Effects of aroclor 1254 on the expression of the KAP3 gene and reproductive function in rats.

The present study investigated the effects of aroclor 1254 (A1254) on the expression of the kinesin superfamily associated protein 3 (KAP3) gene in F1 rat brain during brain sexual differentiation and puberty. In addition, the effects of A1254 on reproductive function were examined. The KAP3 gene is involved in the neurogenesis and synaptogenesis of sexual differentiation in rats and also during puberty.

TTF-1 expression in PACAP-expressing retinal ganglion cells.

In mammals light input resets the central clock of the suprachiasmatic nucleus by inducing secretion of pituitary adenylate cyclase-activating polypeptide (PACAP) from retinal ganglion cells (RGCs). We previously showed that thyroid transcription factor 1 (TTF-1), a homeodomain-containing transcription factor, specifically regulates PACAP gene expression in the rat hypothalamus. In the present study we examined the expression of TTF-1 in PACAP-synthesizing retinal cells.

Beneficial effects of thiazolidinediones on diabetic nephropathy in OLETF rats.

Purpose: Diabetic nephropathy is the most serious of complications in diabetes mellitus. Thiazolidinedione (TZD) is thought to ameliorate diabetic nephropathy; however, the mechanism underlying this effect has not been elucidated. We hypothesized that the vascular endothelial growth factor (VEGF) participates in the pathogenesis of diabetic nephropathy and that TZD may be beneficial for the treatment of diabetic nephropathy because of the effect it has on VEGF.

The prevention of vocal fold scarring using autologous adipose tissue-derived stromal cells.

Prevention and treatment of vocal fold scarring and atrophy remain challenging. The aim of this study was to treat injured vocal folds using autologous adipose tissue-derived stromal cells (ADSCs) and evaluate the ability to prevent vocal fold scarring and atrophy by ADSCs in a canine animal model. Ten adult dogs were used for this experiment.

Heat shock protein 27 is associated with irinotecan resistance in human colorectal cancer cells.

Heat shock protein (Hsp) in tumor cells has been proposed to enhance their resistance to chemotherapeutic agents. In the present study, we investigated the influence of Hsp expression on the irinotecan resistance of human colorectal cancer cells. Among eight Hsp genes tested in this study, we confirmed that the expression of Hsp27 correlated with irinotecan resistance in colorectal cancer cells.

Thyroid transcription factor-1 facilitates cerebrospinal fluid formation by regulating aquaporin-1 synthesis in the brain.

In the brain, aquaporin-1 (AQP-1), a water channel for high osmotic water permeability, is mainly expressed in the apical membrane of the ventricular choroid plexus and regulates formation of cerebrospinal fluid (CSF). Although the physiology of AQP-1 has been the subject of several publications, much less is known about the trans-acting factors involved in the control of AQP-1 gene expression. Here we report that TTF-1, a homeodomain-containing transcriptional regulator, is coexpressed with AQP-1 in the rat brain choroid plexus and enhances AQP-1 gene transcription by binding to conserved core TTF-1-binding motifs in the 5'-flanking region of the AQP-1 gene.

Alternative splicing generates a novel non-secretable cytosolic isoform of NELL2.

NELL2 is as a neuron-specific secreted glycoprotein. The present study provides evidence of an alternatively spliced variant of the rat NELL2 gene that yields cytosolic NELL2 (cNELL2). cNELL2 was initially detected in the thymus and subsequently found to be ubiquitously expressed in many other tissues.

BMAL1 shuttling controls transactivation and degradation of the CLOCK/BMAL1 heterodimer.

CLOCK and BMAL1 are bHLH-PAS-containing transcription factors that bind to E-box elements and are indispensable for expression of core circadian clock components such as the Per and Cry genes. A key step in expression is the heterodimerization of CLOCK and BMAL1 and their accumulation in the nucleus with an approximately 24-h periodicity. We show here that nucleocytoplasmic shuttling of BMAL1 is essential for transactivation and for degradation of the CLOCK/BMAL1 heterodimer.

TTF-1, a homeodomain-containing transcription factor, regulates feeding behavior in the rat hypothalamus.

TTF-1 is a member of the NKx family of homeodomain genes, and is required for morphogenesis and fetal diencephalon development. Our previous studies have shown that TTF-1 expression is maintained in some regions of the postnatal rat brain and transactivates the gene expression of several neuropeptides. In this study, a potential role for TTF-1 in the regulation of feeding behavior was identified.

Munc18 plays an important role in the regulation of glutamate release during female puberty onset.

Munc18, a mammalian homolog of C. elegans Unc, is essential for neurotransmitter release. The aim of this study was to identify estrogen-dependent expression of Munc18-1 and its role in the regulation of glutamate release for puberty onset.

Gastroesophageal flap valve is associated with gastroesophageal and gastropharyngeal reflux.

Background: The endoscopic grade of the gastroesophageal flap valve (GEFV) is suggested to be a good predictor of reflux status. The aim of this study was to investigate the association of the GEFV and gastroesophageal and gastropharyngeal reflux.

Methods: A total of 364 patients (151 men and 233 women; mean age, 52.

NF-kappaB activation is required for cisplatin-induced apoptosis in head and neck squamous carcinoma cells.

This study demonstrates a requirement for NF-kappaB activation in cis-diamminedichloroplatinum (cisplatin)-induced apoptosis in human head and neck squamous cell carcinoma (HNSCC) cell lines. This conclusion was supported by the following observations: cisplatin induced IkappaBalpha degradation and NF-kappaB-dependent transcriptional activation prior to cell death; pyrrolidine dithiocarbamate (PDTC), a chemical inhibitor of NF-kappaB activation, prevented apoptosis; lactacystin, an inhibitor of IkappaBalpha degradation, also prevented apoptosis; and finally, the expression of a super-repressor mutant IkappaBalpha blocked apoptosis. The expression of tumor necrosis factor alpha (TNFalpha) was promoted by cisplatin treatment and was suppressed by PDTC treatment.

A suppressive oligodeoxynucleotide enhances the efficacy of myelin cocktail/IL-4-tolerizing DNA vaccination and treats autoimmune disease.

Targeting pathogenic T cells with Ag-specific tolerizing DNA vaccines encoding autoantigens is a powerful and feasible therapeutic strategy for Th1-mediated autoimmune diseases. However, plasmid DNA contains abundant unmethylated CpG motifs, which induce a strong Th1 immune response. We describe here a novel approach to counteract this undesired side effect of plasmid DNA used for vaccination in Th1-mediated autoimmune diseases.

Antigen microarray profiling of autoantibodies in rheumatoid arthritis.

Objective: Because rheumatoid arthritis (RA) is a heterogeneous autoimmune disease in terms of disease manifestations, clinical outcomes, and therapeutic responses, we developed and applied a novel antigen microarray technology to identify distinct serum antibody profiles in patients with RA.

Methods: Synovial proteome microarrays, containing 225 peptides and proteins that represent candidate and control antigens, were developed. These arrays were used to profile autoantibodies in randomly selected sera from 2 different cohorts of patients: the Stanford Arthritis Center inception cohort, comprising 18 patients with established RA and 38 controls, and the Arthritis, Rheumatism, and Aging Medical Information System cohort, comprising 58 patients with a clinical diagnosis of RA of <6 months duration.

Changes in rhodopsin kinase and transducin in the rat retina in early-stage diabetes.

To establish changes in phototransduction in diabetes, the effects of high glucose on rhodopsin kinase (RK) and transducin (G(t)), as well as recoverin, were examined in the retina of STZ-induced diabetic rats. Diabetes was induced by single intraperitoneal injection of STZ (50mg/kg) to Sprague-Dawley (SD) rats and the animals were sacrificed after 6 weeks. Immunohistochemistry (IHC) and Western blot analysis were carried out using antibodies against RK and G(talpha) (alpha subunit of G(t)) in the STZ-induced diabetic retina and the control retina.

Butyrate response factor 1 enhances cisplatin sensitivity in human head and neck squamous cell carcinoma cell lines.

Cisplatin is a widely used chemotherapeutic agent in head and neck squamous cell carcinoma (HNSCC). Resistance to cisplatin is a common feature of HNSCC. To identify genes that may regulate cisplatin sensitivity, we carried out a cDNA microarray analysis of gene expression in cisplatin-sensitive and cisplatin-resistant HNSCC-derived cell lines.

Immunity to the extracellular domain of Nogo-A modulates experimental autoimmune encephalomyelitis.

Nogo-66, the extracellular 66 aa loop of the Nogo-A protein found in CNS myelin, interacts with the Nogo receptor and has been proposed to mediate inhibition of axonal regrowth. It has been shown that immunization with Nogo-A promotes recovery in animal models of spinal cord injury through induction of Ab production. In this report, studies were performed to characterize the immune response to Nogo-66 and to determine the role of Nogo in experimental autoimmune encephalomyelitis (EAE).

Magnetic resonance imaging and sudden deafness.

Sudden deafness is a disorder defined as acute sensorineural deafness of unknown etiology. To determine whether establishing the pathogenesis of this disease is possible, this study analyzed the magnetic resonance imaging (MRI) of early stages of sudden deafness in combination with the clinical results of treatments. The MRI findings of 18 patients with sudden deafness included three cases of slow blood flow of the vertebrobasilar system, one case of abnormal course of the vertebrobasilar system, and one case of labyrinthine enhancement.

A case of autoimmune hypoglycemia complicated with diabetic ketoacidosis.

Autoimmune hypoglycemia is characterized by hyperinsulinemia, fasting hypoglycemia, and the presence of insulin auto- antibodies without previous exposure to exogenous insulin. We experienced a case of autoimmune hypoglycemia without diabetes mellitus or any evidence of insulinoma. The insulin auto-antibody and insulin receptor auto-antibody were present.

Cloning and cell type-specific regulation of the human tyrosine hydroxylase gene promoter.

Tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis, is predominantly expressed in several cell groups within the brain, including the dopaminergic (DA) neurons of the substantia nigra and ventral tegmental area, and the noradrenergic neurons of the locus coeruleus. To investigate the regulation of cell type-specific TH expression, we cloned and sequenced a 5.5kb fragment of human genomic DNA immediately 5(') of the TH coding region.

Suppression by ethanol of male reproductive activity.

Ethanol has been known to suppress reproductive activity in laboratory animals and humans through the inhibition of luteinizing hormone (LH) release by reduction of gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. There are, however, little data is available regarding the effect of ethanol on GnRH gene expression. Thus, the present study was designed to evaluate the effect of ethanol on GnRH gene expression and reproductive activity at all levels of the hypothalamus-pituitary-gonad (HPG) axis simultaneously.

Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis.

The diversity of autoimmune responses poses a formidable challenge to the development of antigen-specific tolerizing therapy. We developed 'myelin proteome' microarrays to profile the evolution of autoantibody responses in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Increased diversity of autoantibody responses in acute EAE predicted a more severe clinical course.

Docetaxel and Cisplatin Combination Chemotherapy in Patients with Squamous Cell Carcinomas of the Head and Neck.

Purpose: The objective of this phase II study was to assess the clinical antitumor activity and toxicities of docetaxel and cisplatin chemotherapy, in patients with locally advanced and metastatic, recurrent squamous cell carcinomas of the head and neck (SCCHN).

Materials And Methods: All eligible patients with locally advanced and metastatic, recurrent SCCHN had received two courses of chemotherapy followed by repeated head and neck examinations and computed tomography. Patients who had received prior chemotherapy with taxanes were ineligible.

TTF-1, a homeodomain-containing transcription factor, participates in the control of body fluid homeostasis by regulating angiotensinogen gene transcription in the rat subfornical organ.

In recent years, it has become increasingly evident that angiotensins synthesized in the brain contribute to regulating body fluid homeostasis. Although angiotensinogen, the unique angiotensin precursor, is produced in the brain, the factors that regulate its gene expression remain unknown. We recently found that TTF-1, a homeodomain-containing transcription factor essential for the development of the fetal diencephalon, is postnatally expressed in discrete areas of the hypothalamus.

Circadian expression of Mel1a and PL-II genes in placenta: effects of melatonin on the PL-II gene expression in the rat placenta.

In the mammal, melatonin regulates the seasonal and/or circadian rhythm of PRL levels. Since several members of the PRL gene family are expressed during late pregnancy, we investigated the relationship between the expression of placental lactogen (PL)-II-one member of the PRL family- and melatonin, as well as the placental expression of one of the receptors for melatonin, melatonin receptor 1a (Mel(1a())). Herein we provide the first demonstration that Mel(1a) is not only expressed in the rat placenta, but that it is spatially and temporally regulated throughout late pregnancy.