Medicine and Health Sciences Commons^™

Inducible Caspase 9 Suicide Gene To Improve The Safety Of Allodepleted T Cells After Haploidentical Stem Cell Transplantation, Siok-Keen Tey, Gianpietro Dotti, Cliona M. Rooney, Helen E. Heslop, Malcolm K. Brenner

Faculty, Staff and Students Publications

Addback of donor T cells following T cell-depleted stem cell transplantation (SCT) can accelerate immune reconstitution and be effective against relapsed malignancy. After haploidentical SCT, a high risk of graft-versus-host disease (GVHD) essentially precludes this option, unless the T cells are first depleted of alloreactive precursor cells. Even then, the risks of severe GVHD remain significant. To increase the safety of the approach and thereby permit administration of larger T cell doses, we used a suicide gene, inducible caspase 9 (iCasp9), to transduce allodepleted T cells, permitting their destruction should administration have adverse effects. We made a retroviral vector encoding …

Making Minimally Invasive Thr Safe: Conclusions From Biomechanical Simulation And Analysis, P C. Noble, J D. Johnston, J A. Alexander, M T. Thompson, M M. Usrey, E M. Heinrich, G C. Landon, K B. Mathis

Faculty, Staff and Students Publications

The use of smaller surgical incisions has become popularized for total hip arthroplasty (THR) because of the potential benefits of shorter recovery and improved cosmetic appearance. However, an increased incidence of serious complications has been reported. To minimize the risks of minimally invasive approaches to THR, we have developed an experimental approach which enables us to evaluate risk factors in these procedures through cadaveric simulations performed within the laboratory. During cadaveric hip replacement procedures performed via posterior and antero-lateral mini-incisions, pressures developed between the wound edges and the retractors were approximately double those recorded during conventional hip replacement using Charnley …

Ethnic/Racial Diversity, Maternal Stress, Lactation And Very Low Birthweight Infants, C Lau, N M. Hurst, E O. Smith, R J. Schanler

Faculty, Staff and Students Publications

OBJECTIVE: (1) To compare maternal characteristics and psychological stress profile among African-American, Caucasian and Hispanic mothers who delivered very low birthweight infants. (2) To investigate associations between psychosocial factors, frequency of milk expression, skin-to-skin holding (STS), and lactation performance, defined as maternal drive to express milk and milk volume. STUDY DESIGN: Self-reported psychological questionnaires were given every 2 weeks after delivery over 10 weeks. Milk expression frequency, STS, and socioeconomic variables were collected. RESULT: Infant birthweight, education, and milk expression frequency differed between groups. Trait anxiety, depression and parental stress in a neonatal intensive care unit (PSS:NICU) were similar. African-American …

Treatment Of Solid Organ Transplant Recipients With Autologous Epstein Barr Virus-Specific Cytotoxic T Lymphocytes (Ctls), Barbara Savoldo, John A. Goss, Markus M. Hammer, Lan Zhang, Teresita Lopez, Adrian P. Gee, Yu-Feng Lin, Ruben E. Quiros-Tejeira, Petra Reinke, Stephan Schubert, Stephen Gottschalk, Milton J. Finegold, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop

Faculty, Staff and Students Publications

We have investigated the in vivo safety, efficacy, and persistence of autologous Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) for the treatment of solid organ transplant (SOT) recipients at high risk for EBV-associated posttransplantation lymphoproliferative disease (PTLD). EBV-CTLs generated from 35 patients expanded with normal kinetics contained both CD8 and CD4 lymphocytes and produced significant specific killing of autologous EBV-transformed B lymphoblastoid cell lines (LCLs). Twelve SOT recipients at high risk for PTLD, or with active disease, received autologous CTL infusions without toxicity. Real-time polymerase chain reaction (PCR) monitoring of EBV-DNA showed a transient increase in plasma EBV-DNA suggestive …

Beta 1-Integrins Are Required For Hippocampal Ampa Receptor-Dependent Synaptic Transmission, Synaptic Plasticity, And Working Memory, Chi-Shing Chan, Edwin J. Weeber, Lin Zong, Elaine Fuchs, J David Sweatt, Ronald L. Davis

Faculty, Staff and Students Publications

Integrins comprise a large family of cell adhesion receptors that mediate diverse biological events through cell-cell and cell-extracellular matrix interactions. Recent studies have shown that several integrins are localized to synapses with suggested roles in synaptic plasticity and memory formation. We generated a postnatal forebrain and excitatory neuron-specific knock-out of beta1-integrin in the mouse. Electrophysiological studies demonstrated that these mutants have impaired synaptic transmission through AMPA receptors and diminished NMDA receptor-dependent long-term potentiation. Despite the impairment in hippocampal synaptic transmission, the mutants displayed normal hippocampal-dependent spatial and contextual memory but were impaired in a hippocampal-dependent, nonmatching-to-place working memory task. These …

Does The Choice Of Bottle Nipple Affect The Oral Feeding Performance Of Very-Low-Birthweight (Vlbw) Infants?, C E. Scheel, Richard J. Schanler, Chantal Lau

Faculty, Staff and Students Publications

BACKGROUND: There is a continuous debate regarding the best bottle nipple to be used to enhance the bottle-feeding performance of a preterm infant. Aim: To verify that feeding performance can be improved by using the bottle nipple with the physical characteristics that enhance infants' sucking skills. METHODS: Ten "healthy" VLBW infants (941+/-273 g) were recruited. Feeding performance was monitored at two time periods, when taking 1-2 and 6-8 oral feedings/d. At each time and within 24 h, performance was monitored using three different bottle nipples offered in a randomized order. Rate of milk transfer (ml/min) was the primary outcome measure. …

Residency Program At Michael E Debakey Department Of Surgery, Baylor College Of Medicine, F Charles Brunicardi

Faculty, Staff and Students Publications

No abstract provided.

Gene Therapy For Pediatric Cancer: State Of The Art And Future Perspectives, Ettore Biagi, Catherine Bollard, Raphael Rousseau, Malcolm Brenner

Faculty, Staff and Students Publications

While modern treatments have led to a dramatic improvement in survival for pediatric malignancy, toxicities are high and a significant proportion of patients remain resistant. Gene transfer offers the prospect of highly specific therapies for childhood cancer. "Corrective" genes may be transferred to overcome the genetic abnormalities present in the precancerous cell. Alternatively, genes can be introduced to render the malignant cell sensitive to therapeutic drugs. The tumor can also be attacked by decreasing its blood supply with genes that inhibit vascular growth. Another possible approach is to modify normal tissues with genes that make them more resistant to conventional …

Patterns Of Fatty Acid Release From Endogenous Substrates By Human Platelet Homogenates And Membranes, A Derksen, P Cohen

Faculty, Staff and Students Publications

We describe a method for measuring the release of fatty acids from endogenous substrates of human platelet homogenates and membranes. The method depends on the availability of lipids whose fatty acids are odd-chained and therefore suitable as internal reference compounds that, at the time of lipid extraction, can be added to an incubation to permit subsequent quantification of the content of free fatty acids or fatty acids esterified to specific lipids. We found four types of lipolytic activities in human platelets. In homogenates at pH 4.0 a triglyceride lipase operated as shown by the synchrony of triglyceride degradation and release …

Atomic Models For The Polypeptide Backbones Of Myohemerythrin And Hemerythrin, W A Hendrickson, K B Ward

Faculty, Staff and Students Publications

Background: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly after its identification in December 2019 to cause a global pandemic. The respiratory tract is the primary site of infection, and there is a large range in the severity of respiratory illnesses caused by the virus. Defining molecular and cellular factors for protection from severe disease and death has been a goal to better understand and to predict and mitigate the effects of SARS-CoV-2 and future coronaviruses.

Objective: Despite well-known susceptibilities to respiratory viral infections, respiratory allergy and allergic asthma have not been identified as risk factors …

The Parenchymal Cells Of The Rat Pineal Gland, E Tapp, M Blumfield

Faculty, Staff and Students Publications

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare hematologic disorder with improved survival due to advancements in treatment. However, long-term cardiovascular morbidity and mortality remain significant. Established cardiovascular risk calculators, such as the 2008 Framingham Heart Study (FHS) global cardiovascular disease (CVD) and the American College of Cardiology/American Heart Association (ACC/AHA) atherosclerotic CVD (ASCVD) risk estimators, may not adequately account for the elevated and unique cardiovascular risks in iTTP survivors.

Objectives: To evaluate the discrimination and calibration of the ACC/AHA ASCVD and FHS global CVD models in predicting major adverse cardiovascular events (MACEs) among iTTP survivors.

Methods: This retrospective …