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Biomedical subjects

D R Phillips

Publications and source records attributed to D R Phillips.

265 records · Page 15Linked to original sources
PubMed1972

The enzymic conversion of linoleic acid into 9-(nona-1',3'-dienoxy)non-8-enoic acid, a novel unsaturated ether derivative isolated from homogenates of Solanum tuberosum tubers.

1. A major component of the lipids in aqueous (pH7.5) homogenates of tuber tissue from Solanum tuberosum was isolated and characterized as 9-(nona-1',3'-dienoxy)non-8-enoic acid. 2. This novel unsaturated ether fatty acid derivative, which contains a butadienylvinyl ether function, has the structure: [Formula: see text] and is formed from linoleic acid by a sequence of enzymic reactions. 3. A precursor of the unsaturated ether derivative is 9-d-hydroperoxyoctadeca-10,12-dienoic acid, formed by the action of S. tuberosum lipoxygenase on linoleic acid. 4. An enzyme that converts the fatty acid hydroperoxide into the unsaturated ether derivative was isolated from S. tuberosum. The pH optimum of this enzyme is approx. 9, although the overall conversion of linoleic acid into the ether derivative is maximal at pH7.5. 5. An unusual feature of this pathway is the insertion of an oxygen atom into the alkyl chain of a fatty acid. 6. This novel mechanism may play a role in the breakdown of polyunsaturated fatty acids to volatile products in plants.

Carbon Isotopes↗
PubMed1971

Lipoxygenase from potato tubers. Partial purification and properties of an enzyme that specifically oxygenates the 9-position of linoleic acid.

A lipoxygenase (EC 1.13.1.13) was partially purified from potato tubers and was shown to differ from previously characterized soya-bean lipoxygenases in the positional specificity and pH characteristics of the oxygenation reaction. The potato enzyme converted linoleic acid almost exclusively (95%) into 9-d-hydroperoxyoctadeca-trans-10,cis-12-dienoic acid. The 13-hydroperoxy isomer was only a minor product (5%). Linolenic acid was an equally effective substrate, which was also oxygenated specifically at the 9-position. The enzyme had a pH optimum at 5.5-6.0 and was inactive at pH9.0. A half-maximal velocity was obtained at a linoleic acid concentration of 0.1mm. No inhibition was observed with EDTA (1mm) and cyanide (1mm) or with p-chloromercuribenzoate (0.2mm). Haemoproteins were not involved in the lipoxygenase activity. The molecular weight of the enzyme was estimated from gel filtration to be approx. 10(5). Preliminary evidence suggested that the enzyme oxygenated the n-10 position of fatty acids containing a penta(n-3, n-6)diene structure.

Chromatography, Gel↗
PubMedDate not supplied

Immunogold-surface replica study of ADP-induced ligand binding and fibrinogen receptor clustering in human platelets.

Platelet cohesion requires the binding of fibrinogen to its receptor, a heterodimer consisting of the plasma-membrane glycoproteins GPIIb and GPIIIa. Although the GPIIb-IIIa complex is present on the surface of unstimulated platelets, it binds fibrinogen only after platelet activation. We have used an immunogold-surface replica technique to study the distribution of GPIIb-IIIa and bound fibrinogen over broad expanses of surface membranes in unstimulated and ADP-activated human platelets. We found that the gold prove was monodispersed over the surface of unstimulated platelets, although the cell surface lacked immunoreactive fibrinogen. To ascertain whether the receptors clustered prior to ligand binding or as a consequence thereof, we studied the surface distribution of GPIIb-IIIa after stimulation with ADP, which causes activation of the fibrinogen receptor function of GPIIb-IIIa without inducing the secretion of fibrinogen. In the absence of added fibrinogen, the unoccupied, yet binding-competent receptors on ADP-stimulated platelets were monodispersed. The addition of fibrinogen caused the GPIIb-IIIa molecules to cluster on the cell surface. Clustering was also induced by the addition of the GPIIb-IIIa binding domains of fibrinogen--namely, the tetrapeptide Arg-Gly-Asp-Ser on the alpha-chain or the gamma-chain decapeptide gamma 402-411. These results show that receptor occupancy causes clustering of GPIIb-IIIa in activated platelets.

Adenosine Diphosphate↗
PubMedDate not supplied

Platelet secretory products inhibit lipoprotein metabolism in macrophages.

Macrophages possess a receptor that binds low-density lipoproteins (LDL) containing lysine residues modified by acetylation (Ac LDL), acetoacetylation (AcAc LDL) or malondialdehyde treatment. This receptor (referred to as the Ac LDL receptor or scavenger receptor) internalizes the bound lipoprotein. As a consequence, massive amounts of cholesteryl esters accumulate so that macrophages in culture resemble foam cells found in atherosclerotic lesions. In an effort to identify an unmodified mammalian macromolecule that binds to the Ac LDL receptor, we investigated whether platelet secretory products affect the receptor-mediated endocytosis of chemically modified lipoproteins. Platelets are a potential source of such activity because they exist in close association with foam cells in developing atherosclerotic lesions. Our study demonstrates that human blood platelets secrete a product that inhibits the binding and uptake of AcAc LDL by mouse peritoneal macrophages and the subsequent accumulation of cholesteryl esters. This is the first indication that an endogenous macromolecule interacts with Ac LDL receptor on macrophages.

Animals↗
PubMedDate not supplied

Nuclear and mitochondrial distribution of organoamidoplatinum(II) lesions in cisplatin-sensitive and -resistant adenocarcinoma cells.

The DNA binding pattern of the organoamidoplatinum(II) compound 1a is of considerable interest because of its known activity against cisplatin-resistant cells. The activity of 1a appears to be due at least in part to a greater cellular uptake than cisplatin into cisplatin-resistant cells, but little is known of the DNA reactions of the organoamidoplatinum(II) compounds. In this study the level of DNA cross-linking and total DNA lesions formed by 1 a were measured by gene-specific Southern hybridization cross-linking assays and by quantitative PCR in cisplatin-sensitive (2008) and in cisplatin-resistant 2008/R human adenocarcinoma cell lines. The surprising result was that the major difference between cisplatin and 1a was that the number of interstrand cross-links induced by 1a were approximately 5-fold greater than that induced by cisplatin in the nuclear (but not mitochondrial) DNA of resistant cells, even though the total number of lesions were essentially the same in both sensitive and resistant cells. This result suggests that the extent of interstrand cross-linking is a critical determinant of the cellular response to 1a and that the enhanced uptake of 1a into resistant cells results in this elevated level of cross-linking, leading to good activity of 1a against cisplatin-resistant cells. It remains unclear as to why 1a exhibits such selective damage to nuclear DNA, and insight into the molecular aspects of this selectivity will provide new opportunities for the further development of new platinum-based agents with activity against cisplatin-resistant cells.

Adenocarcinoma↗
PubMedDate not supplied

Laparoscopy during pregnancy: a literature review.

OBJECTIVE: To review the literature regarding the role of laparoscopy during pregnancy, particularly adnexal mass and non-obstetric surgery, incorporating the results of a series of 9 cases of laparoscopy during pregnancy at our centers. MATERIALS AND METHODS: A Medline search was performed to review the literature, and the reference lists provided by those articles were further explored for citations regarding laparoscopic adnexal surgery, appendectomy, and cholecystectomy. Our series of 9 patients consisted of pregnant patients with adnexal mass or acute abdomen who would otherwise have undergone exploratory laparotomy. Follow-up data for these 9 cases were collected by office visits, inquiry to the primary referring physicians, and telephone calls to the patient. RESULTS: The literature search yielded 42 additional cases of operative pelvic laparoscopy and 51 cases of abdominal operative laparoscopy (cholecystectomy and appendectomy). The publications, particularly regarding cholecystectomy, were supportive of the laparoscopic approach during pregnancy. All of the patients in our series had favorable outcomes. CONCLUSIONS: Advanced operative laparoscopy has been successfully performed for certain indications during pregnancy.

Adnexal Diseases↗