Advancement of magma fragmentation by inhomogeneous bubble distribution.

Decompression times reported in previous studies suggest that thoroughly brittle fragmentation is unlikely in actual explosive volcanic eruptions. What occurs in practice is brittle-like fragmentation, which is defined as the solid-like fracture of a material whose bulk rheological properties are close to those of a fluid. Through laboratory experiments and numerical simulation, the link between the inhomogeneous structure of bubbles and the development of cracks that may lead to brittle-like fragmentation was clearly demonstrated here. A rapid decompression test was conducted to simulate the fragmentation of a specimen whose pore morphology was revealed by X-ray microtomography. The dynamic response during decompression was observed by high-speed photography. Large variation was observed in the responses of the specimens even among specimens with equal bulk rheological properties. The stress fields of the specimens under decompression computed by finite element analysis shows that the presence of satellite bubbles beneath a large bubble induced the stress concentration. On the basis of the obtained results, a new mechanism for brittle-like fragmentation is proposed. In the proposed scenario, the second nucleation of bubbles near the fragmentation surface is an essential process for the advancement of fragmentation in an upward magma flow in a volcanic conduit.

Characteristic activities of lower limbs with body weight support ratio.

In this study, we investigated a lower limbs muscle activity during body weight support treadmill training (BWSTT). Informed consent was obtained from 16 healthy men. Experimental system consists of force plate, treadmill, three-dimensional motion analysis system, electromyograph, and body weight support device. Body weight support (BWS) was set every 15% increase from 0% to 45%. Walking speed was 4.17 km/h. The measurement data were reaction forces, joint angles, joint moments and lower limbs muscle activities. The vertical reaction force shows two peaks. Two peaks decreased with increase of BWS together. Joint angles did not show significant changes with BWS. However, only the extension of hip angle was decreased with BWS. The peaks of joint moment were decreased. Decrease of ankle joint moment was greatest compared with other moment. Decrease of peaks of muscle activity by BWS was observed during stance phase, and did not almost change during swing phase.

Lambda incision for effective tissue expansion.

By using a rectangular type tissue expander, the skin is expanded as a cuboid. To cover a skin defect effectively, it is necessary to cut the expanded skin and to spread it out as a flap. We designed the lambda incision of the lateral wall of the expanded cuboid. In principle we make one lambda incision on each lateral wall (a total of 2 incisions). However, if the defect is triangular, one lambda on one side is sufficient. If it is a trapezoid, one lambda on one side and two lambdas on the opposite side are used. The lambda incision was applied in 11 cases. In almost all, the expanded skin could be spread out well and the lesions could be resected. There were no complication due to lambda incisions.

Improvement of the maxillary bone growth suppression in the cleft palate operation with cultured dermal substitute: animal experiment and patient reports in preliminary clinical application.

Cleft palate patients often show impaired maxillary bone growth after cleft-palate-correction surgery. We attempted to investigate and elucidate the effects of using allogeneic, cultured dermal substitute (CDS) to cover an exposed, palatal bone surface in animal experiments. Fibroblasts from the abdominal skin of Wistar rats were cultured. Subsequently, the fibroblasts were seeded onto a matrix that composed of hyaluronic acid and atelo-collagen. Forty Wistar rats (3-week-old males) were assigned to one of four groups: control, open-treatment, matrix and CDS groups. The control group (n=5) received no surgical operations. In the open-treatment group (n=11), the mucosa and periosteum of the left-half of the palate were removed surgically and the bone was exposed. In the matrix group (n=11), the area of exposed bone was covered with only the matrix, excluding any cells. In the CDS group (n=10), the area of exposed bone was covered with CDS. At 9 weeks postoperatively, biopsies of the wounds were obtained. Skull preparations were made and the palatal widths were determined. The palatal widths in the CDS group were significantly wider compared to the matrix and open-treatment groups (P<0.05). However, there were no significant differences when the CDS group was compared to the control group. Haematoxylin, eosin and CD31 immunostaining confirmed a larger number of capillaries in the CDS group. This animal experiment suggested that this procedure might provide an optimum wound-healing condition, thus, reducing the maxillary bone-growth suppression. Therefore, a preliminary clinical application in three patients was performed using the autologous CDS after the pushback method.

Functional reconstruction of the upper and lower lips and commissure with a forearm flap combined with a free gracilis muscle transfer.

After resection of an arterio-venous malformation of the upper and lower lips and commissure we performed reconstruction with a forearm flap combined with a free gracilis muscle transfer. First the motor nerve of the gracilis muscle was anastomsed to a buccal nerve branch in the cheek. In a second operation, the red lip was reconstructed with an oral mucosal graft, and the upper lip skin was reconstructed with a local flap. The patient obtained good oral sphincter function for eating, speaking and air inflation.

The ADRB3 Trp64Arg variant and BMI: a meta-analysis of 44 833 individuals.

BACKGROUND: The beta-3 adrenergic receptor gene (ADRB3) is part of the adrenergic system, which is known to play a key role in energy metabolism. The association between the Trp64Arg variant in the ADRB3 and body mass index (BMI) has been widely examined, but previous studies have been small and results have been inconsistent. METHODS: We assessed the association between the ADRB3 Trp64Arg variant and BMI in a large UK population-based cohort of 4854 middle-aged men and women. We also performed a meta-analysis of 97 studies, involving 44 833 individuals, to place our findings in context. RESULTS: Although we found no significant difference in BMI (0.20 kg/m(2), P=0.40) between the Trp64Trp homozygotes and Arg64 allele carriers in our UK population-based cohort, the meta-analysis showed significant association between the Arg64Trp variant and BMI, with Arg64-allele carriers having a 0.24 kg/m(2) (P=0.0002) higher BMI compared with noncarriers. However, we also found substantial heterogeneity among the studies (P=2.2 x 10(-14)). The difference in East Asians (0.31 kg/m(2), P=0.001) was 3.9 times larger than that in Europeans in whom no significant association was observed (0.08 kg/m(2), P=0.36). This was consistent with the chronological cumulative decrease in the effect size, which decreased steadily in Europeans and reached nonsignificance after 11 studies in 1996. In East Asians, the cumulative effect size decreased after the first reports, but reached a steady state at a significant effect size of 0.24 kg/m(2) in 2000. Although the funnel plot indicated no apparent publication bias, smaller studies tended to report greater differences in BMI, compared with larger studies. CONCLUSIONS: Collectively, these data suggest that the Trp64Arg ADRB3 genetic variant might be associated with BMI in East Asians, but not Europeans. More generally, our study shows the importance of meta-analyses in the field of genetic association studies for common traits. Each genetic variant makes only a small contribution to variation in BMI, and large sample sizes are needed to reliably assess and interpret gene-phenotype associations.

Localization of glucagon-like peptide-2 receptor mRNA expression at different sites in the small intestine of rats.

Preproglucagon is known to be processed into glucagon-like peptide (GLP)-1, GLP-2, and glicentin in the L cells of the intestinal tract. GLP-2 has been shown to possess intestinotrophic activity in rodents. However, the ligand-binding mechanisms of GLP-2 receptor (GLP-2R) have not been extensively investigated. The present study sought to determine the localization of GLP-2R in the small intestine by analyzing GLP-2R mRNA expression using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. GLP-2R mRNA expression was detected at all sites in the small intestine; its expression levels were particularly high in the jejunum. Moreover, GLP-2R mRNA expression was detected in both non-mucosal intestinal tissues and intestinal mucosa. These findings suggest that in addition to the intestinal mucosa, the functional sites of GLP-2 may be present in the non-mucosal tissues. These results imply that GLP-2 peptide acts as an intestinotrophic factor that may affect the intestines from outside the mucosa. The intestinotrophic effect of GLP-2 from outside the mucosa may be a function of the enteric neurons transmitting several growth signals to mucosal cells.

Comparison of the effects of glimepiride and glibenclamide on adipose tissue tumour necrosis factor-alpha mRNA expression and cellularity.

AIM: The aim of this study was to compare the effects of glimepiride and glibenclamide on tumour necrosis factor (TNF)-alpha expression and adipocyte cellularity in spontaneously diabetic, obese rats. METHODS: Eight-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomized to receive glimepiride, glibenclamide or control treatment for 12 weeks, after which TNF-alpha mRNA levels, adipose tissue cellularity and physiological parameters were measured. RESULTS: TNF-alpha mRNA expression in retroperitoneal fat tissue was significantly greater in the glibenclamide group (2.2 +/- 1.1), compared with the control group (0.9 +/- 0.4; p<0.05) or the glimepiride group (0.9 +/- 0.2; p<0.01). The mean fat-cell area in retroperitoneal fat tissue was increased at study endpoint in the glibenclamide group (13,764 +/- 7036 microm2), compared with both the control and glimepiride groups (10,755 +/- 6193 microm2 and 11,317 +/- 5646 microm2 respectively; p<0.05). Investigation of cellularity revealed a decrease in the frequency of small fat cells and an increase in the frequency of large fat cells in both the glibenclamide and glimepiride groups compared with the control group, with a greater increase in large fat cells in the glibenclamide group. At study endpoint, insulin and triglyceride values were significantly higher in the active treatment groups compared with the control group; however, insulin levels were significantly greater in glibenclamide-treated animals compared with glimepiride-treated animals. An oral glucose tolerance test performed at the end of the study showed that there were no significant differences among the three groups in terms of plasma glucose and insulin concentrations. CONCLUSIONS: This study suggests that although both glibenclamide and glimepiride may have a hypertrophisizing effect on fat cells in adipose tissues, this effect is greater with glibenclamide, leading to augmentation of TNF-alpha mRNA expression and possible exacerbation of insulin resistance.

Plasma adiponectin levels in women with anorexia nervosa.

Adiponectin is a plasma protein exclusively secreted by adipose tissue, which plays a role in modulating lipid and glucose metabolism. The plasma adiponectin concentration shows an inverse correlation with the body mass index in normal and obese individuals, but it has not been investigated in subjects with an extremely low body weight and undernutrition such as anorexia nervosa patients. We investigated plasma adiponectin levels in 21 females with anorexia nervosa. Nineteen healthy females served as the lean control group. The subjects with anorexia nervosa had a significantly lower weight and showed a tendency towards higher adiponectin levels than the control group. No correlation between adiponectin and BMI was found in patients with anorexia nervosa, while a linear negative correlation was seen in lean controls. The patient who showed the lowest adiponectin level reached a life-threatening state and required intravenous feeding in hospital. In association with improved nutrition and weight gain, the adiponectin level increased gradually until the body mass index was about 16 and then decreased subsequently as would be expected in lean normal subjects. These observations suggest that adipose tissue secretes less adiponectin and the adiponectin levels do not show an inverse correlation simply with body mass index in some subjects with severe undernutrition.

In vitro inhibitory effects of Kampo medicines on metabolic reactions catalyzed by human liver microsomes.

BACKGROUND: Although it is well known that drug-drug interactions may lead to toxicity and therapeutic failure, little is known about the incidence and consequences of herb-drug interactions in patients receiving Kampo medicines. METHODS: We evaluated the frequency of the combined use of Kampo medicines and Western drugs at Osaka University Hospital, and investigated the effects of these formulae on the metabolic activity of different cytochrome P450 (CYP) isoforms using pooled microsomes obtained from human liver. RESULTS: Twenty-two Kampo formulae were used together with 40 Western drugs catalyzed by the CYP isoforms CYP3A4, CYP2C9, CYP2D6 and CYP1A2. Among the Kampo medicines, HOCHUEKKI-TO, SHOSAIKO-TO, NINJINYOUEI-TO, SAIREI-TO and KAKKON-TO were most frequently used during the study period (1996-2000). These were co-administered with 11 categories of drugs, which are substrates for CYP3A4. HOCHUEKKI-TO and SAIREI-TO were competitive inhibitors of CYP3A4 with Ki values of 0.65 and 0.1 mg/mL, respectively. HOCHUEKKI-TO, SHOSAIKO-TO and SAIREI-TO inhibited the metabolic activities of CYP2C9, but had no effect on CYP2D6. HOCHUEKKI-TO and SAIREI-TO exhibited non-competitive inhibition of the metabolic activity of CYP2C9 with a similar Ki value (0.7-0.8 mg/mL). SAIRE-TO (0.25 mg/mL) was a potent inhibitor of CYP1A2 (inhibition > 68%). CONCLUSIONS: Frequently used Kampo medicines may interact with Western drugs, which are substrates for CYP3A4, CYP2C9 and CYP1A2. Their co-administration should be undertaken with care.

Association of BMI with the beta3-adrenergic receptor gene polymorphism in Japanese: meta-analysis.

OBJECTIVE: To assess the effect of the Trp64Arg polymorphism in the beta3-adrenergic receptor gene (ADRB3) on body mass index (BMI) in the Japanese population. RESEARCH METHODS AND PROCEDURES: We selected studies that evaluated the association between BMI and ADRB3 polymorphism among Japanese, using MEDLINE and PubMed. After data collection, an extension of ANOVA was performed to assess the differences according to the genotype. RESULTS: In a total of 35 subgroups including 2316 subjects with the Trp64Arg variant and 4266 subjects without this variant, the weighted mean difference in BMI was 0.26 kg/m(2) (95% confidence interval: 0.18 to 0.42; p < 0.01), indicating that variant carriers exhibited higher BMI than did normal homozygous subjects. DISCUSSION: Although it is known that the allele frequency of the ADRB3 polymorphism differs among races, this study focuses on the Japanese population, which has a high allele frequency of ADRB3 polymorphism. We assumed that statistical errors would be prevented due to the sufficient number of subjects. In conclusion, the results support the hypothesis that ADRB3 gene polymorphism is associated with BMI.

5-HT2A promoter polymorphism is not associated with anorexia nervosa in Japanese patients.

Genetic factors have been implicated in playing a significant role in susceptibility to anorexia nervosa (AN). Among many candidate genes for AN, an association with the A allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor has been reported. However, these findings are controversial and all patients studied to date have been Caucasian. This study was designed to determine whether this association is reproducible in Japanese subjects. This case-control study of a cohort of 75 female Japanese AN sufferers and 127 normal female control subjects revealed no significant association between the 5-HT2A promoter polymorphism and AN. Thus, at least for Japanese subjects, the A-allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor gene does not contribute to a predisposition to AN.

Analysis of tumor necrosis factor-alpha gene promoter polymorphisms in anorexia nervosa.

Elevated plasma tumor necrosis factor-alpha (TNFalpha) levels and enhanced spontaneous TNFalpha release from peripheral blood mononuclear cells in patients with anorexia nervosa (AN) have been reported. TNFalpha activates the hypothalamic-pituitary-adrenal axis and reduces food intake, which is characteristic of eating disorders. Recently, three novel polymorphisms in the 5'-flanking region of the TNFalpha gene were reported at positions -1031 (T --> C substitution), -863 (C --> A) and -857 (C --> T). Differences in these alleles are reportedly related to altered TNFalpha-transcriptional promoter activity. Therefore, we performed a case-control association analysis to determine whether any of those three polymorphisms in the TNFalpha promoter region were involved in a predisposition to AN. The results of our analysis of a cohort of 79 female Japanese AN sufferers and 127 normal female control subjects provide no support for the hypothesis that -1031T/C, -863 C/A and -857C/T polymorphisms in the TNFalpha gene promoter region influence the susceptibility to AN.

Morphology, fluorescence properties, and their photothermal changes of poly(substituted thiophene) films revealed by near-field fluorescence microspectroscopy.

The morphology and fluorescence spectrum of poly(3-[2-(N-dodecylcarbamoyloxy)ethyl]thiophene-2,5-diyl) film were examined with spatial resolution of 100 nm using near-field fluorescence microspectroscopy. Fluorescence spectra observed at protruding domains were blue-shifted compared with flat areas, and further blue-shift was observed there more appreciably by long-time irradiation via a near-field scanning optical microscope probe. It is considered that the polymer chains at the protruding domains take disordered conformations, in which conjugated lengths are shorter and further disordering can be induced more easily by irradiation compared with those in the flat areas.

Protective effect of melatonin on methylmercury-Induced mortality in mice.

Effect of melatonin on the mortality in methylmercury chloride (MMC)-intoxicated mice was evaluated. Mice were given MMC in the diet (40 mg Hg/g) with or without melatonin in drinking water (20 mg/ml) for 5 weeks. In the control group, given MMC alone, 4 of 10 mice began to show neurological signs (e.g., abnormal righting reflex, staggering gaitfallen and posture on its side) concomitant with loss of body weight 4-7 days before death. This group also showed 60% of survival rate on the 35th day. However, the treated group, concomitantly given melatonin, showed a 100% of survival rate on the 35th day, although 1 of 10 mice began to show the neurological signs on the 33rd day. The level of thiobarbituric acid reactive substance in the brain, as an indication of oxidative damage, showed a significant decrease in the treated group compared with the control group. Thus, the 100% survival rate in the treated group may be partly due to antioxidative effect of melatonin on the MMC induced neurotoxicity.

Interrater agreement on the Coping Inventory for Stressful Situations (CISS).

The Coping Inventory for Stressful Situations (CISS) is a 48-item self-report inventory designed to measure three basic coping styles: Task Oriented, Emotion Oriented, and Avoidance Oriented coping. The psychometric properties of this inventory are promising, but CISS scores have not yet been shown to reflect behavioral variation in response to stress. This study was designed as a first step toward this end by examining the relationship between self- and peer-report on the CISS. One hundred and sixty-three pairs of friends completed the CISS, a peer form of the CISS, and a friendship questionnaire. Positive but modest correlations were found for each construct. Higher correlations were obtained when comparing scores across forms completed by the same informant, indicating that examinees believe their friends cope as they do themselves. Actual friend similarity was apparent only on Avoidance Oriented coping. Neither depth of relationship nor item observability moderated peer-self agreement.

Comparative study on germ cell mutation induced by urethane (ethyl carbamate) gas and X-rays in Drosophila melanogaster.

Although its mutagenicity has not been confirmed in mouse germ cells, urethane (ethyl carbamate) gas induces a significant increase of X-linked recessive lethal mutations in the germ cells of Drosophila melanogaster. The mutation frequency increased as the exposure time was changed from 3.5 to 5.5 h. Mutations were also induced by X-rays (20 to 40 Gy) and N-methyl-N-nitrosourea (MNU) (0.06 to 0.10%). However, no significant increase of chromosomal changes (partial loss of the Y chromosome, total loss of X or Y, and translocations) was produced by urethane, although these were readily induced by X-rays. There were large and significant increase in chromosomal changes caused by X-rays (20 Gy) compared to urethane (5.5 h) or MNU (0.06%). In contrast, there were no substantial differences among these three treatments as regards recessive lethal mutations. Urethane-induced DNA lesions detected as recessive lethals appear to be intragenic mutations. Complementation analysis with 15 reference single-site loci (cistrons) in the zeste-white region of the X chromosome revealed that 29 of 723 urethane-induced recessive lethals were located in the zeste-white region and all were restricted to a single locus. However, among 28 of 890 X-ray-induced lethals, 2 were non-complementary to 2 or 3 adjacent loci, indicating deletions encompassing 2 or 3 loci. In addition, 3 of these lethal chromosomes included mutations outside the zeste-white region. Another difference between urethane and X-rays was in the distribution of mutation sites. Urethane-induced mutations were strikingly non-random with two hot spots at zw-1 and zw-2, whereas the distribution of X-ray-induced mutations was more nearly random.

Consecutive maintenance of human solitary and hereditary colorectal polyps in SCID mice.

Recently, the sequential changes from adenoma to adenocarcinoma have been well studied in human colorectal carcinogenesis. To study the precise clonal changes from colorectal polyps to cancer, we have established an experimental system to maintain human colorectal polyps in severe combined immunodeficient (SCID) mice that have been improved by the selective inbreeding of C.B17-scid/scid homozygous male and female showing undetectable serum IgG and IgM (< 1 microgram/ml). Two of two solitary polyps from two nonhereditary colon polyp patients, four of five colon polyps from two Peutz-Jeghers' syndrome patients and one polypoid lesion from a familial polyposis coli (FAP) patient grew very slowly but steadily, at approximately one-tenth the rate of their malignant form, (i.e., adenocarcinoma), in the improved SCID mice and were maintained for a long period (more than 2 years), over several mouse generations. However, two polyps from FAP and Peutz-Jeghers' syndrome patients could not be transplanted further because of microinfection at the transplanted site due to incomplete sterilization of original human tumors prior to surgical operation (endoscopic polypectomy). Transplanted colon polyps had a semitransparent, soft and sticky appearance, with cells containing large amounts of mucin. Malignant transformation of human colon polyp to adenocarcinoma has not been observed during the maintenance period (about 2 years) in SCID mice. In the consecutively maintained human colon polyps, however, K-ras mutations were detected at codon 12, while these mutations were not found in their original polyps in the patients.