Post-exposure targeting of specific epitopes on ricin toxin abrogates toxin-induced hypoglycemia, hepatic injury, and lethality in a mouse model.

Effects in the liver of fatal intoxication with the binary toxin ricin are unclear. We report a robust neutrophil influx into the liver of C57BL/6 mice after lethal parenteral ricin challenge, occurring in peri-portal and centro-lobular hepatic areas within 2 h, followed by the abrupt disappearance of hepatic macrophages/Kupffer cells. Chemokine profiles determined by microarray, ribonuclease protection assays, northern blotting, and enzyme-linked immunosorbent assays showed rapid (2 h) upregulation and persistence of those for neutrophils (CXCL1/KC, CXCL2/MIP-2) and monocytes (CCL2/MCP-1).

Overlapping gene expression profiles of cell migration and tumor invasion in human bladder cancer identify metallothionein 1E and nicotinamide N-methyltransferase as novel regulators of cell migration.

Cell migration is essential to cancer invasion and metastasis and is spatially and temporally integrated through transcriptionally dependent and independent mechanisms. As cell migration is studied in vitro, it is important to identify genes that both drive cell migration and are biologically relevant in promoting invasion and metastasis in patients with cancer. Here, gene expression profiling and a high-throughput cell migration system answers this question in human bladder cancer.

TOR1 and TOR2 have distinct locations in live cells.

TOR is a structurally and functionally conserved Ser/Thr kinase found in two multiprotein complexes that regulate many cellular processes to control cell growth. Although extensively studied, the localization of TOR is still ambiguous, possibly because endogenous TOR in live cells has not been examined. Here, we examined the localization of green fluorescent protein (GFP) tagged, endogenous TOR1 and TOR2 in live S.

Regulation of intracellular signaling cascades by GNRH pulse frequency in the rat pituitary: roles for CaMK II, ERK, and JNK activation.

Pulsatile GnRH (GNRH) differentially regulates LH and FSH subunit genes, with faster frequencies favoring Lhb transcription and slower favoring Fshb. Various intracellular pathways mediate the effects of GNRH, including CaMK II (CAMK2), ERK, and JNK. We examined whether activation of these pathways is regulated by GNRH pulse frequency in vivo.

Review of spinal radiosurgery: a minimally invasive approach for the treatment of spinal and paraspinal metastases.

Intracranial radiosurgery has been proved effective for the treatment of brain metastasis. The treatment of paraspinal and spinal metastasis with spinal radiosurgery represents a natural extension of the principles of intracranial radiosurgery. However, spinal radiosurgery is a far more complicated process than intracranial radiosurgery.

Adaptation to estradiol deprivation causes up-regulation of growth factor pathways and hypersensitivity to estradiol in breast cancer cells.

Deprivation of estrogen causes breast tumors in women to adapt and develop enhanced sensitivity to this steroid. Accordingly, women relapsing after treatment with oophorectomy, which substantially lowers estradiol for a prolonged period, respond secondarily to aromatase inhibitors with tumor regression. We have utilized in vitro and in vivo model systems to examine the biologic processes whereby Long Term Estradiol Deprivation (LTED) causes cells to adapt and develop hypersensitivity to estradiol.

Monocyte-derived dendritic cells as antigen-presenting cells in T-cell proliferation and cytokine production.

Dendritic cells (DC) are widely considered to be the major antigen-presenting cell (APC) type in immune responses. These cells are obtained from adherent cells or are purified CD14(+) monocytes from peripheral blood mononuclear cells (PBMC) by in vitro stimulation with granulocyte, macrophage-colony-stimulating factor (GM-CSF) plus interleukin (IL)-4. They express high levels of MHC class II and costimulatory molecules, internalize Ag rapidly via Fc receptors and mannose receptors, and, by macropinocytosis, produce large amounts of IL-12 on CD40 ligation, and are potent in presenting soluble Ag and in stimulating allogeneic mixed-leukocyte reactions.

RSV 2007: recent advances in respiratory syncytial virus research.

THE SIXTH INTERNATIONAL RESPIRATORY SYNCYTIAL VIRUS (RSV) SYMPOSIUM was held from October 25 through October 28, 2007 in Marco Island, Florida. During this conference, over 200 students and investigators representing 16 countries convened to present and discuss recent advancements in RSV research. Presentations ranged from bench to bedside studies encompassing aspects of basic virology, pathogenesis, and immunology, as well as therapeutic and vaccine designs.

Applications of radiotherapy and radiosurgery in the management of pediatric Cushing's disease: a review of the literature and our experience.

Surgical extirpation of pituitary adenomas is considered the mainstay of therapy in pediatric patients with Cushing's disease. However, a small subset of patients will require adjuvant therapy either due to tumor invasiveness, or disease recurrence. Conventional radiation therapy (or radiotherapy) delivers ionizing radiation to control hormonally active cells in fractionated doses (spread out over time) in order to give normal cells time to recover, while radiosurgery involves focusing a high dose of radiation structures in a single treatment session to the adenoma while generally sparing the normal gland and surrounding of any substantial amount of radiation.

Finding early invasive breast cancers: a practical approach.

Detection of early invasive breast cancer is important, as patient survival is high when the cancer is 2 cm or smaller. Invasive breast cancers typically manifest mammographically as focal asymmetries or masses. Strategies for detecting focal asymmetries and masses on screening mammograms include side-by-side comparison, looking for parenchymal contour deformity, close inspection of the retromammary fat, identifying the presence of associated findings, and comparison with prior mammograms.

Signal transducer and activator of transcription 5b, c-Src, and epidermal growth factor receptor signaling play integral roles in estrogen-stimulated proliferation of estrogen receptor-positive breast cancer cells.

17beta-Estradiol (E2) acts through the estrogen receptor alpha (ERalpha) to stimulate breast cancer proliferation. Here, we investigated the functional relationship between ERalpha and signal transducer and activator of transcription (STAT)5b activity in ER+ MCF-7 and T47D human breast cancer cells after specific knockdown of STAT5b. STAT5b small interfering RNA (siRNA) inhibited E2-induced bromodeoxyuridine (BrdU) incorporation in both cell lines, as well as the E2-induced increase in MCF-7 cell number, cyclin D1 and c-myc mRNA, and cyclin D1 protein expression, indicating that STAT5b is required for E2-stimulated breast cancer proliferation.

Restoration of PTEN expression alters the sensitivity of prostate cancer cells to EGFR inhibitors.

Introduction: Prostate cancer (CaP) progression from an androgen-dependent to an androgen-independent state is associated with overexpression of EGFR family members or activation of their downstream signaling pathways, such as PI3K-Akt and MAPK. Although there are data implicating PI3K-Akt or MAPK pathway activation with resistance to EGFR inhibitors in CaP, the potential cross-talk between these pathways in response to EGFR or MAPK inhibitors remains to be examined.

Methods: Cross-talk between PTEN and MAPK signaling and its effects on CaP cell sensitivity to EGFR or MAPK inhibitors were examined in a PTEN-null C4-2 CaP cell, pTetOn PTEN C4-2, where PTEN expression was restored conditionally.

Invasion and metastasis models for studying RhoGDI2 in bladder cancer.

Invasion and metastasis are the critical steps in cancer progression that lead to death from this disease. Intense investigation into the underlying mechanisms of metastasis has revealed a complex set of signaling pathways that regulate the process. Since the mid-1980s, it has been demonstrated that the Rho family of proteins plays a major role in these pathways.

Angiotensin AT2 receptors: control of renal sodium excretion and blood pressure.

The renin-angiotensin system is a coordinated hormonal cascade of crucial importance in cardiovascular and renal function. The primary effector peptide angiotensin II functions at two major receptors, the AT1 and AT2 receptors. AT2 receptors mediate vasodilation and natriuresis.

Role of smooth muscle cells in the initiation and early progression of atherosclerosis.

The initiation of atherosclerosis results from complex interactions of circulating factors and various cell types in the vessel wall, including endothelial cells, lymphocytes, monocytes, and smooth muscle cells (SMCs). Recent reviews highlight the role of activated endothelium and inflammatory cell recruitment in the initiation of and progression of early atherosclerosis. Yet, human autopsy studies, in vitro mechanistic studies, and in vivo correlative data suggest an important role for SMCs in the initiation of atherosclerosis.

Activation of the DNA-dependent protein kinase stimulates nuclear export of the androgen receptor in vitro.

The androgen receptor undergoes nuclear import in response to ligand, but the mechanism by which it undergoes nuclear export is poorly understood. We developed a permeabilized cell assay to characterize nuclear export of the androgen receptor in LNCaP prostate cancer cells. We found that nuclear export of endogenous androgen receptor can be stimulated by short double-stranded DNA oligonucleotides.

Stereotactic radiosurgery for treatment of epilepsy.

Stereotactic radiosurgery, known for efficacy in the noninvasive treatment of tumors or arteriovenous malformations that are otherwise difficult to access through traditional surgery, is an emerging technology in the treatment of focal epileptic lesions. Recent studies in the treatment of hypothalamic hamartoma and mesial temporal lobe epilepsy further suggest that seizures in these medically intractable syndromes remit at clinically significant rates with stereotactic radiosurgery. Further studies will be required to determine whether efficacy attains that of traditional surgery while offering a noninvasive technique with potentially lower morbidity.

A CD8+/CD103high T cell subset regulates TNF-mediated chronic murine ileitis.

Recruitment of lymphocytes to sites of inflammation requires the sequential engagement of adhesion molecules and chemokine receptors. Of these, the lectin-like molecule CD44 has been particularly implicated in inflammatory trafficking. Using a TNF-driven model of chronic ileitis (i.

A novel oxidized low-density lipoprotein-binding protein from Pseudomonas aeruginosa.

A novel protein, PA0122, has been identified in Pseudomonas aeruginosa and shown to bind to oxidized low-density lipoprotein (Ox-LDL). The PA0122 gene was recognized based on gene expression pattern differences between two strains of P. aeruginosa isolated from the sputum of an individual with cystic fibrosis (CF).

Cellular signaling by fibroblast growth factors (FGFs) and their receptors (FGFRs) in male reproduction.

The major function of the reproductive system is to ensure the survival of the species by passing on hereditary traits from one generation to the next. This is accomplished through the production of gametes and the generation of hormones that function in the maturation and regulation of the reproductive system. It is well established that normal development and function of the male reproductive system is mediated by endocrine and paracrine signaling pathways.

High-resolution in situ hybridization to whole-mount zebrafish embryos.

The in situ hybridization (ISH) technique allows the sites of expression of particular genes to be detected. This protocol describes ISH of digoxigenin-labeled antisense RNA probes to whole-mount zebrafish embryos. In our method, PCR-amplified sequence of a gene of interest is used as a template for the synthesis of an antisense RNA probe, which is labeled with digoxigenin-linked nucleotides.