Search PubMed⌕ Search

Biomedical subjects

J G Bekesi

Publications and source records attributed to J G Bekesi.

At least 55 records · Page 3Linked to original sources
PubMed1987

Immunotoxicology: environmental contamination by polybrominated biphenyls and immune dysfunction among residents of the State of Michigan.

In 1973, inadvertent contamination occurred in a special farm feed supplement for lactating cows. Polybrominated biphenyls (PBBs) were used in place of magnesium oxide resulting in serious harm to farm animals, including cattle, chickens, geese, ducks. Farm families, accustomed to eating their own products, were most heavily exposed. To study the impact of PBBs, 336 adult Michigan farm residents, 117 general consumers for comparison, 75 dairy farm residents in Wisconsin, who had not eaten PBB-contaminated food, were examined, as were 79 healthy subjects in New York City. Abnormalities in the Michigan groups included hypergammaglobulinemia, exaggerated hypersensitive response to streptococci, significant decrease in absolute numbers and percentage of T and B-lymphocytes, and increased number of lymphocytes with no detectable surface markers ("null cells"). Significant reduction of in vitro immune function was noted in 20-25% of the Michigan farm residents who had eaten food containing PBB. The decreased immune function detected among the PBB-exposed farm residents tended to affect families as a unit and was independent of exposed individuals' age or sex, pointing against the possibility of genetic predisposition.

Agricultural Workers' Diseases↗
PubMed1987

Modified nucleosides in patients with acquired immune deficiency syndrome (AIDS) and individuals at high risk of AIDS: correlations with lymphadenomegaly and immunological parameters.

Patients with certain malignant diseases excrete in their urine elevated levels of modified nucleosides originating predominantly from the breakdown of transfer RNA (tRNA). Acquired immune deficiency syndrome (AIDS), often associated with rapidly progressing Kaposi's sarcoma (KS), is currently occurring in many countries. Male homosexuals are considered to be at highest risk of developing these disorders. We have previously reported that patients with AIDS excrete elevated levels of modified nucleosides. In this communication, we report on modified nucleoside levels measured in 77 male homosexuals without clinical manifestations of AIDS at the time of examination. A high frequency of abnormal nucleoside levels was found in this high-risk group. There was a trend towards higher levels in individuals with lymphadenomegaly, considered a prodrome of AIDS. Statistically significant correlations were found between some of the nucleosides (pseudouridine and dimethylguanosine) and degree of lymphadenomegaly. Pseudouridine, 1-methyl-adenosine and dimethylguanosine were inversely related to percentages of total T-lymphocytes (T11), suppressor T-lymphocytes (T8), and number of natural killer cells (Leu-7). These findings suggest that determination of urinary nucleoside levels may help identify individuals at high risk of developing AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Monocytes in AIDS.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1986

High frequency of immune dysfunctions in asbestos workers and in patients with malignant mesothelioma.

We have examined the primary immune responses, the numbers of total T (T11+) cells, T-helper (T4+) cells, T-suppressor (T8+) cells, and natural killer (NK) (Leu7+) cells, in 118 healthy control subjects and compared the data to those obtained from 20 patients with clinically diagnosed malignant mesothelioma and 375 long-term asbestos workers without neoplasia. The absolute numbers of total T (T11+) and T-helper (T4+) cells were normal in asbestos workers without neoplasia but were significantly reduced in patients with mesothelioma. T-suppressor (T8+) cells, on the other hand, remained unchanged in the patients but were significantly elevated among the asbestos workers. This resulted in a marked reduction in T-helper (Th) to T-suppressor (Ts) ratios in mesothelioma patients and in asbestos workers. Seventy percent of the mesothelioma patients (14 of 20) had significantly depressed NK-cell activity which could be augmented but not normalized by coincubation in patients' peripheral blood lymphocytes (PBL) with interferon (IFN). Among the asbestos workers three distinctive subgroups could be identified: heightened (H-NK), normal (N-NK), and low (L-NK) NK activity. The NK activity of the L-NK group could be stimulated but not normalized by coincubation with IFN, a finding closely resembling that in malignant mesothelioma patients. Phenotyping of the circulating NK cells revealed a unique Leu7+ subset in increased numbers with a brightly fluorescent property in stable mesothelioma patients with relatively stable or slowly progressive disease and in more than 30% of the asbestos workers.(ABSTRACT TRUNCATED AT 250 WORDS)

Asbestos↗
PubMed1986

A double-blind clinical trial of the effects of inosine pranobex in immunodepressed patients with prolonged generalized lymphadenopathy.

In a double-blind clinical trial, 61 immunodepressed males with persistent generalized lymphadenopathy (PGL) received one of two doses (1 or 3 g/day) of the immunomodulating drug inosine pranobex (INPX) or placebo for a period of 28 days. In the high-dose group, clinical improvement was reported by 11 of 21 patients (52%), within 5 months of the cessation of treatment. In contrast, 3 of 19 patients (16%) in the placebo group reported clinical improvement by that time. Patients receiving 3 g/day INPX showed a significant increase in NK cell activity by Day 14 and this elevation was still evident at the last follow-up examination 1 year after treatment. Increases in total T lymphocytes (T-11) and the percentage of T helper cells (T-4) were also observed. These responses were delayed and reached their peaks 2 months after the termination of drug treatment. The kinetics of these effects suggest that INPX stimulates the production of precursor cells and initiates a cascade of lymphocyte differentiation capable of producing long-term restoration of cell-mediated immunity. These data indicate that INPX may be beneficial to patients with PGL.

Antigens, Surface↗
PubMed1986

Diagnosis of CNS lymphoma using immunofluorescent phenotyping of CSF mononuclear cells.

We describe the use of a panel of monoclonal antibodies, directed against leukocyte surface antigens to characterize CSF mononuclear cells with regard to malignancy when cytopathology was inconclusive. Cytocentrifuged preparations from three patients in which traditional modalities had not yielded a diagnosis were studied, utilizing a panel of antibodies for B and T cell antigens. All three patients were found to have B cell lymphoma of the CNS. Rapid institution of the appropriate therapy resulted in marked improvement of CNS symptoms in each case. Our results indicate that in patients with CNS disease and CSF pleocytosis of undefined nature, this technique may provide rapid and precise diagnostic information.

Adolescent↗
PubMed1986

Secretory leukemic B cells express T cell markers in vitro. A phenomenon suppressed by TPA.

Immunological and biochemical markers of leukemia/lymphoma cells have provided valuable insight into hematopoietic malignancy and normal differentiation. The general assumption is that as early lymphoid cells become committed towards terminal differentiation they lose their capacity for bimodal differentiation and cells become restricted to B or T cell development and function. We have observed that phenotypically "late" leukemic B cells close to secretory stage can spontaneously express mature T cell antigens (T11, T4 and T8) after culture in vitro. In further studies of these cells, it was found that the biochemical marker lactate Dehydrogenase (LD) follows the intermediate pattern expressed by thymocytes rather than that of typical B cells. The expression of T cell antigens can be blocked by incubating these cells with the phorbol ester TPA (12-0-tetradecanoyl phorbol 13 acetate) which promotes unidirectional B cell maturation to plasmacytoid cells in a way that mimics normal B cell differentiation. These observations indicate that presecretory malignant B cells are still programmed to express T cell biochemical and antigenic markers and this expression can be influenced by environmental conditions in vitro.

Antigens, Surface↗
PubMed1986

Restoration of impaired B- and T-lymphocyte subsets and functions in vitro by isoprinosine in prodromal homosexuals and AIDS patients.

Functional and phenotypical parameters demonstrated significant aberrations in both prodromal males and patients with the acquired immune deficiency syndrome (AIDS). Impaired B-cell functions as quantitated by Staphylococcus aureas Cowan Strain I (SAC) and pokeweed mitogen (PWM)-induced blastogenesis, intracytoplasmic immunoglobulins and spontaneous immunoglobulin were associated with a significant decrease in Leu3+ cells but unrelated to Leu2+ lymphocytes. The functional subsets of the latter were further defined by monoclonal antibodies (Leu8 and HLA-DR) applying dual color flow cytometry. Activated and effector-suppressor subsets with the phenotypes Leu2+ HLA-DR+ and Leu2+ Leu8- were elevated while both subsets of helper and suppressor-inducing helper lymphocytes, Leu3+ Leu8- and Leu3+ Leu8+, were depressed. These data demonstrated a broad spectrum of dysfunction involving all 3 stages of B-cell development in AIDS as well as possible defects in the feedback suppressor loop which regulates both the helper and suppressor T-lymphocyte system and B-cell functions. While in vitro incubation with isoprinosine had no modulative effect on SAC-induced blastogenesis (resting B-cell activities), it did modulate both PHA, PWM-induced transformation and the spontaneous secretion of immunoglobulins (partially and fully activated B-cell activities). In co-incubation with PWM, isoprinosine augmented the expression of inducer cells for helper functions while enhancing to normal level the number of suppressor-inducing helper cells. In addition, it reduced activated and effector-suppressor cells to near normal range in the PBL of high risk homosexuals. Only marginal modulation, however, was observed in suppressor subsets of AIDS subjects. This interference with the defective feedback loop may account for the selective clinical and immunoregulatory actions of this drug.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Interference of mouse mammary tumor virus replication by PTT.119 [p-fluoro-L-phe-m-bis-(2-chloroethyl)amino-L-phe-met ethoxy HCl]--an antitumor agent.

PTT.119 [p-fluoro-L-Phe-m-bis-(2-chloroethyl)-amino-L-Phe-Met ethoxy HCl] is a new bifunctional alkylating compound that possesses both cytolytic and antiviral activities. Continuous treatment of mouse mammary tumor cells with 15 microM PTT.119 reduced production of the B-type retrovirus murine mammary tumor virus (MuMTV). MuMTV levels in PTT.119-treated cultures were reduced by 31% in the first 24 hours; an additional 24 hours of treatment resulted in a further reduction of 70%. These reductions were significantly greater than could be accounted for by the effects of PTT.119 tumor cell metabolism and viability. Under identical treatment conditions, equimolar concentrations of L-phenylalanine mustard reduced MuMTV production by only 3%. PTT.119 inhibition of MuMTV replication was also apparent when mammary tumor cells were exposed for periods as short as 0.5-4 hours; persistent decreases in virus production were detected even 7 days following tripeptide treatment. Analyses of the polypeptide composition of MuMTV by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that virions from these PTT.119-treated mammary tumor cultures contained significant reductions in the relative level of the nonglycosylated 24,000-dalton (p24) viral polypeptide associated with the nucleoprotein core. Decreases in p24 were observed in MuMTV produced in the presence of the tripeptide and 1-7 days after removal of PTT.119. Examination of the steady-state levels and rates of intracellular MuMTV protein synthesis suggested that PTT.119 interferes with late steps in MuMTV processing and maturation.

Animals↗
PubMed1986

Immunoglobulins (Ig) in circulating immune complexes (CIC) in cancer and inflammatory bowel disease (IBD).

Chronically inflamed tissues and most malignancies have antigenic properties. Patients with long-standing inflammatory bowel disease (IBD) are prone to development of colorectal cancer, which is known to shed antigens in the bloodstream. In an effort to study immunological aspects of these diseases, sera from patients with IBD and colorectal cancer were evaluated for presence of circulating antigen-antibody immune complexes (CIC), and compared to normal controls. CIC were precipitated by polyethylene glycol (PEG) and found to be elevated in all diseased groups. Dissociation of CIC and quantification of their antibody component revealed significant elevation of each immunoglobulin in IBD and in patients with colorectal cancer versus control: IgG = 1.776 +/- 1.573 vs 0.734 +/- 0.618 (P less than 0.001); IgA = 0.368 +/- 0.452 vs 0.090 +/- 0.198 (P less than 0.001); IgM = 0.434 +/- 0.235 vs 0.080 +/- 0.285 (P less than 0.001) serum total Ig levels were consistently much higher than CIC Ig. No correlation was found between the individual serum Ig components and the precipitable complexes-bound Ig, suggesting a selective recognition of antigenic components in the CIC, rather than non-specific association and subsequent precipitation of serum Ig. CIC may represent an easily accessible source of immunological determinants for the study of malignant and chronic inflammatory diseases.

Adolescent↗
PubMed1985

PTT.119, p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met ethoxy HCl, a new chemotherapeutic agent active against drug-resistant tumor cell lines.

PTT.119 [p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met ethoxy HCl], a new synthetic tripeptide, was highly effective against the L-phenylalanine mustard (L-PAM) resistant (L1210/L-PAM and P388/L-PAM) tumor lines, as well as the sensitive L1210 leukemia. Cytolytic activity of PTT.119 against all three leukemias was significantly greater than equimolar doses of L-PAM. These in vitro results paralleled the significant increases in mean survival times of hosts and, in some cases, abrogations of tumor formation observed in the in vivo bioassays of PTT.119-treated L1210 and L1210/L-PAM cells. Dose-response studies failed to demonstrate cross-resistance to the tripeptide by L-PAM resistant cells. Doses of PTT.119 required to reduce the viable fraction by 50% (tissue culture dose 50, TCD50) or 100% (TCD100) were 1.3- to 3-fold lower for the L-PAM resistant cells than for the L1210 leukemia. In comparison, L-PAM was unable to completely eliminate cell survival; 0.2 to 3% of the cells in all three leukemias remained viable even at doses of 75 and 163 microM. In similar studies, L1210 leukemia cells made resistant to methotrexate (L1210 MTX) and cisplatin (L1210DDP) were also completely susceptible to PTT.119; TCD50 values of the two resistant lines were 1.94 microM for L1210 MTX and 0.525 microM for L1210DDP compared to 2.38 microM for the susceptible parent L1210S leukemia. Continuous low-dose PTT.119 treatment of MJY-alpha mammary tumor cells for 8 months and exposure of L1210 leukemia to escalating levels of tripeptide for over 100 passages failed to select or induce drug-resistant phenotypes in either cell line. PTT.119 appears to be a poor mutagen and is unlikely to readily increase the probability of drug-resistant mutants in the tumor cell populations.

Animals↗
PubMed1985

Immunopotentiation of impaired lymphocyte functions in vitro by isoprinosine in prodromal subjects and AIDS patients.

Immunomodulative actions of isoprinosine were tested in 100 prodromal homosexual males and 23 patients who have been diagnosed with AIDS. All subjects showed reduced T helper cells although T suppressor cell counts were normal. Proliferative responses, particularly T cell-dependent B cell function, were severely impaired in prodromal and AIDS subjects. Upon co-cultivation of their lymphocytes with isoprinosine, significant upward modulation, and in some cases, normalization, of lymphocyte functions as monitored by PHA- and PWM-induced blastogenesis was achieved in prodromal subjects. Similar degrees of modulation but not normalization of lymphocyte functions were observed in patients with severe symptoms of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Analytical and pharmacological studies on a new antineoplastic tripeptide, PTT.119.

The new synthetic tripeptide, p-fluoro-L-phenylalanyl-m-bis-(2-chloroethyl)-amino-L-phenylalanyl-methi onine ethylester hydrochloride, PTT.119, an alkylating agent, is currently undergoing preclinical trials as an antineoplastic agent. The molecular composition, C29H39N4O4SCl2F, was confirmed by desorption chemical ionization mass spectrometry with accurate mass measurement. A high-performance liquid chromatographic technique was developed for the quantification of PTT.119 in cell culture medium and serum. Incubation of 5 X 10(5) mammary tumor cells (MJY-alpha)/ml tissue culture medium with 25 micrograms PTT.119/ml for 60 min (37 degrees C) removed 68% of the tripeptide from the medium. This corresponds to an uptake of 51 fmol PTT.119/tumor cell. Cell death, assessed 5 days after treatment, was directly proportional to the time-dependent removal of PTT.119 from the cell culture medium.

Antineoplastic Agents↗
PubMed1985

Polybrominated biphenyls in model and environmentally contaminated human blood: protein binding and immunotoxicological studies.

A review and summary is given of analytical, biochemical, and immunological studies made following an immunodiagnostic investigation which revealed significant decreases in the numbers, and changes in the functional integrity, of both T-and B-lymphocytes in a group of Michigan dairy farmers exposed to polybrominated biphenyls (PBB) which had been inadvertently introduced into the food chain in 1973. A quantification technique based on selected ion monitoring of bromine anions, obtained in negative chemical ionization, permitted determination of 10-35 pg of individual PBB congener per mL serum, a 20-fold improvement over electron capture gas chromatography. An in vitro spiked system was established and shown to be a representative model of environmentally contaminated blood. Immunoprecipitation followed by mass spectrometric quantification determined that the distribution of PBB among plasma, erythrocytes, mononucleocytes and polymorphonucleocytes was 89:9:less than 1:less than 1. In plasma 80% of the PBB was bound to apolipoproteins B and A in a 3:1 ratio. No preferential absorption of PBB congeners was found in the blood compartments suggesting that changes in the relative abundances of PBB congeners observed in longitudinal studies on Michigan subjects reflect differences in excretion rates or metabolism. A repeat in 1981 of the immunodiagnostic tests conducted in 1976 revealed a virtually complete persistence of the immune dysfunctions in the Michigan farmers exposed to PBB a decade ago.

Agricultural Workers' Diseases↗
PubMed1985

The expression of Leu M4 on human NK cells.

Previous studies have shown that the Leu M4 monoclonal antibody reacts strongly with human granulocytes in the peripheral blood, has a weak reactivity with monocytes but fails to react with platelets, eosinophils and K-562 cells. In the present study Leu M4 antibody was found to react with human NK cells. Immunofluorescent analysis indicated that about 12% of peripheral blood lymphocytes (PBL) are positive for this marker, and that the reactive cells are concentrated in the Percoll fraction known to display the strongest NK activity. Exposure of PBL to Leu M4 and complement resulted in a significant decrease of their NK activity. The relationship of Leu M4 to other monoclonal antibodies reactive with human neutrophils and NK cells remains to be elucidated.

Antibodies, Monoclonal↗