University of Kansas

About: University of Kansas is a education organization based out in Lawrence, Kansas, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 38183 authors who have published 81381 publications receiving 2986312 citations. The organization is also known as: KU & Univ of Kansas.

Head injury and the risk of AD in the MIRAGE study

Abstract: Objectives: It has been suggested in some studies that head injury is a risk factor for AD, and that this risk is heightened among carriers of the APOE -e4 allele. We examined the effects of head injury and APOE genotype on AD risk in a large family study. Subjects: A total of 2,233 probands who met criteria for probable or definite AD and their 14,668 first-degree family members (4,465 parents, 7,694 siblings, and 2,509 spouses) were ascertained at 13 centers in the United States, Canada, and Germany participating in the MIRAGE (Multi-Institutional Research in Alzheimer Genetic Epidemiology) project. Information on head injury was collected by interview of multiple informants and review of medical records. Nondemented relatives and spouses served as control subjects for this study. Methods: Odds of AD for head trauma with or without loss of consciousness were computed by comparing probands with unaffected spouses using conditional logistic regression analysis. To account for the unique biologic relationship between probands and their parents and siblings, odds of AD were computed using a generalized estimating equation (GEE) Poisson regression approach. GEE logistic regression was used to examine the joint effects of APOE genotype and head injury on the odds of AD in probands and a control group comprised of unaffected siblings and spouses. Results: Comparison of probands with their unaffected spouses yielded odds ratios for AD of 9.9 (95% CI, 6.5 to 15.1) for head injury with loss of consciousness and 3.1 (2.3 to 4.0) for head injury without loss of consciousness. The corresponding odds derived from the comparison of probands with their parents and sibs were 4.0 (2.9 to 5.5) for head injury with loss of consciousness and 2.0 (1.5 to 2.7) for head injury without loss of consciousness. Head injury without loss of consciousness did not significantly increase the risk of AD in spouses (OR = 1.3; 95% CI, 0.4 to 4.1). The joint effects of head injury and APOE genotype were evaluated in a subsample of 942 probands and 327 controls (spouses and siblings). Head injury increased the odds of AD to a greater extent among those lacking e4 (OR = 3.3) than among e4 heterozygotes (OR = 1.8) or homozygotes (OR = 1.3). Conclusion: Head injury is a risk factor for AD. The magnitude of the risk is proportional to severity and heightened among first-degree relatives of AD patients. The influence of head injury on the risk of AD appears to be greater among persons lacking APOE -e4 compared with those having one or two e4 alleles, suggesting that these risk factors may have a common biologic underpinning.

HLA-G and immune tolerance in pregnancy

Abstract: Multiple mechanisms underlie the surprising willingness of mothers to tolerate genetically different fetal tissues during pregnancy. Chief among these is the choice of HLA-G, a gene with few alleles, rather than the highly polymorphic HLA-A and -B genes, for expression by the placental cells that interface directly with maternal blood and tissues. Novel aspects of this major histocompatibility complex class Ib gene include alternative splicing to permit production of membrane and soluble isoforms, deletions that dampen responses to interferons, and a shortened cytoplasmic tail that affects expression at the cell surface. Placental cells migrating into the maternal uterus synthesize both membrane and soluble isoforms, which interact with inhibitory receptors on leukocytes such as ILT2 and ILT4. Cytotoxic T lymphocytes either die or reduce production of one of their major coreceptor/activator cell surface molecules, CD8; natural killer cells are immobilized and mononuclear phagocytes are programmed into suppressive modes characterized by high production of anti-inflammatory cytokines. The idea that placental HLA-G proteins facilitate semiallogeneic pregnancy by inhibiting maternal immune responses to foreign (paternal) antigens via these actions on immune cells is now well established, and the postulate that the recombinant counterparts of these proteins may be used as powerful tools for preventing immune rejection of transplanted organs is gaining in popularity.

Autosomal Dominant Polycystic Kidney Disease

Abstract: Shortly after being elbowed in the flank during a pickup basketball game, a 35-year-old healthy man has severe, colicky abdominal pain followed by gross hematuria. He is hospitalized, and a renal ultrasound scan reveals bilateral polycystic kidneys and liver cysts, previously unknown to the patient. The blood pressure is 160/100 mm Hg. The serum creatinine concentration is 0.9 mg per deciliter (80 μmol per liter). The pain subsides in 2 days with analgesics, rest, and fluids; the gross hematuria resolves in 4 days, although microscopic hematuria persists. How should his case be further evaluated and managed? The Clinical Problem Autosomal dominant polycystic kidney disease is an inherited systemic disorder with major renal manifestations and, in some cases, abnormalities in the liver, the pancreas, the brain, the arterial blood vessels, or a combination of these sites. 1 The disease affects approximately 300,000 to 600,000 Americans of either sex, and without racial predilection. Each child of an affected parent has a 50% chance of inheriting the mutated gene, which is completely penetrant. Autosomal dominant polycystic kidney disease arises as a spontaneous mutation in approximately 5% of cases. However, in about one fourth of newly diagnosed cases, patients report no history of the disease, indicating that many familial cases go undetected. Affected patients have numerous fluid-filled cysts in the kidneys; these cysts may collect blood after mild or severe trauma or may be the site of pyogenic infection. In rare cases, a malignant neoplasm develops, although the incidence of renal cancer among affected patients is not increased, as compared with the incidence in the general population. Autosomal dominant polycystic kidney disease begins in utero, but signs of the disease may not be detected for several decades. Autosomal dominant polycystic kidney disease is caused by mutations in either of the two genes encoding plasma membrane–spanning polycystin 1 and polycystin 2 (PKD1 and PKD2, respectively). The polycystins regulate tubular and vascular development in the kidneys and other organs (liver, brain, heart, and pancreas) 2 and interact to increase the flow of calcium through a cation channel formed in plasma membranes by polycystin 2. A mutation of either polycystin can disrupt the function of the other, resulting in similar clinical presentations. However, mutations of PKD1 are more common than mutations of PKD2 (accounting for 85% of cases), are likely to be associated with more renal cysts, 3,4 and lead to renal insufficiency on average 20 years earlier (median ages at the time of death or end-stage failure, 53 and 69 years, respectively). 5

Observation of the rare B-s(0)->mu(+)mu(-) decay from the combined analysis of CMS and LHCb data

Abstract: The standard model of particle physics describes the fundamental particles and their interactions via the strong, electromagnetic and weak forces. It provides precise predictions for measurable quantities that can be tested experimentally. The probabilities, or branching fractions, of the strange B meson (B-s(0)) and the B-0 meson decaying into two oppositely charged muons (mu(+) and mu(-)) are especially interesting because of their sensitivity to theories that extend the standard model. The standard model predicts that the B-s(0)->mu(+)mu(-) and B-0 ->mu(+)mu(-) decays are very rare, with about four of the former occurring for every billion B-s(0) mesons produced, and one of the latter occurring for every ten billion B-0 mesons(1). A difference in the observed branching fractions with respect to the predictions of the standard model would provide a direction in which the standard model should be extended. Before the Large Hadron Collider (LHC) at CERN2 started operating, no evidence for either decay mode had been found. Upper limits on the branching fractions were an order of magnitude above the standard model predictions. The CMS (Compact Muon Solenoid) and LHCb(Large Hadron Collider beauty) collaborations have performed a joint analysis of the data from proton-proton collisions that they collected in 2011 at a centre-of-mass energy of seven teraelectronvolts and in 2012 at eight teraelectronvolts. Here we report the first observation of the B-s(0)->mu(+)mu(-) decay, with a statistical significance exceeding six standard deviations, and the best measurement so far of its branching fraction. Furthermore, we obtained evidence for the B-0 ->mu(+)mu(-) decay with a statistical significance of three standard deviations. Both measurements are statistically compatible with standard model predictions and allow stringent constraints to be placed on theories beyond the standard model. The LHC experiments will resume taking data in 2015, recording proton-proton collisions at a centre-of-mass energy of 13 teraelectronvolts, which will approximately double the production rates of B-s(0) and B-0 mesons and lead to further improvements in the precision of these crucial tests of the standard model.