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Biomedical subjects

M Shifrine

Publications and source records attributed to M Shifrine.

At least 19 recordsLinked to original sources
PubMed1979

Correlation of in vitro and in vivo tests for cell-mediated immunity in the dog.

Using tuberculin (purified protein derivative) as the test antigen, 29 dogs with different vaccination histories were tested with the lymphocyte transformation (LT) assay, the indirect agarose leukocyte migration inhibition (LMI) assay, and the skin test for delayed type hypersensitivity. All three tests were done simultaneously on each dog. The LT assay results were found to correlate well (r = 0.88) with the skin test results, whereas LMI results were found to correlate poorly (r = 0.55) with the skin test results. It was concluded that the LT assay is a more reliable measure of cell mediated immunity in the dog than is the LMI assay.

Animals↗
PubMed1978

Increased bone marrow production of granulocytes and mononuclear phagocytes induced by mycobacterial adjuvants: improved recovery of leukopoiesis in mice after cyclophosphamide treatment.

The effects of complete Freund adjuvant (CFA) or Mycobacterium bovis BCG on leukopoiesis and on leukopoietic recovery from cyclophosphamide treatment in mice was studied. CFA injected subcutaneously or intraperitoneally resulted in increased blood granulocyte and monocyte counts, increased numbers of bone marrow granulocyte and mononuclear phagocyte progenitors, and increased hematopoietic colony-stimulating factor in the serum. Furthermore, the quantitative cellular response within 24 h to an induced sterile intraperitoneal inflammation (thioglycolate) was augmented by subcutaneous CFA. In mice given CFA subcutaneously, blood granulocyte counts, as well as the peritoneal granulocyte and macrophage response to intraperitoneal thioglycolate, recovered more quickly than did those of the controls after a 250-mg/kg dose of cyclophosphamide. CFA-treated mice consistently maintained blood granulocyte and monocyte counts 1.3-to 4-fold higher than those of the controls for 2 weeks while receiving 75 mg of cyclophosphamide per kg every other day. Mice pretreated with CFA intraperitoneally had higher numbers of bone marrow colony-forming units in culture and higher levels of serum colony-stimulating factor after 250-mg/kg injections of cyclophosphamide. Similarly, BCG resulted in increased bone marrow colony-forming units in culture, increased serum colony-stimulating factor, and a faster return of the peritoneal inflammatory response after cyclophosphamide injection. These results show that mycobacterial adjuvants accelerate recovery of leukopoietic functions after cyclophosphamide treatment and suggest a mechanism whereby such adjuvants afford nonspecific protection against infection in immunosuppressed mice.

Animals↗
PubMed1978

Hypothesis for the mechanism of elevated serum copper in cancer patients.

Neoplastic growths seem to interfere with normal processes regulating the serum level of ceruloplasmin, a copper-containing oxidase, which accounts for 96% of serum copper. Normal catabolism of ceruloplasmin in the liver follows desialylation. However, in patients with tumors, ceruloplasmin may be resialylated at the tumor cell surface or in peripheral blood. Decreased catabolism due to resialylation of asialo-ceruloplasmin could account for the increased concentration of serum copper noted in patients with neoplasia.

Ceruloplasmin↗
PubMed1978

Production of mesenchymal tumors in nude mice by Ph1 negative fibroblasts obtained from a Ph 1 positive CML patient: a preliminary report.

An experimental model system is presented for the investigation in humans of the role of hematopoietic stromal elements in the regulation of hematopoiesis as well as in the pathogenesis of myelofibrosis in myeloproliferative disorders. The model is based on the simultaneous application of three experimental techniques: (1) growth of bone-marrow derived fibroblastic colonies in vitro, (2) cytogenetic demonstration of marker chromosomes associated with hematopoietic malignancies, and (3) the transplantation of isolated stromal elements into athymic (nude) mice. Using this model, we describe the induction of mesenchymal tumors in nude mice by Ph1 negative fibroblasts obtained from the bone marrow of a patient with a Ph1 positive chronic myelogenous leukemia. Mesenchymal tumors also were induced in nude mice with bone marrow-derived fibroblasts from a patient with aplastic anemia, who was successfully treated with bone marrow transplantation, and from a normal human volunteer. Morphologic, cytogenetic and electron microscopic studies of bone marrow mesenchymal elements in culture and of tumors induced in nude mice from the CML patient indicate the cells composing the tumor are of human origin and are negative for the Ph1 chromosome. The results provide the first in vivo morphological and cytogenetic support using human materials, of the hypothesized relationship of progenitors of in vitro fibroblastic colonies to marrow stromal elements.

Animals↗
PubMed1978

Growth of canine T-lymphocyte colonies in vitro.

Canine lymphocytes from peripheral blood, lymph nodes, thymus and bone marrow were stimulated with phytohemagglutinin-P (PHA) or concanavalin-A (CON-A) to form colonies in methylcellulose. Lymphocytes exposed to mitogens in liquid phase formed clumps the size of colonies. Lymphocyte clumping was eliminated by plating cells directly into methylcellulose, but high concentrations of mitogens (CON-A or PHA is greater than 10 mg/10(6) lymphocytes) were required in order to get subsequent colony formation. Thus, in contrast to published reports, exposure of lymphocytes to mitogen prior to plating was not required for cloning of canine peripheral blood lymphocytes. Colonies from thymus, lymph node, or peripheral blood consisted predominantly of T lymphocytes, whereas cultures from bone marrow also produced colonies with macrophage morphology and surface-adherent colonies with mesenchymal morphology.

Animals↗
PubMed1978

Cell surface markers on canine lymphocytes.

Reference values for T and B lymphocytes were determined on lymphocytes from canine thymus, spleen, lymph node, bone marrow, and peripheral blood by use of erythrocyte (E) and erythrocyte-antibody-complement (EAC) rosette assays, plus a direct fluorescent technique for assay of surface immunoglobulins. Numbers of T lymphocytes, indicated by E rosette formation with human erythrocytes, ranged from a low of 1% in the thymus to 13% in the peripheral blood, whereas B-lymphocyte numbers ranged from 3% (thymus) to 41% (bone marrow) and from 6% (thymus) to 36% (bone marrow), as indicated by EAC rosette formation or presence of surface immunoglobulins respectively. Stimulation of peripheral blood lymphocytes with either phytohemagglutinin or concanavalin A increased the total number of E-rosetting cells two to threefold, whereas the number of EAC-rosetting cells decreased by half. Further, the percentage of cells bearing Fc receptors increased after phytohemagglutinin stimulation. These results indicate the E rosette technique can be used to identify and to monitor a population of canine T lymphocytes.

Animals↗
PubMed1978

Comparison of whole blood and purified canine lymphocytes in a lymphocyte-stimulation microassay.

The optimum mitogen concentration and time required for using whole blood from dogs in a microassay were determined, and this test then was compared with a standard lymphocyte-stimulation microtest, using gradient-isolated lymphocytes, 2 different mitogens (phytohemagglutinin and concanavalin A), and 2 different culture media. Statistical analysis of the data from 10 dogs showed that whole blood was significantly more reactive than were gradient-isolated lymphocytes (P less than 0.05). Waymouth's medium was significantly better than RPMI 1640 (P less than 0.001), and concanavalin A was significantly more mitogenic than phytohemagglutinin (P less than 0.001). The interaction between lymphocyte source and mitogens was the only one of the various interactions that was significant at P less than 0.05.

Animals↗
PubMed1978

Delayed cutaneous hypersensitivity in the dog: reaction to tuberculin purified protein derivative and coccidioidin.

A quantitative skin test for delayed-type hypersensitivity was developed in the dog. The test procedure involved testing animals in the pinna of the ear and quantitating the reaction by measuring the change in ear thickness. Skin test reactions to tuberculin-purified protein derivative and coccidioidin were found to be specific and to correlate with the immunization histories of the 27 dogs tested. Kinetic studies on the tuberculin reaction indicated that ear thickness increased slowly following antigen injection, reaching a peak at about 48 hours. Cellular infiltrates at reaction sites were primarily responsible for the increase in ear thickness. They consisted predominantly of mononuclear cells, although a marked number of neutrophils were also present. Multiple skin tests with tuberculin-purified protein derivative and coccidioidin on 8 nonimmunized (normal) dogs indicated that a skin test was capable of actively sensitizing a portion of the animals tested.

Animals↗
PubMed1978

Immunobiology of congenitally athymic-asplenic mice.

Congenitally athymic-asplenic mice on an outbred N:NIH(S) background were produced by the mating of nude by hereditarily asplenic (Dh/+)mice. Athymic-asplenic mice survive for up to 9 months, under specific pathogen free conditions, with no evidence for increased risk of spontaneous neoplasia. Although lymphocyte surface markers and sera immunoglobulin levels of athymic-asplenic mice are similar to their nude and asplenic littermates, there are a number of significant differences. In particular, levels of sera IgA are higher than nude, but lower than either nu/+ or Dh/+ mice, related perhaps to the increased histiocytic engorgement of Peyer's patches. Athymic-asplenic mice have normal haematocrit, haemoglobin, and reticulocyte counts, but are markedly leucopenic, have a thrombocytosis and an increased number of bone marrow CFU-C. As expected, the response of the athymic-asplenic mice to the T cell mitogen PHA is markedly reduced. However, levels of Thy 1.2 bearing cells, while reduced compared to either nu/+ or Dh/+ littermates, are significantly higher than nude mice in both Peyer's patches and lymph nodes. Further, they, like their nude littermates, fail to respond to sheep red blood cell immunization. Nonetheless, athymic-asplenic mice appear more immunologically compromised than nude mice. Indeed, there is an elevated rate of growth and a lower inoculated cell threshold needed for successful transplantation of a human malignant melanoma. Finally, there was no evidence for auto-antibody production in mice up to 9 months of age. Congenitally athymic-asplenic mice can be used for a variety of studies in which other immunologically deprived mouse mutants are desired.

Animals↗
PubMed1977

Increased clonogenic (CFU-C, PFU-C) populations from bone marrow and spleen of nude mice.

Clonogenic populations from bone marrow and spleen of nude mice and their normal littermates were enumerated in vitro using a methylcellulose supported culture system. This technique allows for the simultaneous quantitation of progenitors of granulocyte-monocyte pathways (colony forming units in culture, CFU-C) and for progenitors of "mesenchymal" elements (plaque-forming units in culture or PFU-C). These populations were distinguished in culture by their growth, characteristics and morphology. CFU-C gave rise to suspended colonies of granulocyte-monocyte composition while PFU-C formed surface-adherent colonies of mesenchymal morphological features (fibroblastic and reticuloendothelial morphology). Significant elevations in the relative and absolute numbers of CFU-C and PFU-C were observed in the bone marrow and spleen of 6 wk old nu/nu mice relative to heterozygous littermates. The results are discussed in terms of non-T cells components involved in cell-medited immunity against neoplastic development.

Age Factors↗
PubMed1977

Adjuvant protection against bacterial infection in granulocytopenic mice.

The hypothesis that the induction of nonspecific resistance to infection by immunostimulation prior to drug-induced granulocytopenia would afford increased protection to subsequent bacterial challenge was tested in a murine model of infection with Pseudomonas aeruginosa or Staphylococcus aureus in mice rendered granulocytopenic with cyclophosphamide. Prior intraperitoneal immunostimulation of mice with complete Freund's adjuvant (CFA) or Mycobacterium bovis (Bacille Calmette-Guèrin; BCG) increased the 50% lethal dose in mice challenged subcutaneously with P. aeruginosa, but only CFA protected against challenge with S. aureus. The degree of protection was 1-2 log 10. Corynebacterium parvum provided no protection against infection with P. aeruginosa. The protective effect observed with CFA and BCG substantiates our hypothesis and indicates that nonspecific immunostimulation may be of value in protection of granulocytopenic patients from opportunistic infections.

Adjuvants, Immunologic↗
PubMed1977

Select growth of human T lymphocytes in single phase semisolid culture.

Selective growth and clonal proliferation of human T lymphocytes can be achieved by using a single-phase semi-solid methylcellulose system without the requirement of preincubation with lectins. Significant proliferation, however, depends upon the continued presence of Con A or PHA, but not pokeweed mitogen or lipopolysaccharide within the methylcellulose. This procedure eliminates nonspecific agglutination by lectins and allows for direct visualization of colonies and their specific removal and subsequent cloning in liquid phase. Optimal growth and production of colonies greater than 40-cell size require 3 to 9 days. Individual cells can be identified on the basis of E rosette formation and absence of surface immunoglobulin or ability to phagocytize latex particles. Moreover, proliferation is inhibited by antithymocyte but not anti-B cell sera and can be demonstrated with peripheral blood T and MOLT-4 cells, but not with B or Raji cells. Finally, colony formation is not enhanced by the presence of 2-mercaptoethanol. The clonal proliferation of human T lymphocytes has wide application in the study of both antigen recognition and lymphocyte alterations in specific diseases.

Antilymphocyte Serum↗
PubMed1977

Lymphocyte transformation in the dog: response of lymphocytes from normal and immune dogs to phytohemagglutinin, coccidioidin, and purified-protein derivative.

Antigen- and mitogen-induced in vitro transformation of dog lymphocytes was quantitated by pulse labeling with 3H-thymidine (3H-TdR). Dosages of antigen and duration of incubation were varied to determine the dose and incubation time that would allow a clear distinction between sensitized and nonsensitized dogs. Each of the 2 antigens tested, coccidioidin and purified protein derivative of tuberculin, induced a higher rate of 3H-TdR incorporation in lymphocyte cultures from dogs immunized to the homologous antigen than in lymphocyte cultures from dogs immunized to either the heterologous antigen or no antigen. Lymphocyte cultures from all dogs showed a high rate of 3H-TdR incorporation in response to phytohemagglutinin stimulation. Sequential lymphocyte transformation tests were done on 4 dogs immunized with either Calmette-Guérin bacillus alone or Calmette-Guérin bacillus in Freund's complete adjuvant. A positive response to purified protein derivative became evident in all 4 dogs 11 days after immunization and peaked at 18 days after immunization.

Animals↗
PubMed1976

Copper and zinc levels in serum from human patients with sarcomas.

Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in 19 patients with sarcomas, 12 of which were osteosarcomas at various stages. Patients with primary or metastatic osteosarcoma had elevated SCL, whereas amputated osteosarcoma patients who were clinically tumor-free had nearly normal SCL. Patients with primary osteosarcoma had elevated SZL, those with metastases had depressed zinc levels, and amputated patients who were clinically tumor-free and nearly normal SZL. Thus, the ratio of SCL:SZL in metastatic osteosarcoma patients is higher than in patients with primary osteosarcoma. SCL and SZL are compared to clinical histories for selected patients. Patients with the more advanced disease and poorest prognoses had the most elevated SCL and highest SCL:SZL ratios. It appears that the determination of SCL and SZL in osteosarcoma patients may be of value in prognosis and therapy evaluation; furthermore, the ratio of SCL:SZL may be useful in discriminating between patients with primary and metastatic osteosarcoma.

Adolescent↗