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B Miller

Publications and source records attributed to B Miller.

At least 73 records · Page 4Linked to original sources
PubMed2000

PANORAMA: an integrated Web-based sequence analysis tool and its role in gene discovery.

As the exponential growth of DNA sequence information in databases continues, the task of converting this deposited information into knowledge becomes more dependent on integrative sequence analysis and visualization tools. PANORAMA is an Internet-accessible software package that performs a variety of informatics analyses on a given DNA sequence and returns a visual and interactive representation of the results. Its design is modular, so that further sequence analysis tools can be integrated with minimal effort. The utility of PANORAMA is demonstrated in the analysis of 650 kb of human genomic DNA from chromosome region 3p21.3, a region of potential tumor suppressor genes involved in lung cancer, breast cancer, and other forms of cancer. PANORAMA aided in the discovery of genes and alternate splice forms of known exons, in the demarcation of intron-exon boundaries, and in the identification of promoter regions and polymorphisms, all of which contributed to a better understanding of the region. PANORAMA is available on the World Wide Web at http://atlas.swmed.edu.

Animals↗
PubMed2000

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Animals↗
PubMed2000

Functional involvement of a deoxy-D-xylulose 5-phosphate reductoisomerase gene harboring locus of Synechococcus leopoliensis in isoprenoid biosynthesis.

The present work aimed to proof the functionality of the non-mevalonate pathway in cyanobacteria. It was intended to isolate the 1-deoxy-D-xylulose 5-phosphate (DXP) reductoisomerase gene (dxr), as this gene encodes the enzyme which catalyzes a pathway-specific, indicative step of this pathway. For this purpose, a segment of dxr was amplified from Synechococcus leopoliensis SAUG 1402-1 DNA via PCR using oligonucleotides for conserved regions. Subsequent hybridization screening of a genomic cosmid library of S. leopoliensis with the PCR segment led to the identification of a 26. 5 kbp locus on which a dxr homologous gene and two adjacent open reading frames organized in one operon were localized by DNA sequencing. The functionality of the gene was demonstrated expressing the gene in Escherichia coli and using the purified gene product in a photometrical NADPH dependent test based on the substrate DXP generating system. While the content of one of the central intermediates of the isoprenoid biosynthesis (dimethylallyl diphosphate=DMADP) was significantly (P</=0.001) increased in E. coli cells overexpressing the DXP synthase gene (dxs) of S. leopoliensis, overexpression of dxr does not lead to an elevated DMADP level. Since even in strains harboring an expression fusion of dxs the additional overexpression of dxr does not influence the DMADP content, it is concluded that Dxs but not Dxr catalyzes a rate limiting step of the non-mevalonate isoprenoid biosynthesis.

Aldose-Ketose Isomerases↗
PubMed2000

Evolution of a glucose-regulated ADH gene in the genus Saccharomyces.

To determine when a glucose-repressed alcohol dehydrogenase isozyme and its regulatory gene, ADR1, arose during evolution, we surveyed species of the genus Saccharomyces for glucose-repressed ADH isozymes and for ADR1 homologues. Glucose-repressed ADH isozymes were present in all species of Saccharomyces sensu strictu and also in Saccharomyces kluyveri, the most distant member of the Saccharomyces clade. We cloned and characterized ADH promoters from S. bayanus, S. douglasii, and S. kluyveri. The ADH promoters from S. bayanus and S. douglasii had conserved sequences, including upstream regulatory elements, and an extended polydA tract. The expression of a reporter gene driven by the S. bayanus promoter was glucose-repressed and dependent on the major activator of transcription, ADR1, when it was introduced into S. cerevisiae. One S. kluyveri promoter was also glucose-repressed and ADR1-dependent in S. cerevisiae. The other S. kluyveri ADH promoter was expressed constitutively and was ADR1-independent. Although showing little sequence conservation with the S. cerevisiae ADH2 promoter, the glucose-repressed S. kluyveri promoter contains numerous potential binding sites for Adr1. The glucose-repressed ADH from S. kluyveri is a mitochondrial isozyme most closely related to S. cerevisiae ADHIII. ADR1 homologues from S. douglasii and S. paradoxus contain a trinucleotide repeat encoding polyAsn that is lacking in S. cerevisiae and S. bayanus. No ADR1 homologue could be detected in S. kluyveri, suggesting that the potential for Adr1 regulation may have arisen first, before ADR1 evolved.

Alcohol Dehydrogenase↗
PubMed2000

Contribution of genetic and environmental influences to ankle-brachial blood pressure index in the NHLBI Twin Study. National Heart, Lung, and Blood Institute.

The ankle-brachial index (ABI) is widely used in the clinical diagnosis of peripheral arterial disease. The contributions of genetic and environmental influences to normal and abnormal ABI values are unknown. In this study, the authors used available data on 94 monozygotic pairs and 90 dizygotic pairs of elderly, White, male twins examined in 1995-1997 to investigate the contributions of genetic and environmental influences to normative ABI values. Within-twin-pair correlations for normative ABI values were statistically significant, and the correlation in monozygotic twin pairs was significantly greater than that in dizygotic pairs. Structural equation modeling of the variance-covariance matrices of monozygotic and dizygotic twins indicated that 48% of the observed variability in ABI values could be attributed to additive genetic effects. In contrast, concordance rates for low ABI values (ABI< or =0.9) for both monozygotic and dizygotic twins were significantly greater than would be expected by chance alone, but within-pair monozygotic similarity was not significantly greater than dizygotic similarity. A matched-cotwin analysis in 21 pairs that were discordant for low ABI values found that twins with low ABI values were physically less active and more likely to be persistent smokers than their normal-control brothers. These findings reinforce the role of individual health practices (e.g., physical activity, smoking) in the manifestation of peripheral arterial disease among subjects matched for age, genetics, and early shared environment.

Aged↗
PubMed2000

Modulation of the chemical and biological properties of trans platinum complexes: monofunctional platinum complexes containing one nucleobase as potential antiviral chemotypes.

Replacement of one of the chloride leaving groups in trans-[PtCl2(NH3)(L)] by the nucleobase 9-ethylguanine gives the nucleobase cations [SP-4-2]-[PtCl(9-ethylguanine)(NH3)(L)]+ (L = NH3, 1; L = quinoline, 3), which are models for the monofunctional adduct on DNA. Displacement of Cl- in 1 and 3 by either 5'-guanosine monophosphate (5'-GMP) or N-acetyl-L-methionine (N-AcMet) showed clear kinetic preference for the sulfur (estimated half-lives of 1.5 and 4 h with N-AcMet against 7 and 17 h for 5'-GMP for 1 and 3, respectively). To further examine the kinetic preference, 1-methylcytosine (1-MeCyt) analogs were prepared, [SP-4-2]-[PtCl(1-Me-Cyt)(NH3)(L)]+ (L=NH3, 2; L=quinoline, 4). The -MeCyt compounds, 2 and 4, resulted in slower rates of substitution by both 5'-GMP and N-AcMet in comparison to 1 and 3 (estimated half-lives for N-AcMet of 5 and 13.5 h and for 5'-GMP of 6 and 14 h for 2 and 4, respectively). Interestingly in this case, however, no selectivity for the sulfur site was observed, a possible explanation being that molecular recognition across the square plane enhances the rate of reaction with 5'-GMP. The affinity of 3 towards S-donor ligands was exploited to remove zinc from the zinc-finger site of the C-terminal finger of the HIV-nucleocapsid protein, NCp7. The ability to eject zinc further suggested the biological antiviral application of [SP-4-2]-[PtCl(nucleobase)(NH3)(L)]+. A preliminary survey against HIV and herpes viruses indeed showed encouraging results with some antiviral specificity, dependent on the exact nature of the compound. The initial results suggest consideration of [SP-4-2]-[PtCl(nucleobase)(NH3)(L)]+ as a novel antiviral chemotype.

Anti-HIV Agents↗
PubMed2000

Multiple retinal arteriolar occlusions associated with coexisting primary antiphospholipid syndrome and factor V Leiden mutation.

PURPOSE: To investigate a case of a young woman with both primary antiphospholipid syndrome and factor V Leiden mutation who developed multiple retinal arteriolar occlusions. METHOD: Case report of a 25-year-old woman with history and laboratory tests confirming the diagnosis of both primary antiphospholipid syndrome and factor V Leiden mutation who presented with blurred vision in both eyes. RESULTS: Multiple retinal arteriolar occlusions were observed in both of her eyes. The patient was treated first with heparin and then with warfarin. CONCLUSIONS: Primary antiphospholipid syndrome and factor V Leiden mutation, as well as other forms of thrombophilia, should be considered in the differential diagnosis of unexplained retinal vascular occlusions. The coexistence of several thrombophilic disorders may carry a particularly high risk for thrombotic manifestations.

Activated Protein C Resistance↗
PubMed2000

Frontotemporal dementia.

Frontotemporal dementia (FTD) is a unique neurodegenerative disease that can be differentiated from Alzheimer's disease and other diseases that result in cognitive complaints. The primary anatomic focus of degeneration determines the clinical presentation, which can vary from aphasia to behavioral symptoms. Expanding knowledge about the genetics and biochemistry of FTD may lead to specific treatments.

Aged↗
PubMed2000

Longitudinal changes in the contribution of genetic and environmental influences to symptoms of depression in older male twins.

Genetically informative longitudinal data on self-reported symptoms of depression allow for an investigation of the causes of stability and change in depression symptoms throughout adult life. In this report, the authors investigated the relative contribution of genetic and environmental influences to symptoms of depression in 83 monozygotic and 84 dizygotic male twin pairs from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study. Participants first completed the Center for Epidemiologic Studies-Depression (CES-D) scale in 1985-1986 and again during 1995-1997. Mean age of twins at baseline was 63 years, range 59 to 70. From cross-sectional genetic analyses we estimated the heritability of CES-D to be 25% (95% confidence interval [CI], 11%-39%) at baseline and 55% (95% CI, 40%-71%) at follow-up. Fitting longitudinal genetic models to the two-wave data, we found that stability of symptoms over the 10-year follow-up was due primarily to continuity of genetic influences.

Adult↗
PubMed2000

Corpus cavernosum as an alternative means of intravenous access in the emergency setting.

BACKGROUND: The present study was designed to investigate the feasibility of using the corpus cavernosum as an alternative means of intravenous access in the emergency setting. METHODS: The feasibility of achieving the infusion flow rates was first ascertained using direct intracavernous infusion of normal saline. The effect of atropine and adrenaline when given via this route was then studied. Hypovolaemic shock was then induced in dogs who were then actively resuscitated via this route using normal saline, Haemaccel and whole blood. RESULTS: Infusion flow rates were achieved for normal saline of 32.3, 50.3 and 67.3 mL per min at 100, 200 and 300 mmHg pressure, respectively. The peak effects of atropine and adrenaline via this route were seen at approximately 1 min after injection. Resuscitation using this method was uniformly successful in all dogs via the corpus cavernosum, with all reaching or exceeding their premorbid central venous pressure (CVP), and approaching or reaching their premorbid mean arterial pressure (MAP). In comparison the control dog's CVP and MAP did not rise during the period of observation after it was bled. CONCLUSIONS: The corpus cavernosum is a practical alternative means of intravenous access in the emergency setting in the dog model.

Adrenergic Agonists↗
PubMed2000

Oral health problems and significant weight loss among community-dwelling older adults.

BACKGROUND: Studies of hospitalized and institutionalized older adults suggest a relationship between poor oral health and subsequent weight loss. Given the association between weight loss and subsequent mortality and morbidity, we evaluated how oral health problems contributed to significant weight loss over a 1-year period among a representative sample of community-dwelling older adults. METHODS: The study population consisted of 563 adults aged 70 years and older living at home in rural and urban areas in six New England states. Baseline data included information regarding health status, functional status, physical activity, disease diagnoses, lifestyle behaviors, and cognitive and affective status. Dentists performed oral health assessments. One year later, participants were called and asked questions regarding their health and dietary practices and their current weight. RESULTS: Over the 1-year period of follow-up, approximately one third of the sample had lost 4% or more of their previous total body weight; 6% of men and 11% of women lost 10% or more of their previous body weight. Of the subjects, 37% were edentulous; most of these individuals wore full dentures. With gender, income, advanced age, and baseline weight controlled for, edentulousness remained an independent risk factor for significant weight loss (odds ratio 1.63 for 4% weight loss and 2.03 for 10% weight loss). Individuals with increasing numbers of posterior teeth and functional units were at slightly lower risk for weight loss; however, these associations did not reach statistical significance. CONCLUSIONS: Dentate status is an important risk factor for clinically significant weight loss among community-dwelling older adults.

Aged↗
PubMed2000

Social support for spouse caregivers of persons with dementia.

OBJECTIVES: This study analyzes the value of simultaneously taking helper and caregiver characteristics into account when examining social support received by spouse caregivers of persons with dementia. This study questions whether sources and types of received support vary by the gender and relationship of the helper and/or by the caregiver's race and gender. METHODS: Drawing on a sample of 210 spouse caregivers of persons with dementia, the Generalized Estimating Equation (GEE) method was used to estimate a population-average logistic regression model to address cross-level helper and caregiver interactions. RESULTS: Results indicate that helper and caregiver characteristics interact in complex ways. White male caregivers are more likely to receive emotional support from adult children and to receive practical assistance from formal sources compared with other types of support and to other race-gender caregiver groups. DISCUSSION: Description of social status characteristics of caregivers as determinants of their social network may be less fruitful in understanding the benefits of social support than a focus on which helpers assist with what kinds of task for which groups of caregivers.

Activities of Daily Living↗
PubMed2000

The morphology of human pronuclear embryos is positively related to blastocyst development and implantation.

Human embryos are selected for transfer using morphology at the cleaving and blastocyst stages. Zygote morphology has been related to implantation and pregnancy. The aim of this study was to relate pronuclear morphology to blastocyst development. Zygotes were scored according to distribution and size of nucleoli within each nucleus. Zygotes displaying equality between the nuclei had 49.5% blastocyst formation and those with unequal sizes, numbers or distribution of nucleoli had 28% blastocyst formation. Cleaving embryos that were selected initially by zygote morphology and secondarily by morphology on day 3 had increased implantation (IR) and pregnancy rates (PR; 31 and 57%), compared with those selected by morphology alone (19 and 33% respectively; P: < 0.01). There was a significant difference between zygote-scored and non-scored cycles on day 3 (PR: 57 versus 33%; IR: 31 versus 19%) and on day 5 (PR: 73 versus 58%; IR; 52 versus 39%). Zygote scoring can maintain pregnancy rates for both day 3 and day 5 transfers, increase implantation rates and reduce the numbers of embryos required to achieve a pregnancy.

Adult↗
PubMed2000

Hospitalization of homeless persons with tuberculosis in the United States.

OBJECTIVES: This study assessed whether homeless patients are hospitalized for tuberculosis (TB) more frequently and longer than other patients and possible reasons for this. METHODS: We prospectively studied hospitalizations of a cohort of TB patients. RESULTS: HIV-infected homeless patients were hospitalized more frequently than other patients, while homeless patients who had no insurance or whose insurance status was unknown were hospitalized longer. Hospitalization cost $2000 more per homeless patient than for other patients. The public sector paid nearly all costs. CONCLUSIONS: Homeless people may be hospitalized less if given access to medical care that provides early detection and treatment of TB infection and disease and HIV infection. Providing housing and social services may also reduce hospital utilization and increase therapy completion rates.

Adolescent↗