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Objective: No reports have evaluated the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. The present study aimed to evaluate the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. We therefore divided patients into 2 groups about the age of 70 years and investigated the treatment effects of tadalafil regarding voiding and storage functions by age group. Methods: Changes from baseline in each parameter (International Prostate Symptom Score [IPSS], quality of life [QOL] score, Overactive Bladder Symptom Score [OABSS], and residual urine volume) at 4, 12, and 24 weeks after initiating tadalafil for benign prostatic hyperplasia (BPH) patients were compared between groups (50–69 years vs. ≥70 years). In addition, side effects of tadalafil were investigated by age group. Results: In the 50–69 years group, significant improvements from baseline were seen in IPSS total and QOL score for all time points. In addition, significant improvements in IPSS storage subscore from baseline were observed at the 4- and 24-week time points. In the ≥70 years group, significant improvements from baseline were seen in IPSS total, IPSS voiding and storage subscores, and QOL score at each time point. Conclusions: Tadalafil 5 mg once daily appeared effective in clinical settings for elderly BPH patients even over 70 years old. [ABSTRACT FROM AUTHOR]

Many visual objects are attached with values which were created by our long rewarding history. Such stable object values attract gaze. We previously found that the output pathway of basal ganglia from caudal‐dorsal‐lateral portion of substantia nigra pars reticulata (cdlSNr) to superior colliculus (SC) carries robust stable value signal to execute the automatic choice of valuable objects. An important question here is whether stable value signal in basal ganglia can influence on other inner processing such as perception, attention, emotion, or arousal than motor execution. The key brain circuit is another output path of basal ganglia: the pathway from SNr to temporal and frontal lobes through thalamus. To examine the existence of stable value signal in this pathway, we explored thalamus in a wide range. We found that many neurons in the medial thalamus represented stable value. Histological examination showed that the recorded sites of those neurons included ventral anterior nucleus, pars magnocellularis (VAmc) which is the main target of nigrothalamic projection. Consistent with the SNr GABArgic projection, the latency of value signal in the medial thalamus was later than cdlSNr, and the sign of value coding in the medial thalamus was opposite to cdlSNr. As is the case with cdlSNr neurons, the medial thalamus neurons showed no sensitivity to frequently updated value (flexible value). These results suggest that the pathway from cdlSNr to the medial thalamus influences on various aspects of cognitive processing by propagating stable value signal to the wide cortical area. Stable value signal based on long‐term memory travels across brain. In basal ganglia circuit, stable value signal is used for automatic action through superior colliculus. We found that stable value signal is also sent to prefrontal cortex by medial thalamus. This thalamocortical connection may enable the integration of stable‐ and flexible value signals, which is crucial for cognitive function. Medial thalamus may also modulate inferotemporal–prefrontal circuit using stable value signal. [ABSTRACT FROM AUTHOR]

A prominent target of the basal ganglia is the superior colliculus (SC) which controls gaze orientation (saccadic eye movement in primates) to an important object. This 'object choice' is crucial for choosing an action on the object. SC is innervated by the substantia nigra pars reticulata (SNr) which is controlled mainly by the caudate nucleus (CD). This CD‐SNr‐SC circuit is sensitive to the values of individual objects and facilitates saccades to good objects. The object values are processed differently in two parallel circuits: flexibly by the caudate head (CDh) and stably by the caudate tail (CDt). To choose good objects, we need to reject bad objects. In fact, these contrasting functions are accomplished by the circuit originating from CDt: The direct pathway focuses on good objects and facilitates saccades to them; the indirect pathway focuses on bad objects and suppresses saccades to them. Inactivation of CDt deteriorated the object choice, because saccades to bad objects were no longer suppressed. This suggests that the indirect pathway is important for object choice. However, the direct and indirect pathways for 'object choice', which aim at the same action (i.e., saccade), may not work for 'action choice'. One possibility is that circuits controlling different actions are connected through the indirect pathway. Additional connections of the indirect pathway with brain areas outside the basal ganglia may also provide a wider range of behavioral choice. In conclusion, basal ganglia circuits are composed of the basic direct/indirect pathways and additional connections and thus have acquired multiple functions. Parallel circuits from the caudate nucleus to the superior colliculus choose objects by their values, but selectively: anterior circuit using flexible values, posterior circuit using stable values. In the posterior circuit, the object choice is made by saccading to good objects (by direct pathway) and saccading away from bad objects (by indirect pathway). In contrast, action choice may require interactions among multiple basal ganglia circuits, especially through indirect pathways, according to our hypothesis. [ABSTRACT FROM AUTHOR]

Our gaze tends to be directed to objects previously associated with rewards. Such object values change flexibly or remain stable. Here we present evidence that the monkey substantia nigra pars reticulata (SNr) in the basal ganglia represents stable, rather than flexible, object values. After across-day learning of object-reward association, SNr neurons gradually showed a response bias to surprisingly many visual objects: inhibition to high-valued objects and excitation to low-valued objects. Many of these neurons were shown to project to the ipsilateral superior colliculus. This neuronal bias remained intact even after >100 d without further learning. In parallel with the neuronal bias, the monkeys tended to look at high-valued objects. The neuronal and behavioral biases were present even if no value was associated during testing. These results suggest that SNr neurons bias the gaze toward objects that were consistently associated with high values in one's history. [ABSTRACT FROM AUTHOR]

We understand the world by making saccadic eye movements to various objects. However, it is unclear howa saccade can be aimed at a particular object, because two kinds of visual information, what the object is and where it is, are processed separately in the dorsal and ventral visual cortical pathways. Here, we provide evidence suggesting that a basal ganglia circuit through the tail of the monkey caudate nucleus (CDt) guides such object-directed saccades. First, many CDt neurons responded to visual objects depending on where and what the objects were. Second, electrical stimulation in the CDt induced saccades whose directions matched the preferred directions of neurons at the stimulation site. Third, many CDt neurons increased their activity before saccades directed to the preferred objects and directions of the neurons in a free-viewing condition. Our results suggest that CDt neurons receive both "what" and "where" information and guide saccades to visual objects. [ABSTRACT FROM AUTHOR]

The protective effects of bacteriophages were assessed against experimental Staphylococcus aureus infection in mice. Of the S. aureus phages isolated in the study, φMR11 was representatively used for all testing, because its host range was the most broad and it carries no genes for known toxins or antibiotic resistance. Intra-peritoneal injections (8 × 10[SUP8] cells) of S. aureus, including methicillin-resistant bacteria, caused bacteremia and eventual death in mice. In contrast, subsequent intraperitoneal administration of purified φMR11 (MOI⩾0.1) suppressed S. aureus -- induced lethality. This lifesaving effect coincided with the rapid appearance of φMR11 in the circulation, which remained at substantial levels until the bacteria were eradicated. Inoculation with high-dose φMR11 alone produced no adverse effects attributable to the phage. These results uphold the efficacy of phage therapy against pernicious S. aureus infections in humans and suggest that φMR11 may be a potential prototype for gene-modified, advanced therapeutic S. aureus phages. [ABSTRACT FROM AUTHOR]

Appearance of a color stimulus is significantly affected by the contrast between its luminance and the luminance of the background. In the present study, we used stimuli evenly distributed on the CIE-xy chromaticity diagram to examine how luminance contrast affects neural representation of color in V4 and the anterior inferior temporal (AITC) and posterior inferior temporal (PITC) color areas (Banno et al., 2011). The activities of single neurons were recorded from monkeys performing a visual fixation task, and the effects of luminance contrast on the color selectivity of individual neurons and their population responses were systematically examined by comparing responses to color stimuli that were brighter or darker than the background. We found that the effects of luminance contrast differed considerably across V4 and the PITC and AITC. In both V4 and the PITC, the effects of luminance contrast on the population responses of color-selective neurons depended on color. In V4, the size of the effect was largest for blue and cyan, whereas in the PITC, the effect gradually increased as the saturation of the color stimulus was reduced, and was especially large with neutral colors (white, gray, black). The pattern observed in the PITC resembles the effect of luminance contrast on color appearance, suggesting PITC neurons are closely involved in the formation of the perceived appearance of color. By contrast, the color selectivities of AITC neurons were little affected by luminance contrast, indicating that hue and saturation of color stimuli are represented independently of luminance contrast in the AITC., (Copyright © 2014 the authors 0270-6474/14/3414934-14$15.00/0.)

Clinically high-grade prostate cancers (PC) with high Gleason scores of 8-10 exhibit rapid growth and are more likely to spread beyond the prostate. These cancer types demonstrate a poor response to androgen deprivation therapy and eventually acquire a castration-resistant phenotype. To identify novel molecular cancer drug targets, we previously analyzed the gene expression profiles of high-grade PC using a cDNA microarray combined with laser microbeam microdissection and found a number of genes that are transactivated in high-grade PC. Among these genes, we report the identification of a novel molecular target, small nuclear ribonucleoprotein polypeptide E (SNRPE). Semi-quantitative RT-PCR confirmed that SNRPE is overexpressed in high-grade PC cells compared with normal prostatic epithelial cells. Knockdown of SNRPE expression by short interfering RNA (siRNA) resulted in the marked suppression of PC cell proliferation. By contrast, SNRPE overexpression promoted PC cell proliferation, indicating its oncogenic effects. Furthermore, we demonstrated that SNRPE regulates androgen receptor (AR) mRNA expression in PC cells. Knockdown of SNRPE expression by siRNA resulted in the marked suppression of AR and its downstream target genes at the mRNA level. We suggest that the regulation of AR expression by SNRPE is essential for cell proliferation and progression of high-grade PC and that it may be a novel molecular target for cancer drugs.

Purpose: To report our clinical experience regarding transurethral resection of bladder tumor (TUR-Bt) guided by photodynamic diagnosis (PDD) with intravesical instillations of 5-aminolevulinic acid (ALA) and to assess the usefulness of the therapeutic method., Materials and Methods: TUR-Bt guided by PDD was performed in 57 patients of which 47 were men and 10 women with a median age of 74.3 years (range 45-90), 36 were primary cases and 21 were recurrent cases with non-muscle invasive bladder cancer. Two to two and half hours prior to endoscopy 1.5 g ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHCO3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K.K.) was used. The tumorous lesions under white light guidance and the lesion with fluorescent excitation under blue (fluorescence) light guidance were taken by cold cup as a biopsy and also resected sequentially. To evaluate the accuracy of PDD, the levels in images of the ALA-induced fluorescence were compared with the pathological results. To evaluate the availability of TUR-Bt guided by PDD, survival Analysis regarding vesical recurrence was retrospectively examined compared to the cases underwent conventional TUR-Bt under white light guidance. Moreover, in these cases, multivariate analysis using Cox proportional-hazards model was performed to detect the clinico-pathological factor independently contribute to improving prognosis. (Results) In the 301 specimens obtained from 57 patients, the sensitivity and specificity of PDD were 92.5% and 60.1%, whereas the sensitivity and specificity of conventional endoscopic examination under white light guidance were 81.6% and 79.5%, respectively. Median follow-up period was 19.1 (range 8.6-49.9) months in 57 patients underwent TUR-Bt guided by PDD. Eight of 57 patients recurred and recurrence-free survival rate was 88.2 +/- 0.1% (at 12 months) and 76.2 +/- 0.1% (24-48 months). Median follow-up period was 49.9 (5.0-145.0) months in 149 patients underwent conventional TUR-Bt. Ninety-nine of 149 patients recurred and recurrence-free survival rate was 60.3 +/- 0.0% (12 months) and 31.6 +/- 0.0% (24-48 months). There was statistical significance in recurrence-free survival rate between these 2 therapeutic groups (p < 0.001). Moreover, multivariate analysis revealed the independent factor contribute to improving prognosis was only TUR-Bt guided by PDD (hazard ratio 0.279, p = 0.001)., Conclusion: It was suggested that TUR-Bt guided by PDD might reduce the risk of vesical recurrence in the early stage after operation of non-muscle invasive bladder cancer.

Fournier's gangrene is a rare disease of rapidly progressive necrotising fasciitis of the genital, perineal and perianal regions and leads to sepsis and death. We report 8 cases of Fournier's gangrene treated at our hospital and affiliated hospitals from 1997 to 2007. There were seven males and one female in the series, and the age range was 23-89 years (mean age 56.6 years). Four patients among them had diabetes mellitus. We rescued all patients by broad-spectrum antibacterial chemotherapy and debridement. Good management should be based on broad-spectrum antibacterial chemotherapy, debridement and intensive care.