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Biomedical subjects

S M Davidson

Publications and source records attributed to S M Davidson.

At least 19 recordsLinked to original sources
PubMed2006

Leptin, the obesity-associated hormone, exhibits direct cardioprotective effects.

BACKGROUND AND PURPOSE: Protection against ischaemia-reperfusion (I/R) injury involves PI3K-Akt and p44/42 MAPK activation. Leptin which regulates appetite and energy balance also promotes myocyte proliferation via PI3K-Akt and p44/42 MAPK activation. We, therefore, hypothesized that leptin may also exhibit cardioprotective activity. EXPERIMENTAL APPROACH: The influence of leptin on I/R injury was examined in perfused hearts from C57Bl/6 J mice that underwent 35 min global ischaemia and 35 min reperfusion, infarct size being assessed by triphenyltetrazolium chloride staining. The concomitant activation of cell-signalling pathways was investigated by Western blotting. The effect of leptin on mitochondrial permeability transition pore (MPTP) opening was studied in rat cardiomyocytes. KEY RESULTS: Leptin (10 nM) administered during reperfusion reduced infarct size significantly. Protection was blocked by either LY294002 or UO126, inhibitors of Akt and p44/42 MAPK, respectively. Western blotting confirmed that leptin stimulated p44/42 MAPK phosphorylation significantly. Akt phosphorylation was also enhanced but did not achieve statistical significance. Additionally, leptin treatment was associated with a significant increase in p38 phosphorylation. By contrast, leptin caused downregulation of phosphorylated and non-phosphorylated STAT3, and of total AMP-activated kinase. Cardiomyocytes responded to leptin with delayed opening of the MPTP and delayed time until contracture. CONCLUSIONS AND IMPLICATIONS: Our data indicate for the first time that the adipocytokine, leptin, has direct cardioprotective properties which may involve the PI3-Akt and p44/42 MAPK pathways.

Animals↗
PubMed2001

The bacterial nucleoside N(6)-methyldeoxyadenosine induces the differentiation of mammalian tumor cells.

Contrary to bacterial DNA, mammalian DNA contains very little if any N(6)-methyldeoxyadenosine (MDA). The possible biological effect of this nucleoside on eukaryotic cells has been studied on different tumor cell lines. Addition of MDA to C6.9 glioma cells triggers a differentiation process and the expression of the oligodendroglial marker 2',3'-cyclic nucleotide 3'phosphorylase (CNP). The biological effects of N(6)-methyldeoxyadenosine were not restricted to C6.9 glioma cells since differentiation was also observed on pheochromocytoma and teratocarcinoma cell lines and on dysembryoplastic neuroepithelial tumor cells. The precise mechanism by which MDA induces cell differentiation remains unclear, but is related to cell cycle modifications. These data point out the potential interest of N(6)-methyldeoxyadenosine as a novel antitumoral and differentiation agent. They also raise the intriguing question of the loss of adenine methylation in mammalian DNA. Furthermore, the finding that a methylated nucleoside found in bacterial DNA induces a biological process might have implications in gene therapy approaches when plasmid DNAs are injected into humans.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed2000

Hsp25 and the p38 MAPK pathway are involved in differentiation of cardiomyocytes.

The small heat-shock protein HSP25 is expressed in the heart early during development, and although multiple roles for HSP25 have been proposed, its specific role during development and differentiation is not known. P19 is an embryonal carcinoma cell line which can be induced to differentiate in vitro into either cardiomyocytes or neurons. We have used P19 to examine the role of HSP25 in differentiation. We found that HSP25 expression is strongly increased in P19 cardiomyocytes. Antisense HSP25 expression reduced the extent of cardiomyocyte differentiation and resulted in reduced expression of cardiac actin and the intermediate filament desmin and reduced level of cardiac mRNAs. Thus, HSP25 is necessary for differentiation of P19 into cardiomyocytes. In contrast, P19 neurons did not express HSP25 and antisense HSP25 expression had no effect on neuronal differentiation. The phosphorylation of HSP25 by the p38/SAPK2 pathway is known to be important for certain of its functions. Inhibition of this pathway by the specific inhibitor SB203580 prevented cardiomyocyte differentiation of P19 cells. In contrast, PD90589, which inhibits the ERK1/2 pathway, had no effect. Surprisingly, cardiogenesis was only sensitive to SB203580 during the first 2 days of differentiation, before HSP25 expression increases. In contrast to the effect of antisense HSP25, SB203580 reduced the level of expression of the mesodermal marker Brachyury-T during differentiation. Therefore, we propose that the p38 pathway acts on an essential target during early cardiogenesis. Once this initial step is complete, HSP25 is necessary for the functional differentiation of P19 cardiomyocytes, but its phosphorylation by p38/SAPK2 is not required.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed2000

Phospholipid-bound beta 2-glycoprotein I induces the production of anti-phospholipid antibodies.

Apoptotic-cell-bound beta2-glycoprotein I (beta2GPI), but not apoptotic cells or beta2GPI alone, can induce the production of anti-phospholipid (anti-PL) antibodies (Ab) in normal mice. Although it is presumed that beta2GPI binds to anionic phospholipid (PL) exposed on the apoptotic cell membrane, the precise nature of this complex and its immunogenicity is unclear. To address these issues, we investigated the structure and immunogenicity of human beta2GPI in the presence of different PL that may be expressed on the surface of apoptotic cells. BALB/c mice were immunized intravenously (iv) with beta2GPI in the presence of cardiolipin (CL), phosphatidylglycerol (PG), phosphatidylserine (PS), phosphatidylcholine (PC), or PS/PC (25%/75%) vesicles. Cardiolipin+beta2GPI induced the highest levels of anti-beta2GPI and anti-CL IgG Ab and lupus anticoagulant (LA) activity, while beta2GPI with PC or PS/PC vesicles produced no significant anti-PL Ab. PS+beta2GPI was somewhat immunogenic, but less so than PG+beta2GPI. beta2GPI was immunogenic in the presence of native (CL(N)), but not hydrogenated (CL(H)), CL. Circular dichroism analysis demonstrated that the structure of beta2GPI was altered specifically by interaction with CL(N), but not other anionic PL, including CL(H). Similarly, the structure of CL(N)was affected by interaction with beta2GPI, as detected by(31)P nuclear magnetic resonance. These findings demonstrate that beta2GPI complexed with CL(N)is structurally altered, highly immunogenic, and induces the production of IgG anti-PL Ab. Furthermore, the structural modification and the generation of immunogenic epitopes on beta2GPI upon interaction with CL(N)require the presence of unsaturated fatty acid chains, suggesting a role for oxidation in this process.

Adjuvants, Immunologic↗
PubMed1998

Competition and quality among managed care plans in the USA. Boston University Health Care Management Program Group.

This paper examines the popular idea that competition among managed care plans will lead not only to lower prices, but also to improved quality. We explore the likelihood that competition based on quality will occur and that better quality care will result. First, we discuss key elements of competitive theory and then we attempt to apply them to markets for health care coverage and care. We identify the conditions necessary for competition to have the desired effects and assess the extent to which those conditions do or can exist. We conclude that in the USA, many consumers have no choice among plans and, therefore, cannot select one based on quality. Moreover, the evidence suggests that as long as price varies among health plans, consumers who do have a choice will tend to emphasize price, not quality, in making their selections. We conclude with suggestions to increase the likelihood that quality can improve as a result of competition.

Consumer Behavior↗
PubMed1998

Physician retention in community and migrant health centers: who stays and for how long?

OBJECTIVES: This study used discrete-time survival analysis to estimate the tenure of primary care physicians in Community Health Centers (CHCs), to identify the changing risk of leaving Community Health Center employment as time passes, and to identify factors associated with a physician's likelihood of remaining in a Community Health Center. Because of dramatic differences in physician career trajectories, much of the focus was on differences between physicians with and without National Health Service Corps obligations. METHODS: Beginning with an administrative dataset at the Bureau of Primary Health Care that listed primary care physicians for each Community Health Center, the completeness and accuracy of the information provided were verified and an analytic database of all physicians working in those centers during a 21-month measurement window from January 1, 1990 through September 30, 1992 was constructed. The data included start and end dates, percent full-time equivalent status, and certain demographic characteristics. In addition, several data elements describing the Community Health Center were merged onto each physician record. These included urban or rural location, expenditure level, productivity, and federal grade. Through the use of discrete-time survival analysis, it was possible to include in the analytic sample all 2,654 physicians who worked during the period, even those who started working before January 1, 1990 and those who were still working on September 30, 1992. Survivor functions were estimated showing the proportion of physicians remaining after each quarter of their tenure (ie, after the fourth quarter of work, after the 12th quarter of work, etc). In addition, hazard functions were estimated showing the risk that a physician who had worked through the end of one quarter would leave during the following quarter. Finally, multivariate analysis demonstrated the relation of certain physician and center characteristics to the likelihood of the physician's leaving the center during each quarter. RESULTS: The median tenure of primary care physicians in Community Health Centers was approximately 3 years regardless of whether or not the physician had a National Health Service Corps obligation. But the career trajectories for the two groups of physicians varied dramatically. Most physicians left on or about their anniversary date, probably because it coincided with the end of their contract, but the effect was much more pronounced for National Health Service Corps physicians than for non-National Health Service Corps physicians. By the end of 5 years, approximately 36% of physicians who started without an National Health Service Corps obligation were still working compared with only approximately 17% of those with an National Health Service Corps obligation. CONCLUSIONS: The study demonstrates the value of discrete-time survival analysis in addressing questions related to the tenure of primary care physicians in Community Health Centers, making it possible to use data from physicians whose Community Health Center careers began before or ended after a give measurement window. Second, the study measured primary care physician tenure, providing center directors with a yard-stick against which to compare their own center's performance. Finally, the data provided some help in trying to explain differences in the propensity to stay or leave employment in Community Health Centers.

Career Mobility↗
PubMed1997

Association and release of prostaglandin E1 from liposomes.

PGE1-lipid interactions were studied in several liposome systems. Data from both circular dichroic (CD) measurements and differential scanning calorimetry (DSC) indicated that PGE1 in the protonated form seeks the less polar environment of the lipid bilayer. CD measurements made on PGE1 in solution showed that the wavelength of maximum absorbance red shifted approximately 8 nm with decreasing solvent polarity. The CD spectrum of liposomal PGE1 prepared in pH 4.5 but not pH 7.2 buffer was also red shifted. There was no red shift in the CD spectrum of PGE1 detected at pH 4.5 in the absence of phospholipid. DSC measurements on DSPC bilayers prepared with 5 mol% PGE1 at pH 4.5 but not pH 7.2 revealed an almost complete loss of the pre-transition as well as broadening of the main phase transition. The amount of 3H-PGE1 initially associated with EPC, POPC or DSPC liposomes was determined using size exclusion filters and centrifugation. This amount was found to be dependent on the pH of the buffer (pH 4.5 >> pH 7.2) and fluidity of the bilayer (EPC = POPC > DSPC), but independent of the lamellarity of the liposome. In all cases, addition of cholesterol reduced the amount of PGE1 associated with the liposome. The time-dependent release of PGE1 from the liposomes was determined by rapidly diluting the sample 100-fold into pH 7.2 buffer. Lipid saturation was a key factor influencing this release. Gel-phase liposomes of DSPC showed a rapid initial release (t(1/2) < 2 min) of PGE1, corresponding to the amount in the outer monolayer, followed by a very slow, almost negligible release of the remaining PGE1. A rapid initial release also occurred in fluid-phase membranes, followed by a more gradual release of the remaining PGE1 over several hours. This release rate could be slowed by increasing the lamellarity of these liposomes, or adding cholesterol to decrease the fluidity of the membrane.

Alprostadil↗
PubMed1993

Medicaid: taking stock.

In the last few years, Medicaid has attracted more than casual attention, one reflection of which is the fact that JHPPL has published five papers on the program in its last few issues. This paper, a sixth, takes a broader view of the program than is typically the case. After a critique of the five recent articles, I discuss several questions raised by them and reach the following conclusions: First, the states do not invest enough in producing program data suitable for policy analysis and research. One lesson: Better data and analysis can help the states to avoid expensive mistakes. Second, those policy analyses that have been offered fail to give sufficient attention to the political dimension of policy. That is one reason why policy choices produce unexpected effects. Third, since Medicaid is a relatively small player in the vast medical care market, incentives adopted by Medicaid officials throughout the country rarely have the desired effects. Finally, as long as Medicaid remains the principal mechanism to provide access to health care for the poor, it must be made as efficient and effective as possible. Yet, for both political and economic reasons, Medicaid can never be what its original planners had hoped, the vehicle for providing the poor with reliable access to mainstream medical care.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1992

Prepayment with office-based physicians in publicly funded programs: results from the Children's Medicaid Program.

This paper is a report of the results of a demonstration designed to provide empirical evidence regarding the effects of alternative approaches to paying physicians for serving children in the Medicaid program: (1) visit fees set at twice regular Medicaid fees in return for physician agreement to manage utilization and (2) capitation and financial risk-sharing along with the same physician agreement to manage utilization. Participating physicians were assigned randomly to either of the two payment groups. Comparisons of utilization and expenditures were made between these two plans and the regular Medicaid program (fee-for-service, low fees). Results showed no adverse effect of capitation payments on primary care visits to office-based physicians. Capitation physician referrals to specialists decreased relative to all other groups studied, consistent with the theory that the financial incentives in capitation will lead primary care physicians to reduce referrals to specialists.

Child↗
PubMed1990

Access to office-based physicians under capitation reimbursement and Medicaid case management. Findings from the Children's Medicaid Program.

This study reports the effects of a voluntary Medicaid case-management demonstration on the primary care provided to young children by office-based physicians. The MDs who participated were reimbursed at rates higher than the regular Medicaid fee schedule, either through augmented fees for specific services or through monthly capitation payments. Using the Medicaid Management Information System (MMIS) claims data, we compared the rates at which children in the experimental program and children in the regular Medicaid program were seen by a physician during a one-year period. The majority of experimental children received regular and frequent care from primary care physicians during the demonstration. After controlling for race and prior utilization differences, we found that augmented fee-for-service children received more primary care from office-based physicians than children in the regular Medicaid program. Capitation children received at least the same amount of primary care as children in the regular Medicaid program. We interpret our data to mean that capitation payment, untied to the delivery of services, does not necessarily reduce access to primary care and that higher fees for physicians who treat children may, in fact, increase access.

Capitation Fee↗
PubMed1988

Surgical aspects of international drug smuggling.

The internal concealment of cocaine and other drugs in packets by "body packers"--those who swallow packets of drugs or hide them in their vagina or rectum--to avoid detection by customs officials has been increasing in both the United States and Europe. The types of package and how they are concealed are changing as the traffickers become more sophisticated in their methods. The latest parcels are less likely to burst, but obstruction of the bowel may occur. Awareness of the problem is important for staff of emergency medical services near international ports of arrival.

Adult↗