Showing papers by "Texas Medical Center published in 2001"

The home stretch, a first analysis of the nearly completed genome of Rhodobacter sphaeroides 2.4.1

Abstract: Rhodobacter sphaeroides 241 is an α-3 purple nonsulfur eubacterium with an extensive metabolic repertoire Under anaerobic conditions, it is able to grow by photosynthesis, respiration and fermentation Photosynthesis may be photoheterotrophic using organic compounds as both a carbon and a reducing source, or photoautotrophic using carbon dioxide as the sole carbon source and hydrogen as the source of reducing power In addition, R sphaeroides can grow both chemoheterotrophically and chemoautotrophically The structural components of this metabolically diverse organism and their modes of integrated regulation are encoded by a genome of ∼45 Mb in size The genome comprises two chromosomes CI and CII (29 and 09 Mb, respectively) and five other replicons Sequencing of the genome has been carried out by two groups, the Joint Genome Institute, which carried out shotgun-sequencing of the entire genome and The University of Texas-Houston Medical School, which carried out a targeted sequencing strategy of CII Here we describe our current understanding of the genome when data from both of these groups are combined Previous work had suggested that the two chromosomes are equal partners sharing responsibilities for fundamental cellular processes This view has been reinforced by our preliminary analysis of the virtually completed genome sequence We also have some evidence to suggest that two of the plasmids, pRS241a and pRS241b encode chromosomal type functions and their role may be more than that of accessory elements, perhaps representing replicons in a transition state

Molecular genetics of Rett syndrome and clinical spectrum of MECP2 mutations.

Abstract: Rett syndrome, a neurodevelopmental disorder that is a leading cause of mental retardation in females, is caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). MECP2 mutations have subsequently been identified in patients with a variety of clinical syndromes ranging from mild learning disability in females to severe mental retardation, seizures, ataxia, and sometimes neonatal encephalopathy in males. In classic Rett syndrome, genotype-phenotype correlation studies suggest that X chromosome inactivation patterns have a more prominent effect on clinical severity than the type of mutation. When the full range of phenotypes associated with MECP2 mutations is considered, however, the mutation type strongly affects disease severity. MeCP2 is a transcriptional repressor that binds to methylated CpG dinucleotides throughout the genome, and mutations in Rett syndrome patients are thought to result in at least a partial loss of function. Abnormal gene expression may thus underlie the phenotype. Discovering which genes are misregulated in the absence of functional MeCP2 is crucial for understanding the pathogenesis of this disorder and related syndromes.

The intrinsically unstable life of DNA triplet repeats associated with human hereditary disorders.

Abstract: Expansions of specific DNA triplet repeats are the cause of an increasing number of hereditary neurological disorders in humans. In some diseases, such as Huntington's and several spinocerebellar ataxias, the repetitive DNA sequences are translated into long tracts of the same amino acid (usually glutamine), which alters interactions with cellular constituents and leads to the development of disease. For other disorders, including common genetic disorders such as myotonic dystrophy and fragile X syndrome, the DNA repeat is located in noncoding regions of transcribed sequences and disease is probably caused by altered gene expression. In studies in lower organisms, mammalian cells, and transgenic mice, high frequencies of length changes (increases and decreases) occur in long DNA triplet repeats. These observations are similar to other types of repetitive DNA sequences, which also undergo frequent length changes at genomic loci. A variety of processes acting on DNA influence the genetic stability of DNA triplet repeats, including replication, recombination, repair, and transcription. It is not yet known how these diffirent multienzyme systems interact to produce the genetic mutation of expanded repeats. In vitro studies have identified that DNA triplet repeats can adopt several unusual DNA structures, including hairpins, triplexes, quadruplexes, slipped structures, and highly flexible and writhed helices. The formation of stable unusual structures within the cell is likely to disturb DNA metabolism and be a critical intermediate in the molecular mechnism(s) leading to genetic instabilities of DNA repeats and, hence, to disease pathogenesis.

The high morbidity of blunt cerebrovascular injury in an unscreened population: more evidence of the need for mandatory screening protocols

Abstract: BACKGROUND: Blunt cerebrovascular injuries are rare injuries causing substantial morbidity and mortality The appropriate screening methods and treatment options for these injuries are controversial We examined our experience with these injuries at a community Level I Trauma center over a 51 month period STUDY DESIGN: A retrospective review and analysis was done of all patients with the diagnosis of a blunt cerebrovascular injury during this period RESULTS: Fourteen patients had blunt carotid injury (040%) and three had blunt vertebral injury (009%) out of 3,480 total blunt admissions The overall incidence of blunt cerebrovascular injury was 049% The most common associated injuries were to the head (59%) and chest (47%) regions The overall mortality rate was 59% (10 of 17), with death occurring in 8 of 14 (57%) blunt carotid injury patients and 2 of 3 (67%) blunt vertebral injury patients Eight of ten (80%) deaths were directly attributable to the blunt cerebrovascular injury Median time until diagnosis was 125 h (range 1-336 h) for the entire group and 195 h for nonsurvivors Diagnosis was delayed > 24h in 7 patients and > 48h in 5 patients All five patients whose diagnoses were delayed > 48 h developed complications, and four (80%) of these patients died CONCLUSIONS: Blunt cerebrovascular injury is uncommon, but lethal; particularly when the diagnosis is delayed Aggressive screening protocols based on mechanism of injury, associated injuries, and physical findings are justified to minimize morbidity and mortality Head and chest injuries may serve as markers for blunt cerebrovascular injury Most deaths are directly attributable to the blunt cerebrovascular injury and not to associated injuries

A potentially expanded role for enoxaparin in preventing venous thromboembolism in high risk blunt trauma patients

Abstract: BACKGROUND: Venous thromboembolism (VTE) is a frequent and potentially life-threatening complication after trauma. The purpose of this study is to investigate the effectiveness of enoxaparin in preventing deep venous thrombosis (DVT) and pulmonary embolism (PE) after injury in patients who are at high risk for developing VTE. STUDY DESIGN: A prospective single-cohort observational study was initiated for seriously injured blunt trauma patients admitted to a Level I trauma center during a 7-month period. Patients were eligible for the study if time hospitalized was ≥ 72 hours, Injury Severity Score (ISS) was ≥ 9, enoxaparin was started within 24 hours after admission, and one or more of the following high risk criteria were met: age > 50 years, ISS ≥ 16, presence of a femoral vein catheter, Abbreviated Injury Score (AIS) ≥ 3 for any body region, Glasgow Coma Scale (GCS) Score ≤ 8, presence of major pelvic, femur, or tibia fracture, and presence of direct blunt mechanism venous injury. Patients with closed head injuries and nonoperatively treated solid abdominal organ injuries were also potential participants. The primary outcomes measured were thromboembolic events—either a documented lower extremity DVT by duplex color-flow doppler ultrasonography or a PE documented by rapid infusion CT pulmonary angiography or conventional pulmonary angiography. RESULTS: There were 118 patients enrolled in the study. Two patients (2%) developed DVT, one of which was proximal to the calf (95% confidence interval, 0% to 6%). Two of 12 patients (17%) with splenic injuries who received enoxaparin failed initial nonoperative management. There were no other bleeding complications, and no clinical evidence or documented episodes of PE. One patient died from multiple system organ failure. CONCLUSIONS: Enoxaparin is a practical and effective method for reducing the incidence of VTE in high risk, seriously injured patients. This study supports further investigation into the safety of enoxaparin prophylaxis in patients with closed head injuries and nonoperatively treated solid abdominal organ injuries.

Co-association of parkin and alpha-synuclein.

Abstract: Parkin and alpha-synuclein are two proteins that are associated with the pathophysiology of Parkinson's disease (PD). Parkin is present in Lewy bodies and axonal spheroids in brains affected by PD, and mutations in parkin cause hereditary forms of Parkinsonism. Alpha-synuclein is a major component of Lewy bodies and is associated with rare cases of PD. We now show that parkin binds to alpha-synuclein, including conditions associated with alpha-synuclein aggregation. Parkin and alpha-synuclein complexes were observed in BE-M17 cells under basal conditions, in BE- M17 cells under oxidative conditions and in brains from control or PD donors. Double staining of PD brains shows parkin and alpha-synuclein co-localize to the same pathological structures (both Lewy bodies and axonal spheroids). These results suggest that parkin interacts with alpha-synuclein and could contribute to the pathophysiology of PD more generally than was previously considered.

Stimulation of Cellular Proliferation by Hepatitis B Virus X Protein

Abstract: Chronic infection with the hepatitis B virus (HBV) is a known risk factor in the development of human hepatocellular carcinoma (HCC). The HBV-encoded X protein, HBx, has been investigated for properties that may explain its cancer cofactor role in transgenic mouse lines. We discuss here recent data showing that HBx is able to induce hepatocellular proliferation in vitro and in vivo. This property of HBx is predicted to sensitize hepatocytes to other HCC cofactors, including exposure to carcinogens and to other hepatitis viruses. Cellular proliferation is intimately linked to the mechanism(s) by which most tumor-associated viruses transform virus-infected cells. The HBx alteration of the cell cycle provides an additional mechanism by which chronic HBV infection may contribute to HCC.

Infectious Disease Consultation and Microbiologic Surveillance for Intensive Care Unit Trauma Patients: A Pilot Study

Abstract: Infection remains a major cause of posttrauma morbidity. We retrospectively reviewed 2 cohorts of trauma patients admitted to a regional trauma center before and after a policy change integrating prospective microbiologic surveillance and infectious disease (ID) consultation into management of trauma admissions. Primary interests were effects of this policy change on antimicrobial use and diagnostic precision (particularly differentiation of infection from colonization). Associated costs, microflora, survival, and disability were also compared. Patients were stratified for risk of infection. ID consultation was associated with a 49% increased odds that an infection diagnosis was microbiologically based (P=.006) and 57% reduction of antibiotics costs per hospitalized day (P=.0008). Costs of consultation and an 86% increase (P<10(-6)) in total cultures combined to minimally exceed that financial saving. The observed improvements in diagnostic precision and antimicrobial usage, however, suggest consideration of prospective microbiologic surveillance and multidisciplinary physician teams including ID physicians for high-risk trauma patients.

Early exposure of the rat mammary gland to estrogen and progesterone blocks co-localization of estrogen receptor expression and proliferation.

Abstract: An early single full-term pregnancy induces a long-lasting protective effect against mammary tumor development in humans and rodents. This protective effect can be mimicked in rats by short-term administration of estrogen and progesterone hormones prior to carcinogen administration. The hormones of pregnancy are able to induce a proliferative block upon carcinogen challenge that is not observed in the age-matched virgin. We wished to determine whether carcinogen is needed to induce a paracrine-to-autocrine shift of proliferation in steroid receptor positive cells or if such a cell population already exists in the age-matched virgin mammary gland. Here we show that estrogen receptor positive (ER+) proliferating cells are rare in the developing mammary gland of the virgin rat but represent the majority of the proliferating cells in the mature (96-day-old) mammary gland of the virgin rat. As the majority of the proliferating cells before carcinogen challenge were ER positive, the ER+ proliferating cells in the mature mammary gland may represent the target cells for carcinogen-induced transformation. Importantly, prior exposure of the mammary gland to pregnancy levels of estrogen/progesterone blocked this positive association. This ability to block the proliferation of the ER+ cells may be one factor by which pregnancy induces protection against breast cancer.

Fox (forkhead) genes are involved in the dorso-ventral patterning of the Xenopus mesoderm.

Abstract: Fox (forkhead/winged helix) genes encode a family of transcription factors that are involved in embryonic pattern formation, regulation of tissue specific gene expression and tumorigenesis. Several of them are transcribed during Xenopus embryogenesis and are important for the patterning of ectoderm, mesoderm and endoderm. We have isolated three forkhead genes that are activated during gastrulation and play an important role in the dorso-ventral patterning of the mesoderm. XFKH1 (FoxA4b), the first vertebrate forkhead gene to be implicated in embryonic pattern formation, is expressed in the Spemann-Mangold organizer region and later in the embryonic notochord. XFKH7, the Xenopus orthologue of the murine Mfh1(Foxc2), is expressed in the presomitic mesoderm, but not in the notochord or lateral plate mesoderm. Finally, XFD-13'(FoxF1b)1 is expressed in the lateral plate mesoderm, but not in the notochord or presomitic mesoderm. Expression pattern and functional experiments indicate that these three forkhead genes are involved in the dorso-ventral patterning of the mesoderm.

Virulence factors of Escherichia coli isolated from female reproductive tract infections and neonatal sepsis.

Abstract: Objective: The presence of enterobacteria such as Escherichia coli in the vagina of normal women is not synonymous with infection. However, vaginal E. coli may also cause symptomatic infections. We examined bacterial virulenceproperties that may promote symptomatic female reproductive tract infections (RTI) and neonatal sepsis.

Responding to the need for faculty development: a survey of U.S. and Canadian dental schools.

Abstract: The Office of Professional Development at The University of Texas-Houston Health Science Center Dental Branch was established in November 1996 in order to meet the professional development needs of the faculty, staff, and administration. Although other dental schools share similar needs, our research revealed no study to determine how dental schools managed their faculty development needs. Therefore, a preliminary survey to collect data about offices similar to ours was developed and sent to the deans of fifty-four U.S. schools including Puerto Rico and ten Canadian schools. Thirty-seven schools (58 percent) responded, and it was determined that five schools (14 percent) had Offices of Professional Development and seven (19 percent) had Offices of Faculty Affairs. Based on these results, an expanded follow-up survey was conducted. The respondents were asked to indicate 1) which entity within the school was primarily responsible for handling faculty development, and 2) which entity actually sponsored each of eighteen faculty development activities. With a response from thirty-three U.S. schools (61 percent) and six Canadian schools (60 percent), six administrative structures (models) for faculty development were identified: 1) Office of Academic Affairs, 2) Departmental Chair, 3) a Faculty Development Committee, 4) an Office of the Dean, 5) an Office of Faculty/Professional Development, and 6) Other Resources.

Increased concentrations of cathepsin D in peritoneal fluid from women with endometriosis.

Abstract: To assess the release of the proteolytic enzyme cathepsin D in endometriosis, concentrations in peritoneal fluid and serum were measured by ELISA in 54 women with (n = 33) and without (n = 21) endometriosis. Surgery was scheduled in either the proliferative or secretory phase of the menstrual cycle. The concentrations of cathepsin D in the peritoneal fluid were markedly elevated in the endometriosis patients (median 58 ng/ml, interquartile range 0-166 ng/ml) as compared to the controls (5 ng/ml, 0-86 ng/ml), especially in women with late stage disease (n = 19, stages III/IV) and in those not undergoing gonadotrophin-releasing hormone (GnRH) agonist therapy (n = 15). No significant difference was determined in cathepsin D concentrations of the serum from women with and without endometriosis. We conclude that cathepsin D is an important factor that may contribute to the pathogenesis of endometriosis, possibly by promoting digestion of extracellular matrix proteins. These results have implications for the therapeutic efficacy of GnRH agonists.

Protein minimization by random fragmentation and selection.

Abstract: Protein-protein interactions are involved in most biological processes and are important targets for drug design. Over the past decade, there has been increased interest in the design of small molecules that mimic functional epitopes of protein inhibitors. BLIP is a 165 amino acid protein that is a potent inhibitor of TEM-1 beta-lactamase (K(i) = 0.1 nM). To aid in the development of new inhibitors of beta-lactamase, the gene encoding BLIP was randomly fragmented and DNA segments encoding peptides that retain the ability to bind TEM-1 beta-lactamase were isolated using phage display. The selected peptides revealed a common, overlapping region that includes BLIP residues C30-D49. Synthesis and binding analysis of the C30-D49 peptide indicate that this peptide inhibits TEM-1 beta-lactamase. Therefore, a peptide derivative of BLIP that has been reduced in size by 88% compared with wild-type BLIP retains the ability to bind and inhibit beta-lactamase.

Marijuana (Cannabis) as Medicine

Abstract: The modern published literature on the therapeutic potentials of cannabis has been reviewed. A pure preparation of the major active component, delta-9-tetrahydrocannabinol (THC), Marinol(r) or dro-nabinol, is available for treating nausea and vomiting associated with cancer chemotherapy and as an adjunct to weight loss in patients with wasting syndrome associated with AIDS. Although such approval currently applies only to orally administered THC, for practical purposes smoked marijuana should also be expected to be equally effective.

Clinical experience with nine patients supported by the continuous flow Debakey VAD.

Abstract: Introduction: Pulsatile left ventricular assist devices (LVADs) have been established for bridging of selected patients with advanced congestive heart failure to transplantation. Their clinical application, however, has been complicated by bleeding, thromboembolic and infectious adverse events. Recently, continuous flow LVADs have been introduced. They are expected to be associated with a reduced risk for such complications. Here we report our experience with 9 patients on the continuous flow DeBakey VADTM. Patients and Methods: Since February 2000, 9 patients have been supported by the continuous flow DeBakey VADTM at our institution (all male, 38.6613.1 years, 3 DCM, 3 ICM, 1 congenital, 1 postcardiotomy, 1 myocardial infarction). Before implantation, patients were in severe heart failure (NYHA IV) requiring inotropic support. Cardiac index was 1.6460.49 l/min/m2. All patients fulfilled the requirements for listing to heart transplantation and were put on the waiting list at the time of LVAD implantation. Results: Current total support time (as of October 17, 2000) amounts to 900 patient days (14 2 232 days). One patient was transplanted 226 days following LVAD implantation, six patients are currently still on LVAD support. One patient died on postoperative day (POD) 14 due to multiorgan failure developing following preoperative cardiogenic shock due to myocardial infarction, one patient died on POD 15 after a thrombus generated from the left ventricle had caused the pump to stop. Bleeding complications requiring rethoracotomy occurred in 3 patients. There was no thromboembolic event. No driveline or device infection was observed. Moderate hemolysis was seen in 3 patients. In 4 patients, the LVAD was replaced (POD 76, 76, 137, 170) for another DeBakey VADTM. Device exchanges were associated with thrombus; however, its origin could not be determined. Conclusion: Our experience with the DeBakey VADTM indicates that it is associated with a low risk for bleeding, hemolysis, thromboembolic and infectious complications which makes it a valuable alternative to pulsatile LVADs. Thrombus in the pump may be addressed with improved anticoagulation and platelet inhibition.

Graph Database Systems for Genomics

Abstract: Genome databases have specific requirements which limit the usefulness of some database management systems. By using more appropriate database technology, a database system can be developed for genome data. We have developed a data representation based on graph theory which captures the highly interconnected structure of genome data. Graphs are a language which can be tailored for describing genomic information, and we develop a data model based on graphs which serves as the foundation of a graph database management system. IEEE Engineering in Medicine and Biology special issue on Managing Data for the Human Genome Project.

The effects of Hurricane Mitch on a community in northern Honduras.

Abstract: Introduction: Hurricane Mitch was an event described as one of the most damaging recent natural disasters in our hemisphere. This study examined its effects on a community of 5,000 residents in northern Honduras. Methods: Survey responses of 110 attendants at an ambulatory clinic 4 months after the event were analyzed. Correlates were established between demographic and housing characteristics and morbidity and mortality. Results: The availability of food, water, and medical care decreased significantly immediately after the hurricane, but by four months afterward returned to baseline values. Residents reported emotional distress correlated with the loss of a house or intrafamilial illness or mortality. Diarrheal illnesses more commonly were found in households with poor, chronic access to medical care. The use of cement block housing correlated with availability of food or running water, with access to medical care and vaccinations, and with a reduced frequency of diarrhea or headaches in the immediate post-hurricane phase. Conclusions: Improvements in housing construction appear to be the most effective preventive measure for withstanding the effects of future hurricanes in tropical regions similar to northern Honduras.

Transcriptional activity of HTLV-I Tax influences the expression of marker genes associated with cellular transformation.

Abstract: Human T cell leukemia virus type I (HTLV-I) has been identified as the etiologic agent of adult T cell leukemia (ATL). HTLV-I encodes a transcriptional regulatory protein, Tax, which also functions as the viral transforming protein. Through interactions with a number of cellular transcription factors Tax can modulate cellular gene expression. Since the majority of Tax-responsive cellular genes are important regulators of cellular proliferation, the transactivating functions of Tax appear to be necessary for cellular transformation by HTLV-I. Gaining a complete understanding of the broad range of genes regulated by Tax, the temporal pattern of their expression, and their effects on cell function may identify early markers of disease progression mediated by this virus.

NUDC expression during amphibian development.

Abstract: To identify gene products important for gastrulation in the amphibian Pleurodeles waltl, a screen for regional differences in new protein expression at the early gastrula stage was performed. A 45 kDa protein whose synthesis was specific for progenitor endodermal cells was identified. Microsequencing and cDNA cloning showed that P45 is highly homologous to rat NUDC, a protein suggested to play a role in nuclear migration. Although PNUDC can be detected in all regions of the embryo, its de novo synthesis is tightly regulated spatially and temporally throughout oogenesis and embryonic development. New PNUDC synthesis in the progenitor endodermal cells depends on induction by the mesodermal cells in the gastrula. During development, PNUDC is localized in the egg cortical cytoplasm, at the cleavage furrow during the first embryonic division, around the nuclei and cortical regions of bottle cells in the gastrula, and at the basal region of polarized tissues in the developing embryo. These results show for the first time the expression and compartmentalization of PNUDC at distinct stages during amphibian development.

Significance of indicator bacteria in a regionalised wastewater treatment plant and receiving waters

Abstract: A regional wastewater treatment plant was found to be discharging high concentrations of fecal coliform bacteria in excess of acceptable surface water criteria. An investigation of the sources of those bacteria showed their origins to have been environmental, primarily from a pulp and paper mill. False positive and false negative fecal coliforms were also found and enumerated. These bacteria were found to increase in numbers through the treatment plant, unlike sewage treatment plants in which they decrease to the effluent.

Percutaneous dilatational tracheostomy in a community hospital setting.

Abstract: Background.Over the past 15 years, many large university hospitals have reported their experience with percutaneous dilatational tracheostomy (PDT). The purposes of this study are to evaluate the safety of PDT in a non-university hospital setting and to compare our results with those publish

Palmitate-Induced Apoptosis in Neonatal Cardiomyocytes is Not Dependent on the Generation of Reactive Oxygen Species.

Abstract: The saturated fatty acid palmitate induces apoptosis in neonatal rat cardiomyocytes. This apoptosis is associated with early mitochondrial release of cytochrome c and a subsequent loss of mitochondrial membrane potential. Recent reports implicate a role for reactive oxygen species in palmitate-induced apoptosis. We studied the role of ROS in palmitate-induced apoptosis in the neonatal rat cardiomyocyte and report no evidence of ROS involvement. ROS production, NO production and NFκB activation were not increased above those observed using the non-apoptotic fatty acid, oleate. Indeed, the production of ROS was significantly higher in cells treated with oleate. Furthermore, the presence of antioxidants and ROS scavengers did not attenuate the induction of apoptosis by palmitate. Variations in the fatty acid to albumin ratio from 2:1 to 7:1 had no effect on the absence of ROS production or on the extent of apoptosis. No evidence was found for an increase in oxidative protein modification in palmitate-treated cells. Our results lead us to conclude that oxidative stress does not play a role in palmitate-induced apoptosis.