Sidney R. Cooperband

Immune Specific Induction of Interferon Production in Cultures of Human Blood Lymphocytes

Human blood lymphocytes stimulated with nonviral antigens in vitro produce an antiviral substance with the biological and biochemical characteristics of interferon. The induced response was specific for cells obtained from immune donors. Cells from nonimmune donors did not produce interferon on exposure to these substances. The quantity of interferon produced by antigen stimulation was related to concentration of antigen over a relatively narrow range; with higher concentrations induction was decreased. Interferon production was maximum during days 4 to 7 in culture. In contrast, phytohemagglutinin-induced interferon was primarily produced during the first 4 days in culture.

The Renal Clearance of Amylase in Renal Insufficiency, Acute Pancreatitis, and Macroamylasemia

Abstract The renal handling of amylase was studied in patients with renal insufficiency, acute pancreatitis, and macroamylasemia by measuring the rate of amylase clearance (CAm) relative to the rat...

Association of anergy with an immunosuppressive peptide fraction in the serum of patients with cancer.

Abstract To study the relation between circulating immunosuppressive factors and anergy in patients with cancer, we tested 53 patients with cancer for hypersensitivity to skin-test antigens and 2,4-dinitrochlorobenzene. Of 41 patients with negative skin tests, 27 (66 per cent) had immunosuppressive serum (≥70 per cent inhibition of lymphocyte stimulation by phytohemagglutinin). None of 12 with positive skin tests had immunosuppressive serum. Thus, anergy and serum immunosuppressive activity were correlated (p<0.05). After ion-exchange chromatography, most of the immunosuppressive activity in cancer serum was in the first peak, fraction I. The same fraction from subjects without cancer contained no detectable immunosuppressive activity. Mean total immunosuppressive activity of cancer serum was 166.0 ± 97.5 (S.D.) units, and that of non-cancer serum was 30.4 ± 9.2 units (p<0.05). Diafiltration of fraction I. from cancer serum yielded a fraction (< 10,000 daltons) that was highly immunosuppressive. Thus, ane...

Transformation of Human Lymphocytes: Inhibition by Homologous Alpha Globulin

An alpha globulin fraction prepared from normal human plasma by column chromatography prevents homologous lymphocyte transformation and the stimulation of DNA, and also protein synthesis induced by phytohemagglutinin and specific antigens. These observations support the concept of a normal circulating immunosuppressant factor which prevents lymphoid cell proliferation.

Selective Destruction of Target Cells by Diphtheria Toxin Conjugated to Antibody Directed against Antigens on the Cells

Monkey-kidney cells bearing new surface antigens induced by infection with mumps virus were lysed selectively by diphtheria toxin conjugated to antibody against mumps antigens.

Hyperamylasemia from the Binding of Serum Amylase by an 11S IgA Globulin

Abstract A patient with persistent hyperamylasemia and a low renal clearance of amylase was found to have an abnormally large serum amylase (11S). This large amylase, as shown by preparative ultracentrifugation and gel filtration, comprised 95 per cent of amylase in serum and 5 per cent of that in fasting small-bowel contents. Remaining amylases in serum, intestinal fluid, urine and saliva were of normal size (4–5S). The abnormal amylase was specifically precipitated with anti-IgA antiserum. Mercaptoethanol reduced the sedimentation coefficient of the large amylase to 7–8S; treatment at pH 3.4 reduced its sedimentation coefficient to normal (4–5S). Gel filtration at pH 3.4 resulted in the separation of an amylase that was normal in size and enzyme kinetics. The globulins isolated by acid dissociation bound amylase present in normal serum and increased its size to 11S. These observations are consistent with the hypothesis that hyperamylasemia and large-sized amylase result from the binding of normal amylas...

The effect of levamisole on human lymphocyte mediator production in vitro.

Abstract Levamisole has previously been demonstrated to increase delayed hypersensitivity reactions in anergic patients. In order to elucidate the mechanism by which levamisole stimulates the immune response in vivo , we have studied the effect of this substance on both human lymphocyte proliferation and lymphocyte-mediator production in vitro . Our results indicate that in vitro levamisole augments the production of soluble mediators by mitogen-stimulated lymphocytes, while having no effect on lymphocyte proliferation.

Inhibition of an in vitro antibody response by a suppressor cell in normal bone marrow

Abstract Murine bone marrow cells can suppress the in vitro primary antibody response of normal spleen cells without apparent cytotoxicity. The bone marrow cells suppress the response to both T-dependent (SRBC) and T-independent (DNP-Ficoll) antigens. When bone marrow cells are fractionated on a sucrose density gradient, the suppressive activity is found in the residue rather than the lymphocyte fraction. The suppressive activity is either unaffected or enhanced by treatment with anti-T- and anti-B-cell serums. Pretreatment of mice with phenylhydrazine which reduces the number of pre-B cells did not reduce the suppressive activity of their bone marrow cells. Suppressive activity is abolished by irradiation of the marrow cells in vitro with 1000 R prior to assay. The activity is present in the marrow of thymus deficient (nude) mice, infant mice, and mice which have been made polycythemic by transfusion. Furthermore, the suppressor cell can phagocytize iron carbonyl particles, is slightly adherent to plastic and Sephadex G-10, and can bind to EA monolayers. We conclude that the suppressor cell is not a mature lymphocyte or granulocyte nor a member of the erythrocytic series, but is likely to be an immature cell possibly of the myeloid series. We speculate on the physiologic role of this cell.

Clinical Use of Rabbit Antihuman Lymphocyte Globulin in Cadaver-Kidney Transplantation

Abstract Twenty-six consecutive recipients of cadaver-kidney transplants were treated with rabbit antihuman lymphocyte globulin (ALG) in addition to conventional immunosuppressive therapy. Each of the first 10 of these recipients has been followed for more than 12 months. The one-year transplant survival in this group was 90 per cent. Rabbit ALG administration was well tolerated. Most patients had no symptoms related to ALG injections. There were four acute transplant rejection episodes in the first 10 patients and four episodes in 16 subsequent patients followed for more than four months. All acute rejection episodes occurred six weeks or more after transplantation, and all were easily and promptly reversed by a temporary increase in the dose of steroid therapy. Immediate, hyperacute rejection by preformed antibodies was the only cause of kidney transplant loss in the entire series.

Detection of human melanoma antigens in cell-free supernatants

Abstract Common human melanoma membrane antigens have been demonstrated by immunofluorescent microscopy in cultured melanoma cells using antisera raised in humans by autoimmunization of patients with their own irradiated tumor cells mixed with adjuvant BCG. The melanoma antigens will migrate, cap, and become extruded on the cell surface when they are treated with the postimmune anti-melanoma sera. Some of these antigens are spontaneously shed into the culture media even without added antibody. Those shed antigens are stable to dialysis and lyophilization and may be isolated from a Sephadex G-200 solumn along with proteins of molecular weight 80,000–150,000 by membrane fluorescence inhibition and micro-complement fixation. Further purification of such antigens may facilitate the development of radio or enzymoimmunoassay which will permit sensitive measurement of antigens in melanoma patients.