Biomedical subjects

Akihiro Yamaguchi

Publications and source records attributed to Akihiro Yamaguchi.

At least 19 recordsLinked to original sources

PubMed2006

Coverage of whole proteome by structural genomics observed through protein homology modeling database.

We have been developing FAMSBASE, a protein homology-modeling database of whole ORFs predicted from genome sequences. The latest update of FAMSBASE ( http://daisy.nagahama-i-bio.ac.jp/Famsbase/ ), which is based on the protein three-dimensional (3D) structures released by November 2003, contains modeled 3D structures for 368,724 open reading frames (ORFs) derived from genomes of 276 species, namely 17 archaebacterial, 130 eubacterial, 18 eukaryotic and 111 phage genomes. Those 276 genomes are predicted to have 734,193 ORFs in total and the current FAMSBASE contains protein 3D structure of approximately 50% of the ORF products. However, cases that a modeled 3D structure covers the whole part of an ORF product are rare. When portion of an ORF with 3D structure is compared in three kingdoms of life, in archaebacteria and eubacteria, approximately 60% of the ORFs have modeled 3D structures covering almost the entire amino acid sequences, however, the percentage falls to about 30% in eukaryotes. When annual differences in the number of ORFs with modeled 3D structure are calculated, the fraction of modeled 3D structures of soluble protein for archaebacteria is increased by 5%, and that for eubacteria by 7% in the last 3 years. Assuming that this rate would be maintained and that determination of 3D structures for predicted disordered regions is unattainable, whole soluble protein model structures of prokaryotes without the putative disordered regions will be in hand within 15 years. For eukaryotic proteins, they will be in hand within 25 years. The 3D structures we will have at those times are not the 3D structure of the entire proteins encoded in single ORFs, but the 3D structures of separate structural domains. Measuring or predicting spatial arrangements of structural domains in an ORF will then be a coming issue of structural genomics.

Amino Acid Sequence↗

PubMed2006

Impact of surveillance on survival of patients with initial hepatocellular carcinoma: a study from Japan.

BACKGROUND & AIMS: We investigated trends in the prediagnostic surveillance of patients in whom hepatocellular carcinoma (HCC) was diagnosed, and evaluated the impact of these trends on early detection of HCC and on patient survival. METHODS: We evaluated 1641 patients in whom HCC initially was diagnosed during the period of 1968 to 2004. Patients were grouped by the year of diagnosis: 1968-1980 (n = 151), 1981-1990 (n = 409), 1991-2000 (n = 754), and 2001-2004 (n = 324). They also were classified according to whether they were in surveillance and its context before the diagnosis of HCC: patients undergoing follow-up evaluation in our center (group A), those followed up and referred by a primary care physician (group B), and those not in surveillance (group C). RESULTS: The percentage of patients in groups A and B increased markedly over time. Early stage HCC was significantly more prevalent in groups A and B than in group C, and the frequency of early stage HCC increased sequentially. The patient survival rate was highest in group A, followed by that in groups B and C in that order; patient survival improved sequentially. CONCLUSIONS: The percentage of patients undergoing in-center surveillance or referred by a primary care physician increased, resulting in increased early detection of HCC and improved patient survival.

Adult↗

PubMed2006

Alternative splicing in human transcriptome: functional and structural influence on proteins.

Alternative splicing is a molecular mechanism that produces multiple proteins from a single gene, and is thought to produce variety in proteins translated from a limited number of genes. Here we analyzed how alternative splicing produced variety in protein structure and function, by using human full-length cDNAs on the assumption that all of the alternatively spliced mRNAs were translated to proteins. We found that the length of alternatively spliced amino acid sequences, in most cases, fell into a size shorter than that of average protein domain. We evaluated comprehensively the presumptive three-dimensional structures of the alternatively spliced products to assess the impact of alternative splicing on gene function. We found that more than half of the products encoded proteins which were involved in signal transduction, transcription and translation, and more than half of alternatively spliced regions comprised interaction sites between proteins and their binding partners, including substrates, DNA/RNA, and other proteins. Intriguingly, 67% of the alternatively spliced isoforms showed significant alterations to regions of the protein structural core, which likely resulted in large conformational change. Based on those findings, we speculate that there are a large number of cases that alternative splicing modulates protein networks through significant alteration in protein conformation.

Alternative Splicing↗

PubMed2006

Evaluation of pathological features of hepatocellular carcinoma by contrast-enhanced ultrasonography: comparison with pathology on resected specimen.

Features of hepatocellular carcinoma (HCC) observed by contrast-enhanced ultrasonography (CEUS) were compared to pathological features of corresponding resected HCC specimens, to evaluate the ability of CEUS to depict the pathological features of HCC. We investigated 50 HCC nodules that were treated by surgical resection. All nodules had been examined by CEUS with intravenous contrast agent (Levovist) before surgery. CEUS findings were divided into three phases for evaluation and classification of enhancement patterns: two vascular phases (arterial phase and portal venous phase) and the delayed phase. Pathological examination focused on differentiation and on the presence or absence of a tumor capsule, intratumoral septum, and intratumoral necrosis. All 21 nodules that showed a linear or annular vessel around the tumor margin in the arterial phase had capsular formation. Of the 27 nodules that showed heterogeneous perfusion in the portal venous phase, 21 (77.8%) had an intratumoral septum and 23 (85.2%) showed intratumoral necrosis. All nodules that were depicted as a defect with an unclear margin in the delayed phase were well-differentiated HCCs, whereas all nodules that were depicted as a defect with a clear margin were moderately or poorly differentiated HCCs. From our observations, the arterial, portal venous, and delayed phases of CEUS could reflect different pathological aspects of HCC. Some pathological characteristics of HCC might be evaluated preoperatively and non-invasively, by means of combined analysis of three phases of CEUS findings.

Adult↗

PubMed2006

Polymyositis associated with focal mesangial proliferative glomerulonephritis with depositions of immune complexes.

A 58-year-old man concurrently developed polymyositis (PM), interstitial lung disease, and nephrotic-range proteinuria. Renal biopsy revealed focal mesangial proliferative glomerulonephritis (mesPGN) with depositions of immunoglobulin and complements. A combination therapy of corticosteroid, intravenous immunoglobulin, and cyclosporine was found very effective for the patient. Glomerulonephritis associated with PM/dermatomyositis (DM) is rare. In our review of related literature, mesPGN was exclusively observed in polymyositis while membranous nephropathy in DM. The mechanism underlying the association between myositis and glomerulonephritis remains to be elucidated.

Glomerulonephritis↗

PubMed2006

Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: We conducted a prospective study to evaluate the significance of simultaneous measurement of 3 currently used tumor markers in the evaluation of tumor progression and prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Three tumor markers for HCC, alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), were measured in the same serum samples obtained from 685 patients at the time of initial diagnosis of HCC. Positivity for AFP >20 ng/dL, AFP-L3 >10% of total AFP, and/or DCP >40 mAU/mL was determined. In addition, tumor markers were measured after treatment of HCC. RESULTS: Of the 685 patients, 337 (55.8%) were positive for AFP, 206 (34.1%) were positive for AFP-L3, and 371 (54.2%) were positive for DCP. In a comparison of patients positive for only 1 tumor marker, patients positive for AFP-L3 alone had a greater number of tumors, whereas patients positive for DCP alone had larger tumors and a higher prevalence of portal vein invasion. When patients were compared according to the number of tumor markers present, the number of markers present clearly reflected the extent of HCC and patient outcomes. The number of markers present significantly decreased after treatment. CONCLUSIONS: Tumor markers AFP-L3 and DCP appear to represent different features of tumor progression in patients with HCC. The number of tumor markers present could be useful for the evaluation of tumor progression, prediction of patient outcome, and treatment efficacy.

Adult↗

PubMed2006

Detection method for genetically modified papaya using duplex PCR.

A simple and rapid method for the identification of genetically modified (GM) papaya, derived from Line 55-1, was developed by modifying the Japanese official PCR method. Genomic DNA was directly extracted from the fresh fruit without the lyophilization step, using a commercial silica-based kit. To develop a duplex PCR method which simultaneously detects the GM papaya-specific gene and the intrinsic papain gene, the papain 2-5'/3' (amplicon size; 184 bp) primer pair for the detection of the papain gene was newly designed within the region of the products (211 bp) amplified using the papain 1-5'/-3' primer pair adopted in the Japanese official PCR method. To detect the GM papaya-specific gene, the primer pair Nos C-5'/CaM N-3' described in the Japanese official method was used. The DNA sequences of the GM papaya gene and the intrinsic papain gene were co-amplified using the PCR method in a single tube. The developed duplex PCR method allows the simultaneous detection of the products by means of agarose gel electrophoresis or microchip electrophoresis. The proposed method for GM papaya identification is simple and rapid.

Carica↗

PubMed2006

[Detection of short tandem repeat (STR) polymorphisms by microchip electrophoresis for individual identification of cattle].

A simple and rapid detection of short tandem repeat (STR) markers was studied as a screening test for individual identification of cattle. DNAs were extracted from eight commercial beef samples by a proteinase K-boil method followed by purification with 2-propanol precipitation. Five STR markers, known to be highly polymorphic, were amplified by PCR and analyzed both by a conventional sequencing analysis (SEQ) and by a proposed microchip electrophoresis (MEP). Every marker revealed high polymorphism, such as 5-9 alleles in SEQ analysis, and 4-6 alleles in MEP analysis. This simple and rapid MEP analysis is expected to be an effective screening tool with use of confirmatory SEQ analysis.

Animal Identification Systems↗

PubMed2005

Attenuated phosphorylation of heat shock protein 27 correlates with tumor progression in patients with hepatocellular carcinoma.

Heat shock protein 27 (HSP27) is expressed at high levels in human hepatocellular carcinoma (HCC). We examined correlations of total HSP27 and serine phosphorylated (Ser-15, Ser-78, and Ser-82) HSP27 levels in HCC tissues with clinical and pathologic characteristics in 48 resected HCC specimens. The levels of total and Ser-phosphorylated HSP27 were evaluated by Western blot analysis. Immunohistochemical analysis of HSP27 expression was also performed on some samples. Phosphorylation of HSP27 was detected in all 48 HCC tissues. Levels of phosphorylated HSP27 were correlated inversely with tumor size, microvascular invasion of HCC, and tumor stage by TNM classification. In contrast, only microvascular invasion showed an inverse correlation with total HSP27 levels. The decrease in phosphorylated HSP27 in progressed HCC was also observed by immunohistochemistry. Levels of phosphorylated HSP27 gradually decreased in parallel with HCC progression. Our findings suggest that phosphorylated HSP27 may have a suppressive role in progression of human HCC.

Aged↗

PubMed2005

Structure and properties relationships for aromatic polyimides and their derived carbon membranes: experimental and simulation approaches.

The main objective of this study is to investigate the factors of the chemical structure and physical properties of rigid polyimides in determining the performance of derived carbon membranes through both the experimental and simulation methods. Four polyimides made of different dianhydrides were pyrolyzed at 550 and 800 degrees C under vacuum conditions. The resultant carbon membranes exhibit excellent gas separation performances beyond the traditional upper limit line for polymer membranes. The thermal stability and the fractional free volume (FFV) of polyimides were examined by a thermogravimetric analyzer and a density meter. The chain properties of polyimide, such as flatness, chain linearity, and mobility, were simulated using the Cerius(2) software. All above characterizations of polyimides were related to the microstructure and gas transport properties of the resultant carbon membranes. It was observed that the high FFV values and low thermal stability of polyimide produce carbon membranes with bigger pore and higher gas permeability at low pyrolysis temperatures. Therefore, polyimides with big thermally labile side groups should be preferred to prepare carbon membranes at low pyrolysis temperatures for high permeability applications. On the other side, since the flatness and in-plane orientation of precursors may lead carbon membranes to ordered structure, thus obtaining high gas selectivity, linear polyimides with more coplanar aromatic rings should be first choice to prepare carbon membranes at high pyrolysis temperatures for high selectivity applications. The location of the indan group also affects chain flatness and in-plane orientation. As a result, carbon membranes derived from the BTDA-DAI precursor have superior separation performance to those derived from Matrimid.

Journal Article↗

PubMed2005

Gallstone pancreatitis: positive correlation between severe pancreatitis and passed stone.

BACKGROUND/PURPOSE: Little is known about whether the severity of pancreatitis depends upon persistent stone impaction or stone passage into the duodenum, and the role of endoscopic sphincterotomy (ES) has remained controversial. METHODS: This study reviewed our experience of 183 patients with gallstone pancreatitis, with special attention paid to the relationship between the severity of pancreatitis, the severity of coexisting biliary pathology, and the outcome. RESULTS: Sixteen patients (9%) had severe pancreatitis (SP) and the remaining 167 (91%) had mild pancreatitis (MP). All of the SP patients had pancreatic necrosis, and 6 of them developed multiple organ failure (MOF). No SP patients had stones impacted at the papilla of Vater or persistent stones and purulent bile in the bile duct (severe cholangitis). Most SP patients (94%) had stones in the gallbladder alone, suggesting stone passage into the duodenum. Of the 167 MP patients, on the other hand, 58 (35%) had severe cholangitis. Four patients (25%) with SP died of MOF. There were four deaths in the MP group (2%) and all in patients with coexisting severe cholangitis, 2 of whom were in septic shock at the time of admission. CONCLUSIONS: None of the SP patients had severe cholangitis. The positive correlation between SP and passed stone suggests that early ES should not be advocated for SP patients. MP patients with coexisting severe cholangitis are likely to benefit from ES.

Cholangitis↗

PubMed2005

Repeat hepatectomy for recurrent colorectal metastases.

PURPOSE: To determine the risks and benefits of repeat hepatectomy for hepatic metastases from colorectal cancer. METHODS: During a recent 10-year-period, 106 patients underwent hepatectomy for hepatic metastases from colorectal cancer, in our hospital. Recurrence developed in the liver in 57 of these patients, 27 of whom underwent repeat hepatectomy. We reviewed the outcomes of these 27 patients. RESULTS: There were three complications after the first hepatectomy and six complications after the second hepatectomy, but there was no perioperative mortality after the first or second hepatectomy. The median survival from the date of second hepatectomy was 41 months with an actuarial 5-year survival rate of 48.7%. Patients who underwent repeat hepatectomy had significantly higher survival rates from the time of first hepatectomy than those who did not. Univariate analysis showed that among the prognostic factors of repeat hepatectomy, only a disease-free interval (DFI) between the first and second hepatectomy of more than 1 year was significantly predictive of a better outcome (P = 0.047). CONCLUSION: Repeat hepatectomy for recurrent colorectal metastases can be performed safely with acceptable mortality and morbidity rates, and can help to extend survival, if the DFI between the first and second hepatectomy is longer than 1 year.

Adult↗

PubMed2005

Relationship between Lens culinaris agglutinin-reactive alpha-fetoprotein and pathologic features of hepatocellular carcinoma.

AIM: We investigated pathological features of Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) in order to seek a pathological basis of poor prognosis of HCC patients with elevated AFP-L3. METHODS: A total of 111 patients with HCC < or =5 cm in diameter who underwent hepatic resection were studied. Serum AFP-L3 concentration was measured within a month prior to surgery by lectin-affinity electrophoresis coupled with antibody-affinity blotting, and expressed as AFP-L3 percentage of total AFP. AFP-L3 of 10% or higher was judged to be positive. Pathologic features of resected HCC specimens were evaluated and classified concerning growth pattern (expansive or infiltrative growth), capsule formation, capsule infiltration, septal formation, portal vein invasion, hepatic vein invasion, bile duct invasion, and intrahepatic metastasis. These macroscopic and microscopic findings were compared between AFP-L3-positive and negative HCC specimens. RESULTS: Thirty-three (29.7%) were positive for AFP-L3. The prevalence of HCC with infiltrative growth, with capsule infiltration, with septum formation, with portal vein invasion, and with hepatic vein invasion was significantly higher in AFP-L3-positive group (P=0.0121, 0.0290, 0.0442, 0.0314, and 0.0433, respectively). These pathologic features reportedly indicate the progression of the tumor. CONCLUSIONS: AFP-L3-positive HCC had several pathologic features of progressed state of HCC, which accounted for the AFP-L3 as an indicator of poor prognosis of HCC.

Adult↗

PubMed2005

Comparison of the usefulness of three staging systems for hepatocellular carcinoma (CLIP, BCLC, and JIS) in Japan.

OBJECTIVES: We retrospectively compared the usefulness of three different staging systems for hepatocellular carcinoma (HCC), the Cancer of the Liver Italian Program (CLIP) scoring system, the Barcelona Clinic Liver Cancer (BCLC) classification system, and the Japan Integrated Staging (JIS) system, in terms of patient distribution and survival rates. METHODS: Subjects were 1,508 patients diagnosed as having initial HCC during the period of 1976-2003. The disease was staged in all patients by means of the three staging systems, and the distribution of patients across stages and associated survival rates were compared between systems. In addition, comparisons were made on the basis of the time of diagnosis: 1976-1990 (n = 497) and 1991-2003 (n = 1,011). RESULTS: Patients were evenly distributed across stages within each staging system, and survival rates differed between stages except for BCLC C and D. During the period 1991-2003, when HCCs were smaller at diagnosis, JIS system is in particular yielded even distribution of patient across stages and marked differences in survival rates. CONCLUSIONS: Overall, the CLIP and the JIS scoring systems proved to be suitable for patients in Japan with HCC. The CLIP staging systems proved to be more suitable before 1991. In contrast, the JIS system was the most suitable after 1990, when early detection and early treatment of HCC became common. The JIS system is, therefore, the appropriate system in this era of early detection and treatment of HCC.

Adult↗

PubMed2004

Crucial role of inhibitor of DNA binding/differentiation in the vascular endothelial growth factor-induced activation and angiogenic processes of human endothelial cells.

Angiogenesis plays a pivotal role in the aggressive proliferation of synovial cells in rheumatoid arthritis. We have previously reported the overexpression of inhibitor of DNA binding/differentiation (Id) in the endothelial cells within the synovial tissues of rheumatoid arthritis. In this study, we investigated the role of Id in inflammation and angiogenesis in an in vitro model using HUVECs. Vascular endothelial growth factor (VEGF) and TGFbeta induced the expression of Id1 and Id3 in HUVECs. Forced expression of Id induced proliferative activity in HUVECs accompanied by down-regulation of p16INK4a. Overexpression of Id enhanced expression of ICAM-1 and E-selectin, and induced angiogenic processes such as transmigration, matrix metalloproteinase-2 and -9 expression, and tube formation. In contrast, knockdown of Id1 and Id3 with RNA interference abolished proliferation, activation, and angiogenic processes of HUVECs induced by VEGF. These results indicated that Id plays a crucial role in VEGF-induced signals of endothelial cells by causing activation and potentiation of angiogenic processes. Based on these findings, it was proposed that inhibition of expression and/or function of Id1 and Id3 may potentially be of therapeutic value for conditions associated with pathological angiogenesis.

Angiogenesis Inhibitors↗

PubMed2004

Role of KaiC phosphorylation in the circadian clock system of Synechococcus elongatus PCC 7942.

In the cyanobacterium Synechococcus elongatus PCC 7942, KaiA, KaiB, and KaiC are essential proteins for the generation of a circadian rhythm. KaiC is proposed as a negative regulator of the circadian expression of all genes in the genome, and its phosphorylation is regulated positively by KaiA and negatively by KaiB and shows a circadian rhythm in vivo. To study the functions of KaiC phosphorylation in the circadian clock system, we identified two autophosphorylation sites, Ser-431 and Thr-432, by using mass spectrometry (MS). We generated Synechococcus mutants in which these residues were substituted for alanine by using site-directed mutagenesis. Phosphorylation of KaiC was reduced in the single mutants and was completely abolished in the double mutant, indicating that KaiC is also phosphorylated at these sites in vivo. These mutants lost circadian rhythm, indicating that phosphorylation at each of the two sites is essential for the control of the circadian oscillation. Although the nonphosphorylatable mutant KaiC was able to form a hexamer in vitro, it failed to form a clock protein complex with KaiA, KaiB, and SasA in the Synechococcus cells. When nonphosphorylatable KaiC was overexpressed, the kaiBC promoter activity was only transiently repressed. These results suggest that KaiC phosphorylation regulates its transcriptional repression activity by controlling its binding affinity for other clock proteins.

Bacterial Proteins↗

PubMed2004

Small cell neuroendocrine carcinoma of the ampulla of Vater with foci of squamous differentiation: a case report.

A 54-year-old woman with obstructive jaundice was found to have a 4-cm ulcerated, elevated tumor, located at the papilla of Vater by endoscopy and radiographic investigation. Based on a clinical diagnosis of carcinoma of the ampulla of Vater, a pylorus-preserving pancreaticoduodenectomy was performed. The histologic appearance of the lesion was identical to extrapulmonary small cell carcinoma, with diffuse proliferation of small, spindle-shaped, atypical tumor cells with numerous mitoses. Neuroendocrine differentiation was demonstrated by immunoreactivity with neuron-specific enolase (NSE) and Leu-7, and by the presence of dense core granules ultrastructurally. The tumor was composed mainly of small cell neuroendocrine carcinoma, and partially of an area of squamous differentiation, showing transition from one to the other. Histopathologic investigation disclosed direct invasion deep to the lamina propria, and infiltration of the pancreatic parenchyma, duodenum, and bile duct. Lymph node metastases were present in the superior pancreaticoduodenal chain. The patient died of liver metastases 8 months later. As in previously reported cases of small cell neuroendocrine carcinoma of the ampullary region, the present case showed extremely aggressive clinical behavior with early metastases resulting in fatal outcome.

Ampulla of Vater↗

PubMed2004

Treatment strategies for perianal rhabdomyosarcoma: report of two cases.

Intensive chemotherapy and high-dose radiation with complete excision of the tumor are the treatment of choice for rhabdomyosarcoma (RMS). However, because there are so few reports of perianal RMS, a mainstream treatment has not been established. We report two cases of perianal RMS and review 13 cases documented in Japan since 1990. Case 1 was a 7-year-old boy first treated by tumor excision followed by chemotherapy and external irradiation. He has since been tumor-free but suffered severe perianal erosion and ulceration. Case 2 was a 17-year-old girl first treated by preoperative chemotherapy to reduce the tumor size, after which the tumor was completely excised with anatomical guidance using three-dimensional computed tomography via the posterior sagittal approach, followed by open intraoperative irradiation. She has since been tumor-free with preserved anal function. These case reports show the importance of cogitated treatments for preservation of anal function and optimal therapeutic outcome in patients with perianal RMS.

Adolescent↗