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Biomedical subjects

Michael West

Publications and source records attributed to Michael West.

9 recordsLinked to original sources
PubMed2003

Supported employment for persons with traumatic brain injury: a preliminary investigation of long-term follow-up costs and program efficiency.

OBJECTIVE: To investigate the long-term follow-up costs of supported employment as well as the wage and employment characteristics for individuals with moderate to severe traumatic brain injury (TBI) who participated in supported employment services over a 14-year time period. DESIGN: Longitudinal design with prospectively collected data. SETTING: A university-based supported employment program that uses the individual placement model of supported employment. PARTICIPANTS: Fifty-nine individuals with moderate to severe TBI who were consecutively referred for supported employment services. The sample was restricted to individuals who were placed into a least 1 supported employment position during the study period. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Data were collected on clients placed into at least 1 competitive supported employment position from 1985 to 1999. Analyses were performed to examine the costs of supported employment, employment characteristics (eg, wages, length of employment), and benefit-cost ratios of supported employment for individuals with TBI. RESULTS: The average length of employment for the current sample was 42.58 months. Average gross earnings were US dollars 26,129.74 for individuals during their entire duration of employment. Billing charges accrued for employment services averaged US dollars 10,349.37. Individuals with TBI earned an average of US dollars 17,515 more than the costs associated with their supported employment. CONCLUSIONS: Our investigation provides additional support for the conclusion that supported employment is cost effective for individuals with disabilities, including individuals with TBI, and that the costs of supported employment decrease over time.

Adult↗
PubMed2002

Hydrophobic residue contributions to sequence-specific DNA binding by the bovine papillomavirus helicase E1.

Previously, mutational analyses of the DNA binding domain of the bovine papillomavirus E1 protein (E1DBD) identified several hydrophobic residues that are critical for DNA binding activity (M. West, D. Flanery, K. Woytek, D. Rangasamy, and V. G. Wilson, 2001, J. Virol. 75, 11948-11960). Hydrophobic interactions of nonpolar amino acid side chains can contribute to the function of DNA binding proteins through both conformational effects and direct interaction with nucleotides. To further investigate the role of hydrophobic residues in E1DBD function, a more extensive site-directed mutational analysis of hydrophobic amino acids was conducted. Alanine substitutions were made at residues V196, F197, F217, F, 237, V246, L249, and F276, and the mutants were tested for DNA binding activity in vitro and in vivo. The E1 F237A and F276A mutants were completely defective for site-specific DNA binding, while the other mutants retained partial to full wild-type binding activity. Consistent with their DNA binding defect, the F237A and F276A mutants were severely impaired for the ability to support transient in vivo replication of an origin plasmid. Combined with our previous study, five critical hydrophobic residues have been identified: F175, V193, F237, V246, and F276. These five residues localize to two internal clusters in the E1DBD structure designated hydrophobic clusters A (HCA; includes F175, V193, and F276) and B (HCB; includes F237 and V246). Amino acid side chains from residues in HCA and HCB have little surface accessibility and it is unlikely that they are involved in direct contact with DNA. HCA is distal to the DNA binding surface and presumably contributes to global conformational organization of the E1DBD. HCB is positioned beneath the DNA contact surface and we propose that it serves as an anchor or platform device to stabilize the DNA-binding element. A comparable hydrophobic cluster is present in the corresponding position in the T antigen DBD and likely serves a similar function.

Alanine↗
PubMed2002

Treatment of aerosolized cowpox virus infection in mice with aerosolized cidofovir.

The Brighton strain of cowpox virus causes lethal bronchopneumonia when delivered as a small-particle (1 microm) aerosol to weanling BALB/c mice. We showed previously that this disease can be prevented or cured with one subcutaneous injection of cidofovir (HPMPC, Vistide). To determine whether even better results could be obtained by delivering the drug directly to the respiratory tract, we administered cidofovir by small-particle aqueous aerosol before or after aerosolized cowpox infection. In a series of five experiments, aerosol doses of 0.5-5 mg/kg were always more effective than 25 mg/kg and sometimes more effective than 100 mg/kg injected subcutaneously, as measured by changes in body and lung weight, lung viral titers, pulmonary pathology and survival. A cyclic analog ((1-[(S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl] cytosine) (cHPMPC) was less protective. The results suggest that aerosolized cidofovir would be effective for prophylaxis or early post-exposure therapy of human smallpox or monkeypox virus infection.

Administration, Inhalation↗
PubMed2002

Papillomavirus E1 proteins: form, function, and features.

The E1 proteins are the essential origin recognition proteins for papillomavirus (PV) replication. E1 proteins bind to specific DNA elements in the viral origin of replication and assemble into hexameric helicases with the aid of a second viral protein, E2. The resultant helicase complex initiates origin DNA unwinding to provide the template for subsequent syntheses of progeny DNA. In addition to ATP-dependent helicase activity, E1 proteins interact with and recruit several host cell replication proteins to viral origin, including DNA polymerase alpha and RPA. This review will compare the basic structures and features of the human (HPV) and bovine (BPV1) papillomaviruses with an emphasis on mechanisms of replication function.

Adenosine Triphosphatases↗
PubMed2002

Optimizing higher throughput methods to assess drug-drug interactions for CYP1A2, CYP2C9, CYP2C19, CYP2D6, rCYP2D6, and CYP3A4 in vitro using a single point IC(50).

Drug-drug interactions involving cytochrome P(450) (CYP) are an important factor in whether a new chemical entity will survive through to the development stage. Therefore, the identification of this potential as early as possible in vitro could save considerable future unnecessary investment. In vitro CYP interaction screening data generated for CYP2C9, CYP2D6, and CYP3A4 were initially analyzed to determine the correlation of IC(50) from 10- and 3-point determinations. A high correlation (r = 0.99) prompted the further assessment of predicting the IC(50) by a single value of percent inhibition at either 10, 3, or 1 microM. Statistical analysis of the initial proprietary compounds showed that there was a strong linear relationship between log IC(50) and percent inhibition at 3 microM, and that it was possible to predict a compound's IC(50) by the percent inhibition value obtained at 3 microM. Additional data for CYP1A2, CYP2C19, and the recombinant CYP2D6 were later obtained and used together with the initial data to demonstrate that a single statistical model could be applicable across different CYPs and different in vitro microsomal systems. Ultimately, the data for all five CYPs and the recombinant CYP2D6 were used to build a statistical model for predicting the IC(50) with a single point. The 95% prediction boundary for the region of interest was about +/- 0.37 on log(10) scale, comparable to the variability of in vitro determinations for positive control IC(50) data. The use of a single inhibitor concentration would enable determination of more IC(50) values on a 96-well plate and result in more economical use of compounds, human liver or expressed enzyme microsomes, substrates, and reagents. This approach would offer the opportunity to increase screening for CYP-mediated drug-drug interactions, which may be important given the challenges provided by the generation of orders of magnitude more new chemical entities in the field of combinatorial chemistry. In addition, the algorithmic approach we propose would obviously be applicable for other in vitro bioactivity and therapeutic target enzyme and receptor screens.

Algorithms↗
PubMed2002

Medicaid HCBS Waivers and supported employment pre- and post-Balanced Budget Act of 1997.

Findings from a national survey of state mental retardation/developmental disability agencies regarding use of the Medicaid Home and Community Based Waiver to fund supported employment were reported. Numbers of individuals and funding levels were requested for day habilitation services for FYs 1997 and 1999, before and after the(P.L. 105-33), which removed eligibility restrictions for this service. Findings show that growth rates for this service far exceeded growth rates for other day services, with high growth rates in a small number of states. However, supported employment accounted for less than 16% of those receiving day habilitation services through the Waiver and only 12% of day habilitation funding, with the remainder going to day support, prevocational services, and other segregated options.

Budgets↗
PubMed2002

Return to work after spinal cord injury: a review of recent research.

This manuscript reviews recent research on return to work (RTW) for individuals who sustain spinal cord injury (SCI), including the effects of demographics variables, occupational characteristics, workplace accommodations, quality of life, physical functional limitations, and other variable. Demographic variables that influence RTW for persons with SCI include age at injury onset, chronological age, gender, education, ethnicity, marital status, and per-injury work intensity. Others include satisfaction, and adjustment to sustaining SCI. In an effort to enhance employment opportunities for individuals with disabilities including SCI, Ticket to Work Incentive Improvement Act of 1999 (TWILA) has been passed by Congress and some states have begun implementing targeted initiatives through the State Partnership Systems Change Initiatives (SPI). Future research directions are recommended in light of recent legislative initiatives.

Activities of Daily Living↗