Successful treatment of respiratory failure associated with dermatomyositis.
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Biomedical subjects
Publications and source records attributed to G Bátory.
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Effects of anti-human pan-T-specific monoclonal antibodies of the Second International Workshop on Human Leucocyte Differentiation Antigens were investigated in a number of lymphocyte functional tests. Monoclonal antibodies blocking antibody-dependent cytotoxicity (ADCC), PWM-induced IL-2 release, or Con A- and PWM-induced lymphocyte proliferation were found among anti-CD2 and CD3 reagents. Inhibition of lectin-dependent cellular cytotoxicity (LDCC) was found as an exclusive effect of anti-CD2 (the sheep red cell receptor) antibodies. Several anti-CD2s blocked natural killer (NK) activity and/or PWM-induced interferon production. These two effects were exerted by antibodies against epitopes on resting T cells but not by those directed to activation epitopes. The inhibitory activity of individual antibodies in the LDCC and NK tests showed a good correlation. Also, PHA-mediated cytotoxicity (LDCC) and proliferation were in good correlation. Concerning anti-CD3 (T3) reagents, some effects were characteristic for the majority of the antibodies in this group. Namely, induction of proliferation, enhancement of IL-2-dependent cell division, IL-2 consumption by antibody-triggered cells, inhibition of mitogen-induced proliferation but not IL-2 and interferon production were observed. None of the CD3-specific reagents exerted all of these effects. In general, no correlation of the effects with immunoglobulin subclass or CD3 subcluster specificity could be found. Further epitope analysis and affinity data may be required to understand the basis of heterogeneity in functional effects of monoclonal antibodies to the CD3 molecule.
The high frequency of ANA, A-LDL and RF in advanced age suggests that AABs are present in the majority of aged subjects. CIC incidence determined by three methods is far below AAB incidence; only the Clq solubility test suggests an increased CIC incidence in aged as compared to young subjects. Simultaneous occurrence of AABs of different specificities or CIC determined by two or three methods is rare and both AAB and CIC levels are usually low. AAB prevalence in CIC-positive individuals seems to depend on the specificity of the AAB. CIC positivity is associated with relatively low Clq concentrations; however, usually not with Clq concentrations below the normal range. Neither ANA nor CIC positivity seems to correlate with DNA synthetic response to PHA, but ANA positivity may be associated with low responses to allogeneic cells. ANA positivity and, to a lesser extent, CIC positivity seems to be connected with enhanced killer cell activity. The concept of some AABs and CIC as autoregulatory factors of the humoral immune system compensating for the thymus-dependent regulation in old age is stressed.
IgM and IgG type antibody titers and levels of serum IgG, IgA and IgM were determined in healthy young and aged subjects. The proportion of subjects of low antibacterial agglutinin titers progressively increased during the 7th and 8th decades of life. Anti-streptolysin-O titers were also shifted to the lower values in aged subjects, at least until the 8th decade of life, although subnormal values compared to the young control range were less frequent than in the case of IgM type antibodies. Anti-streptokinase values did not seem affected by age. In contrast to antibody levels, serum IgM was similar or slightly higher in old compared to young subjects. Evidence is presented that the proportion of 7 S IgM drops with aging. Both IgA and IgG levels increased through the 7th, 8th and 9th decades of life. Different class immunoglobulin levels seemed to be considerably correlated and a tendency to correlate was found between IgG type antibody and serum IgG levels. Complex investigations including quantitation of antibodies to extrinsic and intrinsic antigens and serum immunoglobulins are proposed to define the humoral immune status of aged subjects and to understand the causes as well as the diagnostic and prognostic significance of old age 'imbalances'.
The role of the major histocompatibility complex in the genetic control of reactivity of peripheral blood mononuclear cells (T lymphocytes) to lectins and allogeneic cells as a function of age was investigated. In randomly selected aged subjects the frequencies of HLA-A, B, and some C locus alleles did not differ significantly from those in the control group. However, some tendencies of haplotype frequency differences between young and aged subjects were found. Significant associations of impaired or preserved T-lymphocyte function could be detected in connection with some HLA-A (A3, A11) antigens only. The tendency of some phenotypic HLA-A and B or C and B antigen associations to be in correlation with impaired or preserved T-lymphocyte reactivity in old age seemed to be independent of their age-related frequency differences. In family studies of a partially inbred Hungarian population, differences were found in the rate of diminution of allogeneic reactivity in groups sharing different HLA haplotypes. Based on statistical analysis of these data, a genetic factor segregating with the MHC and taking part in the regulation of the age-dependent decline of T-lymphocyte reactivity can be postulated.
Peripheral blood lymphocyte suspensions of healthy young and aged subjects were tested for the percentage of (1) E-rosetting cells by three different modifications of the rosette technique; (2) alpha-naphthylacetate esterase positive cells of different staining patterns; (3) IgG-Fc receptor positive cells; (4) C3 receptor positive cells; (5) labile and stable bound surface immunoglobulin positive cells; and (6) cells bearing different classes of immunoglobulins on their surface or intracytoplasmically. Age dependent changes were registered both within the T-cell and the B-cell subpopulations, some of which may be due to in vivo activation of lymphocytes. Attention is called to some technical aspects of lymphocyte subpopulation determinations and to the significance of quantitative changes in the proportions of lymphocyte subpopulations in respect to the age dependent functional changes of lymphocytes.
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Aged individuals could be divided into two groups according to their T-lymphocyte transformation values. The relationship between the PHA (phytohemagglutinin) stimulation indices and spontaneous thymidine incorporation; the PHA dose-response type distribution and the relative number of resting T lymphocytes was similar to the control group in aged subjects of seemingly intact T lymphocyte transformation values. However, their B cell compartment was found to be reduced. On the other hand, the ratio between the stimulation indices and spontaneous thymidine incorporation values of aged subjects of impaired T lymphocyte reactivity deviated from that of the control group. This group had an increased frequency of subjects giving maximal transformation values at relatively high PHA doses (hyposensitives) at the expense of normosensitives and showed reduced numbers of resting T cells, but normal B cell compartment. These results suggest that immunodeficiencies developing with age can possibly be of individually different types.
Natural cell-mediated cytotoxicity (NCMC) against a cell line (K-562) and antibody-dependent cellular cytotoxicity (ADCC) against the same target and against chicken red blood cells were investigated in two age groups (20--45 and 70--98 years old). Proliferative response to PHA and to allogenic cells as well as some subpopulation determinations were also carried out only lymphocytes of the same subjects. In contrast to the significantly decreased proliferative responses, NCMC showed a moderate, and the two ADCC values a highly significant increase in the group of aged subjects. These increased values showed some similarities with the quantitative changes within the T-lymphocyte subpopulations. The incidence of serum samples of NCMC inhibitory activity was only moderately increased in the group of aged subjects as compared to that of the young individuals. On the basis of these results, we concluded that the immune system of healthy aged subjects seems altered or inbalanced rather than depressed to that of the young individuals.
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In the course of family investigations a linear age-dependent decrease of reactivity against pooled allogeneic lymphocytes was found between 20 and 70 yr of age. This decreasing tendency was ascertained also by the investigation of unrelated people of a more advanced age. In the elderly, maximal transformation values in PHA stimulation investigated at different PHA doses showed a similar degree of reduction as allogeneic reactivity, and a good correlation between the two parameters of T-lymphocyte function has been found.
Six functionally HLA-D homozygous typing cells were identified by a restricted investigation into the Hungarian inbred population of Ivád. These putative HLA-D homozygous typing cells were then tested against a highly selected Scandinavian population sample of 60 individuals previously typed by histocompatibility reference reagents. The different HLA-D specificities could thus be identified: one closely matching HLA-Dw5, another resembling the Oslo LDoH specificity, while the last seems to be unique. Only one of the typing cells thus ascertained were HLA-B homozygous and were selected on the basis of the Ivád family structure and not on the basis of serological HLA typing.
A Hungarian random population sample was tested for six well-known and two new HLA--D specificities. HLA--D antigen and gene frequencies in the studied population agree with the frequencies observed in pooled random Caucasians, only HLA--Dw3 being significantly elevated. The incidences of Dw1 and Dw4 are, however, lower while the incidences of the Dw5 and Dw6 alleles seem to be higher in our population sample without reaching statistical significance. As for the two new specificities, the IVAD-1 specificity has a low frequency, while IVAD-3 occurs quite frequently. HLA--B and HLA--D associations seem to be different in our population sample as compared to others. In spite of the high incidence of the HLA--Bw35 antigen, no HLA--D association was found. The two new HLA--D specificities did not show association with any of the established HLA--B antigens.
Antibacterial antibodies were determined with a passive hemagglutination micromethod using the Boivin extract of eight different strains of bacteria. Correlation between antibody values of different specificities and between the summarized titer values and individual antibody titers were found. A significant decrease in the average of the summarized titer values was observed especially for persons over 70. The possibility of genetic regulation of normal antibody levels is suggested. The question whether the decrease in agglutinating antibody level in old age is due to the decreased activity of the corresponding immunocompetent cells or is secondary to other changes occuring in old age, is discussed.
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