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Biomedical subjects

J Szabó

Publications and source records attributed to J Szabó.

At least 19 recordsLinked to original sources
PubMed1999

Differential patterns of interaction between HIV type 1 and HTLV type I in monocyte-derived macrophages cultured in vitro: implications for in vivo coinfection with HIV type 1 and HTLV type I.

The interaction between human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia-lymphoma virus type I (HTLV-I) has generated substantial interest. However, there is disagreement on the in vivo consequences of the double infection. We investigated the interactions between HIV-1 and HTLV-I in monocyte-derived macrophages cultured in vitro. For study, the T cell-tropic strain IIIB and the macrophagetropic strain Ada-M of HIV-1 were used. The HTLV-I was prepared from the supernatants of the virus-producing MT-2 cell line. We found that coinfection of macrophages with T cell-tropic HIV-1 and HTLV-I significantly enhanced HIV-1 replication, whereas double infection of the cells with macrophage-tropic HIV-1 and HTLV-I resulted in marked upregulation of HTLV-I production. Stimulatory interactions between HIV-1 and HTLV-I were mediated by their trans-acting proteins. Results of study on nuclear translocation of proviral DNA showed that the tax gene product of HTLV-I was able to facilitate the nuclear import of the reverse-transcribed HIV-1(IIIB) DNA. In contrast, the HIV-1 Tat protein did not increase the intranuclear trafficking of HTLV-I DNA, which suggests another mechanism for HTLV-I enhancement by the tat gene product. In conclusion, this study provides possible mechanisms whereby coinfection of an individual with HIV-1 and HTLV-I may influence the clinical outcome of double infection.

Cell Nucleus↗
PubMed1999

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↗
PubMed1999

[Management of craniofacial fractures with titanium mini-plate osteosynthesis and primary bone transplantation].

The frontobasal traumatic lesions are often combined with several type of midface fractures therefore the authors adopted the craniofacial injury definition. In the years 1995-1997, 534 patients with head trauma were operated on by maxillofacial surgeon and neurosurgeon of which 35 (6.5%) cases showed concomitant combined frontonaso-orbital-skull base involvement. In the complex management of the severe craniofacial lesions the cooperative team-work of maxillofacial surgeon, neurosurgeon, otolaryngologist and ophthalmologist is required. Stabilized midface and the "watertight" dura closure or plasty are basically important conditions for the ceasing of cerebrospinal fluid leak. In the instance of optic nerve lesion the exploration and decompression within the eight hours is mandatory by transcranial-subcranial approach. At their cases authors preferred the early, definitive one-stage management with step-by step titanium miniplate reconstructive osteosynthesis and primary bone grafting correct bony restoration could be achieved. According their experiences of new treatment method with definitive one-stage management of complex craniofacial injuries they decreased the incidence of postoperative complications, the time of hospitalisations obtained optimal functional and cosmetic results.

Adult↗
PubMed1999

Ethanol's effect on rat pituitary adrenal axis is prevented by purine metabolic pathway inhibitors.

This study investigated the in vitro dose effects of ethanol (EtOH), adenosine (ADO), and urate (URA) on the basal and CRF stimulated ACTH production of pituitary tissue culture (PTC). Furthermore, the effects of low (LE = 0.5 g/kg bodyweight) and high (HE = 2.5 g/kg bodyweight) concentrations of EtOH were tested in rats on plasma ACTH and corticosterone concentration (PCC), with or without the following ADO metabolic pathway inhibitors: 6-mercaptopurine (6MP) (salvage pathway) and purpurogallin (PPG) (xanthine dehydrogenase). EtOH at 0-50 mM does not increase the in vitro basal or CRF (10-7 M) stimulated ACTH secretion in PTC; in fact doses up to 20 mM tended to be inhibitory. ADO significantly increased only basal ACTH secretion whereas URA increased both basal and CRF-stimulated ACTH secretion. Pretreatment with PPG or 6MP + PPG significantly increased both in vivo ACTH and PCC over control values in rats. HE versus LE significantly increased ACTH and PCC in the control (H2O) and 6MP pretreated groups whereas in the PPG pretreated animals, only ACTH was increased significantly by HE. However, combined pretreatment with 6MP + PPG prevented the effect of HE on ACTH and PCC. The current experiment suggests that purine metabolism is involved in ethanol's effect on the hypothalamic-pituitary-adrenal axis.

Adenosine↗
PubMed1999

Placental macrophage contact potentiates the complete replicative cycle of human cytomegalovirus in syncytiotrophoblast cells: role of interleukin-8 and transforming growth factor-beta1.

Although syncytiotrophoblast (ST) cells can be infected by human cytomegalovirus (HCMV), in vitro studies have indicated that ST cells do not support the complete viral reproductive cycle, or HCMV replication may occur in less than 3% of ST cells. The present study tested the possibility that placental macrophages might enhance activation of HCMV carried in ST cells and, further, that infected ST cells would be capable of transmitting virus to neighboring macrophages. For this purpose, we studied HCMV replication in ST cells grown alone or cocultured with uninfected placental macrophages. Our results demonstrated that HCMV gene expression in ST cells was markedly upregulated by coculture with macrophages, resulting in release of substantial amounts of infectious virus from HCMV-infected ST cells. After having become permissive for viral replication, ST cells delivered HCMV to the cocultured macrophages, as evidenced by detection of virus-specific antigens in these cells. The stimulatory effect of coculture on HCMV gene expression in ST cells was mediated by marked interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1) release from macrophages, an effect caused by contact between the different placental cells. Our findings indicate an interactive role for the ST layer and placental macrophages in the dissemination of HCMV among placental tissue. Eventually, these interactions may contribute to the transmission of HCMV from mother to the fetus.

Antigens, Viral↗
PubMed1999

Role of interleukin-8 and transforming growth factor-beta1 in enhancement of human cytomegalovirus replication by human T cell leukemia-lymphoma virus type I in macrophages coinfected with both viruses.

Human cytomegalovirus (HCMV) is one of the most frequent opportunistic agents causing severe illness in chronic human T cell leukemia-lymphoma virus type I (HTLV-I) infection. Our previous studies have shown that coinfection of macrophages with HCMV and HTLV-I significantly enhances HCMV replication, resulting in release of infectious HCMV from dually infected cells. We found that double infection of macrophages with HCMV and HTLV-I induced a rapid production of substantial amounts of interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1). Results of transfection studies demonstrated that the tax gene product of HTLV-I was able to induce secretion of IL-8 and TGF-beta1. In addition to its cytokine-inducing effect, the Tax protein could interact with HCMV synergistically to result in production of much higher levels of IL-8 and TGF-beta1 than expected on the basis of their separate activities. Treatment of dually infected macrophage cultures with neutralizing antibodies to IL-8 and TGF-beta1 led to a nearly 1000-fold decrease in release of infectious HCMV from coinfected cells. Similar results were obtained when anti-IL-8 and anti-TGF-beta1 treatments were combined in macrophage cultures transfected with the tax gene before HCMV infection. Our results suggest that the stimulatory effect of HTLV-I Tax protein on HCMV replication in coinfected macrophages is largely mediated by high levels of IL-8 and TGF-beta1 production.

Antibodies, Monoclonal↗
PubMed1999

Disturbed LDL and scavenger receptor functions in monocytes from chronic haemodialysed patients.

BACKGROUND: The most frequent complication in patients with end-stage renal failure on chronic haemodialysis (HD) treatment is atherosclerosis, i.e. the different forms of heart and vascular diseases. The complete disorder of serum lipid and lipoprotein patterns is well demonstrated, whereas our knowledge about the low-density lipoprotein (LDL) and scavenger receptor expression and function are poorly understood. METHODS: In our current work, LDL and scavenger receptor expression and functions were simultaneously studied in monocytes obtained from 15 healthy male control subjects and from 11 chronic HD male patients applied with (125)I-labelled LDL, isolated from healthy volunteers. To study the scavenger LDL receptors, labelled acetylated LDL (acLDL) was used. RESULTS: LDL binding to the monocytes of the HD-group was found to be decreased in comparison to that of the controls. As a result, the 50 microg LDL protein-induced inhibition of endogenous cholesterol synthesis was also diminished. In contrast, acLDL binding was greatly increased, though it could trigger only a low apoE synthesis. Consequently the number of cholesterol inclusions in monocytes was increased. CONCLUSIONS: The disturbed expression and function of LDL and scavenger receptors both may play significant roles in pathogenesis of cardiovascular complications in chronic HD patients. Based on our present results, it can be assumed that dysfunction of scavenger receptors is at the centre of cardiovascular complications of HD patients with renal failure.

Anticholesteremic Agents↗
PubMed1999

Antineutrophil cytoplasmic antibodies and other immunologic abnormalities in patients with habitual abortion.

PROBLEM: The immunologic mechanisms of pregnancy loss in habitual aborters with antiphospholipid and antinuclear antibodies have not been fully clarified. The possible association of antineutrophil cytoplasmic antibodies (ANCAs) with recurrent miscarriage was examined. METHOD OF STUDY: In a prospective, controlled trial of 59 women with recurrent abortion, the prevalence of pANCA (antimyeloperoxidase), cANCA (antiproteinase-3), and immunoserologic abnormalities of systemic lupus erythematosus (SLE) anti double-stranded DNA, anti-SSA, anti-SSB, anti-U1RNP, anti-Sm, anticardiolipin and antinuclear antibodies, LE-cell, lupus anticoagulant, and complement-3 were investigated. RESULTS: pANCA occurred in 2, and cANCA in 6 of 59 case patients, but neither was observed in the controls (P = 0.09 for cANCA). cANCA levels were significantly higher in patients than in controls (P = 0.028). Six recurrent aborters were identified as having a group of immunoserologic abnormalities characteristic of SLE. CONCLUSIONS: Immunologic mechanisms detectable in SLE may operate in a subgroup of habitual aborters with suspected immunologic cause. ANCAs occur more frequently in patients with recurrent miscarriage than in controls.

Abortion, Habitual↗
PubMed1999

Altered signal pathway in granulocytes from patients with hypercholesterolemia.

In the present study the signal transduction of the formyl-Met-Leu-Phe receptor was studied in granulocytes obtained from control subjects and patients with elevated low density lipoprotein levels. According to our results, 10 nm formyl-Met-Leu-Phe in control cells activates phospholipase C inducing a pronounced inositol phosphate production followed by a Ca(2+) signal from intracellular pools. The pertussis toxin-sensitive O(2)(-) generation and leukotriene synthesis were moderate. In contrast, in granulocytes from hypercholesterolemic patients, formyl-Met-Leu-Phe triggered an intensive pertussis toxin-insensitive oxidative burst and leukotriene synthesis. The inositol trisphosphate and Ca(2+) signals were decreased significantly in granulocytes of hypercholesterolemic patients and seem to be dependent on the extracellular Ca(2+) content. Furthermore, in the resting granulocytes of hypercholesterolemic patients the [Ca(2+)]i and the membrane-bound protein kinase C activity were higher than in controls, the time of normalization after the low Ca(2+) signal was delayed, while the membrane fluidity was decreased. Our results suggest that in these ex vivo experiments, the high level of circulating low density lipoprotein in patients can affect the membrane composition of granulocytes leading to altered signal transduction by the formyl-Met-Leu-Phe receptor, to altered Ca(2+) pump-activity, and protein kinase C translocation.

Calcium Signaling↗
PubMed1998

[Feto-maternal transfusion following cordocentesis].

Invasive intrauterine diagnostic procedures may be followed by feto-maternal transfusion. The authors studied the feto-maternal transfusion after cordocentesis. 199 women underwent fetal umbilical cord blood sampling for fetal karyotyping in weeks 15-26. Maternal serum alpha-fetoprotein level was measured before and after the procedure. The data were statistically analysed by multiple regression analysis and the paired and unpaired Student's t-tests. Twenty percent of more maternal serum alpha-fetoprotein level increase was observed in 73 (36.7%) women. Maximum feto-maternal transfusion was 0.684 ml. The average feto-maternal transfusion was 0.045 ml. No fetal exsanguination was observed. Positive correlation was found between bleeding time after cordocentesis (p = 0.0171) and feto-maternal transfusion as well as the duration of the procedure (p = 0.0275) and feto-maternal transfusion. Negative correlation was found between the amount of fetal blood sample and feto-maternal transfusion (p = 0.0431). The puncture site also influenced feto-maternal transfusion. If the cordocentesis has been performed at the insertion of the cord the feto-maternal transfusion was less than at the free floating umbilical cord (p = 0.0293). Higher feto-maternal transfusion was seen more often after transplacental cordocentesis (p = 0.002). These data suggest that fetomaternal transfusion in the indicator of the difficulty of the procedure.

Cordocentesis↗
PubMed1998

Reciprocal interactions between human cytomegalovirus and human T cell leukemia-lymphoma virus type I in monocyte-derived macrophages cultured in vitro.

Infection of macrophages with human cytomegalovirus (HCMV) has been shown to be nonlytic and exclusively cell associated. Human T cell leukemia-lymphoma virus type I (HTLV-I) is capable of establishing productive infection in macrophages. We studied the interactions between HCMV and HTLV-I in monocyte-derived macrophages cultured in vitro. We found that coinfection of macrophages with HCMV and HTLV-I significantly enhanced HCMV replication, resulting in release of infectious HCMV from dually infected cells. On the other hand, HCMV inhibited HTLV-I replication in macrophages coinfected with both viruses. Reciprocal interactions between HCMV and HTLV-I were mediated by their trans-acting proteins. Results of transfection studies demonstrated that the tax gene product of HTLV-I alone was capable of upregulating HCMV production. In a transient gene expression assay the immediate-early 2 (IE2) protein of HCMV alone could inhibit HTLV-I replication, whereas the IE1 protein, which had no effect by itself, produced a synergistic inhibitory effect together with the IE2 protein. Results from this study suggest that in vivo double infection of macrophages with HCMV and HTLV-I may contribute to the dissemination of HCMV infection in patients suffering from HTLV-I-associated T cell leukemia-lymphoma.

Antigens, Viral↗
PubMed1998

Altered postreceptor signal transduction of formyl-Met-Leu-Phe receptors in polymorphonuclear leukocytes of patients with non-insulin-dependent diabetes mellitus.

The signal transduction of the formyl-Met-Leu-Phe (FMLP) receptor in polymorphonuclear leukocytes (PMNLs) from patients with non-insulin-dependent diabetes mellitus (NIDDM) was compared to that of PMNLs obtained from healthy volunteers. According to our previous studies in this group of patients neither the decrease in insulin binding capacity nor the enhanced insulin-degrading enzyme activity was involved. In control PMNLs, 10 nM FMLP induced a pertussis toxin-sensitive increase in phosphatidyl inositol (PI) cleavage and a subsequent Ca2+ signaling from the intracellular pools. On the other hand, the FMLP-induced protein kinase C (PKC) activation and translocation into the membrane could not be detected in these cells via the measurement of 32P incorporation into histone. In contrast, in PMNLs of this special group of patients suffering from NIDDM the FMLP stimulus produced a significantly low increase in PI cleavage and Ca2+ signaling from the intracellular pools. Moreover, in resting PMNLs of these patients with NIDDM, not only the [Ca2+]i but also the membrane-bound PKC activity was found to be significantly increased. In addition, PKC translocation into the cell membrane of diabetic PMNLs could be further triggered with FMLP as judged by the measurement of 32P incorporation into histone. Based on these results, it appears that the signaling of FMLP receptors in PMNLs of some NIDDM patients may have an alternative pathway through Ca2+ influx from extracellular medium, arachidonic acid cascade, and PKC activation.

Arachidonic Acid↗
PubMed1998

Attitudes of donors towards organ transplantation in living related kidney transplantations.

The demand for transplantation exceeds the availability of cadaveric organs, which is why the importance of living, related kidney transplantation is increasing. In our study we wanted to evaluate the experiences of living related donors (LRD). Between 1973 and 1996, 1325 kidney transplantations were performed at our Department. Of these 1247 were from cadaver donors while 78 were from LRD. We contacted each living donor by post. We carried out a physical examination, laboratory tests, ultrasound and isotope investigations and they were interviewed and completed a questionnaire. Thirty previous kidney donors came to our Department who were all blood relatives of the recipients. In the recipient group, 16 still have a functioning kidney, the average time since transplantation being 8.92 years. The longest kidney survival time is 18 years. All the donors willingly donated their kidney, none was worried about their own health and their only concern was whether the kidney would function or not. Regarding general attitudes towards living related organ transplantation, all were in favour of blood relative donor transplantation and also husband/wife transplantation. Opinions regarding non-related transplantation were more mixed; 63.3% would have given their kidneys to a friend, only 46.6% to a stranger. Almost two-thirds (63.3%) of donors were not in favour of selling and buying organs but, controversially, they would have bought an organ had one been available. All agreed that the donation did not change their general health. In conclusion, the donors of living, related kidney transplantation all agreed that it was a good thing to donate; All confirmed they would go through the same procedure again in order to help. Apart from one person, who emphasised that he is agnostic, all belonged to a Christian religion.

Adolescent↗
PubMed1998

Specific and scavenger low-density lipoprotein receptors involved in the disturbed lipid metabolism of patients with non-insulin-dependent diabetes mellitus are independent of obesity.

Comparative studies were performed on monocyte-derived macrophages (MDMs), prepared by a 72-hour incubation of blood monocytes obtained from patients with non-insulin-dependent diabetes mellitus (NIDDM) and age-matched obese and non-obese controls. The MDMs, after a 72-hour culturing, expressed both specific and scavenger low-density lipoprotein (LDL) receptors on their surfaces. To study the binding capacity of both receptor types, [125I]LDL and [125I] acetylated LDL (acLDL) were applied to cells and the labeled ligands were then monitored to estimate the rate of intracellular degradations. The LDL-induced inhibition of endogenous cholesterol synthesis and the acLDL-triggered apolipoprotein (apo) E secretion were also studied, as the biological marker of receptor activation. The results indicate that the binding capacities of both specific and scavenger LDL receptors were not reduced in MDMs of diabetic patients. However, the intracellular degradation after LDL incorporation was decreased. The LDL-induced inhibition of cholesterol synthesis and the acLDL-transmitted apo E secretion were also found to be decreased in the MDMs of patients with NIDDM as compared with the obese and non-obese control groups. The NIDDM-induced impaired signal transduction of both specific and scavenger LDL receptors suggests an unclarified functional alteration of both receptor structures.

Acetates↗
PubMed1998

Heterogeneous signal pathways through TSH receptors in porcine thyroid cells following stimulation with Graves' immunoglobulin G.

OBJECTIVE: We compared different signal transduction pathways through thyroid stimulating hormone receptor (TSH-R) in porcine thyroid cells (PTC) following stimulation with thyroid stimulating hormone (TSH) and 11 thyroid stimulating immunoglobulin samples (TSI) obtained from patients with Graves' disease. DESIGN: Following stimulation with TSI, the level of inositol trisphosphate (IP3) and [Ca2+]i, as well as the membrane bound protein kinase C (PKC) activity and the intensity of the arachidonic acid (AA) cascade, were determined in PTC. RESULTS: Seven out of eleven TSI samples activated PTC through IP3 generation, elevated [Ca2+]i from the intracellular pools, exhibited verapamil-insensitive membrane-bound PKC activation, and enhanced release of [14C]AA derivates (however, one of the samples was also able to take up Ca2+ from the extracellular space). Four out of eleven TSI samples did not activate the phospholipase C (PLC) system in which case the Ca2+ signal occurred only in the presence of extracellular Ca2+, the membrane bound PKC activation was verapamil sensitive, and in two of these four TSI samples, the AA release was extremely high. CONCLUSIONS: The simultaneous examination of the majority of the known signal pathways using TSI samples showed that TSI samples from different patients activate thyroid cells through different pathways. Their effects differ from that of TSH and, to a certain extent, from each other. The results give a certain new insight into the intracellular mechanisms exerted by TSI.

Adult↗
PubMed1998

Biopsy-based diagnosis of prostate cancer in 1290 patients referred for prostate examination: results according to the PSA level, digital rectal examination and ultrasonography.

Authors present their retrospective study of 1290 patients referred for prostate evaluation. The risk of cancer was analysed according to PSA, rectal palpation and ultrasound examination. Among the 1290 patients, 54.8% had cancer. The risk of cancer was multiplied by 2.8 when the PSA was between the normal limit and 10 ng/ml, by 7.5 when it exceeded 10 ng/ml, by 4.0 when rectal palpation was abnormal and by 1.6 when a hypoechogenic zone was present. Although a hypoechogenic zone does not improve the detection of cancer compared to PSA and rectal palpation, an increased PSA level even lower than 10 ng/ml indicates biopsies.

Adult↗
PubMed1998

[Sealing effectiveness of root canal fillings pretreated with Gluma Dentin Bond].

The root canals of 41 extracted human teeth with single canal were shaped using hand instruments. The canal walls of test roots [22] were pretreated with Gluma resin. All of the canals were filled using the same method. The sealing ability of root canal fillings was evaluated by dye penetration test and the morphology of canal walls was observed by SEM. In the experimental group the dentin bond covered the canal walls completely and the entrances of dentin tubules were obturated. The dentin bond can be observed in the dentinal tubules as well. The mean value of dye penetration was 0.53 mm for the control group and 0.37 mm for the test group. The Gluma pretreatment of root canals increased the sealing ability of AH 26, however, the difference was statistically not significant.

Dental Bonding↗