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Biomedical subjects

Steve Miller

Publications and source records attributed to Steve Miller.

7 recordsLinked to original sources
PubMed2007

Eukaryotic initiation factor 4E variants alter the morphology, proliferation, and colony-formation properties of MDA-MB-435 cancer cells.

Eukaryotic initiation factor 4E (eIF4E) binds to the 5' m(7)G cap of mRNAs and is a focal point of regulation of initiation of mRNA translation. High levels of expression of eIF4E in many epithelial cancers, including breast, head and neck, colon, and bladder, correlate with increased tissue invasion and metastasis. To further examine the role of eIF4E in the biology of cancer cells, variants of eIF4E with impaired 5' cap binding function were expressed in MDA-MB-435 carcinoma cells. Cell lines overexpressing variants of eIF4E had impaired growth properties and exhibited a different morphology compared to cells expressing similar amounts of exogenous wild-type eIF4E or control cells. Cells expressing variant eIF4E did not form foci in culture and produced smaller colonies in soft agar compared to cells expressing wild-type eIF4E. In addition, analysis of polyribosomes for vascular endothelial growth factor (VEGF) mRNA demonstrated a shift from translationally active to inactive fractions in variant eIF4E cells, while GAPDH mRNA did not. The long G-C rich 5' untranslated region of VEGF mRNA is a feature of other mRNAs encoding growth regulating proteins that are predicted to have their translation enhanced by increases in eIF4E; whereas mRNA with shorter and less structured 5' UTRs, like that of GAPDH, are predicted to be largely unaffected. These data suggest that targeting the 5' cap-binding domain of eIF4E may be a viable option to slow cancer cell growth and alter the malignant phenotype.

5' Untranslated Regions↗
PubMed2006

H3+: the driver of giant planet atmospheres.

We present a review of recent developments in the use of H3+ molecular ion as a probe of physics and chemistry of the upper atmospheres of giant planets. This ion is shown to be a good tracer of energy inputs into Jupiter (J), Saturn (S) and Uranus (U). It also acts as a 'thermostat', offsetting increases in the energy inputs owing to particle precipitation via cooling to space (J and U). Computer models have established that H3+ is also the main contributor to ionospheric conductivity. The coupling of electric and magnetic fields in the auroral polar regions leads to ion winds, which, in turn, drive neutral circulation systems (J and S). These latter two effects, dependent on H3+, also result in very large heating terms, approximately 5 x 10(12) W for Saturn and greater than 10(14) W for Jupiter, planet-wide; these terms compare with approximately 2.5 x 10(11) W of solar extreme UV absorbed at Saturn and 10(12) W at Jupiter. Thus, H3+ is shown to play a major role in explaining why the temperatures of the giant planets are much greater (by hundreds of kelvin) at the top of the atmosphere than solar inputs alone can account for.

Journal Article↗
PubMed2006

Hepatitis C virus complete genome sequences identified from China representing subtypes 6k and 6n and a novel, as yet unassigned subtype within genotype 6.

Here, the complete genome sequences for three hepatitis C virus (HCV) variants identified from China and belonging to genotype 6 are reported: km41, km42 and gz52557. Their entire genome lengths were 9430, 9441 and 9448 nt, respectively; the 5' untranslated regions (UTRs) contained 341, 342 and 339 nt, followed by single open reading frames of 9045, 9045 and 9057 nt, respectively; the 3' UTRs, up to the poly(U) tracts, were 41, 51 and 52 nt, respectively. Phylogenetic analyses showed that km41 is classified into subtype 6k and km42 into subtype 6n. Although gz52557 clustered distantly with subtype 6g, it appeared to belong to a distinct subtype. Analysis with 53 and 105 partial core and NS5B region sequences, respectively, representing 17 subtypes from 6a to 6q and three unassigned isolates of genotype 6 in co-analyses demonstrated that gz52557 was equidistant from all of these isolates, indicating that it belongs to a novel subtype. However, based on a recent consensus that three or more examples are required for a new HCV subtype designation, it is suggested that gz52557 remains unassigned to any subtype.

China↗
PubMed2002

CE on the web.

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Communication↗
PubMed2002

Thalidomide in chronic graft-versus-host disease after stem cell transplantation: effects on quality of life.

Thalidomide is being increasingly used after stem cell transplantation as immunosuppression for patients with chronic graft-versus-host disease, as well as for antiangiogenesis effects in patients with multiple myeloma, brain tumors, leukemia, or other malignancies. The goal of this study was to determine if thalidomide improved the quality of life by virtue of its associated sleep-promoting, anxiety-reducing, antiwasting, and antidiarrheal effects. We therefore studied 28 patients with resistant chronic graft-versus-host disease who were treated with thalidomide (13 patients) or other immunosuppressive drugs (15) and compared them with healthy control subjects (16). All patients completed quality-of-life questionnaires prospectively before beginning regimens of thalidomide or other immunosuppressive drugs and completed similar questionnaires at 3- and 6-month intervals thereafter. The Transplant Symptom Frequency score was similar for healthy control subjects and both groups of patients with chronic graft-versus-host disease, regardless of whether they had received thalidomide or not. Quality of sleep was equally poor in patients who received or did not receive thalidomide. The most common complaint of patients with chronic graft-versus-host disease was fatigue, followed in frequency by overeating. The control group had similar concerns. This pilot study suggests that patients with chronic graft-versus-host disease have a quality of life similar to that of their health care workers, regardless of whether they are treated with thalidomide or other immunosuppressive drug, and that fatigue and overeating are the most common complaints.

Case-Control Studies↗