Digital Commons Network^™

388 A Structure Of Cytoplasmic Polyhedrosis Virus By Cryo-Electron Microscopy, Xuekui Yu, Lei Jin, Z Hong Zhou

Faculty, Staff and Student Publications

Cytoplasmic polyhedrosis virus (CPV) is unique within the Reoviridae family in having a turreted single-layer capsid contained within polyhedrin inclusion bodies, yet being fully capable of cell entry and endogenous RNA transcription. Biochemical data have shown that the amino-terminal 79 residues of the CPV turret protein (TP) is sufficient to bring CPV or engineered proteins into the polyhedrin matrix for micro-encapsulation. Here we report the three-dimensional structure of CPV at 3.88 A resolution using single-particle cryo-electron microscopy. Our map clearly shows the turns and deep grooves of alpha-helices, the strand separation in beta-sheets, and densities for loops and many bulky …

Diviva Is Required For Polar Growth In The Mreb-Lacking Rod-Shaped Actinomycete Corynebacterium Glutamicum, Michal Letek, Efrén Ordóñez, José Vaquera, William Margolin, Klas Flärdh, Luis M Mateos, José A Gil

Faculty, Staff and Student Publications

The actinomycete Corynebacterium glutamicum grows as rod-shaped cells by zonal peptidoglycan synthesis at the cell poles. In this bacterium, experimental depletion of the polar DivIVA protein (DivIVA(Cg)) resulted in the inhibition of polar growth; consequently, these cells exhibited a coccoid morphology. This result demonstrated that DivIVA is required for cell elongation and the acquisition of a rod shape. DivIVA from Streptomyces or Mycobacterium localized to the cell poles of DivIVA(Cg)-depleted C. glutamicum and restored polar peptidoglycan synthesis, in contrast to DivIVA proteins from Bacillus subtilis or Streptococcus pneumoniae, which localized at the septum of C. glutamicum. This confirmed that DivIVAs …

Cd73-Generated Adenosine Restricts Lymphocyte Migration Into Draining Lymph Nodes, Masahide Takedachi, Dongfeng Qu, Yukihiko Ebisuno, Hiroyuki Oohara, Michelle L Joachims, Stephanie T Mcgee, Emiko Maeda, Rodger P Mcever, Toshiyuki Tanaka, Masayuki Miyasaka, Shinya Murakami, Thomas Krahn, Michael R Blackburn, Linda F Thompson

Faculty, Staff and Student Publications

After an inflammatory stimulus, lymphocyte migration into draining lymph nodes increases dramatically to facilitate the encounter of naive T cells with Ag-loaded dendritic cells. In this study, we show that CD73 (ecto-5'-nucleotidase) plays an important role in regulating this process. CD73 produces adenosine from AMP and is expressed on high endothelial venules (HEV) and subsets of lymphocytes. Cd73(-/-) mice have normal sized lymphoid organs in the steady state, but approximately 1.5-fold larger draining lymph nodes and 2.5-fold increased rates of L-selectin-dependent lymphocyte migration from the blood through HEV compared with wild-type mice 24 h after LPS administration. Migration rates of …

Enterococcus Faecalis Pcfc, A Spatially Localized Substrate Receptor For Type Iv Secretion Of The Pcf10 Transfer Intermediate, Yuqing Chen, Xiaolin Zhang, Dawn Manias, Hye-Jeong Yeo, Gary M Dunny, Peter J Christie

Faculty, Staff and Student Publications

Upon sensing of peptide pheromone, Enterococcus faecalis efficiently transfers plasmid pCF10 through a type IV secretion (T4S) system to recipient cells. The PcfF accessory factor and PcfG relaxase initiate transfer by catalyzing strand-specific nicking at the pCF10 origin of transfer sequence (oriT). Here, we present evidence that PcfF and PcfG spatially coordinate docking of the pCF10 transfer intermediate with PcfC, a membrane-bound putative ATPase related to the coupling proteins of gram-negative T4S machines. PcfC and PcfG fractionated with the membrane and PcfF with the cytoplasm, yet all three proteins formed several punctate foci at the peripheries of pheromone-induced cells as …

Intensive Care For Extreme Prematurity--Moving Beyond Gestational Age, Jon E Tyson, Nehal A Parikh, John Langer, Charles Green, Rosemary D Higgins

Faculty, Staff and Student Publications

BACKGROUND: Decisions regarding whether to administer intensive care to extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients.

METHODS: We prospectively studied a cohort of 4446 infants born at 22 to 25 weeks' gestation (determined on the basis of the best obstetrical estimate) in the Neonatal Research Network of the National Institute of Child Health and Human Development to relate risk factors assessable at or before birth to the likelihood of survival, survival without profound neurodevelopmental impairment, and survival without neurodevelopmental impairment at a corrected age of 18 to …

Short-Course Versus Long-Course Antibiotic Therapy For Non-Severe Community-Acquired Pneumonia In Children Aged 2 Months To 59 Months, Batool A. Haider, Muhammad Ammad Saeed, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Background: Pneumonia is the leading cause of mortality in children under five years of age. Treatment of pneumonia requires an effective antibiotic used in adequate doses for an appropriate duration. Recommended duration of treatment ranges between 7 and 14 days, but this is not based on any empirical evidence. Shorter duration of therapy, if found to be effective, could be particularly important in resource-poor settings where there is a high risk of death, poor access to medicines and health care, and limited budgets for medicines.
Objectives: To evaluate the efficacy of short- course versus long-course therapy with the same antibiotic …

Ms211: Letter From John Post To Armin & Karen, Armin Weinberg

Works on Radiation Effects: 1990-2020

This is a letter that accompanied a gift (tube with document inside that was printed by the original Gutenberg printing press) from John Post to Armin. John was a ret. Col. in medical logistics (at the US Dept of State) that helped distribute excess medical and hospital supplies to our AIHA partners in Kazakhstan, Azerbiajan and actually helped with shipment to Gaza as well. Since he lived in DC I invited him to a couple of the non-radiation related Intercultural Cancer Council Biennial Symposia that our Center at BCM coordinated. The page is now at the HRC for viewing. See …

The Aging Services Network: Accomplishments And Challenges In Serving A Growing Elderly Population, Carol O'Shaughnessy

National Health Policy Forum

In 1965, Congress enacted the Older Americans Act, establishing a federal agency and state agencies to address the social services needs of the aging population. The mission of the Older Americans Act is broad: to help older people maintain maximum independence in their homes and communities and to promote a continuum of care for the vulnerable elderly. In successive amendments, the Act created area agencies on aging and a host of service programs. The “aging services network,” broadly described, refers to the agencies, programs, and activities that are sponsored by the Older Americans Act. The Act’s funding for services is …

A Program To Change The Approach To Care Of Children With Asthma In The Primary Care Setting Did Not Reduce Rates Of Hospital Admissions: Lessons Learned From A Descriptive Study, Sheniz Moonie, Robert C. Strunk, Mario Castro

Environmental & Global Health Faculty Research

Asthma is a critical global health issue. It affects people of all ages in countries throughout the world. The prevalence of asthma is increasing in most countries among young children who also represent the greatest proportion of health care utilization. Outpatient asthma-treatment programs managed by chest physicians or allergists have reduced hospitalizations, yet programs in pediatric offices have not successfully impacted hospitalizations. The Community Asthma Program (CAP) was designed to support pediatrician use of clinical guidelines in their everyday office practice. The goal was to reduce asthma hospitalizations by 15 percent from selected pediatric practices. A study was done in …

Knowledge About Osteoporosis Among Healthy Women Attending A Tertiary Care Hospital, Mehmood Riaz, Naushad Abid, Muhammad Junaid Patel, M. Tariq, Muhammad Shoaib Khan, Lubna Zuberi

Section of Internal Medicine

INTRODUCTION: To determinate the knowledge on osteoporosis-risk factors and disease in three age groups of Pakistani women.METHODS: In this exploratory cross-sectional study, an osteoporosis knowledge assessment questionnaire (OKAT) was used to collect data and it was delivered through a face-to-face interview. Questions were asked about symptoms of osteoporosis, knowledge of risk factors, preventive factors and treatment. A convenience sample (n =320) comprising of three groups of healthy women aged 25-35 years, 36-45 years, and over 45 years was taken. The scoring range was 0 to 20. Among-group comparisions of means were analyzed by two-way ANOVA. To determine the overall influence …

Day Care Surgery At A New University Teaching Hospital: A Review Out Of The Aga Khan University Hospital, Nairobi, Edwin Mogere

Master of Medicine in General Surgery

Introduction: Day Care Surgery (DCS) is the surgical care of patients on a planned non-residential basis. The objective of the study was to assess the performance of DCS in the context of a developing country within the private sector. Data from a new DCS unit was compared to internationally accepted indicators of the quality of care. Methodology: A hospital based retrospective chart review of all patients operated on within 10 surgical subspecialties was performed. The review period was the June 2006 to July 2007(12 months). Analysis (SPSS version 11.5): Outcome measures included in-patient to DCS ratio in the various specialties; …

Obstetric Fistula In Mali, Chandler O’Connell

Independent Study Project (ISP) Collection

Obstetric fistula is arguably the most devastating result of childbirth complications, aside from maternal and neonatal mortality, the latter of which almost always occurs during deliveries which result in fistula. Defined as a hole in the birth canal, obstetric fistula is generally caused by prolonged obstructed labor in the absence of prompt medical intervention.20 This injury results in chronic incontinence through the vagina as well as many other secondary health consequences.33 Additionally, it is impossible to measure the extensive social and psychological burdens suffered by women because of this affliction. Despite the fact that obstetric fistula is both preventable and …

Excess Adenosine In Murine Penile Erectile Tissues Contributes To Priapism Via A2b Adenosine Receptor Signaling, Tiejuan Mi, Shahrzad Abbasi, Hong Zhang, Karen Uray, Janci L Chunn, Ling Wei Xia, Jose G Molina, Norman W Weisbrodt, Rodney E Kellems, Michael R Blackburn, Yang Xia

Faculty, Staff and Student Publications

Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. It is common among males with sickle cell disease (SCD), and SCD transgenic mice are an accepted model of the disorder. Current strategies to manage priapism suffer from a poor fundamental understanding of the molecular mechanisms underlying the disorder. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy successfully corrected the priapic activity both in vivo and in vitro, suggesting that it was …

Health State Valuation In Mild To Moderate Cognitive Impairment: Feasibility Of Computer-Based, Direct Patient Utility Assessment, Neal V. Dawson, Mendel E. Singer, Marian B. Patterson, Susie A. Sami, Iahn Gonsenhouser, Heather A. Lindstrom, Kathleen A. Smyth, Melissa Barber Butson, Peter J. Whitehouse

Faculty Scholarship

Background. Most patients with dementia will, at some point, need a proxy health care decision maker. It is unknown whether persons with various degrees of cognitive impairment can reliably report their health-related preferences. Methods. The authors performed health state valuations (HSVs) of current and hypothetical future health states on 47 pairs of patients with mild to moderate cognitive impairment and their caregivers using computer-based standard gamble, time tradeoff, and rating scale techniques. Results. Patients' mean (SD) age was 74.6 (9.3) years. About half of the patients were women (48%), as were most caregivers (73%), who were on average younger (mean …

Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

The role of the renin angiotensin system (RAS) in atherosclerosis is complex because of the involvement of multiple peptides and receptors. Renin is the rate-limiting enzyme in the production of all angiotensin peptides. To determine the effects of renin inhibition on atherosclerosis, we administered the novel renin inhibitor aliskiren over a broad dose range to fat-fed LDL receptor-deficient (Ldlr^-/-) mice. Renin inhibition resulted in striking reductions of atherosclerotic lesion size in both the aortic arch and the root. Subsequent studies demonstrated that cultured macrophages expressed all components of the RAS. To determine the role of macrophage-derived angiotensin in …

Incorporating Ethnicity Into Genetic Risk Assessment For Alzheimer Disease: The Reveal Study Experience, Peter J. Whitehouse, Melissa Barber Butson

Faculty Scholarship

PURPOSE: To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants. METHODS: The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicity-specific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease. RESULTS: Review of epidemiological data suggested notable differences in risk between African …

Social Factors Affecting Treatment Of Cervical Cancer: Ethical Issues And Policy Implications, Shannon N. Westin, Dan Bustillos, Jacalyn B. Gano, Margaret M. Fields, Ann L. Coker, Charlotte C. Sun, Lois M. Ramondetta

CRVAW Faculty Journal Articles

Health care in the United States has become a privilege rather than a right. Patients who have the greatest need are the ones most likely to be denied this privilege. Despite recent advances in disease detection and treatment, many patients do not receive even the bare minimum of care. The high complexity of the health care system in the setting of patients with low levels of health literacy significantly affects the ability to seek and receive treatment in a timely fashion. In addition, lack of insurance, transportation, and social support further complicate access to care. To truly provide a standard …

Clinical And Microbiological Aspects Of Linezolid Resistance Mediated By The Cfr Gene Encoding A 23s Rrna Methyltransferase, Cesar A Arias, Martha Vallejo, Jinnethe Reyes, Diana Panesso, Jaime Moreno, Elizabeth Castañeda, Maria V Villegas, Barbara E Murray, John P Quinn

Faculty, Staff and Student Publications

The cfr (chloramphenicol-florfenicol resistance) gene encodes a 23S rRNA methyltransferase that confers resistance to linezolid. Detection of linezolid resistance was evaluated in the first cfr-carrying human hospital isolate of linezolid and methicillin-resistant Staphylococcus aureus (designated MRSA CM-05) by dilution and diffusion methods (including Etest). The presence of cfr was investigated in isolates of staphylococci colonizing the patient's household contacts and clinical isolates recovered from patients in the same unit where MRSA CM-05 was isolated. Additionally, 68 chloramphenicol-resistant Colombian MRSA isolates recovered from hospitals between 2001 and 2004 were screened for the presence of the cfr gene. In addition to erm(B), …

Radiation-Induced Glutamate Transport Alterations In Neuron-Astrocyte Coupling, Martha Celia Sanchez

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure of the central nervous system (CNS) to ionizing radiation is known to result in behavioral, cognitive, and motor deficits - effects similar to those seen in many neurodegenerative disorders. Neurons and astrocytes, two principal cell types in the brain, coexist as an interdependent metabolic unit via the neurotransmitter glutamate. Disruption of this metabolic coupling would have widespread effects within the CNS, therefore it is hypothesized that ionizing radiation impairs glutamate transport and metabolism, and increases oxidative stress, ultimately impairing neuron-astrocyte coupling. We propose to investigate the mechanism and determine the impetus for radiation-induced neurotoxicity by measuring the temporal sequence …

Cryo-Electron Tomography Of Kaposi's Sarcoma-Associated Herpesvirus Capsids Reveals Dynamic Scaffolding Structures Essential To Capsid Assembly And Maturation, Binbin Deng, Christine M O'Connor, Dean H Kedes, Z Hong Zhou

Faculty, Staff and Student Publications

Kaposi's sarcoma-associated herpesvirus (KSHV) is a recently discovered DNA tumor virus that belongs to the gamma-herpesvirus subfamily. Though numerous studies on KSHV and other herpesviruses, in general, have revealed much about their multilayered organization and capsid structure, the herpesvirus capsid assembly and maturation pathway remains poorly understood. Structural variability or irregularity of the capsid internal scaffolding core and the lack of adequate tools to study such structures have presented major hurdles to earlier investigations employing more traditional cryo-electron microscopy (cryoEM) single particle reconstruction. In this study, we used cryo-electron tomography (cryoET) to obtain 3D reconstructions of individual KSHV capsids, allowing …

Activation Of Heat Shock And Antioxidant Responses By The Natural Product Celastrol: Transcriptional Signatures Of A Thiol-Targeted Molecule, Amy Trott, James D West, Lada Klaić, Sandy D Westerheide, Richard B Silverman, Richard I Morimoto, Kevin A Morano

Faculty, Staff and Student Publications

Stress response pathways allow cells to sense and respond to environmental changes and adverse pathophysiological states. Pharmacological modulation of cellular stress pathways has implications in the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. The quinone methide triterpene celastrol, derived from a traditional Chinese medicinal herb, has numerous pharmacological properties, and it is a potent activator of the mammalian heat shock transcription factor HSF1. However, its mode of action and spectrum of cellular targets are poorly understood. We show here that celastrol activates Hsf1 in Saccharomyces cerevisiae at a similar effective concentration seen in mammalian cells. Transcriptional …

Unique Structures In A Tumor Herpesvirus Revealed By Cryo-Electron Tomography And Microscopy, Wei Dai, Qingmei Jia, Eric Bortz, Sanket Shah, Jun Liu, Ivo Atanasov, Xudong Li, Kenneth A Taylor, Ren Sun, Z Hong Zhou

Faculty, Staff and Student Publications

Gammaherpesviruses, including the human pathogens Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, are causative agents of lymphomas and other malignancies. The structural characterization of these viruses has been limited due to difficulties in obtaining adequate amount of virion particles. Here we report the first three-dimensional structural characterization of a whole gammaherpesvirus virion by an emerging integrated approach of cryo-electron tomography combined with single-particle cryo-electron microscopy, using murine gammaherpesvirus-68 (MHV-68) as a model system. We found that the MHV-68 virion consists of distinctive envelope and tegument compartments, and a highly conserved nucleocapsid. Two layers of tegument are identified: an inner tegument layer …

Psychiatric Outcomes In A Resident-Run Multidisciplinary Hepatitis C Clinic, Nicole M. Agostino Do, Edward Norris Md, Fapm, Joseph L. Yozviak Do, Facp, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Michael Kaufmann Md

Department of Medicine

No abstract provided.

Whiplash: Diagnosis, Treatment, And Associated Injuries., Sanjay Yadla, John K. Ratliff, James Harrop

Department of Neurology Faculty Papers

STUDY DESIGN: Focused review of the current literature.

OBJECTIVE: To identify and synthesize the most current data pertaining to the diagnosis and treatment of whiplash and whiplash-associated disorders (WAD), and to report on whiplash-related injuries.

METHODS: A search of OVID Medline (1996-January 2007) and the Cochrane database of systematic reviews was performed using the keywords whiplash and WAD. Articles under subheadings for pathology, diagnosis, treatment, and epidemiology were chosen for review after identification by the authors.

RESULTS: A total of 485 articles in the English language literature were identified. Thirty-six articles pertained to the diagnosis, treatment, epidemiology of whiplash, and …

What Do Patients Want From Their Psychiatrist? A Cross-Sectional Questionnaire Based Exploratory Study From Karachi, Roomasa Channa, M. N. Siddiqi

Department of Psychiatry

Background: The aspects of consultation that are important for psychiatric Patients have always remained a less acknowledged area. The aim of this study was to identify these aspects. Methods: A Cross- sectional, questionnaire based study was carried out in a psychiatry outPatient clinic of two tertiary care hospitals in a developing country. The Patients were asked to fill out the questionnaire containing a total of 11 close-ended questions plus 1 open- ended question. They graded them as not important, important, very important or do not know. Non-psychotic Patients aged 18 and above, visiting the clinic were recruited into the study …

The Need For Formal Paediatric Resuscitation Training In Pakistan., Adina R., Sheikh Sajjad, Junaid Razzak

Department of Emergency Medicine

No abstract provided.

Oncolog Volume 51, Number 02, February 2006, Sunni Hosemann, Ellen Mcdonald Phd

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Emergency Care for Cancer Patients
• Bringing Clinical Trials to the Community
• House Call: Understanding the Immune System
• DiaLog: Cognitive Dysfunction in Cancer, by Christina Meyers, PhD, Professor and Chief, Section of Neuropsychology

Informed Consent And Some Of Its Problems In Pakistan, Robyna Irshad Khan

Department of Anaesthesia

Informed consent has become an essential element of human subject research. Certain components are essential for a well-understood informed consent. There are problems in procurement of a comprehensive and meaningful consent in the Pakistani research settings. The inefficient healthcare systems, low literacy rate with masses having no concept of individual rights, higher social status enjoyed by physicians inhibiting the patients from questioning them, and unwillingness to hear bad news are some of these factors. Establishing Bioethics education at all levels, encouraging the involvement of families in decision making, using improvisation in procurement of consent are suggested solutions. There needs to …

Role Of Transient Receptor Potential Canonical-6 (Trpc6) Channel In Metastasis Of Glioblastoma Multiforme, Rajarajeshwari Venkataraman

Electronic Theses and Dissertations

Glioblastoma multiforme (GBM) is one of the extremely fatal brain tumors. The main reason that makes it so lethal is its capability to invade and spread to other parts of CNS producing secondary tumors. Among other factors hypoxia, reduced oxygen availability, is linked to higher metastatic potential of cancers. Hypoxia causes numerous changes in genome and proteome of the cell. These changes help a normal cell to adapt to nutritional deficiency, but the same changes can increase the malignancy and metastasis in tumor cells. Extensive research by a number of curious scientists reveal that various pathways involving numerous proteins cross-talk …

Medical Education Digest, Vol. 10 No. 1 (January/February 2008), Nova Southeastern University

Medical Education Digest

No abstract provided.