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Biomedical subjects

R Levy

Publications and source records attributed to R Levy.

At least 577 records · Page 32Linked to original sources

Quantitation and estimation of lymphocyte subsets in tissue sections. Comparison with flow cytometry.

A quantitation method for lymphocyte subsets in immunoperoxidase-stained frozen tissue sections was compared with flow cytometry in 23 cases of non-Hodgkin's lymphoma. Close correlations were obtained, demonstrating the accuracy of the technic. Weak intensity of fluorescence and fragility of the tumor cells during the fluorescence-activated cell sorter (FACS) analyses were the most likely explanations for a number of the discrepancies observed. The tissue quantitation method was precise, particularly at low values, where it was better than the FACS. A simpler and faster estimation method employing categories within 10 percentage units was also tested in this study; this method correlated as well with the FACS as the quantitation method and gave the best interobserver correlations.

Antigens, Differentiation, T-Lymphocyte↗

Platelet membrane properties in Alzheimer and multi-infarct dementias.

Recent investigations revealed that the physical properties of both central and peripheral cell membranes are changed in dementia of the Alzheimer Type (DAT). We attempted to ascertain whether this effect is specific for DAT by studying the polarization of diphenylhexatriene (DPH) fluorescence (an indicator of membrane "microviscosity") in the membranes of platelets isolated from DAT patients, patients with multi-infarct dementia and healthy controls. The 3 groups were matched as closely as possible for age and sex distributions. Platelet phospholipid composition was also examined in an attempt to identify the chemical basis of the membrane change(s). These studies revealed that DPH fluorescence polarization is significantly reduced in platelets from DAT patients, but not in patients with multi-infarct dementia, compared with controls. Analysis of the phospholipid composition of platelets from the 3 groups of subjects did not find any significant differences which might explain the change in membrane properties.

Aged↗

Genetic markers in late paraphrenia: a study of HLA antigens.

Patients with late paraphrenia were typed for HLA-A, -B and -C. Increased frequencies of BW55 (P = 0.036), B37 (P = 0.008) and CW6 (P = 0.056) were found relative to controls. Unlike findings in paranoid schizophrenia, there was no HLA-A9 association, suggesting that paraphrenics may be genetically distinct from schizophrenics. The primary association seems to be with B37, which has the lowest corrected P value and highest relative risk; if this were replicated, it would make possession of this antigen a strong risk factor for developing the disorder.

Aged↗

Comparison of the sensitivity of three instruments for the detection of cognitive decline in elderly living at home.

We followed up 181 elderly living at home over 2 years. The changes shown on a brief dementia rating scale (the Abbreviated Mental Test Score (AMTS] were monitored. At follow-up, subjects were classified as organic or non-organic by three potential screening tools-a screening questionnaire (the Psychogeriatric Assessment Schedule), a psychometric test (the Inglis' Paired Associate Learning Test) and a dementia scale (the AMTS). The value of these as screening tools for community samples was considered as a function of their sensitivity to cognitive decline. The classifications made by each were significantly related to previous cognitive change, but all were conservative, missing many subjects who had declined. Of the three, the AMTS appeared the most useful as a predictor of previous change on the AMTS. It remains to be seen whether it is equally useful with different samples and with different measures of outcome.

Cognition Disorders↗

Studies on B lymphoid tumors treated with monoclonal anti-idiotype antibodies: correlation with clinical responses.

Monoclonal anti-idiotype antibodies can be made which are exquisitely specific for B lymphocytic malignancies. We have conducted a clinical trial in which some patients' tumors regressed after infusion of such antibodies. Here, we evaluated characteristics of the antibodies, the tumors, and the patients to determine which features best correlated with the clinical response. Neither the isotype of the murine antibodies, nor their avidity were predictive of clinical outcome. The specific epitope to which the antibodies bound was characterized by immunochemical techniques. Reactivity with a heavy-light chain combinatorial determinant correlated somewhat with clinical effect. Variations in the characteristics of the individual tumors such as antigen sites per cell and ability to modulate the surface immunoglobulin were not predictive of response. In one patient with prolymphocytic leukemia the anti-idiotype antibody had a direct antiproliferative effect on tumor cells in vitro. This patient's tumor response was explainable by such a direct mechanism. In the other patients, who had lymphomas, therapeutic outcome correlated with the number of host nontumor cells infiltrating the tumor. The vast majority of these nontumor cells were mature T lymphocytes of the Leu 4, Leu 3 (T3, T4) phenotype. Thus, a preexistent host-tumor interaction seems to be important in the in vivo effect of anti-idiotype antibodies in B cell tumors.

Antibodies, Anti-Idiotypic↗

In vitro tests that predict tumor-associated idiotype levels in the serum of patients with B cell lymphomas and leukemias.

The presence of circulating tumor idiotype interferes with the in vivo effectiveness of anti-idiotype antibodies. We developed two assays that permit identification of patients with high levels of serum idiotype without the need for first producing an anti-idiotype antibody. A cell suspension made from the tumor was cultured for seven days with or without phytohemagglutin (PHA) and/or phorbol myristic acetate (PMA). Ig secretion in vitro by patients' tumor cells varied. In 4 patients, no secretion in vitro occurred, 5 patients had low levels, and 5 patients had high levels of Ig secretion. In three patients, Ig secretion occurred only after stimulation with PHA, PMA, or both. Spontaneous or induced immunoglobulin secretion in vitro is related to the levels of tumor idiotype secretion that exist in vivo. Eight patients with serum idiotype levels greater than 100 micrograms/mL (mean 265 micrograms/mL), had a minimum of 1.0 microgram/10(6) cells of idiotype secretion in vitro. Nine patients with serum idiotype levels less than 30 micrograms/mL (mean 3.7 micrograms/mL), had less than or equal to 0.5 microgram/10(6) cells of idiotype secretion in vitro. In another assay, the levels of IgM kappa and IgM lambda in patients' sera were compared with those in normal serum. An imbalance in the relative amounts of IgM kappa and IgM lambda indicated high levels of circulating idiotype in the serum, but this assay was less sensitive than the in vitro secretion assay and limited to IgM-secreting tumors. These assays will be useful for future clinical studies using anti-idiotype antibodies.

Antibodies, Anti-Idiotypic↗

Induction of protection against candidiasis in tumor-bearing mice by vaccination with Candida albicans ribosomes.

The aim of this study was to determine whether vaccination of tumor-bearing mice with ribosomes of Candida albicans would result in the induction of protective immunity. Therefore, (BB)F1 mice were inoculated intraperitoneally with the thymoma, EL-4, then immunized with ribosomes purified from C. albicans, and challenged intravenously with C. albicans to assess the protective response. Unimmunized mice, both normal and tumor-bearing, treated in the same manner served as controls. Both normal and tumor-bearing mice developed protective immunity in response to immunization with ribosomes. The protected mice had fewer colony-forming units in their kidneys 3 days after intravenous challenge than the unimmunized control animals, regardless of tumor status. Moreover, all unimmunized mice, tumor-bearing and normal, developed delayed hypersensitivity to the ribosomes, as well as ribosome-specific antibody, both of which were of the same order of magnitude. Therefore, the EL-4 thymoma does not suppress the immune system of mice, and they are capable of responding immunologically in a normal manner to C. albicans.

Animals↗

Anti-idiotypes in B-cell tumor therapy.

Thirteen patients with B-cell lymphomas were treated with mouse monoclonal anti-idiotype antibodies. All but 1 of the patients in this study had received extensive prior treatment with conventional therapy for lymphoma. The treatment protocol initially included an escalating dose schedule which was intended to help us evaluate toxicity and pharmacokinetics and, eventually, to achieve appreciable levels of free mouse antibody in the circulation. The last 4 patients received substantial initial doses. Tumor sampling was performed before and during therapy for evaluation of tissue penetration by antibody. Patients received antibodies of gamma 1, 2a, or 2b isotype. None of the patients had serum paraproteins by routine clinical testing, but 6 had an idiotype protein detectable by a sensitive immunoassay at levels greater than 1 microgram/ml, two of which were greater than 200 micrograms/ml. These levels were temporarily reduced by plasma-pheresis. However, the presence of serum idiotype increased the requirement for mouse antibody to achieve tumor penetration. Another obstacle to treatment was immune response to mouse Ig that occurred in 5 of the 13 patients. Once an immune response had begun, further infusions of antibody failed to reach the tumor or induce tumor regression and were associated with toxicity. Our initial patient remains in an unmaintained complete remission 50 months after receiving antibody. Six of 12 additional patients have had objective remissions which also were clinically significant. However, these remissions were not complete. This therapy shows promise as an alternative modality for the treatment of B-cell lymphoma. We will need further studies to determine the mechanisms of the antitumor effect and to improve the clinical results.

Antibodies, Monoclonal↗