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Biomedical subjects

V Rotter

Publications and source records attributed to V Rotter.

At least 127 records · Page 7Linked to original sources
PubMed1981

Increased concentration of an apparently identical cellular protein in cells transformed by either Abelson murine leukemia virus or other transforming agents.

Abelson murine leukemia virus (A-MuLV)-transformed cells, simian virus 40 (SV40)-transformed cells, and chemically transformed cells all have increased levels of a 50,000-molecular-weight host cell protein. The protein was detected with sera raised to the A-MuLV-transformed and chemically transformed cells and was tightly bound to T-antigen in extracts of SV40-transformed cells. Partial protease digests showed that the proteins from all three sources were indistinguishable. The three proteins were phosphorylated in cells, and the linkage of phosphate to the A-MuLV-associated P50 was to a serine residue. By immunofluorescence methods, P50-related protein was found on the surface of both normal lymphoid cells and A-MuLV-transformed lymphoid cells, but cell fractionation showed that the majority of P50 was free in the cytoplasm of the transformed cells. Immunofluorescence also showed that P50 was found in granules in the cytoplasm of both untransformed and SV40-transformed fibroblasts. Other cells gave indistinct patterns. Cocapping experiments showed that the A-MuLV-specified P120 protein is weakly associated with the surface P50-related protein of lymphoid cells, but no association of P120 and P50 could be demonstrated by immunoprecipitation methods. Although a monoclonal antiserum to P50 was used in many of these studies, the identity of the bulk P50 protein with the molecules that are reactive at the cell surface requires further study.

Abelson murine leukemia virus↗
PubMed1980

Abelson murine leukemia virus-induced tumors elicit antibodies against a host cell protein, P50.

When BALB/c mice were injected with a syngeneic cell line transformed by Abelson murine leukemia virus (A-MuLV), the tumor was usually lethal. In sera from tumor-bearing mice, and at highest levels in sera from mice that reject their tumors, was an antibody that immunoprecipitates a specific protein from [35S]-methionine-labeled A-MuLV-transformed BALB/c cells. This protein was not the previously characterized A-MuLV-specific protein (P120) but a 50,000-molecular-weight protein (P50). Such sera may also immunoprecipitate P120, but no other protein was reproducibly precipitated by them. A monoclonal antibody (RA3-2C2) that has been shown to stain normal B-lymphocytes also selectively immunoprecipitated P50. P50 was present in A-MuLV-transformed lymphoid and fibroblastic cells of a variety of mouse strains. One A-MuLV-transformed cell line had a very low P50 level, the L1-2 tumor of C57L origin. This tumor was previously shown to be rejected by C57L mice and is used to produce anti-P120 (anti-AbT) sera. P50 was not a Moloney MuLV protein and was found at low levels in normal cells of cells transformed by agents other than A-MuLV; thus, it was probably a host cell protein whose concentration was selectively accentuated by A-MuLV transformation. P50 was phosphorylated and, by using indirect immunofluorescence, anti-P50 serum stained live A-MuLV-transformed cells. The protein was not glycosylated and did not label by lactoperoxidase-catalyzed iodination. Thus, P50 was very like P120 in its cellular localization and properties, but it did not exhibit proptein kinase activity in vitro. The selective accentuation of this protein in A-MuLV transformants and its strong antigenicity in syngeneic animals suggest that it is a unique and functionally important protein.

Abelson murine leukemia virus↗
PubMed1979

Role of thymic hormone (THF) and of a thymic plasma recirculating factor (TPRF) in the modulation of human lymphocyte response to PHA and Con A.

The results presented here point to the possibility that calf thymus extracts contain, in addition to the thymic hormone (THF), a second component: thymic plasma recirculating factor (TPRF). THF, which is involved in the process of T cell maturation and has been characterized as a protein of m.w. 3000 eluted in the void volume of a G-10 Sephadex column (G-10-I), caused an increased level of intracellular cAMP in umbilical cord blood lymphocytes (UCBL). This is in agreement with our previous observation that THF plays a major role in the differentiation of T cells. The second active material, TPRF, also isolated from thymic extract, is of a molecular size below 500 and was eluted in a G-10 Sephadex column at the fourth protein peak; it seems to circulate in the blood. Previously, we had observed in impaired response of UCBL to PHA and Con A stimulation in the presence of dialyzed human plasma (DHP). Our present results indicate that this impaired response is restored exclusively by TPRF. A factor with TPRF-like activity was also isolated from the plasma of normal donors; yet it was not detected in the plasma of thymectomized patients suffering from myasthenia gravis (MG). This suggests that TPRF from plasma is thymus dependent. TPRF does not affect the level of intracellular cAMP in UCBL.

Concanavalin A↗
PubMed1979

Role of L-alanine in the response of human lymphocytes to PHA and Con A.

The response of umbilical cord blood lymphocytes (UCBL) to PHA and Con A is strongly dependent upon the presence of dialyzable plasma components. The impaired response of human cells in the presence of dialyzed human plasma was restored by calf thymus extract. In the present experiments we have further purified calf thymus extract by means of paper electrophoresis and chromatography on thin-layer cellulose plates. We reached the conclusion that the active material in this model is a single amino acid, alanine. When the different isomeric forms of alanine were tested, we found that L-alanine is the only biologically active material. In addition, we have observed here that the allogeneic response of UCBL is also dependent upon the presence of dialyzable plasma components. This impaired allogeneic response of UCBL in the presence of DHP was restored by addition of L-alanine. The present findings suggest that, under in vitro conditions, for human cells to respond to mitogenic or allogeneic stimulation L-alanine is essential.

Alanine↗
PubMed1977

Severe disseminated adenovirus infection successfully treated with a thymic humoral factor, THF.

Adenovirus and other usually benign viral infections may occasionally be associated with severe fulminant disease, often accompanied by acute acquired cellular immunodeficiency. Thymic humoral factor derived from calf thymuses has been demonstrated to have the capacity to restore the immunocompetence of immature, incompetent T cells. This factor was used in the treatment of a 3 1/2-year-old boy who was critically ill with an adenovirus infection and presented evidence of immunocellular deficiency. Within less than 48 hours after the institution of treatment with thymic humoral factor there was a dramatic, progressive clinical improvement, with restoration of the cellular immunocompetence. It is suggested that thymic humoral factor may be beneficial in the treatment of severe viral infections associated with depressed cellular immunocompetence.

Adenoviridae Infections↗
PubMed1977

Thymic hormone (THF) therapy in immunosuppressed children with lymphoproliferative neoplasia and generalized varicella.

Four children with lymphoproliferative malignant disease, two with acute lymphocytic leukemia in remission and two with Hodgkin's disease, were treated with a Thymic Hormone, THF, for disseminated varicella infecition. It is suggested that THF increased significantly the number of peripheral blood lymphocytes and T-rosette forming lymphocytes in 3 out of 4 children, who developed the varicella at the time of impaired cellular immunity. On the other hand, in the fourth child, with Hodgkin's disease, who had a normal number of T-rosettes, a decreased absolute number of lymphocytes as well as T-rosettes was observed over a course of 14 days THF treatment, although the percent of T-cells has not changed significantly. All of the four children recovered, including the child who was at high risk, with a marked lymphopenia, severe bilateral pneumonitis, hepatitis secondary infected skin lesions and psudomonas sepsis. It is indicated that THF therapy may restore the depressed cellular immunity in immunosuppressed children with malignant disease, and has its value as a supportive immunotherapy in life-threatening disseminated varicella infection.

Chickenpox↗
PubMed1977

Effect of thymic hormone on the response of different lymphoid cell populations to T mitogens.

The effect of the thymus humoral factor (THF) on the response of different lymphoid cell populations to T mitogens was studied. Lower THF concentrations were required to increase the response to concanavalin A (Con A) than to increase that to phytohemagglutinin (PHA), suggesting that T cell types at various stages of maturation are activated at different THF concentrations. Lower THF concentrations were required to enhance the mitogenic response of thymus cells than to enhance the mitogenic response of spleen cells, and this may be because of the higher incidence of target cells for THF activity in the thymus cell population. Spleen cells of adult thymectomized mice exhibited a higher sensitivity for THF than cells of intact control mice. Lymph node cells showed no increase in motogenic response after THF treatment. Similarly, THF did not affect the mitogenic response of spleen cells from nude mice. These results confirm our hypothesis that the targets for THF activity are the younger cells within the T cell lineage.

Animals↗
PubMed1976

Depletion of suppressor T cells in syngeneic chimeric mice.

The present results suggest that some T-cell activities of syngeneic chimeric mice such as T-cells involved in the antibody response to SRBC and MLC reaction are intact. On the other hand, suppressor T-cells involved in the regulation of the immune response to PVP and enhancement of 3LL tumor growth, and cells mediating CML reaction are damaged.

Animals↗
PubMed1976

Response of human lymphocytes to PHA and Con A, dependent on and regulated by THF, a thymic hormone.

The response of human lymphocytes to T lectins was shown to be dependent on and regulated by THF (thymus humoral factor). When human lymphocytes were stimulated with T lectins in the presence of dialyzed human plasma (DHP) which probably contains a low thymic hormone concentration, we observed a reduced response to PHA and Con A, compared to that observed in the presence of whole human plasma (WHP). This reduced reactivity to T lectins in the presence of DHP was restored by the addition of plasma dialyzates or THF. On the contrary, addition of THF to cultures in the presence of WHP caused a significant reduction in reactivity to T lectins, suggesting that enhancement or reduction of the response of human lymphocytes to T lectins by THF depends on the endogenous content of the thymic hormone in the plasma. From the present data it is suggested that the response of human cells to PHA behaves differently from that to Con A, as reflected in their dependence on THF. Although the response of human cells to Con A is increased by THF only in the presence of DHP, the response to PHA is also enhanced by THF in the presence of low WHP concentrations of even in the absence of WHP.

Concanavalin A↗
PubMed1975

Restoration of cellular immune response by levamisole in patients with Hodgkin's disease.

Cellular responses were studied in patients with Hodgkin's disease before and after levamisole treatment "in vivo" by measuring delayed skin reactivity to various antigens (PPD, Mumps, Candida and SK-SD), and "in vitro" by evaluating lymphocyte capacity to form spontaneous rosettes and to react to the T-cell mitogen PHA. Levamisole was found to significantly increase both the delayed skin reactivity and the number of T-rosette forming lymphocytes. Patients within two years from irradiation had reduced reactivity to PHA and in them levamisole significantly increased this reactivity. On the other hand, patients who had been irradiated more than two years prior to the study had normal reactivity to PHA which tended to decrease under levamisole treatment. It is concluded that levamisole restores the depressed cellular immunity in patients with Hodgkin's disease and its administration might be indicated in patients, especially in the immediate post-irradiation period.

Hodgkin Disease↗
PubMed1975

Inhibition of tumor growth in syngeneic chimeric mice mediated by a depletion of suppressor T cells.

Syngeneic chimeric (lethally irradiated and reconstituted with syngeneic bone marrow cells) mice manifested an increased resistance to the development of Lewis lung carcinoma. In addition, these mice had a higher response to polyvinylpyrrolidone and a reduced reactivity to T mitogens. The present findings suggest that syngeneic chimeric mice lack suppressor T cells shown to regulate the development of Lewis lung tumor and the response to polyvinylpyrrolidone. Other components of the T cell population, such as helper cells responding to sheep red blood cells or cells involved in allograft rejection, assayed in these syngeneic chimeras were found unaffected. The fact that chimeric mice are deficient in a certain suppressor T cell population whereas other T activities are normal suggests the existence of different cell lines within the T cell population.

Animals↗