Characterization and screening for mutations of the growth arrest-specific 11 (GAS11) and C16orf3 genes at 16q24.3 in breast cancer

BACKGROUND: Both fibroblast-mediated cytokine gene therapy and bone marrow transplantation (BMT) have proven to be efficient protocols for the recovery of bone marrow depression. In this report, the effects of fibroblast-mediated interleukin (IL)-6 gene therapy, in combination with BMT, on the recovery of irradiation-induced bone marrow depression were investigated. METHODS: NIH3T3 fibroblast cells engineered to secrete IL-6 (NIH3T3-IL-6) or NIH3T3 cells transduced with the neomycin gene (NIH3T3-Neo), in combination with 10(7), 10(6), or 10(5) syngeneic bone marrow cells, were implanted into irradiated mice. RESULTS: The platelets and white blood cells in the peripheral blood of the irradiated mice increased greatly 12 days after implantation of NIH3T3-IL-6 cells and BMT, the white blood cell counts were restored to a normal level 32 days after the combined therapy, and the platelet number was obviously higher than that in mice implanted with NIH3T3-Neo and BMT. Twenty and 25 days after the combined therapy, the mice showed accelerated recovery of colony-forming unit (CFU)-granulocyte/macrophages and CFU-megakaryocytes when compared with the mice implanted with NIH3T3-Neo cells and BMT. Ten days after lethal irradiation with gamma rays, the spleens formed more CFU-spleen in mice implanted with NIH3T3-IL-6 cells and BMT than in mice injected with phosphate-buffered saline or NIH3T3-Neo cells. Combined therapy with NIH3T3-IL-6 cell implantation and BMT delayed the survival period of the hematopoietic-depressed mice significantly when compared with therapy with NIH3T3-Neo cell implantation and BMT. CONCLUSIONS: These data demonstrated that the combined therapy of fibroblast-mediated IL-6 gene therapy and BMT could significantly promote the recovery of irradiation-induced hematopoietic depression.     

Consideration of conformational transitions and racemization during process development of recombinant glucagon-like peptide-1

This article summarizes the results of a combined analysis from two identical multicenter clinical trials that investigated the efficacy and safety of sertraline versus placebo for treating panic disorder. Patients with panic disorder who were treated with sertraline had a statistically significant reduction in the mean number of panic attacks per week (the primary efficacy measure) as compared with placebo (4.8 vs. 2.5, p < .001). Sertraline-treated patients also showed greater improvement that was statistically significant on several ratings of panic disorder symptomatology and functioning. The design characteristics, clinical rating measures, and outcome measures in these trials included most of the features deemed essential by Shear and Maser (1994) in their summary of the NIMH Consensus Conference for the development of standardized assessments for panic disorder. This suggests that the NIMH Consensus Conference played a key role in developing successful multicenter pharmacological treatment studies, such as this one that ultimately demonstrated that sertraline was an effective treatment for panic disorder.     

Red nucleus stimulation inhibits within the inferior olive

Red nucleus stimulation inhibits within the inferior olive. J. Neurophysiol. 80: 3127-3136, 1998. In the anesthetized cat, electrical stimulation of the magnocellular red nucleus (RNm) inhibits responses of rostral dorsal accessory olive (rDAO) neurons to cutaneous stimulation. We tested the hypothesis that RNm-mediated inhibition occurs within the inferior olive by using stimulation of the ventral funiculus (VF) of the spinal cord in place of cutaneous stimulation of the hindlimb. Fibers in the VF terminate on hindlimb rDAO neurons, so inhibition of this input would have to occur within the olive. rDAO responses elicited by VF stimulation were inhibited by prior stimulation of the RNm, indicating that inhibition occurs within the olive. In contrast, evoked potentials recorded from the VF or dorsal columns following hindlimb stimulation were not affected by prior stimulation of RNm, indicating that stimulation of the RNm does not inhibit olivary afferents at spinal levels. RNm stimulation that inhibited rDAO responses had little effect on evoked somatosensory responses in thalamus, indicating that inhibition generated by activity in RNm may be specific to rDAO. To test limb specificity of RNm-mediated inhibition, conditioning stimulation was applied to the dorsolateral funiculus at thoracic levels, which selectively activates RNm neurons projecting to the lumbar cord. Stimulation at thoracic levels inhibited evoked responses from hindlimb but not forelimb regions of rDAO, suggesting that inhibitory effects of RNm activity are limb specific. Several studies have reported that olivary neurons have reduced sensitivity to peripheral stimulation during movement; it is likely that RNm-mediated inhibition occurring within the olive contributes to this reduction of sensitivity. Inhibition of rDAO responses by descending motor pathways appears to be a salient feature of olivary function.     

The use of transgenic animals in biotechnology

Conformational effects and affinities of VP-16 (etoposide) and its derivatives to DNA in the presence of Cu(II) ion were examined by circular dichroic (CD) spectra. The Cu(II)/Cu(I) redox kinetics and the hydroxyl radical (.OH) generation from the Cu(II)-complexes were estimated by the stopped-flow kinetics. Based on the results, DNA-cleaving activity of Cu(II)-complexes of VP-16 has been shown to be related with binding affinity of the complex to DNA, Cu(II)/Cu(I) redox and .OH generation, emphasising the mechanism of generated .OH attack to DNA.     

Prevalence of voice problems in teachers

Teachers are frequently cited as experiencing a high rate of vocal dysfunction (1-7). Despite considerable research in the area of voice problems in teachers, the prevalence of voice disorders in this group is unknown. This study investigated the prevalence of self-reported voice problems in teachers using a mail survey of a simple random sample of 1168 state school teachers (preschool-Grade 12) in South Australia. As part of the survey, teachers were asked to report voice problems for the day of the survey, during the current teaching year, and during their careers. The response rate was 75%, with 16% of teachers reporting voice problems on the day of the survey, 20% reporting problems during the current teaching year, and 19% reporting problems at some time during their career. Females were twice as likely as males to report voice problems. These findings clearly indicate a need for further investigation of the causes of vocal dysfunction in teachers and for the development of educational programs aimed at preventing voice problems in this group of professional voice users.     

Assessing obesity: classification and epidemiology

Obesity is generally defined as a body mass index (BMI) of 30 kg/m2 and higher. Overweight is defined as a BMI between 25 and 30 kg/m2. The prevalence varies considerably between countries, and between regions within countries. It is estimated that more than half of adults aged 35-65 living in Europe are either overweight or obese. Overweight is more common among men than among women but obesity is more common among women. The prevalence of obesity in Europe is probably in the order of 10-20% in men and 15-25% in adult women. In most European countries who have reliable data on time-trends the prevalence of obesity seems to be increasing. In most European countries, obesity is usually inversely associated with socio-economic status, particularly among women. New classifications of overweight may be based on cut-off points for simple anthropometric measures which reflects both total adiposity as well as abdominal fatness.     

Nanogoldpharmaceutics (i) The use of colloidal gold to treat experimentally-induced arthritis in rat models; (ii) Characterization of the gold in Swarna bhasma, a microparticulate used in traditional Indian medicine

Nanosized gold particles (27 +/− 3 nm) have been proven to be effective in ameliorating the symptoms of mycobacterial-, collagen- and pristane-induced arthritis in rat models. This contrasts with the drug sodium aurothiomalate that was only effective against mycobacterial-induced arthritis but not to the same extent as Au⁰. Gold in the traditional Indian Ayurvedic medicine,Swarna bhasma (gold ash), has been characterized as globular particles of gold with an average size of 56–57 nm.     

Serotonin and serotonin receptors in the central auditory system

Single channel currents were activated by GABA (0.5 to 5 microM) in cell-attached and inside-out patches from cells in the dentate gyrus of rat hippocampal slices. The currents reversed at the chloride equilibrium potential and were blocked by bicuculline (100 microM). Several different kinds of channel were seen: high conductance and low conductance, rectifying and "nonrectifying." Channels had multiple conductance states. The open probability (Po) of channels was greater at depolarized than at hyperpolarized potentials and the relationship between Po and potential could be fitted with a Boltzmann equation with equivalent valency (z) of 1. The combination of outward rectification and potential-dependent open probability gave very little chloride current at hyperpolarized potentials but steeply increasing current with depolarization, useful properties for a tonic inhibitory mechanism.