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Biomedical subjects

R H Stevens

Publications and source records attributed to R H Stevens.

At least 145 records · Page 8Linked to original sources

Superoxide dismutase activity of Ehrlich ascites tumor cells.

A crude extract of Ehrlich ascites tumor cell homogenate was found to contain three distinct bands of superoxide dismutase activity by polyacrylamide gel electrophoresis. Activity bands migrated approximately the same distance and were inhibited by cyanide ions. Isolated mitochondria produced two bands of activity that were also inhibited by cyanid. Ethanol-chloroform treatment of the homogenate had no observable effect on these bands of activity, which suggested that the cyanide-insensitive mitochondrial superoxide dismutase activity in these malignant cells was either present in concentrations below detectable levels or completely absent. Normal liver was used as a control for the detection system.

Animals↗

Lymphocyte cytotoxicity in X-irradiation-induced adenocarcinoma of the rat small bowel. I. Measurement of target cell destruction by release of radioiodinated membrane proteins: brief communication.

A cell-mediated immune response as denoted by lymphocyte cytotoxicity was detected in Holtzman rats with X-irradiation-induced adenocarcinomas of the small bowel. Cytotoxicity was measured by target cell destruction as determined by release of intracellular 51Cr or radioiodinated (125I) membrane proteins. The radioiodination assay possessed an important advantage over the 51Cr technique in that the radiolabel was spontaneously lost slowly, thus permitting long-term studies.

Adenocarcinoma↗

Immunoglobulin synthesis in hairy cell leukaemia.

In vitro studies were performed with leukaemic cells from two patients with hairy cell leukaemia in order to define the nature and kinetics of immunoglobulin synthesis by the neoplastic cells. Both patients had clinically and morphologically well-defined disease and their cells contained abundant tartrate-resistant acid phosphatase. One patient had associated macroglobulinaemia. The hairy cells had B-lymphocyte characteristics as determined by fluorescent immunoglobulin staining and surface receptor properties. They synthesized monoclonal IgM and IgG respectively in vitro. The kinetics of immunoglobulin synthesis were different in cells from the two patients as measured by equilibration time, intracellular degradation, and secretion. Permanent cell lines were established with cells from these patients. The lines grow as typical B-lymphoblastoid cultures and continue to produce tartrate-resistant acid phosphatase and immunoglobulin. These studies unequivocally demonstrate the B-lymphocyte nature of the hairy cells in these patients and provide evidence for their clonal origin both in terms of immunoglobulin and enzyme synthesis.

Acid Phosphatase↗

Regulation of immunoglobulin production in human peripheral bood leukocytes: cellular interactions.

The intercellular influences regulating immunoglobulin (Ig) synthesis by normal human peripheral blood leukocytes (PBL) were investigated in cells stimulated by pokeweed mitogen (PWM). This system was shown to be totally T lymphocyte dependent as purified B lymphocytes (less than or equal to 1% T lymphocytes) failed to make significant amounts of Ig. No evidence was obtained for an Ig class switch as all classes of Ig (IgM, IgG, IgA) were shown to be produced in increasing amounts over a 6-day time period. T lymphocytes demonstrated maximum helper effect when mixed with equal numbers of B cells. This helper effect was mediated through the dual mechanisms of increasing the number of B lymphocytes containing cytoplasmic Ig and by increasing the maturity of these B lymphocytes as demonstrated by an increasing Ig production per B lymphocyte. When present in higher numbers, T lymphocytes were also capable of suppressing Ig production. This T-mediated suppression was first evident as a decrease in the Ig produced per B lymphocyte (decreased maturity). With maximum T suppression Ig-containing B lymphocyte numbers were also diminished. T lymphocyte help was relatively independent of macrophages (phagocytic cells) and did not require DNA synthesis for expression. Both T help and suppression were shown to cross allogeneic barriers. Immature T lymphocytes (thymocytes) were incapable of mediating either activity. Normal human PBL contain T lymphocytes campable of mediating both T help and suppression and the Ig produced by PBL was shown to be the balance of these activities. This balance probably represent the participation of distinct T lymphocyte subpopulations analogous to the T helper (Ly 1+) and T suppressor (Ly 2+, 3+) populations in the mouse.

Adult↗

Adenosine 3',5'-cyclic monophosphate levels in x-ray-induced small-bowel adenocarcinoma in the rat.

X-ray-induced adenocarcinomas in the small bowels of outbred Lewis Brown Norway and Holtzman rats contained significantly lower concentrations of adenosine 3',5'-cyclic monophosphate than did normal rat intestinal tissue. No significant differences were observed between the intracellular concentrations of the nucleotide in the normal rat small bowel and those occurring in normal-appearing intestinal tissue exposed to tumor induction conditions.

Adenocarcinoma↗

Severe combined immunodeficiency with B lymphocytes: in vitro correction of defective immunoglobulin production by addition of normal T lymphocytes.

A 6 1/2-month-old male with severe combined immunodeficiency (SCID) had a low percentage and number of T cells (11%; 241/mm3) and a high percentage and number of B cells (52%; 1187/mm3) and null cells (37%; 868/mm3). In vitro studies were performed to determine if this child's primary defect involved differentiation of both T and B lymphocytes or if failure of B lymphocytes to differentiate into immunoglobulin producing cells was secondary to T lymphocyte abnormalities. Immunoglobulin production by lymphocytes in response to polyclonal mitogens (pokeweed mitogen and foetal calf serum) was measured by pulse-labelling cells with 3H-leucine and then precipitating cytoplasmic and secreted immunoglobulins with polyvalent anti-human immunoglobulin and S. aureus (Cowan strain I) protein A. The patient's lymphocytes did not synthesize immunoglobulins in vitro in response to mitogens. They did not suppress synthesis of immunoglobulins by normal lymphocytes. However, addition of normal purified T cells, which themselves did not synthesize immunoglobulins, enabled the patient's B lymphocytes to become immunoglobulin synthesizing and secreting cells. Gamma, mu, and light chains were secreted. This suggests that the primary abnormality was in the T-cell axis at the level of lymphoid stem cells or prothymocytes and that failure of B lymphocytes to become immunoglobulin-producing cells was secondary to this defect.

Antibody-Producing Cells↗

Identification and characterization of a circulating tumor-associated oncofetal protein from a radiation-induced adenocarcinoma of the rat small bowel.

A tumor-associated protein from the cellular membranes of a radiation-induced rat small bowel adenocarcinoma was identified, found to be serologically unaltered in the circulatory system, and was observed to be susceptible to acid hydrolysis. The immunochemical reactivity was unchanged by heat, alkali, or neuraminidase digestion. The protein appeared to be a single immunologically active species, but it was structurally composed of a heterogeneous group of proteins.

Adenocarcinoma↗

Immunoglobulin heavy chain mRNA in mitogen-stimulated B cells.

This paper relates the synthesis of DNA, immunoglobulin and heavy chain (H) mRNA in murine spleen cells following activation of B cells with lipopolysaccharide from E. coli (LPS). Spleen cells (CBA/H mice) were cultivated with 10% FCS and 10 mug LPS/ml. 4 h pulses with [3H]thymidine showed that DNA synthesis was stimulated within the first day following LPS activation and exhibited a sharp peak at 24 h. The shape of the DNA synthesis curve suggests that the cells susceptible to LPS stimulation are activated in a synchronous manner. Stimulation of H-chain mRNA (H-mRNA) synthesis proceeded rapidly (within 6 h of LPS addition) and peaked around 24 h, in parallel to DNA synthesis. The H-mRNA was isolated and quantitated by making use of its interaction with IgG[1, 2]. The actual level of H-mRNA in the culture increased threefold during the first 24 h and then doubled within the next 48 h. Estimates of the actual number of H-mRNA were approximately 200 molecules H-m-RNA/cell on day 0 rising to 1800/cell on day 3. In such a mixed cell population these figures will be accurate only within a factor of 2-3 (at least 35% B cells in spleen cell suspensions at the commencement of the culture, with up to 35-60% of plasma blasts by day 3 and 4 of LPS treatment). Translation of the lymphoid cell mRNA in oocytes from Xenopus laevis demonstrated that stimulation of H-mRNA synthesis was restricted to mu-mRNA, although some gamma-mRNA was present in the original spleen cells. High levels of synthesis of immunoglobulin followed after a lag period of about 24 h following LPS addition peaking after 48 and 72 h; the proportional Ig production relative to total protein synthesis reached 26% on days 3 and 4. Stimulation of Ig production was limited to IgM. Rapid stimulation of mitosis and H-mRNA synthesis thus precedes the maximum synthesis of Ig molecules, suggesting a translational block on H-mRNA during cell maturation. There was no apparent block on the transport of H-mRNA from the nucleus during early stages of activation.

Animals↗

Oncofetal protein accompanying irradiation-induced small-bowel adenocarcinoma in the rat.

A tumor-associated protein was found in tissue derived from an X-irradiation-induced adenocarcinoma in the small bowel of the rat. The protein was associated with the cell membranes of the tumor tissue. It shared common antigenic determinants both with a rat fetal protein and a perchloric acid-soluble protein isolated from the serum of the tumor-bearing rat.

Adenocarcinoma↗

Protein kinase translocation as an early event in the hormonal control of uterine contraction.

beta-Adrenergic stimulation with isoproterenol inhibits contractility, increases cyclic adenosine monophosphate (AMP) concentration, decreases the concentration of unsaturated cyclic AMP receptor sites, and increases cyclic AMP-independent kinase in the uterus of ovariectomized rats. The total soluble kinase activity is reduced. The protein kinase activity lost from the cytosol was translocated to the microsomal fraction mostly in a cyclic AMP-independent form, suggesting a particulate substrate for the activated enzyme.

Animals↗