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Biomedical subjects

S Komoly

Publications and source records attributed to S Komoly.

At least 19 recordsLinked to original sources
PubMed1998

JC virus excreted by multiple sclerosis patients and paired controls from Hungary.

JC virus (JCV), a human polyomavirus, is the agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV exists in four main genotypes in the USA. Type 1, including subtypes Type 1A and Type 1B, makes up about 64% of strains in the USA and is thought to be of European origin. Type 2 is found in Asia, and Type 3 in Africa. A fourth type is found only in the USA. In general, these genotypes differ in 1-2.5% of their DNA sequence. Thirty MS patients and 30 paired controls from Budapest were studied. The clinical course of MS was mainly secondary progressive, and patients were stable at the time of testing. Most of the controls were relatives of the probands: a spouse, parent, or child. Overall, 25 of 60 (42%) of the urines tested positive for JCV by PCR. These included 13 of 30 MS patients, and 12 of 30 controls. Genotyping in the VPI gene showed all 25 JCV strains to be Type 1. Among the MS patients, seven were Type 1A and six were Type 1B. Among the controls, nine were Type 1A and three were Type 1B. In five pairs of MS patients and controls, both were positive for JCV by PCR. Two of these were husband/wife pairs of which one pair was matched for subtype (both Type 1A), and the other was not. Two of them were mother/daughter pairs, and both were matched for subtype (both Type 1B). These findings demonstrate that JCV Type 1 predominates among Hungarians, and suggest that parent/child pairs can be used to trace JCV transmission within the MS family.

Adult↗
PubMed1994

Concentric sclerosis (Baló): morphometric and in situ hybridization study of lesions in six patients.

Brain tissues from 6 patients with concentric sclerosis (Baló) were examined by in situ hybridization, immunocytochemistry, morphometry, and histological methods. The patients were 24 to 48 years old and had progressive cerebral symptoms and signs that lasted 15 to 100 days. Large demyelinative lesions, most frequent in the frontal white matter, contained alternating bands of demyelinated and partly myelinated white matter that were arranged in concentric or mosaic patterns. In the areas of demyelination, axons were relatively well preserved and there were perivascular inflammatory infiltrates. In 2 specimens, lesions contained regions with the characteristic appearance of actively demyelinating multiple sclerosis plaques. Oligodendroglial densities were highest in normal-appearing white matter, lower in partially myelinated areas, and lowest in demyelinated areas, which also contained many hypertrophic astrocytes closely associated with oligodendroglia. Messenger RNA levels for myelin-related proteins followed the same pattern; they were lowest in demyelinated areas, higher in partially myelinated areas, and highest in normal-appearing white matter beyond lesion margins. Our findings suggest that concentric sclerosis is a variant of multiple sclerosis, that oligodendroglial loss is important in the pathogenesis of demyelination, and that partially myelinated areas probably represent stages of ongoing myelin breakdown rather than remyelination of previously demyelinated areas.

Adult↗
PubMed1994

Selective up-regulation of neuropeptide synthesis by blocking the neuronal activity: galanin expression in septohippocampal neurons.

Neuronal activity regulates expression of phenotype-specific genes, including galanin, which coexists with choline acetyltransferase in septal and basal forebrain neurons. Transections of the fornix and the diagonal band alter galanin expression in septohippocampal neurons attributed to a deficit in target-derived trophic factors. The present study demonstrates that tetrodotoxin-induced blockade of neuronal activity fully mimicked the effect of axotomy (transection of the septohippocampal fibers) in the neurons of the nucleus of the diagonal band, and caused a dramatic, although temporary, up-regulation of galanin immunoreactivity and galanin mRNA without significant alteration in choline acetyltransferase expression. This finding suggests that in the septohippocampal cholinergic system perturbance of electrical activity alone can lead to temporary up-regulation of galanin expression, previously attributed exclusively to a "lesion effect."

Animals↗
PubMed1993

Many spinal cord cells transiently express low molecular weight forms of glutamic acid decarboxylase during embryonic development.

At early developmental stages in the rat spinal cord (embryonic day 13), when neuronal progenitors are still proliferating, most differentiating neurons express truncated forms of glutamic acid decarboxylase (GAD) (approximately 25 kDa) which are the products of alternative splicing of the GAD67 gene. These truncated proteins do not appear to synthesize gamma-aminobutyric acid (GABA). The amino acid is detected in cells only after alternative splicing of the GAD67 gene generates a full-length, 67 kDa enzymatically active form of GAD. Both the 67 kDa GAD and GABA colocalize and appear diffusely distributed in the cytoplasm of embryonic neurons. GABA does not appear associated with synaptic vesicles until after birth, when its intracellular distribution becomes punctate and it colocalizes with synaptophysin. At this time, it also colocalizes with an immunologically distinct 65 kDa GAD protein encoded by a second GAD gene (GAD65). Expression of different GAD-related proteins with distinct intracellular distributions during development suggests that GABA, the product of these enzymes, may have trophic or metabolic roles during spinal cord differentiation.

Animals↗
PubMed1992

Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination.

To investigate insulin-like growth factor I (IGF-I) and IGF-I receptor gene expression during experimental demyelination and myelin regeneration, young mice were fed cuprizone (( bis(cyclohexanone) oxaldihydrazone )). This copper-chelating agent produces demyelination in the corpus callosum and superior cerebellar peduncles, and when treatment is stopped, there is rapid remyelination. At intervals during cuprizone treatment and recovery, brain sections were hybridized with specific probes and immunostained with antibodies to determine the localization and relative amounts of IGF-I and IGF-I receptor mRNAs and peptides. In untreated littermates, IGF-I and IGF-I receptor mRNAs and peptides were not detected in white matter. In cuprizone-treated mice, high levels of both IGF-I mRNA and peptide were expressed by astrocytes in areas of myelin breakdown. Astrocyte IGF-I expression decreased rapidly during recovery and oligodendroglial expression of myelin-related genes increased. In severely demyelinated areas, immature oligodendroglia exhibited a transient increase in IGF-I receptor mRNA and peptide immunoreactivity during early recovery. This highly specific pattern of IGF-I induction in astrocytes during demyelination and the expression of the IGF-I receptor in regenerating oligodendrocytes during recovery suggest that IGF-I functions in the regulation of oligodendrocyte and myelin metabolism in vivo.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1992

Hypercortisolemia inhibits yohimbine-induced release of norepinephrine in the posterolateral hypothalamus of conscious rats.

Chronic hypercortisolemia attenuates yohimbine (YOH)-induced increments in plasma levels of the sympathetic neurotransmitter norepinephrine (NE). The present study used in vivo microdialysis to study the effects of hypercortisolemia on YOH-induced release of NE in the brain. Cortisol (25 mg/kg.day) or saline was infused sc into rats for 7 days via an osmotic minipump. Microdialysate and plasma concentrations of NE and its metabolites dihydroxyphenylglycol and methoxyhydroxyphenylglycol were measured before and after YOH (1 mg/kg, iv) administration in conscious animals, with microdialysate and plasma collections beginning 20-24 h after probe implantation. Chronic cortisol treatment resulted in attenuated NE, dihydroxyphenylglycol, and methoxyhydroxyphenylglycol responses in both microdialysate and plasma. The results indicate that YOH increases central neural as well as peripheral release, reuptake, turnover, and metabolism of NE and that hypercortisolemia suppresses these responses.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Simultaneous measurement of plasma and brain extracellular fluid concentrations of catechols after yohimbine administration in rats.

The present study examined whether systemic injection of the alpha 2 adrenoceptor blocker, yohimbine, affects concentrations of norepinephrine (NE) and its metabolites in extracellular fluid in the brain and in blood. Microdialysis probes were inserted into the posterior hypothalamus, medulla, and caudate/putamen in rats. Microdialysate and arterial blood were sampled after intravenous administration of yohimbine. In the hypothalamus yohimbine produced significant increases in extracellular fluid concentrations of NE, its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), and methoxyhydroxyphenylglycol (MHPG), a major neuronal and extraneuronal metabolite of NE. The increases in these levels were small or absent in the caudate/putamen, where dopamine is the primary catecholamine transmitter. During systemic infusion of tracer amounts of [3H]NE, little if any radioactive NE or DHPG appeared in the microdialysate, whereas substantial levels of [3H]MHPG were present and increased as plasma [3H]MHPG levels rose. The results support the view that alpha 2 adrenoceptor blockade in the brain increases hypothalamic and medullary release, reuptake, and metabolism of NE. The findings cannot be explained by disruption of the blood-brain barrier for catecholamines by insertion of the microdialysis probes. Enhanced sympathetic outflow and peripheral release of NE when alpha 2 adrenoceptors are blocked appears to be attended by enhanced central NE release, presumably as a result of presynaptic alpha 2 adrenoceptor blockade at noradrenergic terminals in the brain. This is consistent with the hypothesis that central noradrenergic NE release is regulated by presynaptic alpha 2 adrenoceptors.

Animals↗
PubMed1991

Distribution of protein kinase C isozymes in rat optic nerves.

Light (LM) and electron (EM) microscopic immunocytochemical methods were used to study the distribution of protein kinase C (PKC) isozymes in adult rat optic nerves. In cryostat and vibratome sections examined by LM, type II (beta) isozyme was localized almost exclusively in the axons. In the EM, immunoreaction products were found to associate with microtubules and neurofilaments. The inner surface of axonal membranes were occasionally stained. Analysis of PKC isozyme composition of the optic nerves by using immunoblot techniques revealed that type II (beta) isozyme accounted for approximately 80% of the total immunoreactivity. By contrast, type III (alpha) isozyme, which accounted for the remaining 20% of PKC, was found mainly in the astrocytes. Astrocytic processes next to blood vessels and between myelinated axons were stained. In the EM, immunoreaction products were found in the cytoplasm and along astroglial filaments. Segments of plasma membranes also were stained; but nuclei were unstained. Adult glial cells were not stained by an antibody to type II (beta) isozyme except for the occurrence of a few punctate cytoplasmic densities in occasional astrocytes. Very faint or no immunostaining was observed in sections treated with a monoclonal antibody to type I (gamma) isozyme. Immunoblot analyses also did not reveal this subspecies. The absence of type I (gamma) isozyme in optic nerves is not due to a down-regulation of the enzyme during development. In developing (5 and 11 day) rats, immunoreactivity of protein kinase C was very faint or absent. After 15 days, reaction products of both type III (alpha) and type II (beta) isozymes were found throughout the nerve. These findings suggest that type II (beta) isozyme may be involved in axonal transport whereas type III (alpha) isozyme may play a role in some astrocyte functions in mature optic nerves.

Aging↗
PubMed1991

Cerebral ischemia induces transient intracellular redistribution and intranuclear translocation of the raf proto-oncogene product in hippocampal pyramidal cells.

In this report we describe changes in the intracellular redistribution of raf serine/threonine protein kinase (product of the raf proto-oncogene family) in hippocampal neurons following cerebral ischemia in Mongolian gerbils. For immunohistochemical localization studies polyclonal antisera specific for each of the A, B, and Raf-1 isotypes of raf, as well as a pan-raf antisera, were employed. Of these, only sera recognizing B-raf, as well as the general v-raf (raised against the conserved C-terminal region) were positive, indicating that B-raf is the major isotype in this neuronal region. Three different ischemic models were used (repeated 3 times for two min and single 5 or 15 min occlusions, of the common carotid arteries) to demonstrate that ischemic insult causes redistribution of raf protein kinase into the cell nucleus of hippocampal neurons. Increased amounts of raf protein in the nuclei of pyramidal cells following ischemia was confirmed by Western blot analysis of isolated nuclear fractionations. Moreover, an elevation in the level of nuclear raf protein also was detected in the contralateral (i.e. non-occluded hemisphere) neurons of CA1 and CA3 subfields 4 days after the ischemic insult indicating a possible transsynaptic increase in the amount of raf protein along with redistribution. The intranuclear translocation of the immunoreactive material started from the perinucleolar rim and with time extended throughout the nucleus. Enhanced levels and altered redistribution of the raf polypeptide in the nuclei of pyramidal cells of the CA3 subfield appears to be reversible and returns to the normal level 12 days following the ischemic insult.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Sclerosis multiplex in gypsies.

MS rarely occurs in gypsies in Hungary despite the high DR2 frequency. When it does occur, it has special features more resembling that of Asians than Central Europeans. In order to find correlation between the clinical observations and the immunogenetical data, the distribution of DQw1 subtypes was investigated by means of Eco RV - DQ beta RFLP in DR2 positive healthy gypsies and Hungarians, as well asin DR2-positive Hungarian and unselected gypsy MS patients. DQw6 correlated with MS susceptibility in Hungarians. This allotype was completely absent in healthy DR2-positive gypsies. DR2-positive gypsy MS patients, however, carried DQw6. No correlation of complement allotypes with the occurrence of MS was found in Hungarians, while a striking elevation of C4 Q0 occurred in gypsy MS patients compared with healthy individuals in the gypsy group. The absence of the DR2, DW2, DQw6 haplotype, and the frequency of C4A Q0 in healthy gypsies seems to be associated with the low MS prevalence, but genes outside this region might also influence the MS susceptibility.

Alleles↗
PubMed1990

[Herpes zoster infection with acute urinary retention].

The history of a young female patient is presented. She developed urine retention of sudden onset as a complication of herpes zoster infection manifested in the sacral dermatomes. Symptomatic and antiviral treatments were introduced with full recovery of bladder function. The correct diagnosis of this rare and benign complication of herpes zoster infection can help to avoid unnecessary and invasive examinations.

Acyclovir↗
PubMed1989

Cerebrospinal fluid (CSF) investigations in migraine.

A normal cell count as well as normal CSF pressure levels were found in both classic and common migraine patients during and between attacks. Total protein content was significantly lower in the migraine patients than in the controls, but no changes were found in the CSF protein fractions. The CSF 5-hydroxyindoleacetic acid level of the migraine patients proved to be higher than in the controls, whereas the homovanillic acid concentration was within the control limits.

Adult↗
PubMed1987

Decrease in oligodendrocyte carbonic anhydrase activity preceding myelin degeneration in cuprizone induced demyelination.

Both immunohistochemical and biochemical evidence is presented to show for the first time that carbonic anhydrase II (CA II) activity falls in the brain of mice in cuprizone (bis(cyclohexanone)oxalyldihydrazone) induced demyelination well before demyelination develops. This fall began during the first week, whereas the first signs of myelin degeneration induced by cuprizone did not appear until 3 weeks and demyelination in the superior cerebellar peduncle in the mouse took 6-8 weeks to develop. The findings suggest that oligodendrocyte CA II activity is essential either for the survival of oligodendrocytes or for the maintenance of central myelin.

Animals↗