NIRS-based neurofeedback learning systems for controlling activity of the prefrontal cortex.

The aim of this study was to develop a NIRS-based neurofeedback system to modulate activity in the prefrontal cortex (PFC). We evaluated the effectiveness of the system in terms of separability of changes in oxy-Hb and its derivative. Training with neurofeedback resulted in higher separability than training without neurofeedback or no training, suggesting that the neurofeedback system could enhance self-control of PFC activity. Interestingly, the dorsolateral PFC exhibited enhanced activity and high separability after neurofeedback training. These observations suggest that the neurofeedback system might be useful for training subjects to regulate emotions by self-control of dorsolateral PFC activity.

Zonisamide up-regulated the mRNAs encoding astrocytic anti-oxidative and neurotrophic factors.

Zonisamide has been proven as an effective drug for the recovery of degenerating dopaminergic neurons in the animal models of Parkinson's disease. However, several lines of evidence have questioned the neuroprotective capacity of zonisamide in animal models of Parkinson's disease. Although it suppresses dopaminergic neurodegeneration in animal models, the cellular and molecular mechanisms underlying the effectiveness of zonisamide are not fully understood. The current study demonstrates the effects of zonisamide on astrocyte cultures and two 6-hydroxydopamine-induced models of Parkinson's disease. Using primary astrocyte cultures, we showed that zonisamide up-regulated the expression of mRNA encoding mesencephalic astrocyte-derived neurotrophic factor, vascular endothelial growth factor, proliferating cell nuclear antigen, metallothionein-2, copper/zinc superoxide dismutase, and manganese superoxide dismutase. Similar responses to zonisamide were found in substantia nigra where the rats were pre-treated with 6-hydroxydopamine. Notably, pharmacological inhibition of 6-hydroxydopamine-induced toxicity by zonisamide pre-treatment was also confirmed using rat mesencephalic organotypic slice cultures of substantia nigra. In addition to this, zonisamide post-treatment also attenuated the nigral tyrosine hydroxylase-positive neuronal loss induced by 6-hydroxydopamine. Taken together, these studies demonstrate that zonisamide protected dopamine neurons in two Parkinson's disease models through a novel mechanism, namely increasing the expression of some important astrocyte-mediated neurotrophic and anti-oxidative factors.

Malignant transformation in a mature testicular teratoma left untreated for more than 50 years since childhood.

Although testicular teratoma in childhood is regarded as a benign tumor, little is known about the consequences of pediatric teratoma being left untreated. We report herein a case of malignant transformation observed in a mature testicular teratoma that was presumed to have remained benign for >50 years.

Improvement of central motor conduction after bone marrow transplantation in adrenoleukodystrophy.

The case is described of a 20-year-old man with adrenoleukodystrophy who showed right spastic hemiparesis and gait disturbance. Brain magnetic resonance imaging disclosed predominant involvement of the left corticospinal pathway. The clinical symptoms improved after bone marrow transplantation. Transcranial magnetic stimulation disclosed significant improvement in various parameters of central motor conduction.

RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer.

OBJECTIVE: To assess the roles of RhoA small GTPase (RhoA) in upper urinary tract cancer by analysing the mRNA and protein levels of RhoA. PATIENTS AND METHODS: The mRNA and protein levels of RhoA in matched sets of tumour, non-tumour and metastatic lymph node tissues of surgical specimens were analysed in 47 consecutive patients with renal pelvic/ureteric cancer, using the polymerase chain reaction after reverse transcription and Western blotting. The relationship between mRNA and protein levels of RhoA in tumour tissues and the clinicopathological features of the patients was also assessed. RESULTS: The mRNA levels of RhoA and RhoA protein were greater in tumour and metastatic lymph node tissues than in non-tumour tissues (all P < 0.001). The expression levels of RhoA mRNA and protein levels in primary tumours was related to poorly differentiated grade (both P < 0.05) and muscle invasion (P < 0.01 and < 0.001, respectively). Kaplan-Meier plots of survival in patients with low or high RhoA showed that high mRNA and protein levels were associated with a shorter disease-free (P < 0.01) and overall survival (P < 0.001). Multivariate analysis using the Cox proportional hazards model showed that a high RhoA protein level was an independent prognostic factor, second to stage, in disease-free and overall survival (both P < 0.05). CONCLUSIONS: These findings suggest that RhoA is involved in the invasion and metastasis of upper urinary tract cancer, indicating that RhoA may be a useful prognostic factor in this disease.

The rho/rho-kinase pathway is involved in the progression of testicular germ cell tumour.

OBJECTIVE: To clarify the role of one of the downstream effectors of Rho (Rho-kinase) in testicular germ cell tumour (GCT) by quantifying mRNA expression for Rho-kinase in patients with this disease. MATERIALS AND METHODS: The mRNA levels of the RhoA and Rho-kinase genes were analysed in surgical specimens of testicular GCT tissues from 57 consecutive Japanese patients, and in the corresponding non-tumour tissue originating from the same patient, using the polymerase chain reaction after reverse transcription. The expression levels of these genes were compared between the tissues and the relationship between their expression levels evaluated within tumours and with tumour stage. The difference in the expression levels of the mRNAs of RhoA and Rho-kinase genes were also assessed between tumours that were seminoma only and mixed tumours of seminoma and nonseminoma. RESULTS: RhoA and Rho-kinase mRNAs were more abundant in tumour tissue than in non-tumour tissue (P < 0.01 and < 0.05, respectively). High RhoA and Rho-kinase mRNA expressions were related to tumour stage (P < 0.05 and < 0.01, respectively). The mRNA levels of RhoA and Rho-kinase in mixed tumours were higher than in tumours with seminoma only (P < 0.01 and < 0.05, respectively). There was a positive relationship between expression levels of mRNAs of RhoA and Rho-kinase in tumour tissues (P < 0.001). CONCLUSIONS: These findings suggest that the RhoA/Rho-kinase pathway is involved in the progression of testicular GCT. This pathway might be a molecular target for new treatment strategies for this disease.

[Typicality effect on holistic processing in face recognition].

Many studies have claimed that faces are more holistically recognized than other objects. It is unclear, however, whether some faces are more holistically recognized than other faces. This study examined whether typical faces are more holistically recognized than distinctive faces. In order to measure the degree of holistic processing, I used an alignment effect, which is a kind of interference effect on the part processing by the holistic processing. The alignment effect was measured as performance difference between aligned and non-aligned presentation conditions. The size of the alignment effects reflects the degree of the holistic processing. The results showed that the typical and distinctive faces showed an equal size of the alignment effects. These results suggested that the typical faces were not more holistically recognized than the distinctive faces. The implication of this results for face recognition research was discussed.

Involvement of accumulated endogenous NOS inhibitors and decreased NOS activity in the impaired neurogenic relaxation of the rabbit proximal urethra with ischaemia.

1. We examined the effect of ischaemia on the neurogenic and nitric oxide (NO)-mediated urethral relaxation. 2. Rabbits were divided into control and urethral ischaemia (UI) groups, which was prepared by the partial occlusion of bilateral iliac arteries using blood vessel occluders. 3. Neurogenic and NO-mediated proximal urethral relaxation induced by electrical field stimulation (EFS) was greatly impaired in the UI group, while relaxation by sodium nitroprusside (SNP) as a NO donor showed no difference between the two groups. Pretreatment with L-arginine significantly improved but did not normalize the impaired relaxation in the UI group. Not only basal level, but also stimulated production of cyclic GMP with EFS, were significantly decreased in the UI group. 4. The tissue contents of N(G)-methyl-L-arginine (L-NMA) and asymmetric N(G), N(G)-dimethyl-L-arginine (ADMA) in the proximal urethra were increased following ischaemia. While L-arginine and symmetric N(G), N'(G)-dimethyl-L-arginine (SDMA) contents remained unchanged. Exogenously applied authentic L-NMA and ADMA (1 -- 100 microM) concentration-dependently inhibited the EFS-induced urethral relaxation in the control group. The inhibition with L-NMA and ADMA was undetectable in the presence of 3 mM L-arginine. 5. The Ca(2+)-dependent NOS activity in the urethra from the UI group was significantly lower than that from the control group and was not restored by an addition of 3 mM L-arginine. 6. These results suggest that the impaired neurogenic and NO-mediated urethral relaxation with ischaemia is closely related to the increased accumulation of L-NMA and ADMA and decreased NOS activity, which would result in an accelerated reduction in NO production/release.

Overexpression of RhoA mRNA is associated with advanced stage in testicular germ cell tumour.

OBJECTIVE: To clarify the role of Rho small GTP-binding protein (Rho) in the progression of testicular germ cell tumour (GCT), by examining the expression levels of mRNAs of Rho genes in testicular GCT. PATIENTS AND METHODS: The mRNA levels of the RhoA, RhoB and RhoC genes were analysed in the surgical specimens of testicular GCT tissues from 45 consecutive Japanese patients, and in the corresponding unaffected tissue originating from the same patient, using reverse transcription-polymerase chain reaction. The expression levels in tumour tissues were compared with those in unaffected tissues and the relationship between their expression levels in tumours and tumour stage evaluated. The expression levels of mRNAs of the Rho genes were also evaluated between tumours with seminoma only, and mixed tumours with seminoma and nonseminoma. RESULTS: The mRNA levels of RhoA were greater in tumour tissues than in unaffected tissues of the resected testis (P < 0.01); the mRNAs of RhoB and RhoC were not detected in either tissue. The increase in RhoA mRNA levels was related to tumour stage (P < 0.05). The mRNA levels of RhoA in seminomatous and nonseminomatous areas where both were present were higher than those in tumours with seminoma only (P < 0.05). CONCLUSIONS: These results suggest that RhoA is involved in testicular germinal epithelial carcinogenesis and progression in testicular GCT, indicating that RhoA may be a useful prognostic marker for progression in testicular GCT.

Role of a central muscarinic cholinergic pathway for relaxation of the proximal urethra during the voiding phase in rats.

PURPOSE: We examined the role of a central muscarinic cholinergic pathway in proximal urethral function during the voiding phase. MATERIALS AND METHODS: During isovolumetric bladder contraction we independently recorded proximal urethral pressure, external urethral sphincter activity, and hypogastric and pelvic nerve discharge in urethane anesthetized rats. We administered intravenous, intrathecal or intracerebral ventricular atropine sulfate and atropine methyl nitrate. Atropine sulfate crosses the blood-brain barrier, while atropine methyl nitrate does not. RESULTS: Filling the bladder with 0.5 ml saline induced rhythmic urethral relaxation accompanied by efferent burst discharges from the pelvic nerve. When administered intravenously, only atropine sulfate caused the dose dependent inhibition of urethral relaxation and efferent pelvic nerve discharge. Neither atropine sulfate nor atropine methyl nitrate affected the maximum firing rate of the external urethral sphincter or hypogastric efferent discharge. Intrathecal and intracerebral ventricular atropine sulfate and atropine methyl nitrate similarly inhibited urethral relaxation. CONCLUSIONS: These results suggest that excitation of the central muscarinic cholinergic pathway at a supraspinal or spinal site promotes proximal urethral relaxation during the voiding phase through the activation of efferent pathways in the pelvic nerves.

Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis.

BACKGROUND/AIMS: Little is known about endotoxin clearance and secretion of cytokines from macrophages in liver cirrhosis. The aims of this study were to investigate the relationship of endotoxin clearance and release of tumor necrosis factor alpha by various macrophages to hepatic and renal disturbances in liver cirrhosis. METHODS: Male Sprague-Dawley rats were given 0.04% thioacetamide orally for 6 or 12 months. The organ distribution of infused [3H]-endotoxin (10 microg/kg b.w.) was analyzed at 30 min or at 24 h. Uptake of [3H]-endotoxin and secretion of tumor necrosis factor alpha by Kupffer cells, splenic macrophages and peripheral blood monocytes (1 x 10(4) cells/ml) from cirrhotic and control rats were determined. RESULTS: In cirrhotic rats, more endotoxin was left in the body and more endotoxin accumulated in the spleen and kidney, and thus was related to elevation of serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine and tumor necrosis factor alpha. Endotoxin uptake and tumor necrosis factor alpha release by the Kupffer cells were decreased and those by the splenic macrophages and peripheral blood monocytes were increased in cirrhotic rats. CONCLUSIONS: In liver cirrhosis, impaired clearance of endotoxin together with increased secretion of tumor necrosis factor alpha by extrahepatic macrophages may play an important role in the progression of hepatic and renal disturbances.

Higher expression of K-ras is associated with parathyroid hormone-related protein-induced hypercalcaemia in renal cell carcinoma.

OBJECTIVES: To determine whether the K-ras oncogene is associated with parathyroid hormone-related protein (PTHrP) production in renal cell carcinoma (RCC) and whether the serum value of PTHrP is related to the patients' survival. PATIENTS AND METHODS: The serum levels of PTHrP and corrected serum calcium levels were analysed in 51 consecutive patients (29 men and 22 women, mean age 63.7 years, range 33-82) with newly diagnosed RCC. Matched pairs were analysed of the mRNA levels of K-ras and PTHrP in tumour and in corresponding non-tumour tissue originating from the same patient, using the polymerase chain reaction after reverse transcription. RESULTS: Seven patients had elevated serum PTHrP values at the diagnosis of RCC. The mRNA expression of K-ras and PTHrP were detected in both tumour and non-tumour tissues, with K-ras mRNA levels being higher in the former than the latter (P < 0.05), and correlated with tumour stage (P < 0.05). There were no differences in PTHrP mRNA levels between the tissues. Furthermore, the mRNA levels of K-ras and PTHrP in seven tumours from patients with high serum values of PTHrP were higher than in tumours from those with normal values (both P < 0.01). The expression of mRNAs of K-ras and PTHrP was positively correlated (r = 0.771, P < 0.001). In seven patients with high serum PTHrP values the mRNA levels of PTHrP correlated with serum values of PTHrP and calcium (r = 0.875, P < 0.01 and r = 0.762, P < 0.05, respectively). Kaplan-Meier plots of survival rate in patients with elevated or normal serum PTHrP showed that high serum PTHrP was associated with a shorter overall survival (P < 0.05). The Cox proportional hazards model showed that serum PTHrP was an independent predictor of overall survival (P < 0.05). CONCLUSIONS: These findings suggest that K-ras may be associated with PTHrP-induced hypercalcaemia and that PTHrP levels may reflect the aggressiveness of tumour cells through the K-ras oncogene in RCC.

Electrochemotherapy for colorectal cancer with commonly used chemotherapeutic agents in a mouse model.

We examined here the usefulness of electrochemotherapy against colorectal cancer (CRC) using a mouse model. Electropermeabilization profoundly increased the sensitivity of murine CRC, Colon 26, and MC38 cells to bleomycin (BLM) but not to 5-fluorouracil (5-FU) or to cisplatin (CDDP) in vitro. In vivo experiments revealed that electrochemotherapy with 5-FU, CDDP, or BLM was much more effective against CRC compared with the treatment of the drug alone. Electrochemotherapy with BLM or CDDP exhibited profound antitumor effects on subcutaneously established CRC in mice, and complete tumor regression was observed in five and four of eight animals, respectively. Electrochemotherapy with 5-FU also had an impact on CRC development, and complete cure was observed in one of eight animals. Subsequent analyses revealed that electropermeabilization significantly increased intratumoral amounts of BLM and CDDP but not 5-FU. These results indicate that electrochemotherapy may be a promising treatment modality against CRC.

Enhanced urinary excretion of cysteinyl leukotrienes in patients with acute alcohol intoxication.

BACKGROUND & AIMS: Leukotrienes are proinflammatory mediators. Ethanol inhibits the catabolism of both cysteinyl leukotrienes (leukotriene E(4) [LTE(4)] and N-acetyl-LTE(4)) and leukotriene B(4) (LTB(4)) in hepatocytes. We examined the metabolic derangement of leukotriene inactivation by ethanol in humans in vivo. METHODS: LTE(4), N-acetyl-LTE(4), LTB(4), and 20-hydroxy-LTB(4) were quantified in urine samples from 16 patients with acute alcohol intoxication (mean blood ethanol, 75 mmol/L). In 9 healthy volunteers, urinary LTE(4) was determined before and after ethanol consumption (mean blood ethanol, 14 mmol/L). RESULTS: The excretion of LTE(4) during alcohol intoxication was 286 compared with 36 nmol/mol creatinine in healthy subjects (P < 0.01); the corresponding values for N-acetyl-LTE(4) were 101 and 11 nmol/mol creatinine, respectively (P < 0.001). This excretion of cysteinyl leukotrienes decreased when the blood ethanol concentration returned to normal. LTB(4) and 20-hydroxy-LTB(4) were detectable only in patients with excessive blood ethanol concentrations (mean, 95 mmol/L). In healthy volunteers, LTE(4) excretion increased 3-5 hours after ethanol consumption (mean peak concentration of 1.5 nmol/L compared with 0.5 nmol/L for basal values; P < 0.005). CONCLUSIONS: Ethanol at high concentration induces increased leukotriene excretion into urine. These changes are consistent with inhibition of leukotriene catabolism and inactivation induced by ethanol, as well as with a higher leukotriene formation caused by ethanol-induced endotoxemia.

Comparison of prazosin, terazosin and tamsulosin in the treatment of symptomatic benign prostatic hyperplasia: a short-term open, randomized multicenter study. BPH Medical Therapy Study Group. Benign prostatic hyperplasia.

BACKGROUND: The objective of this open randomized clinical study was to compare the short-term efficacy and safety of three alpha-1 blockers, prazosin, terazosin and tamsulosin, in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). METHODS: The study comprised 121 patients with symptomatic BPH who were randomized to receive 0.5 mg of prazosin twice daily, 0.5 mg of terazosin twice daily or 0.1 mg of tamsulosin once daily for the initial 2 weeks. The doses were doubled for the next 2 weeks. The primary variables assessed were a symptom score, changes in maximum and average urinary flow rate (Qmax and Qave), postvoid residual urine volume and blood pressure. RESULTS: The percentage changes in the total symptom score from baseline were 38, 39 and 26% at 4 weeks by prazosin, terazosin and tamsulosin, respectively. Terazosin produced significantly higher improvement in four out of nine individual symptoms than tamsulosin (P < 0.05). A significant increase in Qmax or Qave in uroflowmetry was obtained in the prazosin and tamsulosin groups. Blood pressure remained unchanged in normotensive patients, but significantly decreased in hypertensive patients except for the tamsulosin group. Adverse events were minimal in all treatment groups. CONCLUSIONS: The efficacy and safety profiles were different among the alpha-1 blockers at standard doses. Tamsulosin appears to be safer than the others for aged patients or patients with hypertension who have impaired blood pressure regulation, while terazosin is significantly effective in improving symptomatic score when compared with the others examined. It is recommended that the alpha-1 blocking agent and its optimal dose are selected on the basis of the baseline characteristics of the patients with symptomatic BPH.

[Configural and component processings in face recognition: comparison between inversion and negation effects].

It has previously been reported that subjects show difficulties in recognizing faces which are either inverted or in photographic negative. This study examined whether inversion and negation would disrupt the same aspects of face recognition processes in a same-different decision task for simultaneously presented faces. In a "different" condition, two faces were subtlely changed either in component information (eye size) or configural information (placement of inner features). The results revealed that negation equally disrupted component and configural processings, whereas inversion selectively disrupted configural processing more than component processing. Thus, the negation effect, which has been accounted for in terms of edge vs. surface processing, cannot be accounted for in terms of component vs. configural processing. It is concluded that inversion and negation selectively disrupt different aspects of cognitive processes underlying face recognition.

Late recurrence and progression after a long tumor-free period in primary Ta and T1 bladder cancer.

OBJECTIVE: To determine the probability and risk factors of recurrence and progression (to T2 or worse) after a long tumor-free period in patients with superficial (stage Ta and T1) bladder cancer. PATIENTS AND METHODS: A consecutive series of 100 patients with superficial bladder cancer who remained tumor-free for longer than 4 years after initial treatment were reviewed. The rates of recurrence and progression were statistically assessed and the significance of risk factors was determined. RESULTS: Of the 100 patients, 24 (24. 0%) recurred within 15 years after the initial treatment. The 10- and 15-year recurrence-free rates were 76.0 and 59.6%, respectively. Among the clinicopathological variables examined, intravesical chemotherapy was determined by a log-rank test to be a significant unfavorable risk factor for late recurrence (p < 0.001). Progression of the tumor occurred in 5 patients. Four variables including presence of multiple tumors, involvement of the bladder neck, positive urine cytology, and intravesical chemotherapy were found by a univariate analysis to be significant risk factors for late progression (p < 0.05). Among these factors, initial presence of multiple tumors (3 or more) was determined by a multivariate analysis to be an independent risk factor for late progression. CONCLUSION: Recurrence and progression continue to occur in patients with superficial bladder cancer even after long periods of dormancy. Regular follow-up urological assessments should be continued until at least 15 years of tumor-free existence, especially in patients treated by intravesical chemotherapy or those initially having multiple tumors.

Cytosine deaminase/5-fluorocytosine gene therapy can induce efficient anti-tumor effects and protective immunity in immunocompetent mice but not in athymic nude mice.

Murine hepatocellular carcinoma cells were retrovirally transduced with the bacterial cytosine deaminase (CD) gene. CD-transduced cells exhibited more than 120-fold higher sensitivity to 5-fluorocytosine (5-FC) compared with parental cells. When syngeneic immunocompetent mice were inoculated s.c. with parental hepatocellular carcinoma cells containing as little as 5% CD-transduced cells, significant inhibition of tumor formation was induced by 5-FC treatment. Furthermore, established solid tumors in immunocompetent mice containing only 5% CD-transduced cells were infiltrated markedly with CD4- and CD8+ T lymphocytes and macrophages by 5-FC treatment, such that significant reduction or even complete regression of tumors was observed. These tumor-free mice resisted subsequent rechallenge with wild-type tumor. Conversely, when athymic nude mice were inoculated with a cell mixture containing CD-transduced cells and parental cells at a ratio of 40:60, all developed tumors despite 5-FC treatment. Our results indicate that gene therapy using the CD/5-FC system can induce efficient anti-tumor effects and protective immunity in immunocompetent mice but not in athymic immunodeficient mice, suggesting that the host's immunocompetence may be a critical factor for achieving successful gene therapy against cancer.

Effects of "body compression" on parameters related to ascites formation: therapeutic trial in cirrhotic patients.

Decreased effective circulating blood volume is an important factor in ascites formation in liver cirrhosis. We designed a "body compression" apparatus as a means to restore effective blood volume and investigated its effectiveness in reducing ascites formation in cirrhotics in terms of its effect on parameters of ascites formation noted below. The subjects, eight cirrhotics with ascites and eight cirrhotics without ascites were given spironolactone (50-75 mg/day) and furosemide (40-80 mg/day) while they received a diet containing 85 mEq of sodium per day. All four limbs and the lower abdomen were compressed with constant pressure [height (cm) divided by 13.6 mmHg] once, for 3h, using stroke rehabilitation splints, while patients lay supine. In cirrhotics both with and without ascites, urine volume, urinary sodium excretion, and creatinine clearance during the body compression were greater than values during control (non-compression) periods (urine volume, means 285 vs 169 ml/3h; P < 0.001, urinary sodium excretion 15.8 vs 9.5 mEq/3h; p < 0.001, creatinine clearance 74 vs 59 ml/min, P < 0.001, respectively). The increased basal plasma renin activity, angiotensin II, aldosterone, and norepinephrine levels in all cirrhotics were significantly decreased by the body compression. In another group of six cirrhotics who received no diuretics or albumin, repeat body compression alleviated ascites in three with well preserved renal function, but was ineffective in three with markedly impaired renal function. These results suggest that the improvement in renal function brought about by the body compression is attributable to an increase in effective circulating blood volume. This maneuver may be a useful complementary therapy in patients with cirrhotic ascites with well preserved renal function.

[A case of retroperitoneal hemangiopericytoma].

We report a case of a huge retroperitoneal tumor in a 67-year-old woman. When the patient was taken to another hospital by ambulance, she had lost consciousness because of hypertension and hypoglycemia and abdominal CT revealed a huge retroperitoneal tumor with deviation of the right kidney and inferior vena cava. After further examinations including ultrasonography, MRI and angiography in our hospital, the tumor was extirpated. The tumor, 22 x 17 x 10 cm in size and 2,580 g in weight was diagnosed as hemangiopericytoma histologically. She has remained well with no evidence of recurrence for 9 months since the operation.