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Biomedical subjects

B Szabó

Publications and source records attributed to B Szabó.

At least 19 recordsLinked to original sources

Antiretroviral immune response and plasma interferon in different phases of chronic granulocytic leukemia.

Forty patients with chronic granulocytic leukemia (CGL) were tested for antibodies and lymphocytes reacting with gibbon ape leukemia virus (GaLV) and baboon endogenous virus (BaEV) antigens as well as for plasma interferon levels. Antibodies reacting with envelope antigens of GaLV and BaEV were found frequently and in high titers in patients with the quiescent phase of CGL but rarely and in low titers in the accelerated and blastic phase of the disease. Results of radioimmunoprecipitation studies were in concordance with those obtained in virus neutralization experiments. Cellular and humoral cytotoxic activity of blood plasma and lymphocyte samples against autologous tumor cells showed a similar phase-specific distribution. Most of these activities could be blocked by GaLV and BaEV gp70 antigens. Elevated plasma interferon (IFN)-alpha levels were found in the quiescent and accelerated phase of CGL, whereas no significant differences could be detected between IFN levels of patients with the blastic crisis of CGL and those of the control persons. Follow up studies of four patients confirmed this stage-specific distribution of antiretroviral immune and interferon response.

Animals

Monocytotoxic antibodies in HIV-infected persons. TNF-alpha treatment of U937 cells increases the complement dependent cytotoxicity.

Sera of 40 intravenous drug addicts were tested for the presence of cytotoxic antibodies against uninfected and HIV-infected monocytic U937 cells. Twelve out of 31 seropositive samples proved to be cytotoxic for HIV-infected, untreated target cells in the presence of complement. The TNF-alpha treatment of HIV-infected U937 cells increased the detectability of cytotoxic effect of sera (21/31). The complement dependent cytotoxic activity of sera was reduced by pretreatment with recombinant HIV gp120. This reduction proved to be dose-dependent in the majority of cases. Immunofluorescence studies indicated that the cytotoxic sera interacted with antigens mostly localized on the cell membrane of HIV-infected TNF-alpha treated U937 cells. The specificity, the possible role and origin of monocytotoxic antibodies in HIV-infected persons is discussed.

Binding, Competitive

Prevalence and specificity of lymphocytotoxic antibodies in different stages of HIV infection.

Sera obtained from 27 HIV-infected persons were investigated for complement-dependent humoral cytotoxicity. Uninfected as well as HTLV-IIIB-infected H9 cells were used as cellular targets either before or after stimulation by phytohemagglutinin (PHA) or concanavalin A (Con-A). The degree of cytotoxicity was determined by 51Cr-release assay. Two different antibodies could be found in sera of HIV-infected persons, one being directed against HIV-induced cell surface component(s) and the other reacting with structure(s) present on activated T4 cells. Asymptomatic HIV-carries were found to have antibodies exerting complement-dependent cytotoxicity to HIV-infected T4 cells. These antibodies were reactive mainly after stimulation of HIV-infected target cells by Con-A. Sera of ARC and AIDS patients contained autoantibodies reactive with PHA-stimulated or HIV-infected T4 lymphocytes. These data suggest that HIV-specific antibodies represent an anti-viral immune defense, while autoantibodies may be important in destruction of the immune system in AIDS.

AIDS-Related Complex

Neutralizing and complement-dependent enhancing antibodies in different stages of HIV infection.

Reclustering and indirect immunofluorescence assays on MT-4 cells [carrying both CD4 and complement receptor type 2 (CR2)] were used to measure neutralizing and enhancing antibodies in sera obtained from HIV-1-infected individuals. Heat-inactivated sera were tested before and after mixing 1:1 with fresh seronegative human serum. Using heated samples, neutralizing antibodies were found in 20 out of 20 and 11 out of 19 serum samples of asymptomatic and symptomatic [AIDS, AIDS-related complex (ARC)] HIV-seropositive patients, respectively. In complement-restored samples, neutralizing activity was found in eight sera of asymptomatic patients and in none of the sera of AIDS and ARC patients; enhancing activity could be detected in four and 12 sera, respectively. A significant positive correlation was observed between the titres of neutralizing antibodies measured in the complement-restored samples and the absolute number of CD4+ lymphocytes. These findings indicate that the appearance of complement-dependent enhancing antibodies coincident with the loss of neutralizing antibodies may indicate a poor prognosis in HIV infection.

AIDS-Related Complex

Evaluation of the effectivity of Nitromint spray in comparison with sublingual tablet in emergency and ambulance practice.

The effect of Nitromint sublingual tablet and Nitromint aerosol (EGIS) has been studied in ambulance practice. Both drug forms relieved or controlled the complaints and symptoms, and proved to be effective in a great number of cases. Due to it's easier storage and easier applicability the aerosol is more advantageous than the sublingual tablet. Occasionally the simultaneous use of the two products is also beneficial. Supposedly the indication field of nitroglycerin will be extended in the near future and Nitromint preparations will be used in oxyology also for controlling other clinical conditions in which smooth muscle spasm has a major role.

Administration, Sublingual

Detection of HIV in the peripheral mononuclear cells of asymptomatic haemophiliacs in Hungary.

The presence of virus in peripheral blood mononuclear cells of asymptomatic antibody positive haemophiliacs was detected by assaying for reverse transcriptase and confirmed by electron microscopy and immunofluorescence. HIV has been detected in 5 out of 7 individuals. In order to investigate strain variation, supernatant fluids of cultures were added to H9 and MT-4 cells. Virus was recovered in MT-4 cells in 3 cases, whereas the H9 cells only supported the replication of 2 strains. Viruses isolated from asymptomatic haemophiliacs have a narrower range of infectivity than HTLV-IIIB.

Acquired Immunodeficiency Syndrome

Neutralizing antibodies and serum interferon levels in the different stages of HIV infection.

The sera of patients infected with HIV were investigated for neutralizing antibodies (NA) and interferons. All samples from asymptomatic HIV carriers contained NA in high titres. In the sera of patients with AIDS related complex and AIDS the antibodies were found rarely and in lower titres. An early peak of acid-labile interferon (IFN)-alpha was observed in asymptomatic HIV-infected persons, and a late peak was found in AIDS patients. The data suggest that HIV NA may have beneficial effect in the asymptomatic phase. The presence of acid-labile IFN-alpha may indicate stimulation of IFN system by HIV-infected cells.

AIDS-Related Complex

Complement-dependent cytotoxicity of antibodies reactive with HIV-induced cell surface antigens in HIV-carrying haemophiliacs.

Sera obtained from HIV-infected as well as uninfected haemophiliacs and from healthy subjects were investigated for the presence of lymphocytotoxic antibodies. Using the 51Cr-release test, HIV-infected haemophiliacs were found to produce serum antibodies exerting complement-dependent cytotoxic effect on HIV-infected T4 cells. The antibodies were reactive mainly when HIV-infected target cells were stimulated with concanavalin-A. Results of complement-dependent antibody cytotoxicity and indirect membrane immunofluorescence tests suggest that envelope antigen(s) of HIV may be the target(s) for cytotoxic antibodies.

Acquired Immunodeficiency Syndrome

Retrovirus-neutralizing antibodies in AML and AMMoL patients: stage-specific distribution.

Plasma samples of patients with AML or AMMoL were tested for antibodies reacting with gp70 antigens of BaEV and GaLV as well as for antibodies neutralizing BaEV or GaLV. Both frequency and titer values of antibodies were higher in remission than in blastosis. Neutralizing activity could be detected only in those plasma samples which contained antibodies to the appropriate gp70 antigen. The data suggest the presence of retroviruses in humans as antigenic stimuli for the immune system in AML and AMMoL.

Antibodies, Viral

Interferon production in myelo- and lymphoproliferative diseases. I. Spontaneous interferon production in acute and chronic leukaemias.

Blood plasma interferon (IFN) of patients with acute myeloid (AML) and chronic granulocytic (CGL) and with acute and chronic lymphoid leukaemia (ALL and CLL) was measured by bioassay and characterized by neutralization with anti-human-IFN-alpha treatment. Elevated IFN-alpha level (60-125 IU/ml) was found in the quiescent phase of CGL as compared to the control samples (15 +/- 10 IU/ml). No significant differences could be found between plasma IFN of patients suffering from the blastic crisis of CGL and control persons. Analogous results were obtained in experiments with plasmas of AML patients, regardless the stage of the disease. Elevated IFN-alpha production (60-100 IU/ml) was found in patients being in the remission phase of T-cell ALL but only in one case in the progressive phase of the disease. No significant elevation of plasma IFN level was demonstrated in patients with O-cell ALL and B-cell CLL, as compared to the control samples.

Blast Crisis

Cytotoxic activity of lymphocyte subpopulations against autologous tumour cells in patients with myeloid leukaemias and preleukaemic disorders.

Autologous lymphocyte populations from different phases of chronic granulocytic leukaemia (CGL), acute myeloid leukaemia (AML) and preleukaemic disorders were compared for cytotoxic activity. 51Cr-release tests showed that T lymphocytes from the quiescent phase of CGL and from the remission phase of AML exerted cytotoxic activity against autologous tumour cells. Such activity was also found in patients with potentially preleukaemic haematological disorders characterized by cytopenia, but not in polycythaemia vera patients. In the majority of cases cytotoxic activity of T lymphocytes could be blocked by native gp70 antigens of gibbon ape leukaemia virus (GaLV) and baboon endogenous virus (BaEV). Blocking effect of carbohydrate-free gp70 as well as p15(E) antigens could be observed less frequently. The role of cell-mediated immune response to oncovirus antigens in the course of myeloproliferative diseases is discussed.

Blast Crisis

gamma-Aminobutyric acid stimulates pituitary growth hormone secretion in the neonatal rat. A superfusion study.

The putative inhibitory neurotransmitter gamma-aminobutyric acid (GABA) elicited a dose-dependent increase in GH secretion from the pituitary of newborn rats. GH secretion increased within 3 min after GABA administration with a peak response at 5-6 min. The lowest effective dose of the GABA agonist muscimol was about 10 times smaller than that of GABA. The GABA effect was antagonized by picrotoxin and bicuculline, suggesting that GABA acts at GABA-A type receptors. The pituitary responsiveness to GABA gradually decreased during the second and third postnatal weeks. If the neonatal pituitaries were continuously exposed to GABA for 3 h GH secretion rapidly increased to a maximum within the first 10 min and then gradually decreased to a less elevated level by 1 h and remained at this level for the next 2 h. After 3 h of GABA exposure muscimol had no effect on GH secretion but human pancreatic GH-releasing factor stimulated it, indicating receptor desensitization during prolonged GABA administration. The significance of GABAergic regulation of GH secretion in the neonate is emphasized by the finding that simultaneous administration of picrotoxin diminished the GH releasing activity of the hypothalamic extract of 2-day-old rats by more than 60%. These results indicate that in the postnatal period the regulation of GH secretion differs from that of the adult animal and GABA might play an important role in the maintenance of the high GH secretion during the first days of life.

Animals

Studies on viral etiology of angioimmunoblastic lymphadenopathy.

Plasma samples of patients with angioimmunoblastic lymphadenopathy (AIBL) were tested for anti-HTLV antibodies and for interferon content. Out of 12 patients 4 had antibodies to HTL-III. Two of these plasma samples contained antibodies reacting with HTLV-I and HTLV-II, too. Activated interferon (IFN) system was found in patients with clinical remission of AIBL, as it was detected by IFN titration in their plasma samples. Data suggest the etiological role in AIBL of virus(es) related to the HTLV family.

Adult

Cytotoxicity of lymphocytes and antibodies against autologous tumor cells in patients with myeloid leukaemias and preleukaemic disorders. III. Stage-dependence of oncovirus-specific immune response.

Lymphocyte and plasma samples from the quiescent and blastic phase of chronic granulocytic leukaemia (CGL) and from the blastosis and remission of acute myeloid leukaemia (AML), were compared for cytotoxic activity. Target cells were collected from the blastic phases of diseases. 51Cr-release tests showed that the lymphocytes and plasma samples from blastic crisis of CGL had no cytotoxic activity for autologous blast cells. In contrast, cryopreserved lymphocytes and plasmas from the quiescent phase of CGL proved to be cytotoxic for the autologous tumor cells, and their effect could be blocked by native gp70 antigens of gibbon ape leukaemia virus (GaLV) and baboon endogenous virus (BaEV). A blocking effect was less frequently exerted by carbohydrate-free gp70 and p15(E) antigens. A similar relationship was found between the blastosis and remission stage of AML, however, out of the antigens of BaEV only the native gp70 showed a marked blocking effect.

Antibodies, Neoplasm

Reduced responsiveness of glomerulosa cells after prolonged stimulation with angiotensin II.

The purpose of this study was to examine whether sustained exposition to angiotensin modifies the responsiveness of adrenal glomerulosa cells when extra-adrenal factors are eliminated. Isolated rat glomerulosa cells were stimulated for 6 h in a superfusion system with angiotensin II or potassium. Their responsiveness to angiotensin II, potassium, and corticotropin (ACTH) was examined before and after the superfusion. Stimulation of the cells during the superfusion with angiotensin II or with potassium reduced their responsiveness to all three stimuli. The steroid synthesis inhibitor aminoglutethimide, applied during the superfusion, overcame the effect of potassium but failed to influence that of angiotensin. This suggests that the reduced responsiveness after stimulation with potassium is related to the increased steroid production whereas the action of angiotensin is independent of that. The results establish the existence of desensitization to angiotensin in the absence of modifying extra-adrenal factors.

Adrenal Glands

Detection of main core proteins of simian C-type viruses and human retrovirus HTLV and antibodies to them in patients with lymphoid malignancies.

Peripheral leukocytes or lymph node cells and blood plasma samples from patients with lymphoid malignancies were investigated for immunological markers of BaEV, GaLV and HTLV. Antigens and antibodies were shown with radioimmunoassay. Antigen related to the p30 core protein of BaEV could be detected in each cell type of leukaemias and lymphomas. Antigen related to the GaLV p30 was found mainly in B- and O-cell forms, while that related to the p24 protein of HTLV could be detected only in two T-cell malignancies. Antibodies reactive with these antigens showed a similar distribution.

Animals

Differential translation of virogenic and oncogenic sequences in malignant lymphoproliferative diseases and transfection of coding DNAs into NIH 3T3 cells.

The expression of oncoviral p30 polypeptides and onc gene-specific proteins has been examined in different human lymphoid malignancies. The distribution of antigen(s) related to the p30 of BaEV lacked any specificity. Antigen(s) related to the main core polypeptide of GaLV could be detected mainly in B- and O-cell malignancies. The myc-encoded protein was translated at higher levels in malignant than in normal lymphoid cells. An active src gene was identified in three acute lymphoid leukaemias and in one non-Hodgkin lymphoma of T-cell origin. Human DNAs coding oncoviral antigens or onc gene-specific proteins could be transfected into NIH 3T3 cells. These data suggest that the synergistic effect of the myc and src genes would operate in malignant transformation of some progenitors of T-cell lineage.

Animals

Antibodies to primate retrovirus antigens in circulating immune complexes of patients with acute myeloid leukemia.

Circulating immune complexes were isolated from sera of 8 patients with acute myeloid leukemia (AML) in relapse, and 20 healthy blood donors. F(ab')2 fragments were prepared from the isolated complexes. Using a radioimmunoassay (RIA), these F(ab')2 fragments, the undigested complexes and the original sera were examined for the presence of antibodies against a panel of primate retrovirus antigens: gp70, p15 and p30 of gibbon ape leukemia virus (GaLV) and baboon endogenous virus (BaEV). F(ab')2 fragments derived from the immune complexes of all patients reacted with one or more of the antigens tested, whereas no antibody activity was found in the sera or undigested immune complexes of the same patients. By a competitive RIA, antigens related to GaLV and/or BaEV were found in the serum of 7 out of 8 patients. No markers of these retroviruses were detected in the F(ab')2 preparations, in immune complexes or in sera of any of the 20 control subjects. Our results indicate that a part of the circulating immune complexes in AML contain antigens related to primate retroviruses and specific antibodies to these antigens.

Adult