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Biomedical subjects

E O'Rourke

Publications and source records attributed to E O'Rourke.

27 records · Page 2Linked to original sources
PubMed1990

Identification and preliminary characterization of protein-cysteine farnesyltransferase.

Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to exert their biological activity. Previous studies indicate that an intermediate in the mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group. Inhibition of mevalonate synthesis reverts the abnormal phenotypes induced by the mutant RAS2Val-19 gene in Saccharomyces cerevisiae and blocks the maturation of Xenopus oocytes induced by an oncogenic Ras p21 protein of human origin. These results have raised the possibility of using inhibitors of the mevalonate pathway to block the transforming properties of ras oncogenes. Unfortunately, mevalonate is a precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol. In this study, we describe an enzymatic activity(ies) capable of catalyzing the farnesylation of unprocessed Ras p21 proteins in vitro at the correct (Cys-186) residue. This farnesylating activity is heat-labile, requires Mg2+ or Mn2+ ions, is linear with time and with enzyme concentration, and is present in all mammalian cell lines and tissues tested. Gel filtration analysis of a partially purified preparation of protein farnesyltransferase revealed two peaks of activity at 250-350 kDa and 80-130 kDa. Availability of an in vitro protein farnesyltransferase assay should be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway.

Alkyl and Aryl Transferases↗
PubMed1990

Group A beta-hemolytic streptococcal bacteremia and intravenous substance abuse. A growing clinical problem?

Over an 18-month period, the incidence of group A beta-hemolytic streptococcal bacteremia rose from an average of 2.5 per 10,000 patient discharges to 17.9. A retrospective analysis was performed comparing patients with group A beta-hemolytic streptococcal bacteremia during this 18-month period with those who presented over the preceding 36 months. Most of the increased incidence was attributable to individuals hospitalized with a diagnosis of drug addiction who had concomitant soft-tissue infection, although the absolute number of hospitalized drug addicts did not change during this interval. No common or distinctive group A streptococcal serotypic patterns were discovered. This experience suggests that group A beta-hemolytic streptococcal bacteremia and soft-tissue infection may present in epidemic fashion among parenteral drug addicts in the absence of a common source.

Adult↗
PubMed1989

Chronic recurrent multifocal osteomyelitis. Association with vertebra plana.

In seven children who had chronic recurrent multifocal osteomyelitis, the radiographic and histological findings were consistent with those of osteomyelitis, but the results of cultures were negative. We studied the clinical, radiographic, histological, and microbiological findings in these patients, who had a total of thirty-nine lesions. The lesions occurred most frequently in the spine, tibia, and femur; three patients had vertebra plana. The natural history of chronic recurrent multifocal osteomyelitis appears to be slow, spontaneous resolution of the osseous lesions without specific treatment. The diagnosis is one of exclusion. Biopsy is recommended, and results of cultures must be negative before therapy with antibiotics can be withheld.

Adolescent↗
PubMed1988

Transformation of human mammary epithelial cells by oncogenic retroviruses.

We have introduced viral oncogenes into human mammary epithelial cells through the use of murine retroviruses. A continuous cell line (184A1N4) derived from benzo(a)pyrene treatment of normal breast epithelial cells was used as a recipient for the ras, mos, and T-antigen oncogenes. Each of these oncogenes enabled the 184A1N4 cells to grow in a selective medium, thus demonstrating the potential utility of these cells for oncogene detection and isolation. 184A1N4 cells transformed by T-antigen were nontumorigenic in athymic mice, but v-ras transformants were weakly tumorigenic. Transformants bearing both the T-antigen and ras oncogenes were strongly tumorigenic, however. The karyotype of these double transformants shows a high degree of stability. These results demonstrate the stepwise acquisition of the fully malignant phenotype by normal human epithelial cells in vitro.

Animals↗
PubMed1988

Functional properties of proteins coded by three human alpha-interferon genes and a pseudogene.

We have characterized the functional properties of four highly purified recombinant human class I alpha-interferon subtypes whose biological activities have not been described previously. We selected biological and biochemical activities that may discriminate between different functions of these molecules. We found that the alpha subtypes could be discriminated only by antiviral-host range specificity and natural killer cell activation. Differences in their antiproliferative activity were cell line dependent. Competitive binding, antiproliferative activity in agar, enhancement of expression of HLA-ABC, elevation of 2'-5'-oligoadenylate synthetase levels and enhancement of phosphorylation of the Mr 69,000 protein kinase did not allow discrimination among the alpha I subtypes on the tested cell lines.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

Eastern equine encephalitis in Massachusetts: a report of 16 cases, 1970-1984.

We studied the case records of 16 patients with eastern equine encephalitis (EEE) in Massachusetts from 1970 to 1984 and compared their presentations, courses, and outcomes with the data available from previous epidemics. In recent years, there has been a greater frequency of EEE in adults, whereas in the past it was considered a disease of children. Also, prognosis for a good functional recovery seems to be correlated with age over 40 years, a long prodromal course (5 to 7 days) of constitutional symptoms, and the absence of coma. Previous reports did not mention these significant correlations. We also stress the positive and negative diagnostic correlations, in order to distinguish between EEE and herpes simplex encephalitis.

Adolescent↗