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Thomas Miller

Publications and source records attributed to Thomas Miller.

9 recordsLinked to original sources
PubMed2005

A reassessment of Galileo radiation exposures in the Jupiter magnetosphere.

Earlier particle experiments in the 1970s on Pioneer-10 and -11 and Voyager-1 and -2 provided Jupiter flyby particle data, which were used by Divine and Garrett to develop the first Jupiter trapped radiation environment model. This model was used to establish a baseline radiation effects design limit for the Galileo onboard electronics. Recently, Garrett et al. have developed an updated Galileo Interim Radiation Environment (GIRE) model based on Galileo electron data. In this paper, we have used the GIRE model to reassess the computed radiation exposures and dose effects for Galileo. The 34-orbit 'as flown' Galileo trajectory data and the updated GIRE model were used to compute the electron and proton spectra for each of the 34 orbits. The total ionisation doses of electrons and protons have been computed based on a parametric shielding configuration, and these results are compared with previously published results.

Atmosphere↗
PubMed2004

Histone deacetylase inhibitors.

The base sequence of DNA provides the genetic code for proteins. The regulation of expression or suppression of gene transcription is largely determined by the structure of the chromatin--referred to as epigenetic gene regulation (Agalioti et al., 2002; Jenuwein and Allis, 2001; Richards and Elgin, 2002; Spotswood and Turner, 2002; Zhang and Reinberg, 2001). Posttranslational modifications of the histones of chromatin play an important role in regulating gene expression. Some of the most extensively studied epigenetic modifications involve acetylation/deacetylation of lysines in the tails of the core histones, which is controlled by the action of histone deacetylases (HDACs) and histone acetyltransferases (HATs). A controlled balance between histone acetylation and deacetylation appears to be essential for normal cell growth (Waterborg, 2002). Alterations in the structure or expression of HATs and HDACs occur in many cancers (Jones and Baylin, 2002; Marks et al., 2001, 2003; Timmermann et al., 2001; Wang et al., 2001). A structurally diverse group of molecules has been developed that can inhibit HDACs (HDACi) (Arts et al., 2003; Bouchain and Delorme, 2003; Curtin and Glaser, 2003; Johnstone and Licht, 2003; Marks et al., 2003; Remiszewski, 2003; Richon et al., 1998; Yoshida et al., 2003). These inhibitors induce growth arrest, differentiation, and?or apoptosis of cancer cells in vitro and in in vivo tumor-bearing animal models. Clinical trials with several of these agents have shown that certain HDACi have antitumor activity against various cancers at doses that are well tolerated by patients (Gottlicher et al., 2001; Kelly et al., 2002a,b; Piekarz et al., 2001; Wozniak et al., 1999).

Acetylation↗
PubMed2004

What would be the effect of referral to high-volume hospitals in a largely rural state?

CONTEXT: Volume of certain surgical procedures has been linked to patient outcomes. The Leapfrog Group and others have recommended evidence-based referral using specific volume thresholds for nonemergent cases. The literature is limited on the effect of such referral on hospitals, especially in rural areas. PURPOSE: To examine the impact of evidence-based referral by volume standard for 5 hospital procedures (abdominal aortic artery repair, coronary angioplasty, coronary artery bypass graft, esophageal cancer surgery, and pancreatic resection) in a largely rural state. METHODS: Healthcare Cost and Utilization Project Iowa State Inpatient Dataset was analyzed to identify hospitals meeting the volume standard versus those not meeting the standard. FINDINGS: Relatively few hospitals perform these procedures in Iowa. Hospitals performing the procedures at a volume above the threshold standard set by the Leapfrog Group tend to be larger, receive more transfers from other hospitals for these procedures, and perform fewer of these procedures on an emergency basis. In Iowa, hospitals that met the volume standard did not differ from hospitals that did not meet the volume standard in risk-adjusted mortality rates. The impact of evidence-based referral would be substantial in terms of travel time for some procedures (ie, coronary artery bypass graft, pancreatic resection, and esophageal cancer surgery) and produce considerable lost revenue for some hospitals. CONCLUSIONS: Evidence-based referral would be associated with substantial burden for some patients and hospitals in Iowa. This negative impact does not appear to be offset by improvement in in-hospital mortality rates. These initial findings suggest that there are a number of issues that need to be considered, especially in a rural state, before evidence-based referral is embraced as a means to enhance patient outcomes.

Evidence-Based Medicine↗
PubMed2004

Intensive care unit utilization and interhospital transfers as potential indicators of rural hospital quality.

CONTEXT: Obtaining meaningful information from statistically valid and reliable measures of the quality of care for disease-specific care provided in small rural hospitals is limited by small numbers of cases and different definitive care capacities. An alternative approach may be to aggregate and analyze patient services that reflect more generalized care processes. PURPOSE: To evaluate the applicability of intensive care unit (ICU) utilization and interhospital transfers as potential indicators of quality in rural hospitals. METHODS: Secondary data analysis of ICU utilization and interhospital transfer practices in Iowa's Critical Access (CAH), rural, rural referral, and urban hospitals. FINDINGS: Rural hospitals have fewer resources, provide a more limited range of definitive care services, and rely to a greater extent on transferring patients to other hospitals capable of providing the required definitive care. Examining ICU utilization and interhospital transfer patterns we found (1) that lower percentages of patients receive ICU care in smaller facilities; (2) higher transfer rates for both ICU and non-ICU patients in CAH hospitals; (3) shorter average lengths of stay for ICU patients from smaller hospitals who were transferred; and (4) lower mortality rates for CAH and rural hospital ICU patients. CONCLUSIONS: Examining ICU utilization and interhospital transfer patterns offers potential insights into rural hospital quality measurement and comparisons.

Health Services Accessibility↗
PubMed2004

Histone deacetylase inhibitors: development as cancer therapy.

Histone deacetylase (HDAC) inhibitors represent a new class of targeted anticancer agents. A number of structural classes of HDAC inhibitors have been developed of which several are in clinical trials, including phenylbutyrate (PB) and related compounds; the hydroxamic acids, suberoylanilide hydroxamic acid (SAHA) and depsipeptide (FK-228); and the benzamides, MS-275 and C1-994. This review will focus on our studies with the hydroxamic acid HDAC inhibitors, of which SAHA is the lead agent. X-ray crystallographic studies with a HDAC homologue (HDLP) demonstrated that the hydroxamic acid group, most of the aliphatic chain and part of the phenyl amino group of SAHA inserts into the pocket-like catalytic site of the enzyme, at the base of which is a zinc molecule. SAHA inhibits the activity of class I and II HDACs and is selective in altering gene expression. SAHA is synergistic in its anticancer activity with radiation, kinase inhibitors, cytotoxic agents and differentiating agents. In phase I clinical trial with orally administered SAHA the agent caused accumulation of acetylated histones in peripheral mononuclear cells and tumour cells, has excellent bioavailability and has shown antitumour activity in patients with haematologic and solid tumours.

Histone Deacetylase Inhibitors↗
PubMed2003

Histone deacetylases.

Post-translational modification of the histones of chromatin has a fundamental role in regulating gene expression. Enzymes involved in these epigenetic events include histone deacetylases (class I and class II), which can be inhibited by a structurally diverse group of small molecules. These histone deacetylase inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. Results of clinical trials with several of these agents have indicated that they are well tolerated at doses that have anti-tumour activity.

Animals↗
PubMedDate not supplied

Array-based multiplexed screening and quantitation of human cytokines and chemokines.

HydroGel-coated slide is a porous substrate based on a polymer matrix that provides a three-dimensional hydrophilic environment similar to free solution suitable for biomolecular interactions. This substrate has been used to develop fluorescence-based multiplexed cytokine immunoassays. Forty-three monoclonal antibodies (mAb) of cytokines and chemokines were printed at a volume of 350 pL per spot using a Packard BioChip Arrayer. For each probe, four replicates were printed at a pitch of 500 microm in the layout of a 13 x 16 pattern on a 12 x 12 mm2 HydroGel pad. Cytokines and chemokines that are captured by the arrayed mAbs are detected by using another biotinylated mAb, following by the addition of a Texas Red-conjugated streptavidin. The fluorescent images of arrays were recorded using a Packard ScanArray 5000 confocal slide scanner and quantitated using Packard QuantArray software. Experiments demonstrated that 43 cytokines and chemokines could be simultaneously screened and quantitated in conditioned culture media, cell lysates, and human plasma. Using this chip, we have examined cytokine expression in breast cancer cells and identified the chemokines associated with human cervical cancers.

Breast Neoplasms↗