ChemModLab: a web-based cheminformatics modeling laboratory.

ChemModLab, written by the ECCR @ NCSU consortium under NIH support, is a toolbox for fitting and assessing quantitative structure-activity relationships (QSARs). Its elements are: a cheminformatic front end used to supply molecular descriptors for use in modeling; a set of methods for fitting models; and methods for validating the resulting model. Compounds may be input as structures from which standard descriptors will be calculated using the freely available cheminformatic front end PowerMV; PowerMV also supports compound visualization.

C terminus of Clostridium perfringens enterotoxin downregulates CLDN4 and sensitizes ovarian cancer cells to Taxol and Carboplatin.

Purpose: We have previously shown that CLDN4 (encoding claudin-4), a cell tight junction (TJ) protein, is highly expressed in human epithelial ovarian carcinomas (EOC) but undetectable in normal ovaries. CLDN4 has been identified as a specific receptor for C terminus of Clostridium perfringens enterotoxin (C-CPE), a nontoxic molecule that may disrupt TJ barrier function and enhance cellular absorption. The purpose of this study was to determine the potential clinical applications of C-CPE and its effects on CLDN4 expression in EOC.

Adenosine A2A receptor activation attenuates tubuloglomerular feedback responses by stimulation of endothelial nitric oxide synthase.

Adenosine A(2) receptors have been suggested to modulate tubuloglomerular feedback (TGF) responses by counteracting adenosine A(1) receptor-mediated vasoconstriction, but the mechanisms are unclear. We tested the hypothesis that A(2A) receptor activation blunts TGF by release of nitric oxide in the juxtaglomerular apparatus (JGA). Maximal TGF responses were measured in male Sprague-Dawley rats as changes in proximal stop-flow pressure (ΔP(SF)) in response to increased perfusion of the loop of Henle (0 to 40 nl/min) with artificial tubular fluid (ATF).

Correlates of the preoperative level of CA125 at presentation of ovarian cancer.

Objective: CA125 at presentation of ovarian cancer carries important prognostic significance; but, other than tumor characteristics, little is known about factors that influence CA125 levels. We examined the effect of epidemiologic variables and tumor features on CA125 at diagnosis and their effects on survival.

Methods: CA125 levels before treatment, tumor features, and questionnaire data from 805 women with ovarian cancer receiving care at Partners Hospitals were recorded.

Impaired endothelial function and microvascular asymmetrical dimethylarginine in angiotensin II-infused rats: effects of tempol.

Angiotensin (Ang) II causes endothelial dysfunction, which is associated with cardiovascular risk. We investigated the hypothesis that Ang II increases microvascular reactive oxygen species and asymmetrical dimethylarginine and switches endothelial function from vasodilator to vasoconstrictor pathways. Acetylcholine-induced endothelium-dependent responses of mesenteric resistance arterioles were assessed in a myograph and vascular NO and reactive oxygen species by fluorescent probes in groups (n=6) of male rats infused for 14 days with Ang II (200 ng/kg per minute) or given a sham infusion.

A genetic mosaic approach for neural circuit mapping in Drosophila.

Transgenic manipulation of subsets of brain cells is increasingly used for studying behaviors and their underlying neural circuits. In Drosophila, the GAL4-upstream activating sequence (UAS) binary system is powerful for gene manipulation, but GAL4 expression is often too broad for fine mapping of neural circuits. Here, we describe the development of unique molecular genetic tools to restrict GAL4 expression patterns.

Glomerular tubular balance is suppressed in adenosine type 1 receptor-deficient mice.

Glomerular tubular balance maintains a stable fractional solute and fluid reabsorption in the proximal tubule over a range of glomerular filtration rates. The mediators of this process are unknown. We tested the hypothesis that adenosine, produced in proximal tubule cells acting on adenosine type 1 receptors (A(1)-AR) promotes Na(+) and fluid uptake and mediates glomerular tubular balance.

Angiotensin II and NADPH oxidase increase ADMA in vascular smooth muscle cells.

Asymmetrical dimethylarginine inhibits nitric oxide synthase, cationic amino acid transport, and endothelial function. Patients with cardiovascular risk factors often have endothelial dysfunction associated with increased plasma asymmetrical dimethylarginine and markers of reactive oxygen species. We tested the hypothesis that reactive oxygen species, generated by nicotinamide adenine dinucleotide phosphate oxidase, enhance cellular asymmetrical dimethylarginine.

Up-regulation of stromal versican expression in advanced stage serous ovarian cancer.

Objective: The purpose of this study is to examine the role of versican (VCAN) in advanced stage serous ovarian cancer by investigating its expression, its function, and its correlation with clinical outcomes.

Methods: Microarray analysis was performed on RNA isolated from tumor and stromal components of advanced stage serous ovarian cancer and normal ovarian epithelial tissue to identify genes up-regulated in ovarian tumor stroma. Validation studies using immunohistochemistry and quantitative real-time PCR (Q-RT-PCR) was performed on one of the up-regulated genes, VCAN.

Adenosine A(2) receptors modulate tubuloglomerular feedback.

Adenosine can mediate the tubuloglomerular (TGF) response via activation of A(1) receptors on the afferent arteriole, but both adenosine A(1) and A(2) receptors can regulate preglomerular resistance. We tested the hypothesis that adenosine A(2) receptors offset the effect of A(1) receptors and modulate the TGF. Maximal TGF responses were measured in male Sprague-Dawley rats as changes in proximal stop-flow pressure (DeltaP(SF)) in response to increased perfusion of the loop of Henle (0 to 40 nl/min) with artificial tubular fluid (ATF).

Da Vinci Robot-assisted transoral odontoidectomy for basilar invagination.

The transoral approach is an effective way to decompress the craniocervical junction due to basilar invagination. This approach has been described and refined, but significant limitations and technical challenges remain. Specifically, should the transoral route be used for intradural pathology, such as a meningioma, or should an inadvertent durotomy occur during extradural dissection, achieving a watertight closure of the dura in such a deep and narrow working channel is limited with the current microscopic and endoscopic techniques.

Bow Hunter's Stroke Caused by a Severe Facet Hypertrophy of C1-2.

Bow hunter's stroke is a rare symptomatic vertebrobasilar insufficiency in which vertebral artery (VA) is mechanically occluded during head rotation. Various pathologic conditions have been reported as causes of bow hunter's stroke. However, bow hunter's stroke caused by facet hypertrophy of C1-2 has not been reported.

Myogenic responses of mouse isolated perfused renal afferent arterioles: effects of salt intake and reduced renal mass.

Because defects in renal autoregulation may contribute to renal barotrauma in chronic kidney disease, we tested the hypothesis that the myogenic response is diminished by reduced renal mass. Kidneys from 5/6 nephrectomized mice had only a minor increase in the glomerular sclerosis index. The telemetric mean arterial pressure (108+/-10 mm Hg) was unaffected after 3 months of high-salt intake (6% salt in chow) or reduced renal mass.

Tubuloglomerular feedback is decreased in COX-1 knockout mice after chronic angiotensin II infusion.

Prostaglandins (PGs), produced by two isoforms of cyclooxygenase (COX), COX-1 and COX-2, are important modulators of renal hemodynamics. COX-1 and COX-2 are expressed in the kidney often at distinct sites. Thromboxane (TxA(2)), PGE(2), and prostacyclin (PGI(2)) are the major PGs in the renal cortex of mice.

Blood pressure, blood flow, and oxygenation in the clipped kidney of chronic 2-kidney, 1-clip rats: effects of tempol and Angiotensin blockade.

Angiotensin II maintains renal cortical blood flow and renal oxygenation in the clipped kidney of early 2-kidney, 1-clip Goldblatt hypertensive (2K,1C) rats. The involvement of Ang II is believed to decline, whereas oxidative stress increases during the progression of 2K,1C hypertension. We investigated the hypothesis that the acute administration of drugs to inhibit reactive oxygen species (Tempol), angiotensin II type 1 receptors (candesartan), or angiotensin-converting enzyme (enalaprilat) lowers mean arterial pressure and increases kidney blood flow and oxygenation in the clipped kidney of chronic 2K,1C rats in contrast to sham controls.

A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2.

Advanced stage papillary serous tumors of the ovary are responsible for the majority of ovarian cancer deaths, yet the molecular determinants modulating patient survival are poorly characterized. Here, we identify and validate a prognostic gene expression signature correlating with survival in a series of microdissected serous ovarian tumors. Independent evaluation confirmed the association of a prognostic gene microfibril-associated glycoprotein 2 (MAGP2) with poor prognosis, whereas in vitro mechanistic analyses demonstrated its ability to prolong tumor cell survival and stimulate endothelial cell motility and survival via the alpha(V)beta(3) integrin receptor.

Load sharing and stabilization effects of anterior cervical devices.

Study Design: Biomechanical human cadaveric cervical flexibility testing with direct load-sharing measurement.

Objective: To determine if the flexibility and load-sharing characteristics of a functional spinal unit were affected by anterior treatments for cervical pathologies.

Summary Of Background Data: With advancements in polymers, anterior cervical plates have used thermoplastics including recent designs from biodegradable polylactide acids.

Osteoinductive bone graft substitutes for lumbar fusion: a systematic review.

Object: Autograft and allograft, the standard approaches for lumbar fusion procedures, have important disadvantages. Bone graft substitutes such as recombinant human bone morphogenetic proteins (rhBMP-2 and rhBMP-7) have emerged as viable alternatives. The authors conducted a systematic review to compare the efficacy and safety of osteoinductive bone graft substitutes using autografts and allografts in lumbar fusion.

Autoantibody profiling to identify biomarkers of key pathogenic pathways in mucinous ovarian cancer.

Mucinous epithelial ovarian cancers are clinically and morphologically distinct from the other histopathologic subtypes of ovarian cancer. Unlike other ovarian subtypes, epidemiologic studies have indicated that tobacco exposure is a significant risk factor for developing mucinous ovarian cancer. Detection of autoantibody reactivity is useful in biomarker discovery and for explaining the role of important pathophysiologic pathways in disease.

Renal proximal tubular reabsorption is reduced in adult spontaneously hypertensive rats: roles of superoxide and Na+/H+ exchanger 3.

Proximal tubule reabsorption is regulated by systemic and intrinsic mechanisms, including locally produced autocoids. Superoxide, produced by NADPH oxidase enhances NaCl transport in the loop of Henle and the collecting duct, but its role in the proximal tubule is unclear. We measured proximal tubule fluid reabsorption (Jv) in WKY rats and compared that with Jv in the spontaneously hypertensive rat (SHR), a model of enhanced renal superoxide generation.

Comprehensive simultaneous shipboard and airborne characterization of exhaust from a modern container ship at sea.

We report the first joint shipboard and airborne study focused on the chemical composition and water-uptake behavior of particulate ship emissions. The study focuses on emissions from the main propulsion engine of a Post-Panamax class container ship cruising off the central coast of California and burning heavy fuel oil. Shipboard sampling included micro-orifice uniform deposit impactors (MOUDI) with subsequent off-line analysis, whereas airborne measurements involved a number of real-time analyzers to characterize the plume aerosol, aged from a few seconds to over an hour.

Comparison of inhibitors of superoxide generation in vascular smooth muscle cells.

Background And Purpose: We compared the dose-dependent reductions in cellular superoxide anion (O(2)(-)) by catalytic agents: superoxide dismutase (SOD), polyethylene glycol (PEG)-SOD and the nitroxide 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (tempol) with uncharacterized antioxidants: 5,10,15,20-tetrakis (4-sulphonatophenyl) porphyrinate iron (III)(Fe-TTPS), (-)-cis-3,3',4',5,7-pentahydroxyflavane (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol (-epicatechin), 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) and N-acetyl-L-cysteine (NAC) with the spin trap nitroblue tetrazolium (NBT) and with the vitamins or their analogues: ascorbate, alpha-tocopherol and 6-hydroxy-2,5,7,8-tetramethylkroman-2-carboxy acid (trolox).

Experimental Approach: O(2)(-) was generated in primary cultures of angiotensin II-stimulated preglomerular vascular smooth muscle cells from spontaneously hypertensive rats and detected by lucigenin-enhanced chemiluminescence.

Key Results: SOD, PEG-SOD, NAC and tempol produced a similar maximum inhibition of O(2)(-) of 80-90%.

Regulation of renal arteriolar tone by adenosine: novel role for type 2 receptors.

Tubuloglomerular feedback regulation of glomerular filtration rate (GFR) is mediated by adenosine, which acts on type 1 receptors in the afferent arteriole to increase resistance. However, new findings in isolated mouse tissue suggest that adenosine also dilates the efferent arteriole, which would reinforce the ability of adenosine to reduce GFR. This new information extends the concept that adenosine acts as a paracrine agent on both afferent and efferent arterioles.