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Biomedical subjects

Z Bentwich

Publications and source records attributed to Z Bentwich.

At least 109 records · Page 6Linked to original sources
PubMed1987

Immunoreconstitution of T-cell impairments in asymptomatic male homosexuals by thymic humoral factor (THF).

The feasibility of using Thymic Humoral Factor (THF) for immunomodulation in asymptomatic male homosexuals was evaluated in a study on fifteen subjects with T-cell impairments, selected on the basis of a 2SD reduction in T helper/inducer (T4+) cells and one additional lymphocytic defect. Following two biweekly courses of treatment, mean relative increments of T4+ (P less than 0.002), T3+ (P less than 0.02) and total lymphocyte (P less than 0.05) populations of the group receiving THF (n = 7) were significantly increased when compared to the placebo group (n = 8). In addition, a transient increase in T4+ lymphocytes was observed after the first course in the two individuals of the THF-treated group who were seropositive for HTLV-III/LAV but not in those who were seronegative. No difference was found between the groups in fluctuations of serum interferon (IFN) or proliferation of peripheral mononuclear cells to mitogens. The results of this limited trial demonstrate that THF is capable of correcting T-cell impairments that may predispose asymptomatic homosexuals to infection by HTLV-III, without affecting IFN production. These findings suggest that future strategies for AIDS prevention in high-risk groups should include institution of large controlled trials in immunodeficient, asymptomatic, HTLV-III/LAV-seronegative male homosexuals to study the potential of selective immunoreconstitution as a preventive measure against HTLV-III/LAV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Genetic control of HLA-linked immune responsiveness to (H,G)-A-L.

Fifty-three donors belonging to seven families were tested for their immune response potential to (H,G)-A-L. Most of these donors had been previously tested for their ability to respond to (T,G)-A-L and were all HLA typed as well. The heredity of the ability to respond to (H,G)-A-L by the production of an antigen-specific helper T cell factor is compatible with an autosomal dominant trait linked to HLA. The genotype of an HLA-A/B recombinant individual suggested that a gene controlling the immune response to (H,G)-A-L is linked to HLA-A. Lod scores also suggested a linkage between immune response potential to (H,G)-A-L and HLA-A. The different patterns of responses to (T,G)-A-L and (H,G)-A-L observed in many individuals are compatible with the notion that separate loci are governing the immune responses to the two synthetic polypeptides.

Female↗
PubMed1986

Immunogenetics of rheumatoid arthritis in Israel.

In an attempt to study the variation of associations between HLA and rheumatoid disease a population of 44 Ashkenazi and 29 non-Ashkenazi patients with Rheumatoid Arthritis were tested for HLA-A, B, C and DR antigens and compared with the relevant control groups. In contrast to the results obtained in Middle European or North American Caucasians, Rheumatoid Arthritis in Israel is not associated with B15 and Cw3, indicating that it is very unlikely that B- and C-locus antigens are involved in coding for disease susceptibility for RA. The allele DR4 which is found associated with RA in almost all populations tested so far was in the total patient group (47.9%) slightly but not significantly more frequent than in the control group (38.3%). This difference was entirely due to a nonsignificant increase in the frequency of DR4 in the Ashkenazi patients (54.5%) compared to controls (40%), while the frequency of DR4 in non-Ashkenazi patients and controls was virtually identical (38.0% vs 36.7%). Another surprising finding was that the frequency of HLA-DR1, which has been reported to be increased in different populations of patients with RA was found to be completely normal in the present study on Israeli patients. The alleles of the Bf and the GLO system did not show any significant difference between patients and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antinuclear↗
PubMed1986

Leukocyte adherence inhibition assay in the diagnosis and follow-up of colorectal cancer patients.

Antitumor immune response to colorectal cancer extract was tested by the tube leukocyte adherence inhibition (LAI) assay. Of 70 colorectal cancer patients, 38 (54%) were LAI-positive. In contrast, 15 of 159 (9%) healthy individuals and 2 of 28 (7%) patients with nonmalignant diseases were positive. The LAI activity disappeared a few months after surgery and remained negative in patients with no evidence of disease as well as in patients with disseminated progressed disease. A change of LAI from negative to positive during the follow up period correlated in some cases with the recurrence of the disease, but was observed also in cases with no clinical evidence of disease.

Colonic Neoplasms↗
PubMed1986

Diagnostic value of the computerized tube leukocyte adherence inhibition (LAI) assay for human colorectal, breast and lung cancers.

We have tested by the computerized tube leukocyte adherence inhibition (LAI) assay, 319, 100 and 342 patients and controls for the presence of antitumor immunity to colorectal, breast and lung cancers. The assay was standardized and its sensitivity increased by using, as a challenging antigen, spent medium of human carcinoma cell lines and by the addition of prostaglandin E2 (PGE2). By large, the sensitivity of the assay (after the addition of PGE2) was inversely related to tumor burden, namely, it was 82.7, 78.9, and 88.6% as compared to 57.1, 33.3, and 29.6% for the early and late stages of colorectal, breast and lung cancers, respectively. Calculating the frequency of disease in the population studied and in comparison with known frequencies of the same in the general population, the positive and negative predicting values (PVpos, PVneg) were obtained. Our results demonstrate that the LAI assay cannot be applied for mass screening since its low PVpos would impair its effectiveness. However, its application to a population at high risk for developing a particular malignancy or as a second-line modality to more conventional screening methods would increase its cost-effectiveness and favor its applicability.

Breast Neoplasms↗
PubMed1986

Antigen specific immune response potential and HLA typing of Israeli patients with thyroid autoimmune diseases (TAD).

The immune response potential to the synthetic polypeptide antigen (T,G)-A--L was studied in 35 patients with thyroid autoimmune diseases (TAD). For this purpose the ability of their antigen activated peripheral blood lymphocytes (PBL) to generate a (T,G)-A--L specific helper factor was tested. In addition, the patients were typed for their HLA determinants. The results of the study have shown that 20/35 (57%) patients responded to (T,G)-A--L, a similar proportion to that found among healthy donors that were tested as control. No significant difference was found in the rate of responses between patients with Graves' disease and Hashimoto's thyroiditis. The responses in these groups of patients were shown to be 13/22 (59%) and 7/13 (54%) respectively. HLA typing of 26 patients with TAD did not demonstrate any association of the disease or the immune response potential with any specific HLA determinant. It is proposed that unlike the general lack of regulation that we have previously observed in patients with systemic lupus erythematosus, the abnormal autoimmune reaction in TAD and probably in other organ-specific autoimmune diseases, is towards a specific organ without affecting other arms and functions of the immune system.

Autoimmune Diseases↗
PubMed1986

Organ specific neoantigens reactive in the leukocyte adherence inhibition assay: affinity purification of human colon carcinoma antigen and its cross-reactive protein using monoclonal antibodies.

A monoclonal antibody (mAb) was prepared against a semipurified preparation of an organ specific neoantigen (OSN) reactive in the leukocyte adherence inhibition (LAI) assay. The mAb (LC20.1) induces a positive LAI response when incubated with leukocytes of normal individuals in the presence of OSN derived from either human colon or lung carcinoma cell lines. Absorption of crude OSN preparations from these cell lines on immobilized LC20.1 mAb eliminates all the LAI reactive material suggesting that the mAb recognizes a common determinant on OSN from both colon and lung carcinomas. The LC20 mAb was used to affinity purify the colon cancer OSN as well as a cross-reactive normal protein from the urine of colon cancer patients and healthy donors, respectively. The colon cancer OSN and normal cross-reactive protein display an apparent molecular weight of 29,000, have a similar linear tryptic peptide map, and are indistinguishable by isoelectric focusing analysis. Regardless of the molecular similarity, only the colon cancer OSN preparation could induce a positive LAI when incubated with leukocytes of colon cancer patients. Seven additional anti-colon cancer OSN mAbs were prepared against purified material. These mAbs can be divided into three groups, each of which recognizes a distinct antigenic determinant that is shared by the colon cancer neoantigen and its cross-reactive normal protein.

Animals↗
PubMed1986

Analysis of antigen specific T cell helper function in first degree relatives of patients with systemic lupus erythematosus (SLE).

Fourteen families with first degree relatives of patients with systemic lupus erythematosus (SLE) were studied for the ability of their members to respond to the synthetic polypeptide antigen (T,G)-A-L. The family members were also tested for their HLA determinants. All SLE patients tested responded to (T,G)-A-L as measured by the production of (T,G)-A-L specific T cell helper factors by their antigen activated T cells, confirming our previous findings that 100% of SLE donors responded to (T,G)-A-L in contrast to 50% responders in a control population of healthy donors. The general defect in the regulation of immune responses in SLE patients was further indicated by the demonstration that an SLE patient who is a daughter of non-responder parents to (T,G)-A-L, responded to this genetically regulated antigen. In contrast to our observations with SLE patients, the genetic regulation of the ability to respond to (T,G)-A-L was shown not to be impaired in healthy first degree family members of SLE patients and the segregation of the immune response potential in these families was as expected from an inherited dominant trait.

Animals↗
PubMed1986

Ketotifen, disodium cromoglycate, and verapamil inhibit leukotriene activity: determination by tube leukocyte adherence inhibition assay.

Peripheral blood leukocytes (PBL) from asthmatic individuals lose their former ability to adhere to glass when incubated with leukotriene C4 (LTC4). A modified leukotriene-induced leukocyte adherence inhibition (LAI) assay was therefore used to study the ability of anti-asthmatic drugs to abrogate such activity. Ketotifen, disodium cromoglycate, Verapamil, and dimethpyridene, all at concentrations of 2 X 10(-6) M, were co-cultured with 2 X 10(-7) M LTC4 and their effect on the LTC4-induced LAI determined. Verapamil, Ketotifen, and disodium cromoglycate all inhibited the LTC4 activity while the H1 antagonist, dimethpyridene, did not. These results suggest that the beneficial effect of Verapamil, Ketotifen, and disodium cromoglycate in bronchial asthma is probably as calcium antagonists that cause the inhibition of leukotriene activity.

Calcium↗
PubMed1986

Antitumor immune response to colorectal cancer antigen detected by the leukocyte adherence inhibition test (LAI) in groups at high risk for colorectal cancer.

Colorectal cancer is the second leading cause of cancer death in western populations. As treatment outcome is highly correlated with stage at diagnosis, early detection is a very important task. Three high-risk groups for colorectal cancer (first-degree relatives of colorectal cancer patients; individuals with past history of colorectal neoplasms, polyps, or carcinoma; and patients with ulcerative colitis) were screened for colonic neoplasms. The study program included the leukocyte adherence inhibition test (LAI), a specific immune response test for colorectal cancer antigen; fiberoptic sigmoidoscopy or colonoscopy; and guaiac impregnated slide test. The main finding was the detection of 92 positive LAI tests out of 451 high-risk individuals tested (20%), compared to eight positive tests out of 194 (4.1%) in a control group. Fifty-six colonic neoplasms were found out of 344 (16%) colonoscopies performed, most of them adenomatous polyps and a few carcinomas. Our findings, compared with the expected 2-3% neoplasms in low-risk groups, would prove that the screenees were indeed at high risk. However, only 11/56 (19%) of the polyps identified were LAI positive. The number of polyps found among LAI positive individuals were, so far, 11/92 (11%). The guaiac impregnated slide test for occult blood in the stool was performed in 221 screenees. Of these only 10 were positive (4.5%) compared with the average of 1% positive tests in low-risk groups.

Antigens, Neoplasm↗
PubMed1985

Leukocyte adherence inhibition (LAI) for detecting specific tumor immunity in colorectal cancer.

Immunity to colorectal cancer antigen was tested by the tube leukocyte adherence inhibition (LAI) assay, using spent medium of human carcinoma cell lines as a source of antigen. The assay was positive in 18 out of 43 patients (41%) with colorectal tumor in comparison to only 2 out of 34 (5.8%) of colorectal cancer patients clinically free of disease, and to 4 out of 150 (2.6%) healthy subjects. The frequency of positive results correlated negatively with the tumor burden, 16 out of 29 (55.1%) patients with Dukes' A, B and C being positive compared to only 2 out of 14 (14.2%) patients with Dukes' stage D disease. Addition of PGE2 enhanced the sensitivity of the assay without affecting its specificity. The number of positive assays increased from 18 to 32 (41.8% to 74.4%) in the whole group of 43 colorectal cancer patients without altering significantly the frequency of positive results in the control group. The results with all groups of patients were influenced similarly by the addition of prostaglandins, the frequency of positive assays increasing from 55.1% to 82.7% and from 14.1% to 57.1% in early and advanced disease, respectively. These results lend further support to the value of the LAI assay in diagnosis and monitoring of the immune response in human colorectal cancer.

Antigens, Neoplasm↗
PubMed1985

Interferon modulates the leukotriene C4-induced non-adherence properties of leukocytes: acquisition of an asthmatic phenotype.

We have previously shown that peripheral blood leukocytes (PBL) of asthmatic patients acquire non-adherence properties after challenge with leukotriene C4 (LTC4), whereas PBL of normal individuals do not. Hence the use of the LTC4-induced leukocyte-adherence-inhibition (LAI) assay enables one to recognise an asthmatic phenotype on the basis of the ability of PBL to respond in vitro to LTC4. To examine the possibility that alpha interferon (IFN alpha) may have relevance to the pathogenesis of bronchial asthma, various concentrations of IFN were incubated with normal PBL and the acquisition of non-adhering properties was measured. We found that following 24 h incubation with 500 U/ml IFN, normal PBL were induced to respond to a standard dose of LTC4, and this reaction was abrogated by FPL 55712 and cyclohexamide.

Adult↗
PubMed1985

Leukotrienes (LTC4, LTD4) confer glass non-adherence on leukocytes of asthmatic individuals. Dependency on cyclooxygenase products and calcium ion.

It has been suggested that cysteinyl-containing leukotrienes (LT) are important mediators in bronchial asthma. Since leukotrienes have been shown to mediate the leukocyte adherence inhibition (LAI) phenomenon observed in cancer-bearing host we have devised a modified LAI assay which determines the acquisition of non-adherence properties of leukocytes following a challenge with pure synthetic LT. Our results demonstrate that peripheral blood leukocytes of asthmatic individuals acquire non-adherence properties when challenged with pure synthetic leukotriene C4 and D4, a property not shared by peripheral blood leukocytes of control healthy individuals. Furthermore, we demonstrate that LT activity as manifested by the LAI assay is dependent on cyclooxygenase products, since 2 X 10(-6) M Indomethacin abrogated the LT-induced LAI and is restored by the addition of 2 X 10(-6) M prostaglandin E2 which is also synergistic to LT activity. Our results further suggest the possibility that leukotriene activity is dependent on calcium ions since it was negated by known calcium antagonists. It is thus suggested that the LT-induced LAI may serve as a tool for the study of the interrelationship between the metabolic pathways of arachidonic acid and calcium ion homeostasis.

Asthma↗
PubMed1985

HLA-linked immune responsiveness to (T,G)-A-L: a family study.

The heredity of the immune response potential to the synthetic polypeptide poly(LTyr,LGlu)-poly(DLAla)-poly(LLys) [(T,G)-A-L] and its possible linkage to the major histocompatibility complex of man were studied in 24 families. Peripheral blood lymphocytes (PBL) obtained from 174 donors belonging to 24 unrelated families were educated to (T,G)-A-L on autologous antigen-pulsed adherent cells. The supernatants obtained from these activated PBL were tested for their antigen-specific helper activity in an in vitro antibody production system. All donors were typed for their HLA haplotypes. The results obtained indicated that the ability to respond to (T,G)-A-L by production of an antigen-specific T cell helper factor is inherited as an autosomal dominant trait linked to the responder HLA haplotype.

Alleles↗