Management of angiogram-negative acute colonic hemorrhage: safety and efficacy of colonoscopy-guided superselective embolization.

BACKGROUND: We evaluated the efficacy and safety of superselective embolization with assistance of colonoscopy for acute colonic hemorrhage. METHODS: Of 92 cases of acute colonic hemorrhage requiring colonoscopic intervention, 11 (12 %) could not be successfully treated. Of these, 10 patients (9 men, mean age 65.5 years, range 39-75 years) underwent superselective embolization. Hemorrhage was caused by diverticular disease (n = 8), polypectomy (n = 1), and vascular malformation (n = 1). In all 10 cases, the radiopaque clips were placed at the bleeding point via colonoscopy. Microcatheters were used in all procedures, and embolization was performed at the level of the vasa recta leading to or near the clips with Gelfoam particles, microcoils, or both. RESULTS: Immediate hemostasis was achieved in all patients. In 6 of 10 patients (60 %), selective angiograms showed no active extravasation at the time of the procedure and the embolization was performed using clips as a landmark. In the remaining four patients, selective angiograms showed active extravasation from the vasa recta leading to the clips. The mean number of embolized vessels with no active extravasation and with active extravasation was 1.83 (range 1-3) and 1.25 (range 1-2), respectively. The mean duration of clinical follow-up was 11.6 months (range 1-29 months). One patient (10 %) bled from a different site than the treated site a month after embolization, but the bleeding ceased after endoscopic intervention. All the patients (100 %) were evaluated for objective evidence of ischemia by colonoscopy. Four of the 10 patients (40 %) were found endoscopically to have small areas of ischemia involving only the mucosa, but they remained asymptomatic. There was no bowel infarction or stricture. CONCLUSIONS: Colonoscopy-assisted superselective embolization may be a safe and useful procedure for acute colonic hemorrhage without active extravasation on angiogram.

Decadal stability in coral cover could mask hidden changes on reefs in the East Asian Seas.

Coral reefs in the Central Indo-Pacific region comprise some of the most diverse and yet threatened marine habitats. While reef monitoring has grown throughout the region in recent years, studies of coral reef benthic cover remain limited in spatial and temporal scales. Here, we analysed 24,365 reef surveys performed over 37 years at 1972 sites throughout East Asia by the Global Coral Reef Monitoring Network using Bayesian approaches. Our results show that overall coral cover at surveyed reefs has not declined as suggested in previous studies and compared to reef regions like the Caribbean. Concurrently, macroalgal cover has not increased, with no indications of phase shifts from coral to macroalgal dominance on reefs. Yet, models incorporating socio-economic and environmental variables reveal negative associations of coral cover with coastal urbanisation and sea surface temperature. The diversity of reef assemblages may have mitigated cover declines thus far, but climate change could threaten reef resilience. We recommend prioritisation of regionally coordinated, locally collaborative long-term studies for better contextualisation of monitoring data and analyses, which are essential for achieving reef conservation goals.

Prognostic nutritional index and early mortality with percutaneous endoscopic gastrostomy.

BACKGROUND: Although percutaneous endoscopic gastrostomy (PEG) is a well-accepted and less invasive method of feeding tube placement in patients with swallowing difficulties, complications and early death after PEG have been reported. AIM: This study aimed to evaluate predictive factors associated with 30-day mortality after PEG, and to assess the utility of nutritional supporting period before PEG in reducing early mortality following PEG. DESIGN: An observational study. METHODS: We retrospectively analyzed 268 patients who underwent PEG at Sapporo Shirakaba-dai Hospital from 2006 to 2010, using clinical and laboratory data to analyze predictive factors associated with early death after PEG. Then, we prospectively assessed 152 consecutive patients assessed for eligibility for PEG from 2011 to 2014. We assessed the patients' nutritional condition using Onodera's prognostic nutritional index (PNI), and supported nutrition for more than 10 days before PEG in patients with a poor nutritional index (PNI < 37). RESULTS: In both univariate and multivariate analyses in the retrospective study, Onodera's PNI of less than 37 was the only predictive factor for early mortality. In the second study, among the 115 patients who finally underwent PEG, early mortality rates improved to 1.7% from 5.2% in the first study. Conversely, 32% of patients with malnutrition who did not undergo PEG died within 30 days. CONCLUSION: Nutritional status might be a predictive factor for early mortality after PEG. In patients with poor nutritional status, nutritional supporting period before PEG might improve the outcomes and reduce unnecessary PEG.

Mitotic regulation of protein phosphatases by the fission yeast sds22 protein.

BACKGROUND: Cell cycle progression requires the activity of protein kinases and phosphatases at critical points in the cell cycle in all eukaryotes. We have previously reported that the dis2(+) and sds2(+) genes of fission yeast encode redundant catalytic subunits of a type 1-like protein phosphatase. The sds22(+) gene was shown to be essential for cell viability and to interact genetically with dis2(+) and sds21(+). RESULTS: Here we show by immunoprecipitation that the sds22 protein physically interacts with the dis2 and sds21 proteins, and that sds22-associated phosphatase activity has altered substrate specificity, The loss of sds22 function by a temperature sensitive mutation leads to cell cycle arrest at mid-mitosis, at which point cdc2-dependent histone Hl kinase activity is high while sds22-dependent H1 phosphatase activity is low. To examine the unusual properties of sds22 protein structure, we analyzed a collection of sds22 deletion and point mutants by a variety of functional criteria. CONCLUSION: We propose that sds22 is a regulatory subunit of the dis2/sds21 phosphatase catalytic subunits and that sds22-bound phosphatase carries a key phosphatase activity essential for the progression from metaphase to anaphase. Mutational analysis indicates that dis2/sds21 interacts with the central repetitive domain of sds22, while the C-terminal and central regions of sds22 may be involved in subcellular targeting and the N-terminus is important for stability.

Fission yeast pap1-dependent transcription is negatively regulated by an essential nuclear protein, crm1.

The fission yeast pap1+ gene encodes an AP-1-like transcription factor that contains a leucine zipper motif. We identified a target gene of pap1, the p25 gene. The 5' upstream region of the p25 gene contains an AP-1 site, and by DNase I footprint analysis, we showed that the pap1 protein binds to the AP-1 site as well as to a 14-bp palindrome sequence. p25 is overproduced when the pap1+ gene is overexpressed, whereas p25 is not produced at all in the pap1 deletion mutant. p25 was previously found to be overproduced in strains carrying cold-sensitive crm1 mutations whose gene product is essential for viability and is thought to play an important role in maintenance of a proper chromosomal architecture. Deletion and site-directed mutagenesis of sequences upstream of the p25 gene demonstrated that the AP-1 site as well as the palindrome sequence are crucial for transcriptional activation either by pap1 overproduction or by the cold-sensitive crm1 mutation; pap1+ is apparently negatively regulated by crm1+. Moreover, we found that cold-sensitive crm1 mutations are suppressed by the deletion of pap1+, further indicating a close relationship between crm1+ and pap1+. The crm1 protein is highly conserved; the budding yeast homolog, CRM1, which complements the fission yeast cold-sensitive crm1 mutation, was isolated and found to also be essential for viability. These results suggest the functional importance of chromosome structure on the regulation of gene expression through the pap1 transcription factor.

The problem of de novo colorectal carcinoma.

From April 1985 to March 1995, colonoscopy was carried out at our institution in 24,059 patients, 31,800 times in symptomatic and/or asymptomatic average risk persons. 184 submucosal invasive carcinomas were detected. Unlike protruding-type lesion, the depressed-type invades the submucosal layer, even though the size is within 10 mm. The depressed type of invasive carcinoma accounted for 20 lesions, and represented 10.9% (20 of 184) of all the invasive carcinomas. The pit pattern of depressed-type lesions shows a small round pit (type IIIs pit pattern) and that of carcinoma lesions shows the irregular pit and non-structure (type V pit pattern).

Time trends of the prevalences of hepatitis B e antigen positives among hepatitis B virus carriers in Japan.

In order to examine time trends of the prevalences of HBeAg positives among HBV carriers in Japan, we analysed data on HBeAg of HBsAg positive voluntary blood donors (23,560 males, and 8659 females) at the Osaka Red Cross Blood Centre between January 1977 and March 1984. Age-specific prevalences of HBeAg positives decreased year by year for both sexes, especially for those in their teens and twenties. The prevalences of HBeAg positives decreased with age, but at any given age it was lower for the later than for the earlier birth cohorts. Although reasons for the secular declines are unknown, the findings suggest that the prevalence of HBeAg positives among HBV carriers will continue to decrease in Japan. This, together with the immunization programme implemented this year, may lead to a future reduction in the risk of HBV related liver diseases in Japan.

Study on the interaction between soybean beta-amylase and substrate by the stopped-flow method.

The hydrolysis of substrates (maltoheptaose, maltopentaose, and maltotetraose) catalyzed by soybean beta-amylase [EC 3.2.1.2] at pH 5.4 and 25 degrees C was followed by monitoring small changes in the quenching of fluorescence due to tryptophan residues by the stopped-flow method. By analysis of whole time course, the dissociation constants, KdS, of enzyme-substrate and enzyme-product complexes were reasonably evaluated; and the difference in fluorescence intensities per mol between the enzyme-complex (ES or EP) and the free enzyme, delta F, was determined. The molecular activity, k0, was also determined by a new method of half time analysis. The KdS and k0 values are in good agreement with our kinetic data reported previously. The delta Fs of substrates were of smaller magnitude than those of products (G2 and G3), which means that the higher the binding affinity of the ligand is, the smaller the delta F value is. This indicates that at least two tryptophan residues must be located in the active site if the enzyme is rigid, or that if there is only one, the active site must undergo a structural change caused by the binding of ligand.

Endoscopic mucosal resection of the colon: the Japanese technique.

Early colorectal neoplasms, especially flat-type and depressed-type lesions, should be treated with an EMR technique. In general because depressed-type lesions, in contrast to flat-type or protruded-type lesions, tend to invade the submucosa rapidly, they ought to be treated by EMR at an early stage. Histopathologically in the case of lesions that only minimally invade the submucosa without vessel invasion (sm1a and sm1b without vessel invasion), a treatment can be completed with EMR. Massive submucosal invasive cancers ought to be resected by surgical treatment because of the risk of recurrence or metastasis. In addition, pit pattern diagnosis with magnifying colonoscopy is useful to determine a therapeutic method for colonic neoplasms. Lesions with the type VN pit pattern represent malignancy and usually invade the submucosa massively, so it is better to treat them surgically from the outset. Endoscopic mucosal resection should be conducted under fully controlled endoscopy to prevent complications. EMR is a superior therapeutic method and will be performed frequently in the future. It is necessary for colonoscopists to determine a suitable therapy for each colorectal neoplastic lesion. They also need to master the EMR technique in the correct manner.

Carrier-mediated transport systems for glucose in mucosal cells of the human oral cavity.

The in vitro uptake study was performed using the isolated cells of human oral mucosa, buccal and the dorsum of the tongue, to investigate the mechanisms of glucose uptake. The uptake of D-glucose was much larger in cells of the dorsum of the tongue than in buccal cells and was inhibited more extensively by 2-deoxy-D-glucose, a substrate of facilitative glucose transporters, than by alpha-methyl-D-glucoside, a specific substrate of SGLT1, suggesting the larger contribution of a facilitative transporter than Na(+)/glucose cotransporter. Furthermore, from the results of inhibition studies by several sugar analogues including maltose and D-mannose, GLUT1 and/or GLUT3 were suggested to take part in the glucose uptake by oral mucosa. Therefore, we have attempted to confirm the expression of glucose transporters on the oral mucosa by employing Western blotting. As a result, it was suggested that SGLT1, GLUT1, GLUT2, and GLUT3 are expressed in the epithelial cells of human oral mucosa.

Effects of maternal caffeine with zinc intake during gestation and lactation on bone development in newborn rats.

On day 9 of gestation, pregnant dams were randomly divided into 3 groups. Dams of group 1 were fed a 20% protein diet as a control. Dams of group 2 were fed a 20% protein diet supplemented with caffeine. Dams of group 3 were fed a 20% protein diet supplemented with caffeine and zinc. The amount of caffeine added to the maternal diet was 2 mg/100 g body weight; the amount of zinc was 0.6 g/kg of diet. At birth, pups were mixed within each group, and 8 randomly selected pups from each group were assigned to each dam of the respective group and were continuously fed the same diet. On day 15, the pups were killed and cranial bones, mandibles and femurs removed. The bones were measured, and the mineral content of the mandibles and femurs was determined. Although there were no differences in the dimensions of the cranial bones among the groups, the measurements and mineral content of the mandibles and femurs were consistently affected by the caffeine in the diet. On the other hand, supplementation of the caffeine-added diets with zinc led to greatly improved bone development, reaching values up to or beyond control levels. Thus zinc supplementation of a caffeine diet given to the dams during gestation and lactation can favourably influence the otherwise impaired bone development of their offspring.

delta15N of seagrass leaves for monitoring anthropogenic nutrient increases in coral reef ecosystems.

In a coral reef environment, a slight increase in dissolved inorganic nitrogen (DIN;> or =1.0 micro M) can alter the ecosystem via macroalgal blooms. We collected seagrass leaves from the tropical and subtropical Pacific Ocean in five countries and examined the interactions between nutrient concentrations (C, N, P), molar ratios of nutrients, and delta15N to find a possible indicator of the DIN conditions. Within most sites, the concentrations of nutrients and their molar ratios showed large variations owing to species-specific values. On the other hand, almost identical delta15N values were found in seagrass leaves of several species at each site. The correlations between delta15N and nutrient concentrations and between delta15N and molar ratios of nutrients suggested that nutrient availability did not affect the delta15N value of seagrass leaves by altering the physiological condition of the plants. Increases in delta15N of seagrass leaves mostly matched increases in DIN concentrations in the bottom water. We suggest that delta15N in seagrass leaves can be a good tool to monitor time-integrated decrease/increase of DIN concentrations at a site, both in the water column and the interstitial water.

Transcriptional terminator is a positive regulatory element in the expression of the Escherichia coli crp gene.

Plasmids were constructed that contain deletions in the stem region of the presumed rho-independent terminator of the cloned crp gene of Escherichia coli. The level of cyclic AMP binding activity and the amount of CRP in cells harboring the deletion plasmids were found to be significantly lower than those in cells harboring the wild-type crp plasmid. Quantitative S1 assays indicated that the steady-state levels of crp mRNA were markedly reduced in cells harboring the deletion plasmids. Evidence was also presented to show that the crp mRNAs produced from deletion plasmids are less stable than that from the intact crp gene. In vitro transcription assays revealed that the putative crp terminator is indeed a rho-independent terminator. Using the galK expression system and Northern blot analysis we showed that the crp terminator is functional in vivo. Moreover it was shown that the deletion mutations in the stem region of the crp terminator cause a significant readthrough. We conclude that the 3'-flanking sequence of the crp gene acts to stabilize its own mRNA as well as to terminate transcription.

Phosphorylation of dis2 protein phosphatase at the C-terminal cdc2 consensus and its potential role in cell cycle regulation.

We show that the fission yeast dis2 protein phosphatase, which is highly similar to mammalian type 1 phosphatase, is a phosphoprotein containing phosphoserine (phospho-S) and threonine (phospho-T). It has several phosphorylation sites, two of which locate in the C-terminus. Phospho-T was abolished in the alanine substitution mutant at the C-terminal T316, which is conserved as a residue in the cdc2 consensus, TPPR, in a number of type 1-like phosphatases. In G2-arrested cdc2-L7 cells, the degree of T316 phosphorylation was reduced, whereas it was enhanced in metaphase-arrested nuc2-663 mutant cells. Phospho-T was produced in dis2 by fission yeast cdc2 kinase, but not in the substitution mutant A316, indicating that the T316 residue was the site for cdc2 kinase in vitro. Phosphatase activity of wild type dis2 was reduced by incubation with cdc2 kinase, but that of mutant dis2-A316 was not. Phosphorylation of T316 hence has a potential significance in cell cycle control in conjunction with cdc2 kinase activation and inactivation. Overexpression phenotypes of wild type dis2+, sds21+ and mutant dis2-A316, sds21-TPPR genes were consistent with negative regulation of dis2 by phosphorylation. This type of regulation would explain why cells harboring the dis2-11 mutation enter mitosis but fail to exit from it.