Medicine and Health Sciences Commons^™

Hepatic Steatosis And Its Relationship To Transplantation., Charles J. Imber, Shawn D. St Peter, Ashok Handa, Peter J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

Fatty infiltration of the liver is common in the brain-dead donor population and has a strong correlation with primary nonfunction after cold preservation, a condition that is catastrophic to liver transplant recipients. This literature review examines factors associated with the development, diagnosis, quantification, and clinical management of this difficult condition.

Effectiveness Of Current Therapy Of Bacterial Vaginosis, Petya M Andreeva, Hatim A. Omar

Pediatrics Faculty Publications

The study was conducted in order to evaluate effectiveness of the treatment of bacterial vaginosis (BV) with different therapeutic regimes according to recommendations of the World Health Organization (WHO). During a one-year period (February 2000-February 2001) the Sexually Transmitted Diseases (STD) Center was visited by 482 women aged 14-51. The diagnosis of BV was established by standard methods: Amsel's clinical criteria and Gram stain of vaginal discharge. The first-line treatment was oral Metronidazole 2 g single dose. Second line was Metronidazole 500 mg twice daily orally for 7 days or oral Clindamycin 300 mg twice daily for seven days. BV …

Improved Continuation Rate Of Depot-Medroxyprogesterone Acetate In Adolescent Mothers, Hatim A. Omar, Amy Fowler, Sandy D'Angelo

Pediatrics Faculty Publications

Poor compliance and high discontinuation rates of Depot-Medroxyprogesterone Acetate (DMPA) and other contraceptive methods are major factors in the continuing problem of adolescent pregnancy. In this study we attempted to determine if providing comprehensive health care for teen mothers and their babies would improve continuation rates of DMPA. Patients who started DMPA between 1/1/96 and 1/1/99 were included. Teen mothers and their babies received all their health care in this clinic, supported by State funding. Key elements regarding DMPA in this clinic were continuity of care, phone and mail reminders of appointments, free DMPA for patients without insurance, counseling at …

Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky

Dartmouth Scholarship

All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor α (RARα). Microarray analyses previously revealed induction of UBE1L (ubiquitin-activating enzyme E1-like) after RA treatment of NB4 APL cells. We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target. A 1.3-kb fragment of the UBE1L promoter was capable of mediating transcriptional response to RA in a retinoid receptor-selective manner. PML/RARα, a repressor of RA target genes, abolished this UBE1L promoter activity. A hallmark of …

Breast Cancer On The World Wide Web: Cross Sectional Survey Of Quality Of Information And Popularity Of Websites, Funda Meric, Elmer V Bernstam, Nadeem Q Mirza, Kelly K Hunt, Frederick C Ames, Merrick I Ross, Henry M Kuerer, Raphael E Pollock, Mark A Musen, S Eva Singletary

Faculty, Staff and Student Publications

OBJECTIVES: To determine the characteristics of popular breast cancer related websites and whether more popular sites are of higher quality.

DESIGN: The search engine Google was used to generate a list of websites about breast cancer. Google ranks search results by measures of link popularity---the number of links to a site from other sites. The top 200 sites returned in response to the query "breast cancer" were divided into "more popular" and "less popular" subgroups by three different measures of link popularity: Google rank and number of links reported independently by Google and by AltaVista (another search engine).

MAIN OUTCOME …

A Preliminary Study On The Reliability Of Physical Performance Measures In Older Day-Care Center Clients With Dementia., Vince Salazar Thomas, Patricia A. Hageman

Journal Articles: Physical Therapy

BACKGROUND: Decline in physical functional ability is an intrinsic component of the dementia syndrome. Reductions in muscle mass and strength represent a major factor in the loss of functional ability Although resistance exercise has been studied as a method for maintaining/recovering function in populations of frail older adults, people with dementia have been systematically excluded because of uncertainty about the reliability of outcome measurements.

OBJECTIVE: The purpose of this study was to determine the test-retest reliability of a battery of established performance-based measures of strength and function among subjects with dementia.

SETTING: A hospital-affiliated adult day-care facility.

SUBJECTS: Twelve of …

Short-Circuiting Long-Lived Humoral Immunity By The Heightened Engagement Of Cd40, Loren D. Erickson, Brigit G. Durell, Laura A. Vogel, Brian P. Connor, Marilia Cascalho, Teruhito Yasui, Hitoshi Kikutani, Randolph J. Noelle

Dartmouth Scholarship

Agonistic αCD40 Ab’s have been shown to be potent immune adjuvants for both cell- and humoral-mediated immunity. While enhancing short-lived humoral immunity, the administration of a CD40 agonist during thymus-dependent immune responses ablates germinal center formation, prematurely terminates the humoral immune response, blocks the generation of B cell memory, and prevents the generation of long-lived bone marrow plasma cells. Interestingly, some of these effects of heightened CD40 engagement could be mimicked by enhancing the magnitude of antigen-specific T cell help. Taken together, these studies demonstrate that as the magnitude of CD40 signaling intensifies, the fate of antigen-reactive B cells can …

Circulating Testosterone And Prostate-Specific Antigen In Nipple Aspirate Fluid And Tissue Are Associated With Breast Cancer., Edward R Sauter, David S Tichansky, Inna Chervoneva, Eleftherios P Diamandis

Department of Surgery Faculty Papers

Preliminary evidence has associated testosterone and prostate-specific antigen (PSA) with breast cancer. Our objective was to determine whether a) testosterone levels in nipple aspirate fluid (NAF), serum, or breast tissue are associated with breast cancer; b) testosterone levels in serum are associated with levels in NAF; c) PSA in NAF, serum, or breast tissue is associated with breast cancer; and d) serum PSA is associated with NAF PSA levels. We obtained 342 NAF specimens from 171 women by means of a modified breast pump. Additionally, we collected 201 blood samples from 99 women and 51 tissue samples from 41 subjects …

Reduction In The Incidence Of Type 2 Diabetes With Lifestyle Intervention Or Metformin., William C. Knowler, Elizabeth Barrett-Connor, Sarah E. Fowler, Richard F. Hamman, John M. Lachin, Elizabeth A. Walker, David M. Nathan, P. G. Watson, J. T. Mendoza, K. A. Smith, J. Caro, B. Goldstein, C. Lark, L. Menefee, L. Murphy, C. Pepe, J. M. Spandorfer

Department of Medicine Faculty Papers

BACKGROUND: Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes.

METHODS: We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least …

Triplet Repeat Dna Structures And Human Genetic Disease: Dynamic Mutations From Dynamic Dna., Richard R. Sinden, Vladimir N. Potaman, Elena A. Oussatcheva, Christopher E. Pearson, Yuri L. Lyubchenko, Luda S. Shlyakhtenko

Journal Articles: Pharmaceutical Sciences

Fourteen genetic neurodegenerative diseases and three fragile sites have been associated with the expansion of (CTG)n (CAG)n, (CGG)n (CCG)n, or (GAA)n (TTC)n repeat tracts. Different models have been proposed for the expansion of triplet repeats, most of which presume the formation of alternative DNA structures in repeat tracts. One of the most likely structures, slipped strand DNA, may stably and reproducibly form within triplet repeat sequences. The propensity to form slipped strand DNA is proportional to the length and homogeneity of the repeat tract. The remarkable stability of slipped strand DNA may, in part, be due to loop-loop interactions facilitated …

Spectral And Temporal Processing In Human Auditory Cortex, Deborah A Hall, Ingrid Johnsrude, Mark P Haggard, Alan R Palmer, Michael A Akeroyd, A Quentin Summerfield

Brain and Mind Institute Researchers' Publications

Hierarchical processing suggests that spectrally and temporally complex stimuli will evoke more activation than do simple stimuli, particularly in non-primary auditory fields. This hypothesis was tested using two tones, a single frequency tone and a harmonic tone, that were either static or frequency modulated to create four stimuli. We interpret the location of differences in activation by drawing comparisons between fMRI and human cytoarchitectonic data, reported in the same brain space. Harmonic tones produced more activation than single tones in right Heschl's gyrus (HG) and bilaterally in the lateral supratemporal plane (STP). Activation was also greater to frequency-modulated tones than …

Surveillance For Waterborne-Disease Outbreaks--United States, 1999-2000, Sherline H. Lee, Deborah A. Levy, Gunther F. Craun, Michael J. Beach, Rebecca L. Calderon

Journal Articles: Epidemiology

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency (EPA), and the Council of State and Territorial Epidemiologists (CSTE) have maintained a collaborative surveillance system for the occurrences and causes of waterborne-disease outbreaks (WBDOs).This surveillance system is the primary source of data concerning the scope and effects of waterborne diseases on persons in the United States.

REPORTING PERIOD COVERED: This summary includes data regarding outbreaks occurring during January 1999-December 2000 and previously unreported outbreaks occurring in 1995 and 1997.

DESCRIPTION OF THE SYSTEM: The surveillance system includes data for outbreaks associated with drinking water and recreational water. State, territorial, and …

Associations Between Water-Treatment Methods And Diarrhoea In Hiv-Positive Individuals, J. N. S. Eisenberg, T. J. Wade, A. Hubbard, D. I. Abrams, R. J. Leiser, S. Charles, M. Vu, S. Saha, C. C. Wright, Deborah A. Levy, P. Jensen, J. M. Colford

Journal Articles: Epidemiology

This manuscript extends our previously published work (based on data from one clinic) on the association between three drinking water-treatment modalities (boiling, filtering, and bottling) and diarrhoeal disease in HIV-positive persons by incorporating data from two additional clinics collected in the following year. We conducted a cross-sectional survey of drinking water patterns, medication usage, and episodes of diarrhoea among HIV-positive persons attending clinics associated with the San Francisco Community Consortium. We present combined results from our previously published work in one clinic (n = 226) with data from these two additional clinics (n = 458). In this combined analysis we …

Risk Factors In Hiv-Associated Diarrhoeal Disease: The Role Of Drinking Water, Medication And Immune Status, J. N. S. Eisenberg, T. J. Wade, S. Charles, M. Vu, A. Hubbard, C. C. Wright, Deborah A. Levy, P. Jensen, J. M. Colford

Journal Articles: Epidemiology

In a cross-sectional survey of 226 HIV-infected men, we examined the occurrence of diarrhoea and its relationship to drinking water consumption patterns, risk behaviours, immune status and medication use. Diarrhoea was reported by 47% of the respondents. Neither drinking boiled nor filtered water was significantly associated with diarrhoea (OR = 0.5 [0.2, 1.6], 1.2 [0.6, 2.5] respectively), whereas those that drank bottled water were at risk for diarrhoea (OR = 3.0 [1.1, 7.8]). Overall, 47% always or often used at least one water treatment. Of the 37% who were very concerned about drinking water, 62% had diarrhoea, 70% always or …

Participant Blinding And Gastrointestinal Illness In A Randomized, Controlled Trial Of An In-Home Drinking Water Intervention, John M. Colford, Judy R. Rees, Timothy J. Wade, Asheena Khalakdina, Joan F. Hilton, Isaac J. Ergas, Susan Burns, Anne Benker, Catherine Ma, Cliff Bowen, Daniel C. Mills, Duc J. Vugia, Dennis D. Juranek, Deborah A. Levy

Journal Articles: Epidemiology

We conducted a randomized, triple-blinded home drinking water intervention trial to determine if a large study could be undertaken while successfully blinding participants. Households were randomized 50:50 to use externally identical active or sham treatment devices. We measured the effectiveness of blinding of participants by using a published blinding index in which values >0.5 indicate successful blinding. The principal health outcome measured was "highly credible gastrointestinal illness" (HCGI). Participants (n=236) from 77 households were successfully blinded to their treatment assignment. At the end of the study, the blinding index was 0.64 (95% confidence interval 0.51-0.78). There were 103 episodes of …

Assessment Of Validity Of The National Public Health Performance Standards: The Local Public Health Performance Assessment Instrument., Joyce Beaulieu, F. Douglas Scutchfield

Preventive Medicine and Environmental Health Faculty Publications

The National Public Health Performance Standards Program (NPHPSP) has developed performance standards measurement instruments, based on the 10 "Essential Services of Public Health" that are being tested in several states. This article is a report on the face and content validity of the instrument designed for local public health systems. Judgments about the face validity of the standards were obtained in a survey of local public health systems that had used the instrument in a test state. The validity of each standard was addressed along the following dimensions: the importance of the standard as a measure of the Essential Service; …

Positive And Negative Roles Of Cd72 In B Cell Function., Hsin-Jung Wu, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Regulation of B cell activation depends on integration of signals transmitted by the B cell receptor (BCR) and a variety of co-receptors. CD72 is a B cell co-receptor that is expressed in all stages of B cell development except plasma cells. Ligation of CD72 enhances B cell growth and differentiation. Recently, the class IV semaphoring, CD100, has been identified as the natural ligand for CD72. Cytoplasmic domain of CD72 has been shown to be associated with SHP-1 leading to the proposal that the positive effects of CD72 on B cell response may result from sequestration of negative signals from BCR. …

Retrospective Analysis Of Youth Evaluated For Suicide Attempt Or Suicidal Ideation In An Emergency Room Setting, Julie Hagedorn, Hatim A. Omar

Pediatrics Faculty Publications

Suicide is the third leading cause of death in adolescents and a major contributor to morbidity in this age group. The objective of this study was to look at the demographics, major stressors and factors leading to attempting suicide as well as the methods of attempted suicide in adolescents admitted to two hospitals in a medium size city. Medical records were reviewed of adolescents admitted to two area hospitals for attempted suicide between 7/1/97-12/31/99. Coroner's data on completed suicide were also reviewed. In the study period a total of 287 persons aged 21 years or under were admitted for attempted …

Toward A Cognitive Taxonomy Of Medical Errors, Jiajie Zhang, Vimla L Patel, Todd R Johnson, Edward H Shortliffe

Faculty, Staff and Student Publications

One critical step in addressing and resolving the problems associated with human errors is the development of a cognitive taxonomy of such errors. In the case of errors, such a taxonomy may be developed (1) to categorize all types of errors along cognitive dimensions, (2) to associate each type of error with a specific underlying cognitive mechanism, (3) to explain why, and even predict when and where, a specific error will occur, and (4) to generate intervention strategies for each type of error. Based on Reason's (1992) definition of human errors and Norman's (1986) cognitive theory of human action, we …

Comparing Communication Technology On Chinese, English, And Spanish Diabetes Web Sites, Yanko F Michea, Karen Pancheri, Yang Gong, Elmer Bernstam

Faculty, Staff and Student Publications

Technological and cultural factors influence access to health information on the web in multifarious ways. We evaluated structural differences and availability of communication services on the web in three diverse language and cultural groups: Chinese, English, and Spanish. A total of 382 web sites were analyzed: 144 were English language sites (38%), 129 were Chinese language sites (34%), and 108 were Spanish language sites (28%). We did not find technical differences in the number of outgoing links per domain or the total availability of communication services between the three groups. There were differences in the distribution of available services between …

Nipple Aspirate Cytology And Pathologic Parameters Predict Residual Cancer And Nodal Involvement After Excisional Breast Biopsy., E R Sauter, H Ehya, A Mammen, G Klein

Department of Surgery Faculty Papers

We previously demonstrated that abnormal nipple aspirate fluid (NAF) cytology predicted residual breast cancer (RC) and tumour size after excisional biopsy (EB), although normal NAF cytology did not exclude RC. Tumour size correlates with the risk of lymph node (LN) metastases. LN metastases provide prognostic information allowing medical and radiation oncologists to determine the need for adjuvant therapy. We hypothesized that pathologic factors known after EB, combined with NAF cytology, would predict with a high degree of accuracy the presence of RC and LN spread. NAF cytology and pathologic parameters: tumour distance from biopsy margins, multifocal and multicentric disease, sub-type …

Vdac-Dependent Permeabilization Of The Outer Mitochondrial Membrane By Superoxide Induces Rapid And Massive Cytochrome C Release., M Madesh, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Enhanced formation of reactive oxygen species (ROS), superoxide (O2*-), and hydrogen peroxide (H2O2) may result in either apoptosis or other forms of cell death. Here, we studied the mechanisms underlying activation of the apoptotic machinery by ROS. Exposure of permeabilized HepG2 cells to O2*- elicited rapid and massive cytochrome c release (CCR), whereas H2O2 failed to induce any release. Both O2*- and H2O2 promoted activation of the mitochondrial permeability transition pore by Ca2+, but Ca2+-dependent pore opening was not required for O2*--induced CCR. Furthermore, O2*- alone evoked CCR without damage of the inner mitochondrial membrane barrier, as mitochondrial membrane potential …

Analysis Of Mitotic Microtubule-Associated Proteins Using Mass Spectrometry Identifies Astrin, A Spindle-Associated Protein, Gary J. Mack, Duane A. Compton

Dartmouth Scholarship

We purified microtubules from a mammalian mitotic extract and obtained an amino acid sequence from each microtubule-associated protein by using mass spectrometry. Most of these proteins are known spindle-associated components with essential functional roles in spindle organization. We generated antibodies against a protein identified in this collection and refer to it as astrin because of its association with astral microtubule arrays assembled in vitro. Astrin is approximately 134 kDa, and except for a large predicted coiled-coil domain in its C-terminal region it lacks any known functional motifs. Astrin associates with spindle microtubules as early as prophase where it concentrates at …

Regulation Of Type-Ii Collagen Gene Expression During Human Chondrocyte De-Differentiation And Recovery Of Chondrocyte-Specific Phenotype In Culture Involves Sry-Type High-Mobility-Group Box (Sox) Transcription Factors, David G. Stokes, Gang Liu, Rita Dharmavaram, David Hawkins, Sonsoles Piera-Velazquez, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

During ex vivo growth as monolayer cultures, chondrocytes proliferate and undergo a process of de-differentiation. This process involves a change in morphology and a change from expression of chondrocyte-specific genes to that of genes that are normally expressed in fibroblasts. Transfer of the monolayer chondrocyte culture to three-dimensional culture systems induces the cells to re-acquire a chondrocyte-specific phenotype and produce a cartilaginous-like tissue in vitro. We investigated mechanisms involved in the control of the de-differentiation and re-differentiation process in vitro. De-differentiated chondrocytes re-acquired their chondrocyte-specific phenotype when cultured on poly-(2-hydroxyethyl methacrylate) (polyHEMA) as assayed by morphology, reverse transcriptase PCR of …

Meeting Medical Terminology Needs: The Ontology-Enhanced Medical Concept Mapper, Gondy Leroy, Hsinchun Chen

CGU Faculty Publications and Research

This paper describes the development and testing of the Medical Concept Mapper, a tool designed to facilitate access to online medical information sources by providing users with appropriate medical search terms for their personal queries. Our system is valuable for patients whose knowledge of medical vocabularies is inadequate to find the desired information, and for medical experts who search for information outside their field of expertise. The Medical Concept Mapper maps synonyms and semantically related concepts to a user's query. The system is unique because it integrates our natural language processing tool, i.e., the Arizona (AZ) Noun Phraser, with human-created …

Can Meaningful Effective Connectivities Be Obtained Between Auditory Cortical Regions?, M S Gonçalves, D A Hall, Ingrid Johnsrude, M P Haggard

Brain and Mind Institute Researchers' Publications

Structural equation modeling (SEM) of neuroimaging data can be evaluated both for the goodness of fit of the model and for the strength of path coefficients (as an index of effective connectivity). SEM of auditory fMRI data is made difficult by the necessary sparse temporal sampling of the time series (to avoid contamination of auditory activation by the response to scanner noise) and by the paucity of well-defined anatomical information to constrain the functional model. We used SEM (i.e., a model incorporating latent variables) to investigate how well fMRI data in four adjacent cortical fields can be described as an …

Proteolytic Release Of Cd44 Intracellular Domain And Its Role In The Cd44 Signaling Pathway., I Okamoto, Y Kawano, D Murakami, T Sasayama, N Araki, T Miki, A J Wong, H Saya

Department of Microbiology and Immunology Faculty Papers

CD44 is a widely distributed cell surface adhesion molecule and is implicated in diverse biological processes. However, the nature of intracellular signaling triggered by CD44 remains to be elucidated. Here, we show that CD44 undergoes sequential proteolytic cleavage in the ectodomain and intracellular domain, resulting in the release of a CD44 intracellular domain (ICD) fragment. Consequently, CD44ICD acts as a signal transduction molecule, where it translocates to the nucleus and activates transcription mediated through the 12-O-tetradecanoylphorbol 13-acetate-responsive element, which is found in numerous genes involved in diverse cellular processes. Expression of an uncleavable CD44 mutant as well as metalloprotease inhibitor …

Role Of Protein Kinase C-Delta In The Regulation Of Collagen Gene Expression In Scleroderma Fibroblasts, Sergio A. Jimenez, Svetlana Gaidarova, Biagio Saitta, Nora Sandorfi, David J. Herrich, Joan C. Rosenbloom, Umberto Kucich, William R. Abrams, Joel Rosenbloom

Selected Works of Sergio Jiménez, MD, MACR

Working with cultured dermal fibroblasts derived from control individuals and patients with systemic sclerosis (SSc), we have examined the effects of protein kinase C-delta (PKC-delta) on type I collagen biosynthesis and steady-state levels of COL1A1 and COL3A1 mRNAs. Rottlerin, a specific inhibitor of PKC-delta, exerted a powerful, dose-dependent inhibition of type I and type III collagen gene expression in normal and SSc cells. Optimal rottlerin concentrations caused a 70-90% inhibition of type I collagen production, a >80% reduction in COL1A1 mRNA, and a >70% reduction in COL3A1 mRNA in both cell types. In vitro nuclear transcription assays and transient transfections …

The Chromokinesin Kid Is Necessary For Chromosome Arm Orientation And Oscillation, But Not Congression, On Mitotic Spindles, Aime A. Levesque, Duane A. Compton

Dartmouth Scholarship

Chromokinesins have been postulated to provide the polar ejection force needed for chromosome congression during mitosis. We have evaluated that possibility by monitoring chromosome movement in vertebrate-cultured cells using time-lapse differential interference contrast microscopy after microinjection with antibodies specific for the chromokinesin Kid. 17.5% of cells injected with Kid-specific antibodies have one or more chromosomes that remain closely opposed to a spindle pole and fail to enter anaphase. In contrast, 82.5% of injected cells align chromosomes in metaphase, progress to anaphase, and display chromosome velocities not significantly different from control cells. However, injected cells lack chromosome oscillations, and chromosome orientation …

Eliciting The Low-Activity Aldehyde Dehydrogenase Asian Phenotype By An Antisense Mechanism Results In An Aversion To Ethanol., E Garver, Tu Gc, Q N Cao, M Aini, F Zhou, Y Israel

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism. We have determined whether the administration of antisense phosphorothioate oligonucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian phenotype. Rat hepatoma cells incubated for 24 h with an antisense oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) activity of 55% equivalent to a >90% inhibition in ALDH2 …