Optimal injection points for the neuromuscular blockade of forearm flexor muscles: a cadaveric study.

Botulinum toxin acts at neuromuscular junctions close to muscle motor points and is used to help manage spastic upper-limb deformities. To develop a system allowing clinicians to identify optimal injection sites by an easily reproducible technique, forearm flexor muscles were dissected in 20 formalin-preserved human limbs. Motor points for flexor carpi ulnaris, flexor carpi radialis, flexor digitorum superficialis and pronator teres were (1) identified, (2) related to a reference grid based on lines (proximal, distal, lateral, medial and diagonals) drawn between forearm anatomical landmarks, and (3) defined in terms of their percentage distances along the established grid lines.

A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene.

Desmoplastic small round cell tumor (DSRCT) is a primitive sarcoma characterized by a recurrent chromosomal translocation, t(11;22)(p13;q12), which fuses the 5' exons of the EWS gene to the 3' exons of the WT1 gene. EWS-WT1 chimeras are heterogeneous as a result of fusions of different regions of the EWS gene to the WT1 gene. We report here a rare and novel EWS-WT1 variant, EWS-WT1 5/10, in a 6-year-old boy diagnosed with DSRCT and analyze the potential transactivation effect of the fusion oncoprotein.

Epigenetics and cancer: altered chromatin remodeling via Snf5 loss leads to aberrant cell cycle regulation.

The term 'epigenetics' refers to heritable changes in gene function that occur in the absence of any change in DNA sequence. Perturbations of epigenetic gene regulation may play a critical role in the genesis of most, if not all, cancers. These alterations include changes in covalent modifications of DNA and histones as well as non covalent changes in nucleosome positioning.

Mucosal eosinophilia and response to H1/H2 antagonist and cromolyn therapy in pediatric dyspepsia.

Both eosinophils and mast cells have been implicated in the generation of abdominal pain. The purposes of this retrospective study were to determine the prevalence of duodenal eosinophilia in pediatric dyspepsia and to determine the clinical response rate of these patients to combined H1 and H2 receptor antagonist and mast cell stabilizer therapy. Fifty-nine patients (ages 3.

Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation.

Snf5 (Ini1/Baf47/Smarcb1), a core member of the Swi/Snf chromatin remodeling complex, is a potent tumor suppressor whose mechanism of action is largely unknown. Biallelic loss of Snf5 leads to the onset of aggressive cancers in both humans and mice. We have developed an innovative and widely applicable analytical technique for cross-species validation of cancer models and show that the gene expression profiles of our Snf5 murine models closely resemble those of human Snf5-deficient rhabdoid tumors.

Differential activation of insulin receptor isoforms by insulin-like growth factors is determined by the C domain.

The actions of IGF-I and IGF-II are thought to be largely due to their activation of the IGF-I receptor. However, IGF-II can also bind with high affinity to, and effectively activate, an isoform of the insulin receptor (IR-A) that lacks a sequence at the carboxyl-terminal end of the extracellular alpha subunit due to the alternative splicing of exon 11. This isoform is poorly activated by IGF-I.

Derived trail making test cutoffs and malingering among substance abusers.

The Trail Making test (TMT) is often used to screen for cognitive impairment in substance abusers. A possible limitation of the TMT in clinical settings is that substance abusers may malinger and give poor effort. Data from the Drug Abuse Treatment Outcome Study (DATOS) were analyzed to develop derived TMT cutoffs.

Chronic gastritis is not associated with gastric dysrhythmia or delayed solid emptying in children with dyspepsia.

To determine if chronic gastritis (CG) is associated with gastric dysrhythmia or delayed solid emptying in children with dyspepsia, 22 patients (7-15 years of age) with dyspepsia and normal gross endoscopies were studied. Antral biopsies were evaluated for chronic gastritis, and immunohistology was performed to determine densities of CD3+, CD20+, CD25+, and tryptase-positive cells. Electrogastrography (EGG) and gastric scintiscan evaluation were performed within 2-7 days of endoscopy.

Selective vulnerability of preterm white matter to oxidative damage defined by F2-isoprostanes.

Periventricular white matter injury (PWMI) is the leading cause of cerebral palsy and chronic neurological disability in survivors of prematurity. Despite the large number of affected children, the pathogenetic mechanisms related to PWMI remain controversial. Through studies of 33 human autopsy brains, we determined that early PWMI was related to oxidative damage that particularly targeted the oligodendrocyte lineage, whereas other neuronal and glial cell types were markedly more resistant.

Androgens up-regulate the insulin-like growth factor-I receptor in prostate cancer cells.

In this study, we show that androgens up-regulate insulin-like growth factor-I receptor (IGF-IR) expression and sensitize prostate cancer cells to the biological effects of IGF-I. Both dihydrotestosterone and the synthetic androgen R1881 induced an approximately 6-fold increase in IGF-IR expression in androgen receptor (AR)-positive prostate cancer cells LNCaP. In accordance with IGF-IR up-regulation, treatment with the nonmetabolizable androgen R1881 sensitized LNCaP cells to the mitogenic and motogenic effects of IGF-I, whereas an IGF-IR blocking antibody effectively inhibited these effects.

The CRM1 nuclear export receptor controls pathological cardiac gene expression.

Diverse pathological insults trigger a cardiac remodeling process during which myocytes undergo hypertrophy, with consequent decline in cardiac function and eventual heart failure. Multiple transcriptional regulators of pathological cardiac hypertrophy are controlled at the level of subcellular distribution. For example, prohypertrophic transcription factors belonging to the nuclear factor of activated T cells (NFAT) and GATA families are subject to CRM1-dependent nuclear export but are rapidly relocalized to the nucleus in response to cues for hypertrophic growth.

IGF-1 and prostate cancer.

By virtue of their potent proliferative and anti-apoptotic effects, the insulin-like growth factors (IGFs) have been the subject of long-term scrutiny for their role in tumorigenesis. With regard to prostate cancer in particular, IGF-1 has been shown to stimulate the proliferation of human prostate epithelial cells in culture and to be necessary for normal growth and development of the rat and mouse prostate. Epidemiological studies have established a link between high circulating serum IGF-1 levels and the risk of later developing advanced prostate cancer, and overexpression of IGF-1 in the prostate basal epithelial layer of transgenic mice results in prostate adenocarcinoma that is similar to human disease.

Androgen receptor (AR) expression in AR-negative prostate cancer cells results in differential effects of DHT and IGF-I on proliferation and AR activity between localized and metastatic tumors.

Background: Two features of the progression from organ-confined to metastatic prostate cancer are dysregulation of the androgen receptor (AR) and a decrease in insulin-like growth factor-type-I receptor (IGF-IR) expression. The purpose of this study was to determine the effect of changes in IGF-IR expression on AR activity.

Methods: M12 human prostate cells were stably transfected with an AR expression construct to produce the M12-AR parental (PAR) cell line.

Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5.

A variety of stress signals stimulate cardiac myocytes to undergo hypertrophy. Persistent cardiac hypertrophy is associated with elevated risk for the development of heart failure. Recently, we showed that class II histone deacetylases (HDACs) suppress cardiac hypertrophy and that stress signals neutralize this repressive function by triggering phosphorylation- and CRM1-dependent nuclear export of these chromatin-modifying enzymes.

Safety of infliximab treatment in pediatric patients with inflammatory bowel disease.

Background: Infliximab appears to be efficacious in the treatment of pediatric Crohn disease (CD). There are few large-scale pediatric studies on the complications of infliximab therapy.

Methods: A retrospective review of all infliximab infusions administered to IBD patients at a tertiary children's hospital was undertaken.

Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers.

Context: Intra-amniotic infection (IAI) is commonly associated with preterm birth and adverse neonatal sequelae. Early diagnosis of IAI, however, has been hindered by insensitive or nonspecific tests.

Objective: To identify unique protein signatures in rhesus monkeys with experimental IAI, a proteomics-based analysis of amniotic fluid was used to develop diagnostic biomarkers for subclinical IAI in amniotic fluid and blood of women with preterm labor.

Clinical efficacy and pharmacokinetics of montelukast in dyspeptic children with duodenal eosinophilia.

Background: Montelukast, a competitive cysteinyl leucotriene-1 receptor antagonist, reduces airway eosinophilia in asthmatics. We evaluated the effect of this drug in children with eosinophilic duodenitis, defined histologically as duodenal mucosa with peak eosinophil count of more than 10 eosinophils/hpf.

Methods: Forty children and adolescents (6-18 yr) with dyspepsia and duodenal eosinophilia were enrolled in a double blind, randomized, placebo-controlled, cross-over study of monteleukast therapy.

Crohn's-associated chronic recurrent multifocal osteomyelitis responsive to infliximab.

We report a case of chronic recurrent clavicular osteomyelitis in association with Crohn disease. Steroid therapy resulted in partial remission; however, intractable shoulder pain and an enlarging clavicular mass subsequently recurred. Infliximab therapy resulted in significant improvement in the degree of bone pain and resolution of the large sclerotic clavicular lesion.

Saw palmetto extract suppresses insulin-like growth factor-I signaling and induces stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation in human prostate epithelial cells.

A common alternative therapy for benign prostatic hyperplasia (BPH) is the extract from the fruit of saw palmetto (SPE). BPH is caused by nonmalignant growth of epithelial and stromal elements of the prostate. IGF action is important for prostate growth and development, and changes in the IGF system have been documented in BPH tissues.