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Biomedical subjects

T Wiley

Publications and source records attributed to T Wiley.

14 recordsLinked to original sources
PubMed2000

Inhibition of juvenile myelomonocytic leukemia cell growth in vitro by farnesyltransferase inhibitors.

Juvenile myelomonocytic leukemia (JMML) is an early childhood disease for which there is no effective therapy. Therapy with 13-cis retinoic acid or low-dose chemotherapy can induce some responses, but neither mode is curative. Stem cell transplantation can produce lasting remissions but is hampered by high rates of relapse. The pathogenesis of JMML involves deregulated cytokine signal transduction through the Ras signaling pathway, with resultant selective hypersensitivity of JMML cells to granulocyte-macrophage colony-stimulating factor (GM-CSF). A JMML mouse model, achieved through homozygous deletion of the neurofibromatosis gene, confirmed the involvement of deregulated Ras in JMML pathogenesis. With this pathogenetic knowledge, mechanism-based treatments are now being developed and tested. Ras is critically dependent on a prenylation reaction for its signal transduction abilities. Farnesyltransferase inhibitors are compounds that were developed specifically to block the prenylation of Ras. Two of these compounds, L-739,749 and L-744, 832, were tested for their ability to inhibit spontaneous JMML granulocyte-macrophage colony growth. Within a dose range of 1 to 10 micromol/L, each compound demonstrated dose-dependent inhibition of JMML colony growth. An age-matched patient with a different disease and GM-CSF-stimulated normal adult marrow cells also demonstrated dose-dependent inhibitory effects on colony growth, but they were far less sensitive to these compounds than JMML hematopoietic progenitors. Even if the addition of L-739,749 were delayed for 5 days, significant inhibitory effects would still show in JMML cultures. These results demonstrate that a putative Ras-blocking compound can have significant growth inhibitory effects in vitro, perhaps indicating a potential treatment for JMML. (Blood. 2000;95:639-645)

Adult↗
PubMed1999

Is the presence of surgically treatable coronary artery disease a contraindication to liver transplantation?

Advanced coronary artery disease has been traditionally considered an absolute contraindication to orthotopic liver transplantation where chronic liver failure significantly increases the surgical risk for coronary artery bypass grafting. Performing a simultaneous coronary artery bypass grafting and liver transplant is a theoretically attractive strategy in liver transplant candidates with coronary artery disease in need of revascularization. In the present article, we report a successful simultaneous coronary artery bypass grafting and orthotopic liver transplant with 1-yr post-operative follow-up and we discuss the rationale for this approach. In selected cases, the presence of advanced coronary artery disease should not be considered an absolute contraindication to liver transplantation.

Carcinoma, Hepatocellular↗
PubMed1998

Is age-related maculopathy related to hearing loss?

OBJECTIVE: To describe the relationship of age-related maculopathy (ARM) to hearing loss. DESIGN: Population-based cohort study. PARTICIPANTS: All 3397 adults (age range, 48-92 years) living in Beaver Dam, Wis, who were examined for age-related eye disease and hearing loss from March 1, 1993, to July 18, 1995, and who had analyzable hearing thresholds in at least 1 ear and fundus photographs gradable for ARM in at least 1 eye. METHODS: Characteristics of drusen and other lesions typical of ARM were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. We used standard protocols of pure-tone air-conduction audiometry to assess hearing loss, which was defined as the pure-tone average of hearing thresholds at 500, 1000, 2000, and 4000 Hz greater than 25-dB hearing level. RESULTS: The prevalence of ARM was 25.4% and of hearing loss was 45.0% in this population. Both conditions were present in 15.1%. The relationships between early ARM lesions and hearing loss were not statistically significant. After controlling for age and sex, persons with late ARM were more likely (odds ratio, 3.15; 95% confidence interval, 1.34-7.42) to have hearing loss than persons without late ARM. This relation did not change when other factors related to ARM or hearing loss (eg, cigarette smoking status, history of occupational noise exposure, and history of cardiovascular disease) were entered into multivariate models. CONCLUSIONS: These population-based estimates document the frequent coexistence of signs of ARM and hearing loss. As late ARM is an important cause of loss of vision, and as hearing loss is associated with difficulty in communicating, the high frequencies of sensory comorbidity may affect maintenance of independent functioning as people age. Further study is necessary to examine why late ARM and hearing loss are associated.

Adult↗
PubMed1998

Combined coronary bypass and liver transplantation: technical considerations.

Combined coronary artery bypass grafting and orthotopic liver transplantation was carried out successfully in a 58-year-old man with angina pectoris and end-stage liver disease. To date, only 2 similar cases have been documented worldwide whereby the transplantation was performed either during cardiopulmonary bypass or with femoral-to-axillary venovenous bypass initiated at the termination of cardiopulmonary bypass. In this report we describe our experience with a simplified one-exposure approach for the combined operation using cardiopulmonary bypass in tandem with percutaneous femoral-to-right atrial venovenous bypass.

Angina Pectoris↗
PubMed1983

De novo cholesterogenesis in pregnancy.

Hypercholesterolemia occurs during pregnancy in rats and human beings, beginning in the second trimester and increasing progressively throughout the remainder of pregnancy. The present study quantified de novo cholesterol synthesis in vivo and in vitro in pregnant animals using 3H2O as the substrate for measuring cholesterogenesis. In the third trimester, cholesterol synthesis by pregnant rat gut and carcass (all tissues not specifically studied) was not significantly different from that observed in controls. However, hepatic cholesterol synthesis was markedly stimulated in third trimester pregnant rats. Additionally, cholesterol synthesis in the placenta and fetus occurred at a very substantial rate. The magnitude of placental cholesterol synthesis was similar to that observed in the liver of control animals whereas fetal cholesterogenesis was considerably greater. Cholesterol feeding greatly suppressed hepatic cholesterol synthesis in both control and pregnant animals, so that the difference between control and pregnant animals was obliterated. Cholesterol feeding did not significantly affect the accumulation of newly synthesized cholesterol in either the placenta or fetus. In the Saguines fusciollis monkey, pregnancy similarly stimulated hepatic cholesterol synthesis, and the fetus and placenta were important sites of in vivo de novo cholesterogenesis.

Animals↗
PubMed1975

Effects of solutes on the swelling pressure of the corneal stroma.

The chemical environment of bare, excised rabbit corneal stroma was varied to determine the effects of solutes on the swelling pressure. Measurements of changes in the thickness of the stroma are converted to hydration units which are in turn converted to a change in swelling pressure at the initial hydration. The order of effects on swelling pressure are compared to the Hofmeister series for polyelectrolyte gels and the results are analyzed in the context of a structural theory of the swelling pressure of corneal stroma proposed by Hart and Farrell and based on the gel properties of the stroma.

Animals↗
PubMedDate not supplied

Quality assurance guidelines for a biomedical information web system: the working experience of the BreakIT project.

The paper outlines the quality control issues that arise in the implementation of a Web site which delivers biomedical information. At the heart of this study is the need for a methodology to guarantee that the information contained in the site is viable and accurate from both an informatic and a content point of view. This methodology is currently adopted in the Web development of the BreakIT project sponsored by the EU INFO2000 Programme.

Breast Neoplasms↗
PubMedDate not supplied

Sustaining Oncology Studies--SOS: information and support for training, research and exploitation in cancer and related biomedical disciplines.

This paper outlines the development of the Sustaining Oncology Studies Information Resources (SOS Europe), a multimedia World Wide Web (WWW) prototype providing support to experimental and clinical cancer researchers, general practitioners, industry personnel, and university students in the field of oncology in Europe and Italy. The system utilizes applications developed for the WWW and is designed in the most easily understandable approaches possible. The prototype now structures oncology-related information available on the Internet and also places resources maintained locally at users' disposal. The system utilizes a WWW browser as a design platform and HTML to build its Home and subpages and to create hyperlinks to internal and external resources.

Computer Communication Networks↗