The role of PTEN in prostate cancer cell tropism to the bone micro-environment.

Little is known about the role of the tumor suppressor gene phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in prostate cancer bone metastasis. To explore this, we used a pTetOn PTEN cell line in which PTEN expression was reconstituted in a PTEN-null bone metastatic human prostate cancer cell line, LnCaP-C4-2. We found that C4-2 cells selectively migrated toward conditioned medium from primary mouse calvaria cells compared with that derived from lung fibroblasts.

Proton pump inhibitors: effective first-line treatment for management of dyspepsia.

The aim of this study was to evaluate the reasons for trial exclusion among dyspeptic patients and estimate the proportion that may have benefited from proton pump inhibitor (PPI) therapy. Stringent inclusion criteria for enrollment in two multicenter functional dyspepsia trials included dyspepsia (predominant persistent/recurrent upper abdominal discomfort [UAD] during the prior 3 months) of at least moderate intensity during > or =30% of days during the prior 2 to 3 weeks. Exclusion criteria were mild/infrequent UAD; heartburn and UAD of equal frequency; predominant heartburn with UAD; endoscopic evidence of erosive esophagitis or Barrett's or gastric and/or duodenal erosions (>5) or ulcers; irritable bowel syndrome (IBS); other gastrointestinal diagnoses; or other "non-categorized" disorders.

Prediction of drug combination chemosensitivity in human bladder cancer.

The choice of therapy for metastatic cancer is largely empirical because of a lack of chemosensitivity prediction for available combination chemotherapeutic regimens. Here, we identify molecular models of bladder carcinoma chemosensitivity based on gene expression for three widely used chemotherapeutic agents: cisplatin, paclitaxel, and gemcitabine. We measured the growth inhibition elicited by these three agents in a series of 40 human urothelial cancer cell lines and correlated the GI(50) (50% of growth inhibition) values with quantitative measures of global gene expression to derive models of chemosensitivity using a misclassification-penalized posterior approach.

Contributions of histamine, prostanoids, and neurokinins to edema elicited by edema toxin from Bacillus anthracis.

Bacillus anthracis edema toxin (ET), composed of protective antigen and an adenylate cyclase edema factor (EF), elicits edema in host tissues, but the target cells and events leading from EF-mediated cyclic-AMP production to edema are unknown. We evaluated the direct effect of ET on several cell types in vitro and tested the possibility that mediators of vascular leakage, such as histamine, contribute to edema in rabbits given intradermal ET. ET increased the transendothelial electrical resistance of endothelial monolayers, a response that is mechanistically inconsistent with the in vivo vascular leakage induced by ET.

CXCL1/KC and CXCL2/MIP-2 are critical effectors and potential targets for therapy of Escherichia coli O157:H7-associated renal inflammation.

Neutrophilia is a characteristic of hemolytic uremic syndrome caused by Shiga toxin (Stx2)-producing Escherichia coli. However, the role of neutrophils in the toxin-induced renal injury occurring in enterohemorrhagic E. coli infection remains undefined.

Diverse and potent chemokine production by lung CD11bhigh dendritic cells in homeostasis and in allergic lung inflammation.

Lung CD11c(high) dendritic cells (DC) are comprised of two major phenotypically distinct populations, the CD11b(high) DC and the integrin alpha(E)beta(7)(+) DC (CD103(+) DC). To examine whether they are functionally distinguishable, global microarray studies and real-time PCR analysis were performed. Significant differences between the two major CD11c(high) DC types in chemokine mRNA expression were found.

Commensal bacteria exacerbate intestinal inflammation but are not essential for the development of murine ileitis.

The pathogenesis of Crohn's disease has been associated with a dysregulated response of the mucosal immune system against intraluminal Ags of bacterial origin. In this study, we have investigated the effects of germfree (GF) conditions in the SAMP1/YitFc murine model of Crohn's disease-like ileitis. We show that the bacterial flora is not essential for ileitis induction, because GF SAMP1/YitFc mice develop chronic ileitis.

Fatal encephalitis in a patient with refractory celiac disease presenting with myorhythmia and carpal spasm.

We report the case of a woman with refractory celiac disease who developed abnormal spontaneous movements of the extremities and face consistent with myorhythmia. Investigation led to a diagnosis of encephalitis, confirmed by postmortem examination. The movements were likely caused by nonparaneoplastic encephalitis associated with refractory celiac disease.

Bone morphogenetic protein gene therapy for the induction of spinal arthrodesis.

Gene therapy has many potential applications in neurosurgery. One application involves bone morphogenetic protein-2 (BMP-2), a low-molecular-weight glycoprotein that induces bone formation in vivo. Numerous studies have demonstrated that the BMP-2 protein can enhance spinal fusion.

Ethical dilemmas and moral distress in oncology nursing practice.

Although ethical values and principles guide oncology nursing practice, nurses often are challenged to fulfill every professional core duty and responsibility in their everyday practice. Nurses commonly encounter clinical situations that have ethical conflicts, and they often have difficulty recognizing and articulating them. Unresolved conflicts can cause feelings of frustration and powerlessness, which can lead to compromises in patient care, job dissatisfaction, disagreements among those in the healthcare team, and burnout.

p38 mitogen-activated protein kinase plays an inhibitory role in hepatic lipogenesis.

Hepatic lipogenesis is the principal route to convert excess carbohydrates into fatty acids and is mainly regulated by two opposing hormones, insulin and glucagon. Although insulin stimulates hepatic lipogenesis, glucagon inhibits it. However, the mechanism by which glucagon suppresses lipogenesis remains poorly understood.

The influence of secondary gain on surgical outcome: a comparison between cervical and lumbar discectomy.

Although the expectation of monetary compensation has been associated with failures in lumbar discectomy, the issue has not been investigated in patients undergoing cervical disc surgery. The authors analyzed the relationship between economic forms of secondary gain and surgical outcome in a group of patients with a common pay scale, retirement plan, and disability program. All procedures were performed at the Portsmouth Naval Medical Center between 1993 and 1995; active-duty military servicepersons treated for cervical radiculopathy were prospectively included.

Rare pathological variants and presentations of primary central nervous system lymphomas.

Primary central nervous system lymphoma (PCNSL) is a rare form of primary brain neoplasm, accounting for less than 3% of all primary brain tumors. Ninety percent of cases involve a large B-cell lymphoma that presents as a homogeneously enhancing lesion or lesions, typically deep-seated in the brain parenchyma. The authors describe unusual pathological forms of PCNSLs, including low-grade, T-cell, and Burkitt types, and also rare presentations such as neurolymphomatosis and pituitary lymphomas.

MNK1 and MNK2 regulation in HER2-overexpressing breast cancer lines.

MAPK-interacting protein kinases 1 and 2 (MNK1 and MNK2) function downstream of p38 and ERK MAPK, but there are large gaps in our knowledge of how MNKs are regulated and function. As proteins activated in the HER2/Ras/Raf/ERK pathway, the MNKs are of potential interest in HER2-overexpressing cancers. We utilized a panel of breast cell lines (HCC1419, AU565, SKBR3, MCF7, and MCF10A), three of which overexpress HER2, to characterize the amounts and activation status of MNKs and other pathway enzymes (ERKs and RSKs) in these cells.

Imported platelets demonstrate decreased pH and glucose by reagent strip testing when compared to locally derived platelets.

The most common infectious risk from blood transfusion in the United States is bacterial contamination of platelet components. Although detection of bacterially contaminated platelet components is best achieved with a culture system, AABB standards permit alternatives including the use of staining methods or reagent strips. In this study, 13,216 consecutive platelet components were screened using reagent strips for evidence of the presence of bacteria.

Characterization of a 60S complex of the adenomatous polyposis coli tumor suppressor protein.

The tumor suppressor protein adenomatous polyposis coli (APC) is a multifunctional protein with a well characterized role in the Wnt signal transduction pathway and roles in cytoskeletal regulation and cell polarity. The soluble pool of APC protein in colon epithelial tumor cells exists in two distinct complexes fractionating at approximately 20S and approximately 60S in size. The 20S complex contains components of the beta-catenin destruction complex and probably functions in the Wnt pathway.

Endovascular treatment for symptomatic cerebral vasospasm after subarachnoid hemorrhage: transluminal balloon angioplasty compared with intraarterial papaverine.

The authors retrospectively evaluated the short-term neurological improvement of 69 patients undergoing endovascular treatment for symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The patient group observed here is a subset of patients enrolled in the multicenter North American Trial of Tirilazad in SAH. Thirty-one patients were treated with intraarterial administration of papaverine (IAP).

Cervical spine injuries in pediatric athletes: mechanisms and management.

Sports-related injuries to the spine, although relatively rare compared with head injuries, contribute to significant morbidity and mortality in children. The reported incidence of traumatic cervical spine injury in pediatric athletes varies, and most studies are limited because of the low prevalence of injury. The anatomical and biomechanical differences between the immature spine of pediatric patients and the mature spine of adults that make pediatric patients more susceptible to injury include a greater mobility of the spine due to ligamentous laxity, shallow angulations of facet joints, immature development of neck musculature, and incomplete ossification of the vertebrae.

Pmr1, a Golgi Ca2+/Mn2+-ATPase, is a regulator of the target of rapamycin (TOR) signaling pathway in yeast.

The rapamycin.FKBP12 complex inhibits target of rapamycin (TOR) kinase in TORC1. We screened the yeast nonessential gene deletion collection to identify mutants that conferred rapamycin resistance, and we identified PMR1, encoding the Golgi Ca2+/Mn2+ -ATPase.

Mechanisms of disease: the role of GRK4 in the etiology of essential hypertension and salt sensitivity.

Hypertension and salt sensitivity of blood pressure are two conditions the etiologies of which are still elusive because of the complex influences of genes, environment, and behavior. Recent understanding of the molecular mechanisms that govern sodium homeostasis is shedding new light on how genes, their protein products, and interacting metabolic pathways contribute to disease. Sodium transport is increased in the proximal tubule and thick ascending limb of Henle of the kidney in human essential hypertension.

Emerging and reemerging intestinal protozoa.

The intestinal protozoa have gained importance to physicians practicing medicine in the United States, Canada, and Europe during recent years as a result of increasing world travel, the globalization of the world's economy, and the growing number of chronically immunosuppressed people. During the spring of 1996, Cyclospora cayetanensis caused diarrhea in approximately 1500 people exposed to Guatemalan raspberries. This epidemic recurred in 1997, emphasizing the risks of the global economy and food supply on which we depend.

Stimulation of FSHbeta transcription by blockade of endogenous pituitary follistatin production: Efficacy of adenoviral-delivered antisense RNA in the rat.

This study investigated FSHbeta transcriptional responses to the suppression of endogenous follistatin (FST) production using FST antisense RNA (FST-AS) expressing adenovirus constructs in female rat pituitary cells in vitro. Adenoviral delivery systems were characterized and optimized using an adenovirus-green fluorescent protein construct, and maximal infection (85-90% of cells) was seen 48 h post adenovirus treatment. A 424 bp fragment, which included the translational start site and exons 1-3 of the rat FST gene, was subcloned in the reverse orientation into an adenovirus vector.