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Biomedical subjects

M Molnar

Publications and source records attributed to M Molnar.

At least 19 recordsLinked to original sources
PubMed2005

Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression.

Abnormalities in L-glutamic acid (glutamate) and GABA signal transmission have been postulated to play a role in depression, but little is known about the underlying molecular determinants and neural mechanisms. Microarray analysis of specific areas of cerebral cortex from individuals who had suffered from major depressive disorder demonstrated significant down-regulation of SLC1A2 and SLC1A3, two key members of the glutamate/neutral amino acid transporter protein family, SLC1. Similarly, expression of L-glutamate-ammonia ligase, the enzyme that converts glutamate to nontoxic glutamine was significantly decreased. Together, these changes could elevate levels of extracellular glutamate considerably, which is potentially neurotoxic and can affect the efficiency of glutamate signaling. The astroglial distribution of the two glutamate transporters and L-glutamate-ammonia ligase strongly links glia to the pathophysiology of depression and challenges the conventional notion that depression is solely a neuronal disorder. The same cortical areas displayed concomitant up-regulation of several glutamate and GABA(A) receptor subunits, of which GABA(A)alpha1 and GABA(A)beta3 showed selectivity for individuals who had died by suicide, indicating their potential utility as biomarkers of suicidality. These findings point to previously undiscovered molecular underpinnings of the pathophysiology of major depression and offer potentially new pharmacological targets for treating depression.

Bipolar Disorder↗
PubMed2001

[Postoperative transcutaneous electrical nerve stimulation (TENS) in shoulder surgery (randomized, double blind, placebo controlled pilot trial)].

BACKGROUND: The aim of this study was to determine whether 3 days of TENS therapy postoperatively after shoulder operations would result in better pain relief and/or reduced analgesic intake when compared to placebo. METHOD: The study was carried out randomized, double-blind and placebo controlled. Thirty patients were randomized to two groups. The verum group received TENS SM1AKS 80 Hz 6 mA and the placebo group received TENS SM1AKS 80 Hz 0 mA. The pain was assessed pre-operatively using the Hamburg Pain Adjective List. Premedication and Anaesthesia were standardized. TENS was applied to the patients immediately postoperatively for 8 hours and then on the following days 5 times daily for 45 minutes. The effectiveness was evaluated postoperatively using a visual analogue scale (rest, activity), the Hamburg Pain Adjective List and postoperative analgesic consumption. RESULTS: The visual analogue scale at rest and on activity showed no significant difference between the groups. Postoperative analgesic consumption of morphine hydrochloride in the first 24 hours was at time 8 hours postoperative significantly and at all other time points markedly less in the verum group compared to the placebo group. The sensory secondary scale score of the "Hamburg Pain Adjective List" was significantly lower postoperatively compared to preoperatively in the verum group. CONCLUSION: We were able to show in this study that TENS applied postoperatively after shoulder surgery clearly reduced analgesic consumption in the first 72 hours. Furthermore there was a significant difference in the pain scores using the "Hamburg Pain Adjective List" in favour of the verum group. TENS applied postoperatively is a effective, simple modality with few side-effects.

Double-Blind Method↗
PubMed2001

Characterization of rec7, an early meiotic recombination gene in Schizosaccharomyces pombe.

rec7 is involved in intra- and intergenic meiotic recombination in all tested regions of the genome of the fission yeast Schizosaccharomyces pombe. Segregational analysis in a rec7 gene disruption mutant revealed frequent occurrence of two-spored asci. Spores giving rise to diploid colonies were shown to derive from skipping of the second meiotic division. Nondisjunction of homologous chromosomes at the first meiotic division was also frequent. The cytological structures and processes, such as formation of linear elements, pairing of homologous chromosomes, and clustering of telomeres and centromeres, are regular in the mutant. Northern blot experiments revealed meiosis-specific expression of rec7. Screening of a meiotic cDNA library also identified transcripts from the opposite strand in the rec7 region. A Rec7-GFP fusion protein was localized in the nucleus of whole cells before karyogamy, during prophase, and after meiosis I. On spreads of prophase nuclei approximately 50 foci of Rec7-GFP were counted. Some of the observed phenotypes of the disruption mutant and the N-terminal sequence homology suggest that Rec7p is a functional homolog of Rec114p of Saccharomyces cerevisiae. The observed phenotypes of the disruption and the appearance of Rec7-GFP in mating haploid cells and after meiosis I are consistent with Rec7p functions before, during, and after meiotic prophase.

Blotting, Northern↗
PubMed2001

Live observation of fission yeast meiosis in recombination-deficient mutants: a study on achiasmate chromosome segregation.

Regular segregation of homologous chromosomes during meiotic divisions is essential for the generation of viable progeny. In recombination-proficient organisms, chromosome disjunction at meiosis I generally occurs by chiasma formation between the homologs (chiasmate meiosis). We have studied meiotic stages in living rec8 and rec7 mutant cells of fission yeast, with special attention to prophase and the first meiotic division. Both rec8 and rec7 are early recombination mutants, and in rec7 mutants, chromosome segregation at meiosis I occurs without any recombination (achiasmate meiosis). Both mutants showed distinct irregularities in nuclear prophase movements. Additionally, rec7 showed an extended first division of variable length and with single chromosomes changing back and forth between the cell poles. Two other early recombination deficient mutants (rec14 and rec15) showed very similar phenotypes to rec7 during the first meiotic division, and the fidelity of achiasmate chromosome segregation slightly exceeded the expected random level. We discuss possible regulatory mechanisms of fission yeast to deal with achiasmate chromosome segregation.

Cell Nucleus↗
PubMed2000

Peripheral neuropathy associated with hereditary and sporadic inclusion body myositis: confirmation by electron microscopy and morphometry.

Inclusion body myositis (IBM) is a disabling myopathy affecting proximal and distal muscle groups. The involvement of peripheral nerves in IBM is still a controversial matter. In a previous morphometric study at the light microscopic level only, we described a peripheral neuropathy in sural nerve biopsies of eight patients with sporadic IBM (s-IBM). Here we present a larger series of 14 cases in which a combined muscle and nerve biopsy was available for additional electron microscopic investigation. In two of the new cases, the IBM had a hereditary background (h-IBM). The presence of neuropathy was confirmed in all 14 cases studied. Morphometry using an optic-electronic, digital evaluation system showed large variation of severity presumably due to age and coincidal factors such as diabetes mellitus or lymphoma. Ultrastructural analysis revealed a variety of changes considered to be non-specific. Signs of axonal damage predominated. In addition, there were numerous changes in Schwann cells and myelin sheaths. Neither inflammatory changes nor tubulofilamentous inclusions were detectable in the sural nerves. Peripheral neuropathy, although occasionally without apparent clinical manifestation, appears to be a common and aggravating feature in IBM; its pathogenesis, however, remains elusive.

Adolescent↗
PubMed2000

Novel cluster of tRNALeu(UUR) mutations in a sporadic case of infantile myopathy restricted to muscle tissue.

In a previous study we reported on a case with severe infantile, mitochondrial myopathy caused by somatic mutation [12]. In the present study we give evidence for asymmetric tissue distribution of the mutations. Mitochondrial DNA (mtDNA) analysis showed a cluster of nearly homoplasmic point mutations in the tRNA gene for leucine (UUR) (A3259 G, A3261 G, A3266 G, A3268 G). The mutation is abundant in muscle, but is not found in blood cells. This cluster of mutations is sporadic, because the search for mutant molecules in the blood of the healthy mother and maternal grandmother did not show these alterations.

Base Sequence↗
PubMed2000

Unusual malabsorption of levothyroxine.

We report a 50-year-old woman, with overt hypothyroidism undergoing thyrotropin (TSH)-stimulating hormone suppressive levothyroxine (LT4) treatment after subtotal thyroidectomy. At her first visit to our department, the laboratory results revealed a borderline low free thyroxine (FT4) level accompanied by a clearly elevated TSH level. Both parameters did not significantly change during therapy with an oral dose of 500 microg of LT4. Investigations revealed malabsorption of oral administrated LT4. Thyroid serum hormone levels only became normal during parenteral therapy with LT4.

Administration, Oral↗
PubMed2000

The role of the thalamic reticular neurons in alpha- and gamma-oscillations in neocortex: a mechanism for selective perception and stimulus binding.

The long-term objective is to understand how large masses of neurons in the brain process information during various learning and memory paradigms. Both time- and space-dependent processes have been identified in animals through computer-based analytic quantifications of event-related extracellular potentials. New nonlinear analyses have been introduced that presume that the fine-grain variation in the signal is determined and patterned in phase-space. Some neurons in the primary visual cortex manifest gamma-band oscillations. These cells show both a nonspecific phase-alignment (response synchrony) and a specific tuning (orientation tuning) when stimuli are presented to their receptive fields. This dual regulation of the sensory cells is proposed to underlie stimulus binding, a theoretical mechanism for "object" perception. Nonlinear analytic results from gamma-activities in a simple model neuropil (olfactory bulb) suggest that neuroplasticity may arise through self-organization, a process in which a nonlinear change in the dynamics of the oscillatory field potentials is the hallmark. This self-organization may follow simple dynamical laws in which global cooperativity among the neurons is transiently brought about that, over trials, results in enduring changes in the nonlinear dynamics of some neurons. In conclusion, the sculpturing of the synaptic throughput in the sensory cortex (stimulus binding) may be associated with the irregular phases of the gamma-activities and may result from both specific and nonspecific systems operating together in a nonlinear self-organizing manner.

Alpha Rhythm↗
PubMed2000

Symptom control in advanced cancer: important drugs and routes of administration.

Aggressive symptom control is a vital component of palliative medicine. Frequently both physicians and patients focus on pain control, forgetting the broader issues of symptom control. Pain and other symptoms are inextricably linked. Common symptoms include constipation, nausea and vomiting, insomnia, anorexia, weight loss, and cough. All oncologists should be familiar with the indications, doses, and unwanted effects of drugs commonly indicated for symptom control. This article will discuss some drugs presently available to achieve good symptom control. At the correct dose and dosing schedule, these agents can have a significant impact on quality of life. As in all areas of medicine, it is best to know the benefits and unwanted effects of a few drugs, rather than randomly prescribing different agents for similar clinical situations. This is rational prescribing. While the list presented here is not exhaustive, it does reflect core drugs currently available in the United States.

Drug Administration Routes↗
PubMed1999

Thyroid hemiagenesis in an endemic goiter area diagnosed by ultrasonography: report of sixteen patients.

During a period of 9 years, 71,500 patients underwent thyroid investigations at our department. Sixteen patients with thyroid hemiagenesis, 13 women and 3 men, were seen during this period. Fifteen had no left lobe and only 1 had no right lobe, the isthmus was present in 5 patients. Associated thyroid diseases of the lobe that was present could be observed in 11 patients (9 diffuse or nodular goiters, 2 thyroid autoimmune diseases). One patient was hyperthyroid and 7 were hypothyroid. Hypothyroidism associated with hemiagenesis has rarely been reported in the literature. In our survey, the high percentage of hypothyroidism may be explained by coexisting iodine deficiency, which could be verified in 4 hypothyroid patients. Ultrasonography is the key investigation to diagnose thyroid hemiagenesis. Fine-needle aspiration biopsies, laboratory tests, and scintigraphies are useful to diagnose other diseases within the remaining lobe or to visualize ectopic thyroid tissue. Review of the literature, including our cases, presented a total of 256 patients with thyroid hemiagenesis. Its prevalence can be estimated between 1:1900 and 1:2675. Left to right ratio of thyroid hemiagenesis is 3.6:1 with an isthmus present in 44%. The female-to-male ratio is 3:1; however, the larger number of females is probably based on a bias due to a female predominance of the populations investigated. On the basis of an equal distribution of both sexes, the female-to-male ratio of thyroid hemiagenesis would be only 1.3:1 in our survey.

Adolescent↗
PubMed1999

Rec8p, a meiotic recombination and sister chromatid cohesion phosphoprotein of the Rad21p family conserved from fission yeast to humans.

Our work and that of others defined mitosis-specific (Rad21 subfamily) and meiosis-specific (Rec8 subfamily) proteins involved in sister chromatid cohesion in several eukaryotes, including humans. Mutation of the fission yeast Schizosaccharomyces pombe rec8 gene was previously shown to confer a number of meiotic phenotypes, including strong reduction of recombination frequencies in the central region of chromosome III, absence of linear element polymerization, reduced pairing of homologous chromosomes, reduced sister chromatid cohesion, aberrant chromosome segregation, defects in spore formation, and reduced spore viability. Here we extend the description of recombination reduction to the central regions of chromosomes I and II. We show at the protein level that expression of rec8 is meiosis specific and that Rec8p localizes to approximately 100 foci per prophase nucleus. Rec8p was present in an unphosphorylated form early in meiotic prophase but was phosphorylated prior to meiosis I, as demonstrated by analysis of the mei4 mutant blocked before meiosis I. Evidence for the persistence of Rec8p beyond meiosis I was obtained by analysis of the mutant mes1 blocked before meiosis II. A human gene, which we designate hrec8, showed significant primary sequence similarity to rec8 and was mapped to chromosome 14. High mRNA expression of mouse and human rec8 genes was found only in germ line cells, specifically in testes and, interestingly, in spermatids. hrec8 was also expressed at a low level in the thymus. Sequence similarity and testis-specific expression indicate evolutionarily conserved functions of Rec8p in meiosis. Possible roles of Rec8p in the integration of different meiotic events are discussed.

Amino Acid Sequence↗
PubMed1998

Cholinergic function in the hippocampus of juvenile rats chronically deprived of NGF.

Intracellular and extracellular recordings were used to assess the cholinergic function in hippocampal slices from juvenile rats chronically deprived of NGF. NGF was neutralised by implanting into the lateral ventricle of postnatal (P) day 2 rats, alphaD11 hybridoma cells (secreting monoclonal antibodies specific for NGF). Parental myeloma cells (P3U) were used as controls. At P15-P18, slow cholinergic EPSPs could be elicited in cells from both alphaD11- and P3U-treated rats. However, slices from alphaD11-implanted rats exhibited a 50% reduction in acetylcholine release following stimulation of cholinergic fibres. This effect was associated to a significant increase in the sensitivity of pyramidal cells to carbachol, as suggested by the shift to the left of the dose/response curve. This may reflect a compensatory mechanism for the reduced efficacy of cholinergic innervation in NGF-deprived rats. In both alphaD11- and P3U-treated rats, carbachol was able to induce a similar concentration-dependent depression of the field EPSPs, evoked by Schaffer collateral stimulation, suggesting that presynaptic muscarinic receptors were not altered. In rats implanted with alphaD11 cells at P15 and sacrificed at P21-P24, no changes in the sensitivity to carbachol were found. At this developmental stage, no differences in acetylcholine release were observed between P3U- and alphaD11-treated animals. These results provide physiological evidence for a regulatory role of NGF in the cholinergic function of the hippocampus during postnatal development.

Acetylcholine↗
PubMed1998

Attenuation-corrected thallium-201 single-photon emission tomography using a gadolinium-153 moving line source: clinical value and the impact of attenuation correction on the extent and severity of perfusion abnormalities.

The aim of the study was to test the clinical value of attenuation-corrected (AC) thallium-201 single-photon emission tomography using a moving gadolinium-153 line source in a group of patients in whom coronary angiography was planned because of clinically suspected coronary artery disease (CAD). Furthermore, we wanted to test the impact of AC on assessment of the extent and severity of perfusion abnormalities. A total of 107 patients planned to undergo coronary angiography were included in the study. In each patient, AC and NC (non-corrected) 201Tl SPET was performed. AC and NC images were evaluated visually as well as by a 31-segment semiquantitative analysis and the findings were correlated with angiographic results. Patients were assigned to two groups: group A with angina and no previous cardiac infarction or intervention and group B with known CAD because of previous myocardial infarction or intervention. With visual analysis, NC revealed a sensitivity of 88.9% in group A and 74.3% in group B, compared to 94.4% in group A and 94.3% in group B with AC. Specificity for NC was calculated to be 68.7% for group A and 91.3% for group B. AC demonstrated significantly higher specificity of 83.9% and 100% respectively. This effect was particularly demonstrated for males and bicycle workload. The extent and severity of perfusion abnormalities were significantly influenced by the use of AC, in that significantly fewer abnormal and less severely abnormal segments were demonstrated in the segmental analysis as compared to NC; this was especially true for the vascular territory of the left anterior descending artery and the right coronary artery. It is concluded that AC with a moving line source is feasible in patients with all degrees of probability of CAD. AC has a significant impact on the assessment of the severity and extent of myocardial ischaemia, especially in the posterior and septal wall.

Adult↗
PubMed1998

Pleomorphic mitochondrial and different filamentous inclusions in inflammatory myopathies associated with mtDNA deletions.

Mitochondrial changes are frequently observed in muscle fibers of patients with inclusion body myositis (IBM) and polymyositis (PM), suggesting that mitochondrial function may be especially impaired in these forms of inflammatory myopathies. Intranuclear and cytoplasmic tubulofilamentous inclusions are characteristic, although not totally specific for IBM. In the present cases, the inclusions were strikingly pleomorphic when chloroquine had been given for long periods. The nuclear inclusions were always tubular, whereas the cytoplasmic filaments had either a tubular, a helical, or a cross-striated structure with different diameters and arrangements in association with myelin-like figures, and vacuoles. Abnormal mitochondria containing paracrystalline, globoid, and other inclusions, noted in IBM, were occasionally also seen in PM or vasculitis. By contrast, in the latter, no intranuclear or cytoplasmic tubulofilamentous inclusions were apparent in muscle fibers. This study reports for the first time the presence of membrane-bound crystalloid inclusions in a muscle fiber with numerous abnormal mitochondria; similar structures have thus far only been observed in macrophages. The identity and function of these inclusions remains unknown. Using PCR analysis we detected different mtDNA deletions not only in IBM, but also in PM and vasculitis, indicating at least some degree of association between the structural mitochondrial abnormalities and the mtDNA mutations. There was no topographical correlation between the presence of tubular or helical filaments and the mitochondrial abnormalities. As already noted by others, the mitochondrial changes in IBM were more frequent than expected in this age group. It is suggested that the presence of the mtDNA deletions in IBM and PM are not primary, but rather the result of the underlying, presumably immunological disorder causing nuclear and secondary or simultaneous mitochondrial changes.

Adult↗
PubMed1998

Nitric oxide sensitive depolarization-induced hyperpolarization: a possible role for gap junctions during development.

Electrical coupling is a widespread feature of developing neuronal circuits and it contributes to the generation of patterned activity. In the developing rat hippocampus, release of GABA by coactive hilar interneurones generates widespread synchronized activity. Here it is shown that hilar interneurones strongly rectify in the outward direction when depolarized. This depolarization-induced hyperpolarization, abolished by gap junction uncouplers, is modulated by nitric oxide. This phenomenon might represent a current-shunting mechanism of the excess current by providing functional inhibition at a developmental stage when GABA is excitatory. Spatial buffering of the current might represent an osmotic mechanism for growth and differentiation.

Anesthetics, Inhalation↗
PubMed1998

The effects of anti-nerve growth factor monoclonal antibodies on developing basal forebrain neurons are transient and reversible.

In order to reassess the role of nerve growth factor (NGF) on rat basal forebrain cholinergic neurons (BFCNs) survival and/or phenotype maturation during the early postnatal life, we immunoneutralized NGF in vivo. Hybridoma cells producing the neutralizing anti-NGF monoclonal antibody alphaD11 were implanted in the lateral ventricle of the rat at different postnatal ages (P2, P8 and P15) and the effects on the number and the soma size of cholinacetyltransferase (ChAT) positive neurons were analysed 1, 2 or 3 weeks after the injection. A marked decrease in the number and in the soma size of BFCNs was observed implanting hybridoma cells at P2 and performing the analysis 1 week later. These effects are reversed 3 weeks after the implant of hybridoma cells at P2. At this time point, the levels of alphaD11 antibodies in the brain parenchyma are still in a vast molar excess over endogenous NGF. No effects on BFCNs were observed implanting alphaD11 cells at P15 while LGN neurons showed marked shrinkage. Our results demonstrate that the reduction in the number of ChAT-positive neurons during the first two postnatal weeks of anti-NGF treatment is not due to cell death. We conclude that NGF is not a survival factor for BFCNs, and that the influence of NGF on BFCNs cell maturation during the first 2 postnatal weeks is transient and reversible. Our results on tyrosine kinase (Trk) coexpression, suggest that NGF may cooperate with other factors in the cholinergic phenotype differentiation and maintenance after the second postnatal week.

Age Factors↗
PubMed1998

Epidemiology of thyroid diseases in iodine sufficiency.

Epidemiology of thyroid diseases in iodine-sufficient areas (ISA) deals with sporadic goiter, thyroid autoimmune diseases, and thyroid cancer. A comparison between the different studies performed is difficult because methods have changed over time and selection criteria and definitions such as prevalence or incidence were not used consistently by some authors. Sporadic goiter: in ISA, autoimmune processes play a major role in the development of sporadic goiter. In adults, sporadic diffuse goiter is most frequent in young women (16%), perhaps due to additional relative iodine deficiency especially in pregnancy, and declines with age (<10%). Sporadic nodular goiter increases from 5% in young women to 9% in older women. Autoimmune thyroid disease (AITD): thyroid autoantibodies (TAb) and histopathological lymphocytic infiltration of the thyroid is much more common in ISA (4.6% in women; 1.1% in men) than in iodine-deficient areas (IDA). The prevalence and incidence of hypothyroidism and hyperthyroidism varies, depending on whether overt and subclinical forms are included and whether newly or previously diagnosed dysfunction is considered. In an overview of the literature, the prevalence is 2 in 1000 for overt and 6 in 1000 for subclinical hyperthyroidism in ISA. The values for hypothyroidism are 5 in 1000 and 15 in 1000, respectively. Change from IDA to ISA: in former IDA, the percentage of hyperthyroidism increases up to 4 years after salt iodination. Whereas this effect is transient for Plummer's disease, a change from IDA to ISA seems to lead to a permanent increase in overt and subclinical Graves' disease. Thyroid cancer: most studies demonstrate that the histopathological types of thyroid cancer are different in IDA and ISA. There is a tendency toward an increase in differentiated and decrease of anaplastic cancer. The ratio of papillary to follicular thyroid cancer ranges from 6.5:1 to 3.4:1 in areas with high iodine intake, decreases 3.7:1 to 1.6:1 in areas with moderate iodine intake, and ranges from 1.7:1 to 0.19:1 in IDA.

Adult↗