24 results match your criteria: "The Joan and Sanford I. Weill Medical College[Affiliation]"

CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia.

N Engl J Med

January 2021

From the Sarah Cannon Center for Blood Cancer at the Children's Hospital at TriStar Centennial, Nashville (H.F., J.D.), and St. Jude Children's Research Hospital, Memphis (A.S.) - both in Tennessee; Vertex Pharmaceuticals (D.A., B.K.E., J.L.-H., A.Y.) and Boston University School of Medicine (M.H.S.), Boston, and CRISPR Therapeutics, Cambridge (Y.-S.C., T.W.H., A. Kernytsky, S. Soni) - both in Massachusetts; the University of Milan, Milan (M.D.C.), and Ospedale Pediatrico Bambino Gesù Rome, Sapienza, University of Rome, Rome (F.L.); the University of Regensburg, Regensburg (J. Foell, S.C.), and Children's University Hospital, University of Tübingen, Tübingen (R.H.) - both in Germany; Imperial College Healthcare NHS Trust, St. Mary's Hospital, London (J. de la Fuente); Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (S.G.); the University of Athens, Athens (A. Kattamis); BC Children's Hospital, University of British Columbia, Vancouver (A.M.L.), and the Hospital for Sick Children-University of Toronto, Toronto (D.W.) - both in Canada; Columbia University (M.Y.M.) and the Joan and Sanford I. Weill Medical College of Cornell University (S. Sheth), New York; Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris, Paris (M.M.); and the University of Illinois at Chicago, Chicago (D.R.).

Article Synopsis
  • Transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) are serious genetic disorders that require ongoing medical treatment and can be life-threatening.
  • Researchers utilized CRISPR-Cas9 technology to modify CD34+ stem cells from healthy donors, targeting a specific enhancer to increase fetal hemoglobin production by altering BCL11A, a gene that suppresses it.
  • Two patients, one with TDT and the other with SCD, received these edited cells after a preparative procedure and showed significant improvements after a year, including high fetal hemoglobin levels, independence from blood transfusions, and reduced complications from SCD.
View Article and Find Full Text PDF

Delusional Disorder Arising From a CNS Neoplasm.

J Neuropsychiatry Clin Neurosci

August 2017

From the Joan and Sanford I Weill Medical College of Cornell University, New York (JS); and the Department of Psychiatry, New York-Presbyterian Hospital, New York (JK, DF).

Erotomania arising from a central nervous system (CNS) neoplasm has not been previously described. Here, we present the first known case, to our knowledge, of erotomania with associated persecutory delusions arising following diagnosis and treatment of a left frontal lobe brain tumor.

View Article and Find Full Text PDF

Reducing diabetes mellitus complications has been a major focus for Healthy People 2010. A prior retrospective cohort of our burn center's admissions revealed worse outcomes among diabetic patients, that is, increased infection rates, grafting and graft complications, and increased length of hospital stay. Therefore, a prospective study has been designed to carefully assess wound repair and recovery of diabetic and nondiabetic burn patients.

View Article and Find Full Text PDF

Within the past decade, it has been recognized that a majority of patients with essential mixed cryoglobulinemia (MC) are chronically infected with hepatitis C virus (HCV). Although the underlying mechanisms have not been fully elucidated, cryoglobulin formation is clearly linked to the attempt of the host to clear the significant quantities of virions generated daily by the chronic infection. This review summarizes the current understanding of the relationship between chronic HCV infection and the development of MC, and discusses the interaction between the immune system and HCV and how this interaction can lead to the development of lymphoproliferative disorders.

View Article and Find Full Text PDF

Objectives: To determine the spectrum of pathophysiology underlying the lower urinary tract symptoms (LUTS) persisting for > or = 6 months after brachytherapy for localized prostate cancer.

Patients And Methods: A database of men from two practice settings was searched for men who developed LUTS persisting for > or = 6 months after completing brachytherapy for localized prostate cancer. Patients were evaluated with a structured history and physical examination, International Prostate Symptom Score (IPSS), 24-h voiding diary, noninvasive free-flow uroflowmetry, postvoid residual urine volume (PVR), cystoscopy and a video-urodynamic study.

View Article and Find Full Text PDF

Purpose: This study evaluates the types of instrumental social support that are perceived by patients with coronary artery disease as being most helpful to health behavior modification.

Methods: A purposive sample of 63 patients with coronary artery disease were enrolled in this qualitative study. Patients described lifestyle changes that they made in an effort to stay healthy and the types of instrumental supports provided by their social networks that helped them make these changes.

View Article and Find Full Text PDF

Despite important advances in the management of hypercholesterolemia in recent decades, many patients with lipid disorders remain unidentified or undertreated and so continue to have unfavorable levels of low-density lipoprotein (LDL) cholesterol and an increased risk for coronary events. The statins--which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis--have proved to be the most powerful pharmacologic agents for lowering serum lipids, and newer statins offer even greater efficacy than the agents introduced 10 to 15 years ago. Studies have shown that rosuvastatin, in late-stage development, is a very potent agent for the treatment of primary hypercholesterolemia, and that relatively low doses decrease LDL cholesterol levels to a greater extent than do similar doses of pravastatin, simvastatin, or atorvastatin as evaluated in separate clinical trials.

View Article and Find Full Text PDF

Patients' preoperative expectations of shoulder surgery affect both the decision to proceed with surgery and how patients assess outcomes of surgery. Our goals were to identify patients' expectations of shoulder surgery, to develop and test a patient-derived shoulder surgery expectations survey, and to determine the prevalence of major expectations by diagnosis. An initial sample of 409 patients (mean age, 51 +/- 17 years; 58% men) with diverse shoulder diagnoses were asked open-ended questions preoperatively about their expectations of shoulder surgery.

View Article and Find Full Text PDF

Laser Tissue Welding - Poised for the New Millenium.

Surg Technol Int

October 2000

Director, Pediatric Urology Center / Assistant Professor of the James Buchanan Brady Foundation Department of Urology / The Richard Rodgers Family Assistant Professor of Pediatric Urology and Reconstructive Surgery, New York Presbyterian Hospital, Cornell University, The Joan and Sanford I. Weill Medical College, New York, NY.

Laser tissue welding is a relatively new technique, which was initially described only about 30 years ago. Over the past 10 years, the implementation of protein solders has redefined the field. Alternative methods of wound closure and of tissue approximation have been quickly accepted in clinical medicine.

View Article and Find Full Text PDF

Mutational analysis of endonuclease V from Thermotoga maritima.

Biochemistry

July 2002

Department of Microbiology and Immunology, Hearst Microbiology Research Center and Strang Cancer Prevention Center, The Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Avenue, Box 62, New York, New York 10021, USA.

Endonuclease V nicks damaged DNA at the second phosphodiester bond 3' to inosine, uracil, mismatched bases, or abasic (AP) sites. Alanine scanning mutagenesis was performed in nine conserved positions of Thermotoga maritima endonuclease V to identify amino acid residues involved in recognition or endonucleolytic cleavage of these diverse substrates. Alanine substitution at D43, E89, and D110 either abolishes or substantially reduces inosine cleavage activity.

View Article and Find Full Text PDF

Multiple cleavage activities of endonuclease V from Thermotoga maritima: recognition and strand nicking mechanism.

Biochemistry

July 2001

Department of Microbiology and Immunology, Hearst Microbiology Research Center and Strang Cancer Prevention Center, The Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Avenue, Box 62, New York, New York 10021, USA.

Endonuclease V is a deoxyinosine 3'-endonuclease which initiates removal of inosine from damaged DNA. A thermostable endonuclease V from the hyperthermophilic bacterium Thermotoga maritima has been cloned and expressed in Escherichia coli. The DNA recognition and reaction mechanisms were probed with both double-stranded and single-stranded oligonucleotide substrates which contained inosine, abasic site (AP site), uracil, or mismatches.

View Article and Find Full Text PDF

Exploring the catalytic center of TaqI endonuclease: rescuing catalytic activity by double mutations and Mn2+.

Biochim Biophys Acta

March 2001

Department of Microbiology and Immunology, Hearst Microbiology Research Center and Strang Cancer Prevention Center, The Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Avenue, P.O. Box 62, New York, NY 10021, USA.

TaqI is a metal-dependent endonuclease that recognizes T(downward arrow)CGA, with the arrow indicating the cleavage site. Mutations at K158 render the enzyme inactive and mutations at K157 significantly reduce DNA cleavage activity (W. Cao and F.

View Article and Find Full Text PDF

Arsenicals in hematologic cancers.

Semin Oncol

October 2000

Leukemia and Developmental Chemotherapy Services, Memorial Sloan-Kettering Cancer Center, and the Joan and Sanford I. Weill Medical College of Cornell University, New York, NY 10021, USA.

Arsenic trioxide (AT) has been the object of renewed interest as a therapeutic since studies in China in the late 1980s confirmed its efficacy in the treatment of acute promyelocytic leukemia (APL). These studies have been replicated in the West, with complete remissions achieved in 80% to 90% of patients with refractory or relapsed APL. The drug has been relatively well tolerated.

View Article and Find Full Text PDF

Laser tissue welding - poised for the new millenium.

Surg Technol Int

October 2012

Director, Pediatric Urology Center / Assistant Professor of the James Buchanan Brady Foundation Department of Urology / The Richard Rodgers Family Assistant Professor of Pediatric Urology and Reconstructive Surgery, New York Presbyterian Hospital, Cornell University, The Joan and Sanford I. Weill Medical College, New York, NY.

Laser tissue welding is a relatively new technique, which was initially described only about 30 years ago. Over the past 10 years, the implementation of protein solders has redefined the field. Alternative methods of wound closure and of tissue approximation have been quickly accepted in clinical medicine.

View Article and Find Full Text PDF

Bovine neurophysins, which have typically served as the paradigm for neurophysin behavior, are metastable in their disulfide-paired folded state and require ligand stabilization for efficient folding from the reduced state. Studies of unliganded porcine neurophysin (oxytocin-associated class) demonstrated that its dimerization constant is more than 90-fold greater than that of the corresponding bovine protein at neutral pH and showed that the increased dimerization constant is accompanied by an increase in stability sufficient to allow efficient folding of the reduced protein in the absence of ligand peptide. Using site-specific mutagenesis of the bovine protein and expression in Escherichia coli, the functional differences between the bovine and porcine proteins were shown to be attributable solely to two subunit interface mutations in the porcine protein, His to Arg at position 80 and Glu to Phe at position 81.

View Article and Find Full Text PDF

Objectives: To document changes in serum secretory leukocyte protease inhibitor (SLPI) in human sepsis and in experimental endotoxemia in vivo. To compare changes in serum SLPI in human sepsis with changes in interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha. To determine whether or not changes in SLPI correlate with the severity of multiple organ dysfunction syndrome as measured by the maximal multiple organ dysfunction score.

View Article and Find Full Text PDF

Ligation reaction specificities of an NAD(+)-dependent DNA ligase from the hyperthermophile Aquifex aeolicus.

Nucleic Acids Res

March 2000

Department of Microbiology and Immunology, Hearst Microbiology Research Center and Strang Cancer Prevention Center, The Joan and Sanford I. Weill Medical College of Cornell University, New York, NY 10021, USA.

An NAD(+)-dependent DNA ligase from the hyperthermophilic bacterium Aquifex aeolicus was cloned, expressed in Escherichia coli and purified to homogeneity. The enzyme is most active in slightly alkaline pH conditions with either Mg(2+)or Mn(2+)as the metal cofactor. Ca(2+)and Ni(2+)mainly support formation of DNA-adenylate intermediates.

View Article and Find Full Text PDF

Earlier thermodynamic studies of the intermolecular interactions between mature oxytocin and neurophysin, and of the effects of these interactions on neurophysin folding, raised questions about the intramolecular interactions of oxytocin with neurophysin within their common precursor. To address this issue, the disulfide-rich precursor of oxytocin-associated bovine neurophysin was expressed in Escherichia coli and folded in vitro to yield milligram quantities of purified protein; evidence of significant impediments to yield resulting from damage to Cys residues is presented. The inefficiency associated with the refolding of reduced mature neurophysin in the presence of oxytocin was found not to be alleviated in the precursor.

View Article and Find Full Text PDF

Geriatric psychiatric disorders usually occur in the context of medical illness, disability, and psychosocial impoverishment. Preliminary evidence suggests that psychotherapy can reduce not only psychopathology but also physical complaints, pain, and disability and that it can improve compliance with medical regimens. Psychotherapy has been found effective in treatment of depression related to bereavement and caregiver burden.

View Article and Find Full Text PDF

Background: Previous data indicate that left ventricular ejection fraction (LVEF) provides prognostic information among patients with coronary artery disease (CAD), but the value of such testing specifically for defining benefits of coronary artery bypass grafting (CABG) may relate to severity of exercise-inducible ischemia measured noninvasively before surgery.

Methods And Results: To determine the independent prognostic importance of preoperative ischemia severity for predicting outcomes of CABG among patients with extensive CAD, we monitored 167 stable patients with angiographically documented 3-vessel CAD (average follow-up of 9 years in event-free patients) who previously had undergone rest and exercise radionuclide cineangiography. Their course was correlated with data obtained during initial radionuclide testing, coronary arteriography, and clinical evaluation at study entry.

View Article and Find Full Text PDF

Restriction endonucleases achieve sequence-specific recognition and strand cleavage through the interplay of base, phosphate backbone, and metal cofactor interactions. In this study, we investigate the binding kinetics of TaqI endonuclease using the wild-type enzyme and a binding proficient, catalysis deficient mutant TaqI-D137A both in the absence of a metal cofactor and in the presence of Mg2+ or Ca2+. As demonstrated by gel mobility shift analyses, TaqI endonuclease requires a metal cofactor for achieving high-affinity specific binding to its cognate sequence, TCGA.

View Article and Find Full Text PDF

Biochemical properties of a high fidelity DNA ligase from Thermus species AK16D.

Nucleic Acids Res

February 1999

Department of Microbiology, Hearst Microbiology Research Center, Strang Cancer Prevention Center, The Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Avenue, Box 62, New York, NY 10021, USA.

NAD+-dependent DNA ligases from thermophilic bacteria Thermus species are highly homologous with amino acid sequence identities ranging from 85 to 98%. Thermus species AK16D ligase, the most divergent of the seven Thermus isolates collected worldwide, was cloned, expressed in Escherichia coli and purified to homogeneity. This Thermus ligase is similar to Thermus thermophilus HB8 ligase with respect to pH, salt, NAD+, divalent cation profiles and steady-state kinetics.

View Article and Find Full Text PDF

Identification of TaqI endonuclease active site residues by Fe2+-mediated oxidative cleavage.

J Biol Chem

December 1998

Department of Microbiology, Hearst Microbiology Research Center, Strang Cancer Prevention Center, The Joan and Sanford I. Weill Medical College of Cornell University, New York, New York 10021, USA.

Metal cofactors (Mg2+ and Mn2+) modulate both specific DNA binding and strand cleavage in the TaqI endonuclease (Cao, W., Mayer, A. N.

View Article and Find Full Text PDF