Differential modulation of leukotriene B4 synthesis and degradation in human bronchoalveolar lavage cells by lipopolysaccharide and tobacco smoke.

Leukotrienes have been implicated to play a prominent inductive role in carcinogenesis. We previously reported that bronchoalveolar lavage (BAL) cells from smokers manifested higher levels of leukotriene B4 (LTB4) production than ex-smokers. This study aims to elucidate the underlying mechanism(s).

The synergistic inhibition of atherogenesis in apoE-/- mice between pravastatin and the sPLA2 inhibitor varespladib (A-002).

Secretory phospholipase A2 (sPLA2) activity promotes foam cell formation, increases proinflammatory bioactive lipid levels, decreases HDL levels, increases atherosclerosis in transgenic mice, and is an independent marker of cardiovascular disease. The effects of the sPLA2 inhibitor A-002 (varespladib) and pravastatin as monotherapies and in combination on atherosclerosis, lipids, and paraoxonase (PON) activity in apoE(-/-) mice were investigated. Male apoE(-/-) mice were placed on a 12-week high-fat diet supplemented with A-002 alone or combined with pravastatin.

Potential surgical targets for deep brain stimulation in treatment-resistant depression.

Object: The goal of this study was to evaluate the definition of treatment-resistant depression (TRD), review the literature regarding deep brain stimulation (DBS) for TRD, and identify potential anatomical and functional targets for future widespread clinical application.

Methods: A comprehensive literature review was performed to determine the current status of DBS for TRD, with an emphasis on the scientific support for various implantation sites.

Results: The definition of TRD is presented, as is its management scheme.

Effects of nitric oxide and noradrenergic activation in the posterior hypothalamus on arterial pressure tolerance to nitroglycerin in rats.

The effects of nitric oxide (NO) and noradrenergic activation in the posterior hypothalamus on arterial pressure tolerance induced by subcutaneous injection of nitroglycerin (NTG) was investigated in anesthetized Sprague-Dawley rats. Intravenous injections of NTG (3, 10, and 30 microg/kg) and sodium nitroprusside (1, 3, and 10 microg/kg) produced dose-dependant decreases in arterial blood pressure. Tolerance to NTG was produced by subcutaneous administration of 4.

Epidermal growth factor receptor vIII expression in U87 glioblastoma cells alters their proteasome composition, function, and response to irradiation.

Little is known about the factors that influence the proteasome structures in cells and their activity, although this could be highly relevant to cancer therapy. We have previously shown that, within minutes, irradiation inhibits substrate degradation by the 26S proteasome in most cell types. Here, we report an exception in U87 glioblastoma cells transduced to express the epidermal growth factor receptor vIII (EGFRvIII) mutant (U87EGFRvIII), which does not respond to irradiation with 26S proteasome inhibition.

Factors associated with HIV viral load in a respondent driven sample in Los Angeles.

This study used a modified version of the Behavioral Model for Vulnerable Populations to examine the predisposing, enabling, and need factors associated with detectable viral load (VL). HIV status was measured using saliva and confirmed by blood. Of 797 persons enrolled, 193 were HIV positive and provided VL counts.

The alpha1-adrenergic receptor antagonist doxazosin inhibits EGFR and NF-kappaB signalling to induce breast cancer cell apoptosis.

The selective alpha(1)-adrenergic receptor antagonist doxazosin (dox) has been reported to inhibit prostate cancer proliferation. We now demonstrate that dox-treatment inhibits proliferation and induces apoptosis in breast cancer cells in vitro by mechanisms that do not wholly involve the alpha1-adrenergic receptor. Intriguingly, dox-treatment reduced phosphorylated EGFR expression, decreased pERK1/2 levels and decreased NF-kappaB, AP-1, SRE, E2F and CRE-mediated transcriptional activity.

Minitrephination as an adjunctive measure in the endoscopic management of complex frontal sinus disease.

Background: Frontal sinus disease and its surgical management continues to remain an area of controversy among rhinologists. This is evidenced by the multitude of surgical procedures, both external and endoscopic, that have been developed in its management. This study was performed to evaluate the safety and efficacy of frontal sinus minitrephination in combination with endoscopic frontal sinus exploration for the management of complex frontal sinus disease.

Evidence of enhanced non-enzymatic generation of nitric oxide on the skin surface of acupuncture points: An innovative approach in humans.

The present study quantified total nitrate and nitrite (NOx-) collected from the skin surface along acupuncture points (acupoints) and determined whether non-enzymatic reduction of nitrate by bacteria is involved in chemical generation of nitric oxide (NO) on acupoints. A small plastic tube (0.5 x 7 cm) cut in half lengthwise was taped to the forearm or leg in 50 healthy volunteers.

Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus receptor ectodomain anti-carcinoembryonic antigen bispecific adapter.

Adenovirus vectors have a number of advantages for gene therapy. However, because of their lack of tumor tropism and their preference for liver infection following systemic administration, they cannot be used for systemic attack on metastatic disease. Many epithelial tumors (e.

Extensive sampling changes T-staging of infiltrating lobular carcinoma of breast: a comparative study of gross versus microscopic tumor sizes.

Infiltrating lobular carcinoma represents 7-10% of all invasive breast cancers. The greatest diameter of the tumors in the surgical specimens is required for an accurate T-staging. Tumors with dimension of zero cm, >0 to < or =2 cm, >2 to < or =5 cm, and >5 cm are staged as T0, T1, T2, and T3, respectively.

Pharyngeal diverticulum as a sequela of anterior cervical fusion.

A rarely diagnosed etiology of dysphagia is a pharyngeal diverticula occurring after anterior cervical fusion. Here we review 2 cases where patients developed pharyngeal diverticula following anterior cervical fusion. The first patient was a 28-year-old female who presented with regurgitation following C5 through C6 cervical fusion.

A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer.

Purpose: Overexpression of cyclooxygenase-2 (COX-2) activates extracellular signal-regulated kinase/mitogen-activated protein kinase signaling in an epidermal growth factor receptor (EGFR) tyrosine kinase inhibition (TKI)-resistant manner. Because preclinical data indicated that tumor COX-2 expression caused resistance to EGFR TKI, a phase I trial to establish the optimal biological dose (OBD), defined as the maximal decrease in urinary prostaglandin E-M (PGE-M), and toxicity profile of the combination of celecoxib and erlotinib in advanced non-small cell lung cancer was done.

Experimental Design: Twenty-two subjects with stage IIIB and/or IV non-small cell lung cancer received increasing doses of celecoxib from 200 to 800 mg twice daily (bid) and a fixed dose of erlotinib.

Site-specific estrogen and progestin regulation of orphanin FQ/nociceptin and nociceptin opioid receptor mRNA expression in the female rat limbic hypothalamic system.

The distributions of orphanin FQ (OFQ/N; also known as nociceptin) and its cognate receptor, opioid receptor-like receptor-1 (NOP), overlap steroid-responsive regions throughout reproductive circuits of the limbic system and hypothalamus. For example, in the ventromedial nucleus of the hypothalamus (VMH), OFQ/N facilitates lordosis in female rats through estrogen and progesterone regulation of nociceptin activity. We studied estrogen and progesterone regulation of OFQ/N and NOP mRNA expression in limbic-hypothalamic reproductive circuits.

Assay and properties of the mitochondrial dynamin related protein Opa1.

Opa1, also known as Mgm1 in yeast, is a mitochondrial member of the dynamin family. Unlike other dynamin family members, Opa1 has an N-terminal mitochondrial targeting sequence, suggesting that this protein is imported into mitochondria. Here, we describe biochemical techniques, such as mitochondrial isolation, digitonin extraction, a protease protection assay, and carbonate extraction, that were used to determine that mammalian Opa1 resides in the intermembrane space where it is tightly bound to the inner membrane.

Curcumin suppresses growth of head and neck squamous cell carcinoma.

Purpose: The purpose of this study was to determine whether curcumin would trigger cell death in the head and neck squamous cell carcinoma (HNSCC) cell lines CCL 23, CAL 27, and UM-SCC1 in a dose-dependent fashion.

Experimental Design: HNSCC cells were treated with curcumin and assayed for in vitro growth suppression using 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl tetrazolium bromide and fluorescence-activated cell sorting analyses. Expression of p16, cyclin D1, phospho-Ikappabeta, and nuclear factor-kappabeta (NF-kappabeta) were measured by Western blotting, gel shift, and immunofluorescence.

How do we measure a residual tumor size in histopathology (the gold standard) after neoadjuvant chemotherapy?

Accurate reporting of the residual tumor size by pathologists after neoadjuvant chemotherapy is an important component of a breast cancer. Recent literature reported comparisons regarding the accuracy of clinical and radiological residual tumor size findings using the histopathology as a "gold standard". However, the histopathological methods of measuring the residual tumor size are not standardized.

Prevention of venous thromboembolic disease after total hip and knee arthroplasty.

Patients undergoing total hip and knee arthroplasty are at increased risk for the development of venous thromboembolic disease, and there is general agreement that these patients require prophylaxis. The selection of a prophylactic agent involves a balance between efficacy and safety and often needs to be individualized for specific patients and institutions. Despite extensive research, the ideal agent for prophylaxis against deep venous thrombosis has not been identified.

Do the histologic features and results of breast cancer biomarker studies differ between core biopsy and surgical excision specimens?

Core biopsies are commonly used in the diagnosis of breast cancer and often are the only sample for providing prognostic and predictive markers prior to neoadjuvant chemotherapy. We retrospectively studied 87 patients with breast cancer to compare the concordance rates for tumor type, grade, estrogen receptor/progesterone receptor (ER/PR), p53 status and Her2/neu by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) between core and excisional biopsy specimens. The histologic type of cancer had a 100% concordance rate between core and excisional biopsy specimens.

Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment.

Purpose: We previously reported that autologous dendritic cells pulsed with acid-eluted tumor peptides can stimulate T cell-mediated antitumor immune responses against brain tumors in animal models. As a next step in vaccine development, a phase I clinical trial was established to evaluate this strategy for its feasibility, safety, and induction of systemic and intracranial T-cell responses in patients with glioblastoma multiforme.

Experimental Design: Twelve patients were enrolled into a multicohort dose-escalation study and treated with 1, 5, or 10 million autologous dendritic cells pulsed with constant amounts (100 mug per injection) of acid-eluted autologous tumor peptides.

Optimizing radiolabeled engineered anti-p185HER2 antibody fragments for in vivo imaging.

We have recently described the in vivo properties of an iodinated anti-p185HER2 engineered antibody fragment [minibody (scFv-C(H)3)2; 80 kDa], made from the internalizing 10H8 monoclonal antibody. Although the 10H8 minibody showed excellent binding to the target in vitro, only modest tumor uptake [5.6 +/- 1.

Cortical thinning in cingulate and occipital cortices in first episode schizophrenia.

Background: Postmortem studies examining discrete regions show reduced cortical thickness in schizophrenia. Computational image analysis methods allow spatially detailed cortical thickness measurements across the entire cortex in 3D, but have not addressed thickness changes in cingulate or other cortices bordering the medial walls of the cerebral hemispheres in first episode schizophrenia.

Methods: Magnetic resonance images and cortical pattern matching methods were used to compare gray matter thickness, measured at sub-voxel resolution at thousands of spatially equivalent locations on the medial hemispheric surfaces, between 72 (51m/21f) first episode schizophrenia patients and 78 (37m/41f) healthy controls similar in age.

Cellular distribution and subcellular localization of molecular components of vesicular transmitter release in horizontal cells of rabbit retina.

The mechanism underlying transmitter release from retinal horizontal cells is poorly understood. We investigated the possibility of vesicular transmitter release from mammalian horizontal cells by examining the expression of synaptic proteins that participate in vesicular transmitter release at chemical synapses. Using immunocytochemistry, we evaluated the cellular and subcellular distribution of complexin I/II, syntaxin-1, and synapsin I in rabbit retina.

Prostate stem cell antigen is overexpressed in prostate cancer metastases.

Purpose: Prostate stem cell antigen (PSCA) is expressed by a majority of prostate cancers and is a promising therapeutic target. PSCA protein and mRNA expression was examined in prostate cancer bone, lymph node, and visceral metastases to assess the potential of PSCA as an immunotherapeutic target in advanced prostate cancer.

Experimental Design: Immunohistochemical analysis of PSCA protein expression and quantitative mRNA expression analysis of PSCA was done on clinical specimens of prostate cancer bone, lymph node, and visceral metastases.