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Biomedical subjects

E Ujhelyi

Publications and source records attributed to E Ujhelyi.

At least 19 recordsLinked to original sources

Injecting equipment sharing and perception of HIV and hepatitis risk among injecting drug users in Budapest.

In central European states, rates of HIV among injection drug users (IDUs) have been low although Hepatitis C (HCV) infection is widespread. The goal of our study was to assess HIV infection, risk perceptions and injecting equipment sharing among IDUs in Budapest, Hungary. Altogether 150 IDUs were interviewed (121 structured interviews between 1999 and 2000 and 29 ethnographic interviews between 2003 and 2004). The majority of them injected heroin (52% and 79%) and many injected amphetamines (51% and 35%). One person tested positive for HIV. Two thirds (68%) shared injecting equipment (syringes, cookers and filters). Some participants said they shared syringes because they were not carrying them for fear of police harassment and that they reused filters as a backup drug supply. In multivariate analysis, sharing of injecting equipment was associated with higher perceived susceptibility to HIV/AIDS, lower self-efficacy for sterile equipment use, higher motivation to comply with peer pressure to use dirty injecting equipment and with having a criminal record. The high levels of injecting risk-behaviors found in this study are a cause for serious concern. Interventions for HIV-prevention need to address not only sharing syringes but also sharing and reusing of other injecting equipment and drug filters.

Adolescent↗

Specialization of midgut cells for synthesis of male isoprenoid pheromone components in two scolytid beetles, Dendroctonus jeffreyi and Ips pini.

Endodermal or midgut cells have only recently been recognized as the site of pheromone synthesis in bark beetles. Midgut cells are not only specialized for digestion, but they have also been recruited to form isoprenoid compounds that function as pheromone components in Ips pini and Dendroctonus jeffreyi. Male bark beetle midgut cells are competent to produce isoprenoid pheromones after feeding or stimulation by juvenile hormone (JH) III. Competent midgut cells share many ultrastructural features with cells that do not secrete isoprenoid pheromone, but they are distinguished from these by abundant and highly ordered arrays of smooth endoplasmic reticula. During secretion, both midgut cells that produce pheromone and cells that do not are characterized by the presence of apical extrusions (apocrine secretion) rather than the presence of vesicles that fuse with the apical membrane and undergo exocytosis (eccrine secretion). Pheromone-producing cells of the midgut do not represent a population of cells that are distinct from cells involved in digestion. All, or most, midgut cells of male I. pini and D. jeffreyi can secrete pheromones as well as digestive enzymes.

Animals↗

Sexual activity and condom use among Eastern European adolescents--the Study of Hungarian Adolescent Risk Behaviours.

While rates of HIV and STD infection in Eastern Europe are increasing rapidly, little is known about sexual behaviour, including condom use, among Eastern European youths. The Study of Hungarian Adolescent Risk Behaviours was designed to assess the knowledge, attitudes, and behaviours of adolescents studying in secondary schools in Budapest, Hungary. Students (n =3486) in a random sample of public secondary schools completed a self-administered questionnaire, including measures of sexual activity and condom use. Thirty-eight percent of students reported ever having had vaginal intercourse. Condom use by those reporting having had sex in the past five weeks was classified as consistent/every time (40%); irregular (25.6%); and none (34.3%). Multivariate analysis revealed positive opinions about condoms, fear of AIDS, and initiation of condom use by both partners to predict more frequent condom use. Implications for targeted AIDS/STD education and prevention among adolescents are discussed.

Acquired Immunodeficiency Syndrome↗

[Prinzmetal angina pectoris associated with 3rd degree atrioventricular block].

The authors report on the case of a 61 year-old female patient who was repeatedly taken to hospital because of chest pain and temporary loss of consciousness. During her hospitalization there was no ST elevation on the ECG, sinus bradycardia, other times atrial fibrillation was detected. The diagnosis was made by Holter monitoring three years after the onset of complaints. At this time chest pain set in after midnight, which was followed by loss of consciousness. Significant ST elevation and IIIrd degree AV block were detected. The coronarography showed non-significant coronary stenosis. According to the vasospastic patomechanism nitrate, calcium antagonist and acetylsalicylic acid therapy was administered and because of the complete AV block leading to syncope a VVI, M pacemaker was implanted. During the two years passed since the implantation of the pacemaker the patient had chest pain only once and it was not accompanied by syncope.

Adams-Stokes Syndrome↗

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↗

Characterization of extended-spectrum beta-lactamase (TEM-52)-producing strains of Salmonella enterica serovar typhimurium with diverse resistance phenotypes.

Two Salmonella enterica serovar Typhimurium strains from different clonal origins, both producing an extended-spectrum beta-lactamase (TEM-52), were isolated from a patient. This enzyme was encoded on a single plasmid and was found at very low levels in one strain, while being encoded on multiple plasmids and in multiple different EcoRI fragments in the other strain.

Drug Resistance, Microbial↗

Strong correlation between the complement-mediated antibody-dependent enhancement of HIV-1 infection and plasma viral load.

OBJECTIVE: We have previously demonstrated that complement-mediated antibody-dependent enhancement (C-ADE) of HIV-1 infection correlates with accelerated immunosuppression and disease progression in HIV-1-infected individuals. In the present work the relationship between C-ADE and plasma HIV-1 RNA concentrations was studied to determine the effect of C-ADE on viral replication. METHODS: Three studies were performed: (a) C-ADE and HIV-1 RNA concentrations were determined in the serum and plasma aliquots taken at the same time from 98 HIV patients, mostly in the advanced stage of the disease; (b) the above two parameters as well as HIV enzyme-linked immunosorbent assay (ELISA)-reactive antibodies (Abbott HIV 1/2 test), and p24 antigen levels (Abbott antigen test; Abbott, Delkenheim, Germany) were determined in four seroconversion panels purchased from the Boston Biomedica firm; (c) changes of HIV-1 RNA concentration and C-ADE during a 17 month follow-up period were determined in 18 HIV-infected patients. C-ADE was measured by the method previously established in our laboratories. The results were expressed by an enhancement/neutralization index (E/NI). HIV-1 RNA levels were determined with the Amplicor monitor kit (Roche, Basel, Switzerland), and in some experiments with the nucleic acid sequence based amplification (Organon Teknika, Turnhout, Belgium) kits. RESULTS: (a) We found a highly significant (P<0.0001) positive correlation between E/NI values reflecting the extent of HIV-1 infection enhancement and plasma HIV-1 RNA levels. Both E/NI and HIV-1 RNA levels negatively correlated to the CD4 cell counts. (b) C-ADE was first detected just before, or concomitantly with, seroconversion in 4/4 seroconversion panels. (c) Both E/NI values and HIV-1 RNA levels significantly (P<0.001) increased during a 17 month observation period in 18 HIV-infected patients. CONCLUSION: We found strong association between the extent of the complement-mediated antibody-dependent enhancement of HIV-1 infection and the plasma viral load in HIV patients. On the basis of these findings, C-ADE correlates with HIV replication in vivo, and potentially contributes to the progression of HIV disease.

Adolescent↗

C1q autoantibodies in HIV infection: correlation to elevated levels of autoantibodies against 60-kDa heat-shock proteins.

Antibodies to solid phase C1q (C1qAb) were determined in 295 serum samples from 132 HIV-infected subjects and in sera from 140 HIV-seronegative healthy individuals as control. An ELISA method applied for the determination of C1qAb in other diseases was used. In part of these sera, other autoantibodies (antibodies reacting with 60-kDa human heat shock protein (hsp60) or mycobacterial hsp65; IgA and IgG class antibodies against the Fab and F(ab')2 moieties of IgG) as well as complement-mediated antibody-dependent enhancement/neutralization (C'-ADE) were also determined. Increased amount of C1qAb was found in HIV-infected subjects as compared with HIV-seronegative controls (P = 0.0138). In 17 of 132 (13.0%) seropositive individuals but only in 7/140 (5.0%) samples from the controls, the amount of C1qAb exceeded the upper limit (95th percentile) of the normal values (P = 0.031). The amount of C1qAb significantly decreased during a follow-up period of 65 months. C1qAb levels were found to strongly correlate to hsp60/65 autoantibodies but did not correlate or only weakly correlated to the amount of anti-Fab or anti-F(ab')2 autoantibodies measured in the same serum samples. Anti-C1q antibodies recognized the solid phase hsp60/65. Three predicted epitope regions of M. paratuberculosis hsp65 were able to bind efficiently C1q antibodies. An inverse correlation was found between C1qAb and C'-ADE, neutralization was more frequent in the sera with detectable C1qAb, whereas sera without C1qAb more likely enhanced HIV infection in vitro.

Antigens, Bacterial↗

Production and flow cytometric application of a monoclonal anti-glucocorticoid receptor antibody.

Detection and monitoring the expression and level of intracellular glucocorticoid receptor (GCR) is necessary in many clinical and experimental situations. Binding of radioactive steroids (3H dexamethasone) to the cytosolic fractions of cells has been recently used. However, it is an expensive, time-consuming technique difficult to use in routine diagnostics. In this article we describe a novel, simple method for GCR detection, using a FITC-conjugated anti-GCR monoclonal antibody (mAb) for flow cytometric measurements in permeabilized cells. The monoclonal antibody was raised against a conserved sequence (150-176 amino acids) of the regulatory part of the receptor. Synthetic peptide (called APTEK-26) fragment of the receptor conjugated to different carriers (TG, BSA) was used for immunization and screening of the hybridomas. The a-GCR 8E9, 3C8 and 5E4 clones (IgG1) were further characterized by immunoserological methods for their reactivity against overlapping synthetic peptide fragments of the receptor and by Western blot technique on cytosolic fraction of HEP G2 cells (containing the GCR). Furthermore the mAbs could be used for the FACS based detection of GCR, despite its low number of antigen structure within the cells. Solving the problem of nonspecific binding of the secondary antibodies we used our high affinity IgG1 a-GCR mAbs directly labeled with the fluorescent dye FITC. The fluorescent labeling of the GCRs in HEP G2 cell line and human peripheral blood mononuclear cells (PBMC) were demonstrated by flow cytometric analysis after fixation with 4% paraformaldehyde and permeabilization with saponin. Competition with molar excess of unlabelled antibodies and with the GCR peptide fragment confirmed the specific binding of the 8E9 and 5E4 mAbs to the GCRs. Monitoring the GCR level by flow cytometry would be useful in clinical diagnostics, e.g., in steroid-treated patients and in steroid-resistant states.

Amino Acid Sequence↗

Remodeling of neural, glial, and tracheal cell populations in the developing manduca wing

This ultrastructural examination of sensory nerves of the Manduca wing has revealed that extensive remodeling occurs among insect sensory neurons and their associated glial cells between pupation and adult emergence. Systematic counts of axons in particular wing nerves throughout adult development have shown that a decrease in axon number per nerve occurs after day 6. The neurons and glial cells that die are believed to be cells present at pupation that have no apparent sensory function but that probably function as guidance scaffolding for neurons and glia that are born after pupation. Despite the loss of several axons from each wing nerve, these nerves continue to grow in diameter during the latter half of adult development as some of the surviving axons increase severalfold in diameter. Each growing wing nerve in turn apparently functions as a scaffold for the proximal to distal growth of adult tracheae. A correspondence exists between adult nerve pathways and adult tracheal pathways, with each trachea maintaining intimate contact with a wing nerve along its entire length.

Journal Article↗

Mannan-binding lectin serum concentrations in HIV-infected patients are influenced by the stage of disease.

Serum concentrations of mannan-binding lectin (MBL) were determined in the sera of 67 HIV-seropositive patients in different stages of HIV disease and in the sera of 75 HIV-seronegative healthy individuals. In the asymptomatic (AS) HIV-infected persons MBL concentrations were found to be significantly (P < 0.05) lower than in the HIV-seronegative controls, whereas in the AIDS patients they were not. Very low (< or = 25 ng/ml) MBL serum concentrations were detected in 5/19 (26.3%) and 7/75 (9.3%) of the AS HIV-seropositive and HIV-seronegative individuals, respectively (P = 0.06). In the sera of the HIV-infected patients, MBL levels positively correlated to the neopterin concentrations (Spearman correlation coefficient, 0.401, P = 0.0009) while they negatively correlated to the percentage (-0.447, P = 0.0011) and absolute number (-0.453, P = 0.0012) of the CD4+ lymphocytes. These observations indicate that MBL level, which is under strict genetic control, may influence the susceptibility to HIV infection and the progression of HIV disease.

Blood Proteins↗

Genetic regulation of the impaired immune response to hepatitis-B vaccine associated with low TCR density in end stage renal disease patients: contribution of complement C4 and factor B alleles.

We have studied the relationship between T-cell receptor (TCR) density, genetic factors and the specific immune response in 153 end stage renal disease (ESRD) patients on haemodialysis immunised with HBsAg vaccine. One-hundred and nineteen patients raised a protective (> 10 U/ml) antibody response to hepatitis-B vaccination (responder, R), while 34 patients were found to be non-responders (NR). The density of the T-cell receptors was determined by flow cytometry. Proliferation of the T-cells induced by autologous monocytes presenting HBsAg was also measured and expressed as a stimulation index (SI). MHC class I, II and III alleles of the patients were also determined. The densities of TCR/CD3 receptors in NR patients were found to be significantly decreased as compared to the R patients (189 +/- 22 vs. 282 +/- 58 arbitrary units, P = 1.3 x 10(-7). TCR/CD3 receptor densities were found to be strongly associated (Spearman correlation coefficient: 0.84, P < 0.000001) with the SI values. Both parameters were found to be under dual genetic control: (a) very low density of the TCR/CD3 receptors and very low SI were found mainly in NR patients carrying HLA-A1, HLA-B8 and HLA-DR3 alleles; and (b) TCR/CD3 densities and function in R group were found to be significantly lower in carriers than in non-carriers of two MHC class III complement protein alleles: C4A*6, and Bf*F. Non-responsiveness to hepatitis-B vaccination was found to be associated with extremely increased neopterin levels. These findings indicate that both genetic and acquired factors contribute to the hepatitis-B vaccination failure in ESRD patients.

Alleles↗

Two parallel routes of the complement-mediated antibody-dependent enhancement of HIV-1 infection.

OBJECTIVE: To study the mechanism of the complement-mediated antibody-dependent enhancement (C'-ADE) of HIV infection which may play a significant role in the progression of HIV-disease. METHODS: In vitro complement activating and complement-mediated HIV-infection enhancing abilities of three human anti-gp41 monoclonal antibodies (MAb) were tested. C'-ADE was estimated using HIV-1IIIB and CR2 (CD21)-carrying MT-4 target cells. Normal human serum (NHS), purified C1q, C1q-deficient (C1qD) and C2-deficient (C2D) human sera were applied as complement sources. RESULTS: All MAb mediated increased C1q binding to solid-phase gp41. All MAb had a marked dose-dependent and strictly complement-mediated HIV-infection enhancing effect. Mixtures of the MAb with purified C1q also significantly increased HIV-1 infection. C1qD serum had a markedly lower enhancing effect than NHS, which could be raised to normal level by addition of purified C1q. Pretreatment of the target cells with anti-CR2 antibodies only partially inhibited the enhancing effect of the MAb plus normal human serum. CONCLUSION: These novel findings indicate that besides the well-known facilitation of entry of HIV-1 by the interaction between virus-bound C3 fragments and CR2 present on the target cells, fixation of C1q to intact virions also results in an enhanced productive HIV-1 infection in the MT-4 cell cultures.

Antibodies, Monoclonal↗

Longitudinal immunological follow-up of HIV infected haemophiliacs in Hungary.

Twenty-five haemophiliacs who had been infected with HIV in 1982 or 1983 were followed up from 1986 to 1993. The absolute number of the CD4+ and CD8+ cells, neopterin levels and more recently the percentage of activated, DR+ T lymphocytes were determined twice a year. In most patients a permanent decline in the CD4+ cell count was observed whereas in two HIV-infected haemophiliacs the absolute number of CD4+ cells did not change during the observation period. In these long-term non-progressor patients no clinical symptoms and no increased neopterin levels were observed. T cells subset and neopterin measurements were found to predict the development of AIDS. AIDS developed only in those patients who exhibited both a CD4+ cell count of < 350/microliter and a serum neopterin concentration of > 20 nmol/l. A negative correlation was observed between the percentage of activated. DR+ T lymphocytes and the CD4+ cell counts.

Adolescent↗

Interaction of complement and specific antibodies with the external glycoprotein 120 of HIV-1.

Previously we have investigated the interaction of human complement as well as one polyclonal and three human monoclonal antibody preparations with the human immunodeficiency virus type-1 (HIV-1) transmembrane recombinant glycoprotein (rgp41). A strong competition was found between the antibodies and deposited complement proteins for the same binding sites located within the immunodominant region of rgp41. The aim of the present experiments was to see if the same type of antibody-complement-HIV-1 interactions could be observed with the outer envelope glycoprotein (rgp120) of HIV-1. Three different glycosylated rgp120 preparations, as well as a synthetic peptide corresponding to the V3 loop of the MN strain, were adsorbed to enzyme-linked immunosorbent assay (ELISA) plates and incubated with mixtures of anti-rgp120 antibodies and normal human serum (NHS) as a complement source. Fixed complement proteins and antibodies were detected with specific, peroxidase-labelled antibodies against different complement proteins (C1q, C4b, C3b) and the gamma-chain of antibodies. In the absence of anti-rgp120, high amounts of C3 were deposited to each rgp120 preparation tested (including the V3 peptide) but significant differences in the amounts of bound C1q and C4b were observed. Using sera deficient in different complement proteins, we found that both the classical and the alternative pathways contributed to the C3 binding to rgp120. Addition of specific antibodies did not increase complement activation by rgp120 and only in the case of a monoclonal antibody to the V3-loop could we see complement-dependent inhibition of antibody binding.

Antibodies, Monoclonal↗

Comparative study of antibodies that are associated with disease progression in HIV disease.

Two types of antibodies which previously were found to be inversely associated with CD4+ cell counts and which may contribute to the progression of HIV disease were measured in parallel in 55 serum samples of 7 longitudinally tested HIV-infected patients (4 homosexual men, 3 haemophilic men) and in 15 serum samples from 15 patients with advanced AIDS. HIV-infection enhancing antibodies were determined in the presence of near-physiologic human complement concentration using a complement receptor type 2 (CR2) carrying HIV-target cell line. IgG and IgA class autoantibodies directed against human IgG-Fab fragments were measured in specific ELISA assays. In agreement with our previous studies obtained in HIV-seropositive haemophilic patients, significant negative correlations were found between CD4+ cell counts and IgG anti-Fab and IgA anti-Fab antibodies (Spearman correlation coefficient r = -0.587, P < 0.0001; and r = -0.269, P = 0.024, respectively). A significant positive correlation was observed between complement-dependent enhancing antibodies and IgA anti-Fab antibodies (r = 0.408, P = 0.003), whereas the correlation with IgG anti-Fab antibodies was only weak (r = 0.288, P = 0.034). Serum samples with high titres of complement-dependent enhancing antibodies had almost 3 times higher IgA anti-Fab autoantibody activity than sera with low titres (P = 0.0038). Our findings indicate that the two disease markers in HIV disease, enhancing antibodies and autoantibodies directed against the Fab moiety of IgG, are not identical. However, anti-Fab antibodies may contribute to complement-dependent HIV infection enhancement.

Acquired Immunodeficiency Syndrome↗