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M Molnar

Publications and source records attributed to M Molnar.

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

A large-scale deletion of mitochondrial DNA in a case with pure mitochondrial myopathy and neuropathy.

Here we report the findings from a male patient with myopathy and neuropathy, who has a large-scale deletion of the mitochondrial genome at nucleotides 6570-14150. In the patient's history, muscle cramps with intermittent weakness and polyneuropathy with disturbed micturition were the predominant symptoms. Morphological examination of a muscle biopsy sample revealed numerous ragged red fibers and prominent paracrystalline intramitochondrial inclusions. The sural nerve biopsy sample disclosed a chronically progressive neuropathy, predominantly axonal in type with a minor demyelinating component. In previous studies the clinical symptoms mentioned above have been related to point mutations at various positions in the mitochondrial DNA (mtDNA). The present study is the first to describe a large (8 kb) deletion of the mtDNA which had apparently caused myopathy and polyneuropathy without encephalopathy.

DNA↗
PubMed1995

Posthatching development of preproenkephalin mRNA-expressing cell populations in the pigeon telencephalon.

Enkephalin peptides are highly expressed in the vertebrate telencephalon. Our previous investigations in the pigeon and in the chicken [26] suggested that the cellular distribution of these peptides is conserved in phylogenetically 'old' telencephalic regions (e.g. the basal ganglia), while it has species-specific organizations in areas (e.g. dorsomedial forebrain and bulbus olfactorius) that are likely to play important roles in species-specific behaviors. In the present study, we investigated the posthatching development of preproenkephalin (PPE) mRNA-containing cells in the pigeon forebrain using in situ hybridization histochemistry. These cells are densely distributed in the paleostriatal complex (corresponding to the mammalian caudate-putamen) at hatching, and their density progressively decreases during the first 9 days posthatching, when it is similar to that of adult pigeons. In the dorsomedial forebrain (corresponding to the mammalian hippocampus), PPE mRNA-expressing cells are present at hatching, and their density reaches a peak around the 6th day posthatching. In the bulbus olfactorius, the first PPE mRNA-containing cells are observed after 9 days posthatching. The developmental profile of PPE mRNA expression in these areas of the pigeon telencephalon shows remarkable similarities with the development of enkephalinergic cells in corresponding brain areas of mammals. As in the mammalian caudate-putamen, the developmental expression of enkephalin peptides in the paleostriatal complex is likely to be related to neuronal withdrawal from the mitotic cycle. The developmental pattern of expression of PPE mRNA in the dorsomedial forebrain suggests that enkephalin peptides contribute to the maturation of the behavioral functions of this area.

Animals↗
PubMed1995

Two novel genes involved in the sexual development of Schizosaccharomyces pombe.

We isolated two sterile mutants of Schizosaccharomyces pombe. One of them was mapped close to ste13 (8 cM). Since it turned out to be allelic with the hitherto unmapped ral2, its linkage with ste13 localizes ral2 on the right arm of chromosome II. The other mutant defines a novel class-I ste gene, ste15, closely linked to ste7 (4 cM) on chromosome I. ste15 is conjugation-specific and acts upstream of pat1 and ras1. During its genetic analysis, a phenotypic suppression of ste12-N9 was observed which was caused by mutations in the unlinked gene ssw1.

Epistasis, Genetic↗
PubMed1995

The rec8 gene of Schizosaccharomyces pombe is involved in linear element formation, chromosome pairing and sister-chromatid cohesion during meiosis.

The fission yeast Schizosaccharomyces pombe does not form tripartite synaptonemal complexes during meiotic prophase, but axial core-like structures (linear elements). To probe the relationship between meiotic recombination and the structure, pairing, and segregation of meiotic chromosomes, we genetically and cytologically characterized the rec8-110 mutant, which is partially deficient in meiotic recombination. The pattern of spore viability indicates that chromosome segregation is affected in the mutant. A detailed segregational analysis in the rec8-110 mutant revealed more spores disomic for chromosome III than in a wild-type strain. Aberrant segregations are caused by precocious segregation of sister chromatids at meiosis I, rather than by nondisjunction as a consequence of lack of crossovers. In situ hybridization further showed that the sister chromatids are separated prematurely during meiotic prophase. Moreover, the mutant forms aberrant linear elements and shows a shortened meiotic prophase. Meiotic chromosome pairing in interstitial and centromeric regions is strongly impaired in rec8-110, whereas the chromosome ends are less deficient in pairing. We propose that the rec8 gene encodes a protein required for linear element formation and that the different phenotypes of rec8-110 reflect direct and indirect consequences of the absence of regular linear elements.

Chromatids↗
PubMed1995

Increase of mitochondria in vasa nervorum of cases with mitochondrial myopathy, Kearns-Sayre syndrome, progressive external ophthalmoplegia and MELAS.

Previous studies on patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) revealed accumulations of mitochondria in endothelial cells, smooth muscle cells of pial arterioles, and small intracerebral arteries up to 250 microns in diameter; in pericytes of capillaries, endothelial cells, and smooth muscle cells of small blood vessels in skeletal muscle; and according to preliminary results also in endothelial and smooth muscle cells of capillaries and arterioles in sural nerves. These mitochondria do not show the prominent paracrystalline inclusions which are seen in striated muscle fibres and led to the identification of this group of disorders. To corroborate our preliminary findings in peripheral nerves, additional cases have been evaluated morphometrically by electron microscopy including cases in which mitochondrial DNA (mtDNA) mutations have been identified. In fact, an increase of the mean number and an enlargement of the mean cross-sectional area of mitochondria was noted in endothelial and smooth muscle cells of endoneurial and epineurial arterioles, and in endothelial cells and in pericytes of capillaries in sural nerves of the 20 cases with mitochondrial disorders studied. This increase was statistically significant compared to the control group. However, due to heteroplasmia, which is a common feature in mitochondrial disorders, and because of the limited number of measurable blood vessels and cases, no significant differences could be detected between the various types of mitochondrial diseases which were characterized by different point mutations or deletions of mtDNA. Our findings suggest that the mitochondria play a significant role in the pathogenesis not only of myopathic and encephalopathic symptoms, but also in the pathogenesis of peripheral neuropathy which appears to be regularly associated with mitochondrial disorders.

Adolescent↗
PubMed1994

Distribution of preproenkephalin mRNA in the chicken and pigeon telencephalon.

Bioassay and immunological studies have detected the presence of opioid peptides in the nervous system of representatives of all classes of vertebrates. The present study evaluates the expression and localization of preproenkephalin (PPE) mRNA to determine the sites of synthesis of the enkephalin peptides in the adult chicken and pigeon telencephalon using in situ hybridization histochemistry. We used a 500-base-pair chicken RNA probe corresponding to chicken PPE cDNA. In both the chicken and the pigeon telencephalon, the highest concentration of PPE mRNA-containing cells was observed in the lobus parolfactorius, paleostriatum augmentatum, nucleus accumbens, and septum. Distinct populations of labeled cells were also detected in the hyperstriatum accessorium, hippocampus, area parahippocampalis, nucleus of the diagonal band, cortex dorsolateralis, and cortex piriformis. Differences in PPE mRNA expression between chicken and pigeon were observed in several telencephalic regions. For instance, the bulbus olfactorius was heavily labeled in the pigeon, but was not labeled in the chicken, and numerous PPE mRNA-containing cells were present in the area parahippocampalis of pigeons but not of chickens. In contrast, in the hyperstriatum dorsale and hyperstriatum ventrale, numerous PPE mRNA-expressing cells were detected in the chicken but not in the pigeon. Overall, PPE mRNA-expressing cells were more numerous than enkephalin-immunoreactive cells described in previous studies. In addition, our results suggest that the general pattern of enkephalin expression in the avian telencephalon is similar to that found in other vertebrates. Finally, the results of the present study illustrate some differences in the pattern of PPE mRNA distribution between closely related species, indicating the existence of species-specific neurochemical pathways, which may influence and perhaps mediate different behaviors characteristics of these species.

Animals↗
PubMed1994

Cellular localization and laminar distribution of NMDAR1 mRNA in the rat cerebral cortex.

N-methyl-D-aspartate (NMDA) receptors, which play a critical role in many cortical functions, are composed of a heteromeric assembly of different subunits: of these, the NMDA receptor subunit 1 (NMDAR1) is a constant component of, and thus an excellent marker for, NMDA receptors. In this study, we have investigated the cellular localization and laminar distribution of NMDAR1 mRNA in the cerebral cortex of adult rats by in situ hybridization histochemistry with a 35S-labeled cRNA probe. Specificity and background levels were determined in adjacent sections incubated with a 35S-labeled sense RNA. In sections incubated with the antisense RNA probe, specific hybridization signal was observed in a large number of cells. Some cells, however, did not appear to contain NMDAR1 mRNA. The vast majority of these unlabeled cells were small, suggesting that they are astrocytes or other small nonneuronal cells. Double-labeling studies with in situ hybridization histochemistry and immunocytochemistry with antibodies to glial fibrillary acidic protein (GFAP) showed that about 95.7% of the GFAP-positive cells did not express NMDAR1 mRNA, indicating that virtually all astrocytes do not contain this transcript. A semiquantitative evaluation of cortical neurons, defined as those cells larger than the GFAP-positive astrocytes, revealed that about 80% were associated with silver grains. The number of silver grains associated with every neuron was determined from sections exposed for 15 days, the background level was subtracted, and all labeled neurons were grouped into five groups: A (< or = 10 grains), B (11-20 grains), C (21-30 grains), D (31-40 grains), and E (> 40 grains). The number of neurons belonging to each group was then evaluated according to their occurrence in each cortical layer. In layer I all labeled neurons were in group A, whereas in layers II-III and V-VI positive neurons were in group A-E. In layer IV most neurons were in groups A and B, whereas only a few were in group E. These observations indicate that 1) virtually all cortical cells containing NMDAR1 mRNA in adult rats are neurons; 2) about 80% of all cortical neurons express NMDAR1 mRNA; and 3) labeled neurons can be divided into several groups on the basis of NMDAR1 mRNA levels expressed, which presumably reflect the number of NMDA receptors. The existence of neurons with a different number of receptors may be a critical factor for determining the physiological effect of NMDA receptor activation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Vasoactive intestinal polypeptide/peptide histidine isoleucine messenger RNA in the rat retina: adult distribution and developmental expression.

In the adult nervous system, vasoactive intestinal polypeptide acts as a neurotransmitter or neuromodulator, and during development, it may also act as a neurotrophic factor. In the adult mammalian retina, this peptide is contained in a population of wide-field amacrine cells. Using in situ hybridization histochemistry, we examined the distribution and developmental expression of vasoactive intestinal polypeptide/peptide histidine isoleucine messenger RNA in the rat retina. Retinas collected from birth to adulthood were hybridized with an RNA probe as whole mounts, and then cut either perpendicular or parallel to the vitreal surface. Adult retinas were used in double labeling experiments for the visualization of both the hybridization signal and vasoactive intestinal polypeptide immunoreactivity in the same tissue section. In adult retinas, vasoactive intestinal polypeptide/peptide histidine isoleucine messenger RNA is localized to amacrine cells positioned in the proximal inner nuclear layer, and rarely to displaced amacrine cells in the inner plexiform layer and ganglion cell layer. The neurons expressing this messenger RNA are sparsely distributed, with a non-random distribution and densities of about 190 cells/mm2. An estimate of their total number gives about 12,350 cells/retina. The double labeling experiments showed that the hybridization signal is specifically confined to neurons displaying vasoactive intestinal polypeptide immunoreactivity. Vasoactive intestinal polypeptide/peptide histidine isoleucine messenger RNA is first detected at postnatal day 5 in cells located in the proximal part of the neuroblastic layer. A greater number of these neurons is present in the inner nuclear layer at postnatal day 10, and a few labeled neurons are also detected in the inner plexiform layer and in the ganglion cell layer. At this time, vasoactive intestinal polypeptide/peptide histidine isoleucine messenger RNA-containing amacrines in the inner nuclear layer are non-randomly distributed on the retinal surface, as in adult retinas. At postnatal day 15 (eye opening), there is a peak in both the density and the estimated number of labeled neurons, and their pattern of distribution in the retinal layers is similar to that in the adult. The present study shows that in the adult rat retina vasoactive intestinal polypeptide and peptide histidine isoleucine are synthesized in a sparsely distributed amacrine cell population, extending previous immunohistochemical findings. The appearance of vasoactive intestinal polypeptide peptide histidine isoleucine messenger RNA during the first postnatal week is consistent with the reported appearance of other transmitter-identified amacrine cell populations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

[Results of laryngo-microscopic examinations over a 10-year period at the ORL Department of the Senta Hospital].

In the period from 1980-1989, 199 laryngomicroscopical examinations were conducted at our department. There were 20 cases of laryngeal carcinoma, 55 cases of keratosis with the presence of dysplasia in 21.8%, as well as 19 papillomas in adult individuals. In our material keratoses appear a few years before the onset of laryngeal carcinoma in an average statistical distribution. With one exception, the carcinomas were detected before the appearance of metastases. Our data indicate the exceptional benefit of laryngomicroscopy in the detection of precancerous lesions and carcinoma of the larynx.

Adolescent↗
PubMed1987

Luteinizing hormone-induced intracellular calcium mobilization in granulosa cells: comparison with forskolin and 8-bromo-adenosine 3',5'-monophosphate.

Digitonin-permeabilized avian granulosa cells were used as a model to study the effects of LH, 8-bromo-cAMP (8-Br-cAMP), and forskolin on intracellular calcium mobilization. LH caused a biphasic calcium efflux. There was a small but significant (P less than 0.05) calcium release within 1-2 min (rapid phase) with an ED50 of 35 ng/ml, followed by a larger one after 5 min (slow phase) with an ED50 of 10 ng/ml. The intracellular calcium antagonist TMB-8 inhibited the action of LH in both phases. Forskolin had no effect on calcium efflux during the rapid phase. However, it stimulated intracellular calcium efflux in a dose-dependent manner in the slow phase with an ED50 of 30 microM. Low doses of 8-Br-cAMP caused a small but significant increase in calcium uptake corresponding to the rapid phase, although high concentrations of 8-Br-cAMP caused efflux in the slow phase (ED50, 0.7 mM). Both LH and 8-Br-cAMP mobilized calcium from a nonmitochondrial pool, whereas forskolin induced calcium efflux from a nonendoplasmic reticular site. Apparently receptor-mediated (LH) and nonreceptor-mediated (forskolin and 8-Br-cAMP) intracellular calcium mobilization are qualitatively different, suggesting that rapid intracellular calcium mobilization may represent one of the initial steps in the mechanism of action of LH.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Radioactive iodine exchange reaction of HIPDM: kinetics and mechanism.

In conjunction with single photon emission computed tomography (SPECT), iodine-123 (123I)-labeled N,N,N'-trimethyl-[2-hydroxy-3-methyl-5-iodobenzyl]-1,3-propanediamine (HIPDM) has been used clinically as a regional cerebral perfusion imaging agent. The [123I]HIPDM can be prepared by a simple aqueous exchange reaction in a kit form. We synthesized unlabeled HIPDM by condensation of 2-hydroxy-3-methyl-5-iodobezaldehyde and N,N,N'-trimethyl-1,3-propanediamine, followed by a sodium borohydride reduction reaction. The kinetics of the radioactive iodine exchange reaction for the preparation of [123I]HIDM is controlled by the pH, the temperature, and the presence of reductant (sodium bisulfite), and oxidant (sodium iodate). The reaction is a second order iodine-iodine exchange with an activation energy of 30.6 kcal/mole. The mechanism of this reaction probably involves the formation of an active 1+ or iodine free radical, which is sensitive to the presence of a reductant, such as sodium bisulfite.

Drug Interactions↗
PubMed1985

Synthesis of new bis(aminoethanethiol) (BAT) derivatives: possible ligands for 99mTc brain imaging agents.

In developing new brain perfusion imaging agents for single photon emission computed tomography (SPECT), five 99mTc-labeled neutral bis(aminoethanethiol) (BAT) derivatives capable of crossing the blood-brain barrier are reported. The five ligands are prepared by two versatile synthetic methods that can specifically introduce substituents on one of the carbons between two nitrogens. These ligands formed stable and neutral complexes with the reduced 99mTc, using either Sn(II) or sodium borohydride to reduce sodium [99mTc]pertechnetate. The biodistribution in rats was evaluated with [125I]iodoantipyrine, a freely diffusible tracer, as the internal reference. Compounds with a free hydroxyl group, 6 and 15, showed lower brain uptake. High initial brain uptake was observed for compounds 10 and 14, 1.28 and 2.30% dose/organ, respectively. Compounds of this type may be used as a basis for future structural modification to improve brain uptake and retention.

Animals↗
PubMed1984

Synthesis and biodistribution of neutral lipid-soluble Tc-99m complexes that cross the blood-brain barrier.

Three Tc-99m-labeled neutral 1,2-dithia-5,8-diazacyclodecane (BAT) chelates that are capable of crossing the blood-brain barrier (BBB) were prepared and evaluated. Biodistribution (i.v.) in rats showed a significant brain uptake (1-3%/whole brain) at 2 min. At 15 min the uptake dropped to about a tenth of the original level, indicating free passage in both directions across the BBB. Gamma camera images of a monkey confirmed the high initial brain uptake. This group of Tc-99m BAT compounds clearly exhibited in vivo stability and the ability to cross the BBB after an i.v. injection. Derivatives containing tertiary amine groups should have prolonged brain retention and might be suitable for SPECT studies of brain perfusion.

Animals↗
PubMed1977

Questionable usefulness of gamma-glutamyl transpeptidase test in legal medicine.

Because of the high level of GGT activity in semen, the suggestion was made that this enzyme could serve as a test in forensic medical practice; especially in rape cases. Comparisons of GGT and ACP tests revealed, however, that GGT is not sensitive enough and did not show acceptable specificity. One can conclude that GGT cannot be recommended either as a confirmatory test or as a substitute for ACP determinations in rape cases.

Acid Phosphatase↗