Influence of the storage orientation on the aerodynamic particle size of a suspension metered dose inhaler containing propellant HFA-227.

Presented in this work are the results of a study designed to investigate the impact of the storage position on the particle size distribution (PSD) of a steroid suspension metered dose inhaler (MDI) containing propellant HFA-227. It was hypothesized that the orientation of MDI samples upon storage could influence the PSD of the emitted dose, since it determines the amount of contact the liquid formulation has with the valve and therefore the quantity of nonvolatile leachable materials from the valve components that may enter the product and potentially impact the aerosol spray dynamics. Samples stored in the valve down orientation (i.

Semantic memory deficit with a left thalamic infarct.

Previous studies of patients with thalamic lesions have reported consistent word finding difficulties without a proposed etiology. The authors describe a patient with a focal left thalamic infarct, pronounced word finding problems, and a relatively selective impairment in semantic memory for object recall from features. The thalamus is proposed to facilitate electrical activity between brain regions that encode object features, resulting in object recall.

Ursodeoxycholic acid inhibits Ras mutations, wild-type Ras activation, and cyclooxygenase-2 expression in colon cancer.

K-ras mutations occur frequently in colon cancer and contribute to autonomous growth. In the azoxymethane (AOM) model of colon cancer, in addition to K-ras mutations, we have shown that wild-type (WT) Ras can be activated by upstream pathways, including, e.g.

Structure of Mycobacterium tuberculosis methionine sulfoxide reductase A in complex with protein-bound methionine.

Peptide methionine sulfoxide reductase (MsrA) repairs oxidative damage to methionine residues arising from reactive oxygen species and reactive nitrogen intermediates. MsrA activity is found in a wide variety of organisms, and it is implicated as one of the primary defenses against oxidative stress. Disruption of the gene encoding MsrA in several pathogenic bacteria responsible for infections in humans results in the loss of their ability to colonize host cells.

The effect of immunosuppressive regimens on the recurrence of primary biliary cirrhosis after liver transplantation.

Recurrence of primary biliary cirrhosis (PBC) has been described in liver transplant recipients. Type of immunosuppression has been reported to influence the frequency of recurrence. The aim of this study is to evaluate the occurrence and pattern of recurrent PBC in our liver transplant recipients and determine any association of immunosuppressive agents with its recurrence.

Hepatic manifestations of Jeune syndrome (asphyxiating thoracic dystrophy).

Asphyxiating thoracic dystrophy, or Jeune syndrome, is an autosomal recessive skeletal dysplasia with multiorgan involvement. Most patients develop progressive respiratory insufficiency related to the abnormally small thorax and renal insufficiency. Other clinical manifestations include cystic lesions of the pancreas and retinal abnormalities.

Distinct prefrontal cortex activity associated with item memory and source memory for visual shapes.

In contrast to item memory, which refers to recognition or recall of previously presented information, source memory refers to memory for the context of previously presented information. The relatively few functional MRI (fMRI) source memory studies conducted to date have provided evidence that item memory and source memory are associated with differential activity in right and left prefrontal cortex, respectively. To both confirm this distinction in prefrontal cortex and to determine whether other differences in the neural substrates associated with these cognitive functions exist, an event-related fMRI study was conducted.

Amyloid-like filaments and water-filled nanotubes formed by SOD1 mutant proteins linked to familial ALS.

Mutations in the SOD1 gene cause the autosomal dominant, neurodegenerative disorder familial amyotrophic lateral sclerosis (FALS). In spinal cord neurons of human FALS patients and in transgenic mice expressing these mutant proteins, aggregates containing FALS SOD1 are observed. Accumulation of SOD1 aggregates is believed to interfere with axonal transport, protein degradation and anti-apoptotic functions of the neuronal cellular machinery.

Role of 4-1BB in allograft rejection mediated by CD8+ T cells.

Blockade of traditional costimulatory molecules fails to inhibit rejection in many models where CD8+ T cells are sufficient to mediate rejection. This observation demonstrates that in many settings CD8+ T cells are not dependent upon CD28 or CD154 signals to mediate rejection. 4-1BB (CD137) has been shown to be an important regulatory molecule for CD8+ T cells in a variety of nontransplant models.

Structure-function analysis of the auxilin J-domain reveals an extended Hsc70 interaction interface.

J-domains are widespread protein interaction modules involved in recruiting and stimulating the activity of Hsp70 family chaperones. We have determined the crystal structure of the J-domain of auxilin, a protein which is involved in uncoating clathrin-coated vesicles. Comparison to the known structures of J-domains from four other proteins reveals that the auxilin J-domain is the most divergent of all J-domain structures described to date.

The structure of holo and metal-deficient wild-type human Cu, Zn superoxide dismutase and its relevance to familial amyotrophic lateral sclerosis.

Cu, Zn superoxide dismutase (SOD1) forms a crucial component of the cellular defence against oxidative stress. Zn-deficient wild-type and mutant human SOD1 have been implicated in the disease familial amyotrophic lateral sclerosis (FALS). We present here the crystal structures of holo and metal-deficient (apo) wild-type protein at 1.

Misfolded CuZnSOD and amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of motor neurons. The inherited form of the disease, familial ALS, represents 5-10% of the total cases, and the best documented of these are due to lesions in SOD1, the gene encoding copper-zinc superoxide dismutase (CuZnSOD). The mechanism by which mutations in SOD1 cause familial ALS is currently unknown.

An alternative mechanism of bicarbonate-mediated peroxidation by copper-zinc superoxide dismutase: rates enhanced via proposed enzyme-associated peroxycarbonate intermediate.

Hydrogen peroxide can interact with the active site of copper-zinc superoxide dismutase (SOD1) to generate a powerful oxidant. This oxidant can either damage amino acid residues at the active site, inactivating the enzyme (the self-oxidative pathway), or oxidize substrates exogenous to the active site, preventing inactivation (the external oxidative pathway). It is well established that the presence of bicarbonate anion dramatically enhances the rate of oxidation of exogenous substrates.

Right Hemisphere Language Dominance in a Right-Handed Patient with Late-Onset Seizures.

Right hemisphere language dominance is rare in right-handed individuals and usually the result of language transfer associated with early left hemisphere pathology. We studied a 33-year-old right-handed man, with a normal MRI scan, who developed left frontal lobe seizures at age 15 years. Language lateralization testing by intracarotid amobarbital injection and dichotic listening showed the patient to be strongly right hemisphere language dominant.

cDNA microarray analysis of macroregenerative and dysplastic nodules in end-stage hepatitis C virus-induced cirrhosis.

Hepatocellular carcinoma is a common malignancy causing significant morbidity and mortality worldwide. In this study we use expression microarray technology to identify novel genes that consistently displayed altered expression levels in the earliest identifiable precursors to hepatocellular carcinoma, dysplastic and macroregenerative nodules. The gene expression profiles from nine patients with end-stage hepatitis C cirrhosis that contained a combined 11 dysplastic or macroregenerative nodules were compared to the patient's matched cirrhotic liver tissue.

Rosai-Dorfman disease presenting in the gastrointestinal tract.

Rosai-Dorfman disease (RDD) rarely presents a diagnostic challenge. However, unusual sites of presentation can cause confusion. We present a case of RDD of the colon in a symptomatic 51-year-old woman.

Ursodeoxycholic acid and F(6)-D(3) inhibit aberrant crypt proliferation in the rat azoxymethane model of colon cancer: roles of cyclin D1 and E-cadherin.

We have previously demonstrated that ursodeoxycholic acid(UDCA) and a fluorinated analogue of vitamin D(3), F(6)-D(3),inhibited colonic carcinogenesis in the azoxymethane (AOM) model. Generalized colonic mucosal hyperproliferation and aberrant crypt foci (ACF) are intermediate biomarkers of colon cancer. Using these biomarkers, in this study we examined the anticarcinogenic mechanisms of these chemopreventive agents.

First two patients with ulcerative colitis who developed classical thrombotic thrombocytopenic purpura successfully treated with medical therapy and plasma exchange.

The association of ulcerative colitis (UC) and thrombotic thrombocytopenic purpura (TTP) is rare. Only one prior patient with these two syndromes has been reported in the literature. In that case, splenectomy and proctectomy were performed to control the symptoms of TTP.

Women's health and the internet: understanding emerging trends and implications.

Internet has become a major information source, yet little is known about why women use the internet for obtaining health information. In this paper, we propose and test three exploratory models to explain internet use for obtaining health information: health and wellness model, health needs model, and search costs model. The health and wellness model is based on the notion that internet has become such an integral part of daily life that health-conscious women use the internet in a pro-active manner for health promotion.

Ursodeoxycholic acid inhibits the initiation and postinitiation phases of azoxymethane-induced colonic tumor development.

Colonic tumorigenesis involves the processes of initiation and promotion/progression from normal epithelial cells to tumors. Studies in both humans and experimental models of colon cancer indicate that secondary bile acids promote tumor development. In contrast, we have demonstrated previously that another bile acid, ursodeoxycholic acid (UDCA), inhibits the development of azoxymethane (AOM)-induced colon cancer in rats.

Elevated protein expression of cyclin D1 and Fra-1 but decreased expression of c-Myc in human colorectal adenocarcinomas overexpressing beta-catenin.

Mutations of the adenomatous polyposis coli tumor suppressor gene, or its downstream target beta-catenin, have been implicated in the initiation of most sporadic human colorectal epithelial neoplasms. These mutations, in turn, lead to aberrant nuclear accumulation of beta-catenin and subsequent activation of the beta-catenin/Tcf transcription factor complex. In vitro studies utilizing cultured human colon cancer cell lines have identified c-myc, cyclin D1 and fra-1 as target genes of beta-catenin/Tcf signaling.

Natural history of mucinous ductal ectasia of the pancreas: a case report and review of the literature.

Mucinous ductal ectasia (MDE) remains a less known disease entity of the pancreas. In an attempt to further characterize its natural history, we report the case of a 68-yr-old man with MDE initially unrecognized in an abdominal CT obtained 5 yr before diagnosis and resection. Furthermore, we have reviewed available case reports in the English literature to clarify the differences between MDE and mucinous cystic neoplasm, two entities that have been frequently confused for one another.

Crystal structure of TB-RBP, a novel RNA-binding and regulating protein.

The testis/brain-RNA-binding protein (TB-RBP) spatially and temporally controls the expression of specific mRNAs in developing male germ cells and brain cells, and is implicated in DNA recombination and repair events. We report the 2.65 A crystal structure of mouse TB-RBP.