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Biomedical subjects

D A Clark

Publications and source records attributed to D A Clark.

At least 361 records · Page 20Linked to original sources
PubMed1983

Association of morphological differentiation with enhanced surface antigen expression and susceptibility to natural killer cell lysis in theophylline-treated human melanoma cells.

Human and animal melanomas undergo maturation spontaneously in vivo and in vitro, and as a result of experimental manipulation in vitro. To gain a better understanding of this phenomenon, we studied the effects of theophylline on a cultured human malignant melanoma cell line (CaCL 73-36). We observed a dose-dependent inhibition of cell growth with a reduction in plating efficiency of 16, 64, and 99% at concentrations of theophylline of 0.1, 1.0, and 2.0 mM, respectively. Theophylline-treated cells showed morphological changes consistent with a more differentiated state such as increased dendrite formation and contact inhibition. Expression of surface HLA-A,B,C antigens and beta-2-microglobulin was enhanced 15- and fivefold, respectively. Finally, cells treated with theophylline for 96 h showed a five- to eightfold increase in sensitivity to lysis by natural killer cells. These findings have obvious bearing on the potential use of theophylline in the treatment of malignant melanoma.

Antibodies, Monoclonal↗
PubMed1983

Stage II glottic carcinoma: prognostic factors and management.

Three hundred thirty-six patients with squamous cell carcinoma of the glottic larynx treated at the University of Virginia Medical Center from 1960 through 1977 were reviewed. Seventy patients with T2N0M0 disease, grouped according to the criteria of the American Joint Committee on Cancer, 1978, form the basis of this report. The 5-year actuarial survivals, recurrences, salvages, and prognostic factors were examined. Treatment was radiation, surgery, or a combination of radiation and surgery. Impaired vocal cord mobility in Stage II glottic squamous cell carcinoma is the crucial significant prognostic factor in predicting response to therapy, survival, and response to salvage therapy for recurrences. The 90% 5-year recurrence-free rate with freely mobile cords is comparable to that achieved with Stage I lesions. Impaired mobility resulted in a 5-year recurrence-free rate of 73%, which is comparable to that of T3N0 lesions. We support the concept of reclassifying Stage II disease into Stage IIa (mobile cords) and Stage IIb (impaired mobility). Based on this review and those reported in the literature, we recommend radiation therapy for Stage IIa disease. Surgery results in fewer recurrences and in longer survival than irradiation when the vocal cords are not freely mobile (Stage IIb).

Carcinoma, Squamous Cell↗
PubMed1982

Characteristics of natural killer cells in the murine intestinal epithelium and lamina propria.

Highly purified populations of lymphocytes were obtained from the murine intestinal mucosa using EDTA-collagenase isolation procedures in combination with discontinuous density centrifugation. Intraepithelial lymphocytes (IEL) were separated from lamina propria lymphocytes (LPL) and, within these two populations, fractions enriched or depleted in gut granular lymphocytes (gGL) were obtained. Using these cells in cytotoxic assays, it was shown that both IEL and LPL possess natural killer (NK) activity, and this was associated with gGL. The major effector cells of gut NK activity appeared to be Thy-1.2+, Lyt-1.1-, and Lyt-2.1-. The susceptibility of gut NK cells to anti-Thy-1.2 plus complement (C) was significantly higher than that of splenic NK cells. In contrast, anti-asialo GM1 and anti-NK-1.2 plus C only slightly affected the gut NK activity. Thus, the phenotype of the gut NK cells appears to be different from the splenic one and provides further evidence for NK heterogeneity and establishes the compartmentalization of one NK subpopulation. Beige mice, deficient in splenic NK activity, also had very low gut NK activity. W/Wv mice, which lack mast cell precursors, had normal numbers of gGL and diminished, but still present, gut and splenic NK activity. This deficiency did not segregate with the genes responsible for the basic hemopoietic stem cell defect, and these results argue against a close ontogenetic relationship between IEL, gGL, and intestinal mucosal mast cells. The relevance of these observations to the cell lineage of the effector cell of gut NK activity is discussed.

Animals↗
PubMed1982

Histological and immunological studies of post implantation death of Mus caroli embryos in the Mus musculus uterus.

Mus caroli blastocysts surgically transferred to the Mus musculus uterus implant and develop successfully during the first 9.5 days of gestation. At this time, the trophoblast giant cell area becomes infiltrated with lymphocytes and, subsequently, massive hemorrhage occurs, associated with embryo death. This process is specific for the xenogeneic embryos and does not affect adjacent allogeneic embryos present in the same uterus. Cells taken from the resorbing tissues contain a population of large Thy 1+, Lyt 1+, Lyt 2+ cytotoxic cells capable of lysing Mus caroli concanavalin A blasts in vitro. It is suggested that failure of the Mus caroli embryos in the Mus musculus uterus is mediated by the maternal immune system and that the xenogeneic blastocyst transfer system provides a suitable animal model system for studies of mechanisms that prevent rejection of the fetal allograft.

Animals↗
PubMed1982

Active suppression of host-vs-graft reaction in pregnant mice. IV. Local suppressor cells in decidua and uterine blood.

The mammalian fetus bears a wide variety of antigens against which the maternal immune system can respond. Although some of these antigens are transplantation antigens, the type of immune response mounted by the mother seems incapable of mediating graft rejection. We have previously demonstrated suppressor cells in the lymph nodes draining the uterus (DLN) that regulate the immune response in allogeneically pregnant C3H/HeJ and CBA/J mice. The suppressor cells were shown to be small lymphocytes (sedimenting at 3 mm/h at unit gravity) resistant to anti-T cell serum + complement that elaborated a soluble suppressor activity and selectively inhibited the generation of cytotoxic T lymphocytes (CTL) reactive with paternal alloantigens. Suppression could be induced in the DLN by syngeneic pregnancy or pseudopregnancy, and behaved as an anatomically localized activity during pregnancy. We now report that during first allogeneic pregnancy, the most potent suppressor cell activity is found in lymphocytes in uterine venous blood and in decidual lymphocytes. This suppressor cell population also sediments at 3 mm/h and is associated with production of a soluble suppressor factor. Substantial suppressor cell activity can also be obtained from the deciduomata of pseudopregnant mice. Local suppressor cell activity within the uterus may play an important role in ensuring the immunological success of the fetal allograft.

Animals↗
PubMed1982

Carrageenan stimulates the release of dialyzable helper factors.

We found that 1 mg of carrageenan (CGN) could enhance the primary antibody response of BALB/c spleen cells to sheep erythrocytes (SRBC). This enhancement was dependent on the strain of mouse injected as well as the type of CGN administered. In vitro experiments with spleen cells from mice treated with CGN in vivo showed that these cells release low molecular weight factor(s) which enhanced the in vitro antibody response to SRBC. Thy 1+ cells were clearly involved in the production of this factor since depletion of these cells eliminated the helper effect of CGN-treated spleen cells. Our results suggest one possible mechanism by which CGN can modulate the immune response.

Adjuvants, Immunologic↗
PubMed1982

Interspecific chimeras in mammals: a new experimental system.

The first viable interspecific chimeras in mammals have been made by mixing embryonic cells from two species of mouse, Mus musculus and Mus caroli. These chimeras resemble intraspecific chimeras in M. musculus in their patterns of mosaicism. They provide an interesting experimental system for studying interactions between cells of the two species. Three separate but related areas of investigation utilizing these chimeras are described. 1) In situ DNA-DNA hybridization using a cloned repetitive DNa sequence from M. musculus has enabled M. caroli and M. musculus cells to be distinguished in bone marrow spreads from chimeras. Further refinement of this technique should allow use of this in situ marker system for detailed analysis of cell distribution in chimeras. Such a ubiquitous marker system is not yet available in M. musculus. 2) Breeding interspecific chimeras has increased production of interspecific hybrids, which are very useful for studies of genetic interactions between the two species. 3) Mus caroli embryonic cells can survive in the M. musculus uterus in a chimera, although M. caroli embryos alone die around d 11 to 16 of pregnancy in M. musculus. Investigation of this phenomenon has implicated immune effector mechanisms in death of M. caroli embryos and has revealed the importance of trophoblast genotype for survival of foreign cells in the uterine environment.

Animals↗
PubMed1981

Decrease prostacyclin production: a characteristic of chronic placental insufficiency syndromes.

Prostacyclin production in neonates born at various gestational ages (28 weeks to term) was compared with that in neonates born of pregnancies complicated by various acute and chronic placental insufficiency states. Prostacyclin levels were reflected by the amount of conversion of 14C arachidonic acid to 6-keto-PGF1 alpha (the stable end-product of prostacyclin) by umbilical arteries. The uptake of 14C arachidonic acid by the umbilical arteries was also determined, and since this was similar for all groups it was not the cause of the differences noted in prostacyclin production. Neonates born of normal pregnancies had similar levels of prostacyclin production regardless of gestational age. Prostacyclin production was very low in neonates born of pregnancies complicated by chronic placental insufficiency (intrauterine growth retardation, essential hypertension, and pre-eclampsia), but normal with acute placental insufficiency (abruptio placentae). Hence the decrease in fetal prostacyclin production in pre-eclampsia is not related to gestational age; furthermore, it is also seen in other chronic placental insufficiency states.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Susceptibility to fatal Pichinde virus infection in the Syrian hamster.

The data presented in this paper suggest that the susceptible MHA hamster strain possesses a spleen target cell for Pichinde virus replication which is minimally expressed in the resistant strain. This target cell co-purifies with cells mediating NK activity, raising the possibility that the NK cell itself may be the additional target cell for Pichinde virus replication in the susceptible hamster strain. We hypothesize that early virus replication in the spleens of IP-inoculated hamsters leads to an overwhelming proliferation of virus. In contrast, a footpad inoculation of Pichinde virus retards virus spread into the spleen, and the host's immune response can effectively clear the relatively low amount of virus. In addition, data have been presented that show that a footpad inoculation of Pichinde virus elicits swelling in resistant hamster strains at eight days after infection, but fails to evoke a response in the susceptible MHA hamster strain. The response is controlled by a single autosomal dominant gene, and suggests that the MHA hamster strain has a defective delayed-type hypersensitivity response. The gene responsible for footpad swelling appears to be distinct from the single autosomal dominant gene that controls virus replication in the popliteal lymph nodes of footpad-injected hamsters. The phenotype of survival, then, may be the result of either limited virus replication early in infection, or an effective anti-viral cell-mediated immune response, or both.

Animals↗
PubMed1981

Age-dependent separation of class-specific suppressor cells in thymus of SJL/J mice.

The thymus of SJL/J mice of age 3-6 weeks has been previously shown to contain suppressor cells that inhibit the antibody response to lymph node cells to SRBC. The effect of these suppressor cells disappear as the animals age (24 weeks or more). We find that these aged animals acquire thymic suppressor cells which suppress the generation of cytotoxic T-cells both in vitro and in vivo. Although such suppressors are not present in the thymuses of young SJL/J mice, suppression can be induced by treatment with estrogen and progesterone. The differentiation of functionally different suppressor cell populations in thymus may be affected by both age and hormonal status.

Aging↗