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K Ichiyanagi

Publications and source records attributed to K Ichiyanagi.

At least 19 recordsLinked to original sources
PubMed2005

Comparison of metabolic effects of pioglitazone, metformin, and glimepiride over 1 year in Japanese patients with newly diagnosed Type 2 diabetes.

AIMS: To compare the metabolic effects of pioglitazone, metformin, and glimepiride in the treatment of Japanese patients with newly diagnosed Type 2 diabetes. METHODS: A total of 114 patients with Type 2 diabetes who had never used oral hypoglycaemic drugs were studied for 12 months. Patients were randomly assigned to pioglitazone (30-45 mg/day, n = 38), metformin (750 mg/day, n = 39), or glimepiride (1.0-2.0 mg/day, n = 37). The effect of treatment on fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), 1,5-anhydroglucitol (1,5AG), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, free fatty acids (FFA), and fasting plasma insulin levels was monitored monthly. Body weight and safety data were also collected. RESULTS: Eight patients withdrew from the study (three in the pioglitazone group, two in the metformin group, and three in the glimepiride group). The rate of reduction of HbA(1c) was fastest in patients receiving glimepiride and slowest in patients receiving pioglitazone. Although there were no significant differences among the three groups in HbA(1c) levels at the end of the study, patients taking pioglitazone had relatively lower FPG and 1,5AG levels than patients taking the other two drugs. These results suggest that pioglitazone acts predominantly on nocturnal metabolism rather than at mealtimes. FFA were reduced significantly in those taking pioglitazone (542.2 microEq/l vs. 237.3 microEq/l; P < 0.01) before a decrease in HbA(1c) was apparent. The change in FFA levels correlated with the change in HbA(1c) (r = 0.409, P < 0.01). There were no significant differences in other lipid parameters among the groups. CONCLUSIONS: Pioglitazone, metformin, and glimepiride are equally effective in reducing blood glucose in patients with newly diagnosed Type 2 diabetes. However, their specific characteristics, such as the rapid action on blood glucose levels of glimepiride and the favourable action on FPG and FFA of pioglitazone, should be considered when choosing an appropriate agent.

Aged↗
PubMed2001

A case of double cancers with myocardial metastasis mimicking acute myocardial infarction both on an electrocardiogram and on Tc-99m-MIBI myocardial SPECT.

We report a rare case of double cancers with myocardial metastasis presenting acute myocardial infarction (AMI)-like findings both on an electrocardiogram (ECG) and on Tc-99m-MIBI myocardial SPECT. The ECG showed abnormal Q-waves and ST-segment elevation in leads V1-V4, and Tc-99m-MIBI SPECT showed a photon deficient area in the anteroseptum. These findings were suggestive of AMI, but the patient had been simultaneously suffering from two adenocarcinomas, which were lung cancer and gastric cancer, and consecutive ultrasonic cardiography (UCG) demonstrated a growing mass lesion in the septal aspect of the left ventricle. After a month he died of severe heart failure. The histological diagnosis of a specimen of the cardiac mass lesion was invasive adenocarcinoma infiltrating to the heart, which revealed that the myocardial metastasis had mimicked AMI. This case shows that it is difficult to distinguish between myocardial infarction and myocardial metastasis with myocardial perfusion SPECT. It is necessary to consider the possibility of myocardial metastasis when a patient with malignancy presents AMI-like findings.

Adenocarcinoma↗
PubMed2001

Post-load glucose measurements in oral glucose tolerance tests correlate well with 1,5-anhydroglucitol, an indicator of overall glycaemic state, in subjects with impaired glucose tolerance.

Using both cross-sectional and longitudinal methods, we investigated the relationship between post-load serum glucose concentration in a 75 g oral glucose tolerance test (OGTT) and overall glycaemic state in subjects with impaired glucose tolerance (IGT). Glycaemic state was assessed by measuring glycated haemoglobin (HbA1c) and the serum concentration of 1,5-anhydroglucitol (1,5-AG). In the cross-sectional study, the concentration of 1,5-AG, while remaining within a normal range, was reduced to a degree proportional to the post-load glycaemic level. Although the correlation between HbA1c and post-load plasma glucose was relatively weak (r=0.281, P<0.001), a significant inverse correlation (r=-0.824, P<0.0001) was found between 1,5-AG and mean post-load plasma glucose concentration in 211 subjects with IGT. Fasting plasma glucose (r=-0.539, P<0.0001) and 2 h plasma glucose (r=-0.621, P<0.0001) were correlated with 1,5-AG less strongly than was post-load glycaemia. Both 1,5-AG and HbA1c were correlated weakly but significantly with the fasting insulin concentration. In the longitudinal study we measured 1,5-AG and mean post-load plasma glucose with an OGTT once yearly for 10 years in 15 subjects with IGT. Strong inverse correlations were seen between 1,5-AG and mean post-load plasma glucose in each subject (range of r values among subjects of -0.584 to -0.978). These findings suggest a close relationship between post-load plasma glucose concentration measured by OGTT and overall glycaemic state in subjects with IGT.

Adult↗
PubMed2000

Crystal structure of an archaeal intein-encoded homing endonuclease PI-PfuI.

Inteins possess two different enzymatic activities, self-catalyzed protein splicing and site-specific DNA cleavage. These endonucleases, which are classified as part of the homing endonuclease family, initiate the mobility of their genetic elements into homologous alleles. They recognize long asymmetric nucleotide sequences and cleave both DNA strands in a monomer form. We present here the 2.1 A crystal structure of the archaeal PI-PfuI intein from Pyroccocus furiosus. The structure reveals a unique domain, designated here as the Stirrup domain, which is inserted between the Hint domain and an endonuclease domain. The horseshoe-shaped Hint domain contains a catalytic center for protein splicing, which involves both N and C-terminal residues. The endonuclease domain, which is inserted into the Hint domain, consists of two copies of substructure related by an internal pseudo 2-fold axis. In contrast with the I-CreI homing endonuclease, PI-PfuI possibly has two asymmetric catalytic sites at the center of a putative DNA-binding cleft formed by a pair of four-stranded beta-sheets. DNase I footprinting experiments showed that PI-PfuI covers more than 30 bp of the substrate asymmetrically across the cleavage site. A docking model of the DNA-enzyme complex suggests that the endonuclease domain covers the 20 bp DNA duplex encompassing the cleavage site, whereas the Stirrup domain could make an additional contact with another upstream 10 bp region. For the double-strand break, the two strands in the DNA duplex were cleaved by PI-PfuI with different efficiencies. We suggest that the cleavage of each strand is catalyzed by each of the two non-equivalent active sites.

Amino Acid Sequence↗
PubMed1999

PI-PfuI and PI-PfuII, intein-coded homing endonucleases from Pyrococcus furiosus. I. Purification and identification of the homing-type endonuclease activities.

We screened for proteins with specific binding activity to Holliday junction DNA from the hyperthermophilic archaeon Pyrococcus furiosus and found a protein that has specific affinity for DNA with a branched structure, like a three-way or four-way junction. The protein was identified as one of the two inteins encoded in the gene for ribonucleotide reductase (RNR) by gene cloning. These two inteins were spliced out from the precursor protein as polypeptides with molecular weights of 53.078 and 43.976 kDa, respectively. The amino acid sequences of these inteins have two copies of the LAGLIDADG motif, which is found in the site-specific DNA endonucleases. The purified proteins actually cleaved double-stranded DNA with the sequence of the intein(-)allele, and, therefore, they were designated PI- Pfu I and PI- Pfu II. They generate a 4 bp 3'-OH overhang with a 5'-phosphate, like other known homing endonucleases originating from inteins. The optimal conditions of the DNA cleavage reaction, including temperature, pH, and concentrations of KCl and MgCl(2), have been determined. The high affinity for junction DNA of PI- Pfu I was confirmed using the purified protein.

Amino Acid Motifs↗
PubMed1999

PI-PfuI and PI-PfuII, intein-coded homing endonucleases from Pyrococcus furiosus. II. Characterization Of the binding and cleavage abilities by site-directed mutagenesis.

PI- Pfu I and PI- Pfu II from Pyrococcus furiosus are homing endonucleases, as shown in the accompanying paper. These two endonucleases are produced by protein splicing from the precursor protein including ribonucleotide reductase (RNR). We show here that both enzymes specifically interact with their substrate DNA and distort the DNA strands by 73 degrees and 67 degrees, respectively. They have two copies of the amino acid sequence motif LAGLIDADG, which is present in the majority of homing endonucleases and provides some of the catalytic residues necessary for DNA cleavage activity. Site-specific mutagenesis studies showed that two acidic residues in the motifs, Asp149 and Glu250 in PI- Pfu I, and Asp156 and Asp249 in PI- Pfu II, were critical for catalysis. The third residues of the active site triads, as predicted from the structure of PI- Sce I, were Asn225 in PI- Pfu I and Lys224 in PI- Pfu II. Substitution of Asn225 in PI- Pfu I by Ala did not affect catalysis. The cleavage activity of PI- Pfu II was 50-fold decreased by the substitution of Ala for Lys224. The binding affinity of the mutant protein for the substrate DNA also decreased 6-fold. The Lys in PI- Pfu II may play a direct or indirect role in catalysis of the endonuclease activity.

Amino Acid Motifs↗
PubMed1998

Mutational analysis on structure-function relationship of a holliday junction specific endonuclease RuvC.

BACKGROUND: Escherichia coli RuvC protein is a specific endonuclease that resolves Holliday junctions during homologous recombination. For junction resolution, RuvC undergoes distinct steps such as dimerization, junction-specific binding and endonucleolytic cleavage. The crystal structure of RuvC has been revealed. RESULTS: To identify functionally important residues, we isolated a large number of mutant ruvC genes created by random mutagenesis and characterized their properties in vivo and in vitro. The mutations which were isolated most frequently were mapped to the four acidic residues constituting the catalytic centre. Amongst the several mutant proteins affected in the dimer interface, only one could not form a dimer. The others were able to form a dimer but were defective in cleavage. F69L and K118R mutant proteins could not cleave the junction, but they were able to form a dimer and bind the junction DNA. CONCLUSIONS: Random mutagenesis highlighted many structurally and functionally important residues of RuvC, most of which are highly conserved among RuvC homologues. Dimer formation and also conservation of intact interface interactions between the subunits are important for junction binding and subsequent cleavage. Phe-69 and Lys-118 are critically important for the interactions which lead to junction cleavage.

Amino Acid Sequence↗
PubMed1998

Prediction of prognosis in peripheral facial nerve paralysis using submandibular gland scintigraphy.

UNLABELLED: In this study, we evaluated the ability of submandibular gland scintigraphy to predict the prognosis of peripheral facial nerve paralysis. METHODS: Submandibular gland scintigraphy was performed in 78 patients with acute peripheral facial nerve paralysis. After injection of 180-370 MBq [99mTc]pertechnetate, serial 1-min images were acquired for 25 min. At 15 min after injection of radionuclide, ascorbic acid was administered intraorally to stimulate salivary secretion. Regions of interest were set manually on both submandibular glands, and time-activity curves were generated. The ratios of peak count density (PCR) and washout (WR) of the affected side to the normal side were calculated. Parameters of > or = 0.8 suggested normal affected submandibular function and indicated a good prognosis. RESULTS: Complete recovery of facial nerve paralysis was observed in 52 of 78 patients. The sensitivity, specificity and accuracy of PCR for a good prognosis were 79%, 50% and 69%, and those of WR were 85%, 77% and 82%, respectively. Positive and negative predictive values for a good prognosis were 76% and 54% in PCR and 88% and 71% in WR, respectively. When WR obtained within 14 days of the onset was used, positive and negative predictive values for a good prognosis were 94% and 73%, respectively. None of the eight patients who had values of <0.8 for both parameters within 14 days of the onset recovered completely. CONCLUSION: Submandibular gland scintigraphy can serve as a reliable indicator to predict the prognosis of acute peripheral facial nerve paralysis in its early symptomatic period.

Acute Disease↗
PubMed1997

[Efficiency of segmental SMANCS/Lip-TAE for hepatocellular carcinoma--comparative studies in the efficacy of segmental SMANCS/Lip-TAI].

We compared the segmental SMANCS/Lip-TAI and the segmental SMANCS/Lip-TAE and studied the effectiveness of both treatments and the influence and/or the side effects on liver function. In resected cases, we studied histopathologic examination. The response rate of the group treated by TAI was 28.6%, and that of the group treated by TAE was 76.5%. In the group treated by TAE, the therapeutic effects were good in nodular type HCC, using small doses of SMANCS. In both groups, the incidence and degree of side effects showed no significant difference. Hepatic insufficiency occurred in a few cases of the group treated by TAI. In resected cases, viable areas remained below the tumor capsule. In conclusion, segmental SMANCS/Lip-TAE seemed to be an effective treatment without any serious complications.

Aged↗
PubMed1996

Technetium-99m tetrofosmin uptake in lung cancer: comparison with thallium-201.

Technetium-99m tetrofosmin and thallium-201 lung SPECT imaging were performed in a patient with adenocarcinoma of the lung. Significant activities in the lung lesion were clearly depicted on both technetium-99m tetrofosmin and thallium-201 SPECT imaging. The early uptake, delayed uptake ratios and retention indices of the tumor were 2.75, 2.39 and -1.31 for thallium-201 imaging and 3.09, 2.27 and -26.5 for technetium-99m tetrofosmin imaging, respectively. This preliminary report suggests that technetium-99m tetrofosmin may have potential as a tumor imaging agent.

Adenocarcinoma↗
PubMed1996

Impaired fatty acid uptake in ischemic but viable myocardium identified by thallium-201 reinjection.

Iodine 123-labeled 15-iodophenyl-3-methyl-pentadecanoic acid (BMIPP) has been proposed as a potential myocardial fatty acid probe. We studied BMIPP uptake in ischemic myocardium identified by thallium reinjection. Fifty-five patients with coronary artery disease who had persistent defects on standard exercise-redistribution thallium imaging were investigated. Patients underwent exercise-redistribution-reinjection thallium and resting BMIPP imaging. BMIPP uptake less than that seen with thallium on reinjection imaging was observed in 105 (82%) of 128 myocardial segments with new fill-in after thallium reinjection and 87 (37%) of 238 segments with reversible thallium defects. In contrast, only 32 (19%) of 166 segments with no fill-in showed discordantly decreased BMIPP uptake. Quantitative analysis showed reduction in BMIPP activity compared with differential uptake of thallium, an index of resting myocardial perfusion, especially in the area of fill-in (53.5% +/- 15.0% vs 76% +/- 12.1% of peak; p<0.01). These observations are consistent with impaired fatty acid uptake in ischemic myocardium, particularly in the area of fill-in after thallium reinjection.

Adult↗
PubMed1996

Early and delayed technetium-99m-tetrofosmin myocardial SPECT compared in normal volunteers.

UNLABELLED: This study was performed to test the feasibility of early SPECT imaging with 99mTc-tetrofosmin with the presence of high hepatic activity. METHODS: Thirteen normal volunteers were injected 600-740 MBq of 99mTc-tetrofosmin at rest and were imaged at 10 min and 1 hr after injection. The SPECT images were reconstructed for 180 degrees 360 degrees data. The early and delayed SPECT and anterior planar projection images were analyzed. RESULTS: After excluding one subject because of high hepatic activity overlapping to the myocardium, 4 of 12 subjects (33%) had abnormal scans with reduced uptake in the inferior wall on the early 180 degrees SPECT image. In contrast, only one (8%) showed equivocally reduced uptake on the 360 degrees SPECT image. In the delayed images, all subjects had a normal 180 degrees and 360 degrees SPECT scan. Quantitative data showed reduced regional activities in the inferior wall on the early SPECT scan, especially in the 180 degrees data. There were no changes in the mean anterior-to-inferior ratio in the anterior planar projection images over time, suggesting that the reduced activity in the early SPECT images reflected an artifactual effect. CONCLUSION: Our data indicate that it would be best to perform late imaging in patients with suspected coronary artery disease using 99mTc-tetrofosmin.

Adult↗
PubMed1996

[Residual activity or defect reversibility on stress-redistribution-reinjection 201T1 SPECT: which is the better marker of myocardial viability?].

Although both residual T1 activity and defect reversibility are used as a marker of myocardial viability on stress-redistribution-reinjection T1 (T1-RI) imaging, it is not yet fully understood which marker better predicts reversible dysfunction after revascularization. The aim of this study was to assess the comparative efficacies of these criteria for prediction of functional recovery after revascularization. Twenty-five patients (LVEF 41%) who underwent successful revascularization were studied with T1-RI SPECT and gated blood pool scintigraphy before revascularization. The gated blood pool study was repeated at mean 2 months after revascularization. The left ventricular myocardium was divided into 9 segments and the mean regional activities were calculated for each segment. In this study, two independent criteria were used as a viability index; (A) the presence of residual T1 activity (> 50% of peak) on the final image (reinjection image), (B) reversible defect (> 10% increase on the subsequent images) or normal T1 uptake (> 80% of peak) on the initial image. Functional recovery occurred in 51 of 88 dysfunctional segments. The presence of residual T1 activity was a highly sensitive (96%) but poorly specific (35%) marker of reversible dysfunction, while a reversible defect or normal T1 uptake was a less sensitive (67%) but more specific (59%) predictor of functional recovery. In conclusion, defect reversibility provides unique information on myocardial viability which cannot be obtained by assessing residual T1 activity alone.

Aged↗
PubMed1995

Myocardial viability assessment with technetium-99m-tetrofosmin and thallium-201 reinjection in coronary artery disease.

UNLABELLED: Exercise-rest 99mTc-tetrofosmin myocardial perfusion images with a 2-day protocol was compared to exercise-redistribution-reinjection 201Tl images to assess the ability of 99mTc-tetrofosmin to detect viable myocardium. METHODS: We studied 25 patients with coronary artery disease and regional or global left ventricular dysfunction. Myocardial SPECT images with 99mTc-tetrofosmin were obtained 10 min after injection during exercise and 1 and 3 hr after rest injection. Within 1 wk of the 99mTc-tetrofosmin study, exercise-redistribution-reinjection 201Tl SPECT imaging was performed. RESULTS: Visual analysis demonstrated concordance between 201Tl and 99mTc-tetrofosmin imaging for defect reversibility in 126 of 209 segments (60%), with initial defects on both exercise 201Tl and 99mTc-tetrofosmin images. In the remaining discordant 83 segments (40%), 73 (88%) appeared nonreversible on 99mTc-tetrofosmin imaging but were reversible on 201Tl imaging. CONCLUSION: On the basis of defect reversibility by visual analysis, exercise-rest 99mTc-tetrofosmin imaging underestimates myocardial viability compared to 201Tl reinjection imaging. The identification of viable myocardium with both 99mTc-tetrofosmin and 201Tl can be greatly enhanced to a similar degree if the severity of reduction in activity within nonreversible defects is considered. These two agents may provide comparable information about myocardial viability by quantitative analysis of defect severity.

Coronary Disease↗
PubMed1995

Improved myocardial fatty acid utilization after percutaneous transluminal coronary angioplasty.

Exercise-reinjection 201Tl imaging and resting 20-min and 3-hr BMIPP imaging were performed before and 4 mo after percutaneous transluminal coronary angioplasty (PTCA) in a patient with effort angina. Before PTCA, exercise 201Tl imaging showed decreased 201Tl activity in the septal wall, with significant fill-in on the reinjection 201Tl image. The resting 20-min BMIPP image showed decreased activity in the septal wall, with a slight redistribution on the 3-hr BMIPP image. The 201Tl and BMIPP images 4 mo after PTCA showed significant improvement in the 201Tl pattern and BMIPP uptake in the septal wall with no abnormally decreased activities.

Aged↗
PubMed1995

[Evaluation of myocardial fatty acid metabolism in the area of fill-in after thallium reinjection in patients with prior myocardial infarction].

Myocardial fatty acid utilization in the area with thallium fill-in after reinjection was assessed using 123I-labeled 15-(p-iodophenyl)3R,S-methylpentadecanoic acid (BMIPP). We studied 22 patients with prior myocardial infarction that revealed persistent defects on standard exercise-redistribution thallium imaging. In each patient, exercise-redistribution-reinjection thallium imaging was performed. Within two weeks of the thallium study, resting BMIPP imaging was performed 20 min after injection of BMIPP (148 MBq). Following qualitative analysis of the obtained thallium and BMIPP images, quantitative analysis was performed on the basis of relative regional uptake. Of 199 myocardial segments that showed persistent defects on exercise-redistribution images, 73 segments showed apparent fill-in on the reinjection images (fill-in positive), and the remaining 126 segments did not (fill-in negative). When BMIPP images were compared with the corresponding thallium reinjection images, reduced BMIPP uptake compared with thallium were frequently observed in the area of fill-in positive segments (65 of 73 segments, 89%). Quantitative analysis also showed decrease in BMIPP activity compared to thallium activity in the area of fill-in (49.7 +/- 16.1 vs. 65.8 +/- 16.0%, p < 0.001). In contrast, only 24 of the 126 fill-in negative segments (19%) showed lower BMIPP uptake than thallium. These results suggest that impaired fatty acid utilization in the area of thallium new fill-in after reinjection already exists at resting condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Relationship between various parameters derived from 123I-labelled beta-methyl-branched fatty acid whole-body scintigraphy and left ventricular ejection fraction in patients with ischaemic heart disease.

Heart uptake and clearance of 123I-15-(p-iodophenyl)-3(R,S)-methyl- pentadecanoic acid (BMIPP) by whole-body scintigraphy in relation to left ventricular ejection fraction (LVEF) was evaluated in 34 patients with ischaemic heart disease. At 45 and 210 min after injection, anterior whole-body images were obtained. In each patient, multigated blood pool scintigraphy was also performed, and LVEF was calculated. The percentage heart uptake of BMIPP did not have a significant correlation with LVEF (R = -0.299, NS). In contrast, there was a positive correlation between LVEF measured by multigated blood pool scintigraphy and BMIPP count density of the heart (R = 0.467, P = 0.005). Myocardial BMIPP washout rate also positively correlated with LVEF (R = 0.472, P = 0.005). In addition to these observations, there was a positive correlation between the BMIPP count density of the heart and myocardial BMIPP washout rate (R = 0.0543, P = 0.001). Thus, the BMIPP count density of the heart and myocardial BMIPP washout rate derived from BMIPP whole-body scintigraphy directly correlated with LVEF. However, the correlations between these parameters and LVEF were not strong enough to allow left ventricular dysfunction to be assessed precisely.

Adult↗