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Biomedical subjects

M West

Publications and source records attributed to M West.

At least 19 recordsLinked to original sources
PubMed2001

Magma storage beneath Axial volcano on the Juan de Fuca mid-ocean ridge.

Axial volcano, which is located near the intersection of the Juan de Fuca ridge and the Cobb-Eickelberg seamount chain beneath the northeast Pacific Ocean, is a locus of volcanic activity thought to be associated with the Cobb hotspot. The volcano rises 700 metres above the ridge, has substantial rift zones extending about 50 kilometres to the north and south, and has erupted as recently as 1998 (ref. 2). Here we present seismological data that constrain the three-dimensional velocity structure beneath the volcano. We image a large low-velocity zone in the crust, consisting of a shallow magma chamber and a more diffuse reservoir in the lower crust, and estimate the total magma volume in the system to be between 5 and 21 km3. This volume is two orders of magnitude larger than the amount of melt emplaced during the most recent eruption (0.1-0.2 km3). We therefore infer that such volcanic events remove only a small portion of the reservoir that they tap, which must accordingly be long-lived compared to the eruption cycle. On the basis of magma flux estimates, we estimate the crustal residence time of melt in the volcanic system to be a few hundred to a few thousand years.

Journal Article↗
PubMed2001

Predicting the clinical status of human breast cancer by using gene expression profiles.

Prognostic and predictive factors are indispensable tools in the treatment of patients with neoplastic disease. For the most part, such factors rely on a few specific cell surface, histological, or gross pathologic features. Gene expression assays have the potential to supplement what were previously a few distinct features with many thousands of features. We have developed Bayesian regression models that provide predictive capability based on gene expression data derived from DNA microarray analysis of a series of primary breast cancer samples. These patterns have the capacity to discriminate breast tumors on the basis of estrogen receptor status and also on the categorized lymph node status. Importantly, we assess the utility and validity of such models in predicting the status of tumors in crossvalidation determinations. The practical value of such approaches relies on the ability not only to assess relative probabilities of clinical outcomes for future samples but also to provide an honest assessment of the uncertainties associated with such predictive classifications on the basis of the selection of gene subsets for each validation analysis. This latter point is of critical importance in the ability to apply these methodologies to clinical assessment of tumor phenotype.

Bacillus anthracis↗
PubMed2001

Intracellular vesicular trafficking in the gill epithelium of urea-excreting fish.

Most teleost fish are ammoniotelic, and relatively few are ureotelic, in which the majority of nitrogenous waste is excreted as urea. This study aimed to determine whether the gill ultrastructure of ureotelic fish might have specific, unique characteristics compared with ammoniotelic fish. The gill morphology was studied in three closely related species of the family Batrachoididae: Opsanus beta, the gulf toadfish; Opsanus tau, the oyster toadfish; and Porichthys notatus, the plainfin midshipman, because prior studies have demonstrated that the two former species are ureotelic and excrete urea in unique, short daily pulses, whereas the latter is ammoniotelic. Ultrastructural studies demonstrated significant trafficking of dense-cored vesicles (50-200 nm) between the Golgi apparatus and the apical membrane of epithelial cells surrounding gill filaments and lamellae in these two Opsanus spp. The material constituting the core of these vesicles was intensely stained by lead salt and was unloaded externally when vesicles contacted the apical membrane. Another characteristic of these urea-secreting fish was the presence of numerous large, black-stained lysosomes, which contained cored vesicles, suggesting a second destination for the dense-cored vesicles. As a working hypothesis, the present data suggest that the urea-transporter protein, recently found in toadfish gills, is inserted in the vesicle. Subsequently, it could serve to either sequester cytosolic urea that ultimately is secreted into the water after contact of these vesicles with the pavement cell apical membrane, or it could allow facilitated diffusion of urea across the plasma membrane following insertion into the membrane. As further comparative evidence, the ammoniotelic P. notatus exhibited neither the vesicular trafficking nor the population of lysosomes both found in Opsanus spp.

Ammonia↗
PubMed2001

Oxidative biochemical markers; clues to understanding aging in long-lived species.

Clues as to why long-lived species live so much longer than short-lived species may reside in the amount of reactive oxygen species (ROS) produced and their effect on damaging cell components (especially proteins) and alterations of crucial cellular processes. Rigorous evaluation of these concepts required critical comparisons of oxidative damage markers and/or parameters with assess difference in ROS flux and the critical age-modifying processes they influence. The limited experimental comparative results available implicate that ROS production per unit weight of total oxygen consumed is much less in the longer-lived species than in shorter-lived species. Mitochondria are the major site of ROS production. They are also the functional nexus for intracellular signaling thus modulating stress and growth factor mediated cellular survival, proliferation and apoptotic processes. Mitochondrial DNA mutations, perhaps caused by ROS, increase with age. Mutant mitochondria possess comparative replicative advantage, which leads to age-specific intracellular swarms. General inflammatory stress tends to increase with age. Disruption in coordinated cell-to-cell signaling triggered by alterations in intracellular signaling may be the basis of the age-related increases in tissue inflammation, which may explain some of the differences between long-lived species and short-lived species.

Aging↗
PubMed2001

The development and preliminary validation of a new measure of adult attachment: the adult attachment projective.

In this paper, we describe the development of and our preliminary work to empirically validate the Adult Attachment Projective (AAP), a new adult attachment classification system that is based on the analysis of individuals' responses to a set of seven attachment-related drawings. The AAP classification system uses evaluations of three dimensions (Discourse, Content and Defensive Processing) to designate four major adult classification groups: Secure, Dismissing, Preoccupied, and Unresolved. Preliminary validation of the AAP is based on 75 participants drawn from three separate samples. The results indicate strong interjudge reliability and convergent agreement between the AAP and Adult Attachment Interview (AAI) classifications. The AAP, thus, appears to be a promising developmental measure for assessing the representation of attachment in adults. Contributions of the AAP to attachment theory and research are discussed. The similarities and differences between AAP stories and other child and adult representational measures are also discussed.

Adult↗
PubMed2001

Penetrating esophageal injuries: multicenter study of the American Association for the Surgery of Trauma.

OBJECTIVE: The purpose of this study was to define the period of time after which delays in management incurred by investigations cause increased morbidity and mortality. The outcome study is intended to correlate time with death from esophageal causes, overall complications, esophageal related complications, and surgical intensive care unit length of stay. METHODS: This was a retrospective multicenter study involving 34 trauma centers in the United States, under the auspices of the American Association for the Surgery of Trauma Multi-institutional Trials Committee over a span of 10.5 years. Patients surviving to reach the operating room (OR) were divided into two groups: those that underwent diagnostic studies to identify their injuries (preoperative evaluation group) and those that went immediately to the OR (no preoperative evaluation group). Statistical methods included Fisher's exact test, Student's T test, and logistic regression analysis. RESULTS: The study involved 405 patients: 355 male patients (86.5%) and 50 female patients (13.5%). The mean Revised Trauma Score was 6.3, the mean Injury Severity Score was 28, and the mean time interval to the OR was 6.5 hours. There were associated injuries in 356 patients (88%), and an overall complication rate of 53.5%. Overall mortality was 78 of 405 (19%). Three hundred forty-six patients survived to reach the OR: 171 in the preoperative evaluation group and 175 in the no preoperative evaluation group. No statistically significant differences were noted in the two groups in the following parameters: number of patients, age, Injury Severity Score, admission blood pressure, anatomic location of injury (cervical or thoracic), surgical management (primary repair, resection and anastomosis, resection and diversion, flaps), number of associated injuries, and mortality. Average length of time to the OR was 13 hours in the preoperative evaluation group versus 1 hour in the no preoperative evaluation group (p < 0.001). Overall complications occurred in 134 in the preoperative evaluation group versus 87 in the no preoperative evaluation group (p < 0.001), and 74 (41%) esophageal related complications occurred in the preoperative evaluation group versus 32 (19%) in the no preoperative evaluation group (p = 0.003). Mean surgical intensive care unit length of stay was 11 days in the preoperative evaluation group versus 7 days in the no preoperative evaluation group (p = 0.012). Logistic regression analysis identified as independent risk factors for the development of esophageal related complications included time delays in preoperative evaluation (odds ratio, 3.13), American Association for the Surgery of Trauma Organ Injury Scale grade >2 (odds ratio, 2.62), and resection and diversion (odds ratio, 4.47). CONCLUSION: Esophageal injuries carry a high morbidity and mortality. Increased esophageal related morbidity occurs with the diagnostic workup and its inherent delay in operative repair of these injuries. For centers practicing selective management of penetrating neck injuries and transmediastinal gunshot wounds, rapid diagnosis and definitive repair should be made a high priority.

Adolescent↗
PubMed2001

Functional mapping of the DNA binding domain of bovine papillomavirus E1 protein.

Bovine papillomavirus type 1 (BPV-1) requires viral proteins E1 and E2 for efficient DNA replication in host cells. E1 functions at the BPV origin as an ATP-dependent helicase during replication initiation. Previously, we used alanine mutagenesis to identify two hydrophilic regions of the E1 DNA binding domain (E1DBD), HR1 (E1(179-191)) and HR3 (E1(241-252)), which are critical for sequence-specific recognition of the papillomavirus origin. Based on sequence and structure, these regions are similar in spacing and location to DNA binding regions A and B2 of T antigen, the DNA replication initiator of simian virus 40 (SV40). HR1 and A are both part of extended loops which are supported by residues from the HR3 and B2 alpha-helices. Both elements contain basic residues which may contact DNA, although lack of cocrystal structures for both E1 and T antigen make this uncertain. To better understand how E1 interacts with origin DNA, we used random mutagenesis and a yeast one-hybrid screen to select mutations of the E1DBD which disrupt sequence-specific DNA interactions. From the screen we selected seven single point mutants and one double point mutant (F175S, N184Y/K288R, D185G, V193M, F237L, K241E, R243K, and V246D) for in vitro analysis. All mutants tested in electrophoretic mobility shift assays displayed reduced sequence-specific DNA binding compared to the wild-type E1DBD. Mutants D185G, F237L, and R243K were rescued in vitro for DNA binding by the replication enhancer protein E2. We also tested the eight mutations in full-length E1 for the ability to support DNA replication in Chinese hamster ovary cells. Only mutants D185G, F237L, and R243K supported significant DNA replication in vivo which highlights the importance of E1DBD-E2 interactions for papillomavirus DNA replication. Based on the specific point mutations examined, we also assigned putative roles to individual residues in DNA binding. Finally, we discuss sequence and spacing similarities between E1 HR1 and HR3 and short regions of two other DNA tumor virus origin-binding proteins, SV40 T antigen and Epstein-Barr virus nuclear antigen 1 (EBNA1). We propose that all three proteins use a similar DNA recognition mechanism consisting of a loop structure which makes base-specific contacts (HR1) and a helix which primarily contacts the DNA backbone (HR3).

Amino Acid Sequence↗
PubMed2001

Role for E2F in control of both DNA replication and mitotic functions as revealed from DNA microarray analysis.

We have used high-density DNA microarrays to provide an analysis of gene regulation during the mammalian cell cycle and the role of E2F in this process. Cell cycle analysis was facilitated by a combined examination of gene control in serum-stimulated fibroblasts and cells synchronized at G(1)/S by hydroxyurea block that were then released to proceed through the cell cycle. The latter approach (G(1)/S synchronization) is critical for rigorously maintaining cell synchrony for unambiguous analysis of gene regulation in later stages of the cell cycle. Analysis of these samples identified seven distinct clusters of genes that exhibit unique patterns of expression. Genes tend to cluster within these groups based on common function and the time during the cell cycle that the activity is required. Placed in this context, the analysis of genes induced by E2F proteins identified genes or expressed sequence tags not previously described as regulated by E2F proteins; surprisingly, many of these encode proteins known to function during mitosis. A comparison of the E2F-induced genes with the patterns of cell growth-regulated gene expression revealed that virtually all of the E2F-induced genes are found in only two of the cell cycle clusters; one group was regulated at G(1)/S, and the second group, which included the mitotic activities, was regulated at G(2). The activation of the G(2) genes suggests a broader role for E2F in the control of both DNA replication and mitotic activities.

Animals↗
PubMed2001

Attachment disorganization and dissociative symptoms in clinically treated adolescents.

OBJECTIVE: To examine the association of unresolved and unclassifiable attachment with dissociative symptomatology in a sample of 133 adolescents in psychiatric treatment. METHOD: The study compared 69 adolescents who were unresolved and unclassifiable with 64 adolescents who were not unresolved and unclassifiable. Attachment organization was assessed using the Adult Attachment Interview (AAI). Dissociative symptomatology was assessed using a scale derived from the Youth Self Report (YSR) behaviour checklist. RESULTS: A continuing unresolved and unclassifiable response to attachment-related trauma was correlated with dissociative symptomatology for both male and female adolescents. CONCLUSIONS: Cognitive disorganization may be an important variable mediating between the effects of earlier traumatic caregiving experiences and later dissociative symptoms.

Adolescent↗
PubMed2001

Lipid-lowering efficacy, safety, and costs of a large-scale therapeutic statin formulary conversion program.

STUDY OBJECTIVE: To assess the lipid-lowering efficacy, safety, and costs of a large-scale statin formulary conversion program. DESIGN: Prospective, observational study. SETTING: Tertiary academic medical center. PATIENTS: A total of 980 patients consented to participate; 942 patients completed the study. INTERVENTION: Patients were converted from their current statin therapy to either cerivastatin 0.4 or 0.8 mg/day, or simvastatin 80 mg/day, using a conversion algorithm. MEASUREMENTS AND MAIN RESULTS: Efficacy and safety were evaluated at baseline and after 6 weeks of therapy; costs were also measured. Overall attainment of the National Cholesterol Education Program (NCEP) goal for low-density lipoprotein cholesterol (LDL) increased from 64.8% to 74.5% of patients (p<0.001); mean LDL decreased from 115+/-30 mg/dl to 106+/-25 mg/dl (p<0.001). Adverse events occurred in 3% of patients, and included myositis (0.6%) and increased hepatic transaminases (0.1%). Overall costs were reduced by $115/patient treatment-year. CONCLUSION: Statin therapeutic interchange can improve lipid control at reduced costs. The possibility of uncommon but potentially serious adverse effects suggests that these programs require appropriate monitoring.

Aged↗
PubMed2001

Doctoral students' responses to writing critique: messages for teachers.

Writing is a major part of learning scholarship in a discipline. Therefore, it is important to understand what promotes and what hinders this learning. In transcribed interviews, 15 doctoral students in nursing at a large university described to us what they saw as helpful or not helpful about responses to their writing. The themes take the form of messages for teachers that, when reported in the context of the composition literature, provide helpful suggestions for teachers.

Authorship↗
PubMed2001

A data mart for operations analysis.

In this article we describe the evolution and architecture of a data mart developed to address the modeling and analysis needs of healthcare operations analysts. More specifically, the data mart is used in projects relating to demand analysis, forecasting, capacity planning, and service system design for a healthcare system consisting of a large tertiary care hospital and a smaller community hospital. The primary focus of the mart is on the detailed movement of inpatients through each hospital, although most component data tables include outpatient information such as emergency center visits, surgical cases, cardiac catheterization cases, and short-stay visits. We show that the data mart goes well beyond consolidating data from different sources by including a number of complex, precalculated fields, data structures, and function libraries that are specific to the needs of operations analysts. We discuss several outstanding and challenging design issues that should be of interest to the data warehouse vendor community.

Bed Occupancy↗
PubMed2001

Using data mining to find fraud in HCFA health care claims.

Data mining can be/used to detect health care fraud and abuse through visualization of very large data sets to isolate new and unusual patterns of activity. Data mining has allowed better direction and use of health care fraud detection and investigative resources by recognizing and quantifying the underlying indicators of fraudulent claims, fraudulent providers, and fraudulent beneficiaries. A large amount of work must be performed prior to the actual data mining. These precursory tasks include: customer discussions, data extraction and cleaning, transformation of the database, and auditing (basic statistics and visualization of the information) of the data. This paper describes the tasks performed in support of a project for HCFA (Health Care Financing Administration).

Centers for Medicare and Medicaid Services, U.S.↗
PubMed2000

A consensus sequence for long-chain fatty-acid alcohol oxidases from Candida identifies a family of genes involved in lipid omega-oxidation in yeast with homologues in plants and bacteria.

The yeast Candida cloacae is capable of growing on alkanes and fatty acids as sole carbon sources. Transfer of cultures from a glucose medium to one containing oleic acid induced seven proteins of M(r) 102,000, 73,000, 61,000, 54,000, and 46,000 and two in the region of M(r) 45,000 and repressed a protein of M(r) 64,000. The induction of the M(r) 73,000 protein reached a 7-fold maximum 24 h after induction. The protein was confirmed by its enzyme activity to be a long-chain fatty-acid alcohol oxidase (LC-FAO) and purified to homogeneity from microsomes by a rapid procedure involving hydrophobic chromatography. An internal peptide of 30 amino acids was sequenced. A 1100-base pair cDNA fragment containing the LC-FAO peptide coding sequence was used to isolate a single exon genomic clone containing the full-length coding sequence of an LC-FAO (fao1). The fao1 gene product was expressed in Escherichia coli and was translated as a functional long-chain alcohol oxidase, which was present in the membrane fraction. In addition, full-length coding sequences for a Candida tropicalis LC-FAO (faoT) and a second C. cloacae LC-FAO (fao2) were isolated. The DNA sequences obtained had open reading frames of 2094 (fao1), 2091 (fao2), and 2112 (faoT) base pairs. The derived amino acid sequences of fao2 and faoT showed 89.4 and 76.2% similarities to fao1. The fao1 gene is much more highly induced on alkane than is fao2. Although this study describes the first known DNA sequences encoding LC-FAOs from any source, there are unassigned Arabidopsis sequences and an unassigned Mycobacterium sequence in the GenBank(TM) Data Bank that show strong homology to the described LC-FAO sequences. The conservation of sequence between yeast, plants, and bacteria suggests that an as yet undescribed family of long-chain fatty-acid oxidases exists in both eukaryotes and prokaryotes.

Alcohol Oxidoreductases↗
PubMed2000

EEG effects of ECT: implications for rTMS.

Electroconvulsive therapy (ECT) involves the use of electrical stimulation to elicit a series of generalized tonic-clonic seizures for therapeutic purposes and is the most effective treatment known for major depression. These treatments have significant neurophysiologic effects, many of which are manifest in the electroencephalogram (EEG). The relationship between EEG data and the response to ECT has been studied since the 1940s, but for many years no consistent correlates were found. Recent studies indicate that a number of specific EEG features recorded during the induced seizures (ictal EEG) as well as before and after a course of treatment (interictal EEG) are related to both the therapeutic efficacy and cognitive side effects. Similar to ECT, repetitive transcranial magnetic stimulation (rTMS), which involves focal electromagnetic stimulation of cortical neurons, has also been studied as an antidepressant therapy and also appears to have neurophysiologic effects, although these have not been as fully investigated as is the case with ECT. Given the similarity of these treatments, it is natural to consider whether advances in understanding the electrophysiologic correlates of the ECT response might have implications for rTMS. The present article reviews the literature on the EEG effects of ECT and discusses the implications in terms of the likely efficacy and side effects associated with rTMS in specific anatomic locations, the potential for producing an antidepressant response with rTMS without eliciting seizure activity, eliciting focal seizures with rTMS, and the possibility of using rTMS to focally modulate seizure induction and spread with ECT to optimize treatment.

Brain Mapping↗
PubMed2000

The genotypic landscape during in vitro evolution of a catalytic RNA: implications for phenotypic buffering.

The Tetrahymena group I ribozyme catalyzes the cleavage of a phosphodiester linkage in specific sequences of RNA. This phenotype can be used in an in vitro selection-amplification process to evolve variants that are capable of RNA catalysis in the presence of Ca(2+) as the sole available cation. With sufficient genotypic characterization of the population as it evolves, we have a rare opportunity of observing how the information stored in an evolving population responds to selective pressures, such as the requisite of catalyzing RNA cleavage in the absence of Mg(2+) or Mn(2+). In the present work, we examine the population dynamics of this system using sequence information from previous experimental work. We focus on two issues: How does the information content of the population evolve? and Is the system evolving as an adaptive walk on a rugged landscape? To investigate these questions, information theoretical parameters are examined. The evolution of the population is visualized by mapping the genotypic frequency distribution onto a two-dimensional projection of sequence space. The projection was generated using Hamming distances from the wild-type, starting sequence and a catalytically successful, evolved sequence. The evolution of the information content of the system was measured by calculating the grammar complexity of the observed sequences, which showed a very slight increase over 12 generations. This result is consistent with the system performing a search for a local optimum. The dynamics of the population in this sequence space is consistent with an adaptive walk on an uncorrelated, or "rugged," genotypic landscape, despite the observation that the phenotypic progress of the population appears smooth. The relative insensitivity of the phenotypic landscape to the variegation of the genotypic landscape suggests that the former is buffered against variation in the latter through various epigenetic-like mechanisms.

Evolution, Molecular↗
PubMed2000

No loss of hippocampal neurons in AIDS patients.

Acquired immunodeficiency syndrome (AIDS) is often accompanied by neurological disorders and neuropathological abnormalities. A loss of up to 30% of the neocortical neurons in brains from AIDS patients has been demonstrated in several studies. This neuron loss appeared to have no relationship with either the presence of clinical dementia or HIV encephalitis. The hippocampal region of the brain is an essential component of learning and memory processes and it is severely affected in a number of diseases, including temporal lobe epilepsy and Alzheimer's dementia. In view of the reports of a considerable loss of neocortical neurons, the aim of the present study was to investigate the degree to which neurons may be lost in hippocampus of AIDS patients. A stereological method, the optical fractionator, was used to estimate the total number of neurons in the five subregions of the hippocampus of nine AIDS patients and ten controls. There were no statistically significant differences in the group means of the number of neurons in any of the subdivisions. This result is discussed in the light of the large loss of neurons in the neocortex reported to take place in AIDS patients.

Acquired Immunodeficiency Syndrome↗