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1.
J Fam Pract ; 65(12): 889-899, 2016 12.
Article in English | MEDLINE | ID: mdl-28149972

ABSTRACT

The causes are diverse--from rhinitis and rhinosinusitis to drugs and structural/mechanical abnormalities. Here's how to provide patients with relief.


Subject(s)
Chronic Disease/drug therapy , Family Practice/standards , Nasal Obstruction/diagnosis , Nasal Obstruction/drug therapy , Practice Guidelines as Topic , Rhinitis, Allergic, Perennial/drug therapy , Sinusitis/drug therapy , Humans , Rhinitis, Allergic, Perennial/complications , Risk Assessment , Sinusitis/complications
2.
Contemp Clin Trials ; 36(2): 515-26, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24080100

ABSTRACT

BACKGROUND: Evidence suggests that periodontitis is associated with prevalent and incident type 2 diabetes mellitus (T2DM), raising the question of whether periodontitis treatment may improve glycemic control in patients with T2DM. Meta-analyses of mostly small clinical trials suggest that periodontitis treatment results in a modest reduction in glycosylated hemoglobin (Hb) A1c. PURPOSE: The purpose of the Diabetes and Periodontal Therapy Trial (DPTT) was to determine if periodontal treatment reduces HbA1c in patients with T2DM and periodontitis. METHODS: DPTT was a phase-III, single-masked, multi-center, randomized trial with a planned enrollment of 600 participants. Participants were randomly assigned to receive periodontal treatment immediately (Treatment Group) or after 6 months (Control Group). HbA1c values and clinical periodontal measures were determined at baseline and 3 and 6 months following randomization. Medication usage and dosing were assessed at each visit. Periodontal treatment consisted of scaling and root planing for a minimum of two 90-minute sessions, plus the use of an antibacterial mouth rinse for at least 32 days afterwards. The primary outcome was change in HbA1c from baseline to 6 months and the trial was powered to detect a between-group difference of 0.6%. Secondary outcomes included changes in periodontal clinical measures, fasting plasma glucose, the Homeostasis Model Assessment (HOMA2) and the need for rescue diabetes or periodontal therapy. CONCLUSION: Dental and medical researchers collaborated to recruit, treat and monitor participants with two chronic diseases to determine if treatment of one condition affects the status of the other.


Subject(s)
Diabetes Mellitus, Type 2/complications , Glycated Hemoglobin/analysis , Periodontitis/therapy , Blood Glucose/analysis , Clinical Protocols , Diabetes Mellitus, Type 2/blood , Humans , Mouthwashes/therapeutic use , Periodontitis/blood , Periodontitis/etiology , Severity of Illness Index , Single-Blind Method
3.
Ophthalmology ; 114(6): 1058-64, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17397925

ABSTRACT

PURPOSE: To determine the 9-year incidence of open-angle glaucoma (OAG) in African-descent participants of the Barbados Eye Studies. DESIGN: Nine-year cohort study with 81% to 85% participation. PARTICIPANTS: Three thousand two hundred twenty-two persons without definite OAG at baseline, at risk of developing OAG at follow-up. METHODS: The standardized protocol included automated perimetry and various ophthalmic measurements, with a comprehensive ophthalmologic examination for those referred. Fundus photographs were evaluated independently by masked graders. Incidence was estimated by the product-limit approach. Relative risk (RR) ratios with 95% confidence intervals (CIs) were based on Cox regression models with discrete time. MAIN OUTCOME MEASURE: Nine-year incidence of definite OAG, based on the development of visual field defects and glaucomatous optic neuropathy, with ophthalmologic confirmation. RESULTS: The 9-year incidence of definite OAG was 4.4% (95% CI, 3.7%-5.2%), or an average of 0.5%/year, based on 125 new cases. Incidence increased greatly with age, from 2.2% at ages 40 to 49 years to 7.9% at ages 70 years or older, and tended to be higher in men than women (4.9% vs. 4.1%; RR, 1.3; 95% CI, 0.9-1.8). More than half (53%) of new cases were undetected, and of these, one third had intraocular pressure of 21 mmHg or less. When 141 persons developing suspected/probable OAG were considered, the total incidence was 9.4% (8.4%-10.6%), averaging approximately 1%/year, also increasing with age, and significantly higher in men than women (10.7% vs. 8.6%; RR, 1.31; 95% CI, 1.02-1.67). CONCLUSIONS: These new data provide a measure of the long-term risk of OAG in an African-descent population, which is markedly higher than in persons of European ancestry. Results confirm the increased risk with age and in men. The incidence data fill a gap in our understanding of OAG risk and have implications for public health policy and planning; they also will allow the study of factors related to the risk of OAG development.


Subject(s)
Black People/ethnology , Glaucoma, Open-Angle/ethnology , Adult , Aged , Aged, 80 and over , Barbados/epidemiology , Female , Glaucoma, Open-Angle/diagnosis , Humans , Incidence , Intraocular Pressure , Longitudinal Studies , Male , Middle Aged , Risk Factors , Tonometry, Ocular , Vision Disorders/diagnosis , Visual Field Tests , Visual Fields
4.
Appl Environ Microbiol ; 72(7): 4569-75, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16820445

ABSTRACT

Only limited information is available concerning the effects of low-shear modeled microgravity (LSMMG) on cell function and morphology. We examined the behavior of Saccharomyces cerevisiae grown in a high-aspect-ratio vessel, which simulates the low-shear and microgravity conditions encountered in spaceflight. With the exception of a shortened lag phase (90 min less than controls; P < 0.05), yeast cells grown under LSMMG conditions did not differ in growth rate, size, shape, or viability from the controls but did differ in the establishment of polarity as exhibited by aberrant (random) budding compared to the usual bipolar pattern of controls. The aberrant budding was accompanied by an increased tendency of cells to clump, as indicated by aggregates containing five or more cells. We also found significant changes (greater than or equal to twofold) in the expression of genes associated with the establishment of polarity (BUD5), bipolar budding (RAX1, RAX2, and BUD25), and cell separation (DSE1, DSE2, and EGT2). Thus, low-shear environments may significantly alter yeast gene expression and phenotype as well as evolutionary conserved cellular functions such as polarization. The results provide a paradigm for understanding polarity-dependent cell responses to microgravity ranging from pathogenesis in fungi to the immune response in mammals.


Subject(s)
Gene Expression Regulation, Fungal , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/growth & development , Weightlessness Simulation , Biomechanical Phenomena , Bioreactors , Cell Polarity , Culture Media , Phenotype , Reverse Transcriptase Polymerase Chain Reaction , Saccharomyces cerevisiae/classification , Saccharomyces cerevisiae/metabolism , Space Flight
5.
Mol Plant Microbe Interact ; 18(4): 343-53, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15828686

ABSTRACT

Seven new genes controlled by the quorum-sensing signal molecule N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) have been identified in Erwinia carotovora subsp. carotovora. Using TnphoA as a mutagen, we enriched for mutants defective in proteins that could play a role in the interaction between E. carotovora subsp. carotovora and its plant hosts, and identified NipEcc and its counterpart in E. carotovora subsp. atroseptica. These are members of a growing family of proteins related to Nep1 from Fusarium oxysporum which can induce necrotic responses in a variety of dicotyledonous plants. NipEcc produced necrosis in tobacco, NipEca affected potato stem rot, and both affected virulence in potato tubers. In E. carotovora subsp. carotovora, nip was shown to be subject to weak repression by the LuxR family regulator, EccR, and may be regulated by the negative global regulator RsmA.


Subject(s)
4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/metabolism , Gene Expression Regulation, Bacterial , Genes, Bacterial , Homoserine/analogs & derivatives , Homoserine/metabolism , Pectobacterium carotovorum/genetics , Amino Acid Sequence , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , DNA Transposable Elements , Genetic Complementation Test , Molecular Sequence Data , Mutagenesis , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Sequence Alignment , Solanum tuberosum/genetics
6.
Mol Plant Microbe Interact ; 17(8): 880-7, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15305609

ABSTRACT

Many gram-negative bacteria employ N-acylhomoserine lactones (AHL) to regulate diverse physiological processes in concert with cell population density (quorum sensing [QS]). In the plant pathogen Erwinia carotovora, the AHL synthesized via the carI/expI genes are responsible for regulating the production of secreted plant cell wall-degrading exoenzymes and the antibiotic carbapen-3-em carboxylic acid. We have previously shown that targeting the product of an AHL synthase gene (yenI) from Yersinia enterocolitica to the chloroplasts of transgenic tobacco plants caused the synthesis in planta of the cognate AHL signaling molecules N-(3-oxohexanoyl)-L-homoserine lactone (3-oxo-C6-HSL) and N-hexanoylhomoserine lactone (C6-HSL), which in turn, were able to complement a carI-QS mutant. In the present study, we demonstrate that transgenic potato plants containing the yenI gene are also able to express AHL and that the presence and level of these AHL in the plant increases susceptibility to infection by E. carotovora. Susceptibility is further affected by both the bacterial level and the plant tissue under investigation.


Subject(s)
Carboxylic Ester Hydrolases/metabolism , Pectobacterium carotovorum/pathogenicity , Solanum tuberosum/genetics , Chromatography, Thin Layer , Colony Count, Microbial , Gene Expression Regulation, Bacterial , Pectobacterium carotovorum/genetics , Plant Diseases/microbiology , Plant Tubers/genetics , Plant Tubers/growth & development , Plants, Genetically Modified , Solanum tuberosum/growth & development , Solanum tuberosum/microbiology
7.
Proc Natl Acad Sci U S A ; 101(30): 11105-10, 2004 Jul 27.
Article in English | MEDLINE | ID: mdl-15263089

ABSTRACT

The bacterial family Enterobacteriaceae is notable for its well studied human pathogens, including Salmonella, Yersinia, Shigella, and Escherichia spp. However, it also contains several plant pathogens. We report the genome sequence of a plant pathogenic enterobacterium, Erwinia carotovora subsp. atroseptica (Eca) strain SCRI1043, the causative agent of soft rot and blackleg potato diseases. Approximately 33% of Eca genes are not shared with sequenced enterobacterial human pathogens, including some predicted to facilitate unexpected metabolic traits, such as nitrogen fixation and opine catabolism. This proportion of genes also contains an overrepresentation of pathogenicity determinants, including possible horizontally acquired gene clusters for putative type IV secretion and polyketide phytotoxin synthesis. To investigate whether these gene clusters play a role in the disease process, an arrayed set of insertional mutants was generated, and mutations were identified. Plant bioassays showed that these mutants were significantly reduced in virulence, demonstrating both the presence of novel pathogenicity determinants in Eca, and the impact of functional genomics in expanding our understanding of phytopathogenicity in the Enterobacteriaceae.


Subject(s)
Genome, Bacterial , Pectobacterium carotovorum/genetics , Pectobacterium carotovorum/pathogenicity , Plant Diseases/microbiology , Solanum tuberosum/microbiology , Virulence/genetics , Base Sequence , Biological Evolution , DNA Primers , Environment , Molecular Sequence Data , Polymerase Chain Reaction
8.
Ann Acad Med Singap ; 33(1): 44-8, 2004 Jan.
Article in English | MEDLINE | ID: mdl-15008561

ABSTRACT

The Correction of Myopia Evaluation Trial (COMET), a multicentre clinical trial based in 4 schools of optometry in the United States, evaluated the effect of progressive addition lenses versus single vision lenses on myopia progression in an ethnically diverse group of 469 myopic children aged 6 to 11 years. Completion of the clinical trial phase of the study provides an opportunity to evaluate aspects of the study design that contribute to its success. This article describes aspects of the study design that were influential in ensuring the smooth conduct of COMET. These include a dedicated team of investigators, an organisational structure with strong leadership and an independent Co-ordinating Centre, regular communication among investigators, flexible and creative approaches to recruitment and retention, sensitivity to concerns for child safety and child participation, and methods for enhancing and monitoring data reliability. The experience with COMET has provided a number of valuable lessons for all aspects of the study design that should benefit the development and implementation of future clinical trials, particularly those done in similar populations of children. The use of a carefully designed protocol using standard methods by dedicated members of the study team is essential in ensuring achievement of the study aims.


Subject(s)
Lenses , Myopia/prevention & control , Randomized Controlled Trials as Topic , Research Design , Disease Progression , Humans , Multicenter Studies as Topic , Retrospective Studies
9.
Neurology ; 60(12): 1923-30, 2003 Jun 24.
Article in English | MEDLINE | ID: mdl-12821734

ABSTRACT

OBJECTIVE: To determine whether post Lyme syndrome (PLS) is antibiotic responsive. METHODS: The authors conducted a single-center randomized double-masked placebo-controlled trial on 55 patients with Lyme disease with persistent severe fatigue at least 6 or more months after antibiotic therapy. Patients were randomly assigned to receive 28 days of IV ceftriaxone or placebo. The primary clinical outcomes were improvement in fatigue, defined by a change of 0.7 points or more on an 11-item fatigue questionnaire, and improvement in cognitive function (mental speed), defined by a change of 25% or more on a test of reaction time. The primary laboratory outcome was an experimental measure of CSF infection, outer surface protein A (OspA). Outcome data were collected at the 6-month visit. RESULTS: Patients assigned to ceftriaxone showed improvement in disabling fatigue compared to the placebo group (rate ratio, 3.5; 95% CI, 1.50 to 8.03; p = 0.001). No beneficial treatment effect was observed for cognitive function or the laboratory measure of persistent infection. Four patients, three of whom were on placebo, had adverse events associated with treatment, which required hospitalization. CONCLUSIONS: Ceftriaxone therapy in patients with PLS with severe fatigue was associated with an improvement in fatigue but not with cognitive function or an experimental laboratory measure of infection in this study. Because fatigue (a nonspecific symptom) was the only outcome that improved and because treatment was associated with adverse events, this study does not support the use of additional antibiotic therapy with parenteral ceftriaxone in post-treatment, persistently fatigued patients with PLS.


Subject(s)
Ceftriaxone/therapeutic use , Cognition Disorders/drug therapy , Fatigue/drug therapy , Lipoproteins , Lyme Disease/complications , Lyme Neuroborreliosis/drug therapy , Adult , Aged , Antigens, Bacterial/blood , Antigens, Surface/blood , Bacterial Outer Membrane Proteins/blood , Bacterial Vaccines , Borrelia burgdorferi/immunology , Ceftriaxone/administration & dosage , Chronic Disease , Cognition Disorders/etiology , Double-Blind Method , Fatigue/etiology , Female , Humans , Lyme Disease/drug therapy , Lyme Neuroborreliosis/psychology , Male , Middle Aged , Neuropsychological Tests , Pain/drug therapy , Pain/etiology , Psychomotor Performance , Severity of Illness Index , Treatment Outcome
10.
Control Clin Trials ; 22(5): 573-92, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11578789

ABSTRACT

The Correction of Myopia Evaluation Trial (COMET) is a multicenter, randomized, double-masked, controlled clinical trial evaluating whether there is a difference in the progression of myopia between children wearing progressive addition lenses (PALs) versus conventional single vision lenses (SVLs), as measured by cycloplegic autorefraction. Axial length, measured by A-scan ultrasonography, is an additional outcome measure. To meet the recruitment goal of 450 participants, eligible children ages 6-11 years (inclusive) with myopia in both eyes (spherical equivalent between -1.25 diopters (D) and -4.50 D, astigmatism < or = 1.50 D, and anisometropia < 1.00 D) were recruited at four clinical centers between September 1997 and September 1998. Children who participated were assigned to receive PALs (Varilux Comfort with a +2.00 D addition) or SVLs. Measures include standardized cycloplegic autorefraction (Nidek ARK700A autorefractor), axial length (Sonomed A2500 ultrasound), subjective refraction (Marco TRS system), visual acuity (modified Early Treatment Diabetic Retinopathy Study protocol), accommodation (Canon R-1), and phoria (cover test and Maddox rod). Outcome measures are collected annually; adherence is assessed and prescriptions updated semiannually. Participants are being followed for at least 3 years. COMET enrolled 469 children. Their mean age is 9.3 years (range 6-11 years); 52% are female. COMET children are ethnically diverse, according to a self-report with 46% White, 26% African American, 14% Hispanic, and 8% Asian. Best-corrected visual acuity is better than 20/32 in both eyes. Baseline mean (+/-SD) cycloplegic refractive correction is -2.38 D (+/-0.81) in the right eye and -2.40 D (+/-0.82) in the left eye; mean (+/-SD) axial length is 24.1 mm (+/-0.7) in both eyes. Follow-up of these children will provide a first step in answering the important question of whether there are effective means to slow myopia progression. Study results should be applicable to a large proportion of children with myopia. The study will also provide useful information on myopia progression in children wearing conventional single vision lenses.


Subject(s)
Eyeglasses , Myopia/therapy , Child , Double-Blind Method , Female , Humans , Male , Quality Assurance, Health Care , Visual Acuity
11.
Ophthalmology ; 108(10): 1751-6, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11581045

ABSTRACT

OBJECTIVE: To determine the prevalence and causes of low vision and blindness in a predominantly black population. DESIGN: Population-based prevalence study of a simple random sample of Barbados-born citizens aged 40 to 84 years. PARTICIPANTS: Four thousand seven hundred nine persons (84% participation). METHODS: The standardized protocol included best-corrected visual acuity (with a Ferris-Bailey chart), automated perimetry, lens gradings (LOCS II), and an interview. Participants with visual acuity of worse than 20/30, other positive findings, and a 10% sample also had an ophthalmologic examination that evaluated the cause and extent of vision loss (resulting from that cause), if any. MAIN OUTCOME MEASURES: Low vision and blindness were defined as visual acuity in the better eye between 6/18 and 6/120 and visual acuity worse than 6/120, respectively (World Health Organization [WHO] criteria). RESULTS: Of the 4631 participants with complete examinations, 4314 (93%) reported their race as black, 184 (4%) reported their race as mixed (black and white), and 133 (3%) reported their race as white or other. Low vision was found in 5.9% of the black, 2.7% of the mixed, and 3.0% of white or other participants. Bilateral blindness was similar for black and mixed race participants (1.7% and 1.6%, respectively) and was not found in whites. Among black and mixed participants, the prevalence of low vision increased with age (from 0.3% at 40-49 years to 26.8% at 80 years or older). The prevalence of blindness was higher (P < 0.001) for men than women at each age group (0.5% versus 0.3% at ages 40-49 and 10.9% versus 7.3% at 80 years or more). Sixty percent of blindness was due to open-angle glaucoma and age-related cataract, each accounting for more than one fourth of cases. Other major causes were optic atrophy or neuropathy and macular and other retinal diseases. Few cases of blindness were due to diabetic retinopathy (1.4%), and none were due to age-related macular degeneration. CONCLUSIONS: Using the WHO criteria, prevalence of visual impairment was high in this African-origin population, particularly at older ages. Most blindness was due to open-angle glaucoma and cataract, with open-angle glaucoma causing a higher proportion of blindness than previously reported. The increased prevalence of blindness in men may be due to the increased male prevalence of glaucoma in this population and warrants further investigation. Results underline the need for blindness prevention programs, with emphasis on effective treatment of age-related cataract and enhancing strategies for early detection and treatment of open-angle glaucoma.


Subject(s)
Black People , Blindness/ethnology , Cataract/ethnology , Glaucoma, Open-Angle/ethnology , Vision, Low/ethnology , White People , Adult , Age Distribution , Aged , Aged, 80 and over , Barbados/epidemiology , Blindness/etiology , Cataract/complications , Female , Glaucoma, Open-Angle/complications , Humans , Male , Middle Aged , Prevalence , Risk Factors , Sex Distribution , Vision, Low/etiology , Visual Acuity
12.
Appl Environ Microbiol ; 67(9): 4070-6, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11526007

ABSTRACT

Current identification methods for the soft rot erwinias are both imprecise and time-consuming. We have used the 16S-23S rRNA intergenic transcribed spacer (ITS) to aid in their identification. Analysis by ITS-PCR and ITS-restriction fragment length polymorphism was found to be a simple, precise, and rapid method compared to current molecular and phenotypic techniques. The ITS was amplified from Erwinia and other genera using universal PCR primers. After PCR, the banding patterns generated allowed the soft rot erwinias to be differentiated from all other Erwinia and non-Erwinia species and placed into one of three groups (I to III). Group I comprised all Erwinia carotovora subsp. atroseptica and subsp. betavasculorum isolates. Group II comprised all E. carotovora subsp. carotovora, subsp. odorifera, and subsp. wasabiae and E. cacticida isolates, and group III comprised all E. chrysanthemi isolates. To increase the level of discrimination further, the ITS-PCR products were digested with one of two restriction enzymes. Digestion with CfoI identified E. carotovora subsp. atroseptica and subsp. betavasculorum (group I) and E. chrysanthemi (group III) isolates, while digestion with RsaI identified E. carotovora subsp. wasabiae, subsp. carotovora, and subsp. odorifera/carotovora and E. cacticida isolates (group II). In the latter case, it was necessary to distinguish E. carotovora subsp. odorifera and subsp. carotovora using the alpha-methyl glucoside test. Sixty suspected soft rot erwinia isolates from Australia were identified as E. carotovora subsp. atroseptica, E. chrysanthemi, E. carotovora subsp. carotovora, and non-soft rot species. Ten "atypical" E. carotovora subsp. atroseptica isolates were identified as E. carotovora subsp. atroseptica, subsp. carotovora, and subsp. betavasculorum and non-soft rot species, and two "atypical" E. carotovora subsp. carotovora isolates were identified as E. carotovora subsp. carotovora and subsp. atroseptica.


Subject(s)
DNA, Ribosomal Spacer/genetics , Erwinia/classification , Plant Diseases/microbiology , Polymerase Chain Reaction/methods , Bacterial Typing Techniques/methods , Erwinia/genetics , Polymorphism, Restriction Fragment Length , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 23S/genetics
13.
Ophthalmology ; 107(10): 1803, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11013172
14.
Lett Appl Microbiol ; 30(4): 330-5, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10792657

ABSTRACT

A PCR-based method was developed for the simultaneous detection and quantification of the potato pathogen Erwinia carotovora subsp. atroseptica (Eca) on potato tubers. The method incorporates a competitor PCR template cloned into Escherichia coli in vector pGEM-T (E. coli 4R l/l). Predetermined numbers of E. coli 4R were added to potato peel extract, either pre-inoculated with Eca or from naturally contaminated tubers, and Eca numbers estimated by comparing the ratio of products generated from Eca target DNA and competitor template DNA following PCR. Estimates of Eca numbers were consistent with counts obtained on crystal violet pectate medium and immunofluorescence colony staining. Unlike these methods, however, the PCR-based method is not affected by the presence of other erwinias and saprophytes and is able to detect all serogroups of Eca. Based on this method, a key was produced relating product ratios, obtained following PCR from contaminated tuber stocks, to the likelihood of blackleg disease incidence. This is the first quantitative PCR-based detection method described for Eca and is the first for any bacterial plant pathogen to incorporate a DNA extraction control.


Subject(s)
Pectobacterium carotovorum/growth & development , Pectobacterium carotovorum/isolation & purification , Polymerase Chain Reaction/methods , Solanum tuberosum/microbiology , Colony Count, Microbial , Escherichia coli/genetics , Genetic Vectors , Pectobacterium carotovorum/genetics , Plant Diseases/microbiology , Templates, Genetic
15.
Biochim Biophys Acta ; 1491(1-3): 161-76, 2000 Apr 25.
Article in English | MEDLINE | ID: mdl-10760578

ABSTRACT

Mammalian Elongin C is a 112-amino acid protein that binds to the von Hippel-Lindau (VHL) tumor suppressor and to Elongin A, the transcriptionally active subunit of the RNA polymerase II elongation factor, SIII. It is conserved in eukaryotic cells, as homologs have been identified in Saccharomyces cerevisiae, Drosophila melanogaster and Caenorhabditis elegans. The mammalian protein is thought to function as part of a ubiquitin targeting E3 ligase, yet the function in yeast has not been determined. In this report we examine the role of Elongin C in yeast and establish that yeast Elongin C may function in a mode distinct from its role as an E3 ligase. The RNA is expressed ubiquitously, albeit at low levels. Two hybrid analyses demonstrate that Elongin C in yeast interacts with a specific set of proteins that are involved in the stress response. This suggests a novel role for Elongin C and provides insights into additional potential functions in mammalian cells.


Subject(s)
Carrier Proteins , Drosophila Proteins , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae/metabolism , Transcription Factors/metabolism , AMP-Activated Protein Kinases , Amino Acid Sequence , Caenorhabditis elegans Proteins , Cell Cycle Proteins/metabolism , Consensus Sequence , Elongin , Ligases/metabolism , Molecular Sequence Data , Mutagenesis, Site-Directed , Plasmids , Protein Kinases/metabolism , S-Phase Kinase-Associated Proteins , Saccharomyces cerevisiae/genetics , Ubiquitin-Protein Ligases
16.
Arch Ophthalmol ; 118(3): 351-8, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10721957

ABSTRACT

OBJECTIVES: To describe a case-control study of risk factors for neovascular and non-neovascular age-related macular degeneration (AMD) and to present findings on associations with systemic hypertension and cardiovascular disease. METHODS: Participants with and without neovascular and non-neovascular AMD were recruited from 11 ophthalmology practices in the New York, NY, metropolitan area. Comprehensive data collection included (1) a standardized interview, (2) blood pressure measurements, and (3) blood samples. Cases and controls were classified from fundus photograph gradings. Polychotomous logistic regression analyses were used to evaluate associations. RESULTS: Classification of 1222 sets of available photographs resulted in the inclusion of a neovascular case group (n = 182), a non-neovascular case group (n = 227), and a control group (n = 235). Neovascular AMD was positively associated with diastolic blood pressure greater than 95 mm Hg (odds ratio [OR] = 4.4), self-reported use of potent antihypertensive medication (OR = 2.1), physician-reported history of hypertension (OR = 1.8), use of antihypertensive medication (OR = 2.5), combinations of self-reported and physician-reported data on hypertension and its treatment (OR = 1. 7), high-density lipoprotein level (OR = 2.3), and dietary cholesterol level (OR = 2.2). Non-neovascular AMD was unrelated to hypertension or cholesterol level. No associations were found between either AMD type and other definitions of hypertension or other cardiovascular disease. CONCLUSIONS: These findings suggest that neovascular AMD is associated with moderate to severe hypertension, particularly among patients receiving antihypertensive treatment. They also support the hypotheses that neovascular and non-neovascular AMD may have a different pathogenesis and that neovascular AMD and hypertensive disease may have a similar underlying systemic process.


Subject(s)
Cardiovascular Diseases/complications , Hypertension/complications , Macular Degeneration/etiology , Retinal Neovascularization/etiology , Aged , Antihypertensive Agents/therapeutic use , Blood Pressure , Cardiovascular Diseases/blood , Case-Control Studies , Cholesterol, HDL/blood , Female , Humans , Hypertension/blood , Hypertension/drug therapy , Intraocular Pressure , Macular Degeneration/blood , Male , Middle Aged , Odds Ratio , Risk Factors
17.
J Appl Microbiol ; 87(5): 770-81, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10594720

ABSTRACT

A number of phenotypic and molecular fingerprinting techniques, including physiological profiling (Biolog), restriction fragment length polymorphism (RFLP), enterobacterial repetitive intergenic consensus (ERIC) and a phage typing system, were evaluated for their ability to differentiate between 60 strains of Erwinia carotovora ssp. atroseptica (Eca) from eight west European countries. These techniques were compared with other fingerprinting techniques, random amplified polymorphic DNA (RAPD) and Ouchterlony double diffusion (ODD), previously used to type this pathogen. Where possible, data were represented as dendrograms and groups/subgroups of strains identified. Simpson's index of diversity (Simpson's D) was used to compare groupings obtained with the different techniques which, with the exception of Biolog, gave values of 0.46 (RFLP), 0. 39 (ERIC), 0.83 (phage typing), 0.82 (RAPD) and 0.26 (ODD). Of the techniques tested, phage typing showed the highest level of diversity within Eca, and this technique will now form the basis of studies into the epidemiology of blackleg disease.


Subject(s)
Bacterial Typing Techniques , Molecular Probe Techniques , Pectobacterium carotovorum/classification , Bacteriophage Typing , Genetic Variation , Pectobacterium carotovorum/genetics , Phenotype , Phylogeny , Polymorphism, Restriction Fragment Length , Random Amplified Polymorphic DNA Technique , Serotyping
18.
Ophthalmology ; 106(11): 2144-53, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10571351

ABSTRACT

OBJECTIVES: The Early Manifest Glaucoma Trial (EMGT) will evaluate the effectiveness of reducing intraocular pressure (IOP) in early, previously untreated open-angle glaucoma. Its secondary aims are to explore factors related to glaucoma progression and to study the natural history of the disease. This article describes the EMGT design and presents baseline data. DESIGN: Randomized, clinical trial. PARTICIPANTS: Newly diagnosed patients 50 to 80 years of age with early glaucomatous visual field defects were mainly identified from a population-based screening of more than 44,000 residents of Malmö and Helsingborg, Sweden. Exclusion criteria were advanced visual field loss; mean IOP greater than 30 mmHg or any IOP greater than 35 mmHg; visual acuity less than 0.5; and inability to complete follow-up protocols. INTERVENTIONS: After informed consent, patients were randomized to treatment or no initial treatment with close follow-up. Treated patients had laser trabeculoplasty and started receiving topical betaxolol twice daily in eligible eyes. Follow-up visits include computerized perimetry and tonometry every 3 months and fundus photography every 6 months. Decisions to change or begin treatment are made jointly with the patient when EMGT progression occurs and also later if clinically needed. MAIN OUTCOME MEASURES: The EMGT progression is defined by sustained increases of visual field loss in three consecutive C30-2 Humphrey tests, as determined from computer-based analyses, or by optic disc changes, as determined from flicker chronoscopy and side-by-side comparisons of fundus photographs performed by masked, independent graders. RESULTS: A total of 255 patients were randomized between 1993 and 1997 and will be followed for at least 4 years. All had generally good health status; mean age was 68.1 years, and 66% were women. At baseline, mean IOP was 20.6 mmHg and 80% of eyes had IOP less than 25 mmHg. CONCLUSIONS: The Early Manifest Glaucoma Trial is the first large randomized, clinical trial to evaluate the role of immediate pressure reduction, as compared to no initial reduction, in patients with early glaucoma and normal or moderately elevated IOP. Its results will have implications for: (1) the clinical management of glaucoma; (2) understanding the role of IOP and the natural history of glaucoma; and (3) evaluating the rationale for glaucoma screening.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Betaxolol/therapeutic use , Glaucoma, Open-Angle/therapy , Intraocular Pressure/drug effects , Research Design , Trabeculectomy , Aged , Aged, 80 and over , Disease Progression , Female , Glaucoma, Open-Angle/physiopathology , Humans , Male , Middle Aged , Tonometry, Ocular , Vision Disorders/physiopathology , Visual Acuity , Visual Field Tests , Visual Fields
19.
Ophthalmology ; 106(10): 1893-9, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10519582

ABSTRACT

OBJECTIVE: The distribution of diabetic retinopathy in black populations is largely unknown. The authors present retinopathy data from the predominately black participants of the Barbados Eye Study (BES). DESIGN AND PARTICIPANTS: Prevalence study of 4631 participants based on a random sample of the Barbados population 40 to 84 years of age (84% participation). MAIN OUTCOME MEASURES: Diabetes was defined as self-reported history of physician-diagnosed diabetes or glycosylated hemoglobin greater than 10% (>2 standard deviations above the population mean of persons without a diabetes history). Retinopathy was assessed by independent gradings of 30 degrees color stereo fundus photographs of the disc and macula. RESULTS: Diabetes was present in 19.4% of black (n = 4314), 15.2% of mixed (black and white; n = 184), and 7.5% of white/other (n = 133) self-reported racial groups. In the black/mixed population, regardless of diabetes status, the prevalence of retinopathy was 5.9%. In the 636 black and mixed participants with diabetes, the prevalence of retinopathy was 28.5%: 19.8% had minimum changes, 7.7% had moderate changes, and 0.9% had severe retinopathy. Clinically significant macular edema (CSME) was found in 8.6% of those with diabetes. CONCLUSIONS: In the population of African origin, approximately 1 in 17 persons had retinopathy. Among those with diabetes, 28.5% had retinopathy and 8.6% had CSME. These results highlight the clinical and public health relevance of diabetic retinopathy in the black population.


Subject(s)
Black People , Diabetic Retinopathy/epidemiology , Adult , Age Distribution , Aged , Aged, 80 and over , Barbados/epidemiology , Diabetic Retinopathy/diagnosis , Female , Fundus Oculi , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Photography , Prevalence , Risk Factors , Sex Distribution
20.
Optom Vis Sci ; 76(9): 643-9, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10498006

ABSTRACT

PURPOSE: To estimate the frequency of convergence insufficiency (CI) and its related clinical characteristics among 9- to 13-year-old children. METHODS: Fifth and sixth graders were screened in school settings at three different study sites. Eligible children with 20/30 or better visual acuity, minimal refractive error, no strabismus, and exophoria at near were evaluated according to a standardized protocol to determine the presence and severity of CI. These children were classified according to the presence and number of the following clinical signs: (1) exophoria at near > or =4delta than far, (2) insufficient fusional convergence, and (3) receded nearpoint of convergence. Also, children were classified as accommodative insufficient (AI) if they failed Hofstetter's minimum amplitude formula or had greater than a + 1.00 D lag on Monocular Estimate Method retinoscopy. RESULTS: Of 684 children screened, 468 (68%) were eligible for further evaluation. Of these, 453 had complete data on CI measurements and were classified as: no CI (nonexophoric at near or exophoric at near and < 4delta difference between near and far) (78.6%); low suspect CI (exophoric at near and one clinical sign: exophoria at near > or =4delta than far) (8.4%); high suspect CI (exophoric at near and two clinical signs) (8.8%); and definite CI (exophoric at near and three clinical signs) (4.2%). CI status varied according to ethnicity and study site (p < 0.0005), but not gender. The frequency of AI increased with the number of CI-related signs. For CI children with three signs, 78.9% were classified as also having AI. CONCLUSIONS: These findings suggest that CI (defined as high suspect and definite) is frequent (13%) among fifth and sixth grade children. In addition, there is a high percentage of CI children with an associated AI.


Subject(s)
Convergence, Ocular , Exotropia/epidemiology , Accommodation, Ocular , Adolescent , Black People , California/epidemiology , Chicago/epidemiology , Child , Exotropia/diagnosis , Exotropia/physiopathology , Female , Humans , Male , Philadelphia/epidemiology , Prevalence , Urban Population , White People
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