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Biomedical subjects

J Snider

Publications and source records attributed to J Snider.

At least 19 recordsLinked to original sources
PubMed2001

Waiting times from abnormal breast screen to diagnosis in 7 Canadian provinces.

BACKGROUND: Delay to breast cancer diagnosis following an abnormal screening result is associated with anxiety and personal disruption. We assessed the patterns and timeliness of diagnostic follow-up after breast cancer screening for women with abnormal results who attended organized screening programs in 7 provinces. METHODS: Using data from the Canadian Breast Cancer Screening Database, we identified 203,141 women aged 50-69 years who underwent screening in 1996 through provincially organized breast cancer screening programs in British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Nova Scotia and Newfoundland. We prospectively followed women with an abnormal screening result through to the completion of the assessment process. We evaluated the waiting times from screening examination to first assessment, from screening examination to first imaging, from screening examination to diagnosis and from first assessment to diagnosis for 13,958 women, stratified according to screening program, mode of detection, whether a biopsy was performed and whether cancer was diagnosed. RESULTS: We observed considerable variations between and within programs in the time to diagnosis. The median time from screening examination to first assessment was 2.6 weeks. The median time from screening examination to diagnosis was 3.7 weeks; this time increased to 6.9 weeks for women undergoing biopsy. Even when no biopsy was performed, 10% of the women waited 9.6 weeks or longer for a diagnosis, as compared with 15.0 weeks or longer for 10% of the women undergoing biopsy. Among the women who had a biopsy, the use of core biopsy was associated with a shorter median time to diagnosis than was open biopsy, and those found to have cancer had shorter waiting times than women with benign biopsy findings. INTERPRETATION: Women undergoing assessment of an abnormal breast cancer screening result waited many weeks for a diagnosis, especially when a biopsy was performed. To ensure that targets for timeliness, adopted nationally in 1999, are realized, improved models of care or dissemination of existing efficient techniques to reach a diagnosis will be needed.

Aged↗
PubMed2001

Identification of PEX5p-related novel peroxisome-targeting signal 1 (PTS1)-binding proteins in mammals.

Based on peroxin protein 5 (Pex5p) homology searches in the expressed sequence tag database and sequencing of large full-length cDNA inserts, three novel and related human cDNAs were identified. The brain-derived cDNAs coded for two related proteins that differ only slightly at their N-terminus, and exhibit 39.8% identity to human PEX5p. The shorter liver-derived cDNA coded for the C-terminal tetratricopeptide repeat-containing domain of the brain cDNA-encoded proteins. Since these three proteins specifically bind to various C-terminal peroxisome-targeting signals in a manner indistinguishable from Pex5p and effectively compete with Pex5p in an in vitro peroxisome-targeting signal 1 (PTS1)-binding assay, we refer to them as 'Pex5p-related proteins' (Pex5Rp). In contrast to Pex5p, however, human PEX5Rp did not bind to Pex14p or to the RING finger motif of Pex12p, and could not restore PTS1 protein import in Pex5(-/-) mouse fibroblasts. Immunofluorescence analysis of epitope-tagged PEX5Rp in Chinese hamster ovary cells suggested an exclusively cytosolic localization. Northern-blot analysis showed that the PEX5R gene, which is localized to chromosome 3q26.2--3q27, is expressed preferentially in brain. Mouse PEX5Rp was also delineated. In addition, experimental evidence established that the closest-related yeast homologue, YMR018wp, did not bind PTS1. Based on its subcellular localization and binding properties, Pex5Rp may function as a regulator in an early step of the PTS1 protein import process.

Amino Acid Sequence↗
PubMed2001

Predictors of mammography use among Canadian women aged 50-69: findings from the 1996/97 National Population Health Survey.

BACKGROUND: Screening mammography, although recommended every 2 years for women aged 50-69, is thought to be underused among select groups of Canadian women. METHODS: We used data from the 1996/97 National Population Health Survey to describe current patterns in mammography use (including reasons for not having a mammogram within the 2 years before the survey and future screening intentions) in Canada and to determine factors associated with nonparticipation and time-inappropriate use (mammogram 2 or more years before the survey) among women aged 50-69. RESULTS: Among respondents aged 50-69, 79.1% (95% confidence interval [CI] 76.9%-81.2%) reported ever having had a mammogram, and 53.6% (95% CI 51.4%-55.9%) had had a recent (time-appropriate) mammogram (within the 2 years before the survey). Only 0.6% (95% CI 0.3%-0.9%) of recently screened women reported problems of access, and few reported personal or health system barriers as reasons for not obtaining a recent mammogram. Over 50% of the women who had not had a recent mammogram reported that they did not think it was necessary, and only 28.2% (95% CI 23.8%-32.7%) of those who had never had a mammogram planned to have one within the 2 years following the survey. The rate of time-appropriate mammography varied significantly by province, from 41.1% (95% CI 29.3%-52.9%) in Newfoundland to 69.4% (95% CI 61.3%-77.6%) in British Columbia. Significant predictors of never having had a mammogram included higher age, residence in a rural area, Asia as place of birth, no involvement in volunteer groups, no regular physician or recent medical consultations (including recent blood pressure check), current smoking, infrequent physical activity and no hormone replacement therapy. INTERPRETATION: Despite increases in mammography screening rates since the 1994/95 National Population Health Survey, current estimates indicate that almost 50% of women aged 50-69 have not had a time-appropriate mammogram. Our findings confirm continued low mammography participation rates among older women and those in rural areas, select ethnic groups and women with negative health care and lifestyle characteristics.

Age Factors↗
PubMed2001

Depressive symptoms as measured by the CDI in a population of northern Italian children.

The aim of this study was to evaluate some Children's Depression Inventory (CDI) psychometric properties and the prevalence of depressive symptoms in an unselected Italian sample of two hundred and eighty-four children aged 8 years. The CDI internal consistency was adequate (Cronbach's alpha:.80). The mean and standard deviation of CDI and the percentage of children at risk of depression (10.6%) in this sample are consistent with the figures reported by other studies carried out in northern Europe and North America. There were differences in gender and socioeconomic level in that boys scored higher than girls, and in the lower socioeconomic level there were more children at risk of depression. Ten items best discriminated children at risk for depression with 94% of correct classification. Most of these items consisted of observable signs. It is suggested that the CDI has noteworthy consistency across samples of relatively different cultures, that it can reliably be employed in the assessment of young children, and that observable signs outnumber internalizing symptoms of depression among children at risk

Catchment Area, Health↗
PubMed2001

Posttransfusion purpura secondary to an alloantibody reactive with HPA-5a (Br(b)).

BACKGROUND: Posttransfusion purpura (PTP) is characterized by severe thrombocytopenia following blood transfusion that results from alloimmunization to platelet-specific alloantigens. Most cases involve antibodies against HPA-1a in homozygous HPA-1b persons. CASE REPORT: A patient developed PTP after cardiopulmonary bypass associated with a platelet-specific antibody with strong reactivity against HPA-5a (Br(b)). Geno-typing confirmed that the patient was homozygous for HPA-5b. CONCLUSION: This is the first well-documented occurrence of PTP associated with isolated allosensitization to HPA-5a or Br(b). The case highlights the importance of maintaining a high level of suspicion for PTP in the appropriate clinical setting, even in an atypical patient.

Aged↗
PubMed2000

Performance of screening mammography in organized programs in Canada in 1996. The Database Management Subcommittee to the National Committee for the Canadian Breast Cancer Screening Initiative.

BACKGROUND: The results of randomized trials show that breast cancer screening by mammography reduces breast cancer mortality by up to 40% in women aged 50-69 years. Because of these results, by 1998, 22 countries, including Canada, had established population-based organized screening programs. This paper presents the results of screening mammography in 1996 for 7 provincially organized breast cancer screening programs in Canada. METHODS: Analyses of interim performance indicators for screening mammography have been calculated from data submitted to the Canadian Breast Cancer Screening database. The data set consisted of data from 7 provincial programs and was limited to mammographic screens for women aged 50-69 years (n = 203,303). Screening outcomes and performance indicators were calculated for abnormalities detected by screening mammography only. RESULTS: The abnormal recall rate was 9.5% for first screens and 4.6% for subsequent screens, and the cancer detection rate per 1000 women screened was 6.9 for first screens and 3.8 for subsequent screens. The positive predictive value (i.e., the proportion of women who tested positive by mammography who were found to have breast cancer on screen-initiated diagnostic work-up) increased from 7.2% at the first screen to 8.2% at subsequent screens. Estimated participation rates within organized programs varied from 10.6% to 54.2%, depending on the province. INTERPRETATION: For 1996, organized breast cancer screening programs met or exceeded many of the interim measures used in international programs. It is possible to translate the benefits of breast cancer screening by mammography, as demonstrated in randomized trials, into population-based community programs. Screening mammography through organized programs should increase to allow more comprehensive monitoring in Canada.

Aged↗
PubMed2000

Monoclonal antibodies and synthetic peptides define the active site of FcepsilonRI and a potential receptor antagonist.

Defining the structure of the human high-affinity receptor for IgE, Fc,RI, is crucial to understand the receptor:ligand interaction, and to develop drugs to prevent IgE-dependent allergic diseases. To this end, a series of four anti-FcepsilonRI monoclonal antibodies (mAbs), including three new mAbs, 47, 54, and 3B4, were used in conjunction with synthetic FcepsilonRI peptides to define functional regions of the Fc IgE-binding site and identify an antagonist of IgE binding. The spatial orientation of the epitopes detected by these antibodies and their relationship to the IgE-binding region of FcepsilonRI was defined by a homology model based on the closely related FcepsilonRIIa. Using recombinant soluble FcRI-alpha as well as FcepsilonRI-alpha expressed on the cell surface, a series of direct and competitive binding experiments indicated that the mAbs detected nonoverlapping epitopes. One antibody (15-1), previously thought to be located close to the IgE-binding site, was precisely mapped to a single loop within the IgE-binding site by both mutagenesis and overlapping synthetic peptides encompassing the entire extracellular domain. A synthetic peptide epsilonRI-11, containing the amino acids 101-120 and the mAb 15-1 epitope, inhibited IgE binding and may form the basis for the development of a useful receptor-based therapy.

Amino Acid Sequence↗
PubMed2000

Adenosine kinase of Arabidopsis. Kinetic properties and gene expression.

To assess the functional significance of adenosine salvage in plants, the cDNAs and genes encoding two isoforms of adenosine kinase (ADK) were isolated from Arabidopsis. The ADK1- and ADK2-coding sequences are very similar, sharing 92% and 89% amino acid and nucleotide identity, respectively. Each cDNA was overexpressed in Escherichia coli, and the catalytic activity of each isoform was determined. Both ADKs had similar catalytic properties with a K(m) and V(max)/K(m) for adenosine of 0.3 to 0.5 microM and 5.4 to 22 L min(-1) mg(-1) protein, respectively. The K(m) and V(max)/K(m) for the cytokinin riboside N(6)(isopentenyl) adenosine are 3 to 5 microM and 0.021 to 0.14 L min(-1) mg(-1) protein, respectively, suggesting that adenosine is the preferred substrate for both ADK isoforms. In Arabidopsis plants, both ADK genes are expressed constitutively, with the highest steady-state mRNA levels being found in stem and root. ADK1 transcript levels were generally higher than those of ADK2. ADK enzyme activity reflected relative ADK protein levels seen in immunoblots for leaves, flowers, and stems but only poorly so for roots, siliques, and dry seeds. The catalytic properties, tissue accumulation, and expression levels of these ADKs suggest that they play a key metabolic role in the salvage synthesis of adenylates and methyl recycling in Arabidopsis. They may also contribute to cytokinin interconversion.

Adenosine↗
PubMed1999

Fluorescein monophosphates as fluorogenic substrates for protein tyrosine phosphatases.

A series of novel fluorescein monophosphates aimed as substrates for protein tyrosine phosphatases (PTPs) were synthesized and evaluated against fluorescein diphosphate (FDP), the currently used fluorescent substrate for PTPs. In contrast to FDP, which is dephosphorylated to monophosphate and then to fluorescein in a sequential reaction, these monophosphates are dephosphorylated in a single step. This eliminates the complication in assaying PTPs due to the cleavage of the second phosphate group. The kinetic studies of these substrates with PTPs were performed and Michaelis-Menten parameters were obtained. These designed substrates have Km 0.03-0. 35 mM, kcat/Km of 3-100 mM-1 s-1 with CD45 and PTP1B. The results showed that the substrates with negative charge groups on the fluorescein have higher affinities for PTP1B, which are consistent with other observations. In this series, fluorescein monosulfate monophosphate (FMSP) was the best substrate observed. Since FMSP showed large increases in both absorption and fluorescence upon dephosphorylation by PTPs at pH>6.0, it is one of the most sensitive, stable and high affinity substrates reported for PTPs.

Fluoresceins↗
PubMed1999

Professional preparation of elementary teachers in Ohio: status of K-6 health education.

Improving the health status of children and youth depends to an extent on the adequate preparation of elementary teachers to teach health education. This survey: 1) examined the status of health education preparation that preservice elementary education majors receive from Ohio colleges and universities (n = 50); 2) determined the type of health education courses that Ohio colleges and universities require for elementary education majors; and 3) assessed the extent to which Ohio colleges and universities incorporate health and pedagogy-related content in their courses for elementary education majors. Results showed that 40 of the 50 institutions offered a health course. Twelve different textbooks were used in the courses. Coverage of course content ranged from much to none for 10 survey items ranging from the National Health Education Standards to the K-6 Health Instruction Responsibilities and Competencies.

Curriculum↗
PubMed1996

Trends in mammography and Pap smear utilization in Canada.

We have examined trends in the utilization of two preventive health procedures for women in Canada based on our analysis of the 1994 National Population Health Survey (NPHS) and comparisons with two previous large population health surveys. The NPHS provides evidence that Canadian women's use of mammography has continued to increase between 1990 and 1994, while use of Pap smears has remained steady. Increases in mammographic utilization are seen for all age groups and in all provinces of Canada. Women who are less than the recommended age of 50-69 years for screening mammography access these services in considerable numbers. Large proportions of women aged 18-24 and 65 or over have never had a Pap smear, and recency of Pap smear is associated with age. Income adequacy and educational attainment are still strong predictors of which women utilize Pap smears and mammograms. We conclude that the NPHS is sufficiently broad-based to be used in a surveillance program to track Pap smear and mammography utilization.

Adolescent↗
PubMed1995

Expression of recombinant soluble Fc epsilon RI: function and tissue distribution studies.

Recombinant soluble IgE Fc receptors (rsFc epsilon RI) are potent inhibitors of type I hypersensitivity reactions tested in a local inflammatory setting. However, the fate of these receptors in vivo is dependent on the cellular source of the rsFc epsilon RI. We have produced these by transiently transfecting Cos-7 cells with a cDNA encoding the extracellular domains of human Fc epsilon RI alpha-chain. Following affinity purification, the rsFc epsilon RI was characterized as 58,000 MW, which was reduced to 23,000 MW following endoglycosidase F treatment. The purified rsFc epsilon RI could inhibit mouse IgE binding to Fc epsilon RI+ transfected CHO-K1 cells in vitro, bind sIgE+ B lymphoma cells in vitro, and inhibit the passive cutaneous anaphylaxis model in vivo in Sprague-Dawley rats. Pharmacokinetic studies in vivo involving intravenous injection of radiolabelled rsFc epsilon RI in mice revealed the receptor to have a rapid initial blood clearance (t1/2 early phase of 15 min) and to accumulate in the liver before being detected in urine. The localization of rsFc epsilon RI in the liver could be blocked by administration of mannose glycosylated ovalbumin and mannan, demonstrating that liver uptake involved the mannose receptor that is expressed on liver sinusoid cells and Kupffer cells. The production of rsFc epsilon RI using a stable expression system in CHO-K1 cells produced functional receptor of the same molecular weight as the Cos-7 system by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). However, biodistribution studies demonstrated differences; the CHO-K1 cell-produced material did not localize to the liver in comparison to the Cos-7-produced rsFc epsilon RI.

Animals↗
PubMed1994

Suksdorfin: an anti-HIV principle from Lomatium suksdorfii, its structure-activity correlation with related coumarins, and synergistic effects with anti-AIDS nucleosides.

Suksdorfin (1), which is isolated from the fruit of Lomatium suksdorfii, was found to be able to inhibit HIV-1 replication in the T cell line, H9, with an average EC50 value of 2.6 +/- 2.1 microM. In addition, suksdorfin was also suppressive during acute HIV-1 infections of peripheral blood mononuclear cells, monocyte/macrophages and the promonocytic cell line, U937. Combinations of 1 and the anti-HIV nucleosides ddI and ddC demonstrated statistical synergy in inhibiting HIV-1 replication (ddC > ddI). However, the viral inhibition mediated by combining 1 with AZT was not statistically synergistic. Furthermore, the presence of suksdorfin did not antagonize the suppression mediated by the three nucleoside reverse transcriptase inhibitors. Comparison of the structure and activity of 1 with those of ten related compounds indicated that the dihydroseselin type of pyranocoumarin possessing a 4'-isovaleryl group is important to suksdorfin's enhanced anti-HIV activity.

Antiviral Agents↗
PubMed1994

Endpoints in rheumatoid arthritis.

The Outcome Measures in Rheumatoid Arthritis Clinical Trials Conference has significantly contributed to the field of clinical outcome measurement. Agreement was achieved in designating a preliminary core set of 8 endpoints to be used as a minimum in every rheumatoid arthritis (RA) clinical trial of > or = 1 year: acute phase reactants, disability, pain, patient global assessment, physician global assessment, swollen joint count, tender joint count, and radiographic studies of joints. The discussions and nominal group exercises provided a mandate for full scale testing of approaches to compare the validity of different assessment techniques available for these 8 measures; to determine the minimum level of clinical importance for each of the measures; and to refine and validate the aggregation of outcome measures into indices, taking special care to ensure credibility in the eyes of clinicians, patients, and policy makers. The discussions made it clear that to select one intervention definitively over another, one must additionally consider outcomes such as drug toxicity, costs, and mortality. These aspects need to be explored systematically at subsequent conferences.

Antirheumatic Agents↗