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W M Mitchell

Publications and source records attributed to W M Mitchell.

124 records · Page 7Linked to original sources

Hydrolysis at arginylproline in polypeptides by clostridiopeptidase B.

Clostridiopeptidase B, a sulfhydryl protease from Clostridium histolyticum, hydrolyzes the arginylproline bond in the synthetic polypeptide methionyllysyl-bradykinin. Hydrolysis also occurs at a reduced rate at the lysylarginine bond, further delineating the environment necessary for the minor proteolysis seen with this enzyme at lysine residues. The specificity of clostridiopeptidase B differs from trypsin, which hydrolyzes this synthetic polypeptide only at the lysylarginine bond.

Amino Acid Sequence↗

Pica in adults.

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Adult↗

Mismatched dsRNA (ampligen) induces protection against genomic variants of the human immunodeficiency virus type 1 (HIV-1) in a multiplicity of target cells.

Mismatched double-stranded RNA of the form r(I)n.r(C12-U)n (Ampligen) has been shown to be active against human immunodeficiency virus type 1 (HIV-1) using CEM and C3 cells as targets for infection by the highly similar HIV-1 isolates HTLV-IIIB and LAV (Montefiori, D.C. and Mitchell, W.M., 1987, Proc. Natl. Acad. Sci. U.S.A., 84, 2985-2989). The scope of Ampligen's anti-HIV-1 activity was examined in this study using the genetically divergent HIV-1 isolate HTLV-IIIRF, two additional target T-cell lines, H9 and MT-2, and a monocyte/macrophage cell line, U937. As judged by indirect immunofluorescence, reverse transcriptase activity and vital dye uptake, Ampligen was active against HTLV-IIIRF in H9, MT-2, C3 and U937 cells in addition to being active against HTLV-IIIB in U937 cells. A minimum of 1 h preincubation of cells (MT-2) with Ampligen was required for maximum activity. These results suggest that Ampligen's potential clinical efficacy may not be limited by either the highly variable nature or host cell range of HIV-1.

Antiviral Agents↗

In vivo screening of potential antidotes for chronic cadmium intoxication.

Nineteen chelating agents have been screened under identical conditions of metal loading in an attempt to establish their relative ability to mobilize cadmium from the liver and kidney in mice with chronic cadmium intoxication. The compounds investigated were divided into five groups: polyaminocarboxylic acids, monothiols, dithiols, macrocycles, and a miscellaneous category. Only 2,3-dimercaptopropanol (BAL) and sodium diethyldithiocarbamate (NaDDTC) were able to produce a statistically significant (at the 95% level) reduction in the cadmium content of the kidney. The closely related dithiols sodium 2,3-dimercaptopropane-1-sulfonate and 2,3-dimercaptosuccinic acid produced statistically significant increases in the liver cadmium contents, as did N-(2-mercaptopropionyl)-glycine. The reduction in kidney cadmium levels produced by both BAL and NaDDTC was just under 40%.

Animals↗

Spontaneous and interferon resistant natural killer cell anergy in AIDS.

The acquired immunodeficiency syndrome (AIDS) is characterized by severe unrelenting opportunistic infections and/or Kaposi's sarcoma associated with a dysfunction of cell mediated immune responses. In addition to cutaneous anergy and inversion of T-helper/inducer to T-suppressor cell ratios usually observed in AIDS, we have observed in three AIDS cases with multiple opportunistic infections that spontaneous and interferon (IFN) stimulated natural killer (NK) cell activity against K-562 cells is absent or severely depressed as compared to controls. Spontaneous and IFN stimulated NK cell activity in promiscuous male homosexual controls was similar to that observed in heterosexual controls. The control subjects had T-helper:T-suppressor ratios ranging from 1.1 to 2.4 in contrast to the AIDS subjects who had typical inverted ratios of T-cells ranging from 0.17 to 0.54. HNK-1, a monoclonal antibody that identifies NK and antibody-dependent cytotoxic cells, marked 3-22% of peripheral blood lymphocytes from AIDS patients in comparison to 8-38% of lymphocytes from controls. A larger series will be required in order to ascertain the true incidence of NK cell anergy in AIDS and whether or not subgroups exist based on the association of Kaposi's sarcoma in the disease process.

Acquired Immunodeficiency Syndrome↗