The validation of the Finnish Hospital Discharge Register and Causes of Death Register data on stroke diagnoses.

BACKGROUND AND PURPOSE: Administrative registers, like hospital discharge registers and causes of death registers are used for the monitoring of disease incidences and in the follow-up studies. Obtaining reliable results requires that the diagnoses in these registers are correct and the coverage of the registers is high. The purpose of this study was to evaluate the validity of the Finnish hospital discharge registers and causes of death registers stroke diagnoses against the population-based FINSTROKE register. METHODS: All first stroke events from the hospital discharge registers and causes of death registers from the areas covered by the FINSTROKE register were obtained for years 1993-1998 and linked to the FINSTROKE register. The sensitivity and positive predictive values were calculated. RESULTS: A total of 3633 stroke events, 767 fatal and 2866 non-fatal strokes, were included in the registers. The sensitivity for all first stroke events was 85%, for fatal strokes 86% and for non-fatal strokes 85%. The positive predictive values for all first strokes was 86%, for fatal strokes 92% and for non-fatal strokes 85%. The sensitivity as well as the positive predictive values for subarachnoid haemorrhage and intracerebral haemorrhage was higher than for cerebral infarctions. There were no marked differences in the sensitivity or positive predictive values between men and women. CONCLUSIONS: The sensitivity and the positive predictive values of the Finnish hospital discharge registers and causes of death registers are fairly good. Finnish administrative registers can be used for the monitoring of stroke incidence, but the number of cerebral infarctions should be interpreted with caution.     

Probing the ability of the coat and vertex protein of the membrane-containing bacteriophage PRD1 to display a meningococcal epitope

Bacteriophage PRD1 is an icosahedral dsDNA virus with a diameter of 740 A and an outer protein shell composed of 720 copies of major coat protein P3. Spike complexes at the vertices are composed of a pentameric base (protein P31) and a spike structure (proteins P5 and P2) where the N-terminal region of the trimeric P5 is associated with the base and the C-terminal region of P5 is associated with receptor-binding protein P2. The functionality of proteins P3 and P5 was investigated using insertions and deletions. It was observed that P3 did not tolerate changes whereas P5 tolerated changes much more freely. These properties support the hypothesis that viruses have core structures and functions, which remain stable over time, as well as other elements, responsible for host interactions, which are evolutionally more fluid. The insertional probe used was the apex of exposed loop 4 of group B meningococcal outer membrane protein PorA, a medically important subunit vaccine candidate. It was demonstrated that the epitope could be displayed on the virus surface as part of spike protein P5.     

Quantitative measurement of regional lung gas volume by synchrotron radiation computed tomography

The aim of this study was to assess the feasibility of a novel respiration-gated spiral synchrotron radiation computed tomography (SRCT) technique for direct quantification of absolute regional lung volumes, using stable xenon (Xe) gas as an inhaled indicator. Spiral SRCT with K-edge subtraction using two monochromatic x-ray beams was used to visualize and directly quantify inhaled Xe concentrations and airspace volumes in three-dimensional (3D) reconstructed lung images. Volume measurements were validated using a hollow Xe-filled phantom. Spiral images spanning 49 mm in lung height were acquired following 60 breaths of an 80% Xe-20% O2 gas mixture, in two anaesthetized and mechanically ventilated rabbits at baseline and after histamine aerosol inhalation. Volumetric images of 20 mm lung sections were obtained at functional residual capacity (FRC) and at end-inspiration. 3D images showed large patchy filling defects in peripheral airways and alveoli following histamine provocation. Local specific lung compliance was calculated based on FRC/end-inspiration images in normal lung. This study demonstrates spiral SRCT as a new technique for direct determination of regional lung volume, offering possibilities for non-invasive investigation of regional lung function and mechanics, with a uniquely high spatial resolution. An example of non-uniform volume distribution in rabbit lung following histamine inhalation is presented.     

Whole-exome sequencing of Finnish patients with vascular cognitive impairment

Cerebral small vessel disease (CSVD) is the most important cause of vascular cognitive impairment (VCI). Most CSVD cases are sporadic but familial monogenic forms of the disorder have also been described. Despite the variants identified, many CSVD cases remain unexplained genetically. We used whole-exome sequencing in an attempt to identify novel gene variants underlying CSVD. A cohort of 35 Finnish patients with suspected CSVD was analyzed. Patients were screened negative for the most common variants affecting function in NOTCH3 in Finland (p.Arg133Cys and p.Arg182Cys). Whole-exome sequencing was performed to search for a genetic cause of CSVD. Our study resulted in the detection of possibly pathogenic variants or variants of unknown significance in genes known to associate with CSVD in six patients, accounting for 17% of cases. Those genes included NOTCH3, HTRA1, COL4A1, and COL4A2. We also identified variants with predicted pathogenic effect in genes associated with other neurological or stroke-related conditions in seven patients, accounting for 20% of cases. This study supports pathogenic roles of variants in COL4A1, COL4A2, and HTRA1 in CSVD and VCI. Our results also suggest that vascular pathogenic mechanisms are linked to neurodegenerative conditions and provide novel insights into the molecular basis of VCI.Subject terms: Stroke, Sequencing, Genetics research, Dementia     

Virulence-plasmid is associated with the inhibition of opsonization in Yersinia enterocolitica and Yersinia pseudotuberculosis.

Plasmid-cured variants of virulent strains of Yersinia enterocolitica and Y. pseudotuberculosis were obtained by selection after growth in calcium-deficient medium. To obtain antigen preparations consisting of whole bacteria the original plasmid-containing strains and the plasmid-cured variants were grown in conditions favouring expression of the temperature-inducible outer membrane proteins of Yersinia (YOP) (37 degrees C, calcium-deficient culture medium). The presence or absence of the YOP on the bacteria was verified by immunoblotting. Opsonophagocytosis of YOP-negative Yersinia preparations (YOP-) was compared to that of YOP-containing ones (YOP+) in human polymorphonuclear leukocyte (PMN) chemiluminescence (CL) assay. The attachment of complement C3b on the surface of the bacteria after opsonization with normal human serum was determined by using a fluorescent anti-C3c-antibody and flow cytometry. YOP+ bacteria resisted opsonization in the absence of specific antibodies, as indicated by diminished C3b-fixation on bacteria and weaker CL response. This implies that virulence-plasmid-coded structures provide Y. enterocolitica and Y. pseudotuberculosis with an ability to avoid complement-mediated opsonization and phagocytosis.     

T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens

We show here that T cell cross-reactivity between heterologous viruses influences the immunodominance of virus-specific CD8(+) T cells by two mechanisms. First, T cells specific for cross-reactive epitopes dominate acute responses to viral infections; second, within the memory pool, T cells specific for cross-reactive epitopes are maintained while those specific for non-cross-reactive epitopes are selectively lost. These findings suggest an immunological paradigm in which viral infections shape the available T cell repertoire, causing alterations in the hierarchies of both the primary and memory CD8(+) T cell responses elicited by subsequent viral infections. Thus, immunodominance is a function of the host's previous exposure to unrelated pathogens, and this may have an impact on protective immunity and immunopathology.     

Ontogeny of alloreactivity in the chicken as measured by mixed lymphocyte reaction

Ontogeny of alloreactivity in the chicken thymus and spleen was studied in mixed lymphocyte cultures. Mixed lymphocyte reaction (MLR) to total major histocompatibility complex (MHC) (B-complex in chicken) disparity was first detected in the thymus of 16-day-old embryo and regularly detectable from the 18th embryonal day on. Small strain-specific differences in the strength and appearance of the response were, however, observed. MLR to class I MHC (B-F) antigen disparity was not detectable before hatching. Exogenous interleukin-2-containing supernatant added to the cultures had only a minor effect on MLR of embryonal thymocytes. In the spleen, MLR was first detectable in some strain combinations on day 3 and regularly found on the 7th day posthatching, indicating colonization of peripheral lymphoid organs by thymus-derived mature T cells. Our results show the association of phenotypic and functional maturation of chicken T cells. The ontogeny of alloreactivity can now be compared to the appearance of T cell receptor (TCR), CD4, and CD8-bearing cells in the thymus and peripheral lymphoid organs.