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Biomedical subjects

M Sugimoto

Publications and source records attributed to M Sugimoto.

At least 19 recordsLinked to original sources

Pharmacogenomics-based tailored versus standard therapeutic regimen for eradication of H. pylori.

Helicobacter pylori eradication rates by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin at standard doses depend on bacterial susceptibility to clarithromycin and patient CYP2C19 genotypes. We examined the usefulness of a personalized therapy for H. pylori infection based on these factors as determined by genetic testing. First, optimal lansoprazole dosing schedules that would achieve sufficient acid inhibition to allow H. pylori eradication therapy in each of different CYP2C19 genotype groups were determined by a 24-h intragastric pH monitoring. Next, 300 H. pylori-positive patients were randomly assigned to the standard regimen group (lansoprazole 30 mg twice daily (b.i.d.)), clarithromycin 400 mg b.i.d., and amoxicillin 750 mg b.i.d. for 1 week) or the tailored regimen group based on CYP2C19 status and bacterial susceptibility to clarithromycin assessed by genetic testing. Patients with failure of eradication underwent the second-line regimen. The per-patient cost required for successful eradication was calculated for each of the groups. In the first-line therapy, the intention-to-treat eradication rate in the tailored regimen group was 96.0% (95% CI=91.5-98.2%, 144/150), significantly higher than that in the standard regimen group (70.0%: 95% CI=62.2-77.2%, 105/150) (P<0.001). Final costs per successful eradication in the tailored and standard regimen groups were $669 and $657, respectively. In conclusion, the pharmacogenomics-based tailored treatment for H. pylori infection allowed a higher eradication rate by the initial treatment without an increase of the final per-patient cost for successful eradication. However, the precise cost-effectiveness of this strategy remains to be determined.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Postoperative incision hernia in patients with abdominal aortic aneurysm and aortoiliac occlusive disease: a systematic review.

OBJECTIVES: We conducted a systematic review to determine the incidence of postoperative incision hernia in patients with abdominal aortic aneurysm compared to those with aortoiliac occlusive disease. METHODS: Studies which compared the incidence of postoperative incision hernia in patients with abdominal aortic aneurysm and aortoiliac occlusive disease undergoing midline incision for arterial reconstruction were identified. MEDLINE was searched for articles published between January 1966 and September 2005. RESULTS: Our search identified seven studies including data on 1132 patients, 719 with abdominal aortic aneurysm and 413 with aortoiliac occlusive disease. Pooled analysis demonstrated that patients with abdominal aortic aneurysm had a 2.9-fold increased risk of inguinal hernia (odds ratio 2.85, 95% confidence interval 1.71-4.77, p<0.0001), and a 2.8-fold risk of incisional hernia (2.79, 1.88-4.13, p<0.0001). Adjusting for other known risk factors patients with aortic aneurysm had a 5-fold increased risk of incisional hernia (5.45, 2.48-11.94, p<0.0001). CONCLUSIONS: Patients with abdominal aortic aneurysm appear to have an approximately 3-fold increased risk for both inguinal and postoperative incision hernia compared to patients with aortoiliac occlusive disease. A large multi-centre prospective study is needed to confirm the results of this review.

Aorta, Abdominal↗

Role of COX-1 and COX-2 on skin PGs biosynthesis by mechanical scratching in mice.

We examined the involvement of cyclooxygenase (COX)-1 and COX-2 on mechanical scratching-induced prostaglandins (PGs) production in the skin of mice. The dorsal regions of mice were scratched using a stainless brush. COXs expressions in the skin were analyzed using real-time PCR and Western blotting. The effect of acetylsalicylic acid (ASA) on the ability of PGs production were determined based on skin PGs level induced by arachidonic acid (AA) application. Mechanical scratching increased PGD2, PGE2, PGI2 and PGF(2 alpha). COX-1 was constitutively expressed and COX-2 expression was enhanced by scratching. Intravenous administration of ASA inhibited PGs biosynthesis in the normal skin. PGs levels of the skin 6h after ASA administration (ASA 6 h) were almost equal to those of the skin 10 min after ASA administration (ASA 10 min). In the scratched skin, AA-induced PGE2 and PGI2 of ASA 6 h were significantly higher than those of ASA 10 min. The skin PGD2 and PGF(2 alpha) of ASA 10 min were almost same to those of ASA 6 h. In the normal skin of COX-1-deficient mice, skin PGD2 level was lower than that of wild-type mice, although PGE2, PGI2 and PGF(2 alpha) levels were almost equal to those of wild type. In the scratched skin of COX-1-deficient mice, PGD2, PGE2, PGI2 and PGF(2 alpha) levels were lower than those of wild-type mice. These results suggested that cutaneous PGD2 could be mainly produced by COX-1, and PGE2 and PGI2 could be produced by COX-1 and COX-2, respectively, in mice.

Animals↗

The use of colour Doppler imaging in the diagnosis of retinal detachment.

DESIGN: Prospective study. PURPOSE: To evaluate real-time duplex colour Doppler examination with colour and pulse Doppler ultrasonography (US) (colour Doppler imaging (CDI)) for detection of the retinal detachment from membranous structures in the posterior segment. MATERIALS AND METHODS: In 33 consecutive patients with ophthalmoscopically invisible eyes (34 eyes), CDI was performed to detect the presence or absence of retinal detachment. The diagnostic criterion for retinal detachment was whether or not spectral waveforms were detected in membranous structures with colour and pulse Doppler US. In all cases, the absence or presence of retinal detachment was confirmed by surgery. RESULTS: In 27 of 34 eyes, membranes and/or opacities were observed in the vitreous cavity with CDI. In 12 of these 27 eyes, blood flow in those structures was detected by CDI. In all of these 12 eyes, retinal detachment was confirmed at surgery, and in 14 of the 15 eyes in which blood flow was not detected by CDI, absence of retinal detachment was confirmed at surgery. When a diagnosis confirmed by surgery was used as the definitive finding, CDI had a sensitivity of 92.3%, specificity of 100%, positive predictive value of 100%, negative predictive value of 93.3%, and an accuracy in the detection of retinal detachment from membranes and/or opacities in the vitreous cavity of 96.3%. CONCLUSION: Real-time duplex colour Doppler examination with colour and pulse Doppler US (CDI) is a noninvasive method useful for the detection of retinal detachment from vitreous opacity and/or membrane in the posterior segment.

Adolescent↗

Involvement of IL-31 on scratching behavior in NC/Nga mice with atopic-like dermatitis.

Pruritus is an important symptom in atopic dermatitis (AD), but the major pruritogen has not been identified. NC/Nga mice, spontaneously develop an eczematous AD-like skin lesion when kept under conventional conditions, but not under specific pathogen-free (SPF) conditions, have been thought to be an animal model for AD. In this study, to determine whether newly identified cytokine, IL-31, may be involved in pruritus of AD, we examined the IL-31 expression in spontaneous dermatitis model which showed itch-associated long-lasting (over 1.5 s duration) scratching behavior and compared with that of hapten-induced contact dermatitis model without itch-associated long-lasting scratching behavior, using NC/Nga mice. In NC/Nga mice cohabited with NC/Nga mice which developed severe dermatitis for 2 weeks (conventional NC/Nga mice), the numbers of long-lasting scratching counts were significantly increased. Yet in 2,4,6-trinitrochlorobenzene (TNCB)-sensitized and challenged mice (TNCB-applied NC/Nga mice), no significant increase in long-lasting scratching counts was observed. In conventional NC/Nga mice with long-lasting scratching behavior, expression of IL-31 mRNA was increased, while in TNCB-applied NC/Nga mice without long-lasting scratching behavior, the expression of IL-31 mRNA were unchanged. There was a good correlation between the scratching counts and expression of IL-31 mRNA in conventional NC/Nga mice, but not so in TNCB-applied NC/Nga mice. These results suggest that IL-31 causes the itch-associated scratching behavior in conventional NC/Nga mice, an experimental animal model for AD.

Animals↗

An approach for substrate mapping between ASM and ADM1 for sludge digestion.

Kinetic modelling of the hydrolysis stage of municipal activated sludge, which is presumed to be the rate-limiting step in the anaerobic sludge digestion process, was studied by measuring methane production rate (MPR) in anaerobic batch tests. The MPR curves revealed that the degradable organic components in municipal sludge could be classified into two fractions having different kinetics. The first fraction (XS1) constituted about 55% of the sludge COD and degraded with first-order kinetics. The second fraction (XS2), which degraded during the initial phase, accounted for about 21% of sludge COD. The degradation kinetics for XS2 was expressed by Contois-type equation with respect to concentration of substrate in the fed sludge and that of active biomass in the mixture. Simultaneous batch aerobic respirometric tests showed that the activated sludge was composed of 53% heterotrophic biomass (XH-Aerobe) COD and 20% of slowly biodegradable COD (XS), that had same kinetic expressions as observed in the batch anaerobic tests. The observed correlation between substrate fractions suggests XS1 and XS2 could be directly mapped to the aerobic state variables of XH-Aerobe and Xs respectively. The degradation of XS1 seems to be anaerobic decay of XH-Aerobe while XS2 is thought to be hydrolysis of XS by microcosm of the sludge.

Anaerobiosis↗

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) polymorphism has been associated with the development of lung, liver or oesophageal cancer by detoxification of carcinogen(s) or activation of procarcinogen(s). AIM: To clarify the association between CYP2C19 polymorphisms and gastric cancer development in Japanese. Methods : We determined CYP2C19 genotypes (CYP2C19*1, *2 and *3) in 111 Helicobacter pylori-positive patients with gastric cancer and 315 H. pylori-positive controls without gastric cancer consisting of patients with gastritis only or peptic ulcer. Frequencies of CYP2C19 genotypes and serum pepsinogen I and II levels, a biomarker of gastric atrophy, in the gastric cancers and controls were compared. RESULTS: Frequencies of homozygous extensive metabolizers, heterozygous extensive metabolizers and poor metabolizers were 31.5%, 42.3% and 26.2% in the gastric cancers and 38.1%, 47.0% and 14.9% in the controls, respectively (P = 0.046). Poor metabolizers were associated with an increased risk for developing gastric cancer with the age- and sex-adjusted odds ratio (OR) of 1.975 [95% confidence interval (CI): 1.068-3.649], especially for diffuse type (OR: 3.385, CI: 1.187-9.648). There is no significant association between CYP2C19 genotypes and serum pepsinogen I level or pepsinogen I/II ratios, although serum pepsinogen I level in gastric cancers were significantly decreased. CONCLUSIONS: In H. pylori-positive Japanese, poor metabolizers of CYP2C19 appear to be at an increased risk for developing gastric cancer, especially diffuse type, and may require an intensive follow-up for scrutinizing possible gastric cancer development.

Aged↗

Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype status.

BACKGROUND: Famotidine increases Helicobacter pylori-eradication rates by a triple lansoprazole/amoxicillin/clarithromycin therapy in patients with the rapid extensive metabolizer genotype of CYP2C19. AIM: To determine the effect of famotidine on the gastric acid inhibition by lansoprazole in relation to CYP2C19 genotypes. METHODS: Twenty healthy volunteers with different CYP2C19 genotypes--consisting of six rapid extensive metabolizers, nine intermediate metabolizers and five poor metabolizers--underwent three 7-day courses with placebo, lansoprazole 30 mg twice daily, and lansoprazole 30 mg twice plus famotidine 20 mg twice daily. Lansoprazole was dosed after breakfast and dinner. Famotidine was dosed after lunch and at bedtime. Intragastric pH monitoring was performed for 24 h on day 7 of each course. RESULTS: With placebo, no difference was observed in intragastric pH profiles among the three CYP2C19 genotype groups. With lansoprazole 30 mg twice daily, the median of 24-h intragastric pH in poor metabolizers (6.1) was significantly higher than those of rapid extensive metabolizers (4.5) and intermediate metabolizers (5.0), respectively (P = 0.0176 and 0.0388), whereas with lansoprazole 30 mg twice and famotidine 20 mg twice daily, the medians were 5.4, 5.7, and 6.1, respectively (not significant). CONCLUSION: Acid inhibition by lansoprazole was influenced by CYP2C19 genotype status. This influence was offset by the concomitant use of famotidine.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Concomitant dosing of famotidine with a triple therapy increases the cure rates of Helicobacter pylori infections in patients with the homozygous extensive metabolizer genotype of CYP2C19.

BACKGROUND: Proton-pump inhibitors, such as lansoprazole, are metabolized in the liver by CYP2C19 and cannot inhibit acid sufficiently in homozygous extensive metabolizers of CYP2C19. AIM: To examine whether famotidine would increase the cure rates of Helicobacter pylori infection by a standard triple therapy. METHODS: A total of 177 H. pylori-positive patients were randomly assigned to either lansoprazole 30 mg b.d., clarithromycin 200 mg b.d. and amoxicillin 750 mg b.d. for 1 week (LCA group; n = 89) or famotidine 20 mg b.d., lansoprazole 30 mg b.d., clarithromycin 200 mg b.d. and amoxicillin 750 mg b.d. for 1 week (FLCA group; n = 88). Famotidine was administered after lunch and before sleep, and the others were after breakfast and dinner. CYP2C19 genotypes were determined by a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In the LCA group, the eradication rates for homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers were 63%, 87%, and 100%, respectively (P = 0.014). Those in the FLCA group were 85%, 85%, and 100%, respectively (N.S.). The cure rate for homozygous extensive metabolizers in the FLCA group was significantly higher than that in the LCA group (P = 0.035). CONCLUSION: Famotidine improves the cure rate of H. pylori infection by a triple therapy in CYP2C19 homozygous extensive metabolizers patients.

Adult↗

BMP-2 induces the expression of chondrocyte-specific genes in bovine synovium-derived progenitor cells cultured in three-dimensional alginate hydrogel.

OBJECTIVE: According to recent reports, the synovial membrane may contain mesenchymal stem cells with the potential to differentiate into chondrocytes under appropriate conditions. In order to assess the usefulness of synovium-derived progenitor cells for the purposes of cartilage tissue engineering, we explored their requirements for the expression of chondrocyte-specific genes after expansion in vitro. DESIGN: Mesenchymal progenitor cells were isolated from the synovial membranes of bovine shoulder joints and expanded in two-dimensions on plastic surfaces. They were then seeded either as micromass cultures or as single cells within alginate gels, which were cultured in serum-free medium. Under these three-dimensional conditions, chondrogenesis is known to be supported and maintained. Cell cultures were exposed either to bone morphogenetic protein-2 (BMP-2) or to isoforms of transforming growth factor-beta (TGF-beta). The levels of mRNA for Sox9, collagen types I and II and aggrecan were determined by RT-PCR. RESULTS: When transferred to alginate gel cultures, the fibroblast-like synovial cells assumed a rounded form. BMP-2, but not isoforms of TGF-beta, stimulated, in a dose-dependent manner, the production of messenger RNAs (mRNAs) for Sox9, type II collagen and aggrecan. Under optimal conditions, the expression levels of cartilage-specific genes were comparable to those within cultured articular cartilage chondrocytes. However, in contrast to cultured articular cartilage chondrocytes, synovial cells exposed to BMP-2 continued to express the mRNA for alpha1(I) collagen. CONCLUSIONS: This study demonstrates that bovine synovium-derived mesenchymal progenitor cells can be induced to express chondrocyte-specific genes. However, the differentiation process is not complete under the chosen conditions. The stimulation conditions required for full transformation must now be delineated.

Alginates↗

p53-Dependent and -independent functions of the Arf tumor suppressor.

The Ink4a-Arf locus encodes two closely wedded tumor suppressor proteins (p16(Ink4a) and p19(Arf)) that inhibit cell proliferation by activating Rb and p53, respectively. With few exceptions, the Arf gene is repressed during mouse embryonic development, thereby helping to limit p53 expression during organogenesis. However, in adult mice, sustained hyperproliferative signals conveyed by somatically activated oncogenes can induce Arf gene expression and trigger a p53 response that eliminates incipient cancer cells. Disruption of this tumor surveillance pathway predisposes to cancer, and inactivation of INK4a- ARF by deletion, silencing, or mutation has been frequently observed in many forms of human cancer. Although it is accepted that much of Arf's tumor-suppressive activity is mediated by p53, more recent genetic evidence has pointed to additional p53- independent functions of Arf, including its ability to inhibit gene expression by a number of other transcription factors. Surprisingly, the enforced expression of Arf in mammalian cells promotes the sumoylation of several Arf-interacting proteins, implying that Arf has an associated catalytic activity. We speculate that transcriptional down-regulation in response to Arf-induced sumoylation may account for Arf's p53-independent functions.

Amino Acid Sequence↗

Scratching behavior in spontaneous- or allergic contact-induced dermatitis in NC/Nga mice.

NC/Nga mice have pathological and behavioral features similar to those seen in human atopic dermatitis. There are two known dermatitis models in NC/Nga mice, one being spontaneous-induced dermatitis under conventional conditions and the other 2,4,6-trinitrochlorobenzene (TNCB)-induced allergic contact dermatitis. However, there are significant differences in time course on development of dermatitis. We studied the role of scratching behavior (sign of itch) on the development of dermatitis on spontaneous- and TNCB-induced dermatitis. We measured scratching counts, transepidermal water loss (TEWL), and skin inflammation score, under conventional conditions or by applying 5% TNCB once a week for 6 weeks in NC/Nga mice. In spontaneous-induced dermatitis, scratching counts increased with the passage of time. The scratching counts were significantly increased only 1 week after housing the mice under conventional conditions, but no changes were observed in cases of TNCB-induced dermatitis. In spontaneous-induced dermatitis, TEWL and skin-inflammation score were gradually increased, time-dependently. On the other hand, in TNCB-induced dermatitis, these dependent values rapidly increased and reached a maximum only after 24 h TNCB application. These data suggest that pathogenesis of spontaneous- and allergic contact-induced dermatitis was clearly different. It will be of major interest to identify the pruritic mediators causing profound scratching behavior and scratching-induced aggravation of inflammation in the spontaneous-induced dermatitis, as opposed to the inflammatory mediators that cause contact allergic dermatitis without major scratching.

Animals↗

Increased scratching counts depend on a decrease in ability of cutaneous prostaglandin D2 biosynthesis in NC/Nga mice with atopic dermatitis.

Spontaneous and 2,4,6-trinitrochlorobenzene (TNCB)-induced dermatitis models using NC/Nga mice have been recognized as animal models of atopic dermatitis. We reported that scratching behavior leads to dermatitis in a spontaneous dermatitis but not in a TNCB-induced dermatitis. Prostaglandin D2 (PGD2) suppressed the scratching behavior of NC/Nga mice, suggesting that PGD2 plays a physiological role on inhibiting pruritus. We studied whether there was a difference in skin PG contents between spontaneous and TNCB-induced dermatitis. Spontaneous dermatitis was induced by cohabitation with NC/Nga mice having severe skin lesions. TNCB-induced dermatitis was caused by applications of TNCB. PGD2, PGE2, 6keto-PGF1alpha, and PGF2alpha contents in the skin were examined using enzyme-immunoassay kits. For studying ability to produce skin PGs, PG contents were evaluated after topical treatment of arachidonic acid (AA) or mechanical scratching. In spontaneous dermatitis, PGE2, 6keto-PGF1alpha, and PGF2alpha contents increased with dermatitis, but only PGD2 did not do so. In TNCB-induced dermatitis, PGD2, PGE2, 6keto-PGF1alpha, and PGF2alpha increased. Determination of skin PG contents after AA treatment or mechanical scratching revealed that skin PGD2 production of conventional group of spontaneous dermatitis was lower than the specific pathogen-free group. It seemed that ability of skin PGD2 production was attenuated in spontaneous dermatitis. These results suggest that enhancement of scratching behavior in spontaneous dermatitis was caused by the defect of ability to produce PGD2, which plays a physiological role in inhibiting pruritus, resulting in development of dermatitis.

Administration, Topical↗

Haemostatic management of intraoral bleeding in patients with von Willebrand disease.

OBJECTIVES: To develop plans for the haemostatic management of intraoral bleeding in patients with von Willebrand disease (VWD). SUBJECTS AND METHODS: Thirty-seven episodes of haemostatic management of intraoral bleeding in 19 VWD patients were analysed retrospectively based on the medical records. RESULTS AND CONCLUSIONS: When performing tooth extractions in patients with type 1 or 2A VWD [responsive to 1-deamino-8-D-arginine-vasopressin (DDAVP)], 0.35-0.4 microg kg(-1) of DDAVP should be administered intravenously at three times. In patients with type 2A VWD (unresponsive to DDAVP) or patients with type 2B or 2N VWD, 50-90 U [as ristocetin cofactor (VWF:RCof)] kg(-1) of a factor VIII concentrate containing von Willebrand factor (FVIII/VWF concentrate) should be administered twice in routine extractions, and four to six times in surgical extractions. Gingival bleeding related to primary teeth can be mostly managed by pressure haemostasis alone. However, when treating gingival bleeding caused by marginal periodontitis, it is often necessary to administer 0.4 microg kg(-1) of DDAVP or 40-70 U (as VWF:RCof) kg(-1) of a FVIII/VWF concentrate. As local haemostasis is difficult to achieve in bleeding from the tongue or labial or mandibular haematoma, it is necessary to administer 0.4 microg kg(-1) of DDAVP or 60-80 U (as VWF:RCof) kg(-1) of a FVIII/VWF concentrate. In addition, oral administration of 20 mg kg(-1) day(-1) of tranexamic acid should be combined with the regimens described above.

Adolescent↗

Expression of cholesteryl ester transfer protein (CETP) in germinal centre B cells and their neoplastic counterparts.

AIMS: Cholesteryl ester transfer protein (CETP) is known to facilitate the transfer of lipids between plasma lipoproteins. Previous studies on human tissues have determined that the spleen contains large amounts of CETP mRNA, while the exact location of CETP in such organs remains unknown. In the present study, our aim was to locate CETP protein expression at the cellular level in human normal and neoplastic lymphoid organs. METHODS AND RESULTS: In-situ hybridization (ISH) and immunohistochemistry were applied to pathology specimens. A specific rabbit anti-CETP antibody was used for immunohistochemical analysis, together with another CETP-specific monoclonal antibody. A riboprobe for ISH was derived from CETP cDNA. Immunohistochemically, CETP was localized in germinal centre B cells and a proportion of marginal zone B cells. ISH showed that CETP mRNA was located mostly in the same areas. When 141 malignant lymphomas of various subtypes were studied, high expression of CETP, equivalent to that found in normal germinal centre B cells, was demonstrated in lymphoma subtypes that are currently regarded as the neoplastic counterparts of primarily germinal centre B cells. CONCLUSION: CETP localizes B cells in germinal centres, a proportion of post-germinal centre B cells and their neoplastic counterparts.

Animals↗

Deletion of one of the duplicated Hsp70 genes causes hereditary myopathy of diaphragmatic muscles in Holstein-Friesian cattle.

Heat-shock protein 70 (Hsp70) is a major chaperone that folds protein and prevents aggregation. The Hsp70 family contains both constitutive and stress-inducible forms. In humans, two of the inducible Hsp70 genes are located within the human major histocompatibility complex (MHC) on 6p21.3, as a duplicated locus, 12 kb apart from each other. We report that loss of one of the duplicated Hsp70 genes, the bovine homologue within the bovine MHC, is responsible for hereditary myopathy of diaphragmatic muscles (HMDM) in Holstein-Friesian cattle. Although the remaining Hsp70 gene is intact, Hsp70 protein levels are dramatically decreased in affected cattle. In normal diaphragmatic muscle, Hsp70 binds several proteins involved in energy metabolism including glycogen phosphorylase (PYGM). Immunohistochemical staining indicated that PYGM accumulated in the HMDM-specific core-like structures in affected cattle. Misfolding of energy-related proteins due to Hsp70 deficiency might lead to protein aggregation and muscle fibre degeneration.

Animals↗