Search PubMed⌕ Search

Biomedical subjects

J G Bekesi

Publications and source records attributed to J G Bekesi.

At least 73 records · Page 4Linked to original sources
PubMed1985

Phenotypic and functional correlations in circulating lymphocytes of prodromal homosexuals and patients with AIDS.

Findings of selected phenotypic and functional parameters demonstrated significant aberrations in both prodromal homosexual males and patients with AIDS. An impaired blastogenic response to T-cell dependent B-cell mitogen was associated with a significant decrease in percentage of helper T cells but appeared unrelated to the percentage of suppressor T cells. The functional subsets of the latter were further defined by a panel of monoclonal antibodies (Leu8, Leu15, and HLA-DR) applying dual color flow cytometric techniques. In both homosexuals at risk and in AIDS patients, activated suppressor cells with the phenotype Leu2+Leu15+ and Leu2+HLA-DR+ were elevated while the reciprocal cytotoxic Ts cells (Leu2+Leu15- and Leu2+HLA-DR-) were depressed. Both subsets of suppressor precursor cells and effector cells (Leu2+Leu8+ and Leu2+Leu8-) were elevated particularly in high risk homosexual males. These results suggest a defective feedback loop that regulate both helper and suppressor T cells as well as B-lymphocyte functions and may explain the clinical manifestation of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Tpa-induced maturation in secretory human B-leukemic cells in vitro: DNA synthesis, antigenic changes, and immunoglobulin secretion.

The maturation of malignant cells in response to differentiating agents is interesting as a model of normal differentiation. The response of a freshly explanted neoplastic population of phenotypically well-characterized lymphosarcoma cell leukemia blasts was studied after incubation with the differentiating agent TPA (12-0-tetradecanoyl-phorbol-13-acetate). Terminal differentiation was assessed by measuring the immunoglobulin secreted in culture supernatants and the production of intracytoplasmic immunoglobulins. Activation of the cells was studied using fluorescein-labeled monoclonal antibodies to various antigens in a flow cytometer (fluorescence-activated cell sorter) and 3H-thymidine (3H-Tdr) incorporation was evaluated to measure DNA synthesis in cells grown in complete medium and TPA-supplemented medium. The events induced by TPA were characteristic of B cell maturation and included morphological changes to plasmacytoid cells, reduction in surface immunoglobulins (sIgM, sIgD, and K), enhancement of cytoplasmic immunoglobulin, and amplification of immunoglobulin secretion. Surface antigen changes were accompanied by increased 3H-Tdr incorporation. Cell proliferation and differentiation appeared to be coupled and both were amplified by TPA treatment. These observations indicate that TPA can promote maturation of malignant secretory B cells to a terminal differentiation stage. The significance of these findings to normal B cell differentiation and their potential clinical utility is discussed.

Aged↗
PubMed1985

Urinary excretion of modified nucleosides in patients with acquired immune deficiency syndrome (AIDS) and individuals at high risk of AIDS.

Patients with certain malignant diseases excrete in their urine elevated levels of modified nucleosides originating from breakdown of transfer RNA (tRNA). A high incidence of acquired immune deficiency syndrome (AIDS), often associated with rapidly progressing Kaposi's sarcoma (KS), is currently being observed in many countries. Male homosexuals are considered to be at highest risk of developing these disorders. We have examined 10 patients with AIDS and 77 male homosexuals without clinical manifestations of AIDS at the time of examination. Elevated levels of modified nucleosides were found in all patients with AIDS. Of further interest was the finding of a high prevalence of abnormal nucleoside levels in the high-risk group, with a trend toward higher levels in those high-risk individuals who had lymphadenomegaly, considered a prodrome of AIDS. These findings indicate that determination of urinary nucleoside levels may help identify individuals at high risk of developing AIDS thereby increasing the possibility for prevention and early therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Hormone receptors in rapidly progressing breast cancer.

Biopsy specimens from 85 Tunisian breast cancer patients were compared with those of 95 American breast cancer patients for estrogen receptor (ER) and progesterone receptor (PR) levels. Tunisian patients with rapidly progressing breast cancer (RPBC) had lower ER levels than American patients or Tunisian patients without evidence of RPBC. Lower ER levels in the earliest stage of RPBC, which presents without inflammatory signs, supported epidemiologic and pathologic studies indicating that rapid growth as reported by the patient is an important aspect of RPBC. Low ER levels were generally found in young, premenopausal Tunisian women with advanced RPBC; multivariate analyses suggest that age was the most important correlating factor. In the Tunisian patients, ER levels showed a direct correlation with response to therapy. No consistent relationship between American and Tunisian patients or subgroups was observed for PR levels. These results indicate the need for reevaluating the routine use of oophorectomy in RPBC.

Age Factors↗
PubMed1984

Increased cancericidal activity of PTT.119, a new synthetic bis-(2-chloroethyl)amino-L-phenylalanine derivative with carrier amino acids. I. In vitro cytotoxicity.

A new synthetic tripeptide (p-F-Phe-m-bis-(2-chloroethyl)amino-Phe-Met ethoxy HCl), PTT.119, was demonstrated to have significant cancericidal activity against seven in vitro tumor cell lines of different origins and etiologies and against primary human AMML, ALL, and hairy cell leukemias. Viabilities of each murine tumor and rabbit, marmoset, and human leukemia and lymphoma line were significantly reduced by treatment with 1-50 micrograms PTT.119 in media containing serum. Continuous 24-h exposure or pulse treatment as short as 15 and 30 min with the tripeptide resulted in irreversible damage to the tumor cells. Under identical treatment conditions, freshly isolated human leukemic cells, particularly ALL lymphoblasts, were even more susceptible to PTT.119 than any of the tested tumor cell models. Examination of the parameters of PTT.119 activity revealed that reductions of tumor cell survival were dependent on the concentration of the tripeptide. Prolongation of PTT.119 exposure from 15 min to 24 h increased the rates of tumor cell death but did not proportionally reduce the numbers of surviving cells. Assessment of tumor cell viabilities for 5 consecutive days following pulse exposure to PTT.119 demonstrated increasing reductions in tumor cell survival, which were greatest 5 days after treatment of PTT.119 was compared with its three parental components either as individual agents or as a mixture. Both the alkylator moiety, m-sarcolysin (m.L.SL) alone or together with p-fluoro-phenylalanine and L-methionine ethoxy HCl, and L-PAM (L-phenylalanine and L-methionine ethoxy HCl, and L-PAM (L-phenylalanine mustard), the p-isomer of m.L.SL, were 1,5- to 3-fold less cytotoxic to L1210 leukemia and MJY-alpha mammary tumor cells than PTT.119. Covalent linkage of the amino acid residues to m.L.SL yielded a molecule with greatly augmented cancericidal activity capable of acting against a broad spectrum of tumor cells.

Animals↗
PubMed1984

Increased cancericidal activity of PTT.119; a new synthetic bis-(2-chloroethyl)amino-L-phenylalanine derivative with carrier amino acids. II. In vivo bioassay.

The cancericidal efficacy of a new synthetic tripeptide was demonstrated using both in vitro cultures and in vivo tumorigenic assays. The antitumor agent PTT.119 (p-F-Phe-m-bis-(2-chloroethyl)amino-Phe-Met ethoxy HCl) was highly effective against three virulent murine tumor models: the L1210 leukemia, MJY-alpha mammary tumor and B16 melanoma. Treatment of tumor cells for periods as short as 15 min to 4 h with concentrations of 1-50 micrograms PTT.119/ml irreversibly reduced tumor cell viability, as evidenced by vital dye exclusion and abrogation of tumor formation and prolongation of host survival. Examination of the sensitivity of mice to PTT.119 revealed that the in vitro antitumor activity of the synthetic tripeptide was exerted at concentrations easily attainable and well tolerated in vivo.

Animals↗
PubMed1984

Modulation of T- and B-lymphocyte functions by isoprinosine in homosexual subjects with prodromata and in patients with acquired immune deficiency syndrome (AIDS).

Male prodromal homosexuals and patients with acquired immune deficiency syndrome (AIDS) exhibited similar immunological abnormalities but by different degrees. A reduction in the number of circulating T lymphocytes bearing the T-4 surface marker led to an altered ratio of Th to Ts subpopulations in both groups of subjects. Total numbers of suppressor cells (Ts) remained virtually similar in both study groups to that of the control subjects. Proliferative responses to T-cell mitogen (PHA) and T cell-dependent B-cell mitogen (PWM) were severely impaired in prodromal subjects and more so in the AIDS group. The response to PWM was unrelated to the total number of suppressor T cells but was associated with a significant decrease in helper T-cell number. The impaired lymphocyte functions of immunosuppressed subjects were potentiated by coincubation with isoprinosine in a selective fashion. While the percentage of upward modulation among homosexuals with normal lymphocyte functions was comparable to that obtained in control subjects, a higher degree of augmentation was achieved in AIDS patients and in prodromal subjects with impaired blastogenic responses. In none of the AIDS patients with severe immunodeficiencies, however, was the lymphocyte functions restored to the normal range established in the heterosexual controls. These results suggest the feasibility of eventual prophylactic utilization of isoprinosine in male homosexuals at high risk of developing AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Functional integrity of T, B, and natural killer cells in homosexual subjects with prodromata and in patients with AIDS.

We have examined the numbers of the total T (T11+) cells, T-helper (T4+) cells, T-suppressor (T8+) cells, NK cells (Leu7+), and the functional integrity of T, B, and NK cells in healthy male heterosexuals and compared the data to those obtained from AIDS patients and male homosexuals at risk. The absolute number of total T (T11+) and T-helper (T4+) cell populations were significantly reduced among most of the asymptomatic homosexual males and even more decreased in the AIDS patients. By contrast, the absolute numbers of T-suppressor cells (T8) remained virtually unaltered in the three study populations. The absolute numbers of circulating natural killer cells were similar in the controls and the homosexual subjects, but significantly reduced in the AIDS patients. Proliferative responses to T-cell mitogen (PHA) and T-cell dependent B-cell mitogen (PWM) were severely impaired in prodromal subjects and more so in the AIDS group. Response to PWM was unrelated to the total number of T-suppressor cells, but was associated with a significant decrease in T-helper cell number. Furthermore, all AIDS patients exhibited a significantly depressed NK-cell activity that could not be normalized by addition of alpha IFN or IL-2 and in most cases correlated with the reduced absolute number of NK (Leu7+) cells as well as T-helper cells (T4) and T4/T8 ratios. Three distinctive subgroups with normal (N-NK), significantly heightened (H-NK), and markedly lowered (L-NK) NK activity could be readily identified among the homosexual male population at risk. The N-NK and L-NK groups displayed marginal to no response to in vitro treatment with alpha IFN and interleukin-2. The NK-cell activity, however, in the H-NK group was moderately to strongly inhibited by inclusion of the two immunomodifiers.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Surface antigen determinants in subpopulations of peripheral blood NK- and T-cells separated by Percoll density fractionation.

Subpopulations of NK-cells recovered in various Percoll fractions had similar Leu 7 (HNK-1) antigenicity. Leu 11 paralleled Leu 7 in its expression in the high density Percoll fractions, while cells in the lowest density showed a somewhat higher reactivity with Leu 11 than with Leu 7 antibody. A similar small proportion (20-30%) of NK-cells recovered in all Percoll fractions was susceptible to lysis by treatment with T8 and complement. Exposure to T11 and complement, which eliminate approximately 50% of the NK activity in unfractionated PBL, reduced the cytotoxicity of NK-cells recovered in the high density fraction to a significantly greater extent (60%) than that of those recovered in the low density (30%). Flow microfluorometry analysis using monoclonal anti-T reagents showed that while Leu 4 (pan T-marker) was expressed on all high density T-cells, a subpopulation of low density T-cells did not express this antigen. The proportion of Leu 3a positive (helper T) cells was found to be significantly higher among the high density T-cells than among the low density T-cells. There was a relative enrichment of Leu 2a positive (cytotoxic/suppressor T) cells recovered in the lower density Percoll fractions. Subsets of NK- and T-cells, differing in their density, were thus shown to also differ in their cell surface antigenic markers. Percoll density fractionation may prove to be a valuable tool for separation and analysis of NK- and T-cell subsets.

Antibodies, Monoclonal↗
PubMed1984

Natural killer cell function and modulation by alpha IFN and IL2 in AIDS patients and prodromal subjects.

We have examined the primary immune response, the numbers of the total T (T-11+) cells, T-helper (T4+) cells, T-suppressor (T8+) cells, NK cells (Leu7+) and the level of serum IgG in 83 healthy male heterosexuals and compared the data to those obtained from 12 clinically diagnosed AIDS patients and 92 asymptomatic male homosexuals. The absolute number of total T (T11) and T helper (T4) cell populations were significantly reduced among most of the asymptomatic homosexual males and even more decreased in the AIDS patients. In contrast, the absolute numbers of T suppressor cells (T8) remained virtually unaltered in the 3 study populations. The absolute numbers of circulating killer cells were similar in the controls and the homosexual subjects but significantly reduced in the AIDS patients. Furthermore, all 12 AIDS patients exhibited a significantly depressed NK cell activity which in most cases correlated with the reduced absolute number of NK (Leu7+) cells as well as T helper cells (T4) and T4/T8 ratios. The NK-cell activity in clinically diagnosed AIDS patients could not be normalized by addition of alpha IFN or IL2. Three distinctive subgroups with normal (N-NK), significantly heightened (H-NK) and markedly lowered (L-NK) NK activity could be readily identified among the apparently well homosexual male population. The subgroups responded to alpha IFN and IL2 in an apparently independent fashion. The N-NK and L-NK groups displayed a marginal to no response to in vitro treatment with alpha IFN and IL2. However, the NK cell activity in the H-NK group was moderately to strongly inhibited by inclusion of the 2 immunomodifiers.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1984

E-receptors mediate the attachment of activated T-lymphocytes to human red blood cells: evidence from studies with monoclonal antibodies and simple sugars.

Lectin-stimulated human T-lymphocytes display the capacity of forming stable E-rosettes with sheep red blood cells (SRBC) and of forming rosettes with allogeneic and autologous erythrocytes (RBC). Fractionation experiments indicated that the same subpopulation of lymphocytes displays both of these characteristics. Exposure of T-lymphocytes stimulated with concanavalin A (Con A) or phytohemagglutinin (PHA) to T11 monoclonal antibody (directed against the E-receptor) completely blocked the formation of rosettes with human RBC. Monoclonal antibodies to other T-cell surface markers (Leu 4, T4, T8 and OKT9) had no such effect. The formation of human RBC rosettes and stable E rosettes by PBL stimulated for 2 to 8 days by Con A was inhibited to a similar extent by dilutions of T11 monoclonal antibody. Lectin-stimulated PBL were exposed to various sugars to determine their effect on human RBC rosette formation. Rosette formation was inhibited over 80% with 2-deoxy-D-glucose and by 50-70% with D-mannose, while the other sugars tested had either less effect or none. The present findings support the concept that E-receptors on the surface of human T lymphocytes play a role in the recognition of carbohydrate containing "self" structures.

Adult↗
PubMed1984

Transfer RNA breakdown products in the urine of asbestos workers.

Patients with malignant mesothelioma, a neoplasia strongly associated with previous asbestos exposure, excrete in the urine high levels of modified purines, pyrimidines, and their ribosides, breakdown products of transfer RNA. The urinary excretion levels of modified nucleosides were measured in 47 male insulation workers with long term exposure to asbestos and, therefore, at high neoplastic risk. The nucleoside levels of 44 male control subjects were used for comparison. Asbestos-related radiographic changes were found in 70% of the exposed individuals. An increasing severity of radiographic alterations was associated with a greater frequency of elevated nucleoside clusters, especially in m'A, m'I, m'G, and m2(2)G. Duration since onset of exposure was directly related to pseudouridine, m'I, and m2(2)G. Though cigarette smoking contributes to the development of asbestos-related lung cancer, data are presented that support the hypothesis that asbestos exposure is the more important factor related to the elevated values of nucleosides. It was concluded, therefore, that measuring nucleoside levels in populations at high risk of developing certain kinds of cancer may provide a useful diagnostic tool for detecting "preclinical" biochemical changes that may be predictive of future neoplastic manifestations.

Adult↗
PubMed1984

Inhibition of human natural killer activity by 2-deoxy-D-glucose and other sugars.

The specificity of natural killer (NK) cells is still a matter of debate. In the present study a number of sugars were tested for their capacity to inhibit the NK activity of human peripheral blood lymphocytes (PBL) on K-562 target cells. The most pronounced inhibitory effect was exerted by 2-deoxy-D-glucose and 2-amino-D-glucose. Significant, though more variable inhibition was observed with D-fucose, D-ribose, L-rhamnose, and galactose. The inhibitory activity of the sugars was similar in NK assays carried out with target cells grown either in fetal calf serum or in normal human serum. 2-deoxy-D-glucose and 2-amino-D-glucose were shown to exert their inhibitory activity on effector rather than on target cells. They inhibited to a similar extent the NK activity of both unstimulated and interferon stimulated PBL. These 2 sugars also attenuated the antibody-dependent cell mediated cytotoxicity of PBL. The inhibitory effect of 2-deoxy-D-glucose and 2-amino-D-glucose on NK activity was not reversed by simultaneous exposure of NK cells to these inhibitors and glucose. The inhibitory effect of various sugars could result from the blocking of receptors on NK cells which recognize carbohydrate moieties on target cells. The activity of 2-deoxy-D-glucose and 2-amino-D-glucose could reflect impairment of the glycolytic pathway in the effector cells by the intracellular accumulation of phosphorylated derivatives of these inhibitors.

Adult↗
PubMed1983

Differential susceptibility and cytopathic alterations induced by PTT. 119, a new cancericidal compound, p-fluoro-Phe-L-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met ethoxy HCl.

PTT.119 is a new synthetic compound under assessment as a chemotherapeutic agent against neoplasia. Exposure of three diverse tumor cell lines, L1210 leukemia, MJY-alpha mammary tumor, and B16 melanoma to 1 to 50 micrograms PTT.119/ml for 15, 30 or 60 minutes significantly reduced cell survivals. Each tumor model was differentially susceptible to PTT.119 activity in the extent and kinetics of cell cytolysis. Pathological changes unique to each tumor cell type were also observed and included nuclear fragmentation and lobulation, formation of multinucleated cells, mitotic asynchrony and vacuolization of both nuclear and cytosol compartments. The data demonstrate the necessity of using more than one tumor system for the evaluation of compounds and suggest that PTT.119 exerted its cancericidal activity by more than one mechanism.

Alkylating Agents↗