Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study.

Study Objectives: We report on the long-term safety and efficacy of bosentan treatment in patients with pulmonary arterial hypertension (PAH).

Background: In a preceding study, bosentan was well tolerated and significantly improved the exercise capacity and hemodynamics of patients with PAH after 12 weeks of treatment.

Design: The present study was an open-label extension to the preceding double-blind, placebo-controlled study of 32 patients with PAH (primary or associated with scleroderma) who received bosentan or placebo at 125 mg bid for 3 to 7 months.

Detecting the expression of human endogenous retrovirus E envelope transcripts in human prostate adenocarcinoma.

Background: The expression of human endogenous retrovirus (HERV) mRNA and proteins was associated recently with diseases that include human malignancies. The authors report that, in the current study, transcripts encoding the envelope region of an HERV family, HERV-E, were expressed in human prostate carcinoma.

Methods: RNA was isolated from various prostate tissues and was tested for the expression of various HERV envelope (env) genes by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, RNA in situ hybridization (ISH), and Northern blot analysis.

Fitness of Cuscuta salina (Convolvulaceae) parasitizing Beta vulgaris (Chenopodiaceae) grown under different salinity regimes.

The distribution of saltmarsh dodder (Cuscuta salina) worldwide is restricted to areas of high salinity, where it parasitizes a variety of salt-tolerant plants. Because dodders do not maintain root connections to the soil, this pattern of parasitization may be related to the effects of salt stress on the host that increase the ability of attached dodders to more easily transfer host contents. This study explored whether a saline host environment is required for successful infection and whether stem contents of potential hosts become more concentrated in response to salinity.

LIM kinase 1 is essential for the invasive growth of prostate epithelial cells: implications in prostate cancer.

Mammalian LIM kinase 1 (LIMK1) is involved in reorganization of actin cytoskeleton through inactivating phosphorylation of the ADF family protein cofilin, which depolymerizes actin filaments. Maintenance of the actin dynamics in an ordered fashion is essential for stabilization of cell shape or promotion of cell motility depending on the cell type. These are the two key phenomena that may become altered during acquisition of the metastatic phenotype by cancer cells.

Risk biomarker assessment for breast cancer progression: replication precision of nuclear morphometry.

Nuclear morphometry is a method for quantitative measurement of histopathologic changes in the appearance of stained cell nuclei. Numerous studies have indicated that these assessments may provide clinically relevant information related to the degree of progression and malignant potential of breast neoplasia. Nuclear features are derived from computerized analysis of digitized microscope images, and a quantitative Feulgen stain for DNA was used.

Microvessel density and vascular endothelial growth factor expression in infiltrating lobular mammary carcinoma.

Angiogenesis is an important prognostic factor in infiltrating ductal carcinoma (IDC). Vascular endothelial growth factor (VEGF) stimulates angiogenesis in vivo. VEGF expression has been correlated with high vascularity in IDC.

Race- and age-dependent alterations in global methylation of DNA in squamous cell carcinoma of the lung (United States).

Objective: The current study investigated the race- and age-dependent alterations in global DNA methylation on the development and progression of squamous cell carcinomas (SCCs) of the lung.

Methods: Methylation status was evaluated in SCC and in the associated uninvolved bronchial mucosa (UBM) and epithelial hyperplasia (EH) of 53 Whites and 23 African Americans by using an antibody specific for 5-methylcytosine (5-mc). A low 5-mc score indicates global hypomethylation of DNA.

Clinical variability of Stickler syndrome: role of exon 2 of the collagen COL2A1 gene.

Stickler syndrome (progressive arthro-ophthalmopathy) is a genetically heterogeneous disorder resulting from mutations in at least three collagen genes. The most common disease-causing gene is COL2A1, a 54-exon-containing gene coding for type II collagen. At least 17 different mutations causing Stickler syndrome have been reported in this gene.

Rapid protection of gnotobiotic pigs against experimental salmonellosis following induction of polymorphonuclear leukocytes by avirulent Salmonella enterica.

Oral inoculation of 5-day-old gnotobiotic pigs with Salmonella enterica serovar Typhimurium strain F98 resulted in severe enteritis and invasive disease. Preinoculation 24 h earlier with an avirulent mutant of Salmonella enterica serovar Infantis (1326/28) completely prevented disease for up to 14 days (when the experiment was terminated). S.

Bronchiolitis obliterans: the Achilles heel of lung transplantation.

Operative mortality in lung transplantation in many centers has decreased to less than 10%. Despite this improvement in early survival, delayed graft failure related to chronic graft rejection continues to limit the survival and function of lung transplant recipients. Chronic lung transplant rejection Bronchiolitis obliterans (BO) is an inflammatory process that leads to fibrous scarring of the terminal and respiratory bronchioles and subsequent total occlusion of the airways.

Quantitation of HERV-K env gene expression and splicing in human breast cancer.

Human endogenous retroviruses (HERVs) comprise up to 8% of the human genome. In previous studies, we demonstrated that type 1 HERV-K envelope (env) transcripts are expressed in most human breast cancers, but not in normal breast tissues. In the current study, we report that type 2 HERV-K env transcripts are also present in human breast cancers.

Autosomal dominant macular dystrophy in a large Canadian family.

Background: We studied a large Canadian family (178 total family members) spanning seven generations with autosomal dominant macular dystrophy. We performed a study to identify the gene mutation responsible for the disease in the family.

Methods: Participating family members were evaluated clinically.

Capecitabine induces rapid, sustained response in two patients with extensive oral verrucous carcinoma.

Purpose: Oral verrucous carcinoma (VC) has been traditionally treated with surgery or radiation with frequent recurrences and significant morbidity. We describe rapid and dramatic response to oral capecitabine in two patients with advanced refractory VC.

Experimental Design: VC is a rare tumor of the oral cavity.

Efficacy and safety of treprostinil: an epoprostenol analog for primary pulmonary hypertension.

Intravenous epoprostenol is currently FDA approved for management of primary pulmonary hypertension, but it requires intravenous infusion and is associated with adverse effects. The objective of this study was to evaluate the effects of an epoprostenol analog, treprostinil, for management of pulmonary hypertension. Ten tertiary care academic institutions with pulmonary hypertension programs participated in these pilot trials.

Nuclear accumulation of p53 is a potential marker for the development of squamous cell lung cancer in smokers.

Study Objectives: To determine whether the nuclear accumulation of p53 in patients with early bronchial neoplasia represents an altered susceptibility for the development of lung cancer.

Patients And Measurements: We evaluated the percentage of cells accumulating nuclear p53 immunohistochemically in squamous cell carcinoma (SCC) of the lung, the associated uninvolved bronchial mucosa, and epithelial hyperplasia in 60 archival lung specimens of smokers and in the normal bronchial epithelium and hyperplastic lesions of 60 smokers who had not developed lung cancer.

Results: The percentage of cells accumulating p53 was significantly higher in SCC-associated uninvolved bronchial epithelia of (mean [+/- SD], 4 +/- 0.

Identification of a stop codon mutation in exon 2 of the collagen 2A1 gene in a large stickler syndrome family.

Purpose: To describe the clinical features and identify the mutation responsible for an autosomal dominant vitreoretinal degeneration occurring in a previously unreported large family.

Design: Cohort study.

Methods: Family members were evaluated clinically over a 30-year period.

The docking protein FRS2alpha controls a MAP kinase-mediated negative feedback mechanism for signaling by FGF receptors.

The docking protein FRS2alpha functions as a major mediator of signaling by FGF and NGF receptors. Here we demonstrate that, in addition to tyrosine phosphorylation, FRS2alpha is phosphorylated by MAP kinase on multiple threonine residues in response to FGF stimulation or by insulin, EGF, and PDGF, extracellular stimuli that do not induce tyrosine phosphorylation of FRS2alpha. Prevention of FRS2alpha threonine phosphorylation results in constitutive tyrosine phosphorylation of FRS2alpha in unstimulated cells and enhanced tyrosine phosphorylation of FRS2alpha, MAPK stimulation, cell migration, and proliferation in FGF-stimulated cells.

Noncontact dipole effects on channel permeation. VI. 5F- and 6F-Trp gramicidin channel currents.

Fluorination of peptide side chains has been shown to perturb gramicidin channel conductance without significantly changing the average side chain structure, which, it is hoped, will allow detailed analysis of electrostatic modulation of current flow. Here we report a 1312-point potassium current-voltage-concentration data set for homodimeric channels formed from gramicidin A (gA) or any of eight fluorinated Trp analogs in both lecithin and monoglyceride bilayers. We fit the data with a three-barrier, two-site, two-ion (3B2S) kinetic model.

Microdissection of histologic sections: past, present, and future.

Histologic and cytologic changes are central to the diagnosis and classification of many disease processes, particularly neoplasms. The correlation of these changes with genomics, proteomics, and molecular pathways entails refined microdissection techniques that are frequently used to procure a pure population of cells from complex tissue. Here we review the past, present, and future of some of these new advances in microdissection techniques including manual techniques, laser microdissection, laser capture microdissection, and laser catapulting.

Osteoprotegerin secretion from prostate cancer is stimulated by cytokines, in vitro.

Osteoprotegerin (OPG), a member of the tumor necrosis receptor family, is produced by various tissues and inhibits osteoclast differentiation and activity. Since the metastasis of prostate cancer to bone often induces osteosclerosis, the possibility that these tumor cells secrete OPG is of interest. We have investigated whether the prostate cancer cell lines LNCaP, PC-3, and DU-145 produce and secrete OPG in vitro and if the production might be regulated by cytokines involved in remodeling of bone.

Down-regulation of Cdc6, a cell cycle regulatory gene, in prostate cancer.

CDC6 plays a critical role in regulation of the onset of DNA replication in eukaryotic cells. We have found that Cdc6 expression is down-regulated in prostate cancer as detected by semiquantitative reverse transcriptase-PCR of prostate cell lines and laser-captured microdissected prostate tissues. This result was substantiated by immunohistochemical analysis of paraffin-embedded tissue sections and immunoblot analysis of benign (BPH-1) and adenocarcinomatous prostatic cells.

Scedosporium apiospermum fungemia in a lung transplant recipient.

Scedosporium apiospermum, the asexual anamorph of the cosmopolitan fungus Pseudallescheria boydii, is emerging as an important cause of disseminated infection in immunocompromised patients. We present our experience with the first reported case of S apiospermum fungemia in a lung transplant patient. Disseminated infection resulted in sepsis, multiorgan failure, and death.

Fine needle aspiration biopsy of the islet cell tumor of pancreas: a comparison between computerized axial tomography and endoscopic ultrasound-guided fine needle aspiration biopsy.

The objective of the present study is to compare the cytologic features of islet cell tumor (ICT) of pancreas obtained by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and computed tomography guided FNA (CT-FNA). We also describe the cytologic features associated with malignant ICT. Eleven cytology samples from 121 CT- FNA and 30 EUS- FNA of the pancreas were obtained from nine patients with ICT.