Pituitary Apoplexy Following Elective Total Hip Replacement.

Pituitary apoplexy is an endocrine-related emergency most commonly caused by hemorrhage into a preexisting pituitary adenoma. Known risk factors for such hemorrhage include major surgical procedures, head trauma, pregnancy, anticoagulation, and the administration of hormone therapies for the correction of primary hypothalamic deficiencies. Elective orthopedic surgery is an uncommon precipitator of pituitary apoplexy that is rarely described. We report the case of a patient with a previously unknown pituitary macroadenoma who developed apoplexy as a complication of elective right total hip arthroplasty.

Changes in IgA Protease Expression Are Conferred by Changes in Genomes during Persistent Infection by Nontypeable Haemophilus influenzae in Chronic Obstructive Pulmonary Disease.

Nontypeable Haemophilus influenzae (NTHi) is an exclusively human pathobiont that plays a critical role in the course and pathogenesis of chronic obstructive pulmonary disease (COPD). NTHi causes acute exacerbations of COPD and also causes persistent infection of the lower airways. NTHi expresses four IgA protease variants (A1, A2, B1, and B2) that play different roles in virulence. Expression of IgA proteases varies among NTHi strains, but little is known about the frequency and mechanisms by which NTHi modulates IgA protease expression during infection in COPD. To assess expression of IgA protease during natural infection in COPD, we studied IgA protease expression by 101 persistent strains (median duration of persistence, 161 days; range, 2 to 1,422 days) collected longitudinally from patients enrolled in a 20-year study of COPD upon initial acquisition and immediately before clearance from the host. Upon acquisition, 89 (88%) expressed IgA protease. A total of 16 of 101 (16%) strains of NTHi altered expression of IgA protease during persistence. Indels and slipped-strand mispairing of mononucleotide repeats conferred changes in expression of igaA1, igaA2, and igaB1 Strains with igaB2 underwent frequent changes in expression of IgA protease B2 during persistence, mediated by slipped-strand mispairing of a 7-nucleotide repeat, TCAAAAT, within the open reading frame of igaB2 We conclude that changes in iga gene sequences result in changes in expression of IgA proteases by NTHi during persistent infection in the respiratory tract of patients with COPD.

Triple Staining Including FOXA2 Identifies Stem Cell Lineages Undergoing Hepatic and Biliary Differentiation in Cirrhotic Human Liver.

Recent investigations have reported many markers associated with human liver stem/progenitor cells, "oval cells," and identified "niches" in diseased livers where stem cells occur. However, there has remained a need to identify entire lineages of stem cells as they differentiate into bile ducts or hepatocytes. We have used combined immunohistochemical staining for a marker of hepatic commitment and specification (FOXA2 [Forkhead box A2]), hepatocyte maturation (Albumin and HepPar1), and features of bile ducts (CK19 [cytokeratin 19]) to identify lineages of stem cells differentiating toward the hepatocytic or bile ductular compartments of end-stage cirrhotic human liver. We identified large clusters of disorganized, FOXA2 expressing, oval cells in localized liver regions surrounded by fibrotic matrix, designated as "micro-niches." Specific FOXA2-positive cells within the micro-niches organize into primitive duct structures that support both hepatocytic and bile ductular differentiation enabling identification of entire lineages of cells forming the two types of structures. We also detected expression of hsa-miR-122 in primitive ductular reactions expected for hepatocytic differentiation and hsa-miR-23b cluster expression that drives liver cell fate decisions in cells undergoing lineage commitment. Our data establish the foundation for a mechanistic hypothesis on how stem cell lineages progress in specialized micro-niches in cirrhotic end-stage liver disease.

Small RNAs derived from lncRNA RNase MRP have gene-silencing activity relevant to human cartilage-hair hypoplasia.

Post-transcriptional processing of some long non-coding RNAs (lncRNAs) reveals that they are a source of miRNAs. We show that the 268-nt non-coding RNA component of mitochondrial RNA processing endoribonuclease, (RNase MRP), is the source of at least two short (∼20 nt) RNAs designated RMRP-S1 and RMRP-S2, which function as miRNAs. Point mutations in RNase MRP cause human cartilage-hair hypoplasia (CHH), and several disease-causing mutations map to RMRP-S1 and -S2. SHAPE chemical probing identified two alternative secondary structures altered by disease mutations. RMRP-S1 and -S2 are significantly reduced in two fibroblast cell lines and a B-cell line derived from CHH patients. Tests of gene regulatory activity of RMRP-S1 and -S2 identified over 900 genes that were significantly regulated, of which over 75% were down-regulated, and 90% contained target sites with seed complements of RMRP-S1 and -S2 predominantly in their 3' UTRs. Pathway analysis identified regulated genes that function in skeletal development, hair development and hematopoietic cell differentiation including PTCH2 and SOX4 among others, linked to major CHH phenotypes. Also, genes associated with alternative RNA splicing, cell proliferation and differentiation were highly targeted. Therefore, alterations RMRP-S1 and -S2, caused by point mutations in RMRP, are strongly implicated in the molecular mechanism of CHH.

Effect of specific anion on templated crystal nucleation at the liquid-liquid interface.

In this work, we have investigated the effect of potassium salts of different anions upon the crystal nucleation of K(2)SO(4) as interfacially templated by a surfactant monolayer of 1-octadecylamine (ODA), in an aqueous microdroplet system bounded by a liquid-liquid interface with 1-decanol. The salts used were K(2)HPO(4), KCl, KBr, KI, KNO(3), and KSCN, present at an initial concentration of 10 mM within an aqueous microdroplet containing K(2)SO(4) at an initial concentration of 287 mM. Supersaturation and subsequent crystallization were isothermally induced by droplet dissolution into the dehydrating decanol phase. The K(2)SO(4) solute crystallization behavior was studied by measurement of the calculated concentration of the solute in the microdroplet at the onset of crystallization, i.e., at the first perceptible microscopic appearance of a solid phase, and by crystal habit. Certain salts, e.g., K(2)HPO(4), had almost no influence on the templating ability of ODA, while the ability of ODA to template nucleation and direct the formation of regular crystal habit of K(2)SO(4) became appreciably disrupted in the presence of more chaotropic anions, such as SCN(-) or NO(3)(-). The propensity for anions to disrupt crystal templating was clearly seen to follow a Hofmeister trend. For crystallization events induced in the absence of ODA, however, these added salts had no influence on the outcome of the events. Microdroplets bounded by an ODA monolayer were also found to undergo droplet shrinkage into the surrounding dehydrating phase at a rate which generally depended upon the nature of the anion in the droplet, with chaotropic anions having an apparent effect of promoting shrinkage. Our findings suggest that the packing or ordering of an ODA monolayer at a liquid-liquid interface is strongly influenced by an interaction between anions in the aqueous phase and the surfactant monolayer at the liquid-liquid interface, which is manifested in its effect upon the crystal templating behavior. These intriguing results can have important implications for the understanding of biomineralization processes which occur in heterogeneous environments.