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K Sugano

Publications and source records attributed to K Sugano.

At least 37 records · Page 2Linked to original sources
PubMed2001

Optimized conditions of bio-mimetic artificial membrane permeation assay.

Effects of pH and co-solvents on the bio-mimetic artificial membrane permeation assay were investigated to determine the optimal conditions for the prediction of oral absorption. The permeability (P(am)) of 33 structurally diverse drugs to the PC/PE/PS/PI/CHO/1,7-octadiene membrane system (bio-mimetic lipid (BML) membrane) was measured at pH 5.5, 6.5, and 7.4. The pH dependence of P(am) was in accordance with the pH partition theory. The better prediction of oral absorption (fraction of a dose absorbed) was shown under the pH 5.5 condition (r=0.866, n=25) and/or pH 6.5 (r=0.865, n=28), rather than pH 7.4 (r=0.767, n=24). Then, the appropriate conditions for determining the permeability of poorly soluble compounds were examined. Dimethysulfoxide (DMSO), ethanol (EtOH) and polyoxyethyleneglycol 400 (PEG 400) were added up to 30% to the transport medium as solubilizers. DMSO, EtOH and PEG 400 decreased P(am) of hydrocortisone and propranolol. For example, DMSO (30%) decreased P(am) of hydrocortisone by 60% and by 70% in the case of propranolol. DMSO and PEG 400 also decreased P(am) of ketoprofen. In contrast, EtOH produced an opposite effect on permeability, i.e. an increased P(am) of ketoprofen. Therefore, the high concentration of these co-solvents could lead to the under- or overestimation of drug permeability.

Algorithms↗
PubMed2001

Opposite association of two PPARG variants with cancer: overrepresentation of H449H in endometrial carcinoma cases and underrepresentation of P12A in renal cell carcinoma cases.

Peroxisome proliferator activated receptor gamma (PPARgamma) is a nuclear hormone receptor that has been shown to regulate differentiation and cell growth. Studies of the differentiative effects of PPARgamma agonists on several cancer cell lines led to the hypothesis that dysfunction of PPARgamma contributes to tumorigenesis. These functional observations were strengthened by genetic evidence: somatic loss-of-function mutations in PPARG, encoding PPARgamma, in sporadic colorectal carcinomas and somatic translocation of PAX8 and PPARG in follicular thyroid carcinoma. Recently overrepresentation of the H449H variant was found in a cohort of American patients with glioblastoma multiforme. The glioblastoma multiforme data suggest that PPARG contributes common, low-penetrance alleles for cancer susceptibility. To test this hypothesis in a broader range of cancers we examined a series of carcinomas of the cervix, endometrium, ovary, prostate, and kidney for germline sequence variation in PPARG. In addition to the two common sequence variants, P12A and H449H, there were five other sequence variants. P12A alleles were underrepresented in renal cell carcinoma patients compared to country-of-origin race-matched controls (3.75% vs. 12.1%, P<0.04). In contrast, the H449H variant was overrepresented in individuals with endometrial carcinoma compared to controls (14.4% vs. 6.25%, P<0.02). These observations lend genetic evidence consistent with our hypothesis that PPARG serves as a common, low-penetrance susceptibility gene for cancers of several types, especially those epidemiologically associated with obesity and fat intake.

Adenocarcinoma↗
PubMed2001

Cholangiographic findings of early-stage extrahepatic bile duct carcinoma.

BACKGROUND: To clarify the cholangiographic findings of early-stage (T1, tumor confined to the mucosal or fibromuscular layer) extrahepatic bile duct carcinoma. METHODS: Cholangiographic images were retrospectively analyzed without other information in 55 patients with extrahepatic bile duct carcinoma who underwent surgical treatment. Tumor stages were T1 (n = 10). T2 (n = 17), and T3 (n = 28). Cholangiographic findings were classified as "diffuse sclerosis," "stenosis," "papillary polypoid filling defect," or "nodular polypoid filling defect". "Papillary polypoid filling defect" was the term used when the width of the base was smaller than the width of the polypoid filling defect. RESULTS: T1 patients showed papillary polypoid filling defects (n = 8) or nodular polypoid filling defects (n = 2) on cholangiography. When cholangiography showed papillary polypoid filling defects, 8 of the 14 resected patients showed T1 stage tumor histologically. CONCLUSIONS: In this study, 57% (8/14) of resected patients with papillary polypoid filling defects showed T1 stage tumor. No T1 stage tumor showed stenosis or diffuse sclerosis.

Adult↗
PubMed2001

Looping technique for transpapillary selective biopsy of the left hepatic duct.

PURPOSE: Because biopsy forceps tend to turn towards the right hepatic duct during endoscopic retrograde cholangiopancreatography (ERCP), selective access to the left hepatic duct is difficult. METHODS: In this study, we managed to insert biopsy forceps selectively into the left hepatic duct, by using a looping technique, in three patients. Biopsy forceps were inserted into the right hepatic duct by the conventional method. The elevator of the endoscope was kept down, and the shaft of the biopsy forceps was then advanced to the duodenal cavity until it formed a loop between the endoscope and the papilla. During the procedure, the tip of the forceps was kept at the hepatic hilus. RESULTS: In this condition, we were able to slowly rotate the tip of the forceps and direct the forceps towards the left. Sufficient material from the left hepatic duct was obtained in all patients. CONCLUSIONS: The looping technique was useful for selective access to the left hepatic duct.

Adult↗
PubMed2001

Transpapillary intraductal US prior to biliary drainage in the assessment of longitudinal spread of extrahepatic bile duct carcinoma.

BACKGROUND: The utility of intraductal US via the transpapillary route prior to biliary drainage in the assessment of longitudinal extension of extrahepatic bile duct carcinoma was investigated. METHODS: In 19 patients with extrahepatic bile duct carcinoma who underwent surgical resection, an ultrasonic probe (diameter, 2.0 mm; frequency, 20 MHz) was inserted into the bile duct via the transpapillary route prior to biliary drainage. Longitudinal cancer extension along the bile duct was prospectively determined and compared with the histologic findings in the resected specimens. RESULTS: Results on the hepatic side were as follows: Intraductal US demonstrated more extensive longitudinal cancer spread than cholangiography in 9 of 19 patients with one instance of overdiagnosis. The accuracy of intraductal US in assessing the extent of spread (84%) was superior to that of cholangiography (47%) (p < 0.05). Results on the duodenal side were as follows: In patients with suprapancreatic bile duct cancer (n = 14), intraductal US demonstrated more extensive longitudinal cancer spread than cholangiography in 8 of 14 patients. The accuracy of intraductal US in assessing the extent of the spread (86%) was superior to that of cholangiography (43%) (p < 0.05). CONCLUSIONS: Transpapillary intraductal US prior to biliary drainage is useful in demonstrating longitudinal extension of bile duct cancer. However, the surgical margins were inaccurate in some patients.

Aged↗
PubMed2001

Comparative analysis of colonization of Helicobacter pylori and glycolipids receptor density in Mongolian gerbils and mice.

The Mongolian gerbil has been used as an excellent experimental animal model for studying Helicobacter pylori infection because it can stably colonize and induce severe chronic gastritis, ulceration, and cancer-simulating human diseases in this animal. In contrast, H. pylori can only induce mild inflammation in many mouse models. The aim in this study is to clarify the difference of induction of pathological lesions in the two animal models. SPF ICR mice and Mongolian gerbils were inoculated with a clinically isolated strain of H. pylori. Six weeks after inoculation, bacteria colonizing the stomach were counted. Immunohistochemical staining and biochemical analyses of three putative receptor glycolipids were performed with monoclonal antibodies to the respective glycolipids. Significantly higher numbers of H. pylori were recovered from the stomachs of Mongolian gerbils than mice (5.77 +/- 0.46 log CFU vs 4.17 +/- 0.55 log CFU, P < 0.01). Immunohistochemical studies showed that sulfatide expression in the gastric mucosa of Mongolian gerbils was much stronger than that in mice, whereas the expression of Lewis(b) glycolipid and GM3 were almost equal. Quantitative analysis of each glycolipid by thin-layer chromatography confirmed the results of immunohistochemical study, showing 4.1 times higher sulfatide content in the Mongolian gerbil stomach. The content of both Lewis(b) and GM3 was almost equivalent in these two animals. In conclusions, higher levels of sulfatide expression, a putative adhesion receptor, in the gastric mucosa of Mongolian gerbils may allow abundant colonization by H. pylori, resulting in the development of gastric lesions in this animal model.

Animals↗
PubMed2001

Comparison of intraductal ultrasonography with percutaneous transhepatic cholangioscopy for the identification of residual bile duct stones during lithotripsy.

BACKGROUND: An imaging modality that can be used to identity small stones after a biliary lithotripsy is required. Intraductal ultrasonography was evaluated by using percutaneous transhepatic cholangioscopy as the gold standard. METHODS: Lithotripsy, under percutaneous transhepatic cholangioscopy guidance, was performed in 20 patients. A thin-caliber ultrasonic probe (2.0 mm in diameter and 20 MHz frequency) was inserted into the bile duct through the percutaneous tract after lithotripsy, and residual stones were identified. This was followed by percutaneous transhepatic cholangioscopy. RESULTS: In the extrahepatic bile ducts, intraductal ultrasonography provided images of all the stones demonstrated on cholangioscopy (n = 11). The sensitivity was superior to that of cholangiography (P < 0.005). However, in the intrahepatic bile ducts, intraductal ultrasonography only visualized the stones located in the cannulated lobe. Extrahepatic stones smaller than 5.0 mm in diameter or in a common hepatic duct larger than 15.0 mm in diameter were missed by cholangiography, but were visualized by the use of intraductal ultrasonography (P < 0.05). CONCLUSIONS: Intraductal ultrasonography is equivalent to cholangioscopy in the extrahepatic bile ducts. Cholangiography and intraductal ultrasonography should be used in combination to image intrahepatic and extrahepatic stones.

Aged↗
PubMed2001

Epinephrine irrigation for the prevention of pancreatic damage after endoscopic balloon sphincteroplasty.

BACKGROUND AND AIM: Endoscopic balloon sphincteroplasty (EBS) is an alternative to sphincterotomy for the treatment of bile duct stones. The purpose of this study was to determine if epinephrine irrigation of the papilla can prevent the pancreatic damage associated with EBS. METHODS: A total of 173 patients with bile duct stones were treated by EBS. After conventional endoscopic retrograde cholangiography, EBS was performed by using a biliary dilatation catheter (balloon diameter: 8 mm). The duct was then cleared by using Dormia baskets or retrieval balloon catheters. Mechanical lithotripsy was performed before extraction when the stones were greater than 8 mm in diameter. In 81 patients, the dilated orifice was irrigated with 40-120 mL (50 +/- 37 mL) of 1:1,000,000 epinephrine (epinephrine group). In the remaining 92 patients, epinephrine irrigation was not performed (control group). Acute pancreatitis was defined by a serum amylase concentration fivefold greater than the upper limits of normal in association with abdominal pain. RESULTS: After EBS, serum amylase concentrations were significantly increased in both groups. However, the degree of hyperamylasemia was less in the epinephrine group than in the control group (617 +/- 611 vs 1037 +/- 1491 IU/L, P < 0.05). The incidence of pancreatitis was lower in the epinephrine group than in the control group (1.2 vs 7.6%, P < 0.05). CONCLUSIONS: Epinephrine irrigation is a simple and useful method to prevent post-EBS pancreatic damage and pancreatitis.

Adult↗
PubMed2001

Intraductal ultrasonography for hepatocellular carcinoma with tumor thrombi in the bile duct: comparison with polypoid cholangiocarcinoma.

BACKGROUND AND AIM: Tumor thrombi in the bile duct caused by hepatocellular carcinoma (HCC), and cholangiocarcinoma show polypoid lesions on cholangiographic findings. This study prospectively compared the images of intraductal ultrasonography between HCC and polypoid cholangiocarcinoma. METHODS: In five patients with tumor thrombi in the bile duct caused by HCC, a 2.0 mm diameter ultrasonic probe with a frequency of 20 MHz was inserted into the bile duct via the transpapillary route (n = 4) or the transhepatic route (n = 1). The images were compared to that of 65 patients with cholangiocarcinoma. RESULTS: In all patients with HCC, intraductal ultrasonography showed a 'polypoid tumor with a narrow base'. In 16 of 65 patients with cholangiocarcinoma, it showed a 'polypoid tumor with a narrow base'. When intraductal ultrasonography showed a 'polypoid tumor with a narrow base', the findings of a positive 'nodule within a nodule' (40 vs 0%; P < 0.05), and the absence of a 'papillary-surface pattern' (80 vs 13%; P < 0.05) were more highly associated with tumor thrombi caused by HCC than to polypoid-type cholangiocarcinoma. CONCLUSIONS: Intraductal ultrasonography was useful to distinguish between tumor thrombi caused by HCC and polypoid-type cholangiocarcinoma.

Aged↗
PubMed2001

p53 expression in the gastric mucosa before and after eradication of Helicobacter pylori.

BACKGROUND: Accumulation of p53 has been recognized in the gastric mucosa infected with Helicobacter pylori. We investigated the prevalence of p53-positive cells in the gastric mucosa before and one month after eradication of H. pylori and the relationship between p53 positivity and inflammation and cell proliferation. METHODS: The subjects included 24 H. pylori-positive patients. They achieved eradication one month after anti-H. pylori therapy. Biopsies were taken from the greater curvatures of the antrum and middle body. H. pylori status was assessed using culture and tissue section (Giemsa stain). Serial sections were used for examination of gastritis (hematoxylin and eosin stain) and for immunostaining of p53, Ki-67 and myeloperoxidase (MPO). p53 index and Ki-67 labeling index (LI) were calculated by counting p53-positive and Ki-67-positive cells in the entire gastric pits longitudinally sectioned and expressing them as a percentage of the total cells in a gastric pit. In the neck regions with and without p53-positive cells, polymorphonuclear leukocytes (PMNs) were counted in the corresponding area (/50 x 50 microm2) of the sections stained both with p53 and MPO. RESULTS: p53-positive cells decreased significantly after eradication of H. pylori. Before eradication, the number of PMNs was significantly higher in the neck regions with p53-positive cells than in those without. CONCLUSIONS: In the gastric mucosa infected with H. pylori, p53-positive cells were found in the neck region infiltrated with PMNs. p53 expression decreased significantly one month after eradication of H. pylori.

Adult↗
PubMed2001

Guidelines in the management of Helicobacter pylori infection in Japan.

BACKGROUND: In preparation of the approval of Helicobacter pylori therapy by the Japanese national health system, the board of directors of the Japanese Society for Helicobacter Research decided to prepare guidelines on the diagnosis and treatment of H. pylori infection for physicians in routine medical practice. METHODS: A guidelines preparation committee was formed and six meetings were held. Then, in December 1999, a consensus meeting was held in Kobe to obtain the opinions of general practitioners as well as experts from Europe, North America, and Asia. RESULTS: Helicobacter pylori eradication therapy is recommended in gastric or duodenal ulcer patients. Helicobacter pylori eradication therapy is recommended or gastric mucosa associated lymphoid tissue (MALT) lymphoma but it should be done at specialist institutions. The significance of H. pylori eradication therapy is still under evaluation in patients with hyperplastic polyps, chronic atrophic gastritis, non-ulcer dyspepsia and in patients after endoscopic mucosal resection of gastric cancer and after gastrectomy for gastric cancer. When diagnosing H. pylori infection, at least one of the tests requiring endoscopic biopsy (e.g. rapid urease test, histology, or culture) and tests not requiring biopsy (e.g. measurement of H. pylori antibody or urea breath test) should be used. Multiple tests are recommended to increase the accuracy. The drugs of first choice currently covered by the national health insurance system in Japan are: lansoprazole (30 mg) 1 capsule twice daily, amoxicillin (250 mg) 3 capsules twice daily, and clarithromycin (200 mg) 1-2 tablets twice daily. These three drugs should be administered after breakfast and dinner for 1 week. CONCLUSION: These guidelines are intended for utilization in routine medical practice after the Japanese national health system begins to cover the management of H. pylori infection.

Amoxicillin↗
PubMed2001

Evaluation of water and electrolyte transport of tubular epithelial cells under osmotic and hydraulic pressure for development of bioartificial tubules.

Our aim was to develop bioartificial tubules using tubular epithelial cells and artificial membranes and evaluate the function of water and electrolyte transport by various tubular epithelial cells. The cells were cultivated onto extracellular matrix (ProNectin F) coating polycarbonate membrane. Water transport from the apical to the basolateral site of cells was examined using a modified Ussing chamber module. Water transport under colloidal osmotic pressure on the apical site and hydraulic pressure on the basolateral site were higher in JTC-12, LLC-PK1 cells than in MDCK cells. Water transport under osmotic plus hydraulic pressure was highest in LLC-PK1 cells. We made bioartificial tubules using LLC-PK1 cells and polysulfone hollow fiber cartridges. Water and Na ion transport function was high, and BUN and creatinine passage was recognized in these bioartificial tubules. BUN and creatinine concentrations of reabsorption fluid in these bioartificial tubules were significantly lower than those concentrations of control media and of noncell attached polysulfone hollow fiber cartridges. Though LLC-PK1 cells were more preferable cells for the use of bioartificial tubules in terms of water and electrolyte transport, the passage of BUN and creatinine was not appropriate for clinical use. To select more preferable cells for bioartificial tubules which transport water and electrolytes and do not induce passage of uremic toxins is necessary.

Animals↗
PubMed2001

Extensive methylation of hMLH1 promoter region predominates in proximal colon cancer with microsatellite instability.

BACKGROUND & AIMS: Methylation of the hMLH1 promoter region has been suggested to cause microsatellite instability (MSI) in sporadic colorectal carcinoma (CRC). We studied the methylation profile in a wide region of the hMLH1 promoter and compared with the hMLH1 protein expression and MSI status in 88 cases of sporadic CRC. METHODS: Na-bisulfite treatment and polymerase chain reaction single-strand conformation polymorphism analysis was performed using 5 sets of polymerase chain reaction primers spanning the promoter region of the hMLH1 to examine methylation status. Results were compared with immunostaining using anti-hMLH1 monoclonal antibody and MSI status of the tumor samples. RESULTS: Methylation status was classified as full or partial methylation. Full methylation indicates the methylation of all CpG sites in the examined regions. Methylation of the hMLH1 promoter was observed in 88.9% (16 of 18) of CRCs showing high frequency MSI (MSI-H), among which 89% (14 of 16) had full methylation with reduced hMLH1 protein expression. All cases showing full methylation were proximal colon tumors with MSI-H. In cases with partial methylation, only the upstream region of the hMLH1 promoter was methylated. Partial methylation was also shown in 33.3% (6 of 18) of the normal mucosa of MSI-H cases. Frequencies of methylation were significantly correlated with female gender (P = 0.0009) and aging (P = 0.007). CONCLUSIONS: Full methylation of the hMLH1 promoter region and subsequent gene inactivation may play a crucial role in the carcinogenesis of MSI-H CRCs in the proximal colon. Methylation upstream of the hMLH1 promoter appears to be an early event in the carcinogenesis of MSI-H tumors.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Endoscopic partial resection of a duodenal duplication cyst.

A case of symptomatic duodenal duplication cyst is reported. The patient underwent endoscopic partial resection of the cystic wall using the O-ring ligation kit. After resection, the abdominal pain disappeared. Endoscopic partial resection is useful for diagnosis and treatment of duodenal duplication cyst.

Adult↗
PubMed2001

Ropeway-type bile duct biopsy forceps with a side slit for a guidewire.

BACKGROUND: Transpapillary procurement of bile duct biopsy specimens is an effective diagnostic technique in cases of biliary structure. The utility of new ropeway-type bile duct biopsy forceps with a side slit for a guidewire was investigated in this study. METHODS: The 12 patients in this study had bile duct cancer (n = 3), cancer of the head of the pancreas (n = 4), gallbladder cancer (n = 1), and benign bile duct stenosis (n = 4). After endoscopic retrograde cholangiography, a guidewire was placed in the bile duct across the stenosis. The new forceps (1.8-mm diameter clamshell-type biopsy forceps without needle) was then introduced through the intact papilla along the guidewire. RESULTS: In all patients, sufficient tissue for histopathologic evaluation was obtained without complication. In one patient, biopsy specimens were selectively obtained of the left hepatic duct, which was impossible with conventional forceps. In another patient, histologic examination of specimens obtained by using this new forceps showed adenocarcinoma, whereas specimens obtained with a conventional forceps did not contain adenocarcinoma. However, in another patient, biopsy specimens obtained with a conventional forceps contained adenocarcinoma that was not evident in specimens obtained with the new forceps. Dislodgement of the guidewire during procurement of biopsy specimens occurred in 1 patient. In the other 11 patients, an endoscopic biliary drain was inserted over the guidewire. CONCLUSION: The new ropeway-type biopsy forceps is useful for selectively obtaining biopsy specimens of the bile duct. With this system, access for subsequent endoscopic biliary drainage is maintained.

Aged↗
PubMed2001

Total enteroscopy with a nonsurgical steerable double-balloon method.

BACKGROUND: Deep insertion of an enteroscope by use of a push technique is difficult. A new method of enteroscopy was developed, a double-balloon method, to improve the access to the small intestine. METHODS: The new method uses 2 balloons, one attached to the tip of the endoscope and another at the distal end of an overtube. By using these balloons to grip the intestinal wall, the endoscope can be inserted further without forming redundant loops in the small intestine. This method was tried with a standard upper endoscope in 3 patients and with a longer enteroscope in 1 patient. RESULTS: Despite its short length the upper endoscope was successfully inserted as far as 30 to 50 cm beyond the ligament of Treitz in the 3 patients. In the fourth patient the longer enteroscope was successfully inserted beyond the ileo-cecal valve. CONCLUSIONS: The double-balloon method facilitates endoscopic access to the small intestine.

Adolescent↗