Overexpression of laminin-5 gamma2 chain and its prognostic significance in urothelial carcinoma of urinary bladder: association with expression of cyclooxygenase 2, epidermal growth factor receptor [corrected] and human epidermal growth factor receptor [corrected] 2

Laminin-5 (LN-5) and cyclooxygenase 2 (COX-2) play important roles in many kinds of cancers. Recently, it has been reported that epidermal growth factor receptor [corrected] (EGFR) and/or human epidermal growth factor receptor [corrected] 2 (HER2) expressions are associated with LN-5 and/or COX-2 expressions in a few carcinoma cell lines and human tumor tissue. LN-5, COX-2, EGFR, and HER2 expressions were examined immunohistochemically in 67 patients with urothelial carcinomas (UCs), and associations among these 4 biomarkers and clinicopathologic characteristics were investigated. Patients were classified into transurethral resection group and cystectomy group based on clinical end points, and prognostic significances of increased expressions were evaluated. Overexpression of LN-5, COX-2, EGFR, and HER2 was observed in 16 (23.9%), 34 (50.7%), 42 (62.7%), and 15 (22.4%) of 67 patients, respectively. LN-5 overexpression was associated high-grade (P = .002), invasive (pTa+1 versus pT2-4, P = .011), and nonpapillary (P = .027) UCs. Concerning EGFR and HER2, high-grade (EGFR, P = .0009; HER2, P = .003) and nonpapillary (EGFR, P = .016; HER2, P = .0002) UCs had a significantly higher overexpression rate. UCs penetrating basal membrane (pT1-4) showed significantly higher overexpression rates than pTa UCs on all biomarkers. In transurethral resection group, LN-5 overexpression could be proved as an independent prognostic parameter for intravesical recurrence (P = .007), whereas in cystectomy group, nodal involvement was an independent prognostic parameter for cause-specific survival (P = .025). The current study showed that the 4 biomarkers were associated with aggressive behaviors of UCs. Above all, LN-5 overexpression was considered to play an important role in intravesical recurrence of superficial UCs.     

Effects of the critical band on auditory-evoked magnetic fields

Changes in the bandwidth affect the perceived loudness of a stimulus even when the level of the stimulus remains fixed. If the bandwidth of a sound is varied while maintaining the overall intensity, the loudness remains constant as long as the bandwidth is less than the critical bandwidth. If the bandwidth is increased beyond the critical bandwidth, the loudness increases with increasing bandwidth. Human cortical responses as a function of stimulus bandwidth were examined by recording auditory-evoked magnetic fields. The results showed that the N1m magnitudes, that is, the estimated equivalent current dipole moments, increased with increasing bandwidth when the bandwidth was increased beyond the critical bandwidth.     

Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice

We compared the effects of hematopoietic stem cell and marrow stromal cell transplantation for spinal cord injury in mice. From green fluorescent protein transgenic mouse bone marrow, lineage-negative, c-kit- and Sca-1-positive cells were sorted as hematopoietic stem cells and plastic-adherent cells were cultured as marrow stromal cells. One week after injury, hematopoietic stem cells or marrow stromal cells were injected into the lesioned site. Functional recovery was assessed and immunohistochemistry was performed. In the hematopoietic stem cell group, a portion of green fluorescent protein-positive cells expressed glial marker. In the marrow stem cell group, a number of green fluorescent protein and fibronectin-double positive cells were observed. No significant difference was observed in the recovery between both groups. Both hematopoietic stem cells and marrow stromal cells have the potential to restore the injured spinal cord and to promote functional recovery.     

Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis

To clarify the molecular mechanisms underlying multiple sclerosis (MS)-promoting autoimmune process, we have investigated a comprehensive gene expression profile of T cell and non-T cell fractions of peripheral blood mononuclear cells (PBMC) isolated from 72 MS patients and 22 age- and sex-matched healthy control (CN) subjects by using a cDNA microarray. Among 1258 genes examined, 173 genes in T cells and 50 genes in non-T cells were expressed differentially between MS and CN groups. Downregulated genes greatly outnumbered upregulated genes in MS. More than 80% of the top 30 most significant genes were categorized into apoptosis signaling-related genes of both proapoptotic and antiapoptotic classes. They included upregulation in MS of orphan nuclear receptor Nurr1 (NR4A2), receptor-interacting serine/threonine kinase 2 (RIPK2), and silencer of death domains (SODD), and downregulation in MS of TNF-related apoptosis-inducing ligand (TRAIL), B-cell CLL/lymphoma 2 (BCL2), and death-associated protein 6 (DAXX). Furthermore, a set of the genes involved in DNA repair, replication, and chromatin remodeling was downregulated in MS. These results suggest that MS lymphocytes show a complex pattern of gene regulation that represents a counterbalance between promoting and preventing apoptosis and DNA damage of lymphocytes.     

Mortality and cause of death after hospital discharge in 10,981 patients with ischemic stroke and transient ischemic attack

BACKGROUND: The aim of this study was to examine the 1-year cumulative mortality rate and cause of death, and to identify the predictive factors for death after hospital discharge following ischemic stroke and transient ischemic attack (TIA) using data from the Japan Multicenter Stroke Investigators' Collaboration study. METHODS: We prospectively registered 16,922 consecutive patients with acute ischemic stroke or TIA from May 1999 to April 2000 in 156 Japanese hospitals. We mailed a questionnaire to the 15,322 patients who were alive at hospital discharge. RESULTS: 10,981 patients (6,945 men, 4,036 women, age 70 +/- 11 years, median 71, range 19-100 years) were enrolled in the follow-up study. The mean follow-up period was 271 +/- 110 days (median 272 days; range 1-487 days). The 1-year cumulative mortality was 6.8% (7.0% for 10,234 stroke patients and 3.5% for 747 TIA patients). The causes of death were: cerebrovascular disease, 24.1%; pneumonia, 22.6%; heart disease, 18.1%; cancer, 11.0%, and miscellaneous causes, 24.1%. Multivariate analysis suggested that male gender, age, diabetes mellitus, atrial fibrillation, history of stroke, nonlacunar stroke, functional disability and transfer to another hospital or nursing home on discharge were significant independent predictors of death during the follow-up period. CONCLUSIONS: The major causes of death after hospital discharge were found to be cerebrovascular diseases, pneumonia and heart diseases. Thus, in order to improve survival after hospital discharge, in addition to appropriate management of vascular risk factors following stroke, it appears to be important to take measures to prevent pneumonia and to discharge patients to their own home, if possible.     

The development of a brief screening instrument for depression and suicidal ideation for elderly: the Depression and Suicide Screen

The early detection of depression and suicidal ideation is essential for the prevention of suicide in the community. This study therefore aimed to develop a brief screen for depression and suicidal ideation that can be easily administered in primary-care settings. The Self-rating Depression Scale (SDS), the Hospital Anxiety and Depression Scale (HADS) and a modified version of the Composite International Diagnostic Interview (CIDI) were administered by 353 residents of a single community aged 64 years and over. A five-item screen was derived from SDS and HADS, using CIDI as the external criterion (study 1). The scale was modified so that it was more appropriate for our use, and was labeled the Depression and Suicide Screen (DSS). Its validity and reliability were examined among a further 382 residents of the same community aged 64 years and over, using the Short-Form Geriatric Depression Scale (GDS-S) as the external criterion (study 2). The DSS was internally consistent (Cronbach's alpha=0.62). Its reliability in detecting depression (defined as >or= 6 in GDS-S) and suicidal ideation (screened out by the inquiry by our trained staff) was 0.768 and 0.721, respectively. For depression, the sensitivity was 0.705; specificity, 0.729; positive predictive value (PPV), 0.446; negative predictive value (NPV), 0.888; and the overall diagnostic power, 0.723. For suicidal ideation, its sensitivity was 0.698; specificity, 0.693; PPV, 0.317; NPV, 0.926; and overall diagnostic power, 0.694. The DSS demonstrated a reasonable level of sensitivity and specificity in identifying both depression and suicidal ideation among the elderly within a community.