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Biomedical subjects

Makoto Okamoto

Publications and source records attributed to Makoto Okamoto.

At least 19 recordsLinked to original sources

Dysregulated expression of stem cell factor Bmi1 in precancerous lesions of the gastrointestinal tract.

PURPOSE: It is important to identify the definitive molecular switches involved in the malignant transformation of premalignant tissues. Cellular senescence is a specific characteristic of precancerous tissues, but not of cancers, which might reflect tumorigenesis-protecting mechanisms in premalignant lesions. Polycomb protein Bmi1, which is a potent negative regulator of the p16INK4 gene, suppresses senescence in primary cells and is overexpressed in various cancers. We hypothesized that Bmi1 expression would also be dysregulated in precancerous lesions in human digestive precancerous tissues. EXPERIMENTAL DESIGN: Bmi1 expression was investigated in cancerous and precancerous tissues of the digestive tract. The expression of p16, beta-catenin, and Gli1 and the in vivo methylation status of the p16 gene were also analyzed in serial sections of colonic precancerous lesions. RESULTS: Bmi1 was clearly overexpressed across a broad spectrum of gastrointestinal cancers, and the expression of Bmi1 increased in a manner that reflected the pathologic malignant features of precancerous colonic tissues (low-grade dysplasia, 12.9 +/- 2.0%; high-grade dysplasia, 82.9 +/- 1.6%; cancer, 87.5 +/- 2.4%). p16 was also strongly expressed in high-grade dysplasia, but not in cancers. p16 promoter methylation was detected only in some Bmi1-positive neoplastic cells. CONCLUSIONS: Bmi1 overexpression was correlated with the malignant grades of human digestive precancerous tissues, which suggests that advanced Bmi1 dysregulation might predict malignant progression. The abnormal Bmi1 expression might link to malignant transformation via the disturbance of orderly histone modification.

Cell Line, Tumor↗

A randomized controlled trial evaluating the usefulness of a transparent hood attached to the tip of the colonoscope.

OBJECTIVES: Considering the increasing demand for colonoscopy, auxiliary devices that could facilitate the examination would be useful. A hood attached to the tip of the colonoscope has been reported to be helpful in detecting and removing colorectal polyps. However, its usefulness in aiding scope intubation has not been fully evaluated. METHODS: Patients for colonoscopy between July 2004 and May 2005 in Tokyo University Hospital were enrolled to this randomized controlled trial, and assigned to colonoscopy with a transparent hood, a short hood, or no hood. Colonoscopies were conducted by trainees without sedation. The evaluated outcomes were cecal intubation rate, trainee intubation rate (cecal intubation within 15 min), cecal intubation time, and polyp detection rate. RESULTS: Enrolled 684 patients were randomly assigned to transparent hood (N = 221), short hood (N = 228), and no hood (N = 235) groups. The overall cecal intubation rate was 95.3% (652/684) and did not differ among the groups. The overall trainee intubation rate was 55.1% (377/684) and significantly higher in the transparent hood group than in the no hood group for female patients (60.7%vs 37.4%, P = 0.003). Cecal intubation time was 11.5, 13.5, and 14.0 min in the transparent, short, and no hood groups, respectively, and significantly shorter in the transparent hood group than in the no hood group among overall (P = 0.008), female (P = 0.001), and old (P = 0.04) patients. Polyp detection rate was higher in the transparent hood group than in the no hood group (49.3%vs 39.1%, P = 0.04). CONCLUSIONS: The transparent hood was useful in shortening the cecal intubation time especially in difficult cases.

Clinical Competence↗

Right-side shift of colorectal adenomas with aging.

BACKGROUND: Although it is known that right-side colon cancers increase with aging, the location of adenomas according to age has been controversial. Adenomas found at initial colonoscopies may be a mixture of polyps that arose at various earlier ages. OBJECTIVES: To elucidate the relationship between location and age at which adenomas actually developed. DESIGN: Prospective cohort study. SETTING: A large-scale health appraisal institution in Japan. PATIENTS: A total of 23,444 consecutive, asymptomatic Japanese who underwent total colonoscopy at their annual medical health check-up. INTERVENTIONS: We analyzed newly developed adenomas after confirmation of the absence of colorectal neoplasms by two serial total colonoscopies. MAIN OUTCOME MEASUREMENTS: The results of follow-up colonoscopies in 6304 subjects with no colorectal neoplasms at 2 initial colonoscopies were analyzed. The locations were separated into right-side colon and left-side colon from the splenic flexure. The locations of new adenomas found for the first time during the follow-up term were analyzed. RESULTS: A total of 1472 subjects developed new colorectal adenomas. In 1255 cases with single adenomas, the ratios of number of cases with right-side lesions to that with left-side lesions at the ages of <40 years, 40 to 49 years, 50 to 59 years, 60 to 69 years, and > or =70 years were 1.18, 1.00, 1.29, 1.31, and 1.89, respectively. In 217 cases with multiple adenomas found concurrently, the percentage of cases with adenomas only on the right side at the ages of <40 years, 40 to 49 years, 50 to 59 years, 60 to 69 years, and > or =70 years were 0%, 25%, 34%, 37%, and 63%, respectively. LIMITATIONS: Small lesions might have been missed even by 2 serial colonoscopies. CONCLUSIONS: Adenomas on the right-side colon increased with aging.

Adenoma↗

Risk assessment for delayed hemorrhagic complication of colonic polypectomy: polyp-related factors and patient-related factors.

BACKGROUND: Hemorrhage is among the most serious complications of colorectal polypectomy and may occur after a longer postprocedure interval. OBJECTIVE: We aimed to elucidate the risk factors for delayed postpolypectomy hemorrhage, including both polyp characteristics and the general condition of the patients. DESIGN: Retrospective cohort study. PATIENTS: A total of 6617 cases of colorectal polypectomy was performed in 3138 consecutive patients in Japan. MAIN OUTCOME MEASUREMENTS: The risk factors for delayed postpolypectomy hemorrhage were assessed among polyp characteristics (form, size, histologic features) and the method of resection by unconditional logistic regression. Patient conditions (smoking, alcohol, hypertension, diabetes mellitus, hyperlipidemia) were compared between case-control pairs matched on polyp-related characteristics by conditional logistic regression. RESULTS: Hemorrhage occurred in 38 lesions (0.57%) of 37 patients (1.2%): 22 required endoscopic hemostasis and 1 required blood transfusion. Although polyp size was associated with the occurrence of delayed hemorrhage (10.0 +/- 6.9 mm in hemorrhage cases vs 5.6 +/- 3.8 mm in others, P < .0001), other polyp-related factors were not significant. Hypertension was a complication in 25 of 37 (68%) cases and in 21 of 74 (28%) matched controls, showing an adjusted odds ratio of 5.6 (95% CI 1.8-17.2, P = .001). Other patient characteristics were not significant. The interval between polypectomy and hemorrhage was significantly longer in patients with hypertension (median 6 days, range 2-14 days) than in those without hypertension (2.5 days, 1-9 days; P = .019). LIMITATIONS: This study does not provide information regarding prevention of hemorrhage. CONCLUSIONS: Hypertension is a significant risk factor for delayed colorectal postpolypectomy hemorrhage. The interval between polypectomy and hemorrhage can be as long as 14 days in the presence of hypertension.

Aged↗

A case of rectal Dieulafoy's ulcer and successful endoscopic band ligation.

Dieulafoy's ulcer is a rare cause of gastrointestinal bleeding. The lesion is usually located in the stomach, although it may occur anywhere in the gastrointestinal tract. A 44-year-old man was admitted to hospital due to cerebral infarction. On the 23rd day of hospitalization, he showed massive hematochezia. He underwent an urgent colonoscopy. There was a visible protuberant vessel without significant ulceration at the fundus of the rectum, consistent with a Dieulafoy's ulcer. It was treated by endoscopic hemoclipping. However, rebleeding occurred three times despite repeated hemoclipping. Finally, endoscopic band ligation was successfully performed to achieve permanent hemostasis. Endoscopic band ligation is an effective treatment for bleeding rectal Dieulafoy's ulcer.

Adult↗

The malignant potential of freshly developed colorectal polyps according to age.

BACKGROUND: Although malignant colorectal neoplasms are found more frequently in older population, polyps found at one-time colonoscopy may be a mixture of lesions that developed at various earlier ages. Newly developed adenomas found at the follow-up colonoscopies will reflect the exact relation between malignant potential and the age of development of colorectal polyps. METHODS: The results of 44,065 follow-up colonoscopies on 11,912 subjects were analyzed. The proportion of invasive cancer or high-grade dysplasia among all neoplasms, "proportion of malignancy," was evaluated in relation to age groups (young: <50 years old; middle: 50-59 years old; and old: >or=60 years old). RESULTS: At the follow-up colonoscopies, a total of 8,271 newly developed neoplasms were found, of which 41 (0.50%) lesions were malignant. The proportion of malignancy was 0.35%, 0.31%, and 1.07% in the young, middle, and old age groups, respectively (P(trend) = 0.002). This trend remained significant when stratified by the size of polyps. The proportion of malignancy was higher on the left-side colon than on the right-side colon, except in the old age group, where it was similar on either side. The proportion of malignancy at the follow-ups was not associated with the lesions found at the initial colonoscopies. CONCLUSIONS: The development of malignant lesions in small sizes increased on the colon or rectum at older ages.

Adenocarcinoma↗

Effect of adhesive primer developed exclusively for heat-curing resin on adhesive strength between plastic artificial tooth and acrylic denture base resin.

Despite progress in the development of denture base resin and artificial tooth materials, dental clinics are still plagued with artificial teeth falling off the denture base--due to poor bond strength--after denture delivery. Against this background, this study sought to examine the effect and durability of an adhesive primer developed exclusively for heat-curing resin on the adhesive strength of heat-curing denture base acrylic resin to plastic artificial tooth. Test specimens were divided into four groups according to the treatment method of the artificial tooth's test bonding surface: air abrasion, adhesive primer application, adhesive primer application after air abrasion, and pretreatment only (control). After heat curing of acrylic resin onto the bonding surface, shear test was performed for two storage periods: 24-hour versus 100-day water storage. From the results obtained, it was revealed that the evaluated adhesive primer was significantly effective in increasing adhesive strength between artificial tooth and acrylic resin, although specimens were stored in water for 100 days.

Acrylic Resins↗

Rectosigmoid findings are not associated with proximal colon cancer: analysis of 6 196 consecutive cases undergoing total colonoscopy.

AIM: To review the risk of proximal colon cancer in patients undergoing colonoscopy. METHODS: We estimated the risk of advanced proximal adenomas and cancers in 6 196 consecutive patients that underwent colonoscopy (mean age 60 years, 65% males, without prior history of colorectal examination). Neoplasms were classified as diminutive adenoma (5 mm or less), small adenoma (6-9 mm), advanced adenoma (10 mm or more, with villous component or high-grade dysplasia) and cancer (invasive adenocarcinoma). The sites of neoplasms were defined as rectosigmoid (rectum and sigmoid colon) and proximal colon (from cecum to descending colon). RESULTS: The trend of the prevalence of advanced proximal adenoma was to increase with severe rectosigmoid findings, while the prevalence of proximal colon cancer did not increase with severe rectosigmoid findings. Among the 157 patients with proximal colon cancer, 74% had no neoplasm in the rectosigmoid colon. Multivariate logistic-regression analysis revealed that age was the main predictor of proximal colon cancer and existence of rectosigmoid adenoma was not a predictor of proximal colon cancer. CONCLUSION: Sigmoidoscopy is inadequate for colorectal cancer screening, especially in older populations.

Adenoma↗

Flat-type early colorectal cancer preferentially develops in right-sided colon in older patients.

BACKGROUND: Flat-type colorectal cancer is frequently reported in Japan and Europe, but its clinical features remain obscure. Thus, we investigated the clinical features of flat-type early colorectal cancer with respect to tumor location and patient age and compared them with those of polypoid-type early and advanced cancer. METHODS: Between January 1999 and June 2001, total colonoscopy was performed in 6,178 patients (mean age, 61 years; 4,290 males and 1,888 females). Of these patients, 402 patients with 429 colorectal cancers were found: 202 at advanced stage (invading beyond muscularis propria) and 227 at early stage (carcinoma in situ or invading within submucosa). Early-stage cancer was classified into two macroscopic subgroups: flat-type and polypoid-type. RESULTS: Out of 227 early cancers, 44 were flat type and 183 were polypoid. Flat-type early cancer was more frequently located in the right colon (57 percent, 25/44) than polypoid-type cancer (19 percent, 35/183; P < 0.001). Adenomatous component in flat-type early cancer was less frequent than in polypoid-type cancer (23 percent vs. 92 percent, P < 0.001). The proportion of right-sided colon in flat-type early cancer increased with age (33 percent in patients < or = 59 years, 50 percent in patients between 60 and 69 years, and 72 percent in patients > or = 70 years), whereas polypoid-type early cancer showed minimal change (16 percent, 18 percent, and 25 percent, respectively). An increase in the proportion of right-sided colon with age was also found in advanced cancer (20 percent, 38 percent, and 52 percent, respectively). CONCLUSION: The incidence of flat-type early cancer in right-sided colon increased with age, similar to the pattern of advanced cancer. This suggests that flat-type early cancer may be a precursor of advanced cancer in the right colon, especially in older people.

Adenoma↗

Ultrathin colonoscope with a diameter of 9.8 mm for total colonoscopy.

BACKGROUND: The pediatric colonoscope is superior to the standard colonoscope in some patients with a fixed, angulated colon. A colonoscope thinner than the pediatric one is thought to outperform even the pediatric colonoscope in such cases. This study was conducted to assess the efficacy of an ultrathin colonoscope, 9.8 mm in diameter, comparing it with pediatric and standard colonoscopes. METHODS: Three types of colonoscopes were used: ultrathin, pediatric, and standard. A total of 287 consecutive patients were assigned to three groups: ultrathin (n=94), pediatric (n=98), and standard (n=95). First assessment was the ratio of cecal intubation and the reasons for unsuccessful colonoscopy. The second was the time to cecal intubation. RESULTS: Cecal intubation rates were not different among three groups (96% in each). The main reasons for failed colonoscopy were looping in the ultrathin group, and angulation or stricture in the pediatric and standard groups. Mean time to the cecum was slightly longer in the ultrathin group (6.5 minutes) than the pediatric group (5.6 minutes) and standard group (6.1 minutes), but there were no significant differences among three groups. CONCLUSION: Colonoscopy with the ultrathin colonoscope was as successful as with the pediatric and standard colonoscopes. The advantage of the ultrathin colonoscope might be notable in cases with stricture or severe angulation.

Adult↗

Pancreas duct abnormalities in patients with ulcerative colitis: a magnetic resonance pancreatography study.

BACKGROUND: The presumed etiology and prevalence of pancreatic abnormalities in patients with ulcerative colitis (UC) have been controversial. We conducted a controlled (cross-sectional) study of patients with UC compared with non-UC controls to determine the prevalence of pancreatic duct abnormalities in patients with UC and to determine if these are specific to UC using magnetic resonance cholangiopancreatography. METHODS: Magnetic resonance cholangiopancreatography was performed on 79 unselected patients with UC and 45 non-UC controls, without a history of pancreatitis attack, between February 2000 and May 2003. RESULTS: Among patients with UC, the prevalence of pancreatic duct abnormalities was 16.4% (95% confidence interval, 8.3%-24.6%): coexisting dilatation and narrowing of the main pancreatic duct were found in 5; diffuse narrowing of pancreatic ducts in 5; and dilatation of pancreatic ductal branches in 3. These abnormalities were compatible with chronic pancreatitis. Among the controls, no pancreatic duct abnormality was found. CONCLUSIONS: Changes in the pancreatic duct were found in approximately one-sixth of patients with UC, none of whom had a history of overt pancreatitis. These pancreatic duct abnormalities are likely to be specific to patients with UC.

Adolescent↗

Amebic colitis in asymptomatic subjects with positive fecal occult blood test results: clinical features different from symptomatic cases.

Amebiasis is a common parasitic infectious disease in developing countries. In developed countries, it is occasionally encountered in travelers to the tropics and in homosexual males. During the past eight years, we detected four cases of amebic colitis among 5,193 subjects who underwent colonoscopy because of positive fecal occult blood test results in a mass screening. All four cases did not have any abdominal symptoms. Ulcerative lesions were observed only in the cecum and ascending colon; another portion of the colon and rectum appeared normal. We may encounter amebic colitis during colonoscopic examination even in subjects who are asymptomatic.

Animals↗

Rapid detection of mutations in the BRAF gene using real-time polymerase chain reaction and melting curve analysis.

The BRAF gene is mutated in 66% of melanomas and less frequently in various human cancers. More than 80% of these mutations are T to A transversions at nucleotide 1796 (T1796A), leading to a substitution of glutamic acid for valine at amino acid 599 (V599E). We established a new method for rapidly detecting V599E mutations using real-time polymerase chain reaction and melting curve analysis. Furthermore, we examined mutations in gastrointestinal cancer cell lines using this method. We found a mutation in 1 of 12 (8%) colorectal cancer cell lines, but no mutation was detected in 9 gastric cancer cell lines. These results suggest that the BRAF mutation is unlikely to be involved in gastric carcinogenesis.

Amino Acid Substitution↗

[Peritonsillar abscess associated with infectious mononucleosis: retrospective study of three cases].

Three cases with infectious mononuculeosis associated with peritonsillar abscess were reviewed. The initial diagnoses in these three cases were tonsillitis or peritonsillitis. However, infectious mononucleosis was suspected because of an elevation in aminotransferases and was later confirmed by elevations in the titers of antibodies for Epstein-Barr virus. Peritonsillar abscesses developed and surgical drainage was performed in all three cases. The present study suggests a higher incidence of peritonsillar abscess in patients with infectious mononucleosis than previously expected.

Adult↗

Effect of plasma treatment on adhesion of self-curing repair resin to acrylic denture base.

Plasma irradiation on surface of heat-cured acrylic resin prior to processing self-curing acrylic resin is likely to effectively increase the adhesive strength between these materials for short-term period. However, long-term reliability of adhesive strength between these materials has not been clarified yet. In the present study, these materials were stored in water for a long period (100 days), and the effect on their shear bond strength was investigated. Forty-four test specimens with flat bonding test surface were made with heat-cured acrylic resin. They were divided into four groups according to treatment procedures for bonding surface: plasma treatment, adhesive primer application, adhesive primer application after plasma treatment, and no treatment (for control). Self-curing acrylic resin was processed against all bonding surfaces. After storage in water for 100 days, shear bond strength values between heat-cured and self-cured acrylic resins were measured. Specimens in plasma treatment group exhibited higher shear bond strength value than those in control, although the difference was not significant.

Acrylic Resins↗

Complexity of terminal airspace geometry assessed by computed tomography in asthma.

Low attenuation areas in computed tomography images from patients with chronic obstructive pulmonary disease have been reported to represent macroscopic and/or microscopic emphysema. The cumulative size distribution of the clusters has been shown to follow a power law characterized by the exponent D, a measure of the complexity of the terminal airspace geometry. We have previously found increased low attenuation areas in nonsmoking subjects with asthma. We examined the size distribution of the clusters in nonsmoking subjects with asthma compared with both nonsmoking control subjects and subjects with asthma with a smoking history. The percentage of lung field occupied by low attenuation areas (LAA%) and D in subjects with asthma with a smoking history differed significantly from nonsmoking subjects with asthma and control subjects. In nonsmoking subjects with asthma, both parameters differed significantly between severe asthma and mild or moderate asthma. The LAA% differed significantly between moderate and mild asthma, but D did not. In mild and moderate asthma, a highly significant correlation between LAA% and D was observed in patients with a smoking history, but not in nonsmoking subjects with asthma. Our results suggest that decreased D is mostly related to emphysematous change, and both measurements of LAA% and D may provide useful information to characterize low attenuation areas in subjects with asthma.

Aged↗