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Biomedical subjects

R H Stevens

Publications and source records attributed to R H Stevens.

At least 127 records · Page 7Linked to original sources
PubMed1979

The production of a soluble human T-lymphocyte derived factor which substitutes for helper T lymphocytes in the in vitro production of immunoglobulin.

A soluble factor(s), human T-lymphocyte derived help factor (HHF), generated following pokeweed mitogen (PWM) activation of irradiated human peripheral blood T lymphocytes was shown to substitute partially for T-lymphocyte helper activity in the T-lymphocyte dependent PWM-stimulated synthesis of immunoglobulin by B cells. The degree of help provided was proportional to the number of cultured irradiated T-lymphocytes producing factor as well as the amount of factor added to the B-cell culture. The helper effect was equally provided by HHF syngeneic and allogeneic to the B lymphocyte. Although there was little stimulation of total protein synthesis, the synthesis and secretion of IgG, IgM and IgA were all stimulated three- to ten-fold by this factor. The B cells required a minimum of 40--55 h exposure to the factor from the initiation of the culture for an increase in Ig synthesis on day 5 to be observed. Addition of HHF to B cells pre-incubated with PWM for different time intervals showed that a maximum helper effect was exerted when the factor was added on day 0. Addition on day 1 provided less than 20% of maximum help. The factor did not promote significant increases in either B-cell or T-cell cell division.

B-Lymphocytes↗
PubMed1979

Human lung tumor-associated antigens of 32,000 daltons molecular weight.

Lung tumor-associated antigens of approximately 32,000 daltons were recognized by the use of sensitive radioimmunoassays and rabbit antisera, one raised against an extract of pooled human malignant lung tissues and another raised against a cell line derived from a human squamous cell carcinoma of the lung. These antigens differ from antigens described previously, including carcinoembryonic antigen and alpha-fetoprotein. The antigens were detected on 13 of 13 lung tumors (of all histologic types), fetal tissue, normal brain, 2 of 8 colon tumors, 2 of 9 prostate tumors, and 2 of 3 breast tumors, as well as on cell lines derived from lung tumors, neuroblastoma, human amnion, colon adenocarcinoma, and bladder tumors. They were not detectable on normal lung, liver, kidney, colon, or prostate tissues or on cell lines derived from osteosarcoma, fetal lung fibroblasts, transitional cell carcinoma, and squamous cell carcinoma of the skin. Lung tumors of different histologic types were concluded to express common, tumor-associated oncofetal antigens that are found less often on tumors of other organs.

Antibodies, Neoplasm↗
PubMed1978

Cyclic nucleotide concentrations in 1,2-dimethylhydrazine induced rat colon adenocarcinoma.

The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) in colonic tumors induced in adult male Holtzman rats by 1,2-dimethylhydrazine (DMH) were found to be 1/2 the concentration found in normal large bowel tissue. Intracellular concentrations of guanosine 3'-5'-cyclic monophosphate (cGMP) in the neoplastic cells were twice the normal colon level. The concentrations of these two cyclic nucleotides were relatively constant throughout the normal colon. Thus, the anomalous tumor cyclic nucleotide concentrations are attributed to the specific cell population of the lesion and not to the site of development within the colon.

Adenocarcinoma↗
PubMed1978

Cyclic nucleotide concentrations in 1,2-dimethylhydrazine and x-ray induced rat small intestinal cancer.

The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) were determined in adult male Holtzman rat small intestinal tumors induced by subcutaneous administration of 1,2-dimethylhydrazine (DMH) or X-irradiation of only the hypoxic ileum and jejunum. The levels of cAMP and cGMP in the cancer cells from DMH-treated animals were 50% and 200%, respectively, of the values measured for intestinal tissue. The amounts of cGMP in the lesion of the X-irradiation induced rat small bowel adenocarcinoma determined in the present investigation and of cAMP measured previously were observed to be only 50% of the value for unirradiated intestine. It has thus been shown that in the DMH-induced colon and small intestinal tumors, the X-irradiation induced rat small bowel adenocarcinoma and the human colon adenocarcinoma, the cAMP concentrations are consistently about 50% of the levels measured in comparable normal tissues. These findings of diminished intracellular cAMP concentrations imply a serious cellular defect mechanism occurring in intestinal cancer. However, there appears to be no similar pattern of change for the intracellular concentrations of cGMP, which suggests that different biochemical pathways exist in these malignancies.

Adenocarcinoma↗
PubMed1978

Cyclic nucleotide concentrations in 7.12-dimethylbenz[a]anthracene-induced pancreatic cancer in rats.

Pancreas cancer was induced in noninbred male Holtzman rats by the implantation of beeswax containing 7.12-dimethylbenz[a]anthracene (DMBA) into the "head" of the pancreas. The tumors that developed 4--6 months later were examined for their cyclic AMP and cyclic GMP levels. The lesions could be considered in one of two categories according to their cyclic nucleotide contents: lesions with significantly smaller amounts and those with greater amounts, compared with levels measured in the pancreas tissues of the control rats. The existence of two biochemically distinct groups may indicate different growth patterns of the DMBA-induced pancreatic neoplasia.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Glucocorticoids administered in vivo inhibit human suppressor T lymphocyte function and diminish B lymphocyte responsiveness in in vitro immunoglobulin synthesis.

The effects of corticosteroid given in vivo on human lymphocyte subpopulation function were investigated using an in vitro system of pokeweek mitogen-stimulated immunoglobulin production. Peripheral blood lymphocytes were obtained from normal volunteers before and 4 h after the intravenous administration of methylprednisolone. Unfractioned peripheral blood lymphocytes showed a consistent decrease (mean congruent with 50%) in immunoglobulin and total protein synthesis after steroid administration. Utilizing separated thymus-derived (T) and bone marrow-derived (B) lymphocyte fractions, the pathophysiology of this alteration in immunoglobulin production was elucidated. B lymphocytes obtained after steroid treatment showed a markedly diminished immunoglobulin response (20% of normal) to normal T lymphocytes and to normal T cells that had been irradiated to remove suppressor T lymphocyte function. All major classes of immunoglobulin (IgG, IgM, and IgA) were affected. T lymphocytes procured after steroid administration were capable of providing normal amounts of T cell help for B cells in immunoglobulin production. However, suppressor T lymphocyte activity, observed with normal T lymphocytes at high T to B cell ratios, was absent from the post-steroid T lymphocytes. This loss of suppressor T lymphocyte function was not due to the presence of excess help as irradiated pre- and poststeroid T cells provided equal amounts of helper activity. On recombining the poststeroid treatment B cells, which are hyporesponsive in immunoglobulin synthesis, with the posttreatment T lymphocytes, which lack suppressor activity, diminished amounts of immunoglobulin were produced which correlate well with the effects observed with unseparated cells. Thus, corticosteroids have differential effects on the lymphocyte populations involved in immunoglobulin biosynthesis. B cell responsiveness is diminished, suppressor T lymphocyte activity is removed, and helper T lymphocyte function is unaffected.

Adult↗
PubMed1978

Immunoregulation in humans: control of antitetanus toxoid antibody production after booster immunization.

Booster immunization of normal individuals with soluble tetanus toxoid resulted in the ability of the individuals' peripheral blood lymphocytes to synthesize immunoglobulin (Ig)G antitetanus toxoid antibody in vitro when stimulated by pokeweed mitogen. The capacity for this in vitro antitetanus toxoid antibody response developed within 14 days after booster immunization, reached a peak between days 36--50, and disappeared by day 60. The inability of pokeweed mitogen to stimulate antitetanus toxoid antibody synthesis in vitro before booster immunization was not due to excess suppression by thymus-derived (T) lymphocytes but reflected insufficient numbers of functionally specific helper T lymphocytes and bone marrow-derived (B) lymphocytes. Antigen-specific T-lymphocyte suppression and decreased B-lymphocyte function were associated with the observed reduction of in vitro synthesis of antitetanus toxoid antibody from 20--60 days post-immunization. The in vitro kinetics of antitetanus toxoid antibody synthesis paralleled the synthesis of total IgG in that stimulation by pokeweed mitogen was required and that antibody secretion into the medium initiated by day 4 and increased through day 9.

Adult↗
PubMed1978

Lymphocyte cytotoxicity in the X-irradiation induced rat small bowel adenocarcinoma. II. Presence of cytotoxic lymphocytes in irradiated animals.

Cytotoxic peripheral blood lymphoid cells were demonstrated in both Holtzman and Lewis Brown-Norway rats which had received 2000R of local X-irradiation to the temporarily hypoxic, exteriorized, ileum and jejunum regardless of whether a small bowel adenocarcinoma subsequently developed. The cytotoxic response, which was detectable at two days, was quite evident by day 5 post-irradiation. No evidence of cross-reacting tumor antigens was obtained when similarly processed effector cells from Holtzman rats bearing a spontaneous mammary carcinoma were incubated with cell cultures derived from the small bowel adenocarcinoma. These findings indicate X-irradiation of the small bowel initiates lymphocyte sensitization that is manifested as in vitro cytotoxicity against cell cultures of the adenocarcinoma.

Adenocarcinoma↗
PubMed1978

T-lymphocyte variant of hairy-cell leukemia.

Immunohematologic studies on cells from a patient with the clinicopathologic syndrome of hairy-cell leukemia showed that the neoplastic cells had receptors for sheep erythrocytes and therefore had human T-lymphocyte characteristics. The leukemic cells did not have the membrane receptors or immunoglobulin markers of B lymphocytes or monocytes nor did they synthesize immunoglobulin. A lymphoid cell line established in vitro from the cells had the same T-lymphocyte characteristics. The lymphoid cell line is positive for tartrateresistant acid phosphatase, forms rosettes with untreated sheep erythrocytes, and reacts with an anti-T-lymphocyte antiserum. Thus the syndrome of hairy-cell leukemia may occasionally result from the neoplastic proliferation of T-lymphocytes as well as from the more usual B-lymphocyte form. This situation is analogous to that described previously in chronic lymphocytic leukemia and other lymphoproliferative disorders.

Acid Phosphatase↗
PubMed1978

Immunologic characterization of hairy cell leukemias in continuous culture.

The immunobiologic characteristics of three continuous cell lines established from hairy cell leukemia cells were investigated. All three cell lines continued to produce tartrate-resistant acid phosphatase, the enzymatic marker of hairy cells. Two of these cell lines were B lymphoid in nature. They carried Fc and C receptors, had surface and internal immunoglobulin, and did not form spontaneous sheep red blood cell rosettes. Experiments employing biosynthetic radiolabeling of immunoglobulin demonstrated distinctive immunoglobulin kinetics for each of these two hairy cell lines. One cell line remained quite similar to the original hairy cells from which it was derived whereas the other B lymphoid hairy cell line had undergone a switch in the immunoglobulin isotype produced. The third hairy cell leukemia line was shown to be of thymic derivation. These cells formed spontaneous sheep red blood cell rosettes and did not carry Fc or C receptors. The spontaneous sheep red blood cell rosette-forming cells contained tartrate-resistant acid phosphatase. They did not possess surface on internal immunoglobulin and did not synthesize immunoglobulin in vitro. Hairy cell leukemia cells maintained in permanent cell culture retain their immunobiologic properties and offer the opportunity for indepth study of these unusual cells.

Acid Phosphatase↗
PubMed1978

Lymphocyte cytotoxicity in x-irradiation-induced rat small bowel adenocarcinoma. III. Blocking by 3 M KCL extract.

Hypertonic salt extracts (3 M KCl) of x-irradiation-induced Holtzman rat small bowel adenocarcinomas blocked the in vitro destruction of allogeneic cultured cells of this malignancy by sensitized lymphoid cells obtained from tumor-bearing animals. The protective effect were mediated by a blocking action at both the effector and the target cell level. The extracts were separated into 50% ammonium sulfate soluble and insoluble fractions with the soluble fraction being more effective in blocking the cytotoxic responses through interaction with the lymphoid cells whereas the insoluble one had a greater effect upon tumor target cells. Associated with both fractions was the oncofetal glycoprotein previously identified with the cellular membrane of this x-ray-induced malignancy. Immunoglobulins were identified with insoluble fraction; some were able to bind the oncofetal protein, thus clasifying it as a fetal antigen. The protective effects of the soluble fraction and this neoantigen were found to be citric acid labile, whereas the effects due to the insoluble fraction were unchanged.

Adenocarcinoma↗