A5045151645- Protein Kinase Regulation and GTPase Signaling
- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Gastroesophageal reflux and treatments
- Chronic Myeloid Leukemia Treatments
- Plant-based Medicinal Research
- Drug Transport and Resistance Mechanisms
- Intestinal Malrotation and Obstruction Disorders
- Gastrointestinal Tumor Research and Treatment
- DNA Repair Mechanisms
- Tracheal and airway disorders
- Aldose Reductase and Taurine
- Esophageal and GI Pathology
- Chronic Lymphocytic Leukemia Research
- Schizophrenia research and treatment
- Melanoma and MAPK Pathways
- Appendicitis Diagnosis and Management
- Eosinophilic Esophagitis
- Polish Legal and Social Issues
- IgG4-Related and Inflammatory Diseases
- Liver Disease and Transplantation
- Oral Health Pathology and Treatment
- Digital and Traditional Archives Management
- Parkinson's Disease and Spinal Disorders
- Treatment of Major Depression
AstraZeneca (United Kingdom)
2018-2023
Maudsley Hospital
2007
National Health Service
2007
University of California, Los Angeles
2001
Kaiser Foundation Hospital
2000
Tufts University
1989-1992
Children's Hospital of Los Angeles
1991
University of Southern California
1991
University of Toronto
1983-1987
Sunnybrook Health Science Centre
1983-1987
Abstract Purpose: Osimertinib is a potent and selective EGFR tyrosine kinase inhibitor (EGFR-TKI) of both sensitizing T790M resistance mutations. To treat metastatic brain disease, blood–brain barrier (BBB) permeability considered desirable for increasing clinical efficacy. Experimental Design: We examined the level penetration 16 irreversible reversible EGFR-TKIs using multiple in vitro vivo BBB preclinical models. Results: In osimertinib was weakest substrate human efflux transporters...
Abstract Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare, but devastating genetic disease characterized by segmental premature aging, with cardiovascular being the main cause of death. Cells from HGPS patients accumulate progerin, permanently farnesylated, toxic form Lamin A, disrupting nuclear shape and chromatin organization, leading to DNA-damage accumulation senescence. Therapeutic approaches targeting farnesylation or aiming reduce progerin levels have provided only partial health...
Gemcitabine (dFdC) is a common treatment for pancreatic cancer; however, it thought that may fail because tumor stroma prevents drug distribution to cells. pro-drug with active metabolites generated intracellularly; therefore, visualizing the of parent as well its important. A multimodal imaging approach was developed using spatially coregistered mass spectrometry (MSI), cytometry (IMC), multiplex immunofluorescence microscopy (mIF), and hematoxylin eosin (H&E) staining assess local...
Article AbstractBackground: Clozapine is uniquely effective in refractory schizophrenia, but treatment attrition high. There has been minimal formal study of the outcomes stopping clozapine, beyond published observations time period immediately after cessation. Our aim was to establish medium-term outcome patients clozapine normal clinical practice. Method: This a retrospective analysis all subjects registered with Clozaril Patient Monitoring Service and treated South London Maudsley...
Background Minimally invasive esophagomyotomy, consisting of a laparoscopic or thoracoscopic approach, has become preferred surgical treatment for adults with achalasia. This multicenter study reports on the clinical status children who have undergone minimally esophagomyotomy Methods Symptomatology achalasia was assessed in 22 pediatric patients underwent between 1995 and 2000. All were evaluated duration hospitalization, postoperative resumption feeds, complications, symptomatic relief....
The effect of Ca++ mobilizing agonists arginine vasopressin and phenylephrine on Na+/H+ exchange was studied in freshly isolated hepatocytes perfused rat livers. activity determined from the rate H+ efflux, 22Na uptake pHi recovery. Arginine stimulated efflux increased recovery acid-loaded hepatocytes. These effects were inhibited by amiloride. vasopressin- phenylephrine-induced increases also dependent extracellular Na+. intracellular concentration, pH decreased preloaded with...
Medical records of 18 pediatric acquired immunodeficiency syndrome patients with 24 central venous catheters (CVCs) were reviewed to determine the rates and types CVC complications evaluate influence selected social factors, absolute granulocyte counts CD4+ T cell on rate infections. CVCs in place for a total 4233 days. used blood sampling, administration products infusions intravenous immune globulin, parenteral nutrition medications. Complications included catheter-related infections (8...
Objective: To evaluate the effectiveness of aripiprazole in clinical practice. Method: Prospective follow‐up patients consecutively prescribed an acute mental health unit. Retrospective analysis outcome from casenotes. Results: Data were available on 228 patients. Fifty‐one per cent discontinued over 6‐month follow‐up. Continuation with treatment was more likely out‐patients [relative risk (RR) 1.50; 95% CI: 1.13–2.00], those never before considered for clozapine (RR 1.61, 1.06–2.44) and...
A more complete and holistic view on host-microbe interactions is needed to understand the physiological cellular barriers that affect efficacy of drug treatments allow discovery development new therapeutics. Here, we developed a multimodal imaging approach combining histopathology with mass spectrometry (MSI) same section cytometry (IMC) study effects Salmonella Typhimurium infection in liver mouse model using S. strains SL3261 SL1344. This enables correlation tissue morphology specific...
Phosphorylated biomarkers are crucial for our understanding of drug mechanism action and dose selection during clinical trials, particularly drugs that target protein kinases, such as DNA-damage-response (DDR) inhibitors. However, tissue fixation conditions needed to preserve DDR-specific phospho-biomarkers have not been previously investigated. Using xenograft tissues tightly controlled formalin conditions, we assessed how preanalytical factors affect phosphorylated DDR pRAD50(Ser635),...
AbstractIt has been identified that patients with multiple dysplastic naevi are at risk of melanomas. By accurately documenting the whole patient's body photographically, a method was obtained for identifying new or changing lesions over period time.
Bile acid-induced HCO3(-)-rich choleresis may be due to primary activation of sinusoidal Na(+)-H+ exchange or biliary reabsorption unconjugated bile acid. To test these hypotheses, we studied the effect cholate and taurocholate (TC) (infused at 10 mumol/min for 20 min) on net H+ efflux, [HCO3-], flow in perfused rat livers intracellular pH (pHi) isolated hepatocytes. Cholate, but not TC, produced choleresis. Amiloride taurine decreased cholate-induced HCO3- excretion cholate. Amiloride,...
The well-documented benefits of minimally invasive surgery include more rapid recovery, less patient discomfort, better cosmesis, and earlier hospital discharge. price these is an increased demand on the operating surgeon's skill available technology. Endoscopic in pediatric offers several challenges above beyond what a surgeon finds adult correlate. body cavities are smaller, impact tremor loss dexterity enhanced, visibility further limited. In recent reviews it has been noted that both...
Abstract AZD4625 is a potent, selective, and orally bioavailable inhibitor of oncogenic KRASG12C as demonstrated in cellular assays vivo preclinical cell line–derived patient-derived xenograft models. In vitro have shown selective binding inhibition the mutant isoform, which carries glycine to cysteine mutation at residue 12, with no wild-type RAS or isoforms carrying non-KRASG12C mutations. The pharmacology shows that it has potential provide therapeutic benefit patients cancer either...