A5060735489- Atrial Fibrillation Management and Outcomes
- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Venous Thromboembolism Diagnosis and Management
- Renal Transplantation Outcomes and Treatments
- HIV/AIDS drug development and treatment
- Acute Myocardial Infarction Research
- HER2/EGFR in Cancer Research
- Hepatitis C virus research
- Protein Degradation and Inhibitors
- Cardiac Arrhythmias and Treatments
- Cutaneous lymphoproliferative disorders research
- Blood Coagulation and Thrombosis Mechanisms
- Biosimilars and Bioanalytical Methods
- Hepatitis B Virus Studies
- Cancer and Skin Lesions
- Peptidase Inhibition and Analysis
- Multiple Myeloma Research and Treatments
- Advanced Drug Delivery Systems
- Protein purification and stability
- Pharmaceutical studies and practices
- Advanced Biosensing Techniques and Applications
- Genital Health and Disease
- S100 Proteins and Annexins
- Immune Cell Function and Interaction
Bristol-Myers Squibb (United States)
2023-2024
Boehringer Ingelheim (United States)
1991-2017
Boehringer Ingelheim (Germany)
1994-2016
King's College London
2012
Texas Tech University
1989-1995
Texas Tech University Health Sciences Center
1989-1995
Santa Clara Valley Medical Center
1991
Community Hospital
1991
University of Chicago
1973
Symptomatic pulmonary aspergillosis has rarely been reported in patients with the acquired immunodeficiency syndrome (AIDS). We describe predisposing factors, clinical and radiologic features, therapeutic outcomes 13 aspergillosis, all of whom had human virus (HIV) infection 12 AIDS.
Idarucizumab, a monoclonal antibody fragment that binds dabigatran with high affinity, is in development as specific antidote for dabigatran. In this first-in-human, single-rising-dose study, we investigated the pharmacokinetics, safety and tolerability of idarucizumab. Healthy male volunteers aged 18-45 years received between 20 mg 8 g idarucizumab 1-hour intravenous infusion 10 sequential dose groups, or 1, 2 4 5-minute infusion. Subjects within each group were randomised 3:1 to placebo. A...
Abstract Objective . To assess the safety and efficacy of a monoclonal antibody (MAb) to intercellular adhesion molecule 1 (ICAM‐1; CD54) in rheumatoid arthritis (RA). Methods A phase I/II, open‐label, dose‐escalation study 32 patients. Results During treatment, peripheral CD 3+ /CD4+ lymphocytosis was noted, several patients demonstrated transient cutaneous anergy, which suggests that therapy modified T cell recirculation. Thirteen 23 who received 5 days treatment clinical improvement...
Modulating the chemical composition of cereblon (CRBN) binders is a critical step in optimization process protein degraders that seek to hijack function this E3 ligase. Small structural changes can have profound impacts on overall profile these compounds, including depth on-target degradation, neosubstrate degradation selectivity, as well other drug-like properties. Herein, we report design and synthesis series novel CRBN binding moieties. These were evaluated for common neosubstrates Aiolos...
Idarucizumab is an antibody fragment that specifically reverses dabigatran-mediated anticoagulation. Safety, pharmacokinetics and pharmacodynamics of idarucizumab were investigated in dabigatran-treated, middle-aged, elderly renally impaired volunteers with characteristics similar to patients receiving anticoagulant therapy.In this randomized, double-blind, crossover study, 46 subjects (12 45-64 years; 16 elderly, 65-80 18 mild or moderate renal impairment) received dabigatran etexilate (DE;...
<b>Background and Purpose:</b> To obtain information on the safety, pharmacokinetics biological activity of enlimomab (anti-ICAM-1 antibody) in stroke patients. <b>Methods:</b> An open, uncontrolled, dose titration study was conducted 32 patients hospitalized for stroke. Patients received one four fixed regimens enlimomab. A loading administered within 24 h onset symptoms followed by daily maintenance doses; total doses ranged from 140 to 480 mg....
To characterize the steady-state pharmacokinetic combination of nonpeptidic protease inhibitor tipranavir (TPV) with ritonavir (RTV) in 95 healthy adult volunteers, a phase 1, single-center, open-label, randomized, parallel-group trial was conducted.Participants received 250-mg self-emulsifying drug delivery system (SEDDS) capsules TPV at doses between 250 mg and 1250 twice daily for 11 days, then one or two RTV 100-mg SEDDS capsules, addition to next 21 days.Coadministration (TPV/r)...
The studies reported were done with the objectives of preparing several different peroxidase-labeled antibody conjugates and testing their usefulness for detection soluble insoluble tissue antigens. Glutaraldehyde, toluene diisocyanate N,N'-dicyclohexyl carbodiimide used to cross-link horseradish peroxidase goat anti-rabbit immunoglobulin G; resulting characterized by molecular size enzymatic immunologic activity. They then tested properties as immunohistologic reagents using 0.5-µ sections...
Construction of a series chimeric antibodies (murine variable region and human constant region) derived from the murine antibody BIRR1, which recognizes intercellular adhesion molecule 1 (ICAM-1), has revealed differences in relative binding abilities to antigen. The show ranking their ability compete with BIRR1 for antigen on surface cells order = cIgG1 (100%) > cIgG4 (30%) cIgG2 (10%) as demonstrated by solid-phase competitive enzyme-linked immunosorbent assay. Papain digestion yielded Fab...
JAO, WELLINGTON M.D.; POLLAK, VICTOR E. NORRIS, STEPHEN H. LEWY, PETER PIRANI, CONRAD L. M.D. Author Information
Abstract The androgen receptor (AR) is a key driver of the cellular processes that contribute to pathology prostate cancers at most stages, and drugs inhibit activity this or interfere with biosynthesis have become cornerstone treatments for cancer. While both types therapy had significant positive impact on disease progression overall survival, de novo acquired resistance remains an impediment durable clinical response in patients metastatic castration-resistant cancer (mCRPC). mechanisms...
This is an unusual case of fatal hepatic necrosis caused by disseminated type 5 adenovirus in a renal transplant recipient. adult patient may have been colonized at the time transplantation with kidney from pediatric donor. The became invasive when host's cellular immune system was suppressed high doses corticosteroids given to reverse acute allograft rejection.
The pharmacokinetic and metabolite profiles of the antiretroviral agent tipranavir (TPV), administered with ritonavir (RTV), in nine healthy male volunteers were characterized. Subjects received 500-mg TPV capsules 200-mg RTV twice daily for 6 days. They then a single oral dose 551 mg containing 90 microCi [(14)C]TPV 200 on day 7, followed by twice-daily doses unlabeled up to 20 Blood, urine, feces collected mass balance profiling. Metabolite profiling identification was performed using flow...
A novel class of lymphocyte function-associated antigen-1 (LFA-1) inhibitors is described. Discovered during the process to improve physicochemical and metabolic properties BIRT377 (1, Figure 1), a previously reported hydantoin-based LFA-1 inhibitor, these compounds are characterized by an imidazole-based 5,5-bicyclic scaffold, 1,3,3-trisubstituted 1H-imidazo[1,2-α]imidazol-2-one (i.e. structure 3). The structure−activity relationship (SAR) shows that electron−withdrawing groups at C5 on...
Idarucizumab is a humanized monoclonal antibody fragment that specifically binds with high affinity to dabigatran.This study investigated the safety, tolerability and pharmacokinetics of idarucizumab alone dabigatran at steady state, effects on dabigatran-induced anticoagulation.This was two-part, phase I, randomized, placebo-controlled, double-blind, rising-dose trial in healthy Japanese males. Part 1: 32 subjects (males) received single doses (1, 2, 4 or 8 g [n=6/dose group]) placebo...
Idarucizumab, a humanized monoclonal anti-dabigatran antibody fragment, is effective in emergency reversal of dabigatran anticoagulation. Pre-existing and treatment-emergent anti-idarucizumab antibodies (antidrug antibodies; ADA) may affect the safety efficacy idarucizumab. This analysis characterized pre-existing ADA assessed their impact on pharmacokinetics pharmacodynamics (PK/PD) idarucizumab.Data were pooled from three Phase I, randomized, double-blind idarucizumab studies healthy...
Abstract In this study, tipranavir (TPV) biotransformation and disposition when co-administered with ritonavir (RTV) were characterized in Sprague–Dawley rats. Rats administered a single intravenous (5 mg kg−1) or oral (10 dose of [14C]TPV co-administration RTV kg−1). Blood, urine, faeces bile samples collected at specified time-points over period 168 h. Absorption TPV-related radioactivity ranged from 53.2–59.6%. Faecal excretion was on average 86.7% 82.4% (intravenous) 75.0% 82.0% (oral)...