is emphasized.

Adult↗