[Quality control and quality assurance in medicine].
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Biomedical subjects
Publications and source records attributed to Z Bentwich.
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Seventy-four women admitted for breast biopsy were monitored before surgery for anti-tumor cell-mediated immunity using a computerized tube leukocyte adherence inhibition (LAI) assay. Spent medium from breast, lung and colon adenocarcinoma cell lines was used as the source of organ-specific neoantigens for standardization of the assay. Peripheral blood leukocytes from 25/40 (62.5%) patients diagnosed after surgery as breast cancer responded to spent medium with a positive non-adherence index (NAI). A positive NAI was inversely related to tumor mass because only 7/18 (38.8%) of those with Stage III or IV had a positive NAI; while 18/22 (81.8%) of those with Stage I or II were positive. Cross-reactive antigenicity was not observed when spent medium from breast cancer was incubated with leukocytes from patients with several other solid tumors nor when leukocytes from breast cancer patients were incubated with spent medium from lung or colon carcinoma cell lines. The antigenic material in the spent medium appears to be an organ-specific neoantigen because only 1/34 patients with benign breast disease had a positive NAI and all normal healthy control individuals were negative. The results of this study show that spent medium of a breast carcinoma cell line is more reliable than crude cancer extracts for use in LAI to detect specific anti-tumor cellular immune responses. The improved method presented in this report can be a useful tool in the early diagnosis of breast cancer and for monitoring of patients with this disease.
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A study of 191 screenees at high risk for colorectal neoplasm was undertaken to evaluate the value of the leukocyte adherence inhibition (LAI) test in detecting colorectal neoplasms. All screenees underwent total colonoscopy and LAI test. Results show that 94/191 (49.2%) screenees had neoplasms. Overall LAI positivity was 18.3% (35/191), which was highly significant, versus an asymptomatic comparison group (7.5%, 11/146). LAI test sensitivity, specificity, and positive and negative predictive values were, respectively, 19.8, 82.7, 45.7, and 58.5%. In this study the LAI test was not found to be a sensitive screening test for colorectal neoplasms. However, as the LAI test result was a significant finding within the study group, it may possibly be a risk factor and identify a subgroup that will require careful prospective evaluation.
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The relationship between release of leukotriene C4 (LTC4) from nasal mucosa in vivo and from peripheral blood leukocytes (PBLs) in vitro was examined in 18 patients with untreated rhinitis allergic to the house dust mite, Dermatophagoides pteronyssinus, and in 20 nonallergic control subjects following challenge with the specific allergen. Allergic patients were subjected to intranasal and PBL challenge with D pteronyssinus and a nonrelevant allergen, Artemisia vulgaris. In all allergic patients, intranasal challenge by D pteronyssinus, but not by A vulgaris, resulted in a release of substances from the nasal mucosa that reacted in a radioimmunoassay with antiserum to LTC4. Dermatophagoides pteronyssinus challenge in vitro of PBLs from the same patients, but not A vulgaris challenge, induced release of the same immunoreactive material into the supernatant. By comparison, the nonallergic subjects challenged with D pteronyssinus showed significantly lower LTC4 levels in their nasal secretions and PBL supernatants. The results show that, following specific allergen challenge, the release of LTC4 by the allergic nasal mucosa is similar in extent and nature to that of PBLs, indicating that these procedures can be used as tools to measure the efficacy of topically and systemically administered antiallergic drugs.
To test the possibility that T cell antigen receptor (TcR) genes are linked to the genes involved in the pathogenesis of systemic lupus erythematosus (SLE), genomic DNA restriction fragment length polymorphisms were studied, using the Southern blot technique, in 5 families with multiple members with SLE, 14 unrelated SLE patients, and 14 normal controls. Polymorphic patterns were detected with probes for all 3 TcR chains, but there was no significant difference in the distribution of the restriction fragment length polymorphism pattern among the patients, the relatives, and the controls. Furthermore, in the families with at least 2 individuals with the disease, each of the 3 TcR chain genes did not cosegregate with the disease. We conclude that TcR alpha, beta, and gamma chain genes are not likely to be linked to genes related to SLE.
Human immunodeficiency virus (HIV 1) strains were isolated from peripheral blood lymphocytes of eight homosexual men (two asymptomatic and six with lymphadenopathy syndrome) and of the wife of an AIDS patient with AIDS-related complex. All except one had antibodies to HIV in their serum. Virus isolation was carried out by cocultivation of the donors' peripheral lymphocytes with HUT-78 cells or with phytohemagglutinin-stimulated normal cord blood lymphocytes. Identification of the virus was based on detection of specific cytopathogenic effects, determination of reverse transcriptase activity, specific immunofluorescence and Southern blot analysis of HIV proviral DNA in the infected cell cultures.
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Israel is still a low incidence country for AIDS and thus the temporal relationships between various cofactors and HIV infection can be more easily determined. We have studied a cohort of 243 asymptomatic male homosexuals (MHS) during the last 4 years. At the beginning of the study, 40% had significant decreases in the peripheral blood lymphoid populations, signs for reactivation of CMV and EBV infections, and elevated serum levels of interferon. There was no difference in the prevalence of these immune derangements between seropositive and seronegative individuals. In the course of 4 years' follow-up, the prevalence of these immune derangements has remained the same though being significantly more severe in the HIV seropositive subjects. HIV seroconversion did not exceed 8% (about 2% annually) and was related to the immune impairments found when first seen at the beginning of the study. The results suggest that immune impairments are common among asymptomatic MHS, precede HIV infection, and probably contribute to the increased risk for AIDS among male homosexuals.
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We have studied 288 Israeli asymptomatic male homosexuals (MHS) to determine the prevalence of antibodies to HTLVI and HTLVIII and their correlation with impairments of the immune system and serum interferon (IFN). Seropositivity for HTLVI, HTLVIII, or both was found in 1.4, 8.3, and 0%, respectively. Significant decreases in the total peripheral T cells, TH cells, and TH/TS ratio as well as elevated alpha IFN serum levels were found in the MHS group in comparison with normal controls. Although no difference in the prevalence of either immune derangements or elevated serum IFN was observed between HTLVIII/LAV-seropositive and HTLVIII/LAV-seronegative MHS, the decreases in total T cells, TH cells, and TH/TS ratios were significantly greater in the seropositive MHS. These results indicate that (a) immune impairments and IFN system activation occur commonly in homosexuals, precede their exposure to HTLVIII/LAV, and probably reflect this group's increased risk for AIDS and (b) HTLVIII/LAV infection of MHS aggravates further their preexisting immune impairments.
An allergen-specific tube leukocyte adherence inhibition (LAI) assay has been developed in order to study the mechanism by which leukocytes lose their normal property of adherence to glass. Peripheral blood leukocytes (PBL) from 27 individuals allergic to Dermatophagoides farinae (DF), 10 with seasonal rhinitis not induced by DF and 49 non-allergic healthy volunteers were challenged in vitro with DF and a non-relevant allergen, Artemisia vulgaris (AV) and then assayed for the ability to adhere to glass tubes. Challenge by DF, but not by AV, resulted in loss of adherence by PBL from patients allergic to DF, but not in those of normal controls. The specific LAI response was dose-dependent and occurred only when a critical dose of 0.5 X 10(3) was employed. Following in vitro challenge with DF, radio-immunoassay using an antiserum to LTC4 detected immunoreactive material in supernatants of PBL from DF-allergic individuals. When highly enriched mononuclear cells from non-allergic individuals were armed with cytophilic allergen-specific IgE and challenged with the specific allergen, they lost the property of glass adherence and released a substance that was immunoreactive with LTC4. The results suggest that the chain of events leading to the LAI response in PBL from allergic individuals involves primary recognition of the allergen by specific IgE antibodies bound to receptors on mononuclear cells. The cells are thus triggered to synthesize cysteinyl-containing leukotrienes which mediate the LAI phenomenon. The results suggest that this assay may be used to study allergen-antibody interaction and the subsequent events leading to the clinical picture of atopic diseases.