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Biomedical subjects

R M Williams

Publications and source records attributed to R M Williams.

246 records · Page 14Linked to original sources
PubMedDate not supplied

Arglabin-DMA, a plant derived sesquiterpene, inhibits farnesyltransferase.

Arglabin [1(R),10(S)-epoxy-5(S),5(S),7(S)-guaia-3(4),11(13)-dien-6, 12-olide], a sesquiterpene gamma-lactone is isolated from Artemisia glabella, a species of wormwood endemic to the Karaganda region of Kazakstan. The compound has been modified to render it water-soluble through addition of a dimethylaminohydrochloride group to the C(13) carbohydride moiety to yield Arglabin-DMA. Arglabin-DMA is a registered antitumor substance in the Republic of Kazakstan. Previously, we have shown that this compound prevents protein farnesylation without altering geranylgeranylation. We now report that Arglabin-DMA inhibits the incorporation of [(3)H]farnesylpyrophosphate into human H-ras protein by FTase with an IC(50) of no greater than 25 microM. Kinetic studies show that the phosphorylated form of this compound competitively inhibits the binding of farnesyl diphosphate to FTase. This mechanism of action is different from other reported peptidomimetic FTIs which lower the affinity of ras protein to FTase. Our in vitro studies confirm that Arglabin-DMA inhibits post-translational modification of ras protein in cells. Arglabin-DMA inhibits anchorage-dependent proliferation of NB cells (IC50=10 microg/ml) and inhibits anchorage-independent growth of NB and KNRK cells with about the same IC(50). Soft-agar colony formation assay of H-ras and K-ras transformed cells show IC(50)s to be 2 and 5 microg/ml, respectively. In primary cultures of human tumor cells, Arglabin-DMA inhibits cell proliferation of a variety of tumor types with IC(90)s in the range of 0.85 to 5.0 microg/ml. Because of these pharmacologic properties, we propose that Arglabin-DMA is suitable for the treatment of ras related malignancies.

3T3 Cells↗
PubMedDate not supplied

Rx: social reconnaissance.

The Kaiser Foundation's grassroots approach enables communities to set their own health priorities. The technique works--and it's become contagious.

Community Participation↗
PubMedDate not supplied

To lead or lag?

Health care policy is the hottest of all emerging issues. Although the largest foundations have changed to meet the challenge, one question remains: should health funders advocate as well as explore solutions?

Financing, Organized↗
PubMedDate not supplied

For fee or charity?

Explore the source record for details and available documents.

Charities↗
PubMedDate not supplied

Development of GM-CSF antagonist peptides.

Granulocyte/macrophage colony stimulating factor (GM-CSF) is both a hematopoietic growth factor and a cytokine implicated in inflammatory disease. The development of GM-CSF antagonist peptides corresponding to the GM-CSF native sequence should allow their modification into higher affinity analogs, but this is hampered by the low affinity of linear peptides. To adequately evaluate such low affinity peptides, the use of several independent assays should allow specific versus nonspecific inhibitors to be distinguished. In this study, inhibition of GM-CSF-dependent cell growth, inhibition of GM-CSF binding and immunologic cross-reactivity between GM-CSF-derived peptides and native protein by neutralizing antibodies have been used to evaluate peptide analogs with potential bioactivity. The GM-CSF sequence was divided into 6 peptides ranging in size from 15-24 amino acids. Antisera were raised to these peptides in mice and assayed for immunologic cross-reactivity. 4/6 anti-peptide antisera bound GM-CSF on ELISA and 3/6 on immunoprecipitation. Antisera to two of the peptides (corresponding to residues 17-31 and 96-112) inhibited GM-CSF-dependent cellular proliferation in two cell lines, with one peptide derived from residues 17-31 demonstrating inhibition of GM-CSF binding and direct biological inhibitory activity. A peptide that did not elicit native GM-CSF reactive antibodies, corresponding to residues 54-78, was recognized by two neutralizing monoclonal antibodies. It exhibited inhibition of GM-CSF binding and direct biological antagonist activity. These studies implicate two sites in mediating GM-CSF biological activity, and indicate that biological antagonists can be developed based on these sites.

Amino Acid Sequence↗
PubMedDate not supplied

Histopathology: its role in the diagnosis of a child with intussusception.

Spontaneous expulsion of a small portion of the intestinal mucosa per rectum, in an infant, associated with ileocolic intussusception is an extremely rare condition. This appears to be the first report of such a clinical presentation. The initial diagnosis was raised by the histopathologist following examination of the eliminated piece of tissue. Subsequent barium enema and laparotomy confirmed the diagnosis and the ileocolic intussusception was successfully reduced. This unusual presentation, together with a review of the pertinent literature, is discussed. Our findings indicate that both the clinicians and histopathologists should be aware of this phenomenon and stress the importance of the histological examination of any unusual faecal matter. This may prove to be a simple, quick and cheap method of investigation of this condition.

Colon↗
PubMedDate not supplied

Pneumococcal vaccination.

Streptococcus pneumoniae community-acquired pneumonia (CAP) results in 40,000 deaths each year (Atkinson, 1997), making it the leading cause of death secondary to infection. Of these deaths, 50% could be prevented with the use of the pneumococcal vaccine. Developed 20 years ago, only 28% of patients 65 years and older receive the vaccine despite a prevention rate of invasive pneumococcal infections of 56-81% in immunocompetent adults. The overall cost for treating patients with CAP is more than $23 billion per year. More than $3.5 billion was spent on Medicare patients alone. Immunizing identified high-risk patients for CAP can improve morbidity and mortality rates for this group and ultimately reduce the amount of health care dollars spent on this preventable disease. Guidelines for identifying high-risk groups, a description of the vaccine, vaccination recommendations, and the signs and symptoms of CAP are discussed.

Adult↗