PubMed Health⌕ Search

Biomedical subjects

S Flynn

Publications and source records attributed to S Flynn.

At least 19 recordsLinked to original sources
PubMed2006

The incidence of schizophrenia in European immigrants to Canada.

OBJECTIVE: The risk for schizophrenia in immigrants to Europe is approximately three times that of native-born populations. Discrimination and marginalization may influence the risk for schizophrenia within migrant populations. The primary objective of the present study was to determine whether the risk associated with migration was also evident 100 years ago. A second objective was to determine whether changing social stresses are associated with changes to the incidence of schizophrenia. METHOD: During the first two decades of the twentieth century, the Provincial Mental Hospital was the sole provider of psychiatric services in British Columbia, Canada. Detailed clinical records have been preserved for 99.5% of 2477 patients who had a psychiatric admission between 1902 and 1913. Diagnoses were made after a detailed file review and 807 patients met DSM-IV criteria for first-episode schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychosis not otherwise specified. Diagnoses had high inter-rater reliability. The incidence of schizophrenia in migrants from Britain or Continental Europe was compared with that in the Canadian-born population using indirect standardization and Poisson models. RESULTS: Migration from Britain or Continental Europe to Canada in the early twentieth century was associated with an increased rate of schizophrenia; IRR=1.54, (95% CI=1.33-1.78). Incidence increased over time in immigrants but not in the native-born population and this increase occurred during a period of economic recession. CONCLUSIONS: Migration was a risk factor for schizophrenia a century ago as it is today. This risk occurred in white migrants from Europe and increased during a period of increased social stress.

Adolescent↗
PubMed2004

Neuropsychological correlates of the PANSS Cognitive Factor.

OBJECTIVE: Factor analytic studies of the Positive and Negative Syndrome Scale (PANSS) have consistently isolated a factor that is frequently labeled as 'cognitive'. The present study sought to further explore the factor by examining the relationships between 4 versions of the cognitive factor and a set of neuropsychological tests. METHOD: Thirty-seven inpatients diagnosed with schizophrenia or schizoaffective disorder were assessed with the PANSS and neuropsychological measures. RESULTS: Verbal intelligence and verbal memory were found to be most closely associated with cognitive factor scores. A global rating of illness severity showed greater relationships to cognitive variables than any cognitive factor. CONCLUSIONS: The PANSS cognitive factor may reflect verbal ability and memory, but is not sufficiently comprehensive to be considered as a replacement for direct assessment of cognitive functioning.

Adolescent↗
PubMed2004

In vitro inhibition of Eimeria tenella invasion by indigenous chicken Lactobacillus species.

The aim of this study was to determine the effects of indigenous chicken Lactobacillus species isolates from different parts of the gastrointestinal tract on Eimeria tenella invasion in vitro and to characterise the nature of inhibition, if any. The effects of competitive exclusion, steric interference and bacterial extracellular factors on E. tenella invasion were examined in an MDBK cell model. Several Lactobacillus species were initially isolated from chickens and identified by biochemical characteristics and 16S-rRNA. All Lactobacillus species isolates tested, significantly inhibited E. tenella invasion. Steric interference did not affect parasite invasion. Extracellular metabolic factors secreted by Lactobacillus species isolates into the surrounding media were shown to inhibit parasite invasion and these factors appeared to be heat stable. These results show that the natural microflora of poultry can provide a source of E. tenella-inhibiting Lactobacillus species in vitro, and thus may contribute to the control of Eimeria infection.

Animals↗
PubMed2003

Cigarette smoking and risk of non-Hodgkin lymphoma subtypes among women.

Previous studies of the relationship between cigarette smoking and non-Hodgkin lymphoma (NHL) have yielded conflicting results, perhaps because most studies have evaluated the risk for all NHL subtypes combined. Data from a population-based case-control study conducted among women in Connecticut were used to evaluate the impact of cigarette smoking on the risk of NHL by histologic type, tumour grade, and immunologic type. A total of 601 histologically confirmed, incident cases of NHL and 718 population-based controls provided in-person interviews. A standardised, structured questionnaire was used to collect information on each subject's current smoking status, age at initiation, duration and intensity of smoking, and cumulative lifetime exposure to smoking. Our data suggest that cigarette smoking does not alter the risk of all NHL subtypes combined. However, increased risk of follicular lymphoma appears to be associated with increased intensity and duration of smoking, and cumulative lifetime exposure to smoking. Compared with nonsmokers, women with a cumulative lifetime exposure of 16-33 pack-years and 34 pack-years or greater experience 50% increased risk (OR=1.5, 95% CI 0.9-2.5) and 80% increased risk (OR=1.8, 95% CI 1.1-3.2), respectively, of follicular lymphoma (P for linear trend=0.05). Our study findings are consistent with several previous epidemiologic studies suggesting that cigarette smoking increases the risk of follicular lymphoma. This research highlights the importance of distinguishing between NHL subtypes in future research on the aetiology of NHL.

Adult↗
PubMed2003

Novel strategy for identification of candidate cytotoxic T-cell epitopes from human preproinsulin.

We describe a strategy for identifying ligands of human leukocyte antigen (HLA) class I molecules based on a peptide library-mediated in vitro assembly of recombinant class I molecules. We established a microscale class I assembly assay and used a capture ELISA to quantify the assembled HLA-peptide complexes. The identity of the bound ligands was then deduced by mass spectrometry. In this method, HLA complexes assembled in vitro in the presence of components of a mixture of peptides were immunoprecipitated and the bound peptide(s) identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. This process of epitope extraction is robust and can be used with complex mixtures containing in excess of 300 candidate ligands. A library of overlapping peptides representing all potential octamers, nonamers and decamers from human preproinsulin was synthesized using unique library chemistry. Peptides from the library were used to initiate assembly of recombinant HLA-B8, HLA-B15 and HLA-A2, facilitating the identification of candidate T-cell epitopes from preproinsulin.

Epitopes, T-Lymphocyte↗
PubMed2001

Reliability and validity of a chronic care facility adaptation of the Clinical Dementia Rating scale.

OBJECTIVE: This study investigated the reliability and validity of a chronic care facility adaptation of the Clinical Dementia Rating scale (CDR-CC). METHOD: Sixty-two residents in a chronic care facility participated in an inter-rater and 1 month test-retest reliability study. The instrument was validated against the Mini-Mental State Examination (MMSE). RESULTS: Inter-rater and 1 month test-retest reliability for the global CDR-CC score were excellent (intraclass correlation coefficients 0.99 and 0.92, respectively). The CDR-CC domain and global scores were negatively correlated with the MMSE. CONCLUSIONS: The CDR-CC is a global assessment tool that reliably and validly measures cognitive and functional impairment in a chronic care setting.

Activities of Daily Living↗
PubMed2001

In vitro selection criteria for probiotic bacteria of human origin: correlation with in vivo findings.

The enteric flora comprises approximately 95% of the total number of cells in the human body and can elicit immune responses while protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract may also be implicated in the pathogenesis of diseases such as inflammatory bowel disease (ulcerative colitis and Crohn disease). The objectives of the Probiotic Research Group based at University College Cork were to isolate and identify lactic acid bacteria exhibiting beneficial probiotic traits, such as bile tolerance in the absence of deconjugation activity, acid resistance, adherence to host epithelial tissue, and in vitro antagonism of pathogenic microorganisms or those suspected of promoting inflammation. To isolate potentially effective probiotic bacteria, we screened the microbial population adhering to surgically resected segments of the gastrointestinal tract (the environment in which they may subsequently be reintroduced and required to function). In total, 1500 bacterial strains from resected human terminal ilea were assessed. From among these organisms, Lactobacillus salivarius subsp. salivarius strain UCC118 was selected for further study. In mouse feeding trials, milk-borne L. salivarius strain UCC118 could successfully colonize the murine gastrointestinal tract. A human feeding study conducted in 80 healthy volunteers showed that yogurt can be used as a vehicle for delivery of strain UCC118 to the human gastrointestinal tract with considerable efficacy in influencing gut flora and colonization. In summary, we developed criteria for in vitro selection of probiotic bacteria that may reflect certain in vivo effects on the host such as modulation of gastrointestinal tract microflora.

Animals↗
PubMed2000

Co-stimulation and selection for T-cell help for germinal centres: the role of CD28 and OX40.

Given the importance of responding to infections with the right defensive strategy, much interest has focused on cytokine differentiation in CD4+ T cells. However, relatively little is known of the logistics of T-cell help for B cells. Here, Lucy Walker and colleagues propose key roles for CD28 and OX40 in coordinating the selection, expansion and migration of CD4+ T cells to B-cell follicles.

Animals↗
PubMed1999

Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers.

Mice rendered deficient in CD28 signaling by the soluble competitor, cytotoxic T lymphocyte-associated molecule 4-immunoglobulin G1 fusion protein (CTLA4-Ig), fail to upregulate OX40 expression in vivo or form germinal centers after immunization. This is associated with impaired interleukin 4 production and a lack of CXC chemokine receptor (CXCR)5 on CD4 T cells, a chemokine receptor linked with migration into B follicles. Germinal center formation is restored in CTLA4-Ig transgenic mice by coinjection of an agonistic monoclonal antibody to CD28, but this is substantially inhibited if OX40 interactions are interrupted by simultaneous injection of an OX40-Ig fusion protein. These data suggest that CD28-dependent OX40 ligation of CD4 T cells at the time of priming is linked with upregulation of CXCR5 expression, and migration of T cells into B cell areas to support germinal center formation.

Abatacept↗
PubMed1999

CD4 T cell traffic control: in vivo evidence that ligation of OX40 on CD4 T cells by OX40-ligand expressed on dendritic cells leads to the accumulation of CD4 T cells in B follicles.

We report here that CD40- but not lipopolysaccharide (LPS)-activated murine dendritic cells (DC) express OX40-ligand (OX40L) as has been reported in humans. To understand how OX40 ligation affects differentiation of CD4 T cells at the time of priming, we constitutively expressed OX40L on DC using the DC-specific promoter of CD11c. Transgenic mice showed greatly increased numbers of CD4 but not CD8 T cells in their B cell areas. This effect was to a great extent immunization dependent, as spleen and lymphoid tissue with no germinal center reactions from mice which had not been deliberately immunized did not show marked CD4 T cell accumulation. The increased numbers of CD4+ CD62low cells in transgenic mice suggest that it is activated CD4 T cells that accumulate within B cell follicles. These data are consistent with the notion that physiological engagement of OX40 (CD134) on activated CD4 T cells either initiates their migration into or causes them to be retained in B follicles. In contrast, LPS-treated CD did not up-regulate OX40L expression. This dichotomy provides a molecular explanation of how DC might integrate environmental and accessory signals to control cytokine differentiation and migration in CD4 effector cells.

Animals↗
PubMed1999

Familial medullary thyroid carcinoma: presymptomatic diagnosis and management in children.

Two kindreds with familial medullary thyroid carcinoma (MTC) are described in which affected family members had variable clinical and pathologic manifestations. Genetic testing in 2 children from one kindred revealed a mutation in exon 10, codon 618 (TGC to AGC) in the extracellular cysteine-rich region of the RET gene. In this kindred an 11-year-old had microscopic evidence of MTC; however, a 17-year-old had no evidence of pathology on thyroidectomy. In a second kindred a rare mutation in exon 14, codon 804 (GTG to TTG) of the intracellular tyrosine kinase region of the RET gene was detected. In this kindred MTC has occurred in the 4th to 5th decades of life, with a clinical spectrum in mutation-positive family members ranging from no disease and C-cell hyperplasia to carcinoma with lymph node metastasis; a 7-year-old with the mutation and a normal response to provocative testing was also identified. Management recommendations in children from families with clearly defined familial MTC may be individualized to reflect emerging genotype-phenotype correlations.

Adolescent↗
PubMed1999

Affective verbal memory in patients with temporal lobe epilepsy.

Eighteen epileptic patients with unilateral temporal lobe epilepsy (9 left, 9 right) were evaluated with a verbal memory task involving recall of 2 stories, 1 with affective content and 1 that was neutral. A trend for better performance by the group with intact left hemispheres was found for a quantitative score of number of story units recalled. For a qualitative score of number of symbolic distortions, a main effect of affective load was found, such that more distortions were made for the story with affective than neutral content. This effect remained significant when the left temporal lobe epilepsy patients were analyzed separately and was not found for the right temporal lobe epilepsy patients alone. Additional analyses for the subset of 5 patients with left and 6 patients with right temporal lobectomies involving removal of the hippocampus and amygdala were in the same direction as the analyses for all 18 participants. These findings are consistent with other reports of material-specific memory deficits, such that verbal memory deficits are associated with left temporal lobe epilepsy. The differences between performance on the affective and neutral stories for the left and right temporal lobe epilepsy patients are discussed and related to the role of the amygdala in affective processing.

Adult↗
PubMed1999

Administering intravenous antibiotics at home.

Many patients with orthopaedic infections spend weeks or months in hospital for administration of i.v. antibiotics. Peripherally inserted central venous catheters can be used to give patients their medication at home. Some patients can be taught to administer their own antibiotics, relieving pressure of work in hospitals and the community and encouraging multidisciplinary practice.

Anti-Bacterial Agents↗
PubMed1998

Targeting the PML/RAR alpha translocation product triggers apoptosis in promyelocytic leukemia cells.

The t(15;17) rearrangement found in acute promyelocytic leukemia (APL) yields a fusion transcript, PML/RAR alpha. PML/RAR alpha expression is linked to leukemogenesis and to clinical sensitivity to all-trans retinoic acid (RA). Paradoxically, RA treatment causes transient complete remissions in most t(15;17) APL cases. The precise roles of PML/RAR alpha in triggering leukemia or in causing a maturation block are not yet known. This study explores directly these PML/RAR alpha functions in the growth and differentiation of APL cells using a hammerhead ribozyme to target PML/RAR alpha mRNA in the NB4 APL cell line. When the PML/RAR alpha cleaving but not the non-catalytic control ribozyme is introduced into the NB4 APL cell line, PML/RAR alpha protein expression is reduced. This catalysis signals growth suppression, cytotoxicity, and apoptosis without overcoming the maturation block found in these leukemic cells. These biologic effects depend on the selective pressure used to express the ribozyme from an episomal vector. Introduction of a non-catalytic, control ribozyme into NB4 cells caused no observed phenotype due to anti-sense activities. Expression of the catalytic or non-catalytic ribozymes in control cells lacking PML/RAR alpha mRNA yielded no apparent growth or differentiation effects. Thus, use of a hammerhead ribozyme that targets PML/RAR alpha expression in APL cells reveals the anti-apoptotic function of this translocation product and demonstrates that PML/RAR alpha cleavage is insufficient to overcome the differentiation block observed in these leukemic cells. Taken together, these findings indicate that persistent PML/RAR alpha expression is required to maintain basal leukemic cell growth and point to the therapeutic potential of targeting PML/RAR alpha in APL.

Apoptosis↗
PubMed1998

CD4 T cell cytokine differentiation: the B cell activation molecule, OX40 ligand, instructs CD4 T cells to express interleukin 4 and upregulates expression of the chemokine receptor, Blr-1.

This report investigates the role of OX40 ligand (OX40L) and its receptor, OX40, expressed on activated B and T cells, respectively, in promoting the differentiation of T helper type 2 (Th2) CD4 T cells. These molecules are expressed in vivo by day 2 after priming with T cell- dependent antigens. Their expression coincides with the appearance of immunoglobulin (Ig)G switch transcripts and mRNA for interleukin (IL)-4 and interferon (IFN)-gamma, suggesting that this molecular interaction plays a role in early cognate interactions between B and T cells. In vitro, we report that costimulation of naive, CD62Lhigh CD4 T cells through OX40 promotes IL-4 expression and upregulates mRNA for the chemokine receptor, blr-1, whose ligand is expressed in B follicles and attracts lymphocytes to this location. Furthermore, T cell stimulation through OX40 inhibits IFN-gamma expression in both CD8 T cells and IL-12-stimulated CD4 T cells. Although this signal initiates IL-4 expression, IL-4 itself is strongly synergistic. Our data suggest that OX40L on antigen-activated B cells instructs naive T cells to differentiate into Th2 cells and migrate into B follicles, where T cell-dependent germinal centers develop.

Animals↗
PubMed1998

The relationship between apolipoprotein E, dementia, and vascular illness.

The purpose of this study was to concurrently assess the relationship of Apolipoprotein E (APOE) with both dementias and vascular illnesses in the very old. Nine hundred and fifty nine subjects (mean age 85 years) in a long-term care facility were genotyped and cognitively tested with the Mini Mental State Exam. All subjects were studied for the relationship of APOE with atherosclerotic heart disease, hypertension, or stroke without concomitant dementia. Four hundred fifty individuals met criteria for inclusion into one of the following groups: Alzheimer's disease (n = 318), vascular dementia (n = 49), or not demented controls (n = 83) and were investigated for the relationship between APOE and these diagnostic categories. APOE epsilon4 was not associated with atherosclerotic heart disease, hypertension, or stroke without concomitant dementia. The APOE epsilon3 allele was more common in men with atherosclerotic heart disease. In contrast, the APOE epsilon4 allele was more common in patients with Alzheimer's disease (22%) and vascular dementia (26%) than in not demented controls (7%). APOE epsilon4 is associated with dementias in the very old, whereas its relationship with either peripheral or central nervous system vascular disease without dementia is not as robust.

Aged↗