Current-feedback-stabilized laser system for quantum simulation experiments using Yb clock transition at 578 nm.

We developed a laser system for the spectroscopy of the clock transition in ytterbium (Yb) atoms at 578 nm based on an interference-filter stabilized external-cavity diode laser (IFDL) emitting at 1156 nm. Owing to the improved frequency-to-current response of the laser-diode chip and the less sensitivity of the IFDL to mechanical perturbations, we succeeded in stabilizing the frequency to a high-finesse ultra-low-expansion glass cavity with a simple current feedback system. Using this laser system, we performed high-resolution clock spectroscopy of Yb and found that the linewidth of the stabilized laser was less than 320 Hz.

Relationships between transepidermal water loss, cutaneous microcirculatory function and autonomic nervous activity.

OBJECTIVE: Several studies have shown that a deterioration of skin properties, an impaired cutaneous microcirculatory function and an imbalance of autonomic nervous activity are observed in smokers and in patients with diabetes mellitus or Raynaud's phenomenon. These observations suggest that skin properties are associated with cutaneous microcirculatory function and autonomic nervous activity in pathological conditions. However, there is no published evidence to support the concept that these two functions have any relationship with skin properties even in healthy subjects. To investigate the hypothesis that these properties are related, we conducted a survey of healthy adult subjects to investigate the relationships between cutaneous microcirculatory function and autonomic nervous activity and skin properties. METHODS: The hydration of the stratum corneum and transepidermal water loss (TEWL) were investigated as skin properties, and the responsiveness of skin blood flow (SkBF) to local warming was examined as an index of cutaneous microcirculatory function in 19 healthy adult male subjects. Electrocardiograms were monitored for 24 h and heart rate variability was analysed considering low-frequency power (LF: 0.04-0.15 Hz), high-frequency power (HF: 0.15-0.40 Hz) and a ratio of low- to high-frequency power (LF/HF) as indices of autonomic nervous activity; HF is an index of parasympathetic activity, whereas LF/HF is an index of sympathovagal balance. The relationships between those indices were then analysed. RESULTS: A moderate negative correlation was found between TEWL and the relative maximum rate of increases in the responsiveness of SkBF on local warming. A moderate positive and a moderate negative correlation were observed between TEWL and LF/HF or HF, respectively. Moreover, a moderate negative and a moderate positive correlation were shown between the responsiveness of SkBF and LF/HF or HF, respectively. The hydration of the stratum corneum showed no correlations with any indices of microcirculation or autonomic nervous activity. CONCLUSION: These results indicate that skin barrier function, cutaneous microcirculatory function and autonomic nervous activity are mutually associated in healthy adults.

Subcutaneous abscess due to the basidiomycete Phellinus mori in a patient with chronic granulomatous disease.

Chronic granulomatous disease (CGD), a primary immunodeficiency caused by impaired phagocyte killing of intracellular pathogens, is characterized by recurrent, life-threatening, bacterial and fungal infections. As a result of improvements in microbiologic culture and identification techniques, a number of unique filamentous fungi have been reported as significant pathogens in patients with CGD. We report a case of subcutaneous basidiomycete Phellinus mori infection in a patient with CGD. To the best of our knowledge, this is the first reported case of human infection by this fungus. The causative fungus was identified on the basis of its morphological characteristics and nucleotide sequence on the internal transcribed spacer region of the ribosomal RNA gene. This is the fifth case report of filamentous basidiomycetes infecting a patient with CGD; all of these cases have been caused by Phellinus species. We highlight the importance of recognizing filamentous basidiomycetes Phellinus species as possible agents of non-Aspergillus fungal infections in patients with CGD.

Pattern classification in kampo medicine.

Pattern classification is very unique in traditional medicine. Kampo medical patterns have transformed over time during Japan's history. In the 17th to 18th centuries, Japanese doctors advocated elimination of the Ming medical theory and followed the basic concepts put forth by Shang Han Lun and Jin Gui Yao Lue in the later Han dynasty (25-220 AD). The physician Todo Yoshimasu (1702-1773) emphasized that an appropriate treatment could be administered if a set of patterns could be identified. This principle is still referred to as "matching of pattern and formula" and is the basic concept underlying Kampo medicine today. In 1868, the Meiji restoration occurred, and the new government changed its policies to follow that of the European countries, adopting only Western medicine. Physicians trained in Western medicine played an important role in the revival of Kampo medicine, modernizing Kampo patterns to avoid confusion with Western biomedical terminology. In order to understand the Japanese version of traditional disorders and patterns, background information on the history of Kampo and its role in the current health care system in Japan is important. In this paper we overviewed the formation of Kampo patterns.

Ovulation day after onset of vulval bleeding in a beagle colony.

This study investigated the duration of the interval between the onset of vulval bleeding at pro-oestrus and ovulation estimated from the plasma progesterone concentration in a large number of beagle bitches. The influence and association of individual variation, ageing and duration of the oestrous cycle were also investigated. The mean time of ovulation after the onset of vulval bleeding was 11.1 ± 0.2 days, but it widely ranged from 3 to 31 days. This timing was not influenced by age or duration of the oestrous cycle, and within-individual variation was small. As there has been no previous report in which the ovulation day was investigated by the age, these data may be very valuable.

Down-regulation of single immunoglobulin interleukin-1R-related molecule (SIGIRR)/TIR8 expression in intestinal epithelial cells during inflammation.

Single immunoglobulin (Ig) interleukin-1R-related molecule (SIGIRR) is an Ig-like membrane protein critical for negative regulation of Toll-like receptor (TLR)-4-mediated signalling. We investigated SIGIRR expression and its regulation mechanism in intestinal epithelial cells (IECs) during inflammation. Endoscopic biopsy specimens were obtained from active and inactive colonic mucosa of ulcerative colitis (UC) patients, then SIGIRR expression was examined using real-time polymerase chain reaction (PCR) and immunohistochemistry (IH). Mice experimental colitis models were established by administrations of sulphonic acid (TNBS) and dextran sodium sulphate (DSS), and epithelial expression of SIGIRR was examined using real-time PCR, IH and flow cytometry. The effects of lipopolysaccharide (LPS) and tumour necrosis factor (TNF)-α on SIGIRR expression were evaluated in vitro using cultured IECs. To elucidate SIGIRR expression regulation in IECs, binding ability of the transcription factor SP1 at the responsive element of the SIGIRR promoter was examined using gel-shift and chromatin immunoprecipitation (ChIP) assays. In human colonic samples, SIGIRR was expressed mainly in IECs at levels significantly higher in inactive compared to active mucosa. In the mice, SIGIRR colonic expression decreased rapidly after colitis development and returned gradually to basal levels. Experimental colitis-mediated down-regulation of SIGIRR in IECs was also confirmed by IH and flow cytometry results. Further, inflammatory conditions induced by TLR ligands and TNF-α caused significant down-regulation of SIGIRR expression in IECs, which was dependent upon decreased SP1 binding at the responsive element of the SIGIRR promoter. We found that SIGIRR is expressed in IECs and serves as a negative regulator to maintain gut innate immunity, which is down-regulated during inflammation by inhibition of an SP1-mediated pathway.

Hemostasis for severe hemorrhage with photocrosslinkable chitosan hydrogel and calcium alginate.

In patients with severe hemorrhage, complications such as shock or death may occur if the patient is not treated appropriately and expeditiously. To create a hemostat kit for severe hemorrhage, ultraviolet light irradiation was applied to photocrosslinkable chitosan hydrogel and calcium alginate. As a hemorrhage model, the femoral arteries and veins of anesthetized rats were cut. Hemodynamics and hematological parameters including red blood cell (RBC) count, hemoglobin concentration, hematocrit, white blood cell (WBC) count, and platelet count, and serum parameters including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured as a marker of hemostasis. In rats for which no procedure was used, death occurred within 30 min. By using the hydrogel hemostat, the survival rate rose to 75% or more. RBC count, hemoglobin, hematocrit, and platelet levels were not significantly changed for 3 days. WBC count increased 1 day after hemostasis. AST and ALT increased 1 day after hemostasis, but it decreased 3 days later. The photocrosslinkable chitosan hydrogel and calcium alginate were biodegraded at 3 and 28 days, respectively, by neutrophils and keratinocyte chemoattractant.

Oolong tea is useful for lens cleansing in transnasal small-caliber esophagogastroduodenoscopy.

BACKGROUND AND STUDY AIMS: Unsedated transnasal small-caliber esophagogastroduodenoscopy (EGD) has been used to examine the upper gastrointestinal tract with proven feasibility and tolerability. However, a limitation of transnasal EGD is the poor lens-cleansing function of the scope due to the small-caliber water-jet nozzle. Therefore, this trial was designed to evaluate the cleansing effect of oolong tea for transnasal small-caliber EGD. PATIENTS AND METHODS: Oolong tea (O), barley tea (B), and distilled water (W) were prepared as washing solutions for endoscopic lenses. Study I: after the lenses were soiled by lard oil, they were washed with one of the three washing solutions, and the image quality of photographs was judged. Study II: 982 patients who were due to undergo transnasal EGD were enrolled and randomly assigned to the O-, B-, or W-groups. The level of lens cleansing, the overall time required for endoscopy, and the volume of washing solution used were measured. RESULTS: Study I: the image quality of photographs taken with lenses washed with oolong tea was significantly superior to that associated with other solutions. Study II: the level of lens cleansing in the O-group was significantly superior to that of the B- and W-groups ( P < 0.001). The volume of solution used for lens cleansing in the O-group was significantly smaller than that in the W-group ( P < 0.05). Endoscopic examination times in the O-group were shorter than those in the B- and W-groups ( P < 0.05). CONCLUSIONS: In transnasal small-caliber EGD, oolong tea instead of water as a washing solution for endoscopic lens cleansing is useful to maintain good visibility.

A20 is an early responding negative regulator of Toll-like receptor 5 signalling in intestinal epithelial cells during inflammation.

Several negative regulatory mechanisms control Toll-like receptor (TLR)-mediated inflammatory responses and restore immune system balance, including the zinc-finger protein A20, a negative regulator of TLR signalling that inhibits nuclear factor kappa B (NF-kappaB) activity. In the present study, we investigated TLR-5-mediated A20 expression and its role in intestinal epithelial cells (IECs) during inflammation. HCT-15 and HT-29 cells were stimulated with flagellin, then the expressions of A20, interleukin-1 receptor-associated kinase (IRAK-M) and Tollip were evaluated using RNase protection assay. Furthermore, experimental colitis was induced in tlr4-deficient CH3/HeJ mice by administration of dextran sodium sulphate (DSS), then flagellin was injected anally, and the colonic expression of A20 was examined by real-time polymerase chain reaction (PCR) and immunohistochemistry. To confirm flagellin-induced expression of A20, we employed an organ culture system. The role of A20 in flagellin-induced tolerance induction was evaluated in vitro, using a gene knock-down method targeting A20. A20 expression increased rapidly and peaked at 1 h after flagellin stimulation in cultured IECs, then declined gradually to the basal level. In vivo, anal injection of flagellin induced epithelial expression of A20 in injured colonic tissue, whereas flagellin did not cause a significant increase in A20 expression in non-injured normal tissue, which was also confirmed in vitro using the organ culture system. Gene knock-down using A20 siRNA did not influence tolerance induced by restimulation with flagellin. A20 is an early response negative regulator of TLR-5 signalling in IECs that functions during intestinal inflammation. Our results provide new insights into the negative feedback regulation of TLR-5 signalling that maintains the innate immune system in the gut.

Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions.

BACKGROUND AND PURPOSE: Inhibition of squalene synthesis could transform unstable, macrophage/lipid-rich coronary plaques into stable, fibromuscular plaques. We have here treated WHHLMI rabbits, a model for coronary atherosclerosis and myocardial infarction, with a novel squalene synthase inhibitor, lapaquistat acetate (TAK-475). EXPERIMENTAL APPROACH: Young male WHHLMI rabbits were fed a diet supplemented with lapaquistat acetate (100 or 200 mg per kg body weight per day) for 32 weeks. Serum lipid levels were monitored every 4 weeks. After the treatment, lipoprotein lipid and coenzyme Q10 levels were assayed, and coronary atherosclerosis and xanthomas were examined histopathologically or immunohistochemically. From histopathological and immunohistochemical sections, the composition of the plaque was analysed quantitatively with computer-assisted image analysis. Xanthoma was evaluated grossly. KEY RESULTS: Lapaquistat acetate decreased plasma cholesterol and triglyceride levels, by lowering lipoproteins containing apoB100. Development of atherosclerosis and xanthomatosis was suppressed. Accumulation of oxidized lipoproteins, macrophages and extracellular lipid was decreased in coronary plaques of treated animals. Treatment with lapaquistat acetate increased collagen concentration and transformed coronary plaques into fibromuscular plaques. Lapaquistat acetate also suppressed the expression of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 in the plaque and increased peripheral coenzyme Q10 levels. Increased coenzyme Q10 levels and decreased very low-density lipoprotein cholesterol levels were correlated with improvement of coronary plaque composition. CONCLUSION AND IMPLICATIONS: Inhibition of squalene synthase by lapaquistat acetate delayed progression of coronary atherosclerosis and changed coronary atheromatous plaques from unstable, macrophage/lipid accumulation-rich, lesions to stable fibromuscular lesions.

Immediate effects of a rucksack type orthosis on the elderly with decreased lumbar lordosis during standing and walking.

The spinal orthosis, the so-called rucksack type orthosis (RO), has been used to relieve low back pain and fatigue during prolonged standing and walking for the elderly with spinal deformities. However, little is known about the RO's kinematical effects. Twenty-three elderly (78.9 +/- 6.9 years old) participated in experiment 1, and 13 elderly (78.4 +/- 7.9 years old) in experiment 2. They had decreased lumbar lordosis or lumbar kyphosis. In experiment 1, using the "Spinal Mouse", which can measure spinal curvature, the effects of the RO on posture during standing were investigated. In experiment 2, using electromyography, the effects of the RO on muscle activity during standing and walking were clarified. Lumbar curvature and the trunk angle of inclination during standing improved significantly when the RO was used. Back extensor muscle activities (T9, L3, and L5) during standing and walking decreased significantly when the RO was used. There were no significant differences in the activities of the upper trapezius and vastus lateralis during standing and walking. The present study suggests that the elderly with lumbar deformities might be able to stand and walk more efficiently with the RO. The RO could prove to be valuable in preservation therapy for the elderly with decreased lumbar lordosis or lumbar kyphosis.

Pre-exposure to infectious hypodermal and haematopoietic necrosis virus or to inactivated white spot syndrome virus (WSSV) confers protection against WSSV in Penaeus vannamei (Boone) post-larvae.

Larvae and post-larvae of Penaeus vannamei (Boone) were submitted to primary challenge with infectious hypodermal and haematopoietic necrosis virus (IHHNV) or formalin-inactivated white spot syndrome virus (WSSV). Survival rate and viral load were evaluated after secondary per os challenge with WSSV at post-larval stage 45 (PL45). Only shrimp treated with inactivated WSSV at PL35 or with IHHNV infection at nauplius 5, zoea 1 and PL22 were alive (4.7% and 4%, respectively) at 10 days post-infection (p.i.). Moreover, at 9 days p.i. there was 100% mortality in all remaining treatments, while there was 94% mortality in shrimp treated with inactivated WSSV at PL35 and 95% mortality in shrimp previously treated with IHHNV at N5, Z1 and PL22. Based on viral genome copy quantification by real-time PCR, surviving shrimp previously challenged with IHHNV at PL22 contained the lowest load of WSSV (0-1x10(3) copies microg-1 of DNA). In addition, surviving shrimp previously exposed to inactivated WSSV at PL35 also contained few WSSV (0-2x10(3) copies microg-1 of DNA). Consequently, pre-exposure to either IHHNV or inactivated WSSV resulted in slower WSSV replication and delayed mortality. This evidence suggests a protective role of IHHNV as an interfering virus, while protection obtained by inactivated WSSV might result from non-specific antiviral immune response.

Interobserver agreement on classifying endoscopic diagnoses of nonerosive esophagitis.

BACKGROUND AND STUDY AIMS: The majority of patients with gastroesophageal reflux disease in Japan have low-grade esophagitis, including minimal changes. A modified Los Angeles classification of esophagitis, consisting of erosive esophagitis (grades A - D) and nonerosive esophagitis (grades M and N) has been proposed and is in clinical use in Japan. However, it is unclear whether nonerosive esophagitis with only undemarcated mucosal discoloration (grade M) is clinically significant, since interobserver variations in classification have not been investigated. The aim of the present study was therefore to evaluate interobserver variance and diagnostic agreement in the diagnosis of nonerosive esophagitis (grades M and N). MATERIALS AND METHODS: A total of 84 endoscopists were enrolled to assess the grade of esophagitis in 30 patients by viewing endoscopic images of the gastroesophageal junction. The images were projected onto a screen, and all of the endoscopists reviewed them concurrently. The diagnosis was selected from the following three categories in the modified Los Angeles classification: grades N, M, or A. The endoscopists were grouped according to their experience, whether they had a board license, and whether they had received specialist training in esophagitis. The kappa coefficient of reliability was calculated. RESULTS: The kappa coefficient of reliability for all the endoscopists in the diagnosis of cases of grade M and N nonerosive esophagitis was unacceptably low at 0.22 (95 % CI, 0.21 - 0.24). Endoscopists with a board license and those who had completed a special esophagitis diagnostic course had slightly higher kappa values (0.26; 95 % CI, 0.23 - 0.30 and 0.29; 95 % CI, 0.26 - 0.32), respectively. CONCLUSIONS: Interobserver agreement on the endoscopic diagnosis of nonerosive esophagitis (grades M and N) is too low to be of clinical value.

Evaluation of modified crystal violet chromoendoscopy procedure using new mucosal pit pattern classification for detection of Barrett's dysplastic lesions.

BACKGROUND: Pit pattern diagnosis is important for endoscopic detection of dysplastic Barrett's lesions, though using magnification endoscopy can be difficult and laborious. We investigated the usefulness of a modified crystal violet chromoendoscopy procedure and utilised a new pit pattern classification for diagnosis of dysplastic Barrett's lesions. METHODS: A total of 1,030 patients suspected of having a columnar lined oesophagus were examined, of whom 816 demonstrated a crystal violet-stained columnar lined oesophagus. The early group of patients underwent 0.05% crystal violet chromoendoscopy, while the later group was examined using 0.03% crystal violet with 3.0% acetate. A targeted biopsy of the columnar lined oesophagus was performed using crystal violet staining after making a diagnosis of closed or open type pit pattern with a newly proposed system of classification. The relationship between type of pit pattern and histologically identified dysplastic Barrett's lesions was evaluated. RESULTS: Dysplastic Barrett's lesions were identified in biopsy samples with an open type pit pattern with a sensitivity of 96.0%. Further, Barrett's mucosa with the intestinal predominant mucin phenotype was closely associated with the open type pit pattern (sensitivity 81.9%, specificity 95.6%). CONCLUSIONS: The new pit pattern classification for diagnosis of Barrett's mucosa was found to be useful for identification of cases with dysplastic lesions and possible malignant potential using a crystal violet chromoendoscopic procedure.

Helicobacter pylori infection influences symptomatic response to anti-secretory therapy in patients with GORD--crossover comparative study with famotidine and low-dose lansoprazole.

BACKGROUND AND AIM: Helicobacter pylori infection was reported to affect gastric acid secretion. We investigated the heartburn symptoms of patients with gastro-oesophageal reflux disease during sequential treatment with 40 mg of famotidine or 15 mg of lansoprazole to clarify whether H. pylori infection influences symptomatic response to anti-secretory therapy. SUBJECTS AND METHODS: The subjects were 33 gastro-oesophageal reflux disease patients, who had already been treated with a full dose of H2 receptor antagonist. First, famotidine at 20 mg b.i.d. was administered to the patients for 8 weeks. Second, famotidine was replaced with 15 mg of lansoprazole once in the morning for 8 weeks. Finally, 20 mg of famotidine was administered b.i.d. for 8 weeks instead of lansoprazole. Gastro-oesophageal reflux disease symptoms were assessed using an original visual analogue scale. RESULTS: The sequential symptomatic responses to famotidine and lansoprazole administration indicated that gastro-oesophageal reflux disease symptoms of patients during low-dose lansoprazole treatment were significantly less than those during famotidine treatment. Remission of symptoms was obtained significantly more often by famotidine therapy in patients with H. pylori infection than in patients without H. pylori infection. CONCLUSION: Low-dose lansoprazole is more effective than full-dose famotidine for the control of symptoms in patients with gastro-oesophageal reflux disease, and H. pylori infection influences the symptomatic response to H2 receptor antagonists.

Barrett's oesophagus with predominant intestinal metaplasia correlates with superficial cyclo-oxygenase-2 expression, increased proliferation and reduced apoptosis: changes that are partially reversed by non-steroidal anti-inflammatory drugs usage.

BACKGROUND: Cyclo-oxygenase-2 expression has been reported to play an important role in the metaplasia-dysplasia-carcinoma sequence in Barrett's oesophagus. However, the existence of cyclo-oxygenase-2 expressing cells in Barrett's epithelium is still uncertain. AIM: To identify the cells that express cyclo-oxygenase-2 protein and to investigate the relationship between cyclo-oxygenase-2 expression and mucin-phenotype of Barrett's epithelium. METHODS: Sections from 466 biopsy samples of Barrett's epithelium from 358 non-medicated patients were immunohistochemically examined for the cyclo-oxygenase-2 expression, mucin-phenotype, cell proliferation and apoptosis. RESULTS: Cyclo-oxygenase-2 expression was detected in 71.0% of Barrett's epithelium biopsy samples. In Barrett's epithelium with the gastric predominant mucin-phenotype, cyclo-oxygenase-2 expression was mainly found in stromal and deep epithelial cells, whereas in intestinal predominant mucin-phenotype, it was mostly in superficial epithelial cell. A significant elevation of proliferating cell nuclear antigen index and suppression of apoptotic index was observed in Barrett's epithelium with superficial epithelial cyclo-oxygenase-2 expression. Neither such elevation of proliferating cell nuclear antigen index nor the suppression of apoptotic index could be found in chronic non-steroidal anti-inflammatory drugs users. CONCLUSIONS: Barrett's epithelium with intestinal mucin and superficial epithelial cyclo-oxygenase-2 expression possess a higher proliferation potential, but this risk may be thwarted by non-steroidal anti-inflammatory drugs administration.

Correlation between dietary glycemic index and cardiovascular disease risk factors among Japanese women.

OBJECTIVE: To examine the correlation between dietary glycemic index (GI) and cardiovascular disease (CVD) risk factors among subjects who consume white rice as a staple food. DESIGN: A cross-sectional study was conducted to explore the associations between dietary GI, dietary glycemic load (GL) and dietary intakes, and CVD risk factors. Dietary GI and GL were calculated from a 3-day (including two consecutive weekdays and one holiday) dietary records. SETTING: A weight-reduction program at a municipal health center in Tokyo, Japan. SUBJECTS: A total of 32 women aged 52.5+/-7.2 y participated in the weight-reduction program. RESULT: The GI food list made for the current study calculated for 91% of carbohydrate intakes measured. The mean dietary GI was 64+/-6, and the mean dietary GL was 150+/-37. Individuals in the highest tertile of GI consumed more carbohydrate, mostly from white rice (P<0.001), and less fat (P<0.01). Individuals in all three groups by tertile of GL showed similar tendencies. In the lowest GI tertile, the highest concentration of HDL-cholesterol and lowest concentration of triacylglycerol and immunoreactive insulin were observed (P<0.01). In the lowest GL tertile, the highest concentration of HDL-cholesterol and the lowest concentration of triacylglycerol were observed (P<0.05). CONCLUSION: Calculated dietary GI and GL were positively associated with CVD risk factors among the Japanese women who consumed white rice as a staple food.