- Nicotinic Acetylcholine Receptors Study
- Bladder and Urothelial Cancer Treatments
- Ion channel regulation and function
- Prostate Cancer Treatment and Research
- Hormonal and reproductive studies
- Urinary and Genital Oncology Studies
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Advanced Causal Inference Techniques
- Prion Diseases and Protein Misfolding
- Protist diversity and phylogeny
- Venous Thromboembolism Diagnosis and Management
- Health Systems, Economic Evaluations, Quality of Life
- Statistical Methods in Clinical Trials
- Photoreceptor and optogenetics research
- Prostate Cancer Diagnosis and Treatment
- Diabetes Management and Research
- Statistical Methods and Bayesian Inference
- Urological Disorders and Treatments
- Estrogen and related hormone effects
- Geology and Paleoclimatology Research
- Diabetes Treatment and Management
- Pharmaceutical industry and healthcare
- COVID-19 Clinical Research Studies
- Healthcare Policy and Management
Harvard Pilgrim Health Care
2022-2025
Harvard University
1993-2025
Brigham and Women's Hospital
2012-2020
Centers for Medicare and Medicaid Services
2019
Singapore Immunology Network
2012-2018
Pharmac
2015
National University of Singapore
2013
Agency for Science, Technology and Research
2013
Eli Lilly (United States)
2012
University of Strathclyde
1997-2009
A family of genes coding for proteins homologous to the alpha subunit muscle nicotinic acetylcholine receptor has been identified in rat genome. These are transcribed central and peripheral nervous systems areas known contain functional receptors. In this paper, we demonstrate that three these genes, which call 3, 4, beta 2, encode form receptors when expressed Xenopus oocytes. Oocytes expressing either 3 or 4 protein combination with 2 produced a strong response acetylcholine. only gave...
Abstract Natural killer (NK) cells rely on surface receptors to distinguish healthy from cancer cells. We designed a receptor termed NKG2D-DAP10-CD3ζ that is composed of the NK cell activating molecule NKG2D plus 2 key signaling molecules, DAP10 and CD3ζ, evaluated its capacity promote killing. Retroviral transduction markedly increased expression in cells, which became consistently more cytotoxic than mock-transduced against leukemia solid tumor lines. In contrast, there was no increase...
A new type of agonist-binding subunit rat neuronal nicotinic acetylcholine receptors (nAChRs) was identified. Rat genomic DNA and complementary encoding this (alpha2) were cloned analyzed. Complementary expression studies in Xenopus oocytes revealed that the injection messenger RNAs (mRNAs) for alpha2 beta2 (a nAChR subunit) led to generation a functional nAChR. In contrast other known nAChRs, receptor produced by mRNAs resistant α-neurotoxin Bgt3.1. situ hybridization histochemistry showed...
We have identified two additional members of the neuronal nicotinic acetylcholine receptor (nAChR)-related gene family. cDNA clones for one new gene, designated alpha 5, were isolated from rat hippocampus and PC12 cell line libraries. The 5 encodes a protein 48,800 daltons (424 amino acids) which exhibits significant overall acid sequence identity with previously cloned nAChR subunits 1 (49%), 2 (55%), 3 (52%), 4 (49%). Features characteristic other alpha-subunits are present such as...
Patients with muscle invasive carcinoma of the bladder treated radical radiation were prospectively documented and followed in an attempt to identify prognostic factors predictive response treatment. Data on 121 consecutive patients between 1981 1985 are presented. Over-all actuarial survival patient population (median age 70 years) was 31.6% at 5 years cause-specific 44.8%. At analysis 33 (27.3%) alive preserved function. Independent for complete tumor configuration, hemoglobin level...
Importance The incidence of arterial thromboembolism and venous in persons with COVID-19 remains unclear. Objective To measure the 90-day risk patients hospitalized before or during vaccine availability vs influenza. Design, Setting, Participants Retrospective cohort study 41 443 (April-November 2020), 44 194 (December 2020-May 2021), 8269 influenza (October 2018-April 2019) US Food Drug Administration Sentinel System (data from 2 national health insurers 4 regional integrated systems)....
No AccessJournal of Urology1 Aug 1989M-Vac (Methotrexate, Vinblastine, Doxorubicin and Cisplatin) Chemotherapy for Transitional Cell Carcinoma: The Princess Margaret Hospital Experience Ian Tannock, Mary Gospodarowicz, John Connolly, Michael Jewett TannockIan Tannock More articles by this author , GospodarowiczMary Gospodarowicz ConnollyJohn Connolly JewettMichael View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)38733-5AboutPDF ToolsAdd to favoritesDownload CitationsTrack...
Background To the extent that outcomes are mediated through negative perceptions of generics (the nocebo effect), observational studies comparing brand-name and generic drugs susceptible to bias favoring drugs. We used authorized (AG) products, which identical in composition appearance products but marketed as generics, a control group address this an evaluation aiming compare effectiveness versus brand medications. Methods findings For commercial health insurance enrollees from US,...
Previous observational studies have suggested that fluoroquinolones are associated with aortic aneurysm or dissection, but these may be subject to confounding by indication surveillance bias.To assess the association of risk dissection (AA/AD) while accounting for potential fluoroquinolone and bias owing differential surveillance.In an cohort study using a US commercial claims database, 2 pairwise 1:1 propensity score-matched cohorts were identified: patients aged 50 years older diagnosis...
We have studied the effects of acute ethanol (EtOH) exposure on agonist responses rat neuronal nicotinic receptors expressed in Xenopus oocytes by means voltage clamp techniques. In some cells, agonist‐induced current with α3β4 subunit combination could be either significantly potentiated or inhibited (range 25% to 237% control response) low concentrations (1–30 m ). At high (100–300 ) robust potentiations were observed 135% 305% control). The EtOH concentration subtype exhibited tolerance...
Partially observed confounder data pose a major challenge in statistical analyses aimed to inform causal inference using electronic health records (EHRs). While analytic approaches such as imputation are available, assumptions on underlying missingness patterns and mechanisms must be verified. We develop toolkit streamline missing diagnostics guide choice of based meeting necessary assumptions.
Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from European Medicines Agency, Health Canada, and United States (US) Food Drug Administration established a collaboration to evaluate arterial (ATE) venous (VTE) in 90 days after diagnosis ambulatory (eg, outpatient, emergency department, nursing facility) setting seven countries North America (Canada, US) Europe (England, Germany, Italy,...
Xenopus oocytes were injected with various muscle and neuronal nicotinic acetylcholine receptor (ACh receptor, cholinoceptor) subunit RNA combinations their pharmacological properties studied using two‐electrode voltage clamp. The functional expression of one these combinations, rat α4–2β2, has not been previously described. α4–2 mRNA is a splicing variant transcribed from the α4 gene. In experiments reported here, α4–2β2 subtype was functionally indistinguishable α4–1β2 subtype. For each...
<h3>Abstract</h3> <h3>Objectives</h3> To compare rates of switchbacks to branded drug products for patients switched from authorized generic products, which have the same active ingredients, appearance, and excipients as product, with ingredients product but may differ in appearance excipients. <h3>Design</h3> Observational cohort study. <h3>Setting</h3> Private (a large commercial health plan) public (Medicaid) insurance programs US. <h3>Participants</h3> Beneficiaries a US insurer between...
Thiazolidinediones, a class of medications indicated for the treatment type 2 diabetes mellitus, reduce inflammation and have been shown to provide therapeutic benefit in animal models Parkinson disease. We examined association between with thiazolidinediones onset disease older individuals. performed cohort study 29,397 Medicare patients enrolled state pharmaceutical benefits programs who initiated or sulfonylureas during years 1997 through 2005 had no prior diagnosis New users were...
Objective: Partially observed confounder data pose challenges to the statistical analysis of electronic health records (EHR) and systematic assessments potentially underlying missingness mechanisms are lacking. We aimed provide a principled approach empirically characterize missing processes investigate performance analytic methods. Methods: Three empirical sub-cohorts diabetic SGLT2 or DPP4-inhibitor initiators with complete information on HbA1c, BMI smoking as confounders interest (COI)...
Abstract Multiple imputation (MI) models can be improved with auxiliary covariates (AC), but their performance in high-dimensional data remains unclear. We aimed to develop and compare MI (HDMI) methods using structured natural language processing (NLP)-derived AC studies partially observed confounders. conducted a plasmode simulation acute kidney injury as outcome simulated 100 cohorts null treatment effect, incorporating creatinine labs, atrial fibrillation (AFib), other...