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Article: Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary.

Nagahashi, Masayuki / Ajioka, Yoichi / Lang, Istvan / Szentirmay, Zoltan / Kasler, Miklos / Nakadaira, Hiroto / Yokoyama, Naoyuki / Watanabe, Gen / Nishikura, Ken / Wakai, Toshifumi / Shirai, Yoshio / Hatakeyama, Katsuyoshi / Yamamoto, Masaharu

World journal of gastroenterology

2007 Volume 14, Issue 1, Page(s) 70–75

Abstract: ... of gallbladder carcinoma: 22 Japanese and 20 Hungarian cases. p53 mutations at exons 5 to 8 and K-ras mutations ... of 6 Hungarian cases; the difference was marginally significant (0/11 vs 2/6, P = 0.110). K-ras ...

Abstract	Aim: To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary. Methods: We examined 42 cases of gallbladder carcinoma: 22 Japanese and 20 Hungarian cases. p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of five-microsatellite markers (BAT-25, BAT-26, D2S123, D5S346, and D17S250). Results: Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases (11/22 vs 6/18, P = 0.348). Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant (0/11 vs 2/6, P = 0.110). K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 (42.1%) Japanese cases were MSI-high (presence of novel peaks in more than one of the five loci analyzed), whereas only 1 of 15 (6.7%) Hungarian cases was MSI-high (P = 0.047). Conclusion: It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.
MeSH term(s)	Aged ; Aged, 80 and over ; Female ; Gallbladder Neoplasms/ethnology ; Gallbladder Neoplasms/genetics ; Genes, ras/genetics ; Genetic Predisposition to Disease/ethnology ; Humans ; Hungary/epidemiology ; Incidence ; Japan/epidemiology ; Male ; Microsatellite Instability ; Middle Aged ; Tumor Suppressor Protein p53/genetics
Chemical Substances	Tumor Suppressor Protein p53
Language	English
Publishing date	2007-05-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.14.70
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Article: Infrequent K-ras codon 12 mutation in serrated adenomas of human colorectum.

Ajioka, Y / Watanabe, H / Jass, J R / Yokota, Y / Kobayashi, M / Nishikura, K

Gut

1998 Volume 42, Issue 5, Page(s) 680–684

Abstract: ... investigated.: Aims: To determine the frequency of K-ras mutation in serrated adenoma.: Methods ... The frequency of K-ras codon 12 point mutation in 20 serrated adenomas, five atypical hyperplastic polyps, and ... 11.4 mm) and polypoid, K-ras codon 12 point mutation was detected in only one of the 20 (5 ...

Abstract	Background: Serrated adenoma is a new morphological subtype of colorectal adenoma. The lesion provides a distinct morphological route to carcinoma, but the underlying genetic changes have not yet been investigated. Aims: To determine the frequency of K-ras mutation in serrated adenoma. Methods: The frequency of K-ras codon 12 point mutation in 20 serrated adenomas, five atypical hyperplastic polyps, and 58 sporadic polypoid adenomas was investigated by nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Results: Although most of the serrated adenomas were large (average size 11.4 mm) and polypoid, K-ras codon 12 point mutation was detected in only one of the 20 (5%), which is a significantly lower frequency than that in sporadic polypoid adenomas (18/60; 30%) (p = 0.017). No mutation was detected in the atypical hyperplastic polyps. Three of 20 (15%) serrated adenomas contained a focus of carcinoma in situ, indicating their malignant potential and the existence of a serrated adenoma-carcinoma sequence, but no mutation was detected in the foci of carcinoma in situ. Conclusions: K-ras mutation is uncommon in serrated adenomas, indicating a different spectrum of genetic alterations in these lesions from those in typical polypoid sporadic adenomas. This subtype of colorectal adenoma represents a new genetic pathway in the histogenesis of colorectal carcinoma.
MeSH term(s)	Adenoma/genetics ; Adenoma/pathology ; Codon/genetics ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Genes, ras ; Humans ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length
Chemical Substances	Codon
Language	English
Publishing date	1998-05
Publishing country	England
Document type	Journal Article
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gut.42.5.680
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Article ; Online: Entirely zero-contrast diagnosis and revascularization for bilateral stenotic iliac disease with advanced chronic kidney disease: a case report.

Wakabayashi, Kohei / Suzuki, Toshiaki / Sato, Chisato / Nishikura, Tenjin

European heart journal. Case reports

2023 Volume 7, Issue 8, Page(s) ytad338

Abstract: Background: Peripheral artery disease (PAD) is usually diagnosed with non-invasive arterial testing methods such as Doppler ultrasound or computed tomography angiography and treated with revascularization using contrast media, which increases the risk ... ...

Abstract	Background: Peripheral artery disease (PAD) is usually diagnosed with non-invasive arterial testing methods such as Doppler ultrasound or computed tomography angiography and treated with revascularization using contrast media, which increases the risk of contrast nephropathy and the need for subsequent renal replacement therapy, especially in patients with advanced chronic kidney disease (CKD). Therefore, it is important to identify a worthy alternative strategy for use in high-risk patients. Case summary: We present the case of a 79-year-old man with bilateral claudication and advanced CKD. The patient had a high risk of sustained reduction in renal function and requirement of renal replacement therapy in the event that contrast media was used. Therefore, we planned a zero-contrast strategy for diagnosis and treatment. The case was diagnosed as bilateral stenotic iliac disease with non-contrast magnetic resonance angiography. Zero-contrast intervention was conducted successfully under magnetic resonance angiography and intra-vascular ultrasound guidance, resulting in an excellent clinical outcome and avoidance of worsening renal function. Discussion: This zero-contrast strategy appears to be a viable alternative to angiography using contrast for diagnosis and treatment in patients with PAD and advanced CKD where contrast use is relatively contraindicated.
Language	English
Publishing date	2023-07-21
Publishing country	England
Document type	Case Reports
ISSN	2514-2119
ISSN (online)	2514-2119
DOI	10.1093/ehjcr/ytad338
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Article ; Online: Oesophageal cancer: RNA editing of SLC22A3 mRNAs: causative relevance to familial ESCC?

Nishikura, Kazuko

Nature reviews. Gastroenterology & hepatology

2017 Volume 14, Issue 10, Page(s) 569–570

MeSH term(s)	Carcinoma, Squamous Cell ; Esophageal Neoplasms ; Humans ; RNA Editing ; RNA, Messenger
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2017-07-26
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2493722-8
ISSN	1759-5053 ; 1759-5045
ISSN (online)	1759-5053
ISSN	1759-5045
DOI	10.1038/nrgastro.2017.102
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Zs.A 6020: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 97: Show issues

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Article ; Online: A-to-I editing of coding and non-coding RNAs by ADARs.

Nishikura, Kazuko

Nature reviews. Molecular cell biology

2016 Volume 17, Issue 2, Page(s) 83–96

Abstract: Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA. This A-to-I editing occurs not only in protein-coding regions of mRNAs, but also frequently in non-coding regions that contain inverted Alu repeats. Editing ... ...

Abstract	Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA. This A-to-I editing occurs not only in protein-coding regions of mRNAs, but also frequently in non-coding regions that contain inverted Alu repeats. Editing of coding sequences can result in the expression of functionally altered proteins that are not encoded in the genome, whereas the significance of Alu editing remains largely unknown. Certain microRNA (miRNA) precursors are also edited, leading to reduced expression or altered function of mature miRNAs. Conversely, recent studies indicate that ADAR1 forms a complex with Dicer to promote miRNA processing, revealing a new function of ADAR1 in the regulation of RNA interference.
MeSH term(s)	Adenosine/metabolism ; Adenosine Deaminase/genetics ; Adenosine Deaminase/metabolism ; Alu Elements ; Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Genome ; Humans ; Inosine/metabolism ; Isoenzymes/genetics ; Isoenzymes/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; RNA Editing ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Ribonuclease III/genetics ; Ribonuclease III/metabolism ; Signal Transduction
Chemical Substances	Isoenzymes ; MicroRNAs ; RNA, Messenger ; Inosine (5A614L51CT) ; Ribonuclease III (EC 3.1.26.3) ; Adenosine Deaminase (EC 3.5.4.4) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2016-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2031313-5
ISSN	1471-0080 ; 1471-0072
ISSN (online)	1471-0080
ISSN	1471-0072
DOI	10.1038/nrm.2015.4
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Zs.A 5446: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: A Case of Suspected T-cell Intravascular Lymphoma Mimicking Multiple Hepatic Abscesses and Adult-Onset Still's Disease.

Ohjino, Yutaka / Nishikawa, Kasumi / Nishikura, Nozomi / Sano, Chiaki / Ohta, Ryuichi

Cureus

2023 Volume 15, Issue 10, Page(s) e47534

Abstract: Diagnosing hyperferritinemia can be challenging due to the nonspecific nature of symptoms and various potential causes. This case report discusses the intricacies faced when diagnosing an elderly individual with hyperferritinemia, which eventually led to ...

Abstract	Diagnosing hyperferritinemia can be challenging due to the nonspecific nature of symptoms and various potential causes. This case report discusses the intricacies faced when diagnosing an elderly individual with hyperferritinemia, which eventually led to a specific diagnosis. An elderly patient presented with two months of fatigue, fever, and malaise, initially receiving several diagnoses. Despite some treatments, the patient's condition worsened, prompting further evaluation. Further investigation revealed a rare diagnosis. The progression of the disease led to the decision of palliative care. This case emphasizes the challenges in diagnosing elderly individuals and the importance of comprehensive follow-up and broad differential diagnosis. The need for a thorough investigation in the face of specific indicators is underscored. The patient's non-response to certain treatments required the consideration of less common conditions in the differential diagnosis. The case offers insights into addressing treatment suitability and making necessary adjustments. The situation underscores the need for careful evaluation, especially in unusual presentations, and the importance of timely conversations about care options. Lessons from this case assist healthcare professionals in understanding and managing intricate presentations in the elderly.
Language	English
Publishing date	2023-10-23
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.47534
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Article: Diagnosing Infectious Hepatic Cysts in an Older Patient With Multiple Skin Masses: A Case Report.

Murakami, Kotaro / Nishikura, Nozomi / Mishiro, Tsuyoshi / Sano, Chiaki / Ohta, Ryuichi

Cureus

2023 Volume 15, Issue 3, Page(s) e35993

Abstract: Among the most severe complications of hepatic cystic diseases is infectious hepatic cysts (IHCs). IHCs may appear mainly among immunocompromised hosts. However, older patients have a variety of immunological conditions. The detection of the factors ... ...

Abstract	Among the most severe complications of hepatic cystic diseases is infectious hepatic cysts (IHCs). IHCs may appear mainly among immunocompromised hosts. However, older patients have a variety of immunological conditions. The detection of the factors suppressing immunity is essential for patients with IHCs. Herein, we present the case of an 86-year-old woman admitted to the emergency department with a fever. We suspected IHCs based on changes in abdominal ultrasound findings. After multiple follow-ups to determine the cause of the fever that was unresponsive to treatment, we discovered debris in the cyst that had not been present at the time of the initial presentation. The patient was subsequently treated with percutaneous transhepatic drainage and tazobactam/piperacillin. The investigation of the causes of immunosuppression clarified the multiple skin masses. The biopsy of the mass clarified diffuse large B cell lymphoma without lymph node swellings. Consecutive ultrasound can detect findings missed during the initial presentation and changes that occur within a short period. The detection of the causes of immunosuppression is essential even among older patients with IHCs for better care among older patients.
Language	English
Publishing date	2023-03-10
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.35993
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Article: Thrombocytopenia in Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis Indicating the Presence of Cytomegalovirus Infection: A Case Report.

Ohta, Ryuichi / Naito, Yumi / Nishikura, Nozomi / Inoue, Keita / Sano, Chiaki

Cureus

2023 Volume 15, Issue 5, Page(s) e38850

Abstract: Although cytomegalovirus (CMV) usually colonizes the human body without causing symptoms, CMV infections often develop in immunocompromised hosts. Immunosuppression can trigger CMV infection, and its prediction is essential; however, this is challenging ... ...

Abstract	Although cytomegalovirus (CMV) usually colonizes the human body without causing symptoms, CMV infections often develop in immunocompromised hosts. Immunosuppression can trigger CMV infection, and its prediction is essential; however, this is challenging without specific criteria. We present the case of an 87-year-old male patient who visited a rural community hospital with the chief complaint of persistent cough, productive of bloody sputum. Initially, the patient developed thrombocytopenia without any abnormalities of liver function; however, a positive myeloperoxidase antineutrophil cytoplasmic antibody (ANCA) test and the presence of alveolar hemorrhage and glomerulonephritis confirmed ANCA-associated vasculitis. The patient's symptoms and thrombocytopenia resolved transiently after treatment with prednisolone and rituximab. However, the recurrence of thrombocytopenia and the appearance of urinary intracytoplasmic inclusion bodies during the treatment course were investigated using an antigenemia test, which ultimately confirmed CMV viremia. Valganciclovir treatment resolved all the symptoms. This case report showed that thrombocytopenia might indicate the presence of CMV infection in ANCA-associated vasculitis and that intracytoplasmic inclusion bodies in immunosuppressed patients require investigation of CMV infection for effective treatment.
Language	English
Publishing date	2023-05-10
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.38850
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Article: Different amounts of K-ras mutant epithelial cells in pancreatic carcinoma and mass-forming pancreatitis.

Matsubayashi, H / Watanabe, H / Ajioka, Y / Nishikura, K / Yamano, M / Seki, T / Saito, T / Matsubayashi, T

Pancreas

2000 Volume 21, Issue 1, Page(s) 77–85

Abstract: ... pancreatitis (MFP)" is difficult. We analyzed the amount, ductal level, and K-ras mutation of ductal ... extracted from microdissected epithelial foci were analyzed for K-ras codon 12 mutation ... about 4 and 15 times more than those of MFP, respectively. The frequency of K-ras mutation in hyperplastic ...

Abstract	Clinically, differential diagnosis of pancreatic carcinoma (PC) and so-called "mass-forming pancreatitis (MFP)" is difficult. We analyzed the amount, ductal level, and K-ras mutation of ductal hyperplasia and intraductal carcinoma in surgically resected cases of MFP (n = 18) and PC (n = 16). DNAs extracted from microdissected epithelial foci were analyzed for K-ras codon 12 mutation by nested polymerase chain reaction and restriction fragment length polymorphism. The histology of MFP showed severe destruction of exocrine tissue and pancreatic stones and/or protein plugs (72%, 13 of 18 cases) in mostly peripheral ducts. The average basal membrane lengths of nonpapillary and papillary hyperplasia in cases of carcinoma were about 4 and 15 times more than those of MFP, respectively. The frequency of K-ras mutation in hyperplastic foci increased from nonpapillary [six (27%) of 22] to papillary foci [16 (64%) of 25] in K-ras mutant PCs, but there was no difference between nonpapillary [one (6%) of 18] and papillary foci (none of 19) in K-ras wild-type PCs, and also between nonpapillary (none of 24) and papillary foci [one (7%) of 14] in MFPs.
MeSH term(s)	Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Adenocarcinoma/surgery ; Adult ; Aged ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/pathology ; Carcinoma, Pancreatic Ductal/surgery ; Cell Membrane/pathology ; Chronic Disease ; Codon ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Female ; Genes, ras ; Humans ; Hyperplasia ; Male ; Middle Aged ; Mutation ; Pancreatic Ducts/metabolism ; Pancreatic Ducts/pathology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/surgery ; Pancreatitis/genetics ; Pancreatitis/pathology ; Pancreatitis/surgery ; Retrospective Studies
Chemical Substances	Codon
Language	English
Publishing date	2000-02-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	632831-3
ISSN	1536-4828 ; 0885-3177
ISSN (online)	1536-4828
ISSN	0885-3177
DOI	10.1097/00006676-200007000-00055
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Zs.A 2160: Show issues

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Article: Differences in mucus and K-ras mutation in relation to phenotypes of tumors of the papilla of vater.

Matsubayashi, H / Watanabe, H / Yamaguchi, T / Ajioka, Y / Nishikura, K / Kijima, H / Saito, T

Cancer

1999 Volume 86, Issue 4, Page(s) 596–607

Abstract: Background: To investigate their hypothesis that K-ras mutation is correlated with epithelial ... ordinary or metaplastic) and analyzed the tumors for K-ras mutation during tumorigenesis.: Methods ... MUC5AC, sialyl Lewis(a) (CA 19-9), HID-AB, and ConA III stainings. K-ras codon 12 mutation was detected ...

Abstract	Background: To investigate their hypothesis that K-ras mutation is correlated with epithelial metaplastic change, the authors classified tumors of the papilla of Vater histologically and according to mucin histochemistry as either intestinal type (complete or incomplete) or pancreaticobiliary type (ordinary or metaplastic) and analyzed the tumors for K-ras mutation during tumorigenesis. Methods: Fifty-two tumors of the papilla of Vater (5 adenomas, 24 carcinomas with adenoma component, and 23 carcinomas) obtained from surgical specimens were evaluated. The mucus phenotype was analyzed with MUC1, MUC2, MUC5AC, sialyl Lewis(a) (CA 19-9), HID-AB, and ConA III stainings. K-ras codon 12 mutation was detected by nested polymerase chain reaction (PCR)-restriction fragment length polymorphism and enriched PCR-enzyme-linked minisequence assay. Results: The presence of adenoma component and intramucosal tumor spreading in the ampulloduodenum was significantly higher in intestinal-type tumors (90%, 27 of 30 tumors, and 100%, 30 of 30 tumors, respectively) than in pancreaticobiliary-type tumors (9%, 2 of 22 tumors, and 23%, 5 of 22 tumors, respectively) (P < 0.0001). MUC2 expression was positive in intestinal-type tumors but not in pancreaticobiliary-type tumors. K-ras mutation rates for incomplete intestinal-type tumors (78%, 7 of 9) and metaplastic pancreaticobiliary-type tumors (64%, 7 of 11), which showed MUC5AC (gastric-type apomucin) expression in cytoplasm, were significantly higher than in complete intestinal-type tumors (33%, 6 of 21) and ordinary pancreaticobiliary-type tumors (18%, 2 of 11) (P = 0.01 and P = 0.03, respectively). In pancreaticobiliary-type tumors, K-ras mutation was more frequently recognized in tumors with ampullopancreatic duct tumor extension (75%, 3 of 4) than in those with ampullobiliary duct extension (0%, 0 of 6) (P = 0.01). Furthermore, sequences of K-ras codon 12 were common in 17 carcinomas with adenoma component that were analyzed for both adenoma and carcinoma. Conclusions: Tumors of the papilla of Vater can be classified histologically as either intestinal type or pancreaticobiliary type, and they have different features according to tumor location, association with adenoma, and MUC2 expression. Furthermore, K-ras mutation is supposed to be associated with tumors arising in the area from the ampulloduodenum to the ampullopancreatic duct, with metaplastic mucus occurring in both intestinal and pancreaticobiliary types.
MeSH term(s)	Adenoma/genetics ; Adenoma/pathology ; Aged ; Aged, 80 and over ; Amino Acid Sequence ; Ampulla of Vater ; Carcinoma/genetics ; Carcinoma/pathology ; Cell Transformation, Neoplastic/genetics ; Common Bile Duct Neoplasms/genetics ; Common Bile Duct Neoplasms/pathology ; DNA Mutational Analysis ; DNA, Neoplasm/analysis ; Female ; Genes, ras ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Molecular Sequence Data ; Mucus ; Polymerase Chain Reaction
Chemical Substances	DNA, Neoplasm
Language	English
Publishing date	1999-08-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
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