Effect of Bacillus subtilis C-3102 on loose stools in healthy volunteers.

Ingestion of Bacillus subtilis C-3102 spores (C-3102) has relieved the symptoms of diarrhoea in piglets and changed the composition of gut microbiota in humans. Recently, it was suggested that the composition of the human gut microbiota affects stool consistency. In this study, a double-blind, randomised, placebo-controlled trial was conducted to assess the preventive effects of chronic diarrhoea in healthy volunteers with loose stools by ingestion of C-3102. The results showed that oral doses of C-3102 tablets significantly decreased the Bristol Stool Scale score and stool frequency, and also significantly improved abdominal sounds. With regard to gut microbiota, the relative abundance of Lachnospira, Actinomyces and SMB53 were significantly changed. This study shows that C-3102 could be effective for treating loose stools (Trial registration: UMIN000022583, http://tinyurl.com/ya4refqn ).

Flywheel induction motor-generator for magnet power supply in small fusion device.

A flywheel motor-generator (MG) for the toroidal field (TF) coils of a small fusion device was developed which utilizes a commercially available squirrel-cage induction motor. Advantages of the MG are comparably-long duration, quick power response, and easy implementation of power control compared with conventional capacitor-type power supply. A 55-kW MG was fabricated, and TF coils of a small fusion device were energized. The duration of the current flat-top was extended to 1 s which is much longer than those of conventional small devices (around 10-100 ms).

Development of 3D microwave imaging reflectometry in LHD (invited).

Three-dimensional (3D) microwave imaging reflectometry has been developed in the large helical device to visualize fluctuating reflection surface which is caused by the density fluctuations. The plasma is illuminated by the probe wave with four frequencies, which correspond to four radial positions. The imaging optics makes the image of cut-off surface onto the 2D (7 × 7 channels) horn antenna mixer arrays. Multi-channel receivers have been also developed using micro-strip-line technology to handle many channels at reasonable cost. This system is first applied to observe the edge harmonic oscillation (EHO), which is an MHD mode with many harmonics that appears in the edge plasma. A narrow structure along field lines is observed during EHO.

Simultaneous projection and detection system of four different frequencies for microwave imaging reflectometry in Large Helical Device.

A simultaneous projection/detection system of four different frequencies for microwave imaging reflectometry (MIR) was developed for three-dimensional observation of electron density fluctuations in the Large Helical Device (LHD). The microwave with four frequency components at 60.410, 61.808, 63.008, and 64.610 GHz is projected in a continuous-wave mode to illuminate the target LHD plasma. A two-dimensional horn-antenna mixer array (2D HMA) receives the reflected wave from the plasma as well as the wave from the local oscillator operating at 55.800 GHz. The first intermediate frequency (IF) signals at 4.610, 6.008, 7.208, and 8.810 GHz were confirmed to be obtained by downconversion of these microwaves using the 2D HMA. Each of these first IF components is filtered from each other and downconverted again for the superheterodyne detection. It was confirmed that both the amplitudes and the phases of the detected signals reflect the fluctuations in LHD plasmas.

Development of electron cyclotron emission imaging system on Large Helical Device.

A combined system of microwave imaging reflectometry and electron cyclotron emission (ECE) imaging has been developed for the Large Helical Device. This system includes a wide-band two-dimensional horn-antenna mixer array (HMA). The HMA consists of horn antennas, waveguides, mixers, and intermediate frequency circuits. The frequency response of the HMA is between 50 and 110 GHz. The ECE signal is selected using a 95 GHz local oscillator and a 93 GHz high-pass filter.

Changes of optical properties of retroreflector installed in LHD.

This article describes changes of optical properties of retroreflectors installed on the inner wall of the vacuum vessel of the Large Helical Device. They were made of stainless steel and were used for a CO(2) laser polarimeter. The reflectivity for a CO(2) laser beam dropped up to 40% after the start of glow discharge cleanings and main plasma experiments. Then it decreased gradually. The reflectivity in a wavelength range shorter than 10 mum decreased significantly through one experimental campaign (about 4 months). On the other hand the reflectivity in a wavelength range longer than 50 mum was larger than 70%. Decrease in the reflectivity in the central region of mirrors was more significant (the reflectivity for visible beams became almost zero) than that in the edge. The distribution of the reflectivity along the radial direction is expected to be related to the shape of the retroreflector. The parallelism of the reflected beam to an incident one also deteriorated. The changes in the polarization angle and in the ellipticity of reflected light polarization were not observed from the visible to the far infrared range.

Significance of serum soluble Fas antigen level in chronic hepatitis C patients treated with interferon: relationship to the therapeutic response.

BACKGROUND AND AIM: Fas system-mediated cytotoxicity is thought to be involved in the development of liver injury in hepatitis C virus (HCV) infection. In this study, we investigated serum soluble Fas antigen levels in chronic hepatitis C patients treated with interferon and their correlation with the therapeutic response. METHODS: The subjects were 67 chronic hepatitis C patients who underwent a 24-week course of alpha-interferon therapy. Patients were categorized into three groups; sustained responders (n = 22), transient responders (n = 24), and non-responders (n = 21), according to changes in the serum alanine aminotransferase level during and after therapy. The viral genotype, viremic level and diversity in the hypervariable region were examined before therapy. Serum soluble Fas antigen levels were assayed by using serum samples taken at the beginning and the end of therapy. RESULTS: In the univariate analysis, serum soluble Fas antigen levels tended to be higher in non-responders (10.0 +/- 3.4 ng/mL) than in sustained responders (8.5 +/- 3.0 ng/mL) and transient responders (8.2 +/- 2.1 ng/mL; P = 0.13 and P < 0.05). The non-response to therapy was observed in eight of the 15 (53%) patients with serum soluble Fas antigen > or = 11 ng/mL, compared with 13 of the 52 (25%) patients with serum soluble Fas antigen < 11 ng/mL (P < 0.05). As for the multivariate analysis, the only significant factor contributing to the sustained response was a low HCV viremic level (P = 0.0046). Significant factors contributing to the non-response were a high serum alanine aminotransferase (P = 0.0407) and a high serum soluble Fas antigen level (P = 0.0483). CONCLUSIONS: High production levels of soluble Fas antigen may be associated with a poor response to interferon therapy in chronic hepatitis C patients.

Influence of transfusion-transmitted virus infection on the clinical features and response to interferon therapy in Japanese patients with chronic hepatitis C.

Recently, the genome of a novel DNA virus, transfusion-transmitted virus (TTV), was cloned from the plasma of a blood donor who had an elevated aminotransferase level but no serological markers of known hepatitis viruses. In this study, we investigated the influence of TTV infection on the clinical features and response to interferon (IFN) therapy in patients with chronic hepatitis C. We studied 247 patients who had received a 16- or a 24-week course of IFN-alpha therapy. The serum of these patients was analysed for TTV DNA using a hemi-nested polymerase chain reaction and TTV was detected in 114 patients (46%). No significant differences were found with respect to clinical features (gender, age, liver-related biochemical tests, hepatitis C virus (HCV) genotype and serum HCV RNA levels) between the patients who were positive for TTV DNA and those who were negative for TTV DNA. The fibrosis score was higher in TTV-positive patients (2.1 +/- 1.1) than in TTV-negative patients (1.7 +/- 1.1, P = 0.023). The biochemical sustained-response rate was 25% in TTV-positive patients and 25% in TTV-negative patients (not significant). A sustained HCV clearance rate was achieved in 26% of TTV-positive patients and in 22% of TTV-negative patients (not significant). TTV DNA clearance after IFN therapy was observed in 36 of 69 patients (52%) for whom stored serum samples were available. The disappearance of TTV DNA had no effect on the biochemical response to IFN therapy. In conclusion, TTV co-infection is frequently observed in Japanese patients with chronic hepatitis C. In chronic hepatitis C, TTV does not modify the clinical features or the response to IFN.

Serum levels of soluble Fas antigen in chronic hepatitis C patients.

BACKGROUND/AIMS: In chronic hepatitis C, the expression of Fas antigen on hepatocytes is upregulated and Fas ligand expression is detected on liver-infiltrating mononuclear cells. Thus Fas antigen/Fas ligand-mediated apoptosis is thought to be involved in hepatic injury in chronic hepatitis C. The soluble form of Fas antigen has been detected in serum and shown to inhibit Fas-mediated apoptosis. The present study was done to evaluate the relationship of serum soluble Fas antigen levels with disease activity. METHODS: Serum soluble Fas antigen levels were measured by enzyme-linked immunosorbent assay for 68 chronic hepatitis C patients and compared with those in normal volunteers, chronic hepatitis B patients and autoimmune hepatitis patients. These levels were compared with histological activity, ALT levels, HCV-RNA titer and Fas expression on hepatocytes. RESULTS: Serum soluble Fas antigen levels in chronic hepatitis C patients (3.24+/-1.55 ng/ml) were significantly higher than those in normal volunteers (1.70+/-1.01 ng/ml) (p<0.01). They showed no difference from those in chronic hepatitis B or autoimmune hepatitis patients. Histologically, soluble Fas antigen levels showed correlation with the levels of liver inflammation (p<0.01). However, no relationship was observed between serum soluble Fas antigen and serum ALT levels or HCV-RNA titer. Serum soluble Fas antigen levels showed correlation with the levels of Fas antigen expression in liver tissue (p<0.05). CONCLUSIONS: These findings suggest that serum soluble Fas antigen may reflect the expression levels of Fas antigen on hepatocytes and the severity of liver inflammation in chronic hepatitis C.

GBV-C/HGV infection in chronic hepatitis C patients: its effect on clinical features and interferon therapy.

A novel virus (GBV-C/HGV) may be associated with some liver diseases including fulminant hepatitis and acute and chronic hepatitis. On the other hand, many investigations showed that this infection does not contribute to liver disease. GBV-C/HGV has been found to occur in association with infection with other hepatitis viruses. We investigated the effect of GBV-C/HGV infection on the clinical features and interferon treatment in patients with chronic hepatitis C. A total of 262 hepatitis C virus (HCV) RNA positive patients with chronic hepatitis were examined in this study. The detection of serum GBV-C/HGV RNA was done by RT-PCR using specific primers from the NS5 regions. Interferon-alpha was given at a dose of 6 MU/day for 16 or 24 weeks. A responder was defined as a patient with ALT normalization and HCV RNA disappearance after treatment. GBV-C/HGV RNA was detected in 28 (11%) patients. No significant difference was detected in clinical features (age, sex, liver-related biochemical tests, and histological examination) between the 28 GBV-C/HGV-positive patients and the GBV-C/HGV-negative patients. Using interferon therapy for hepatitis C, the responder rates of GBV-C/HGV-positive and -negative patients were 14% and 20%, respectively. Of the 28 patients with GBV-C/HGV RNA, GBV-C/HGV RNA was tested after interferon therapy in 16 and of these GBV-C/HGV RNA was not detected in nine patients after therapy. These findings suggest that GBV-C/HGV infection dose not affect the clinical features in patients with HCV and the efficacy of interferon therapy for chronic hepatitis C.

Binding cells of 125I-iodoamphetamine in rat liver.

We recently reported that transrectal or intestinal portal scintigraphy with 123I-iodoamphetamine (IMP) could be a useful method for the non-invasive and quantitative evaluation of the portosystemic shunt in portal hypertension, but what cells in the liver trap IMP has not been clarified. This study was aimed at elucidating whether IMP was extracted by parenchymal cells, sinusoidal endothelial cells, Kupffer cells or fat storing cells. Each type of liver cell was isolated from rats and cultured. The cells were incubated with 125I-IMP and the radioactivity of the lysate was determined. Nonspecific binding was assessed in the presence of an excess of unlabeled IMP, and specific binding was determined by subtracting the nonspecific from total binding. Specific binding observed in parenchymal cells, endothelial cells and Kupffer cells was 70.2 +/- 0.4, 4.2 +/- 1.4 and 2.3 +/- 0.8 pmol/well, respectively, but no specific binding was observed in fat storing cells. The binding in parenchymal cells was much higher than that in endothelial cells or Kupffer cells (p < 0.005). In addition, the binding to parenchymal cells reached equilibrium within 20 min and was not saturable over the concentration range tested (0.5-10 microM). These findings indicate that IMP is mostly extracted by parenchymal cells in the liver.

Role of Fas ligand in apoptosis induced by hepatitis C virus infection.

To investigate the role that Fas ligand plays in the apoptosis of hepatocytes induced by hepatitis C virus infection, we isolated a cDNA clone for human Fas ligand and examined the expression of Fas ligand in liver-infiltrating mononuclear cells obtained from patients with chronic hepatitis C. The amino acid sequence of human Fas ligand showed 76% and 77% identity with those of rat and mouse Fas ligand, respectively. When the expression of Fas ligand transcripts was tested by reverse transcription-polymerase chain reaction, the amplified signal was detected in liver-infiltrating mononuclear cells and peripheral blood mononuclear cells, whereas only a weak signal or none at all was detected in liver tissues. These findings suggest that the Fas ligand-Fas antigen system may play an important role in liver cell injury by hepatitis C virus infection.

Endogenous nitric oxide attenuates ethanol-induced perturbation of hepatic circulation in the isolated perfused rat liver.

The purpose of this study was to clarify the role of endogenous nitric oxide in ethanol-induced perturbation of microcirculation and hepatic injury in perfused rat liver. Infusion of ethanol into the portal vein at 25 and 100 mmol/L increased portal pressure, which is an indicator of hepatic vasoconstriction, in a concentration-dependent fashion. Portal pressure started to rise immediately after ethanol load, then decreased gradually and remained at higher than basal levels throughout the period of ethanol infusion. Release of lactate dehydrogenase into the effluent perfusate began to increase after 30 min of ethanol infusion and continued to increase during the 60-min period of ethanol infusion. The lactate dehydrogenase level in the effluent perfusate at 60 min was dependent on the ethanol concentration (0 mmol/L, 8 +/- 3 IU/L; 25 mmol/L, 16 +/- 2 IU/L; 100 mmol/L, 52 +/- 6 IU/L). Simultaneous infusion of NG-monomethyl-L-arginine, a nitric oxide synthesis inhibitor, enhanced significantly the ethanol-induced increase in portal pressure by 100% to 400% and increased lactate dehydrogenase release by 40% to 80%. The effect of NG-monomethyl-L-arginine on the ethanol-induced increase in portal pressure was completely reversed by the co-infusion of an excess dose of L-arginine. Change in portal pressure averaged over 60 min of ethanol infusion correlated with levels of lactate dehydrogenase release 60 min after the initiation of ethanol infusion (r = 0.77, p < 0.01). In conclusion, inhibition of the action of endogenous nitric oxide was associated with an increase in hepatic vasoconstriction and hepatocellular damage.(ABSTRACT TRUNCATED AT 250 WORDS)

[Urodynamic evaluation for bladder dysfunction after radical hysterectomy].

Bladder dysfunction after radical hysterectomy and/or radiotherapy for uterine cancer is a serious problem. Its pathogenesis has not been well elucidated. Urodynamic and clinical evaluations were performed in 53 patients; 24 of them underwent radical hysterectomy and postoperative radiotherapy (RH + RT), 13 had radical hysterectomy alone (RH), 7 had modified radical hysterectomy (mRH), 9 had radiotherapy alone (RT). Nine preoperative patients without micturition disturbance were examined, serving as controls. Patients with more than 50 ml of residual urine were only 3 in RH + RT, 2 in RH and 1 in RT. Bladder volumes at maximum desire to void were significantly lower in RT than in controls. Intravesical pressures at maximum desire to void were significantly higher in RH + RT and RH than in controls, but there were no significant differences between mRH or RT and controls. Detrusor compliances significantly decreased after radical hysterectomy and/or radiotherapy. Maximum urethral closure pressures significantly decreased after radical hysterectomy with or without radiotherapy. In RH + RT, 18 patients (75%) of them mainly complained of urinary incontinence. Their functional profile lengths were significantly shorter than in controls. We conclude that the pelvic plexus injury by radical hysterectomy compromise both urethral closure function and bladder compliance.

Bilateral ureterovaginal fistula treated by psoas hitch and uretero-appendicocystostomy.

Reconstruction of bilaterally damaged ureters after pelvic surgery is challenging. We successfully treated such a patient with a uretero-appendicocystostomy on the right side and a psoas hitch on the left side.

[Urodynamic study on urinary disturbance after therapy of uterine cancer].

It is well known that urinary disturbance often appears after radical hysterectomy for uterine cancer and is aggravated by additional radiation therapy. The aim of this study is to elucidate the pathogenesis and to establish the treatment method of urinary disturbance after therapy for uterine cancer. Forty-five patients with urinary disturbance and ten normal controls were subjected to this study. Changes in clinical symptoms and findings in the Urodynamic study (UDS) in 12 severe cases were investigated before and after treatment with beta 2-stimulant (Mabuterol HCL). Clinical symptoms in cases treated by radiation therapy alone were rare and mild without any pad exchanges, and appeared 5 years after treatment for uterine cancer. Findings of UDS in these cases were mild low compliance of detrusor at maximum desire to void (Cmdv) and mild low bladder volume at maximum desire to void (Vmdv). In cases treated by radical hysterectomy alone, Cmdv decreased immediatelly after the operation and then maximum urethral closure pressure (cPura) gradually decreased. Concerning the cases treated by radical hysterectomy and radiation, severe low Cmdv and severe low Vmdv appeared 5 years after the treatment for uterine cancer in almost all cases, and low cPura appeared immediately after the operation in half of the cases. Treatment with beta 2-stimulant significantly improved urinary frequency, voided volume and urinary incontinence. In UDS findings, Vmdv and Cmdv were significantly improved by the treatment with beta 2-stimulant. The functional profile length and cPura value were not significantly changed. In uroflowmetry, the maximum flow rate and average flow rate were significantly improved by the treatment with beta 2-stimulant.(ABSTRACT TRUNCATED AT 250 WORDS)

Architecture of mixed calcium oxalate dihydrate and monohydrate stones.

Calcium oxalate dihydrate (COD) and monohydrate (COM) are the most frequent constituents of urinary stones, and there still exist some questions about the interrelation between the two hydrates. Architecture of mixed COD and COM stones was observed by electron microscopy to solve the questions. The fractured surface of a stone is composed of the fractured face of the crystals. In this situation a morphological criterion of typical dipyramid shape is useless to identify COD. But we could identify COD using the partial dissolution method, which etched square pits on COD crystals. COD and COM formed distinctly separate layers. COD was always found in the stone surface and COM in the center. The stone surface was covered by a thick layer of organic matrix, and the intercrystalline space was filled with matrix. The crystals were grown thrusting the matrix aside to minimize the space. Although COD is more soluble than COM, the urine contains specific substances that favor the formation of COD. Supposing the stone matrix excludes these substances selectively, the gel-state matrix provides a preferable condition for COM formation. This hypothesis is suitable to explain the high incidence of COM stones. An abrupt change of the crystalline constituent can be explained by COD crystal deposition on COM stones. Frequent COD crystalluria can explain why COD is always found in the stone surface. Once the stone surface is covered with COD crystals, they continue to grow in the gel-state matrix or deposit further to form the bulk of the stone.

Release of calcitonin gene-related peptide-like immunoreactive substance from neuromuscular junction by nerve excitation and its action on striated muscle.

In a rat phrenic nerve-hemidiaphragm preparation, calcitonin gene-related peptide (CGRP) increased the twitch contraction induced by nerve or transmural stimulation dose dependently. Either electrical or high K+ stimulation of the phrenic nerve caused release of a CGRP-like immunoreactive substance (CGRP-LIS) in a Ca2(+)-dependent manner. Electrical stimulation of the phrenic nerve also increased the cyclic AMP content in diaphragm. This increase was not observed in Ca2(+)-free medium and was blocked by antiserum against CGRP. These results indicate that excitation of the motor nerve causes release of CGRP-LIS at nerve terminals and that the released CGRP-LIS increases the cyclic AMP content of skeletal muscles and potentiates twitch contraction.