Sudden infant death "syndrome"-Insights and future directions from a Utah population database analysis.

"Sudden Infant Death syndrome" (SIDS) represents the commonest category of infant death after the first month of life. As genome scale sequencing greatly facilitates the identification of new candidate disease variants, the challenges of ascribing causation to these variants persists. In order to determine the extent to which SIDS occurs in related individuals and their pedigree structure we undertook an analysis of SIDS using the Utah Population Database, recording, for example, evidence of enrichment for genetic causation following the back-to-sleep recommendations of 1992 and 1994.

CDX2 protein expression compared to alcian blue staining in the evaluation of esophageal intestinal metaplasia.

Aim: To compare the sensitivity and specificity of CDX2 and alcian blue (AB) pH 2.5 staining in identifying esophageal intestinal metaplasia.

Methods: One hundred and ninty-nine biopsies from 186 patients were retrospectively reviewed and categorized as Barrett's esophagus (BE) (n = 108); non-Barrett's esophagus (NBE) (n = 48); columnar blue cells (CB) and esophageal glands (EG) (n = 43).

ADAM "sequence" part II: hypothesis and speculation.

Noted for centuries in humans, a relatively hairless mammal [e.g., Hallero, 1766; Hohl, 1828 in Klunker, 2003], the so-called amniotic deformities, adhesions, mutilations (ADAM) sequence remains causally and pathogenetically incognito.

Postmortem ultrasonography of the macerated fetus complements autopsy following in utero fetal demise.

Postmortem evaluation following an in utero fetal demise is essential for determining cause of death and counseling regarding future pregnancies. Severe maceration and fetal size along with patient desires may limit the physician's ability to perform a complete autopsy. In the cases presented, we demonstrate the utility of postmortem ultrasonography as an adjunct to traditional autopsy following fetal demise.

Call for participation in the neurogenetics consortium within the Human Variome Project.

The rate of DNA variation discovery has accelerated the need to collate, store and interpret the data in a standardised coherent way and is becoming a critical step in maximising the impact of discovery on the understanding and treatment of human disease. This particularly applies to the field of neurology as neurological function is impaired in many human disorders. Furthermore, the field of neurogenetics has been proven to show remarkably complex genotype-to-phenotype relationships.

Disruption of cAMP and prostaglandin E2 transport by multidrug resistance protein 4 deficiency alters cAMP-mediated signaling and nociceptive response.

Multidrug resistance protein 4 (MRP4; ABCC4) is a member of the MRP/ATP-binding cassette family serving as a transmembrane transporter involved in energy-dependent efflux of anticancer/antiviral nucleotide agents and of physiological substrates, including cyclic nucleotides and prostaglandins (PGs). Phenotypic consequences of mrp4 deficiency were investigated using mrp4-knockout mice and derived immortalized mouse embryonic fibroblast (MEF) cells. Mrp4 deficiency caused decreased extracellular and increased intracellular levels of cAMP in MEF cells under normal and forskolin-stimulated conditions.

Age-related differences in vincristine toxicity and biodistribution in wild-type and transporter-deficient mice.

The impact of mouse multidrug resistance genes mdrla/b and mrpl on age-related differences in the toxicity and biodistribution of vincristine (VCR) was evaluated in wild-type, mrpl(-/-), mdrla/b(-/-), and combined mdrla/b(-/-), mrpl(-/-) weanling and adult mice given a single IP dose of VCR ranging from 0.0625 to 6 mg/kg. Weanling mice of all four genotypes were more sensitive than adult animals as determined by survival rate, average time of death, and pathologic findings.

Comparative study of the importance of multidrug resistance-associated protein 1 and P-glycoprotein to drug sensitivity in immortalized mouse embryonic fibroblasts.

Multidrug resistance-associated protein 1 and P-glycoprotein are major ATP-binding cassette transporters that function as efflux pumps and confer resistance to a variety of structurally unrelated anticancer agents. To evaluate the comparative importance of these transporters with respect to anticancer agents, we established and characterized SV40-immortalized [mrp1(-/-)] (KO), [mdr1a/1b(-/-)] (DKO), and combined [mrp1 (-/-), mdr1a/1b(-/-)] (TKO) deficient fibroblast lines derived from primary embryonic fibroblasts of knockout mice. Western blot analyses demonstrated that KO and DKO fibroblasts exhibited similar levels of P-glycoprotein and mrp1, respectively, to that of wild-type (WT) fibroblasts.