Management of gastric variceal bleeding.
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Endoscopes, Gastrointestinal↗
Biomedical subjects
M Matsushita
Publications and source records attributed to M Matsushita.
Preventive effects of glycaemic control on ocular complications of Spontaneously Diabetic Torii rat.
AIM: Spontaneously Diabetic Torii (SDT) rat is a new model of non-obese type 2 diabetes. SDT rats show severe ocular complications such as cataracts, tractional retinal detachment with fibrous proliferation and massive haemorrhaging in the anterior chamber. In the present study, blood glucose levels of SDT rats were controlled in order to examine whether these ocular complications are caused by hyperglycaemia. METHODS: SDT rats were treated with an insulin implant to control blood glucose. To evaluate retinal function, we used electroretinograms (ERG) and measured vascular endothelial growth factor (VEGF) concentrations within the aqueous humour. Finally, we studied retinal flat-mounts and trypsin digestion to evaluate vascular abnormalities in SDT rats. RESULTS: Forty-four-week-old SDT rats displayed an increase in VEGF concentrations within the aqueous humour and significant prolongation of the peak latencies in ERG (Sigma(OP(1)-OP(4)); Sprague-Dawley (SD): 146.2 +/- 1.06 ms; SDT: 166.3 +/- 2.38 ms; SDT + insulin: 149.2 +/- 1.83 ms). Retinal flat-mounts of SDT rats showed venous dilation and meandering vascular networks. Furthermore, acellular capillaries were observed in the retinal trypsin digestion. Insulin treatment prevented these ocular abnormalities in SDT rats. CONCLUSIONS: These findings indicate that ocular complications of SDT rats are caused by hyperglycaemia. The features of SDT rats indicate their usefulness for the future study of diabetic retinopathy.
Animals↗
JTP-426467 acts as a selective antagonist for peroxisome proliferator-activated receptor gamma in vitro and in vivo.
AIM: JTP-426467 was identified as a result of screening in search of selective antagonist for peroxisome proliferator-activated receptor gamma (PPARgamma). We examined whether JTP-426467 functioned as a PPARgamma antagonist in vitro and in vivo and investigated physiological effects of JTP-426467. METHODS: The effect of JTP-426467 as a PPARgamma antagonist was studied in a cell-based reporter assay and an adipocyte differentiation assay. Target mRNA expression levels were determined by branched DNA (bDNA) assay. To examine the effects as a PPARgamma antagonist in vivo, a competitive study between JTP-426467 and BRL49653 (rosiglitazone), a PPARgamma agonist, was performed using KK-Ay mice. The effects of JTP-426467 alone after administration to KK-Ay mice were also explored. JTP-426467 antagonized PPARgamma activity in a reporter assay system, but not PPARalpha. RESULTS: JTP-426467 inhibited the expression of hormone-sensitive lipase (HSL) mRNA, an adipocyte-abundant gene, but not PPARgamma itself or cyclophilin mRNA (as constitutive mRNA), and also suppressed triglyceride accumulation in differentiated stromal vascular fraction cells (SVFs). JTP-426467 antagonized PPARgamma agonistic action by BRL49653 in KK-Ay mice on high-fat diet, in terms of plasma glucose, body weight gain and interscapular brown adipose tissue (IBAT) weight. JTP-426467 alone inhibited body weight gain and decreased plasma leptin level in KK-Ay mice. CONCLUSIONS: JTP-426467 acted as a pure and potent PPARgamma antagonist in vitro. Interestingly, JTP-426467 completely antagonized the effects of PPARgamma agonist BRL49653 in an obese diabetic model. JTP-426467 may be a useful tool for the study of PPARgamma in biological and physiological function.
Adipocytes↗
Carbohydrate-binding specificities of mouse ficolin A, a splicing variant of ficolin A and ficolin B and their complex formation with MASP-2 and sMAP.
Ficolins are a group of proteins mainly consisting of collagen-like and fibrinogen-like domains and are thought to play a role in innate immunity via their carbohydrate-binding activities. Two types of ficolins have been identified in mice, ficolin A, and ficolin B. However, their structure and function are not fully understood. In this study, we isolated the cDNA encoding a novel variant of ficolin A having a shorter collagen-like domain and a longer gap sequence, which was generated from the ficolin A gene by alternative splicing. We delineated the structure and function of mouse ficolins, including this splicing variant, by preparing the respective recombinants. Recombinant ficolin A, its splicing variant, and ficolin B showed multimeric structures and revealed binding to both N-acetylglucosamine and N-acetylgalactosamine. Interestingly, ficolin B specifically recognized sialic acid residues. Ficolin A and its variant, but not ficolin B, bound to mannose-binding lectin (MBL)-associated serine protease-2 (Masp-2) and small MBL-associated protein (smap), and the resulting complexes showed a potent complement activating capacity. In addition, smap competed with Masp-2 in association with ficolin A and its variant, and inhibited the complement activation by the ficolin A (or ficolin A variant)/MASP-2 complex, indicating its regulatory role in the lectin pathway. These results suggest that ficolin A and its variant function as recognition molecules of the lectin pathway, and ficolin B plays a distinct role through its unique carbohydrate-binding specificity.
Adaptor Proteins, Signal Transducing↗
The clinical and genetic spectrum of spinocerebellar ataxia 14.
Spinocerebellar ataxia 14 (SCA14) is associated with missense mutations in the protein kinase C gamma gene (PRKCG), rather than a nucleotide repeat expansion. In this large-scale study of PRKCG in patients with ataxia, two new missense mutations, an in-frame deletion, and a possible splice site mutation were found and can now be added to the four previously described missense mutations. The genotype/phenotype correlations in these families are described.
Adolescent↗
A case of gastrointestinal stromal tumour of the ampulla of Vater.
Gastrointestinal stromal tumour rarely develops in the duodenal ampulla region. We report here a case of gastrointestinal stromal tumour of the ampulla of Vater found in a 44-year-old Japanese man presenting with biliary obstruction. He died of hepatic failure with diffuse liver metastasis. The postmortem examination showed a large Borrman type III-like tumour in the duodenal ampullary region with direct invasion of the pancreas and extrahepatic bile duct as well as metastases to the liver and regional lymph nodes. The duct orifice was located at the centre of the tumour. Microscopically, the tumour consisted of anaplastic spindle cells with high mitotic activity (90 mitoses per 50 high-power fields). Immunohistochemically, the spindle cells were positive for KIT and CD34. The final diagnosis was high-grade malignant gastrointestinal stromal tumour of the ampulla of Vater. Considering the recent advances in the diagnosis and treatment of gastrointestinal stromal tumour, this neoplasm should be included in the differential diagnosis of the tumours appearing in the duodenal ampulla region.
Adult↗
A genome scan in multigenerational families with dyslexia: Identification of a novel locus on chromosome 2q that contributes to phonological decoding efficiency.
Dyslexia is a common and complex developmental disorder manifested by unexpected difficulty in learning to read. Multiple different measures are used for diagnosis, and may reflect different biological pathways related to the disorder. Impaired phonological decoding (translation of written words without meaning cues into spoken words) is thought to be a core deficit. We present a genome scan of two continuous measures of phonological decoding ability: phonemic decoding efficiency (PDE) and word attack (WA). PDE measures both accuracy and speed of phonological decoding, whereas WA measures accuracy alone. Multipoint variance component linkage analyses (VC) and Markov chain Monte-Carlo (MCMC) multipoint joint linkage and segregation analyses were performed on 108 families. A strong signal was observed on chromosome 2 for PDE using both VC (LOD=2.65) and MCMC methods (intensity ratio (IR)=32.1). The IR is an estimate of the ratio of the posterior to prior probability of linkage in MCMC analysis. The chromosome 2 signal was not seen for WA. More detailed mapping with additional markers provided statistically significant evidence for linkage of PDE to chromosome 2, with VC-LOD=3.0 and IR=59.6 at D2S1399. Parametric analyses of PDE, using a model obtained by complex segregation analysis, provided a multipoint maximum LOD=2.89. The consistency of results from three analytic approaches provides strong evidence for a locus on chromosome 2 that influences speed but not accuracy of phonological decoding.
Adolescent↗
Management of anomalous pancreaticobiliary union.
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Biliary Tract↗
Distally migrated and impacted biliary metallic stents: removal versus trimming.
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Biliary Tract Surgical Procedures↗
Metastatic ovarian tumour 14 years after initial surgery for a gastric cancer.
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Adenocarcinoma↗
Plasminogen activator inhibitor-1 is elevated, but not essential, in the development of bleomycin-induced murine scleroderma.
Accumulative data have demonstrated that plasminogen activator inhibitor-1 (PAI-1) plays an important role in the extracellular matrix metabolism; however, the involvement of PAI-1 in scleroderma has not been fully elucidated. In this study, we investigated the role of PAI-1 in bleomycin-induced murine scleroderma. 100 microg of bleomycin was injected subcutaneously to the back skin of C3H/HeJ mice on alternate day for 4 weeks. Histopathological findings revealed that PAI-1 was positive in macrophage-like cells and fibroblastic cells in the dermis, in parallel with the induction of dermal sclerosis. PAI-1 mRNA expression in the whole skin was up-regulated at 1 and 4 weeks. The production of active PAI-1 protein in the lesional skin was significantly increased 3 and 4 weeks after bleomycin treatment. Next, we examined whether dermal sclerosis is induced by bleomycin in PAI-1-deficient (PAI-1-/-) mice. 10 microg of bleomycin was subcutaneously injected to PAI-1-/- and wild type (WT) mice 5 days per week for 4 weeks. Histological examination revealed that dermal sclerosis was similarly induced even in PAI-1-/- as well as WT mice. Dermal thickness and collagen contents in the skin were significantly increased by bleomycin injection in both PAI-1-/- and WT mice, and the rate of increase was similar. These data suggest that PAI-1 plays an important role, possibly via TGF-beta pathway activation. However, the fact that PAI-1 deficiency did not ameliorate skin sclerosis suggest that PAI-1 is not the essential factor in the development of bleomycin-induced scleroderma, and more complex biochemical effects other than PA/plasmin system are greatly suspected.
Animals↗
Daily inhibition of postprandial hyperglycaemia with JTT-608, a novel oral antidiabetic agent, ameliorates pancreatic function in neonatally streptozotocin-treated rats.
AIM: Chronic glycaemic control, in particular, the control of postprandial hyperglycaemia, is essential for preventing the development of diabetic complications. We therefore evaluated the chronic treatment effect of a new antidiabetic agent, JTT-608 [trans-4-(methylcyclohexyl)-4-oxobutyric acid], in neonatally streptozotocin-treated rats. METHODS: The rats were maintained with liquid meal three times a day and treated orally with JTT-608 10 min before each meal for 12 weeks. Haemoglobin A1C (HbA1C) and fasting blood glucose levels were measured at 4-week intervals, and effects of JTT-608 on pancreatic function and diabetic complications were examined after dosing period. RESULTS: The postprandial hyperglycaemia was suppressed by JTT-608 administration, and both HbA1C levels and fasting blood glucose levels were reduced during the experimental period. After the treatment period of 12 weeks, JTT-608 further improved the early insulin secretion and the impaired glucose tolerance after meal loading in the diabetic rats. Also, pathological examination revealed that JTT-608 reduced the incidence of the decrease in immunoreactivity of insulin. In examination of other diabetic complications, JTT-608 ameliorated the reduced motor nerve conduction velocities observed in diabetic rats and inhibited the incidence of cataracts with diabetes. CONCLUSIONS: We conclude that a newly developed antidiabetic agent, JTT-608, improves the pancreatic function and prevents the development of diabetic complications by inhibition of daily postprandial hyperglycaemia and could be useful for the treatment of diabetic subjects with impaired insulin secretion.
Animals↗
Novel protein kinase C-beta isoform selective inhibitor JTT-010 ameliorates both hyper- and hypoalgesia in streptozotocin- induced diabetic rats.
AIM: Activation of protein kinase C (PKC) is thought to play an important role in the pathogenesis of diabetic microvascular complications. PKC-beta is elevated in hyperglycaemic conditions, both in vivo and in vitro. In this study, pharmacological effects of a novel PKC-beta isoform selective inhibitor, JTT-010 ((2R)-3-(2-aminomethyl-2,3-dihydro-1H-3a-azacyclopenta(a)inden-8-yl)-4-phenylaminopyrrole-2,5-dione monomethanesulphonate), on diabetic neuropathy were examined. METHODS: PKC inhibitory activity of JTT-010 was evaluated with an enzyme assay. For the in vivo study, streptozotocin (STZ)-induced diabetic rats were treated with JTT-010 for 12 weeks and tail/sciatic nerve conduction velocity (NCV) evaluated. Hyper/hypoalgesia was evaluated using tail-flick and formalin tests. RESULTS: JTT-010 inhibited PKC-betaI and -betaII with IC50 values of 4.0 and 2.3 nm respectively. For other PKC isoforms, IC50 values were 54 nm or greater. In STZ-induced diabetic rats showing a reduction in tail/sciatic nerve conduction velocities, JTT-010 (0.3-3 mg/kg) ameliorated the reduction of these velocities. In a formalin test, STZ-induced diabetic rats had hyperalgesia in the first phase. JTT-010 reduced nociceptive response at doses of 0.1 mg/kg or higher. Furthermore, STZ-induced diabetic rats showed hypoalgesia in the second phase of the formalin test and tail-flick test. JTT-010 also ameliorates these symptoms at doses of 0.1 mg/kg or higher. CONCLUSIONS: These observations suggest that PKC-beta contributes not only to diabetic hyperalgesia, but also to hypoalgesia and also contributes to defects in NCV. PKC-beta inhibitor, JTT-010, may be beneficial in suppressing the development of diabetic nerve dysfunction, including hyperalgesia and hypoalgesia.
Animals↗
Association of a polymorphism of the transforming growth factor-beta1 gene with cerebral amyloid angiopathy.
BACKGROUND: A recent study showed that transforming growth factor-beta1 (TGF-beta1) induces amyloid-beta deposition in cerebral blood vessels and meninges of a transgenic mouse model of Alzheimer's disease (AD), and that TGF-beta1 mRNA levels are correlated with cerebral amyloid angiopathy (CAA) in human AD brains. A T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 gene has been reported to be associated with the serum TGF-beta1 concentration. We investigated whether the TGF-beta1 polymorphism is associated with the risk of CAA. METHODS: The association between the severity of CAA and the T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 was investigated in 167 elderly Japanese autopsy cases, including 73 patients with AD. The apolipoprotein E (APOE) genotype was also determined. RESULTS: The genotypes (TT/ TC/ CC) were associated with the severity of CAA significantly in all patients (p = 0.0026), in non-AD patients (p = 0.011), and APOE non-epsilon4 carriers (p = 0.0099), but not in AD patients or APOE epsilon4 carriers. The number of the T alleles positively correlated with the severity of CAA in all patients (p = 0.0011), non-AD patients (p = 0.0026), and APOE non-epsilon4 carriers (p = 0.0028), but not in AD patients or APOE epsilon4 carriers. The polymorphism was not significantly associated with AD. CONCLUSIONS: Our results suggest that the polymorphism in TGF-beta1 is associated with the severity of CAA, especially in non-AD patients and APOE non-epsilon4 carriers.
Aged↗
Healing of implanted expanded polytetrafluoroethylene vascular access grafts with different internodal distances: a histologic study in dogs.
OBJECTIVE: We assessed characteristics of healing, over time, of two types of expanded polytetrafluoroethylene grafts. STUDY DESIGN: An experimental histological study in dogs. METHODS: The graft types studied had the same internal diameter (5 mm) but different internodal distances. In one, the internodal distance was 60 microm in the external surface and 20 microm in the luminal surface. In the other, the internodal distance was 30 microm throughout the material. Sixteen grafts of each type were implanted between the femoral artery and vein in 16 dogs; explanted 1, 2, 4 or 12 weeks later; and examined histologically. RESULTS: In both graft types, infiltrating-cell density and maximum cell-penetration depth increased significantly between 1 and 2 weeks after implantation, but no significant increases occurred after 2 weeks. The number of inflammatory cells peaked 1 week after implantation and decreased significantly by 2 weeks. Subsequently, there were no significant changes in inflammatory cell numbers, suggesting that the inflammatory phase was over by 2 weeks after implantation and the grafts had become attached to surrounding tissue. There were no significant differences between the two graft types in cell density, cell-penetration depth, or number of inflammatory cells at any assessment time. CONCLUSION: Our results provide histologic support for guidelines recommending that synthetic vascular grafts for hemodialysis access should not be cannulated until 2 weeks after implantation. Since increasing the internodal distance to 60 microm in the external surface had no effect on graft healing, methods other than manipulation of internodal distance should be used in developing a graft suitable for early cannulation.
Animals↗
Effects of atherosclerotic plaque on the enlargement of an experimental model of abdominal aortic aneurysm in rabbits.
PURPOSE: Abdominal aortic aneurysm (AAA) usually is associated with atherosclerosis. We attempted to create an abdominal aortic aneurysm with atherosclerotic plaque in rabbits to investigate the relationship between atherosclerosis and enlargement of AAA. METHODS: An isolated segment of rabbit abdominal aorta was perfused with pancreatic elastase. Animals were fed a cholesterol-enriched diet to induce atherosclerotic plaque formation. Eight animals received perfusion with elastase and were fed a cholesterol-enriched diet (group EC), eight animals received perfusion with elastase and were fed a normal diet (group EN), eight animals received perfusion with saline and were fed a cholesterol-enriched diet (group SC), and eight animals received perfusion with saline and were fed a normal diet (group SN). Four animals served as a sham group. Each animal was killed after aortography at 4 or 12 weeks. The perfused segment was excised and examined histologically. RESULTS: No animal treated with saline and fed normal diet (groups SN) developed either an aneurysm or atherosclerosis. Atherosclerotic plaque was observed in animals fed the cholesterol-enriched diet (groups SC and EC) at 4 weeks, and the plaque had thickened further by 12 weeks. All animals treated with elastase (groups EN and EC) developed an AAA. Maximum internal diameter in groups EN and EC (4.1 mm) was equal at 4 weeks, but at 12 weeks, the diameter was less for group EC than for group EN (4.0 mm versus 4.8 mm, P<0.05). CONCLUSION: Cholesterol-enriched diet following the intra-luminal perfusion of an isolated aortic segment with elastase produced an AAA with atherosclerotic plaque in rabbits. It is likely that the thickened intima with atheroma suppressed continued enlargement of the aneurysm in this model.
Animals↗
L-ficolin in children with recurrent respiratory infections.
The lectin pathway of complement activation is used by a collectin, mannan-binding lectin (MBL), and two ficolins, L-ficolin and H-ficolin, to opsonize microorganisms for phagocytosis. We published evidence recently that MBL insufficiency is associated with recurrent respiratory infections in childhood. We have now measured serum L-ficolin in 313 respiratory infection patients and 74 healthy control children. L-ficolin concentrations below the lower limit of the control group were found in 6% of the patients (P <0.02) and were associated most strongly with children having co-existing atopic disorders (11%; P=0.002). We suggest that L-ficolin may have a role in protection from microorganisms complicating allergic disease.
Adolescent↗
[Leaflet extension technique in a congenital aortic valve regurgitation].
A 17-year-old boy who was diagnosed as congenital aortic valve regurgitation underwent the leaflet extension technique in 3 aortic leaflets using glutaraldehyde-preserved autologous pericardium. Intraoperative transesophageal echocardiography and postoperative cardiac catheter revealed grade I regurgitation and the patient has been doing well for more than 4 months after the surgery. The leaflet extension technique is considered to be an acceptable surgical treatment for aortic valve disease especially in young patients to whom valve replacement or Ross procedure might not be suitable. A careful long-term follow-up will be necessary to evaluate the durability of the leaflet extension technique with autologous pericardium.
Adolescent↗