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Biomedical subjects

Y Hirshaut

Publications and source records attributed to Y Hirshaut.

At least 37 records · Page 2Linked to original sources

An enzyme-linked immunosorbent assay (ELISA) for the detection of monoclonal antibodies recognizing surface antigens expressed on viable cells.

A solid-phase enzyme-linked immunosorbent assay (ELISA) has been developed for detecting monoclonal antibodies binding to surface antigens expressed on viable adherent cells of tumor cell lines. This assay utilizes a sheep anti-mouse IgG to which a beta-galactosidase is linked. It is highly sensitive and permits quantification of IgG monoclonal antibody levels. In studies of monoclonal antibodies prepared against human tumors, the ELISA assay revealed the presence of antigens which were not seen using acetone-fixed cell immunofluorescence methods. This assay is safe, rapid, low cost, and gives reproducible quantitative results. As such it should prove useful to laboratories engaged in the study of antigens expressed on cell membranes.

Animals↗

Lipid-associated sialic acid test for the detection of human cancer.

A rapid method for the measurement of serum and/or plasma, lipid-associated sialic acid levels has been developed. This test has been applied to 850 human sera of which 670 came from patients with nine categories of malignant disease, 80 from persons with benign disorders, and 100 from normal individuals. Lipid-associated sialic acid concentrations were found to be significantly increased (p less than 0.001) in all groups of cancer patients as compared to both those with benign diseases and normal controls. Test sensitivity in the detection of cancer ranged from 77 to 97%. Specificity was, respectively, 81 and 93% for the benign and normal groups. In small samples of patients, no association between test values and tumor burden was found. This test compares favorably with the most widely used tumor marker test, that for carcinoembryonic antigen.

Breast Neoplasms↗

Surgical adjuvant therapy of malignant melanoma with corynebacterium parvum.

The authors' previous surgical adjuvant trial in patients with malignant melanoma at high risk of recurrence has shown no difference in disease-free interval or survival between patients randomized to surgery + BCG or surgery alone. Reported here is a subsequent nonrandomized trial in 30 similar patients who received surgery + Corynebacterium parvum (CP) 4 mg I.V. daily x 5, followed by 4 mg S.C. weekly for up to three years. After I.V. C. parvum, chills, fever, headache, and hypertension were common. After S.C. C. parvum, varying degrees of local induration, erythema, and pain were experienced. Dose reduction was necessary for 14 patients during I.V. treatment and for six patients during S.C. treatment. A marked decrease in absolute lymphocyte count and a decreased proliferative response of lymphocytes to common antigens in vitro was observed after 2-3 days of I.V. C. parvum. Lymphocyte reactivity to mitogens decreased, particularly with Con A. Marked increase in nitroblue tetrazolium reduction by granulocytes was seen in 20 patients. Although changes in delayed cutaneous hypersensitivity reactions to recall antigens followed no consistent pattern, reactivity to DNCB increased in 18 patients. In addition, median time to recurrence was 33 weeks, significantly shorter than in the previous trial, but the survival distribution was no different from before. It can be concluded, therefore, that the administration of C. parvum in this dose and schedule had essentially no effect on the outcome of these patients.

Adolescent↗

Characterization of human sarcoma antigen S3.

An antigen common to human sarcomas, S3, has been further characterized. It is antigenically distinct from human blood-group substances A and B and from heterophile antigens such as Forssman, infectious mononucleosis and serum sickness antigens. Whilst S3 antigen preparations may contain small amounts of CEA and AFP there is no correlation between S3 antigen and the presence or amount of these known tumour-associated substances. S3 antibody can be fully absorbed with guinea-pig kidney but not boiled beef or SRBC. S3, therefore, is a heterophile substance which has not previously been identified. A seroepidemiological survey confirms that S3-antibody prevalence is significantly increased in persons with a wide variety of malignant disease, as well as in family members of patients with sarcoma.

Absorption↗

Choice and specificity of complement in complement fixation assay.

This study examines the relative activity of various complement sources in a variety of antigen-antibody (Ag-Ab) complement fixation assay systems. Studied were Ag-Ab systems of cytomegalovirus, adenovirus, Pneumococcus, Coccidiodes, and guinea pig kidney. Ab titers in each system were determined by microcomplement fixation assay using two batches of titrated rabbit, monkey, cat, dog, human cord, human adult, and guinea pig sera as complement sources. Assay sensitivity and Ab titers proved to be strongly related to the complement sources. There was considerable variation in the ability of Ag-Ab complexes to bind the complement of each of the species tested. Guinea pig, rabbit, and monkey sera gave comparable titers in four of the five Ag-Ab systems tested. Cat serum complement was able to detect anti-adenovirus and anti-Pneumococcus reactivity only. Human adult, human cord, and dog sera exhibited anti-complementary activity. The study emphasizes the importance of complement source in determining both the specificity and sensitivity of complement fixation assays in a given Ag-Ab system.

Animals↗

Effect of short-term levamisole therapy on delayed hypersensitivity.

A randomized trial of short-term Levamisole treatment was undertaken in a cancer population unresponsive to dinitrochlorobenzene (DNCB) to determine whether this agent increased delayed hypersensitivity. Of 100 patients entered, 50 received Levamisole (150 mg daily x 3) during DNCB challenge. The other 50 patients were challenged but not given the drug. The conversion rate to DNCB+ was 20% (10/50) for those treated and 12% (6/50) for controls. The difference is not significant. When all 100 patients were considered there was a statistically significant inverse relationship between extent of disease and the incidence of conversion to a DNCB reactive state. Levamisole as given does not appear to have a major influence on delayed cutaneous hypersensitivity.

Adult↗

Intralesional injection of the methanol extraction residue of Bacillus Calmette-Guerin (MER) into cutaneous metastases of malignant melanoma.

Twenty-two patients with cutaneous metastases of malignant melanoma were treated with intralesional injections of the methanol extraction residue of bacillus Calmette-Guerin (MER). The local reaction consisted of erythema and pustule formation followed by ulceration and tumor necrosis. Side effects included fever, chills, headache and malaise in the majority of patients; nausea, vomiting, cyanosis and hypotension occurred infrequently. Hypersensitivity reactions were not observed. Temporary abnormalities in liver function were seen in 11 of 19 patients tested. Reversible lymphopenia and thrombocytopenia developed in 7 of 17 and 7 of 18 patients, respectively. Immune function, as measured by skin tests for delayed hypersensitivity and the in vitro response of isolated lymphocytes to mitogens and microbial antigens, was not influenced by treatment with MER. Transient increases were observed in total hemolytic complement, complement components and the reduction of nitroblue-tetrazolium by neutrophils. Eight of eighteen evaluable patients showed a complete disappearance of all injected lesions. We conclude that intratumoral injection of MER is effective treatment for cutaneous metastases of malignant melanoma, with a complete response rate comparable to that observed after intralesional injection of BCG.

Adult↗

Two dimensional view of combination chemotherapy in vitro.

A newly developed micromethod to evaluate the cytotoxic effects of drugs on rapidly growing lymphoid cell lines is described, which permits evaluation of more than one variable. This technique allows a checkerboard titration of two drugs to determine the optimum concentration of each needed for the augmentation of the other's cell-killing activity. Such studies have shown that the minimum concentration of vincristine capable of killing a human lymphoid cell population is 5.6 ng/ml. The addition of prednisolone at a concentration of 460 ng/ml reduces the minimum lethal concentration of vincristine to 1.6 ng/ml. When prednisolone is added to vincristine at concentrations of 2.8 mu/ml (a level readily achieved in the serum in vivo) concentrations of vincristine as low as 200 pg/ml are clearly cytotoxic. Similar potentiation of cytotoxicity following the addition of prednisolone has been demonstrated for cytosine arabinoside, but not for daunorubicin and only slightly for methotrexate. The micromethod for the study of optimal doses to be used in drug combinations is simple and gives healthy reproducible results. It should be of considerable utility to anyone interested in screening a wide variety of drug combinations for augmentation or synergistic effects.

Cell Line↗

Potentiation of vincristine cytotoxicity by hormones: corticosteroids, androgens, estrogens and progestins.

Using an in vitro system to evaluate the simultaneous use of two drugs, we previously have confirmed the synergism of vincristine and prednisolone cytotoxicity against lymphoid cells. Experiments were now carried out to determine whether other steroid hormones can be substituted for prednisolone. Partial or complete potentiation of vincristine cytotoxicity comparable to that achieved by the addition of prednisolone was observed when the latter drug was replaced by a variety of mineralocorticoids (aldosterone, desoxycorticosterone and fludrocortisone), glucocorticoids (hydrocortisone, dexamethasone), androgens (testosterone, methyltestosterone, androsterone, dehydroepiandrosterone, etiocholanolone), estrogens (estrone, 17-beta estradiol) and progestins (progesterone, pregnanediol). No potentiation of cytotoxicity was observed when nonsteroidal hormones (thyroxin, ACTH) were added to vincristine. It is concluded that a wide variety of compounds with the basic perhydrocyclopentanophenanthrene nucleus of the steroid molecule are capable of enhancing the cytotoxicity achieved with vincristine.

Adrenal Cortex Hormones↗