Exposure to chemicals and systemic sclerosis.
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Biomedical subjects
Publications and source records attributed to Z Nagy.
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BACKGROUND AND PURPOSE: Vasogenic brain edema is a frequent complication of ischemic stroke. The mechanism of the blood-brain barrier opening that underlies the edema formation is poorly understood. In the present study we examined the response of endothelial cells cultured from adult human brain to thrombogenic and fibrinolytic factors that possibly accumulate in the occluded vascular segments in ischemic stroke. METHODS: The changes in the morphology of cultured human brain microvascular endothelial cells were observed by phase-contrast light microscopy and quantified with computerized morphometry. RESULTS: Active proteases (eg, thrombin, plasmin, urokinase) as well as heparin and protamine, but not fibrinogen and antithrombin III, produced significant changes in endothelial cell morphology. Two shape patterns of contraction were observed: protamine treatment resulted in rounded cells with a decrease in both cell perimeter and area, whereas all other agents induced spiderlike cell morphology with increased perimeter and reduced area. The rate of contraction was dose dependent, and at comparable enzyme concentrations plasmin produced faster contraction than thrombin. The observed changes were reversed 3 hours after abrogating the treatment. CONCLUSIONS: In an in vitro model we have demonstrated that factors involved in thrombus formation and dissolution induce endothelial cell contraction, which could affect focally the permeability of the blood-brain barrier by opening paracellular avenues between endothelial cells in vivo. Thus, the genesis of brain edema in thromboembolic stroke or occasionally during fibrinolytic therapy can be attributed in part to the contact of these factors with the microvascular endothelium.
Stroke is unique among neurological diseases since it has a high incidence rate, severe burden of illness, high economic cost, and it may be preventable [1]. Described here is a system for screening the cerebral and vascular status of individuals to detect the initial stages of vascular disorders. The computer based polygraphic system (CERBERUS) questions subjects about risk factors, stresses, neurologic symptoms and monitors impedance pulse waves of the head and extremities, EEG, and ECG. The system has been tested in 691 cases. Doppler control studies were carried out on approximately 300 of these cases. Additional somatic measures and psychological tests related to stroke risk factors were carried out for wide biological basis of possible correlation of CERBERUS data base. The high incidence of cerebrovascular disturbance was established by CERBERUS data, further confirmed by additional data gathered, and moreover was compared by traditional medical records. The polygraphic system is more sensitive at detecting physiological asymmetries of blood flow than even a Doppler measurements. This suggests that it may be a significantly improved means for the differential diagnosis of neurological disease and the screening of subjects for arteriosclerosis, transient ischemic attack and stroke prevention to be offered at the lowest level of medical service.
From October 1992 to December 1994, 2732 cycles of treatment by intracytoplasmic sperm injection (ICSI) were carried out in couples mainly with severe male-factor infertility. The overall fertilization rate in these 2732 cycles was 71% of intact oocytes. However, in 76 (72 couples) of these cycles, none of the injected oocytes became fertilized, so the total fertilization failure rate was 3% (76/2732 cycles). Details of these 76 cycles were analysed. The results show that total fertilization failure after ICSI may be explained by different factors related to (i) semen characteristics (only immotile or round-headed spermatozoa for ICSI) or (ii) the oocytes (number, abnormal morphology, damage after ICSI). Of 26 couples, 22 achieved fertilization in their subsequent ICSI cycles. In conclusion, total fertilization failure after ICSI for the treatment of severe male-factor infertility was mainly caused by the poor viability of the spermatozoa used for injection; it was also associated with a low number and poor quality of oocytes. Repeated ICSI treatment may be useful or necessary in couples with total fertilization failure.
The mortality of stroke in Hungary is 208 out of 100,000 inhabitants, which is very high in an international comparison. The age-group most in danger is between 35 and 50. There are 40-50 thousand hospital admissions each year because of stroke, the majority of them are unexpected crisis cases. In 1992, the government announced the National Stroke Program, which includes prevention, emergency, acute treatment and rehabilitation. Simultaneously with the medical-professional program, the National Stroke Program Information System (NSPI) has also been launched. Its aim is the direct backing up of the medical activity, the aiding of epidemiological tasks and preventive follow-up of patients. The system consists of an interactive database network in that it can guarantee accessibility, thus making every endeavour to assist in solving medical-professional problems with the help of modern information technology (smart care, telecommunication-device, etc.).
In this report the indications for, and the results of, 1275 consecutive ICSI cycles carried out between October 1991 and December 1993 are described. Failure of fertilization in at least one previous IVF cycle, semen parameters below the threshold for standard IVF treatment and successful MESA or TESE procedure performed in patients with obstructive or non-obstructive azoospermia, respectively, were the indications in these ICSI cycles. In 1194 cycles, ejaculated spermatozoa were used, whereas 59 and 17 cycles were performed with epididymal and testicular spermatozoa, respectively. The normal fertilization rate was significantly higher with ejaculated spermatozoa than with epididymal or testicular spermatozoa, but no differences were observed with regard to embryo quality, the percentages of transfer after ICSI and the clinical pregnancy rates in the three groups of patients.
We describe here a new method for predicting class II major histocompatibility complex-binding peptides, based on the preferences observed in a systematic series of peptide binding experiments where each position in a "minimal" peptide was replaced individually by every amino acid. The DRB1*0401 peptide binding preferences were determined and incorporated into a computer program that looks through sequences for potential epitopes and assigns each a score. These scores correlate well with previously determined T cell epitopes of foreign antigens and endogenous peptides from self proteins. Our findings hold implications for the design of subunit vaccines and in the identification of autoantigenic peptide regions within self proteins.
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The influenza virus hemagglutinin is synthesized as a single polypeptide chain, but upon maturation it will posttranslationally be modified by a host cell related trypsin-like enzyme. The enzymatic cleavage attacks the so-called intersubunit region of the molecule giving rise to covalently linked HA1 and HA2 subunits. An I-Ed-restricted T cell epitope was identified in the highly conserved intact intersubunit region of the influenza virus hemagglutinin. T cell recognition of a 25-mer synthetic peptide comprising the intact intersubunit region does not require further processing and the elimination of the intervening Arg residue coupling the fusion peptide to the C-terminal segment of HA1 does not abolish the T cell activating capacity. The fine specificity pattern of a T cell hybridoma similar to that of the polyclonal T cell response demonstrates that a single T cell receptor is able to recognize peptides of different sizes representing not only the uncleaved but also the cleaved form of this hemagglutinin region. Based on specificity studies the epitope was localized to the C-terminal 11 amino acids of the HA1 subunit. The cross-reactivity of peptide-primed T cells with influenza virus infected antigen-presenting cells shows that fragments comprising the identified epitope of the intersubunit region can be generated as a result of natural processing of the hemagglutinin molecule. As antigen-presenting cells are lacking the enzyme which is responsible for the posttranslational modification of newly synthesized hemagglutinin molecules, the role of immature viral proteins in immune recognition is discussed.
OBJECTIVE: To present and assess the efficacy of a new approach for the treatment of infertility due to congenital bilateral absence of the vas deferens. DESIGN: A retrospective study of consecutive trials. SETTING: Centre for Reproductive Medicine, which is a tertiary referral institution. PATIENTS: Twelve couples suffering from infertility because of congenital bilateral absence of the vas deferens. INTERVENTIONS: A microsurgical epididymal sperm aspiration procedure was performed in the husbands, followed by intracytoplasmic sperm injection of oocytes recovered from the wives. Cleaving embryos were transferred to the uterine cavity 48 hours after the intracytoplasmic sperm injection procedure. MAIN OUTCOME MEASURES: Sperm parameters after microsurgical epididymal sperm aspiration, fertilization, cleavage, and pregnancy rates. RESULTS: In all 14 microsurgical epididymal sperm aspiration procedures, sperm was retrieved. Notwithstanding the poor quality of this epididymal sperm, a fertilization rate of 58% was achieved after intracytoplasmic sperm injection. On 10 occasions, embryos were transferred and five patients became pregnant, i.e., an overall pregnancy rate of 35.7% per started trial and 50.0% per transfer. Another two patients became pregnant after replacement of frozen-thawed embryos, which increases the pregnancy rate to 50.0% per microsurgical epididymal sperm aspiration procedure. Early pregnancy wastage was 57%, limiting the ongoing pregnancy rate to 21.4% per microsurgical epididymal sperm aspiration procedure. CONCLUSION: This study shows the combined microsurgical epididymal sperm aspiration-intracytoplasmic sperm injection procedure to be highly efficient in achieving fertilization in vitro, even after recovery of grossly impaired epididymal sperm.
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Intracytoplasmic sperm injection (ICSI) is a promising assisted fertilization technique that may benefit women who have not become pregnant by in-vitro fertilization. ICSI and subzonal insemination (SUZI) were used to treat couples who failed fertilization after standard IVF or who could not be accepted for IVF because too few motile spermatozoa were present in the ejaculate. This paper describes the outcome of 750 consecutive cycles of SUZI and ICSI. Different aspects of these novel assisted fertilization procedures are described: patient management, ovarian stimulation, semen evaluation and treatment, oocyte collection and preparation, SUZI and ICSI techniques, assessment of fertilization and embryo cleavage, outcome of embryo transfers and the evolution of the pregnancies.
The results of 600 consecutive treatment cycles of subzonal insemination (SUZI) and intracytoplasmic sperm injection (ICSI) are described in couples with failed fertilization after standard IVF or insufficient spermatozoa in the ejaculate for IVF. More oocytes were damaged by ICSI (16.3%) than by SUZI (8.5%) and the normal fertilization rate was substantially higher after ICSI (49.1% v. 16.6%). Subsequent development of two-pronuclear oocytes in vitro was 80% after SUZI and 73.9% after ICSI. Significantly more triple embryo replacements were carried out after ICSI than after SUZI. Embryo transfers were possible in 421 of the 600 cycles. There were 63 pregnancies after ICSI (215 transfers) and 23 after SUZI (156 transfers); 10 additional pregnancies were achieved after 50 transfers of a mixture of SUZI and ICSI embryos. The results of fetal karyotypes and follow-up of the children do not indicate an increase in congenital malformations.
In order to assess whether specific treatment of spermatozoa is required prior to intracytoplasmic sperm injection (ICSI), three methods of sperm preparation were compared in this study. These three methods were (A) incubation of spermatozoa with pentoxifylline (PTX) and 2-deoxyadenosine (DOA), (B) electroporation followed by incubation in medium with PTX, and (C) no further treatment with the Percoll gradient. Controlled comparisons were carried out between method A and method B in 21 patients, and between method A and method C in 32 patients. There was no difference in the rates of fertilization and embryo cleavage when ICSI was done with spermatozoa treated by procedures A, B or C. Furthermore, the sperm selection procedure prior to ICSI was done in two different media: T6 medium containing 1.78 mM CaCl2.2H2O and a final washing step after the Percoll gradient in T6 medium containing 5.0 mM CaCl2.2H2O, and Earle's medium containing 1.78 mM CaCl2.2H2O. The results of ICSI on sibling oocytes from 12 patients revealed no difference in the fertilization and embryo cleavage rates between the two different media used during the sperm selection procedures. In conclusion, it appears that high fertilization and pregnancy rates can be obtained in couples with severe male-factor infertility by ICSI and that no special treatment of the spermatozoa prior to ICSI is required.
The influenza virus haemagglutinin has an important role in the infectious cycle of the virus and carries multiple B and T cell epitopes. It is synthesized as a single polypeptide chain but viral infectivity depends on its post-translational enzymatic cleavage. The cleavage site of a trypsin-like enzyme responsible for this modification is found in the most conserved intersubunit region of the molecule. In this study the role of this region in antibody recognition was investigated. Synthetic peptides comprising the intact and cleaved forms of the intersubunit segment were used to examine the specificity of virus- or peptide-induced antibodies. The immune response elicited by viral infection resulted in the appearance of antibodies capable of neutralizing the virus without interfering with its binding to the receptor. A monoclonal antibody (MoAb) of such functional properties was shown to recognize the intact intersubunit region both in the uncleaved haemagglutinin molecule and in a 25-mer synthetic peptide comprising the intact intersubunit region. Specificity and functional studies revealed the conformation-dependent recognition of the C-terminal segment of the haemagglutinin 1 subunit by this MoAb. The binding of the antibody was shown to inhibit the trypsin-mediated cleavage of the haemagglutinin molecule and the membrane fusion event. The enzymatic cleavage of the haemagglutinin was demonstrated to abolish antibody recognition of the infective virus suggesting an escape mechanism mediated by the functional destruction of this highly conserved region. The synthetic peptide corresponding to the intact intersubunit region is characterized by an ordered structure and is able to elicit an antibody response in BALB/c mice while its subfragments are nonimmunogenic. Furthermore, this peptide elicited a protective immune response demonstrated by in vivo experiments.
Authors describe the results of the application of the "Pain drawing test" patients examined and operated for degenerative lumbal spinal stenosis. Attention is called to the special view-points of the assessment. This method is judged useful both in preoperative and postoperative examinations as a supplementary diagnostic procedure.
Eight cases are reported here. Isolated Penicillin resistant Streptococcus pneumoniae strains were also resistant to Oxacillin, Erythromycin, Ampicillin, Cotrimoxazole. In five cases resistance to second generation cephalosporines (Cefaclor, Cefuroxime) also could be demonstrated. All of these multiply resistant strains retained their susceptibility to the third generation cephalosporines (Cefotaxime, Ceftriaxone). Claforan treatment resulted recovery in all of the patients.