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Biomedical subjects

L Kiss

Publications and source records attributed to L Kiss.

At least 19 recordsLinked to original sources
PubMed2004

Natural variation of drug susceptibility in wild-type human immunodeficiency virus type 1.

Wild-type viruses from the ViroLogic phenotype-genotype database were evaluated to determine the upper confidence limit of the drug susceptibility distributions, or "biological cutoffs," for the PhenoSense HIV phenotypic drug susceptibility assay. Definition of the natural variation in drug susceptibility in wild-type human immunodeficiency virus (HIV) type 1 isolates is necessary to determine the prevalence of innate drug resistance and to assess the capability of the PhenoSense assay to reliably measure subtle reductions in drug susceptibility. The biological cutoffs for each drug, defined by the 99th percentile of the fold change in the 50% inhibitory concentration distributions or the mean fold change plus 2 standard deviations, were lower than those previously reported for other phenotypic assays and lower than the clinically relevant cutoffs previously defined for the PhenoSense assay. The 99th percentile fold change values ranged from 1.2 (tenofovir) to 1.8 (zidovudine) for nucleoside reverse transcriptase RT inhibitors (RTIs), from 3.0 (efavirenz) to 6.2 (delavirdine) for nonnucleoside RTIs, and from 1.6 (lopinavir) to 3.6 (nelfinavir) for protease inhibitors. To evaluate the potential role of intrinsic assay variability in the observed variations in the drug susceptibilities of wild-type isolates, 10 reference viruses with different drug susceptibility patterns were tested 8 to 30 times each. The median coefficients of variation in fold change for the reference viruses ranged from 12 to 18% for all drugs except zidovudine (32%), strongly suggesting that the observed differences in wild-type virus susceptibility to the different drugs is related to intrinsic virus variability rather than assay variability. The low biological cutoffs and assay variability suggest that the PhenoSense HIV assay may assist in defining clinically relevant susceptibility cutoffs for resistance to antiretroviral drugs.

Anti-HIV Agents↗
PubMed2003

Multilevel callus distraction: a novel idea to shorten the lengthening time.

Lower extremity inequality is a common problem in everyday orthopaedic practice. The leg discrepancy can lead to variety of other problems, i.e., spinal problems. Surgical intervention is very demanding and requires patient compliance. Wagner's and Ilizarov's elongation technique are most commonly used worldwide, but it gives satisfactory results only in a long period of time and as we know there could be several inconvenient outcomes. Our idea aims at shortening this time period, and avoiding some of the inconvenient outcomes. Unfortunately we do not have the opportunity to go further in our investigations, but we hope that someone interested in this field will have an idea which would make continuation possible.

Bone Lengthening↗
PubMed2002

Contradictions of derotation in scoliosis surgery using the CD principle.

Current literature has increasingly emphasized the problem of derotation in scoliotic deformities. The Cotrel-Dubousset (CD) principle as a means of correcting rotation has been questioned by various authors. This paper aims to draw attention, using algebraic methods, to the importance of the remaining rotational deformities, and to suggest the introduction of the notion 'rotational balance'.

Humans↗
PubMed2002

Advances in the identification of emerging powdery mildew fungi using morphological and molecular data.

Recently, the classical morphological criteria and host range data used in the identification of powdery mildew fungi were supplemented with scanning electron microscope (SEM) and molecular phylogenetic analyses. This paper discusses the joint use of these methods in the identification of powdery mildew anamorphs causing new or emerging plant diseases in different parts of the world.

Ascomycota↗
PubMed2001

Cyclic stretch enhances the expression and activity of coronary endothelium-derived hyperpolarizing factor synthase.

Endothelium-derived hyperpolarizing factor (EDHF) mediates NO/prostacyclin-independent relaxation in the coronary circulation. Because hemodynamic stimuli modulate endothelial gene expression and because coronary arteries are subjected to pronounced variations in vessel distension, we determined the effects of cyclic stretch on the expression and activity of the coronary EDHF synthase/cytochrome P450 (CYP) 2C8/9. In cultured porcine coronary and human umbilical vein endothelial cells, acute application of cyclic stretch (6%, 1 Hz, 10 minutes) elicited the generation of 8,9-epoxyeicosatrienoic acid (EET), 11,12-EET, and 14,15-EET. Prolonged stretch (4 to 36 hours) increased the expression of CYP 2C mRNA and protein 5- to 10-fold and was accompanied by a 4- to 8-fold increase in EET generation. A corresponding increase in CYP 2C mRNA and protein was also observed in pressurized segments of porcine coronary artery perfused under pulsatile conditions (8%, 1 Hz) for 6 hours. Although in cultured endothelial cells, cyclic stretch elicited the rapid activation of tyrosine kinases as well as Akt and the p38 mitogen-activated protein kinase, the mechanism by which cyclic stretch induces the expression of CYP 2C could not be elucidated, because inhibitors of these pathways induced CYP 2C expression in cells maintained under static conditions. These results have identified coronary EDHF synthase/CYP 2C as a novel mechanosensitive gene product in native and cultured endothelial cells. Because this enzyme generates both EETs and superoxide anions, this finding has wide-reaching implications for vascular homeostasis in conditions of manifest endothelial dysfunction.

8,11,14-Eicosatrienoic Acid↗
PubMed2001

Chiroptical properties of 2,3-dihydrobenzo[b]furan and chromane chromophores in naturally occurring O-heterocycles.

The correlation between the helicity (absolute conformation) of the O-heterocyclic ring of chiral 2,3-dihydrobenzo[b]furan (1) and chromane (2) derivatives and their (1)L(b) band CD was investigated. The same helicity rule was found for both unsubstituted chromophores: P/M helicity of the heterocyclic ring leads to a negative/positive CD within the (1)L(b) band. While the substitution of the fused benzene ring by achiral substituents does not change this helicity rule for the chromane chromophore, it leads to its inversion for the 2,3-dihydrobenzo[b]furan chromophores. On the basis of these observations, the published absolute configurations of natural flavonol and pterocarpan derivatives were confirmed and the configurational assignments of several natural neolignans revised.

Benzofurans↗
PubMed2001

The coronary endothelium-derived hyperpolarizing factor (EDHF) stimulates multiple signalling pathways and proliferation in vascular cells.

In the present study we determined whether the endothelium-derived hyperpolarizing factor (EDHF), in addition to its acute effects on vascular tone, activates intracellular signalling pathways other than those associated with Ca2+-dependent K+ channels. EDHF was generated by rhythmic distension of porcine coronary arteries under conditions of combined nitric oxide (NO) synthase/cyclo-oxygenase blockade, and the EDHF-containing luminal incubate was applied to cultured human coronary endothelial or smooth muscle cells. In both cell types, the luminal incubate activated tyrosine kinases, the mitogen-activated protein (MAP) kinases, extracellular signal regulated kinases 1 and 2 (Erk1/2) and p38, as well as protein kinase B/Akt. The constituent responsible for Erk1/2 phosphorylation was identified as a cytochrome P450 (CYP) metabolite, as Erk1/2 activation was attenuated by pretreating the EDHF donor with the CYP 2C inhibitor sulfaphenazole as well as by CYP 2C antisense oligonucleotides. Erk1/2 phosphorylation in detector cells was also observed following the transfer of supernatant from cultured endothelial cells treated with the CYP inducer beta-naphthoflavone. The CYP 2C product 11,12-epoxyeicosatrienoic acid (11,12-EET) also activated tyrosine kinases, Erk1/2 and p38 MAP kinase. Overexpression of CYP 2C8 in native porcine coronary artery endothelial cells resulted in an increase in endothelial 11,12-EET production and Erk1/2 phosphorylation compared to that detected in untreated cells or cells transfected with an antisense CYP 2C8. Endothelial cell number was unaffected by transfection with LacZ or CYP 2C8 antisense but was significantly enhanced in cells overexpressing CYP 2C8. These observations indicate that EDHF/11,12-EET is not simply a vasodilator and that its continuous release under pulsatile conditions in vivo may affect vascular cell signalling and proliferation.

8,11,14-Eicosatrienoic Acid↗
PubMed2001

[The "hospital review" in 1865: the first journal for hospital service in Hungary].

This article is a concise history of the first Hungarian journal for hospital medicine published in Pozsony (Bratislava, Pressburg) from the year 1865. The editorial board of the Kórházi Szemle (Hospital Review) consisting of young physicians (Zlamál, Gotthard, Kanka) attempted to give a complete overview on Hungarian hospital research, including new ways of therapies and hospital statistics as well. Analysing the publications of the journal author concludes, that the hospital of Pozsony (Bratislava) founded in 1864 represented a rather high niveau of healing. The first tracheotomies, and the first histologic tests have been performed here in the region.

History, 19th Century↗
PubMed2000

Targeting lipopolysaccharides by the nontoxic polymyxin B nonapeptide sensitizes resistant Escherichia coli to the bactericidal effect of human neutrophils.

The nonapeptide of polymyxin B (PMBN) has been reported to sensitize various pathogenic gram-negative bacteria to the direct bactericidal effect of human serum. To investigate the impact of PMBN on human neutrophil-effected killing of the serum- and phagocytosis-resistant Escherichia coli strains C14 and O111, serum was coapplied with PMBN or with neutrophils, but this did not result in decreased numbers of viable bacteria. In contrast, the most potent bacterial killing occurred in the presence of neutrophils plus serum components plus PMBN. The effect of this on E. coli C14 was the appearance of inositol phosphates, diacylglycerol, respiratory burst, elastase liberation, and generation of lipid mediators (leukotriene B(4), 5-HETE, and platelet-activating factor). Strong neutrophil activation required early, but not late, complement components and was blocked by inhibition of phagocytosis with cytochalasin D. PMBN seems to cause dramatic support of natural host defense by complement-dependent sensitization of E. coli to the bactericidal efficacy of human neutrophils.

Anti-Bacterial Agents↗
PubMed2000

Prevention of corticosteroid-induced osteoporosis by alfacalcidol.

We studied the effect of alphacalcidol (1-alpha-hydroxycholecalciferol) on bone metabolism in patients who were placed on glucocorticoid therapy. We selected 41 women (age: 32-52 yrs) who were recently diagnosed with systemic lupus erythematodes, multiple sclerosis, rheumatoid arthritis or asthma bronchiale. Patients did not have other disease or take drugs known to influence bone metabolism. Patients were randomly enrolled into two groups and were given 5-25 mg prednisone daily. After 4 weeks, group A (n = 21) received 0.5-1.0 microgram (mean = 0.54 +/- 0.03 microgram) alphacalcidol and group B (control; n = 20) was given 500 mg calcium daily for three years. There were no significant differences in age and steroid doses between groups. Serum calcium (Ca), osteocalcin (OC), collagen I C-terminal propeptide (PICP), parathyroid hormone (PTH), and urinary calcium and deoxypyridinoline crosslink excretion (DPD) were measured before corticosteroid administration, and before alphacalcidol or calcium treatment as well as 6 weeks, 6 months, and 1, 2, and 3 years later. Bone mineral density (BMD) was examined before treatment and 6 months, 1, 2, and 3 years later by DEXA and SPA. OC and PICP decreased significantly after 4 weeks on steroid in both groups and increased in group A but not in group B after 6 weeks of treatment with alphacalcidol and remained unchanged for 3 years. Serum PTH increased in both groups after 4 weeks of glucocorticoid treatment and was reduced in group A, but not in group B, after 6 weeks on alphacalcidol. Serum Ca, urinary Ca, and DPD did not change significantly in either group during the study period. Lumbar spine and femoral neck BMD were significantly reduced in group B after 6 months and 1 year, respectively, and continued to decrease during the study, while no significant change in group A was observed. BMD of the radius did not change in either group for 2 years but there was a significant reduction by the third year in group B. Based on these results, alphacalcidol treatment appears to be effective in preventing glucocorticoid-induced bone loss in these patients by reducing secondary hyperparathyroidism and stimulating bone formation.

Adjuvants, Immunologic↗
PubMed2000

Enhancement of presynaptic neuronal excitability by correlated presynaptic and postsynaptic spiking.

Use-dependent modifications, such as long-term potentiation (LTP) of synaptic efficacy, are believed to be essential for information storage in the nervous system. Repetitive correlated spiking of presynaptic and postsynaptic neurons can induce LTP at excitatory glutamatergic synapses. In cultured hippocampal neurons, we show that repetitive correlated activity also results in a rapid and persistent enhancement of presynaptic excitability, decreasing the threshold for spiking and reducing the variability of interspike intervals. Furthermore, we found that correlated activity modified sodium channel gating in the presynaptic neuron. This modification of presynaptic excitability required a temporal order between presynaptic and postsynaptic spiking and activation of postsynaptic NMDA receptors. Presynaptic inhibition of protein kinase C abolished the change in excitability without affecting LTP. Such rapid activity-dependent changes in the efficacy of presynaptic spiking may be involved in the processing and storage of information within the nervous system.

Action Potentials↗
PubMed2000

The presence of a glycosyl phosphatidylinositol-anchored alpha-mannosidase in boar sperm.

alpha-Mannosidase and beta-galactosidase were released from boar sperm into the medium by treatment with calcium ionophore A23187 or by 0.2% Brij-35/2% acetic acid. About half as much alpha-mannosidase activity as that in the acid extract was recovered by digestion with phosphatidylinositol-specific phospholipase C (PI-PLC), whereas the liberation rate of beta-galactosidase treated with PI-PLC was low. These results suggest that some alpha-mannosidase is anchored in the plasma membrane of the acrosomal region by attachment to the lipid phosphatidylinositol and that beta-galactosidase is localized mainly in the acrosome or integrated in the plasma membrane by a spanning stretch of hydrophobic peptides. beta-Galactosidase, which is present as an oligomers in the acid extract of sperm, dissociated into monomers under weakly alkaline conditions; under acidic conditions, the monomers associated again. No pH-sensitive association-dissociation of alpha-mannosidase was observed.

Acrosome↗
PubMed2000

PAF-induced synthesis of tetraenoic and pentaenoic leukotrienes in the isolated rabbit lung.

In an isolated rabbit lung model, we tested the hypothesis that platelet-activating factor (PAF)-induced leukotriene (LT) synthesis is critically dependent on the free precursor fatty acid supply and the possible substitution of arachidonic acid (AA) by eicosapentaenoic acid (EPA). To augment the intravascular polymorphonuclear neutrophils (PMNs) in the isolated lung, human PMNs were infused into the pulmonary artery. LTs and hydroxyeicosatetra(penta)enoic acids were quantified with HPLC techniques. Application of PAF (5 microM) or AA (10 microM) provoked the generation of limited quantities of 4-series LTs and 5-hydroxyeicosatetraenoic acid (total sum of 5-lipoxygenase products approximately 7 and approximately 27 pmol/ml in lungs both with and without infused PMNs, respectively). Combined administration amplified 5-lipoxygenase product formation, with a predominance of cysteinyl-LT synthesis in lungs both without (total sum approximately 67 pmol/ml) and, much more strikingly, with (total sum approximately 308 pmol/ml) an infusion of neutrophils. EPA (10 microM) elicited exclusive generation of 5-series LTs and 5-hydroxyeicosapentaenoic acid (total sum approximately 82 pmol/ml). Dual stimulation with PAF and EPA provoked amplification of EPA-derived 5-lipoxygenase product formation, again with predominance of cysteinyl-LTs in lungs without (total sum approximately 224 pmol/ml) and, in particular, with (total sum approximately 545 pmol/ml) preceding microvascular PMN entrapment. Combined application of PAF, AA, and EPA resulted in the synthesis of LTs derived from both fatty acids, with a predominance of 5-series products. We conclude that the PAF-evoked 5-lipoxygenase product formation in the neutrophil-harboring lung capillary bed is critically dependent on intravascular precursor fatty acid supply, with EPA representing the preferred substrate compared with AA. PMN-related transcellular eicosanoid synthesis is suggested to underlie the predominant generation of cysteinyl-LTs. The supply of n-3 versus n-6 precursor fatty acid may thus have a major impact on inflammatory mediator generation.

Animals↗