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Biomedical subjects

James E Bailey

Publications and source records attributed to James E Bailey.

At least 19 recordsLinked to original sources

Perceived impact of TennCare reform on patients' health in a medical teaching practice.

From 1994-2005, TennCare, Tennessee's innovative Medicaid managed care program, dramatically expanded coverage to around 1.3 million Tennesseans (roughly 23 percent of the state population) by employing cost savings achieved through capitation and managed care. Rising healthcare costs and a static state budget resulted in program downsizing that started in mid-2005. This cross-sectional survey sought to document the perspectives of TennCare enrollees before disenrollment about the likely impacts of changes in TennCare coverage and benefits. In February 2005, a convenience sample of 89 patients served by an internal medicine resident staffed teaching practice in Memphis, TN, participated in a survey to assess their perspectives about the potential impact of the upcoming disenrollment and benefits limitations. Ninety percent or more expressed concerns that loss of TennCare would lead to health problems, difficulty with paying for prescriptions and difficulty finding alternative health insurance. This survey suggests that before disenrollment, most people served by TennCare believed that loss of TennCare would have serious negative consequences on their health. Further studies are needed to assess the true impact of the disenrollment and benefit cuts and the effectiveness of alternative safety net services for vulnerable Tennessee citizens.

Adult↗

Public reporting needed to improve the health of Tennesseans.

Tennessee providers are recognizing an urgent need for a new and improved model of healthcare, characterized by transparent accountability to consumers. Meaningful health system improvements will require broad public disclosure of healthcare performance data at the hospital, clinic and community levels using nationally recognized standards. All Tennessee communities need a routine community health report card, to help their citizens to work together toward their most important health goals.

Efficiency, Organizational↗

Impact of a statewide Medicaid managed care system on healthcare utilization and outcomes for people living with HIV.

BACKGROUND: Medicaid managed care (MMC) systems provide insurance for many persons living with HIV and AIDS (PLWH). This study sought to assess the impact of a statewide MMC system (TennCare) on healthcare utilization and outcomes for PLWH. METHODS: A retrospective longitudinal analysis of trends in population characteristics was performed. The study population included all Tennessee PLWH identified by State Health Department, enrolled for 1 year or longer in Medicaid (1992-1993) or TennCare (1994-1997). Main outcome measures included health care utilization, incidence of opportunistic infections, and mortality. RESULTS: From 1992 to 1997, the following decreased: average number of hospitalizations for HIV (0.72 to 0.37) and AIDS (1.27 to 0.52); emergency visits for HIV (1.70 to 1.12) and AIDS (1.65 to 1.02); outpatient visits for HIV (5.94 to 5.00) and AIDS (8.37 to 7.35), percentage of persons diagnosed with Pneumocystis carinii pneumonia for AIDS (10% to 6%) and percentage of persons diagnosed with community-acquired pneumonia for HIV (14% to 9%) and AIDS (27% to 12%), annual incidence of AIDS in the HIV population (33% to 10%), and annual mortality for HIV (3% to 1%) and AIDS (16% to 3%). The average number of antiretroviral medication prescriptions filled increased for HIV (1.27 to 2.45) and AIDS (1.31 to 3.34). CONCLUSIONS: This study documents improvements in utilization patterns, morbidity, and mortality in a statewide MMC system. These findings suggest that MMC patients are benefiting from recent advances in therapy.

Adult↗

Alphavirus cDNA-based expression vectors: effects of RNA transcription and nuclear export.

The construction of layered DNA-RNA replicons has facilitated and expanded the use of alphavirus vectors to vaccine development, construction of packaging cell lines and long-term heterologous gene expression. In these vector systems, the alphavirus replicon is under the control of a strong RNA polymerase II promoter and replicon RNA is transcribed from DNA before transport to the cytoplasm. Efficient RNA amplification catalyzed by the viral replicase results in high levels of mRNA and the recombinant protein. Recently, we developed a temperature-regulated Sindbis replicon-based DNA expression system characterized by a linear increase of expression upon decrease of the temperature from 37 degrees C to 29 degrees C. Modifications known to affect transcription and nuclear export of RNA led to a 5-fold increase in expression in BHK cells and up to over 80-fold increase in CHO cells and BF fibroblasts in transient transfection experiments. Furthermore, reducing cell proliferation resulted in a further 2- to 3-fold higher expression. While increased expression per cell was responsible for some of the enhanced production, it was primarily the number of expressing cells that made the difference in most cell lines. Further experiments indicated that a threshold amount of replicon RNA had to reach the cytoplasm in order for replication to occur. Thus, alterations that improve transcription, nuclear export and stability of the RNA had a significant impact on protein production in the pCytTS expression system and probably in other layered DNA-based viral vectors. Furthermore the results indicate that RNA replication is differentially regulated in DNA layered RNA replicons versus viral infection.

Active Transport, Cell Nucleus↗

Improvements in access to care for HIV and AIDS in a statewide Medicaid managed care system.

BACKGROUND: Some experimental Medicaid managed care systems have expanded eligibility criteria for chronically ill persons, but these systems' impact on access to care remains unknown. OBJECTIVE: To determine whether initiating a statewide Medicaid managed care system (TennCare) guaranteeing universal access for persons living with HIV or AIDS (PLWHs) increased their enrollment in public sector insurance. DESIGN, SETTING, AND PARTICIPANTS: A retrospective longitudinal descriptive analysis of trends in population characteristics during the study period was performed. The study population included all PLWHs in Tennessee (1992-1997) identified by the State Health Department. These data linked with Medicaid/TennCare enrollment files identified percentages of Tennessee's HIV/AIDS population enrolled in Medicaid (1993) or TennCare (1994-1997) and eligi-bility/demographics changes during program initiation. MAIN OUTCOME MEASURE: Annual percentage of PLWHs enrolled in Medicaid/TennCare. RESULTS: Absolute numbers of PLWHs served by Medicaid/TennCare increased 475% from 1992 (n = 593) to 1997 (n = 2818). Similar increases in Tennessee's overall HIV-positive population occurred. Percentages of PLWHs enrolled in Medicaid/TennCare increased (1993 to 1997): HIV (28% to 34%) and AIDS (32% to 44%). The largest percentage of PLWHs added to the program were uninsured/uninsurable. CONCLUSIONS: Absolute numbers of PLWHs covered by Medicaid/TennCare substantially increased. Percentages of PLWHs covered increased more modestly, partly owing to large increases in overall numbers of HIV-positive Tennesseans during the study period. Increases in coverage were greatest for the AIDS population. Tennessee's broad expansion of eligibility for PLWHs resulted in improved access, but did not result in enrollment of most PLWHs. States contemplating similar Medicaid expansions should not expect all PLWHs to crowd into public sector insurance programs.

Adolescent↗

Diabetic patient experiences in a Medicaid managed care system.

OBJECTIVE: When Tennessee received a federal waiver to place all Medicaid enrollees in managed care organizations (MCOs), patients with chronic conditions such as diabetes were deemed especially vulnerable. This survey assessed patients' perceptions of diabetic care, self-care procedures, and satisfaction with medical care before and after enrollment in a Medicaid MCO. METHODS: A telephone survey was designed and pilot tested before surveying 57 patients meeting inclusion criteria of continuous enrollment in Medicaid for two years before, and in the MCO for two years after, the initiation of Tennessee's Medicaid managed care system (TennCare). RESULTS: On average, patients were 56.1 +/- 8.9 years old (mean +/- SD), African American (87.7%), female (73.7%), disabled (64.8%), with 8.4 +/- 2.8 years of education and annual incomes below $10,000 (54.4%). Mean age at diagnosis was 39.5 +/- 11.5 years, and most (75.5%) were currently prescribed insulin. Over one-third (39.6%) described the quality of healthcare received under managed care as excellent or very good and 38.9% felt prior Medicaid care was worse or much worse. Compared to Medicaid, patients reported no difference in being denied a test under managed care because of lack of approval (P = .754). However, significant improvements were reported in receiving detailed information about diabetes (89.5% vs. 73.7%, P = .022), and diet (89.5% vs. 77.2%, P = .039) for the TennCare period. Patients were more likely to perform finger stick blood glucose tests under the MCO (76.8% vs. 40.7%, P = .001), but did not report that blood glucose was controlled more of the time (P = .332). CONCLUSION: Most patients were satisfied with their MCO care, and most reported that finger stick glucose monitoring increased under the MCO. However, no significant gains in controlling blood sugar were reported. From the perspective of most patients, enrollment in an MCO had positive outcomes and resulted in improved access to diabetes-related health information.

Diabetes Mellitus↗

QSource quality initiative. Reversing the diabetes epidemic in Tennessee.

This paper summarizes the results of a recent report on diabetes in Tennessee. Diabetes has reached epidemic proportions in Tennessee. In 2001, an estimated 7.7% of the population was diabetic, an increase from 5.8% a decade earlier. This increase is largely due to widespread unhealthy eating habits, physical inactivity, and associated obesity. The majority of diabetes is preventable and can be effectively treated through daily exercise and a healthy diet. Diabetes prevention efforts in Tennessee schools and communities, however, are grossly inadequate. Providers and payers underemphasize prevention. Since the causes of diabetes can be traced to childhood habits, early prevention is the key to reversing the diabetes epidemic. Immediate statewide action must be taken to promote daily exercise and decrease access to high-calorie, high-fat "junk" food in our schools and communities. Physicians, health professional organizations, health plans, government, churches, schools, and employers must work together to battle the diabetes epidemic through public education, community-wide health promotion programs, and efforts to improve quality of diabetes care for all Tennesseans.

Adolescent↗

Structure-function relationships in immobilized chymotrypsin catalysis.

Specific activities and the amounts of active immobilized enzyme were determined for several different preparations of alpha-chymotrypsin immobilized on CNBr-activated Sepharose 4B. Electron paramagnetic resonance (EPR) spectroscopy of free and immobilized enzyme with a spin label coupled to the active site was used to probe the effects of different immobilization conditions on the immobilized enzyme active site configuration. Specific activity of active enzyme decreased and rotational correlation time of the spin label increased with increasing immobilized enzyme loading. Enzyme immobilized using an intermediate six-carbon spacer arm exhibited greater specific activity and spin label mobility than directly coupled enzyme. The observed activity changes due to immobilization were completely consistent with corresponding active site structure alterations revealed by EPR spectroscopy.

Animals↗

Analysis of growth rate effects on productivity of recombinant Escherichia coli populations using molecular mechanism models.

The influence of growth rate on Escherichia coli plasmid content and expression of a cloned-gene product has been described by a mathematical model based upon the molecular mechanism of lambdadv plasmid replication and known relationships between growth rate and transcription and translation activities of the host cell. The model simulates correctly decreases in plasmid content with increasing growth rate as observed experimentally for pBR322, NR1, R1, and Col E1 plasmids. A maximum with respect to growth rate in intracellular product accumulation is indicated by the model, as is a transient overshoot in product concentration following a shift from smaller to larger growth rate. Available data, although very limited, show the same trends. These results, obtained without parameter or kinetic form adjustments or manipulation, clearly illustrate the advantages of kinetic descriptions of recombinant systems based upon the pertinent molecular mechanisms.

Cell Size↗

Intracellular expression of Vitreoscilla hemoglobin modifies microaerobic Escherichia coli metabolism through elevated concentration and specific activity of cytochrome o.

The function of the reversible oxygen-binding hemoprotein from Vitreoscilla (VHb), which enhances oxygen-limited cell growth and recombinant protein production when functionally expressed in Escherichia coli, was investigated in wild-type E. coli and in E. coli mutants lacking one of the two terminal oxidases, cytochrome o complex (aerobic terminal oxidase, Cyo) or cytochrome d complex (microaerobic terminal oxidase, Cyd). Deconvolution of VHb, cytochrome o, and cytochrome d bands from in vivo absorption spectra revealed a 5-fold enhancement in cytochrome o content and a 1.5-fold increment in cytochrome d by VHb under microaerobic environments (dissolved oxygen less than 2% air saturation). Based upon oxygen uptake kinetics measurements of these mutants, the apparent oxygen affinity of the Cyo(+), Cyd(-) E. coli was increased in the presence of VHb, but no difference in the apparent K(m) was observed for the Cyo(-), Cyd(+) strain. Results suggest that the expression of VHb in E. coli increases the level and activity of terminal oxidases and thereby improves the efficiency of microaerobic respiration and growth.

Aerobiosis↗

Inverse metabolic engineering: a strategy for directed genetic engineering of useful phenotypes.

The classical method of metabolic engineering, identifying a rate-determining step in a pathway and alleviating the bottleneck by enzyme overexpression, has motivated much research but has enjoyed only limited practical success. Intervention of other limiting steps, of counter-balancing regulation, and of unknown coupled pathways often confounds this direct approach. Here the concept of inverse metabolic engineering is codified and its application is illustrated with several examples. Inverse metabolic engineering means the elucidation of a metabolic engineering strategy by: first, identifying, constructing, or calculating a desired phenotype; second, determining the genetic or the particular environmental factors conferring that phenotype; and third, endowing that phenotype on another strain or organism by directed genetic or environmental manipulation. This paradigm has been successfully applied in several contexts, including elimination of growth factor requirements in mammalian cell culture and increasing the energetic efficiency of microaerobic bacterial respiration.

Animals↗

Engineering of coordinated up- and down-regulation of two glycosyltransferases of the O-glycosylation pathway in Chinese hamster ovary (CHO) cells.

Production of O-linked oligosaccharides that interact with selectins to mediate cell-cell adhesion occurs in one segment of a branched glycan biosynthesis network. Prior efforts to direct the branched pathway towards selectin-binding oligosaccharides by amplifying enzymes in this branch of the network have had limited success, suggesting that metabolic engineering to simultaneously inhibit the competing pathway may also be required. We report here the partial cloning of the CMP-sialic, acid:Galbeta1,3GalNAcalpha2,3-sialyltransferase (ST3Gal I) gene from Chinese hamster ovary (CHO) cells and the simultaneous inhibition of expression of CHO cell ST3Gal I gene and overexpression of the human UDP-GlcNAc:Galbeta1,3GalNAc-R beta1,6-N-acetylglucosaminyltransferase (C2GnT) gene. A tetracycline-regulated system adjoined to tricistronic expression technology allowed "one-step" transient manipulation of multiple enzyme activities in the O-glycosylation pathway of a previously established CHO cell line already engineered to express alpha1,3-fucosyltransferase VI (alpha1,3-Fuc-TVI). Tetracycline-regulated co-expression of a ST3Gal I fragment, cloned in the antisense orientation, and of C2GnT cDNA resulted in inhibition of the ST3Gal I enzymatic activity and increase in C2GnT activity which varied depending on the extent of tetracycline reduction in the cell culture medium. This simultaneous regulated inhibition and activation of the two key enzyme activities in the O-glycosylation pathway of mammalian cells is an important addition to the metabolic engineering field.

Amino Acid Sequence↗

Macrolide-based transgene control in mammalian cells and mice.

Heterologous mammalian gene regulation systems for adjustable expression of multiple transgenes are necessary for advanced human gene therapy and tissue engineering, and for sophisticated in vivo gene-function analyses, drug discovery, and biopharmaceutical manufacturing. The antibiotic-dependent interaction between the repressor (E) and operator (ETR) derived from an Escherichia coli erythromycin-resistance regulon was used to design repressible (E(OFF)) and inducible (E(ON)) mammalian gene regulation systems (E.REX) responsive to clinically licensed macrolide antibiotics (erythromycin, clarithromycin, and roxithromycin). The E(OFF) system consists of a chimeric erythromycin-dependent transactivator (ET), constructed by fusing the prokaryotic repressor E to a eukaryotic transactivation domain that binds and activates transcription from ETR-containing synthetic eukaryotic promoters (P(ETR)). Addition of macrolide antibiotic results in repression of transgene expression. The E(ON) system is based on E binding to artificial ETR-derived operators cloned adjacent to constitutive promoters, resulting in repression of transgene expression. In the presence of macrolides, gene expression is induced. Control of transgene expression in primary cells, cell lines, and microencapsulated human cells transplanted into mice was demonstrated using the E.REX (E(OFF) and E(ON)) systems. The macrolide-responsive E.REX technology was functionally compatible with the streptogramin (PIP-regulated and tetracycline (TET-regulated expression systems, and therefore may be combined for multiregulated multigene therapeutic interventions in mammalian cells and tissues.

Alkaline Phosphatase↗

Expressing creatine kinase in transgenic tobacco--a first step towards introducing an energy buffering system in plants.

Creatine kinase a key enzyme in cellular energy homeostasis of vertebrates offers the promise of engineering plants with enhanced stress tolerance. In order to provide plants with such an energy buffering system, tobacco was transformed with a cDNA, encoding the cytosolic brain-type isoform of chicken creatine kinase (BB-CK), the expression of which was under the control of the cauliflower mosaic virus 35S (CaMV 35S) promoter. Transgenic tobacco plants were selected and suspension cultures generated. Both transgenic plants and suspension cultures were shown to stably express enzymatically active BB-CK in vitro and in vivo, and in most cases for three successive generations (T0-T2). Exogenously supplied creatine was shown to enter the plant cells and resulted in only a slight reduction in root growth at concentrations up to 10 mM. Furthermore, the BB-CK expressing tobacco plants and cell suspension cultures were able to convert creatine into phosphocreatine.

Animals↗

Teaching resident physicians to provide exercise counseling: a needs assessment.

PURPOSE: To determine the behaviors, knowledge, and attitudes of resident physicians regarding exercise counseling. METHOD: In 1997, a self-administered questionnaire was sent to 313 internal medicine resident physicians at six U.S. training programs. Pearson correlation coefficients examined associations between the resident physicians' practices, attitudes, and personal habits. Stepwise multiple linear regression identified predictors of exercise counseling by the resident physicians. RESULTS: A total of 251 resident physicians responded. Only 15.5% reported counseling more than 80% of the clinic patients about exercise. Over 93% understood the benefits of exercise, and almost all (96%) felt that it was a physician's responsibility to counsel patients about exercise. Only 29% felt successful at getting their patients to start exercising, and only 28% felt confident in their skills to prescribe exercise for patients. Ninety-one percent felt that training in exercise counseling would be worthwhile. The significant predictors of physician exercise counseling were perception of exercise counseling as a priority (p <.001), confidence in exercise-counseling skills (p <.001), and postgraduate year of training (p <.05) (R(2) =.18). The significant predictors of physicians' confidence in exercise-counseling skills included physician's gender (i.e., men) (p <.001), perception that exercise is important for a healthy 35-year-old (p <.01), feeling successful at exercise counseling (p <.001), perceiving less interference with counseling by barriers (p <.001), and prior training in exercise counseling (p <.05) (R(2) =.44). CONCLUSIONS: Resident physicians' perceptions of exercise counseling as a priority, confidence in counseling skills, and postgraduate year of training are important predictors of their providing exercise counseling. These factors should be addressed in future educational programs.

Adult↗

Polycistronic gene expression in yeast versus cryptic promoter elements.

Saccharomyces cerevisiae is a much preferred host for biotechnological applications. However, the expression of entire heterologous pathways, required for some potential products, is technically challenging in yeast. A possible tool would be polycistronic gene expression. Recent studies demonstrated that short 5' untranslated regions (5'UTRs) found upstream of certain genes support cap-independent translation in vitro. In this study 5'UTRs were used as linkers between genes in polycistronic constructs. Expression levels of genes located in the first, second and third position after a promoter were studied by replacing the respective gene by a promoterless green fluorescence protein (GFP) gene. S. cerevisiae transformed with these constructs was grown on different carbon sources and GFP expression was assayed. Our results demonstrate that (i) ribosomal read-through does not suffice for polycistronic gene expression in vivo, (ii) 5'TFIID and 5'HAP4 but not 5'L-A significantly improve the expression of a reporter gene located second in a bicistron, (iii) 5'TFIID, 5'HAP4 and 5'YAP1 but not 5'L-A can drive expression of a promoterless reporter gene, and (iv) expression driven from 5'TFIID, 5'HAP4 and 5'YAP1 is induced in the presence of raffinose or galactose but not in the presence of glucose. This implies that these elements unlike typical internal ribosome entry site-like structures contain small, potentially useful promoters which support carbon source-regulated expression.

5' Untranslated Regions↗

Intracellular carbon fluxes in riboflavin-producing Bacillus subtilis during growth on two-carbon substrate mixtures.

Metabolic responses to cofeeding of different carbon substrates in carbon-limited chemostat cultures were investigated with riboflavin-producing Bacillus subtilis. Relative to the carbon content (or energy content) of the substrates, the biomass yield was lower in all cofeeding experiments than with glucose alone. The riboflavin yield, in contrast, was significantly increased in the acetoin- and gluconate-cofed cultures. In these two scenarios, unusually high intracellular ATP-to-ADP ratios correlated with improved riboflavin yields. Nuclear magnetic resonance spectra recorded with amino acids obtained from biosynthetically directed fractional (13)C labeling experiments were used in an isotope isomer balancing framework to estimate intracellular carbon fluxes. The glycolysis-to-pentose phosphate (PP) pathway split ratio was almost invariant at about 80% in all experiments, a result that was particularly surprising for the cosubstrate gluconate, which feeds directly into the PP pathway. The in vivo activities of the tricarboxylic acid cycle, in contrast, varied more than twofold. The malic enzyme was active with acetate, gluconate, or acetoin cofeeding but not with citrate cofeeding or with glucose alone. The in vivo activity of the gluconeogenic phosphoenolpyruvate carboxykinase was found to be relatively high in all experiments, with the sole exception of the gluconate-cofed culture.

Bacillus subtilis↗

TennCare--Medicaid managed care in Tennessee in jeopardy.

TennCare, the statewide Medicaid managed care system implemented in Tennessee on January 1, 1994, sought to reduce state and federal healthcare expenditures while enhancing access to and quality of care. TennCare currently covers 1.32 million enrollees (25% of the citizens of Tennessee), including more than 520,248 citizens previously not covered by health insurance. It is one of the largest Medicaid managed care enterprises in the nation and the only program to cover uninsurables regardless of income. Utilization of preventive and primary care services has increased, and selected measures of quality of care have improved. Program costs from 1994 through 1998 rose at a rate below that of overall US Medicaid costs during the same period, resulting in modest savings. However, managed care plans, hospitals, and individual providers continue to report substantial fiscal losses, and managed care organizations--including the 3 largest plans in the program--have closed, been placed under receivership, or threatened to withdraw from the market. Furthermore, safety net hospitals, academic medical centers, and community mental health programs have fared financial cutbacks that have limited their ability to serve the remaining uninsured as well as the insured. Because of these fiscal difficulties, the TennCare program is now in significant jeopardy despite its important clinical successes. Major structural and fiscal changes will be required if the program is to continue to enhance services and remain financially viable. This report focuses on TennCare's successes and failures to offer lessons for Medicaid managed care programs nationwide.

Academic Medical Centers↗