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1.
World J Gastroenterol ; 21(41): 11832-41, 2015 Nov 07.
Article in English | MEDLINE | ID: mdl-26557007

ABSTRACT

Superficial non-ampullary duodenal epithelial tumor (SNADET) is defined as a sporadic tumor that is confined to the mucosa or submucosa that does not arise from Vater's papilla, and it includes adenoma and adenocarcinoma. Recent developments in endoscopic technology, such as high-resolution endoscopy and image-enhanced endoscopy, may increase the chances of detecting SNADET lesions. However, because SNADET is rare, little is known about its preoperative endoscopic diagnosis. The use of endoscopic resection for SNADET, which has no risk of metastasis, is increasing, but the incidence of complications, such as perforation, is significantly higher than in any other part of the digestive tract. A preoperative diagnosis is required to distinguish between lesions that should be followed up and those that require treatment. Retrospective studies have revealed certain endoscopic findings that suggest malignancy. In recent years, several new imaging modalities have been developed and explored for real-time diagnosis of these lesion types. Establishing an endoscopic diagnostic tool to differentiate between adenoma and adenocarcinoma in SNADET lesions is required to select the most appropriate treatment. This review describes the current state of knowledge about preoperative endoscopic diagnosis of SNADETs, such as duodenal adenoma and duodenal adenocarcinoma. Newer endoscopic techniques, including magnifying endoscopy, may help to guide these diagnostics, but their additional advantages remain unclear, and further studies are required to clarify these issues.


Subject(s)
Adenocarcinoma/pathology , Duodenal Neoplasms/pathology , Duodenoscopy/methods , Image Enhancement/methods , Adenocarcinoma/surgery , Biopsy , Diagnosis, Differential , Duodenal Neoplasms/surgery , Humans , Narrow Band Imaging , Neoplasm Staging , Predictive Value of Tests , Preoperative Care , Reproducibility of Results
3.
J Atheroscler Thromb ; 22(3): 235-46, 2015.
Article in English | MEDLINE | ID: mdl-25342477

ABSTRACT

AIM: The role of gastrectomy in glycemic control has been established in the current era of bariatric surgery for obesity. Gastrectomy in obese patients is associated with increased levels of high-density lipoprotein cholesterol (HDL-C). However, limited data on the effects of gastrectomy in nonobese patients are available. We herein investigated the long-term plasma lipid changes in nonobese patients who had undergone gastrectomy. METHODS: Patients were enrolled as part of routine healthcare examinations from 1984 to 2003. Preoperative and postoperative data from patients who had undergone curative gastrectomy were analyzed for up to 10 years postoperatively. Three age- and sex-matched controls were assigned to each case. RESULTS: Sixty-four nonobese patients without diabetes mellitus or a history of having taken lipid-lowering drugs who underwent curative gastrectomy during the study period were enrolled (60 subtotal gastrectomies, four total gastrectomies). The median follow-up period was 7.6 years. The mean body mass index was 9.6% lower one year after gastrectomy (p < 0.01), then plateaued with a slight recovery. Intriguingly, the preoperative HDL-C level was 21% higher one year after gastrectomy (p < 0.01), increased by another 30% six years after gastrectomy and remained at this level for the rest of the follow-up period. No significant changes in the HDL-C level were observed in the controls. The degree of HDL-C elevation was consistently significant, irrespective of the baseline triglyceride level, HDL-C level or body weight. CONCLUSIONS: Gastrectomy in nonobese patients was associated with consistent and distinct long-term HDL-C elevations and body mass index reductions.


Subject(s)
Cholesterol, HDL/metabolism , Gastrectomy , Case-Control Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Obesity/metabolism
4.
PLoS One ; 9(7): e100857, 2014.
Article in English | MEDLINE | ID: mdl-24988209

ABSTRACT

OBJECTIVES: Magnifying narrow-band imaging (M-NBI) is more accurate than white-light imaging for diagnosing small gastric cancers. However, it is uncertain whether moving M-NBI images have additional effects in the diagnosis of gastric cancers compared with still images. DESIGN: A prospective multicenter cohort study. METHODS: To identify the additional benefits of moving M-NBI images by comparing the diagnostic accuracy of still images only with that of both still and moving images. Still and moving M-NBI images of 40 gastric lesions were obtained by an expert endoscopist prior to this prospective multicenter cohort study. Thirty-four endoscopists from ten different Japanese institutions participated in the prospective multicenter cohort study. Each study participant was first tested using only still M-NBI images (still image test), then tested 1 month later using both still and moving M-NBI images (moving image test). The main outcome was a difference in the diagnostic accuracy of cancerous versus noncancerous lesions between the still image test and the moving image test. RESULTS: Thirty-four endoscopists were analysed. There were no significant difference of cancerous versus noncancerous lesions between still and moving image tests in the diagnostic accuracy (59.9% versus 61.5%), sensitivity (53.4% versus 55.9%), and specificity (67.0% versus 67.6%). And there were no significant difference in the diagnostic accuracy between still and moving image tests of demarcation line (65.4% versus 65.5%), microvascular pattern (56.7% versus 56.9%), and microsurface pattern (48.1% versus 50.9%). Diagnostic accuracy showed no significant difference between the still and moving image tests in the subgroups of endoscopic findings of the lesions. CONCLUSIONS: The addition of moving M-NBI images to still M-NBI images does not improve the diagnostic accuracy for gastric lesions. It is reasonable to concentrate on taking sharp still M-NBI images during endoscopic observation and use them for diagnosis. TRIAL REGISTRATION: Umin.ac.jp UMIN-CTR000008048.


Subject(s)
Gastroscopy/methods , Stomach Neoplasms/pathology , Case-Control Studies , Female , Humans , Male , Prospective Studies , Sensitivity and Specificity
5.
PLoS One ; 9(6): e101337, 2014.
Article in English | MEDLINE | ID: mdl-24968310

ABSTRACT

BACKGROUND: Laparoscopic and endoscopic cooperative surgery (LECS) is a minimally invasive surgical technique used to resect gastric submucosal tumors with intraluminal growth. Endoscopic submucosal dissection is used to determine the appropriate resection line from within the stomach lumen as it minimizes the stomach wall resection area and prevents postoperative stomach deformity. Although LECS is intended to preserve gastric function, few reports have evaluated postoperative residual gastric motility. Therefore, we conducted a retrospective analysis of patients who underwent LECS to determine the effects of LECS on residual gastric motility. METHODS: Twenty-two patients underwent endoscopy 3 to 12 months after LECS. Patients were evaluated for endoscopic evidence of gastric motility disorder, namely food residue and occurrence/exacerbation of reflux esophagitis. We considered patients with new onset of gastric symptoms and endoscopic evidence of gastric motility disorder to have clinically relevant gastric motility disorder. We described patient characteristics, tumor location, and surgical findings. RESULTS: Two of 22 patients developed clinically relevant gastric motility disorder after LECS. In one of these patients, the symptoms were not severe; only one had reduced dietary intake and had lost weight. We identified clinically relevant gastric motility disorder in two patients with gastrointestinal stromal tumors located in the lesser curvature of the stomach. The major axis of these two tumors was 34 mm and 38 mm. CONCLUSIONS: Many patients did not have clinically relevant gastric motility disorder after LECS. Further investigation is required to identify predisposing factors for gastric motility disorder.


Subject(s)
Gastrointestinal Motility , Gastrointestinal Stromal Tumors/surgery , Laparoscopy/adverse effects , Stomach Neoplasms/surgery , Adult , Aged , Female , Humans , Male , Middle Aged
6.
Gastrointest Endosc ; 79(4): 558-64, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24246793

ABSTRACT

BACKGROUND: Nonmagnifying observation by using narrow-band imaging (NBI) is useful for detecting pharyngeal lesions. Magnifying observation by using NBI can distinguish between cancerous and noncancerous lesions and is therefore useful for the early detection of pharyngeal cancer. OBJECTIVE: To evaluate the usefulness of observation of the pharynx by using NBI in the overall population undergoing upper GI endoscopy. DESIGN: Retrospective study. SETTING: Single tertiary referral center. PATIENTS: A total of 11,050 upper GI endoscopies between January 2009 and December 2012. INTERVENTIONS: Observation of the pharynx by using NBI. MAIN OUTCOME MEASURES: The rate of detection of pharyngeal cancer, the rates of detection according to the reason for endoscopy, and the types of cancers detected. RESULTS: Thirty-eight cancerous lesions were detected in 29 patients (0.26%, 29/11,050). The rate of detection of pharyngeal cancer was significantly higher in patients with a history of head and neck cancer (9.7%, 3/31) or a history of esophageal cancer (3.5%, 10/282). In patients undergoing endoscopy for screening, pharyngeal discomfort, and a history of gastric cancer, the rates of detection of pharyngeal cancer were 0.11% (10/8872), 1.1% (3/265), and 0.19% (3/1600), respectively. Two patients (6.9%) were female. One had a history of esophageal cancer, and the other had pharyngeal discomfort. LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: Observation of the pharynx by using NBI in patients with previous head and neck cancer or esophageal cancer or who have pharyngeal discomfort is very important. Moreover, pharyngeal cancer was certainly found in the male patients undergoing screening endoscopy, although the rate was lower.


Subject(s)
Endoscopy, Digestive System/methods , Narrow Band Imaging , Pharyngeal Neoplasms/diagnosis , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Time Factors
7.
Dig Endosc ; 26(2): 178-82, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23730976

ABSTRACT

BACKGROUND: Narrow-band imaging (NBI) is useful for detecting superficial oropharyngeal lesions. However, the diagnostic and treatment guidelines for NBI are not established. The aim of the present study was to evaluate the treatment strategy for these microlesions. METHODS: From October 2008 to September 2009, 68 flat-type brownish microlesions were observed in the orohypopharynx using NBI. Lesions were examined via magnifying NBI (M-NBI) and followed up without biopsy or endoscopic resection for >12 months. To clarify the characteristics, lesions were compared with the endoscopic characteristics of flat-type lesions diagnosed by biopsy and endoscopic resection as squamous cell carcinoma and high-grade intraepithelial neoplasia. RESULTS: The average diameter of the 68 lesions was 1.6 mm (range, 0.5-5 mm). At the 1-year follow up, 19 lesions had disappeared. No size increases or morphological changes wereobserved among 49 lesions followed for >1 year. At 2 years, 10 patients had dropped out and 11 lesions had disappeared. No changes were observed among 28 lesions followed for >2 years. Of the flat-type lesions as squamous cell carcinoma and high-grade intraepithelial neoplasia, a distinct border and irregular distribution of atypical vessels were observed in all cases using M-NBI. These findings were observed in two of 68 flat-type brownish microlesions during follow up. CONCLUSION: Although there is some possibility of squamous cell carcinoma or high-grade intraepithelial neoplasia, flat-type microlesions of ≤5 mm diameter in the orohypopharynx may be followed for up to 2 years without biopsy or endoscopic resection.


Subject(s)
Carcinoma in Situ/diagnosis , Carcinoma, Squamous Cell/diagnosis , Digestive System Surgical Procedures/methods , Endoscopy, Gastrointestinal/methods , Esophageal Neoplasms/diagnosis , Narrow Band Imaging/methods , Oropharyngeal Neoplasms/diagnosis , Aged , Biopsy , Carcinoma in Situ/surgery , Carcinoma, Squamous Cell/surgery , Diagnosis, Differential , Esophageal Neoplasms/surgery , Female , Follow-Up Studies , Humans , Male , Neoplasm Staging , Oropharyngeal Neoplasms/surgery , Retrospective Studies
8.
Dig Endosc ; 26(3): 344-9, 2014 May.
Article in English | MEDLINE | ID: mdl-24283625

ABSTRACT

BACKGROUND AND AIM: Transoral endoscopy with narrow band imaging (NBI) is useful for identifying early-stage head and neck cancer. However, the screening capability of transoral upper gastrointestinal endoscopy has not yet been systematically evaluated. We evaluated the usefulness of transoral upper gastrointestinal endoscopy for pharyngeal examination. METHODS: This cross-sectional study evaluated 480 patients. All endoscopic pharyngeal examinations with NBI were carried out in accordance with prescribed procedures, consisting of 10 images each and all images were assessed by a blinded reviewer. We examined the association between the diagnostic usefulness of pharyngeal examination and other factors. RESULTS: Median subject age was 64 years (range 22-90 years), and 64% were male. Almost all patients (98%) had an Eastern Cooperative Oncology Group Performance Status of 0 or 1.Butylscopolamine bromide was given to 382 patients (80%), and a sedative was given to 460 (96%) patients. Median observation time was 74 s (range, 16-362 s), resulting in a mean of 9.0 usable images per patient. However, photographs of the right and left pyriform sinuses were consistently poor. Ordered logistic regression analysis showed that quality images were positively correlated with increased patient age. CONCLUSIONS: Transoral endoscopic examination was possible in most patients for screening of the head and neck. However, results were poor in the pyriform sinuses, indicating that additional improvements of examination methods and instruments are needed to enhance screening accuracy.


Subject(s)
Endoscopy, Gastrointestinal/statistics & numerical data , Narrow Band Imaging , Natural Orifice Endoscopic Surgery , Pharyngeal Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Analysis of Variance , Cross-Sectional Studies , Early Detection of Cancer/methods , Endoscopy, Gastrointestinal/methods , Female , Head and Neck Neoplasms/diagnosis , Humans , Logistic Models , Male , Middle Aged , Mouth , Pharyngeal Neoplasms/pathology , Young Adult
9.
Intern Med ; 51(16): 2231-4, 2012.
Article in English | MEDLINE | ID: mdl-22892510

ABSTRACT

Severe hypomagnesemia is a serious clinical condition. Proton pump inhibitor (PPI) induced hypomagnesemia has been recognized since 2006. In March 2011 the U.S. Food and Drug Administration advised that long-term use of PPI can induce hypomagnesemia. We report the first Japanese case of hypomagnesemia associated with chronic use of PPIs in a 64-year-old man hospitalized for nausea, bilateral ankle arthritis, and tremor of the extremities who had convulsions 3 days after admission. Blood analysis showed severe hypomagnesemia. He had been taking rabeprazole (10 mg/day) for 5 years. After stopping rabeprazole and correcting the electrolytes imbalances, his symptoms improved without recurrence.


Subject(s)
2-Pyridinylmethylsulfinylbenzimidazoles/adverse effects , Magnesium/blood , Proton Pump Inhibitors/adverse effects , 2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use , Gastroesophageal Reflux/chemically induced , Humans , Magnesium Deficiency/chemically induced , Male , Middle Aged , Proton Pump Inhibitors/therapeutic use , Rabeprazole
10.
Gastric Cancer ; 15(2): 170-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22407064

ABSTRACT

BACKGROUND: In biopsy specimens with low grade adenomas, it is often difficult to identify the presence of high grade adenomas or early carcinomas and low grade adenomas preoperatively, and clear guidelines have not yet been defined for the applicability of endoscopic treatment to low grade adenomas identified in biopsy specimens. METHODS: We aimed to clarify the usefulness of magnifying endoscopy with narrow band imaging (NBI) compared to conventional white light endoscopy for diagnosing actual high grade adenomas or early carcinomas with low grade adenomas, using the VS (microvascular pattern [V] and microsurface pattern [S]) classification for low grade adenomas in biopsy specimens. The study cohort consisted of 135 patients who were diagnosed with low grade adenomas in preoperative biopsy specimens and received endoscopic submucosal dissection. RESULTS: In the elevated type of lesion, magnifying endoscopy with NBI diagnosed high grade adenomas or early carcinomas at a higher sensitivity and specificity than conventional white light endoscopy (82.4 vs. 70.6%, P = 0.391, 97.3 vs. 54.7%, P < 0.0001). In the depressed macroscopic type of lesion, magnifying endoscopy with NBI also diagnosed high grade adenomas or early carcinomas at a higher sensitivity (95.5 vs. 68.2%, P = 0.0459) than conventional white light endoscopy. Although the specificity was high, at 100%, the difference when compared to conventional white light endoscopy was not significant (100 vs. 100%, P > 0.99). CONCLUSIONS: For low grade adenomas in biopsy specimens, it is vital to take sufficient consideration of endoscopic findings and not take action based only on the biopsy results. If a decision is made using the VS classification with magnifying endoscopy with NBI, actual high grade adenomas or early carcinomas can be differentiated from low grade adenomas so that endoscopic treatment can be performed more strictly.


Subject(s)
Adenoma/pathology , Early Detection of Cancer/methods , Endoscopy, Gastrointestinal/methods , Neoplasm Grading/methods , Stomach Neoplasms/pathology , Aged , Biopsy/methods , Female , Humans , Male , Preoperative Period
11.
Int J Colorectal Dis ; 26(11): 1453-62, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21674139

ABSTRACT

BACKGROUND: Although adrenomedullin (AM) is known to ameliorate inflammatory processes, few data exist regarding the effect of AM on inflammatory colitis. Therefore, we examined the effect of AM on inflammatory response in vitro and in vivo colitis model. METHODS: In mice experimental colitis induced by 3% dextran sulfate sodium (DSS) in drinking water for 7 days, AM with 225-900 µg/kg in 0.5 ml of saline or saline alone were given intraperitoneally once a day. In the in vitro experiment, we determined the cytokine response in THP-1 cell activated by lipopolysaccharide with or without AM of 10 nM. Additionally, we performed wound healing assay in Caco-2 cell interfered by DSS with or without AM of 100 nM. RESULTS: In the colitis model, AM significantly reduced the disease activity index, histological score, and local production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in accordance with reduction of serum amyloid A levels. Secretion of TNF-α in lipopolysaccharide-stimulated THP-1 cells was significantly reduced in the presence of AM. The distance of wound healing interfered by 0.25% DSS was significantly improved in the presence of AM of 100 nM. CONCLUSIONS: These results demonstrate that AM could ameliorate DSS-induced experimental colitis possibly through suppression of systemic and local production of cytokines such as TNF-α, associated with acceleration of ulcer reepithelialization and colon tissue regeneration.


Subject(s)
Adrenomedullin/therapeutic use , Colitis/drug therapy , Inflammation/drug therapy , Adrenomedullin/pharmacology , Animals , Body Weight/drug effects , Cell Line , Cell Movement/drug effects , Colitis/chemically induced , Colitis/complications , Colon/drug effects , Colon/enzymology , Colon/pathology , Cytokines/biosynthesis , Dextran Sulfate , Epithelium/drug effects , Epithelium/pathology , Humans , Inflammation/complications , Inflammation/pathology , Inflammation Mediators/metabolism , Male , Mice , Mice, Inbred BALB C , Peroxidase/metabolism , Serum Amyloid A Protein/metabolism , Ulcer/complications , Ulcer/pathology , Up-Regulation/drug effects
12.
J Gastroenterol ; 45(11): 1163-71, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20533066

ABSTRACT

BACKGROUND: Iron overload syndromes include a wide spectrum of genetic and acquired conditions. Recent studies suggest suppressed hepcidin synthesis in the liver to be the molecular basis of hemochromatosis. However, a liver with acquired iron overload synthesizes an adequate amount of hepcidin. Thus, hepcidin could function as a biochemical marker for differential diagnosis of iron overload syndromes. METHODS: We measured serum iron parameters and hepcidin-25 levels followed by sequencing HFE, HJV, HAMP, TFR2, and SLC40A1 genes in 13 Japanese patients with iron overload syndromes. In addition, we performed direct measurement of serum hepcidin-25 levels using liquid chromatography-tandem mass spectrometry in 3 Japanese patients with aceruloplasminemia and 4 Italians with HFE hemochromatosis. RESULTS: One patient with HJV hemochromatosis, 2 with TFR2 hemochromatosis, and 3 with ferroportin disease were found among the 13 Japanese patients. The remaining 7 Japanese patients showed no evidence for genetic basis of iron overload syndrome. As far as the serum hepcidin-25 was concerned, seven patients with hemochromatosis and 3 with aceruloplasminemia showed markedly decreased serum hepcidin-25 levels. In contrast, 3 patients with ferroportin disease and 7 with secondary iron overload syndromes showed serum hepcidin levels parallel to their hyperferritinemia. Patients with iron overload syndromes were divided into 2 phenotypes presenting as low and high hepcidinemia. These were then associated with their genotypes. CONCLUSION: Determining serum hepcidin-25 levels may aid differential diagnosis of iron overload syndromes prior to genetic analysis.


Subject(s)
Antimicrobial Cationic Peptides/blood , Hemochromatosis/diagnosis , Iron Overload/diagnosis , Adult , Aged , Aged, 80 and over , Biomarkers , Ceruloplasmin/deficiency , Ceruloplasmin/genetics , Chromatography, Liquid/methods , Diagnosis, Differential , Female , Genotype , Hemochromatosis/genetics , Hepcidins , Humans , Iron Metabolism Disorders/diagnosis , Iron Metabolism Disorders/genetics , Iron Overload/genetics , Japan , Male , Middle Aged , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/genetics , Receptors, Transferrin/genetics , Tandem Mass Spectrometry/methods
13.
Intern Med ; 49(9): 809-15, 2010.
Article in English | MEDLINE | ID: mdl-20453399

ABSTRACT

OBJECTIVE: This study evaluated the current state of patients with Wilson disease in central Japan. PATIENTS AND METHODS: Between 1999 and 2007, 30 patients were diagnosed as having Wilson disease with an International Diagnostic Score of 4 or more. The phenotypes, genotypes and post-diagnostic courses of these patients were analyzed. RESULTS: Twenty-six patients had ATP7B mutations responsible for Wilson disease. Four patients had a single mutant chromosome. There were 2 major mutations of 2333 G>T and 2871 delC (40%), and 6 novel mutations (13%) in our patients. The first clinical manifestation was the hepatic form in 22, neurological form in 5, and hemolysis in 3 patients. The hepatic form was diagnosed around the age of 13 years, followed by neurological complication with a time lag of 9 years. Thus, some patients, especially patients with the neurological form, did not undergo early diagnostic tests including ATP7B analysis. During the post-diagnosis period, 3 patients were hospitalized for recurrent liver disease, and 2 patients committed suicide. One female patient died from acute hepatic failure associated with encephalopathy after fertilization therapy, while 2 male patients recovered from encephalopathy-free, prolonged hepatic failure after noncompliance with drug therapy. The King's Scores for liver transplantation were below the cut-off in both cases. CONCLUSION: To minimize delayed diagnosis, ceruloplasmin determination and ATP7B analysis may be recommended to patients showing hepatic damage of unknown etiology. At gene diagnosis, appropriate management of patients including compliance education and emotional care to prevent suicide might be important.


Subject(s)
Cation Transport Proteins/genetics , Hepatolenticular Degeneration/epidemiology , Hepatolenticular Degeneration/genetics , Liver Failure, Acute/mortality , Suicide, Attempted/statistics & numerical data , Adolescent , Adult , Age Distribution , Chelation Therapy/methods , Child , Cohort Studies , Delayed Diagnosis , Disease Progression , Female , Gene Expression Regulation , Genetic Testing , Hepatolenticular Degeneration/therapy , Humans , Incidence , Japan/epidemiology , Liver Failure, Acute/diagnosis , Male , Prognosis , Psychotic Disorders/diagnosis , Psychotic Disorders/epidemiology , Retrospective Studies , Risk Assessment , Sex Distribution , Survival Rate , Young Adult
14.
Scand J Gastroenterol ; 45(10): 1232-7, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20491539

ABSTRACT

OBJECTIVE: Although many mutations of the Wilson's disease (WD) gene (ATP7B) have been reported, few data exist regarding the occurrence of fulminant hepatic failure (FHF). We sought to determine if genotypic assignment according to type of protein-product could be related to the prevalence of FHF among patients with WD. MATERIAL AND METHODS: We performed gene analysis in Japanese patients with WD as well as genotype-phenotype analysis in 51 patients. We divided genotypes into two groups according to type of ATP7B product: truncated group [T] consisted of two truncated alleles including nonsense, insertion, deletion, or splice site mutation, and missense group [M] consisted of one or two missense alleles. We also divided phenotypes into two groups: [FHF] group and [non-FHF] group. RESULTS: We were able to determine genotype in 42 patients. Genotypically, 11 patients were assigned to [T] group and 31 to [M] group. Phenotypically, 4 patients were [FHF] and 38 were [non-FHF]. All patients in [FHF] group belonged to [T] group. The prevalence of [FHF] in [T] group was 36.4% and was significantly higher than in [M] group (p < 0.003). CONCLUSIONS: These results demonstrated that genotypes for truncation of ATP7B are associated with high prevalence of FHF.


Subject(s)
Adenosine Triphosphatases/genetics , Cation Transport Proteins/genetics , Hepatolenticular Degeneration/genetics , Liver Failure, Acute/epidemiology , Liver Failure, Acute/genetics , Mutation , Adolescent , Alleles , Base Sequence , Biomarkers/metabolism , Child , Codon, Nonsense , Copper-Transporting ATPases , Female , Genotype , Humans , Japan/epidemiology , Male , Mutagenesis, Insertional , Mutation, Missense , Pedigree , Phenotype , Prevalence , Sequence Deletion
15.
Cancer Sci ; 101(7): 1686-94, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20487262

ABSTRACT

Type I interferon (IFN) protein is a cytokine with pleiotropic biological functions that include induction of apoptosis, inhibition of angiogenesis, and immunomodulation. We have demonstrated that intratumoral injection of an IFN-alpha-expressing adenovirus effectively induces cell death of cancer cells and elicits a systemic tumor-specific immunity in several animal models. On the other hand, reports demonstrated that an elevation of IFN in the serum following an intramuscular delivery of a vector is able to activate antitumor immunity. In this study, we compared the intratumoral and systemic routes of IFN gene transfer with regard to the effect and safety of the treatment. Intratumoral injection of an IFN-alpha adenovirus effectively activated tumor-responsive lymphocytes and caused tumor suppression not only in the gene-transduced tumors but also in distant tumors, which was more effective than the intravenous administration of the same vector. The expression of co-stimulatory molecules on CD11c(+) cells isolated from regional lymph nodes was enhanced by IFN gene transfer into the tumors. Systemic toxicity such as an elevation of hepatic enzymes was much lower in mice treated by intratumoral gene transfer than in those treated by systemic gene transfer. Our data suggest that the intratumoral route of the IFN vector is superior to intravenous administration, due to the effective induction of antitumor immunity and the lower toxicity.


Subject(s)
Colonic Neoplasms/immunology , Gene Transfer Techniques , Interferon-alpha/genetics , Kidney Neoplasms/immunology , Adenoviridae/genetics , Animals , CD11c Antigen/genetics , Cell Death , Cell Line, Tumor , Colonic Neoplasms/pathology , DNA Primers , Genetic Vectors , Interferon-alpha/blood , Interferon-alpha/therapeutic use , Kidney Neoplasms/pathology , Mice , Mice, Inbred BALB C , RNA, Neoplasm/genetics , Reverse Transcriptase Polymerase Chain Reaction , Safety
16.
World J Gastroenterol ; 15(36): 4587-92, 2009 Sep 28.
Article in English | MEDLINE | ID: mdl-19777620

ABSTRACT

We report a case of two pseudolymphomas of the liver in a 63-year-old Japanese woman with primary biliary cirrhosis. One of the lesions was found incidentally during a medical examination, presenting as a 10 mm hypodense nodule that revealed hyperdensity in the early phase and hypodensity in the late phase in computed tomography (CT) after injection of contrast medium. Retrospectively, the 10 mm nodule had first been discovered as a 4 mm nodule during CT 4 years previously. Superparamagnetic iron oxide-enhanced MRI revealed another 4 mm hyperintense nodule in segment 6 in addition to the 10 mm hyperintense nodule in segment 7. CT during arterial portography revealed two hypointense nodules. Findings with other imaging modalities such as ultrasonography, magnetic resonance imaging, and hepatic angiography were consistent with hepatocellular carcinoma. A right posterior segmentectomy was performed, and the lesions were microscopically diagnosed as pseudolymphoma. To the best of our knowledge, only 31 other cases of this disease have ever been reported, with a highly asymmetrical male:female ratio of 1:9.7. Although we could find only one case of transformation of hepatic pseudolymphoma into lymphoma in the liver, the exact nature of development from benign pseudolymphoma to malignant lymphoma is still not fully understood and cases of hepatic lymphoma need to be followed carefully.


Subject(s)
Liver Cirrhosis, Biliary/complications , Liver Diseases/diagnosis , Pseudolymphoma/diagnosis , Antigens, CD20/metabolism , B-Lymphocytes/metabolism , CD3 Complex/metabolism , Female , Humans , Japan , Liver/pathology , Liver Diseases/etiology , Magnetic Resonance Imaging , Middle Aged , Pseudolymphoma/etiology , T-Lymphocytes/metabolism , Tomography, X-Ray Computed
17.
Clin Chim Acta ; 399(1-2): 64-8, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18848826

ABSTRACT

BACKGROUND: Familial hypobetalipoproteinemia (FHBL) is a hereditary disorder characterized by decreased plasma concentrations of low-density lipoprotein cholesterol. The best-characterized causes of FHBL are apolipoprotein B (apoB) gene mutations, which produce truncated apoB proteins. Fatty liver is thought to be frequent in FHBL, owing to impaired secretion of very-low-density lipoprotein from the liver. Homozygotes for FHBL present with extremely low concentrations of plasma lipids, and may suffer from deficiencies of fat-soluble vitamins. The objectives of this study were to identify apoB-defective FHBL subjects and investigate fatty liver in Japanese population. METHODS: We screened 14 hypocholesterolemic subjects for apoB gene mutations by PCR-SSCP and performed liver ultrasonography in a Japanese population. RESULTS: We identified an apoB-82 homozygote in one subject and an apoB-13.7 heterozygote in another subject. Four of 6 individuals with FHBL presented with fatty liver in those 2 FHBL families. Liver biopsy of the apoB-13.7 heterozygote, which had obesity and insulin resistance, showed severe fatty liver. The apoB-82 homozygote was asymptomatic with fat-soluble vitamin concentrations being normal, possibly due to spared secretion of apoB-48 from the intestine and increased plasma concentrations of high-density lipoprotein cholesterol. CONCLUSION: ApoB gene mutations might not be rare and that fatty liver might be frequent in Japanese FHBL.


Subject(s)
Apolipoproteins B/genetics , Asian People/genetics , Fatty Liver/genetics , Hypobetalipoproteinemias/genetics , Mutation/genetics , Adult , Aged , Apolipoproteins B/metabolism , Base Sequence , Cholesterol, LDL/genetics , Cholesterol, LDL/metabolism , Fatty Liver/diagnostic imaging , Fatty Liver/metabolism , Fatty Liver/pathology , Female , Genotype , Humans , Hypobetalipoproteinemias/diagnostic imaging , Hypobetalipoproteinemias/metabolism , Hypobetalipoproteinemias/pathology , Insulin Resistance/genetics , Male , Middle Aged , Obesity/genetics , Ultrasonography
19.
Nihon Shokakibyo Gakkai Zasshi ; 104(12): 1772-80, 2007 Dec.
Article in Japanese | MEDLINE | ID: mdl-18057856

ABSTRACT

A 50-year-old man was admitted because of increasing massive ascites. While lymphoma cells (diffuse large B-cell lymphoma: DLBCL) were detected in the ascites, pleural effusion, cerebrospinal fluid and bone marrow, no tumor masses other than a submucosal lymphoma lesion in the stomach only 1 cm in diameter were identified. The patient was treated with chemotherapy including rituximab (R-CHOP-ESHAP) and injection of methotrexate and dexamethasone into the medullary cavity as well as radiation to the whole brain, and achieved complete remission 4 months later. The present case suggests that DLBCL can initially manifest as a form of effusion lymphoma with minimum solid tumor component. The distinctive clinical features of Japanese patients with primary effusion lymphoma are also reviewed.


Subject(s)
Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Primary Effusion/diagnosis , Ascites/complications , Diagnosis, Differential , Humans , Lymphoma, Primary Effusion/complications , Male , Middle Aged , Stomach Neoplasms/pathology
20.
Biosci Biotechnol Biochem ; 71(9): 2198-205, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17827685

ABSTRACT

We estimated the nutritional availability of selenium (Se) in Se-enriched Kaiware radish sprouts (SeRS) by the tissue Se deposition and glutathione peroxidase (GPX) activity of rats administered the sprouts, and examined the effect of SeRS on the formation of aberrant crypt foci (ACF) in the colon of mice administered 1,2-dimethylhydrazine (DMH) to evaluate anti-tumor activity. Male weanling Wistar rats were divided into seven groups and fed a Se-deficient basal diet or the basal diet supplemented with 0.05, 0.10, or 0.15 microg/g of Se as sodium selenite or SeRS for 28 d. Supplementation with Se dose-dependently increased serum and liver Se concentrations and GPX activities, and the selenite-supplemented groups showed a higher increase than the SeRS-supplemented groups. The nutritional availability of Se in SeRS was estimated to be 33 or 64% by slope ratio analysis. Male 4-week-old A/J mice were divided into seven groups and fed a low Se basal diet or the basal diet supplemented with selenite, SeRS, or selenite + non-Se-enriched radish sprouts (NonSeRS) at a level of 0.1 or 2.0 microg Se/g for 9 weeks. After 1 week of feeding, all mice were given six subcutaneous injections of DMH (20 mg/kg) at 1-week intervals. The average number of ACF formed in the colon of mice fed the basal diet was 4.3. At a supplementation level of 0.1 mug Se/g, only SeRS significantly inhibited ACF formation. At a supplementation level of 2.0 microg Se/g, both selenite and SeRS significantly inhibited ACF formation. The addition of NonSeRS to the selenite-supplemented diets tended to inhibit ACF formation, but this was not statistically significant. These results indicate that SeRS shows lower nutritional availability but higher anti-tumor activity than selenite.


Subject(s)
Neoplasms/diet therapy , Neoplasms/pathology , Raphanus/chemistry , Selenium/metabolism , Selenium/therapeutic use , Animals , Glutathione Peroxidase/metabolism , Male , Mice , Nutritive Value , Rats
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