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Biomedical subjects

G Barnes

Publications and source records attributed to G Barnes.

At least 19 recordsLinked to original sources
PubMed2006

Multi-center evaluation of analytical performance of the microparticle enzyme immunoassay for sirolimus.

OBJECTIVES: This study evaluated the analytical characteristics of the new Abbott microparticle enzyme immunoassay (MEIA) for sirolimus. DESIGN AND METHODS: The protocol consisted of nine sections: evaluation of antibody specificity, linearity, detection limit, quantification limit, endogenous interferents, exogenous interferents, precision, proficiency testing panel, and method comparison. RESULTS: The mean analytical detection limit was 0.68 microg/L. The sirolimus concentration corresponding to a total CV of 20% was 1.5 microg/L. Linearity of response was demonstrated across the dynamic range of the assay. Total precision (CVs) at QC control levels from 5 to 22 microg/L ranged from 5.7 to 12.6%. Assay standardization was found to be in good agreement with LC/MS/MS as compared with target values for spiked sirolimus proficiency samples from an international sirolimus proficiency testing program. Good correlations (R values) of the immunoassay were observed in comparisons to LC/MS/MS. R values tended to be lower in comparisons with LC/UV methods. Across both LC-based methods and all study sites, there was approximately 25% overall positive slope bias due to cross reactivity of the MEIA antibody to metabolites of sirolimus. The assay cross-reactivity to metabolites of sirolimus parent drug ranged from 6 to 63%. Assay interferences were minimal with the exception of hematocrit, which presented a negative relationship to measured sirolimus concentration. CONCLUSIONS: The MEIA demonstrated acceptable analytical characteristics for use for routine monitoring of sirolimus immunosuppressive therapy, and is a viable alternative to HPLC-based methods for sirolimus monitoring.

Calibration↗
PubMed2003

How many positions can we perceptually encode, one or many?

Here we show that our sensitivity for discriminating relative position across the visual field is limited. In experiment 1 we show that we are much worse at detecting a texture defined by the relative position of elements within an array than would be expected if we had access to multiple estimates of relative position across the visual field. In experiment 2 we show that human performance is impaired for positional judgments when there is uncertainty as to which of a number of possible elements is misaligned. This impairment is greater than one would expect from an ideal observer model and greater than that found for a comparable task involving orientation. It is consistent with positional thresholds being determined by only one estimate of relative position. In experiment 3 we estimate the number of suprathreshold positional signals that can be pooled at the same time across the visual field using a standard summation variance paradigm. The results suggest that the human visual system is limited to one estimate of position, but additional estimates can be built up serially over time; however, this process is slow and probably cognitive in nature. These experiments taken as a whole suggest that only one estimate of relative position (i.e. relative to a predefined reference) at a time is accessible at the perceptual level.

Attention↗
PubMed2003

Measurement of serum albumin by capillary zone electrophoresis, bromocresol green, bromocresol purple, and immunoassay methods.

BACKGROUND/AIMS: The introduction of capillary zone electrophoresis (CZE) to this laboratory has highlighted discrepancies in albumin measured on an Abbott Aeroset by bromocresol green (BCG) and that calculated by CZE on the basis of total protein measured by Biuret. METHODS: This study examined differences in albumin estimation by CZE, Abbott Aeroset BCG, and Aeroset bromocresol purple (BCP), and compared these with albumin estimated by Beckman Array immunoassay. RESULTS: Altman and Bland analysis of results showed a positive bias of BCG with CZE (4.51 g/litre; 95% limits of agreement, 3.77 to 5.26; n = 72) and BCP (3.85 g/litre; 95% limits of agreement, -1.42 to 9.12; n = 72). CZE and BCP agreed closely (0.67 g/litre; 95% limits of agreement, -4.39 to 3.06; n = 72). Analysis of 57 of those samples in which BCG and CZE differed > or = 5 g/litre showed a positive bias of BCG with immunoassay (8.35 g/litre; 95% limits of agreement, 1.54 to 15.16; n =57), with good agreement between CZE and immunoassay (-0.44 g/litre; 95% limits of agreement, -2.82 to 1.94; n = 57). CONCLUSIONS: BCP is superior to BCG for the assay of albumin and has replaced BCG as the routine test for albumin in this laboratory.

Bromcresol Green↗
PubMed2002

CNS angiitis in graft vs host disease.

Graft-vs-host disease (GVHD) is a potentially treatable cause of progressive neurologic decline after bone marrow transplantation (BMT). The authors present histologic confirmation of CNS granulomatous angiitis in a child with chronic GVHD after BMT. Since cranial MRI showed only nonspecific findings, CNS vasculitis associated with GVHD after BMT may be underdiagnosed.

Adolescent↗
PubMed2001

Implication of a novel multiprotein Dam1p complex in outer kinetochore function.

Dam1p, Duo1p, and Dad1p can associate with each other physically and are required for both spindle integrity and kinetochore function in budding yeast. Here, we present our purification from yeast extracts of an approximately 245 kD complex containing Dam1p, Duo1p, and Dad1p and Spc19p, Spc34p, and the previously uncharacterized proteins Dad2p and Ask1p. This Dam1p complex appears to be regulated through the phosphorylation of multiple subunits with at least one phosphorylation event changing during the cell cycle. We also find that purified Dam1p complex binds directly to microtubules in vitro with an affinity of approximately 0.5 microM. To demonstrate that subunits of the Dam1p complex are functionally important for mitosis in vivo, we localized Spc19-green fluorescent protein (GFP), Spc34-GFP, Dad2-GFP, and Ask1-GFP to the mitotic spindle and to kinetochores and generated temperature-sensitive mutants of DAD2 and ASK1. These and other analyses implicate the four newly identified subunits and the Dam1p complex as a whole in outer kinetochore function where they are well positioned to facilitate the association of chromosomes with spindle microtubules.

Antigens, Neoplasm↗
PubMed2001

Functional cooperation of Dam1, Ipl1, and the inner centromere protein (INCENP)-related protein Sli15 during chromosome segregation.

We have shown previously that Ipl1 and Sli15 are required for chromosome segregation in Saccharomyces cerevisiae. Sli15 associates directly with the Ipl1 protein kinase and these two proteins colocalize to the mitotic spindle. We show here that Sli15 stimulates the in vitro, and likely in vivo, kinase activity of Ipl1, and Sli15 facilitates the association of Ipl1 with the mitotic spindle. The Ipl1-binding and -stimulating activities of Sli15 both reside within a region containing homology to the metazoan inner centromere protein (INCENP). Ipl1 and Sli15 also bind to Dam1, a microtubule-binding protein required for mitotic spindle integrity and kinetochore function. Sli15 and Dam1 are most likely physiological targets of Ipl1 since Ipl1 can phosphorylate both proteins efficiently in vitro, and the in vivo phosphorylation of both proteins is reduced in ipl1 mutants. Some dam1 mutations exacerbate the phenotype of ipl1 and sli15 mutants, thus providing evidence that Dam1 interactions with Ipl1-Sli15 are functionally important in vivo. Similar to Dam1, Ipl1 and Sli15 each bind to microtubules directly in vitro, and they are associated with yeast centromeric DNA in vivo. Given their dual association with microtubules and kinetochores, Ipl1, Sli15, and Dam1 may play crucial roles in regulating chromosome-spindle interactions or in the movement of kinetochores along microtubules.

Animals↗
PubMed2001

Volitional selection of direction in the generation of anticipatory ocular smooth pursuit in humans.

Anticipatory smooth pursuit eye movements cannot normally be generated in the absence of a moving target. However, repeated presentation of identical target motion stimuli, preceded by warning cues, leads to the build up of anticipatory smooth pursuit prior to target onset. These anticipatory responses arguably depend more on motor habit than cognitive expectations. Here, we show that directional cues, concomitant with a timing cue, may be used to initiate predictive (velocity scaled) movements in response to target stimuli of random direction. Furthermore, we show stored velocity and timing information may be directionally transferred, thus allowing predictive movements in a novel direction. This demonstrates the internal origin of these movements and their volitional as opposed to reflexive nature.

Brain↗
PubMed2001

Fine-scale mapping of a locus for severe bipolar mood disorder on chromosome 18p11.3 in the Costa Rican population.

We have searched for genes predisposing to bipolar disorder (BP) by studying individuals with the most extreme form of the affected phenotype, BP-I, ascertained from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The results of a previous linkage analysis on two extended CVCR BP-I pedigrees, CR001 and CR004, and of linkage disequilibrium (LD) analyses of a CVCR population sample of BP-I patients implicated a candidate region on 18p11.3. We further investigated this region by creating a physical map and developing 4 new microsatellite and 26 single-nucleotide polymorphism markers for typing in the pedigree and population samples. We report the results of fine-scale association analyses in the population sample, as well as evaluation of haplotypes in pedigree CR001. Our results suggest a candidate region containing six genes but also highlight the complexities of LD mapping of common disorders.

Alleles↗
PubMed2001

An fMRI study of anticipation and learning of smooth pursuit eye movements in humans.

We studied the neural substrate of anticipation and learning of smooth pursuit eye movements in humans using fMRI. Both predictable and non-predictable eye movements, compared to baseline, activated a common network previously associated with oculomotor function. The temporal dynamics of activity in a subset of these areas suggested a strong correlation with type of condition. Specifically, differential decreases in activity were seen in dorsolateral prefrontal cortex and the intraparietal sulcus during the predictable condition. During the non-predictable condition the same areas exhibited evidence of high levels of activity that further increased throughout the condition. In contrast, differential increases associated with the predictable condition were seen in anterior cingulate and preSMA cortex regions. These changes in activity mirror the time course of the short-term learning of eye movements seen behaviourally, and are congruent with learning-related changes that have been reported for other motor paradigms.

Adult↗
PubMed2001

Activation of the Arp2/3 complex by the actin filament binding protein Abp1p.

The actin-related protein (Arp) 2/3 complex plays a central role in assembly of actin networks. Because distinct actin-based structures mediate diverse processes, many proteins are likely to make spatially and temporally regulated interactions with the Arp2/3 complex. We have isolated a new activator, Abp1p, which associates tightly with the yeast Arp2/3 complex. Abp1p contains two acidic sequences (DDW) similar to those found in SCAR/WASp proteins. We demonstrate that mutation of these sequences abolishes Arp2/3 complex activation in vitro. Genetic studies indicate that this activity is important for Abp1p functions in vivo. In contrast to SCAR/WASp proteins, Abp1p binds specifically to actin filaments, not monomers. Actin filament binding is mediated by the ADF/cofilin homology (ADF-H) domain of Abp1p and is required for Arp2/3 complex activation in vitro. We demonstrate that Abp1p recruits Arp2/3 complex to the sides of filaments, suggesting a novel mechanism of activation. Studies in yeast and mammalian cells indicate that Abp1p is involved functionally in endocytosis. Based on these results, we speculate that Abp1p may link Arp2/3-mediated actin assembly to a specific step in endocytosis.

Actin-Related Protein 2↗
PubMed2001

Mitotic spindle integrity and kinetochore function linked by the Duo1p/Dam1p complex.

Duo1p and Dam1p were previously identified as spindle proteins in the budding yeast, Saccharomyces cerevisiae. Here, analyses of a diverse collection of duo1 and dam1 alleles were used to develop a deeper understanding of the functions and interactions of Duo1p and Dam1p. Based on the similarity of mutant phenotypes, genetic interactions between duo1 and dam1 alleles, interdependent localization to the mitotic spindle, and Duo1p/Dam1p coimmunoprecipitation from yeast protein extracts, these analyses indicated that Duo1p and Dam1p perform a shared function in vivo as components of a protein complex. Duo1p and Dam1p are not required to assemble bipolar spindles, but they are required to maintain metaphase and anaphase spindle integrity. Immunofluorescence and electron microscopy of duo1 and dam1 mutant spindles revealed a diverse variety of spindle defects. Our results also indicate a second, previously unidentified, role for the Duo1p/Dam1p complex. duo1 and dam1 mutants show high rates of chromosome missegregation, premature anaphase events while arrested in metaphase, and genetic interactions with a subset of kinetochore components consistent with a role in kinetochore function. In addition, Duo1p and Dam1p localize to kinetochores in chromosome spreads, suggesting that this complex may serve as a link between the kinetochore and the mitotic spindle.

Amino Acid Sequence↗
PubMed2001

Dad1p, third component of the Duo1p/Dam1p complex involved in kinetochore function and mitotic spindle integrity.

We showed recently that a complex between Duo1p and Dam1p is required for both spindle integrity and kinetochore function in the budding yeast Saccharomyces cerevisiae. To extend our understanding of the functions and interactions of the Duo1p/Dam1p complex, we analyzed the novel gene product Dad1p (for Duo1 and Dam1 interacting). Dad1p physically associates with Duo1p by two-hybrid analysis, coimmunoprecipitates with Duo1p and Dam1p out of yeast protein extracts, and shows interdependent localization with Duo1p and Dam1p to the mitotic spindle. These results indicate that Dad1p functions as a component of the Duo1p/Dam1p complex. Like Duo1p and Dam1p, Dad1p also localizes to kinetochore regions in chromosomes spreads. Here, we also demonstrate by chromatin immunoprecipitation that Duo1p, Dam1p, and Dad1p associate specifically with centromeric DNA in a manner that is dependent upon Ndc10 and partially dependent upon the presence of microtubules. To explore the functions of Dad1p in vivo, we generated a temperature-sensitive allele, dad1-1. This allele shows spindle defects and a mitotic arrest phenotype that is dependent upon the spindle assembly checkpoint. In addition, dad1-1 mutants undergo chromosome mis-segregation at the restrictive temperature, resulting in a dramatic decrease in viability.

Alleles↗
PubMed2001

Development of the fallopian canal in humans: a morphologic and radiologic study.

AIMS: This study investigated the development of the fallopian canal with particular reference to the mode of ossification and dehiscences, sites of incomplete closure around the facial nerve. BACKGROUND: The precise sequence of events surrounding ossification of the tissues around the facial nerve is uncertain. Incomplete ossification results in dehiscence of the adult structure, which places the nerve at increased risk of damage from disease processes in the middle ear and iatrogenic trauma during otologic surgery. METHODS: Twenty-four temporal bones from 12-to 36-week human fetuses were resected. Eight temporal bones from 22-to 36-week fetuses were microsliced to produce 1.5-mm horizontal sections and radiographed. Sixteen temporal bones from 12-to 35-week fetuses were serially microtomed to produce 7-microm slices, which were stained with hematoxylin and eosin. Quantitative and qualitative analyses of these sections were performed to document patterns of closure of the primitive canal and dehiscence formation. RESULTS: The tympanic part of the primitive fallopian canal, the facial sulcus, developed anteroposteriorly from the geniculate fossa to enclose the facial nerve. The mesenchyme that formed the facial sulcus underwent endochondral ossification, while the bone which capped or closed the sulcus developed in membrane. In the tympanic segment, permanent congenital dehiscences were elliptical and about 1 mm in length. CONCLUSIONS: This study clarifies the mode of development of the fallopian canal, with particular reference to dehiscences, and provides a scientific basis for otologic practice.

Facial Nerve↗
PubMed2001

Asthma care by nurse practitioners in the United States.

PURPOSE: To survey nurse practitioners (NPs) in the United States on their level of input to asthma care prior to enrolling in The National Asthma and Respiratory Training Centre (NARTC) specialist asthma education program in the UK. DATA SOURCES: Responses of 134 (66%) of the 202 NPs who self-selected for enrollment in the NARTC program on a preliminary questionnaire. CONCLUSIONS: Nearly all (133 or 99%) currently work with asthmatics and 122 (91%) prescribe asthma drugs. Only 92 (69%) measure peak flow(PF), 84 (63%) check inhaler technique, 76 (57%) teach use of a home PF meter and diary, and 63 (47%) provide written self-management plans on any regular basis. Many have not established follow-up procedures (56 or 42%), or evaluated their asthma management practices (55 or 41%). IMPLICATIONS FOR PRACTICE: Successful asthma management requires correct medication, systematic follow-up, patient education, and self-management. Specialist asthma training should encourage practitioners to combine effective drug usage with a long-term preventative approach.

Asthma↗
PubMed2001

Alcohol and gambling pathology among U.S. adults: prevalence, demographic patterns and comorbidity.

OBJECTIVE: This study was designed to determine the prevalence and demographic distribution of problem gambling, pathological gambling, alcohol abuse and alcohol dependence in the United States, and to examine the co-occurrence of gambling pathology and alcohol pathology in the United States. METHOD: A representative sample (N = 2,638) of U.S. adults age 18 and older was surveyed in the year 2000 using computer-assisted telephone interviewing. Respondents' gambling pathology and alcohol dependence were assessed by the South Oaks Gambling Screen (SOGS) and the Diagnostic Interview Schedule (DIS). RESULTS: Current pathological gambling had an overall prevalence of 1.3% as measured by the DIS and 1.9% as measured by the SOGS, with a higher prevalence among minorities and lower socioeconomic status (SES) respondents. Current and lifetime alcohol pathology was more common among males and young adults than among females and older adults. Current pathological gambling and alcohol dependence were correlated, and the highest correlation was found among higher SES respondents. CONCLUSIONS: The rate of current pathological gambling in the United States is higher than reported in past surveys. Minorities and lower SES Americans have higher than average rates of current pathological gambling. However, when higher SES persons are classified as current pathological gamblers, they are more likely than lower SES persons to be dependent on alcohol.

Adolescent↗
PubMed2001

Report of the Australian Rotavirus Surveillance Program, 2000/2001.

The National Rotavirus Reference Centre together with 15 collaborating laboratories Australia-wide conducted rotavirus surveillance from June 1999. The serotypes of rotaviruses that are responsible for the hospitalisation of children with acute diarrhoea were determined for the period June 2000 to May 2001. We examined 1108 rotavirus specimens using a combination of monoclonal antibody immunoassay, reverse transcription-PCR, and Northern hybridisation. Serotype G1 strains were the most prevalent overall (49.5%), and found in all centres. Serotype G9 rotaviruses, which were first identified in 1997, were second in importance (18.1%). Serotype G2 viruses were next (12.5%), followed by the re-emergence of serotype G4 viruses (9.7%). The findings of this study have implications for vaccine development strategies where protection against serotypes additional to G1-G4 may be required.

Australia↗