Association of Chlamydia pneumoniae with coronary artery disease and its progression is dependent on the modifying effect of mannose-binding lectin

Background— The possible association between coronary artery disease (CAD) and Chlamydia pneumoniae (C pneumoniae) infection is controversial. On the basis of the recent suggestion that mannose-binding lectin (MBL) variant alleles are related to an increased risk of severe atherosclerosis, and on the in vitro interaction of MBL with C pneumoniae, we asked whether MBL might contribute to CAD in conjunction with C pneumoniae. Methods and Results— Antibodies to C pneumoniae were measured by immunofluorescence and MBL alleles were determined by polymerase chain reaction technique in samples from 210 patients with CAD and 257 healthy subjects from Hungary collected between 1995 and 1996. A higher percentage of patients with CAD were anti-C pneumoniae positive as compared with the control group (P=0.058). However, at logistic regression analysis adjusted to age, sex, and serum lipid levels, this difference was confined only to subjects carrying MBL variant alleles (P=0.035, odds ratio 2.63, [95% CI: 1.07 to 6.45]). In contrast, no significant difference was seen in those homozygous for the normal MBL allele (P=0.412). During a 65±5.8-month follow-up period, major outcomes (new myocardial infarction, and/or bypass operation or cardiovascular death) occurred in 11 C pneumoniae positive and 3 C pneumoniae negative patients. In the C pneumoniae positive group, the odds ratio of development of outcomes was 3.27 (95% CI: 1.10 to 9.71, P=0.033) in the carriers of the MBL variant alleles compared with the homozygous carriers of the normal MBL allele. Conclusions— These results indicate that infection with C pneumoniae leads mainly to the development and progression of severe CAD in patients with variation in the MBL gene

Alta frecuencia de un haplotipo susceptible del gen Mannose Binding Lectin, en las islas AnapiaSuana del lago Titicaca

We have analized the combination of variants at 4 sites of the gene MBL (mannose binding lectin) which is part of the immune system, in 19 normal individuals from the islands of Anapia-Suana in the Lake Titicaca. OnIy 3 combinations (haplotypes) were registered: LYPB, HYPA and LYPA; the proportion of the pressumed defective haplotype LYPB is 0.58 being the highest ever recorded. This haplotype is rare among European, Asian and African populations. It predisposes to infectious diseases as tuberculosis and AIDS as well as autoimmune diseases like reumatoid arthritis and lupus erithematosumo This finding lead our future efforts to elucidate the reason of this high frequency of LYPB and to determine its proportion in other islands of the Titicaca Lake.Se determinaron las combinaciones de variantes genéticas en 4 sitios del gen de la proteína asociada al sistema inmune MBL (mannose binding lectin), en 19 pobladores de las islas de AnapiaSuana del Lago Titicaca. Se encuentran solamente 3 combinaciones (haplotipos): LYFB, HYPA Y LYPA y se observa alta frecuencia (0.58) del haplotipo defectuoso LYPB en las mencionadas islas sobrepasando a otras frecuencias previamente reportadas en el mundo. Este haplotipo es poco frecuente en poblaciones europeas, asiáticas y africanas. La deficiencia sérica de LYPB predispone a infecciones como tuberculosis, VIH-1 y a enfermedades autoinmunes como artritis reumatoide y lupus eritematoso entre otras. Con estos antecedentes nuestros futuros esfuerzos se dirigirán a investigar la razón de la alta frecuencia de LYPB en estas islas y determinar la de las otras islas aledañas

Reviews

Reviews: Arne Skjølsvold: Slettabøboplassen. Et bidrag til diskusjonen om forholdet mellem fangst- og bondesamfunnet i yngre steinalder og bronsealder. Stavanger 1977. (by Svend Nielsen). Klaus Ebbesen: Tragtbægerkultur i Nordjylland. Nordiske Fortidsminder. Ser. B, Vol. 5, 197 8. (by P. 0. Nielsen). Birgitta Hulthen: On Ceramic Technology during the Scanian Neolithic and Bronze Age. Stockholm 1977. (by Ulla Engberg). Renate Rolle: Totenkult der Skythen I. Das Steppengebiet. Vorgeschichtliche Forschungen 18,I, I and I,2. Berlin-N.Y. 1979. (by Ole Klindt-Jensen). Werner Haarnagel: Die Grabung Feddersen Wierde. Methode, Hausbau, Siedlungs- u. Wirtschaftsformen sowie Sozialstruktur. Wiesbaden 1979. (by Steen Hvass). U. Nasman and E. Wegraeus (eds.): Eketorp. Fortification and Settlement on Öland/Sweden. The Setting. Stockholm 1979. (by Ulla Lund Hansen). Ingrid Ulbricht: Die Geweihverarbeitung in Haithabu. Die Ausgrabungen in Haithabu, Vol. 7. Neumünster 1978 . Heid Gjöstein Resi: Die Specksteinfunde aus Haithabu. Berichte über die Ausgrabungen in Haithabu, Vol. 14. Neumünster 1979. (by Hans Jørgen Madsen)

Beneficial effect of early initiation of lipid-lowering therapy following renal transplantation

Background. Renal transplant recipients have a significantly reduced life expectancy, largely due to premature cardiovascular disease. The aim of the current analysis was to investigate the importance of time of initiation of therapy after transplantation, on the benefits of statin therapy. Methods. 2102 renal transplant recipients with total cholesterol levels of 4.0-9.0 mmol/l were randomly assigned to treatment with fluvastatin (n = 1050) or placebo (n = 1052) and followed for a mean time of 5.1 years. The end-points were major cardiac events. The average median time from transplantation to randomization was 4.5 years (range: 0.5-29 years). Results. In patients starting treatment with fluvastatin 6 years, respectively. The risk reduction for patients initiating therapy with fluvastatin at years 0-2 (compared with >6 years) following transplantation was 59% (RR: 0.41; 95% CI: 0.18-0.92; P = 0.0328). This is also reflected in total time on renal replacement therapy: in patients in the first quartile (120 months) (P = 0.033). Conclusions. Our data support an early introduction of fluvastatin therapy in a population of transplant recipients at high risk of premature coronary heart diseas

Characteristics of white blood cell count in acute lymphoblastic leukemia : A COST LEGEND phenotype-genotype study

Background White blood cell count (WBC) as a measure of extramedullary leukemic cell survival is a well-known prognostic factor in acute lymphoblastic leukemia (ALL), but its biology, including impact of host genome variants, is poorly understood. Methods We included patients treated with the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol (N = 2347, 72% were genotyped by Illumina Omni2.5exome-8-Bead chip) aged 1-45 years, diagnosed with B-cell precursor (BCP-) or T-cell ALL (T-ALL) to investigate the variation in WBC. Spline functions of WBC were fitted correcting for association with age across ALL subgroups of immunophenotypes and karyotypes. The residuals between spline WBC and actual WBC were used to identify WBC-associated germline genetic variants in a genome-wide association study (GWAS) while adjusting for age and ALL subtype associations. Results We observed an overall inverse correlation between age and WBC, which was stronger for the selected patient subgroups of immunophenotype and karyotypes (rho(BCP-ALL )= -.17, rho(T-ALL )= -.19; p < 3 x 10(-4)). Spline functions fitted to age, immunophenotype, and karyotype explained WBC variation better than age alone (rho = .43, p << 2 x 10(-6)). However, when the spline-adjusted WBC residuals were used as phenotype, no GWAS significant associations were found. Based on available annotation, the top 50 genetic variants suggested effects on signal transduction, translation initiation, cell development, and proliferation. Conclusion These results indicate that host genome variants do not strongly influence WBC across ALL subsets, and future studies of why some patients are more prone to hyperleukocytosis should be performed within specific ALL subsets that apply more complex analyses to capture potential germline variant interactions and impact on WBC.Peer reviewe

Differences in hip bone mineral density may explain the hip fracture pattern in osteoarthritic hips

Introduction In patients with osteoarthritis of the hip (OAH), trochanteric fractures are much more common than femoral neck fractures. One reason may be altered bone composition in the proximal femurs. OAH often leads to a fixed external rotation of the hip, leading to difficulties in positioning during DXA measurements. We compared BMD in OAH-affected legs and healthy legs

All-sky search for time-integrated neutrino emission from astrophysical sources with 7 years of IceCube data

Since the recent detection of an astrophysical flux of high energy neutrinos, the question of its origin has not yet fully been answered. Much of what is known about this flux comes from a small event sample of high neutrino purity, good energy resolution, but large angular uncertainties. In searches for point-like sources, on the other hand, the best performance is given by using large statistics and good angular reconstructions. Track-like muon events produced in neutrino interactions satisfy these requirements. We present here the results of searches for point-like sources with neutrinos using data acquired by the IceCube detector over seven years from 2008--2015. The discovery potential of the analysis in the northern sky is now significantly below $E_\nu^2d\phi/dE_\nu=10^{-12}\:\mathrm{TeV\,cm^{-2}\,s^{-1}}$, on average $38\%$ lower than the sensitivity of the previously published analysis of four years exposure. No significant clustering of neutrinos above background expectation was observed, and implications for prominent neutrino source candidates are discussed.Comment: 19 pages, 17 figures, 3 tables; ; submitted to The Astrophysical Journa