Biomedical subjects

Samuel Wagner

Publications and source records attributed to Samuel Wagner.

7 recordsLinked to original sources

PubMed2006

Rationalizing membrane protein overexpression.

Functional and structural studies of membrane proteins usually require overexpression of the proteins in question. Often, however, the 'trial and error' approaches that are mainly used to produce membrane proteins are not successful. Our rapidly increasing understanding of membrane protein insertion, folding and degradation means that membrane protein overexpression can be more rationalized, both at the level of the overexpression host and the overexpressed membrane protein. This change of mindset is likely to have a significant impact on membrane protein research.

Animals↗

PubMed2006

New Escherichia coli outer membrane proteins identified through prediction and experimental verification.

Many new Escherichia coli outer membrane proteins have recently been identified by proteomics techniques. However, poorly expressed proteins and proteins expressed only under certain conditions may escape detection when wild-type cells are grown under standard conditions. Here, we have taken a complementary approach where candidate outer membrane proteins have been identified by bioinformatics prediction, cloned and overexpressed, and finally localized by cell fractionation experiments. Out of eight predicted outer membrane proteins, we have confirmed the outer membrane localization for five-YftM, YaiO, YfaZ, CsgF, and YliI--and also provide preliminary data indicating that a sixth--YfaL--may be an outer membrane autotransporter.

Bacterial Outer Membrane Proteins↗

PubMed2006

Addressing the issue of channeling bias in observational studies with propensity scores analysis.

Randomized Clinical Trials (RCTs) remain the gold standard for determining the utility of pharmaceuticals especially from a safety and efficacy standpoint. However, restrictive entry criteria and stringent protocols can be barriers to generalizing RCT findings to real world practices and outcomes. Observational studies overcome these limitations of RCTs since they are representative of real world populations and practices. Nonetheless, attributing causality remains a major limitation in observational studies, due to the non-random assignment of subjects to treatment. Non-random assignment can lead to imbalances in risk-factors between the groups being compared and thus bias the estimates of the treatment effect. Non-random assignment can be particularly problematic in observational studies comparing older versus newer pharmaceuticals from similar therapeutic classes due to the phenomenon of channeling. Channeling occurs when drug therapies with similar indications are preferentially prescribed to groups of patients with varying baseline prognoses. In this manuscript we discuss the phenomenon of channeling and the use of a statistical technique known an propensity scores analysis which potentially adjusts for the effects of channeling. During the course of this manuscript we discuss tests for determining the quality of the derived propensity score, various techniques for utilizing propensity scores, and also the potential limitations of this technique. With the increasing availability of high quality pharmaceutical and medical claims data for use in observational studies, increased attention must be given to analytic techniques that adjust optimally for non-random assignment and resulting channeling bias. For research studies using observational study designs, propensity score analysis offers a reasonable solution to address the limitation of non-random assignment, especially when RCTs are too costly, time-consuming or not ethically feasible.

Bias↗

PubMed2005

Defining the role of the Escherichia coli chaperone SecB using comparative proteomics.

To improve understanding and identify novel substrates of the cytoplasmic chaperone SecB in Escherichia coli, we analyzed a secB null mutant using comparative proteomics. The secB null mutation did not affect cell growth but caused significant differences at the proteome level. In the absence of SecB, dynamic protein aggregates containing predominantly secretory proteins accumulated in the cytoplasm. Unprocessed secretory proteins were detected in radiolabeled whole cell lysates. Furthermore, the assembly of a large fraction of the outer membrane proteome was slowed down, whereas its steady state composition was hardly affected. In response to aggregation and delayed sorting of secretory proteins, cytoplasmic chaperones DnaK, GroEL/ES, ClpB, IbpA/B, and HslU were up-regulated severalfold, most likely to stabilize secretory proteins during their delayed translocation and/or rescue aggregated secretory proteins. The SecB/A dependence of 12 secretory proteins affected by the secB null mutation (DegP, FhuA, FkpA, OmpT, OmpX, OppA, TolB, TolC, YbgF, YcgK, YgiW, and YncE) was confirmed by "classical" pulse-labeling experiments. Our study more than triples the number of known SecB-dependent secretory proteins and shows that the primary role of SecB is to facilitate the targeting of secretory proteins to the Sec-translocase.

Bacterial Outer Membrane Proteins↗

PubMed2003

The prevalence of cardiorenal risk factors in patients prescribed nonsteroidal anti-inflammatory drugs: data from managed care.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to cause abnormalities in renal function. This is an important concern in patients with cardiorenal risk factors, including hypertension, congestive heart failure, edema, renal impairment, and advanced age. OBJECTIVES: The goals of this study were to determine the prevalence of cardiorenal risk factors in patients with rheumatoid arthritis (RA) or osteoarthritis and ascertain whether these risk factors are associated with prescribing patterns of cyclooxygenase (COX)-2-selective inhibitors and other NSAIDs. METHODS: This was a retrospective, longitudinal claims analysis using data from 19 large independent-practice-model managed care health plans in the United Stated. Three cohorts were identified based on claims for celecoxib, rofecoxib, or other NSAIDs from October 1, 1999, through September 30, 2000. Logistic regression models were used to explore whether baseline cardiorenal risk factors were related to choice of therapy. RESULTS: A total of 77,552 patients received celecoxib (n = 6779 [8.74%]), rofecoxib (n = 7189 [9.27%]), or other NSAIDs (n = 63,584 [81.99%]). Patients prescribed COX-2-selective inhibitors were older than those receiving other NSAIDs and had a diagnosis of RA more often. Overall, 42% of patients had >or=1 cardiorenal risk factor, and approximately one third had hypertension. Cardiorenal risk factors were not related to physicians' prescribing of celecoxib or rofecoxib, but the presence of any cardiorenal risk factor was associated with an increase in the use of COX-2-selective inhibitors compared with other NSAIDs, from 12% for cerebrovascular disease (point estimate, 1.124; P<0.001) to 74% for chronic renal failure/nephritis (point estimate, 1.738; P=0.025). RA and advanced age were associated with the use of celecoxib rather than rofecoxib. CONCLUSIONS: The prevalence of cardiorenal risk factors was found to be similar in patients prescribed celecoxib or rofecoxib for arthritis. Patients with these risk factors were more likely to receive a COX-2-selective inhibitor than other NSAIDs.

Adult↗

PubMed2003

Persistence with COX-2 inhibitors in managed care: an analysis of claims data.

Drug tolerability strongly influences patients' persistence with treatment. In this study, patterns of medication persistence with cyclooxygenase 2 (COX-2)-specific inhibitors and nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs) were compared in a managed care setting. Pharmacy, enrollment, and medical claims data from 19 health plans were used to match subjects newly treated with celecoxib, rofecoxib, ibuprofen, naproxen, or diclofenac between July 1, 1999 and June 30, 2000. By using multiple regression analysis, users of COX-2-specific inhibitors were found to be 56.8% less likely to discontinue medication use and 60.3% less likely to switch treatment than were users of nonspecific NSAIDs (P < .001). Celecoxib users were 4.6% less likely to discontinue treatment than were rofecoxib users (P < .001). The greater persistence observed among users of COX-2 inhibitors might reflect improved treatment efficacy and patient satisfaction.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMedDate not supplied

Eye care in the skilled nursing facility: a pilot study of prevalence and treatment patterns of glaucoma.

OBJECTIVE: The objective of this study was to determine the rates of ophthalmic examinations for glaucoma, prevalence rates of glaucoma, ongoing evaluation (follow-up) rates and rates of treatment for a population of residents in a skilled nursing facility. DESIGN: We conducted a retrospective evaluation and chart review of glaucoma-related ophthalmology services. SETTING: This study was conducted in a skilled nursing facility located in a large metropolitan area located in the Midwest. PARTICIPANTS: We studied all nursing home residents of the facility on October 1, 2002 (n = 160). METHODS: We conducted a retrospective evaluation and chart review of glaucoma-related ophthalmology services for 160 patients. The medical records used for review included admission records, physician history and physical records, hospital notes, nursing assessments, consultation notes, and medication reviews (including medications administered during hospital stays). Minimum data set (MDS) data and individual patient interviews were used to supplement and verify chart abstraction findings. RESULTS: Eighty-three residents (52%) had evidence of assessment for glaucoma. Thirty-three of these residents (40%) had documentation of a diagnosis of glaucoma; 25 (76%) had current treatment orders for a topical ophthalmic agent. Nine patients were using combination therapy; four used topical and oral beta-adrenergic-blocking agents. CONCLUSIONS: Visual impairment remains a serious problem for nursing facility residents. Assessment of visual abilities is infrequent or nonexistent. Education for nursing home personnel, discussion and activation among nursing home thought leaders, and guidelines for the evaluation and management of glaucoma in this care environment are needed.

Adrenergic beta-Antagonists↗