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Biomedical subjects

A Horváth

Publications and source records attributed to A Horváth.

At least 19 recordsLinked to original sources
PubMed2001

[Interferon-alpha and PUVA therapy for mycosis fungoides].

14 patients suffering from early stage mycosis fungoides were treated with interferon alpha 2-a and PUVA/1 patient in stage I a, 3 patients in stage I b, 4 patients in stage II a and 6 patients in stage II b/during 3-21 months time course. Interferon alpha 2-a was administered 3 times a week, in escalating dose from 3 MU to 9 MU, determining the individual maximal tolerated dose. All of the patients responded well to the treatment. Partial remission was observed after 4-13 weeks of treatment. Total remission developed in 8 cases, after 8 weeks- 9 months of the treatment. Side effects occurred frequently: weight loss, pain, fever, fatigue, leucopenia, thrombopenia, liver enzyme elevation. Because of the side effects the dose of the interferon was reduced individually, the dose reduction did not cause relapse.

Aged↗
PubMed2001

[Vascular diseases, spina bifida and schizophrenia in a single family associated with the heterozygote mutation of the heat-sensitive variant of methylenetetrahydrofolate reductase].

Homozygous mutation of the thermolabile variant of methylene tetrahydrofolate reductase (MTHFR) may result in hyperhomocystinemia, leading to an increased risk for early cardiovascular disease, neural tube defects, and possibly major depression, schizophrenia. According to recent studies heterozygosity for the thermolabile variant of the MTHFR gene mutation is also more frequent in patients with thrombotic disease compared to that in the average population. We report on a family with different types of early vascular disease. In four consecutive generations MTHFR heterozygosity was detected: in the proband and in her mother, grandfather and daughter. Further conditions of the family members, possibly due to carrying the mutation, came to light by the pedigree analysis and examinations. The patient had pulmonary emboli at young age, her aunt died of spina bifida shortly after birth. The patient's mother suffers from schizophrenia and depression. The grandfather had pulmonary emboli, her sister with spina bifida occulta also carries the same mutation, as does her daughter who is sofar asymptomatic. In other asymptomatic members of the family no mutations were found. Unexpectedly, hyperhomocystinemia was detected in all heterozygote individuals. Our study demonstrates the necessity for folic acid therapy in mutation carriers to prevent early vascular events, depression and schizophrenia, and also to reduce the risk for neural tube defects in a preconception setting.

Adult↗
PubMed2001

Anti-cholesterol antibodies (ACHA) in patients with different atherosclerotic vascular diseases and healthy individuals. Characterization of human ACHA.

In animal experiments the protective role of anti-cholesterol antibodies (ACHA) in the development of atherosclerosis has been demonstrated. Despite the fact that ACHA are present in the serum of healthy humans, no data on the occurrence of these antibodies in human diseases are available. We determined serum concentrations of IgG type ACHA by an enzyme immunosorbent assay in 600 patients with atherosclerotic vascular diseases (86 patients with peripheral occlusive atherosclerosis, 146 patients with cerebrovascular diseases, 341 patients with severe coronary heart disease (CHD) who received aorto-coronary by-pass, 27 patients with myocardial infarction who did not undergo by-pass operation), in 57 patient controls (complaints of CHD, without coronarographic alterations) and in 218 healthy individuals. ACHA were present in the sera of all persons tested. No serum cofactor is needed for the binding of human ACHA to solid phase cholesterol, binding can be inhibited dose-dependently by LDL and even more strongly with LDL/VLDL preparations purified from human serum. ACHA levels were found to be considerably lower in patients with peripheral occlusive atherosclerosis and cerebrovascular diseases compared with the levels in healthy individuals. By contrast, the ACHA levels of patients with CHD were considerably higher. No differences in the IgG subclass distribution and binding efficiency of ACHA in the sera of CHD patients and controls were found. Thus, our present findings indicate that both low and high ACHA production may be associated with different atherosclerotic vascular diseases.

Adult↗
PubMed2001

Serum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies.

Serum amyloid P component (SAP) binds in vitro Ca(2+)-dependently to several ligands including oligosaccharides with terminal mannose and galactose. We have earlier reported that SAP binds to human influenza A virus strains, inhibiting hemagglutinin (HA) activity and virus infectivity in vitro. These studies were extended to comprise five mouse-adapted influenza A strains, two swine influenza A strains, a mink influenza A virus, a ferret influenza A reassortant virus, a influenza B virus and a parainfluenza 3 virus. The HA activity of all these viruses was inhibited by SAP. Western blotting showed that SAP bound to HA trimers, monomers and HA1 and HA2 subunits of influenza A virus. Binding studies indicated that galactose, mannose and fucose moieties contributed to the SAP reacting site(s). Intranasal administration of human SAP to mice induced no demonstrable toxic reactions, and circulating antibodies against SAP were not detected. Preincubation of virus (A/Japan/57) with SAP prevented primary infection of mice and development of antiviral antibodies. After a single intranasal administration of SAP (40 microg) 1 h before primary infection with virus (2LD(50)), nine out of 10 mice survived on day 10 and these mice approached normal body weight, whereas control mice (one out of five surviving on day 10) died. The data provide evidence of the potential of intranasally administered SAP for prophylactic treatment of influenza A virus infections in humans.

Animals↗
PubMed2001

High level of anticholesterol antibodies (ACHA) in HIV patients. Normalization of serum ACHA concentration after introduction of HAART.

Anticholesterol antibodies (ACHA) are natural antibodies against the 3beta-OH group of cholesterol. Since lipid disorders are common in HIV infection and HAART may further enhance dislipidaemia, we determined by using an ELISA method serum ACHA concentrations in HIV patients and healthy HIV-seronegative controls. ACHA levels were almost 4 times higher in the sera of 46 patients than in 110 controls. No difference in the specificity of ACHA was found between HIV-seropositive and HIV-seronegative sera. Binding of ACHA to cholesterol-coated plates from a HIV-seropositive serum was dose-dependently inhibited by preincubation with HIV-1(BA-L) preparation. Serum concentration of ACHA was significantly higher in the patients with low serum cholesterol levels than in those with normal cholesterol levels. HAART induced a marked drop of ACHA concentration. We found a significant negative correlation between the length of HAART and the ACHA levels. By contrast, HAART did not significantly influence total IgG concentration and titers of antibodies against 60 kD heat shock protein. Our findings indicate that high levels of ACHA in HIV-infection may contribute to the development of hypocholesterolaemia frequently observed in this disease.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Identification of a novel mutation in 3beta-hydroxysteroid-Delta8-Delta7-isomerase in a case of Conradi-Hünermann-Happle syndrome.

The X-linked dominant Conradi-Hünermann-Happle (CDPX2, MIM 302960) syndrome belongs to the rare, heterogeneous group of diseases called chondrodysplasia punctata. The disease has been connected recently with deficiency of 3beta-hydroxysteroid-Delta8-Delta7-isomerase (also called emopamil-binding protein, EBP), catalysing an intermediate step in the conversion of lanosterol to cholesterol (1, 2). We report a case of CDPX2 with a new missense mutation (C-->G 439) in exon 4, leading to a R147G aminoacid substitution in the EBP.

Adolescent↗
PubMed2001

Comparison of the quantitative competitive and semiquantitative RT-PCR methods for the determination of interferon-gamma mRNA levels in AIDS-free HIV-infected individuals.

IFN-gamma mRNA expression was evaluated in nonstimulated peripheral blood mononuclear cells (PBMC) of HIV-infected and seronegative individuals using quantitative competitive and semiquantitative RT-PCR and the sensitivity of these methods was compared. A significant correlation was found between quantitative competitive and semiquantitative RT-PCR in samples of both HIV-seronegative (P = 0.004) and HIV-infected individuals (P = 0.0004). PBMC from HIV-infected individuals presented a remarkable increase of IFN-gamma mRNA expression, as determined by both types of RT-PCR methods. Semiquantitative RT-PCR even without an internal standard is also acceptable for measuring cytokine mRNA expression, but less reliable if small amounts are quantified. Moreover, we found that increased IFN-gamma mRNA expression is independent of CD4+ cell count in AIDS-free HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed2000

[CT- and MRI-guided conformal interstitial and external beam radiotherapy of primary brain tumors: prospects in Hungary].

The technical improvements gained over the last decade in neuroradiology and radiotherapy have brought significant theoretical and experimental changes in the treatment of primary glial brain tumours. The follow-up of patients with CT, MRI and isotope diagnostic examinations proves that the relapses take place in the vicinity of the primary site in most cases. Consequently, the conventional large fields or whole brain irradiation techniques have been phased out and the conformal irradiation methods focused on the tumorous targets have gained ground. The exact neuroanatomic projection, the image based 3-dimensional treatment planning methods and the conformal irradiation techniques ensure that only the tumorous or the potentially infiltrated regions become irradiated with maximal protection of the normal brain tissues. The increased protection of the normal tissues makes a dose escalation possible, which may result in the augmentation of the therapeutic benefits. In Hungary both the interstitial and the external beam conformal radiotherapies of the CNS have become accessible in practice over the recent years. In possession of manifold treatment modalities (percutaneous fractionated conformal radiotherapy, stereotactic radiosurgery, high dose rate after-loading and low dose rate interstitial irradiation), it is found necessary to overview the indicative territories, advantages, limitations and possible complications of different interventions. The authors describe the possible routes of further improvements and ways of dose escalation. Nevertheless, it is emphasised that gliomas--with reduced radiosensitivity and high potential to infiltrate the adjacent brain tissues-represent the illness in the whole CNS. It implies that in the future it will probably be necessary to initiate systemic therapeutic modalities in the course of routine treatment strategies in addition to the focused and more effective radiotherapy regimens.

Brain Neoplasms↗
PubMed2000

Mapping of a protective helper T cell epitope of human influenza A virus hemagglutinin.

The synthetic peptide comprising the 317-341 region of human influenza A virus (H1N1 subtype) hemagglutinin elicits peptide-specific antibody and helper T cell responses and confers protection against lethal virus infection. Molecular mapping of the 317-329 region, which encompasses the epitope recognized by peptide-specific T cells, revealed that the minimal size required for T cell activation was the 317-326 segment. The most likely peptide alignment, which placed 320Leu to pocket 1 of the I-E(d) peptide binding groove, was predicted by molecular mechanics calculations performed with the parental and with the Ala-substituted analogs. In line with the prediction data, the results of the peptide binding assay, where the relative binding efficiency to I-E(d) molecules expressed on the surface of antigen-presenting cells was monitored, identified the 320-326 core sequence interacting with the major histocompatibility class II peptide binding groove. Functional analysis of Ala-substituted variants by functional assays and by calculating the surface-accessible areas of the single peptidic amino acids in the I-E(d)-peptide complexes demonstrated that 324Pro is a primary contact residue for the T cell receptor. Our results show that this type of analysis offers a suitable tool for molecular mapping of helper T cell epitopes and thus provides valuable data for subunit vaccine design.

Alanine↗
PubMed2000

Translation of the edited mRNA for cytochrome b in trypanosome mitochondria.

The type of RNA editing found in the kinetoplast-mitochondria of trypanosomes and related protozoa, involving uridylate insertions and deletions, creates translatable messenger RNAs (mRNAs) out of nonsense pre-edited RNAs by correcting encoded defects that vary from simple frameshifts to large "cryptic" regions. However, any evidence for translation of these mRNAs in the kinetoplast has been missing for decades. We identified a kinetoplast-encoded protein, apocytochrome b, whose mRNA is edited in the 5' region. The determined amino-terminal sequence of the protein coincides with the predicted sequence derived from the edited region, demonstrating that the cognate apocytochrome b mRNA is translated into a functional protein. This finding represents the first direct evidence for a functional translation system in the kinetoplasts.

Amino Acid Sequence↗
PubMed2000

Soluble interleukin-6 receptor (sIL-6R) makes IL-6R negative T cell line respond to IL-6; it inhibits TNF production.

The receptor for interleukin-6 (IL-6) consists of two subunits: a ligand specific IL-6Ralpha and gp130 that is responsible for signal-transduction. A soluble form of the ligand specific chain was described that when complexed to IL-6 is capable of binding to the membrane-bound gp130 subunit and thus can elicit signal-transduction. This soluble receptor can act on cells that express only the gp130 but not the ligand-specific subunit of the IL-6R. This phenomenon, called trans-signaling, introduced a novel aspect of cytokine action. In this study we examined the response of Jurkat cells, that are known not to express IL-6Ralpha, to IL-6, the soluble IL-6 receptor (sIL-6R) and a covalent complex of IL-6 and sIL-6R termed Hyper-IL-6. We studied the expression of tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma). The complex of IL-6+sIL-6R and Hyper-IL-6 inhibited significantly the production of TNF in a gp130-dependent manner, whereas no differences in IFN-gamma expression were found. IL-6 and sIL-6R alone were not effective. Because we did not detect major differences in the TNF mRNA levels upon treatments, we conclude that the inhibition of TNF production should occur at the post-transcriptional level. These results provide another example of trans-signaling and underline the physiological importance of sIL-6R, and in the case of Hyper-IL-6 its possible therapeutic application can also be considered.

Antigens, CD↗
PubMed2000

[Dermatomyositis: clinical study of 34 patients].

Clinical data of 34 patients with DM, who have been treated during the years 1971 and 1998 were evaluated. 79% of the patients (27 patients) were female, 21% of them (7 patients) were male. 59% of the patients (20 pts) were between the ages of 41 and 50 years. The characteristic heliotrop rash were observed in 26 patients, Gottron's papules in 20 patients, poikiloderma in 2 patients, calcification, ulcers, Raynaud syndrome in 1 patient. 3 of the 34 patients presented with strongly itching erythematopapulosus symptoms, most prominently on the scalp. Cardiac involvement were present in 10 patients (29%), lung involvement in 8 patients (23%), gastrointestinal complaints in 11 patients, dysphagia, dysphonia in 4 patients, joint pain in 5 patients. Overlap syndrome--scleroderma-dermatomyositis, SLE-dermatomyositis--was present in 2 patients. 9 of the 34 patients (26%) suffered from malignant tumours: gastric, breast, lung, epipharynx carcinoma, malignant melanoma. 13 of the 34 patients have been treated with corticosteroids together with immunosuppressor agents, in most cases azathioprin was administered. Cyclosporin was given in 7 cases, chloroquine in 2 cases.

Adult↗
PubMed2000

Distribution of Q188R and N314D mutations in the Hungarian galactosemic population.

The most common causes of galactosemia are mutations of the gene coding galactose-1-phosphate uridyltransferase. Since genotype may correlate with the outcome of the disease, and probably not all of the naturally occurring disease associated mutations are described, characterization of the genotypes in different galactosemic populations are in progress. So far the most extensively examined mutations are the Q188R and the N314D. The first one is associated with the classical galactosemia producing a severe clinical picture with an early onset in homozygous patients. The N314D mutation is associated with the Duarte phenotype, which means a milder form of the disease with a later onset of the symptoms. We studied these mutations in the whole Hungarian galactosemic population by PCR and restriction analysis. We have found the frequency of the Q188R mutation at 33.3%, and the N314D mutation at 11.1%. These results differ from other published data in any other populations. Since the incidence of the disease is the same in Hungary as in other European countries, our study suggests that it is worth to investigate for other mutations in the Hungarian population, of which frequency should be consequently higher.

Amino Acid Substitution↗
PubMed2000

Leishmania tarentolae: a parallel isolation of cytochrome bc(1) and cytochrome c oxidase.

A rapid and simple method which allowed for a parallel isolation of cytochrome c reductase (cytochrome bc(1) ) and cytochrome c oxidase from kinetoplast-mitochondria of Leishmania tarentolae was developed. The method involved the lysis of kinetoplasts with dodecyl maltoside in the presence of 260 mM NaCl, followed by purification of bc(1) complexes on DEAE-sepharose CL-6B. The oxidase which was found in the flow-through fractions of the first chromatographic step was diluted and then repurified on a similar DEAE-sepharose column. The investigated properties of the isolated cytochrome c oxidase and reductase, such as their absolute and difference spectrum absorption maxima, heme content, specific activity, and subunit composition, confirm the usefulness of this method for obtaining highly active preparations of the enzymes.

Amino Acid Sequence↗
PubMed2000

Mitochondria--tool for taxonomic identification of yeasts from Saccharomyces sensu stricto complex.

Mitochondrial genomes of Saccharomyces and close relatives previously used for transplacement of mitochondria to S. cerevisiae were examined. The origins of replication in mitochondrial DNA, the presence of nuclear and mitochondrial polymorphic loci and the ability to produce mitochondrial respiration-deficient mutants were used to reclassify some collection yeasts and to assign others into four separate subgroups. The first included isolates identical to Saccharomyces cerevisiae (S. italicus, S. oviformis, S. chevalieri and S. capensis) which possess 5 or more replication origins. The second group consists of S paradoxus (var douglasii) mitochondrial genome with the equal number of ori sequences but incompatible mitochondria. The third group represents Saccharomyces sensu stricto petite-positive species (S. carlsbergensis, S. heterogenicus, S. uvarum, S. willianus) with 1-2 origins of replication significantly different from S. cerevisiae. In addition, the locus between tRNA(fMet) and tRNA(Pro) is about one-half of the 1400 bp members of S. cerevisiae complex. The last group includes isolates that do not belong to Saccharomyces sensu stricto group as they are petite-negative and devoid of any S. cerevisiae-like replication origins.

DNA, Fungal↗
PubMed2000

Unique morphological alterations of the HTLV-I transformed C8166 cells by infection with HIV-1.

C8166 cells express T lymphocyte markers, a monocyte-specific esterase, taxpolypeptide of HTLV-I. In spite of this transactivator, their HIV-1 yield is low. Their culture conditions were modified, and infected cells were immobilized on a poly-L-lysine sheet under semisolid overlays to study their phenotypic alterations and HIV-1 production by microscopy and electron microscopy. Another lymphoid cultures (MT-4, CEM, CEM-ss, AdCEM) similarly treated were infected with either HIV-1/RF or IIIB. Specificity of HIV-1 was compared to the effects of vesicular stomatitis virus (VSV). Unlike other cultures, HIV-1/RF infected C8166 cells in Eagle s MEM exhibited surface projections resembling hairy leukemia cells, which was followed by balloon degeneration and apoptosis. Immobilized HIV-1 infected cultures formed flat syncytia with several interdigitating dendritic projections. Syncytia shrunk with condensed nuclear material and axon-like filaments characteristic for infected macrophages. VSV induced enlargement and necrotic lysis of all cell types. Early postinfection with HIV-1, electron microscopy revealed irreversible membrane fusion above cell nuclei, and transient fusion between filaments. Transient presence of coated vesicles containing intact HIV-1 particles, Birbeck granule-like structures of Langerhans cells, fibrillar-lamellar structures resembling hairy leukemia or Sézary cells were detected. Late postinfection, high proportion of HIV-1 bud from polarized cytoplasm was empty particle, while that bud and entrapped in cytoplasmic vacuoles contained two or multiple cores in a fused envelope. The effect of early gene products of HIV-1 on HTLV-I and C8166 cells might elicit their latent potentials for monocyte or interdigitating dendritic cells, while in the later phase HTLV-I products might alter HIV-1 virion assembly.

Apoptosis↗