Biomedical subjects

G Tusnády

Publications and source records attributed to G Tusnády.

At least 19 recordsLinked to original sources

PubMed2001

Validity and reliability of leonhard's classification of endogenous psychoses: preliminary report on a prospective 25- to 30-year follow-up study.

A 25- to 30-year controlled follow-up investigation of endogenous psychoses started in 1997. The research program labeled "Budapest 2000" was initiated in 1967 as a controlled prospective study. The assessment of 108 patients and 24 normal control persons has so far been completed. With regard to the "middle groups" in the Leonhardian classification, diagnoses of bipolar manic-depressive psychosis, cycloid psychosis, periodic catatonia, systematic paraphrenia, systematic catatonia and hebephrenia proved to be valid in the long term. Revision of the category affect-laden paraphrenia seems to be called for.

Female↗

PubMed2001

Some aspects of complementarity in the immune system. A bird's eye view.

The burden of this paper is the suggestion that the defence capacity of the immune system is rather limited. It cannot stand in readiness to deal with a practically endless diversity and abundance of microbes. In contrast to conventional thinking the current model proposes: (1) The core idea that cells of the immune system are basically and constantly interconnected with host cells (e.g., through TCR-MHC interactions) and that foreign antigens (peptides) may tend to obstruct such interactions. Peptides presented during a viral infection typically decrease complementarity between the structures that are the products of the major histocompatibility complex (MHC) genes (or other genes related to it) and T cells. The altered MHC profile exposes infected cells to a polyclonal immune attack from other T cells such that tissue destruction occurs in an allograft rejection-like fashion. This may explain why a substantial portion of T cell numbers is activated when only a small number of specific T cells is 'obstructed' from functioning by the presence of nonself peptides. (2) Phagocytes 'see' targets even in a non-immune host because complement distribution associated with polyreactive natural antibodies magnifies sensitization differences between pathogens and host cells. (3) There is only a probability that hypermutation will successfully change the genome in some B cell clones to produce high affinity antibodies that prevent the re-infection of the host by the same pathogen, but cannot conquer primary infections. (4) The history of the development of the immune responses suggests that during prolonged interaction between host and microbes in our natural habitat, carried on over many generations, the adaptive antibody population may facilitate the evolution of the natural antibody repertoire. The model predicts that microbes, which are not a part of the local environment, may invade the organism without significant resistance. The model is discussed in various interactions for survival in the context of infection and tumorigenicity.

Adaptation, Physiological↗

PubMed1997

[PATHYPRE: Pascal program for the estimation of the individual course of patients with papillary thyroid cancer].

Individual survival probability estimation provided by mathematical models based on cases with a known clinical course is of great help as concerns the treatment strategy decision relating to malignant tumours. Data on four hundred Hungarian papillary thyroid cancer patients were used together with the Markov method to construct a survival model (Orv. Hetil. 1996 137: 1067-1078,) for prediction of the individual clinical course of newly diagnosed cases for 30 years following surgical intervention. Input data included the age, the primary tumour size and extent (pT), distant metastasis at presentation, the extent of the surgical intervention, the external irradiation dosage and the degree of TSH suppression. From the input data, the PATHYPRE program can estimate the individual local/regional/distant relapse-free survival probabilities and overall cause-specific survival probability. The survival probabilities may be predicted for variations in the treatment parameters, and thus the model helps in the selection of the most appropriate therapy for the patient. The PATHYPRE software is available through the Internet connections on the home page of the National Institute of Oncology, Budapest (www.oncol.hu).

Adult↗

PubMed1997

Survival chance in papillary thyroid cancer in Hungary: individual survival probability estimation using the Markov method.

PURPOSE: The typically benign, but occasionally rapidly fatal clinical course of papillary thyroid cancer has raised the need for individual survival probability estimation, to tailor the treatment strategy exclusively to a given patient. MATERIALS AND METHODS: A retrospective study was performed on 400 papillary thyroid cancer patients with a median follow-up time of 7.1 years to establish a clinical database for uni- and multivariate analysis of the prognostic factors related to survival (Kaplan-Meier product limit method and Cox regression). For a more precise prognosis estimation, the effect of the most important clinical events were then investigated on the basis of a Markov renewal model. The basic concept of this approach is that each patient has an individual disease course which (besides the initial clinical categories) is affected by special events, e.g. internal covariates (local/regional/distant relapses). On the supposition that these events and the cause-specific death are influenced by the same biological processes, the parameters of transient survival probability characterizing the speed of the course of the disease for each clinical event and their sequence were determined. The individual survival curves for each patient were calculated by using these parameters and the independent significant clinical variables selected from multivariate studies, summation of which resulted in a mean cause-specific survival function valid for the entire group. On the basis of this Markov model, prediction of the cause-specific survival probability is possible for extrastudy cases, if it is supposed that the clinical events occur within new patients in the same manner and with the similar probability as within the study population. RESULTS: The patient's age, a distant metastasis at presentation, the extent of the surgical intervention, the primary tumor size and extent (pT), the external irradiation dosage and the degree of TSH suppression proved to be statistically significant and independent prognostic factors with regard to cause-specific survival in multivariate studies. During follow-up, 14, 14, 9 and 12% of the patients underwent local/regional/distant relapses or thyroid cancer-related death, respectively. Through use of the above six independent clinical variables and the parameters relating to the four clinical events and their interrelations, mean cause-specific survival probabilities of 88, 83 and 78% were determined at 10, 20 and 30 years, respectively. The survival-predicting software (PATHYPRE) written on the basis of the biostatistical model is available through Internet connections on the home page of the National Institute of Oncology, Budapest (www.oncol.hu). CONCLUSION: Prediction of the individual survival probability for extrastudy cases affords a rationale for individualization of the treatment of papillary thyroid cancer patients.

Adolescent↗

PubMed1996

[Survival potentials of patients with papillary carcinoma of the thyroid gland in Hungary].

The typically benign, but occasionally rapid fatal clinical course of papillary thyroid cancer has raised the need for individual survival probability estimation, to tailor the treatment strategy exclusively to the given patient. A retrospective study was performed on 400 papillary thyroid cancer patients, with a mean follow-up time of 10.3 years, to establish a clinical database for uni- and multivariate analysis of the survival probability-related prognostic factors (Kaplan-Meier product limit method and Cox regression). For a more precise prognosis estimation, in the next step the most important clinical events were investigated and survival functions for each patient were calculated on the basis of a Markov renewal model. The basic concept of this approach is as follows: each patient has an individual disease course, which (besides the initial clinical categories) is affected by special events, e.g. internal covariates (local/regional/distant relapses), that a patient experiences throughout the course of the disease. On the supposition that these events and the cause-specific death are influenced by the same biological process, the parameters of transient survival probability characterizing the speed of the course of the disease for each sequence of clinical events were determined. The individual survival curves for each patients were calculated by using the former parameters and the independent, significant clinical variables, summation of which resulted in an overall cause-specific survival function valid for the entire group. The patient's age, a distant metastasis at presentation, the extent of the surgical intervention, the primary tumour size, the dosage of the external irradiation and the degree of the TSH suppression proved to be statistically significant (in that sequence) and independent prognostic factors as concerns cause-specific survival in multivariate studies. During follow-up 14%, 14%, 9% and 12% of the patients underwent local/regional/distant relapses and thyroid cancer-related death. Through use of the above six independent clinical variables and the parameters relating to the interrelations of the four clinical events, mean cause-specific survival probabilities of 88%, 83% and 78% were determined at 10, 20 and 30 years, respectively. The 30-year individual survival probability prediction for these study cases showed that no cancer-related death occurred > or = 92% (low-risk group), while the tumour-related deaths were considerable (31%) < or = 78% (high-risk group), and there were only 6% deaths in the intermediate-risk group. The constructed survival function permits a prediction of the individual survival probability of extra-study cases under the given treatment conditions and within the given population, and thus affords a rationale for individualization of the treatment of papillary thyroid cancer patients.

Adult↗

PubMed1996

[Malignant thyroid tumors in Hungary: morbidity and mortality].

In 1993, 181 new cases (36 men and 145 women) of thyroid cancer were diagnosed pathologically in Hungary, i.e. a morbidity of 1.8/100,000 for the total population, and of 0.7/100,000 and 2.7/100,000 for men and women, respectively. The distribution of the histological diagnoses: 61% papillary, 25% follicular, 5% medullary and 3% anaplastic carcinomas, and 6% others. In the same year, 125 patients (31 men and 94 women) died from thyroid cancer, i.e. a mortality rate of 1.2/100,000 for the total population, and of 0.6/100,000 and 1.8/100,000 for men and women, respectively. The relatively low morbidity reflects the fact that no new strong aetiological factor is operative in Hungary. The substantial mortality rate, however, is influenced by the geographically determined aggressivity of the disease, the inadequacy of the diagnostic procedures and therapeutic measures, and lack of the active follow-up. The latter facts are especially prominent in centres with a low patient turnover. In the field of health care, various measures must be introduced to prevent an increase in the morbidity and to diminish the mortality. Reduction of the iodine deficiency, rationalization of the medical use of ionizing irradiation, and implementation of the necessary hormonal medication for all patients operated by resection for thyroid diseases are needed for tumour prophylaxis. Before any medical decision-making, the achievement of complete diagnostic information, including the pathological revision of clinically questionable cases, is of paramount importance. The fundamental goals as concerns the treatment modalities are as follows: increased surgical skill and level of performance of external irradiation, the availability of radionuclide therapy, and guidance of all types of thyroxine medication by endocrine experts.

Adult↗

PubMed1995

Independence divergence-generated binary trees of amino acids.

The discovery of the relationship between amino acids is important in terms of the replacement ability, as used in protein engineering homology studies, and gaining a better understanding of the roles which various properties of the residues play in the creation of a unique, stable, 3-D protein structure. Amino acid sequences of proteins edited by evolution are anything but random. The measure of nonrandomness, i.e. the level of editing, can be characterized by an independence divergence value. This parameter is used to generate binary tree relationships between amino acids. The relationships of residues presented in this paper are based on protein building features and not on the physico-chemical characteristics of amino acids. This approach is not biased by the tautology present in all sequence similarity-based relationship studies. The roles which various physico-chemical characteristics play in the determination of the relationships between amino acids are also discussed.

Amino Acid Sequence↗

PubMed1994

An indirect effect of an antibody on complement deposition and lysis of differently sensitized surrounding cells.

Lysis of papain-treated group A and B erythrocytes by human complement was studied by an anti-A (BRIC. 131) and an anti-B (BRIC. 30) IgM monoclonal antibody in 51Cr release assays. The indirect effect of membrane-bound antibody, i.e. its influence on complement binding to sensitized surrounding cells, was examined in a cold target competition test in which sensitized, non-labelled cells are present along with sensitized labelled cells and complement. The mode by which anti-A antibodies indirectly suppressed lysis of sensitized B cells up to 20-fold was studied by following C1q and C3b binding. C1q binding to both types of erythrocytes was not altered in mixed populations of erythrocytes in the presence of both antibodies. Binding of C3b to a mixture of both cell types was, however, suppressed, when both antibodies were present. C3b deposition in mixed cell populations did not reach a significantly higher extent than deposited to one type of erythrocyte alone. This was consistent with the results from competitive lysis and suggests that the anti-A captured most C3b at high anti-A concentrations and deprived the similarly sensitized B erythrocytes of complement. We think that this phenomenon is not due to an uneven removal of complement regulatory proteins from A and B erythrocytes by papain. Instead, the phenomenon might be due to an inherent property of anti-A mAb to better produce nucleation sites for C3 convertases which, upon binding factor B, better compete for the limiting factor D. A mathematical analysis of cold target competition experiment (containing 2430 individual measurements) also shows that the distribution of complement between the competing A and B erythrocyte population is uneven, since it predicts that in any given antibody combination the majority of complement is bound to A erythrocytes. This is consistent with the measured average percentage of lysis.

ABO Blood-Group System↗

PubMed1993

Environmental trichlorfon and cluster of congenital abnormalities.

Of 15 live births in one Hungarian village in 1989-90, 11 (73%) were affected by congenital abnormalities and 6 were twins. Of the 11, 4 had Down syndrome. Likely causes of such clusters (known teratogenic factors, familial inheritance, consanguinity) were excluded. A case-control study and environmental investigations pointed the finger of suspicion at the excessive use of trichlorfon at local fish farms. The content of this chemical was very high in fish (100 mg/kg) and several pregnant women, including all mothers of babies with Down syndrome, had consumed contaminated fish in the critical period for the congenital abnormalities observed.

Abnormalities, Drug-Induced↗

PubMed1993

Red-cell bound anti-A is more efficient than anti-B in competition for fluid phase complement.

Lysis of group A and B erythrocytes by human complement was studied by an anti-A (BRIC.131) and an anti-B (BRIC.30) IgM monoclonal antibody in a 51Cr-release assay. The relative concentration of membrane-bound immunoglobulins was detected by flow cytometric analysis, and the amount of C1q and C3 bound to the sensitized red cells was measured by using purified, 125I-labelled molecules. The direct haemolysis was identical with both reagents in the presence of excess and suboptimal complement over a wide range of antibody concentration (between 50 and 7000 ng/ml). The indirect effect of membrane-bound antibody, i.e. its influence on complement binding by sensitized bystander cells, was examined in a cold target competition assay in which sensitized, non-labelled cells are present when complement is incubated with sensitized labelled cells. We have found that the competitive capacity of sensitized erythrocytes correlated with the amount of membrane-bound immunoglobulins. In accordance with our earlier findings, an equal level of target and competitor cell lysis was obtained only if the fluid phase anti-B antibody concentration was 2 to 4 times higher than that of the anti-A antibodies. We demonstrate in this paper that the different competitive activity of IgM anti-A and anti-B monoclonal antibodies might be accounted for by differences in their C1q and C3 binding capacities.

ABO Blood-Group System↗

PubMed1993

Interactions in the complement-mediated lysis of blood group AB erythrocytes sensitized simultaneously with anti-A and anti-B monoclonal antibodies.

The lysis of group AB erythrocytes by human complement was studied by different anti-A and anti-B IgM monoclonal antibodies (mabs) in a 51Cr-release assay. The concentration of membrane-bound immunoglobulin was detected by ELISA, and the amount of C1q and C3 bound to sensitized red cells was measured by using purified, 125I-labelled molecules. We have demonstrated that there is an exponential relationship between the concentration of the sensitizing IgM mabs and C1q binding to the sensitized AB cell. The efficiency of binding was related to the number of antibodies bound; thus, anti-A sensitized cells bound 3-6 times more C1q than anti-B sensitized cells did. AB cells, on the other hand, bound similar amounts of C3 whether anti-A or anti-B was present. The lytic efficiencies of the various IgM mabs during short incubation times were different, suggesting that the complement activation rates vary widely with different antibodies on the AB cell membrane. The binding of C1q to an antibody-sensitized target activates a cascade, whose components may migrate away from the sensitizing antibody; interactions between the activation processes generated by the anti-A and anti-B antibodies may thus occur. Choosing appropriate pairs of anti-A and anti-B mabs for the simultaneous sensitization of AB cells has indeed resulted in stimulation in some and inhibition in other combinations of mabs. It is suggested that stimulation is observed when the activated intermediates are produced in excess, whereas inhibition occurs when a shortage of activated intermediates prevents mutual utilization.

ABO Blood-Group System↗

PubMed1992

Cold target competition analysis of the classical activation pathway of complement-mediated cytotoxicity: a non-interaction model for competing lysis.

A mathematical analysis of cold target competition experiments of complement-mediated lysis is presented, aimed at developing a minimal model of lysis where no interaction between the competing populations of sensitized blood group A and B erythrocytes is presumed. The model is able to predict the extent of lysis from the input values with remarkable accuracy suggesting that under the conditions used no stimulation and/or inhibition of the lysis of the sensitized erythrocytes occurs. The distribution of complement between the competing A and B erythrocyte populations is approximated by the model and found to be proportional to the 5th and 4th power of the ratios of the antibody and target cell concentrations, respectively. In accordance with earlier observations, suggesting that the interaction between the antibody and the C1q molecules is based on polar electrostatic charges, we propose that the sensitizing antibody provides an electrostatic field around the erythrocytes which attracts C1q molecules towards their membranes.

Antibodies, Monoclonal↗

PubMed1992

Haemolysis mediated by anti-D monoclonal antibodies in direct and cold target competition ADCC assays.

Thirteen IgG anti-D human monoclonal antibodies (mAbs) were compared for their ability to mediate lysis of D-positive erythrocytes by PBMC in direct and cold target competition antibody-dependent cell-mediated cytotoxicity (ADCC) assays. In the latter assay, lysis of fluid-phase anti-D-sensitised O Rh D-positive papainised erythrocytes (E-IgG) was inhibited by A (or B) Rh D-negative papainised erythrocytes sensitised by fluid-phase anti-A (or anti-B) mAbs. The competitive and lytic activities of the anti-D mAbs were characterised by the equilibrium dilution (ED) values, which were the reciprocal of the dilution of anti-A (or anti-B) at which lysis of target E-IgG and competitor E-IgG were identical. There was a poor correlation between the number of erythrocyte-bound anti-D molecules and either the sensitivity of E-IgG anti-D to haemolysis in the direct ADCC assay, or to the ED values of the mAbs obtained in the cold target competition ADCC. The discriminatory power of the cold target competition ADCC was better than than of the direct ADCC to detect differences in the lytic potential of the anti-D mAbs.

Antibodies, Monoclonal↗

PubMed1991

Convex constraint analysis: a natural deconvolution of circular dichroism curves of proteins.

A new algorithm, called convex constraint analysis, has been developed to deduce the chiral contribution of the common secondary structures directly from experimental CD curves of a large number of proteins. The analysis is based on CD data reported by Yang, J.T., Wu, C.-S.C. and Martinez, H.M. [Methods Enzymol., 130, 208-269 (1986)]. Application of the decomposition algorithm for simulated protein data sets resulted in component spectra [B (lambda, i)] identical to the originals and weights [C (i, k)] with excellent Pearson correlation coefficients (R) [Chang, C.T., Wu, C.-S.C. and Yang, J.T. (1978) Anal. Biochem., 91, 12-31]. Test runs were performed on sets of simulated protein spectra created by the Monte Carlo technique using poly-L-lysine-based pure component spectra. The significant correlational coefficients (R greater than 0.9) demonstrated the high power of the algorithm. The algorithm, applied to globular protein data, independent of X-ray data, revealed that the CD spectrum of a given protein is composed of at least four independent sources of chirality. Three of the computed component curves show remarkable resemblance to the CD spectra of known protein secondary structures. This approach yields a significant improvement in secondary structural evaluations when compared with previous methods, as compared with X-ray data, and yields a realistic set of pure component spectra. The new method is a useful tool not only in analyzing CD spectra of globular proteins but also has the potential for the analysis of integral membrane proteins.

Algorithms↗

PubMed1990

Differences in the competitive capacity of monoclonal antibody sensitized human A and B erythrocytes in complement mediated cytotoxicity.

Lysis of group A and B erythrocytes by human complement was studied using 9 anti-A (IgM) and 10 anti-B (IgM) monoclonal antibodies in direct and cold target competition 51Cr-release assays. The relative concentration of membrane-bound immunoglobulins was detected by indirect immunofluorescence in flow cytometric analysis. The number of binding sites/cell and affinity of the monoclonal antibodies was measured in ELISA assays. Complete haemolysis was obtained at 2 micrograms.ml-1 antibody concentrations with the majority of reagents when only a small proportion of the antibody binding sites were occupied. The influence of membrane-bound antibody on complement binding was examined by the complement consumption capacity of sensitized erythrocytes at supra-haemolytic antibody concentration. We found that complement consumption correlated with the amount of membrane-bound immunoglobulins. To obtain equal level of target and competitor cell lysis group B erythrocytes had to be equipped with higher amounts of antibodies than group A erythrocytes. The different lytic activity of IgM anti-A and anti-B monoclonal antibodies could not be accounted for merely by differences in their surface density.

ABO Blood-Group System↗

PubMed1988

Skeletal maturation in streak gonad syndrome.

Skeletal ages of patients with streak gonad syndrome were determined by the Schinz and TW2 methods as well as by bone scans. Seventy-three subjects were examined. They were classified according to their chromosomal complement, body height, chronological age and previous hormonal treatment. Retarded bone age was a common finding on the hand, wrist, hip, knees and spine with significant coexistence; however, the extent of delay in skeletal maturation on various bones differed considerably. There was no significant correlation between bone age and chronological age, karyotype, body height and previous hormonal replacements, respectively. This finding suggests that retarded skeletal maturity in streak gonad syndrome is neither the consequence of estrogen deficiency nor due to sex chromosome abnormalities and probably is not dependent on growth hormone secretion. Its pathogenesis appears to be multifactorial and remains to be determined.

Adolescent↗

PubMed1988

Thymidylate synthetase and thymidine kinase activities and methotrexate cytotoxicity during growth of L1210 and Ehrlich ascites tumor.

The specific activities of TS and TK determined in the cytosols of Ehrlich and L1210 ascites tumor cells changed significantly during their logarithmic growth. In both tumors, the highest activity of TK was in early log phase while that of TS occurred in late logarithmic growth. The activity curves of TS were practically the same and those of TK were similar in the two tumors; however, the absolute values of the latter were different. TK/TS activity ratios in the early and late log growth of Ehrlich tumor were 20 and 2, in those of L1210 tumor 4 and 0.15 respectively. MTX cytotoxicity was considerable throughout the logarithmic growth of L1210 tumor, significantly higher values were observed however when TS activity increased. The variable degree of MTX cytotoxicity indicated an intracellular manifestation of the changes in TS activity determined in vitro. The different patterns for the specific activities of TS and TK, as well as, the parallel changes of TS activity and MTX cytotoxicity during tumor growth may be useful information for the antimetabolite research carried out with experimental tumors.

Animals↗

PubMed1986

A multidimensional threshold model for multiple congenital abnormalities.

Analysis of the data of 2.762 infants with "unidentified" (i.e., no identified as dysmorphological entities) multiple congenital abnormalities from the Hungarian Congenital Malformation Registry, 1970-1976 showed that the majority of congenital abnormalities in newborns with multiple congenital abnormalities was not due to random combinations. The ratio of expected random combination and observed causal effect was 1: 6, 1: 225-1: 14,000 and 1: 2.10(6) in two, three, four, and five or more congenital abnormalities, respectively. Our multidimensional threshold model supposes specified liabilities for each congenital abnormality, and the correlation structure of these liabilities explains nearly all associations of congenital abnormalities in unidentified multiple congenital abnormalities. According to this hypothesis, the expected and the observed occurrences do not differ significantly either in the sum or in the various possible threefold associations of congenital abnormalities. The biological reasons for the phenomenon are being studied.

Abnormalities, Multiple↗