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Biomedical subjects

M Tateno

Publications and source records attributed to M Tateno.

At least 55 records · Page 3Linked to original sources

[Survival in patients with clear cell carcinoma of the ovary].

Thirty-one patients with clear cell ovarian carcinoma who underwent primary surgery and postoperative therapy were retrospectively evaluated. Eighteen patients (58%) had International Federation of Gynecology and Obstetrics (FIGO) stage I disease, 3 patients (9.7%) stage II disease, and 10 patients (32.3%) stage III and IV disease. Patients with stage III and IV disease demonstrated a significantly poor prognosis compared with patients who had stage I or II disease (p < 0.01). No patients with stage III and IV disease survived 5 years. p53 protein expression and proliferative activity (PA) were studied by immunohistochemical methods using p53 molecule and antibodies to PCNA (proliferative cell nuclear antigen). Intranuclear accumulations of p53 product were observed in 15 of 31 (48.4%). On the other hand, 15 of 31 (48.4%) patients stained positively for PCNA (> or = 60% of cancer cells stained positively). Positive p53 staining and highly PA were associated with poor survival. Two patients with stage I a relapsed were positive p53 and highly PA. Accordingly, consolidation chemotherapy is necessary for patients with stage I a who are positive p53 and highly PA. Platinum-based chemotherapy for patients who had minimal residual tumor was effective, but 5 patients who had > or = 2 cm tumor burden were not effective at all. The response rate for platinum-based chemotherapy was 20% (1/5) among p53 positive, in contrast to 66.7% (4/6) among p53 negative patients. So it seems that p53 positive patients are chemoresistant.

Adenocarcinoma, Clear Cell↗

Use of a 3D structure data base for understanding sequence-dependent conformational aspects of DNA.

The roll-twist-slide correlation in the DNA crystal structures that are collected in the Nucleic Acid Data Base is analyzed in order to obtain a general understanding of the effects of the nucleotide sequence on the 3D structure of a dinucleotide step. It is concluded that the differences between the pyrimidine bases and the purine bases in terms of their physical shapes are the major factors that determine the stereochemical characteristics of the steps through base to backbone and base to base interactions. The characteristics are further modulated by the differences between the A:T and G:C base-pairs, which can be explained by enhancement of the purine-pyrimidine asymmetry in the A:T base-pair.

Computational Biology↗

A metalloproteinase inhibitor prevents lethal acute graft-versus-host disease in mice.

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), which is a major complication after allogeneic bone marrow transplantation. We examined here the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in a lethal acute GVHD model in mice. Administration of KB-R7785 into (BALB/c x C57BL/6) F1 that received C57BL/6 spleen cells markedly reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues. The ameliorating effect of KB-R7785 was superior to that of anti-TNF-alpha antibody. Our results suggest that KB-R7785 could be a potent therapeutic agent for GVHD.

Animals↗

Application of telomerase assay for the screening of cervical lesions.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends. The expression of telomerase is thought to be required for cellular immortality and oncogenesis. Telomerase activity has been detected not only in most cancers but also in some types of premalignant lesions, such as squamous intraepithelial lesions (SILs). In the present study, we used the telomerase assay to detect uterine cervical lesions in cervical scraping samples. A total of 82 cervical scraping samples were obtained from women with or without cervical lesions and examined by nonradioisotope telomeric repeat amplification protocol assay. Fifteen of 17 (88%) cervical cancer specimens exhibited telomerase activity, whereas 5 of 8 (63%) and 14 of 24 (58%) specimens from low-grade and high-grade SILs, respectively, also exhibited telomerase activity. In contrast, 3 of 33 (9%) specimens from normal cervices exhibited telomerase activity. Dilution telomeric repeat amplification protocol assay was performed to estimate telomerase activity; it revealed that high levels of activity were often expressed in cervical cancer. Cytological examination was also performed by Pap smear test, and 4 of 8 (50%) low-grade SILs, 21 of 24 (88%) high-grade SILs, and 16 of 17 (94%) cervical cancers were found to have cytological abnormalities. There were discordances in some cases between findings of smear abnormality and telomerase positivity. In particular, we found five cases of SILs without smear abnormality but with telomerase activity, suggesting that some lesions with false negative cytology can be detected by telomerase assay. These findings suggest that telomerase assay using cervical scrapings might be a useful screening method for cervical lesions especially when combined with a Pap smear test.

Biomarkers, Tumor↗

Amyloid beta protein and transthyretin, sequestrating protein colocalize in normal human kidney.

The localization of amyloid beta protein (A beta), A beta 40, A beta 42, and transthyretin (TTR) was investigated immunohistochemically in the autopsied human kidney, using polyclonal antibodies against TTR, A beta and C-terminal end-specific antibodies against A beta 40 and 42. Immunoreactivities of A beta and A beta 40 were found both in the proximal and distal tubular epithelial cells. But the immunolocalization of A beta 40 was observed predominantly in the distal tubules whereas that of A beta 42 was predominantly recognized in the proximal tubules. TTR, sequestrating protein for A beta, was present in the proximal tubules. The mechanism by which A beta does not form amyloid in Alzheimer's disease outside the brain remains unknown. The tubular epithelial cells in the kidney may provide a useful system to shed light on this issue.

Amyloid beta-Peptides↗

DNA recognition by beta-sheets.

The modes of DNA recognition by beta-sheets are analyzed by using the known crystal and solution three-dimensional structures of DNA-protein complexes. Close fitting of the protein surface and the DNA surface determines the binding geometry. Interaction takes place so that essentially the N-to-C direction of the beta-strands either follows or crosses the DNA groove. Upon following the major groove a two-stranded antiparallel beta-sheet dives into the groove and contacts DNA bases with its convex side facing the DNA, while upon following the minor groove, it binds around the sugar-phosphate backbones, with its opposite concave side shielding the DNA. In order for the beta-strands crossing the minor groove to interact with the DNA, the dinucleotide steps need to almost totally helically untwist and roll around major groove. The beta-sheet, on the other hand, needs to adopt a concave curvature on the binding surface in the direction that follows the DNA minor groove, and a convex surface in the direction that bridges the sugar-phosphate backbones across the groove. The result is to produce a hyperbolic paraboloidal DNA-binding surface.

Amino Acid Sequence↗

A clearer distinction between HIV-1 paired isolates from peripheral blood mononuclear cells of asymptomatic carriers with and without CD8+ T-cells at nef rather than env V3 loci.

In asymptomatic carriers, the vast majority of human immunodeficiency virus type 1 (HIV-1) infection is non-productive whilst the clinical stage of disease is associated with significant virus expression. Virus-specific CD8+ T-cell functions are believed to play a major role in the generation of heterogeneous virus populations and in subsequent disease progression. Here, we prepared two types of HIV-1 isolate by culturing whole and CD8+ T cell-depleted peripheral blood mononuclear cells (PBMCs) from five asymptomatic carriers. The former is expected to be escape variant populations, whereas the latter would be mixed populations including the former viruses. The analyses of Nef and Env V3 sequence variations of viruses in a total of 77 and 44 DNA clones, respectively, allowed a direct comparison to be made of the differences between the paired isolates. Comparison of Nef sequences between the paired isolates showed them to be more distinct in two carriers with a relatively stable CD4/CD8 ratio (Nos 68 and 69), than in two other carriers with similar CD4/CD8 ratios (Nos 53 and 57), or in carrier No. 67, which had an extremely lower CD4/CD8 ratio. By contrast, a distinction between the paired isolates by use of the Env V3 sequences was only apparent in the latter three carriers. These results indicate that the predominant populations of HIV-1 in Nos 68 and 69 were sensitive to selective pressure from Nef-specific CD8+ T-cells, while those in Nos 53, 57, and 67 were sensitive to pressure from V3-specific CD8+ T-cells. It is noteworthy that Nos 53 and 57 progressed to an AIDS-related complex shortly and several years after this examination. These data suggest that HIV-1-induced pathogenesis is more strongly associated with the generation of variant nef alleles than with env V3 variants, and that these arise by CD8+ T-cell pressure.

Amino Acid Sequence↗

Human papillomavirus infection and risk determinants for squamous intraepithelial lesion and cervical cancer in Japan.

A case control design was used to investigate human papillomavirus (HPV) prevalence and risk factors associated with development of cervical squamous intraepithelial lesion (SIL) and cervical cancer (CC) in Japan. One hundred and twenty-three women with histologically confirmed SIL or CC were compared to a control group of 778 cytologically normal women. With the use of a polymerase chain reaction (PCR)-based method for detection of low-risk (types 6 and 11) and high-risk (types 16, 18, 31, 33, 35, 52 and 58) HPVs, a high prevalence of HPV infection was observed in smokers among the controls. Logistic regression analysis demonstrated that high-risk HPV infection was the most significant risk determinant for LSIL (OR=9.4, 95% CI=4.5-19), HSIL (OR=77, 95% CI=28-217) and CC (OR=97, 95% CI=35-269). It also showed that unmarried women, women married for 5 to 19 years and smokers represented high risk groups for SIL, while smokers and women with a history of many pregnancies/parities had increased risk for CC. Smoking was the only HPV infection-independent factor for CC, suggesting that smoking may have a carcinogenic effect on the cervix. Since neither history of other cancer nor family cancer history was associated with SIL or CC, genetic factors appear to play little role in cervical carcinogenesis. The risk for cervical neoplasia due to HPV infection increased after marriage in Japan, suggesting a role for husbands as carriers of HPV transmission. Protection from high-risk HPV infection may be of greatest importance for prevention of cervical cancer.

Adolescent↗

Major identity determinants in the "augmented D helix" of tRNA(Glu) from Escherichia coli.

By a kinetic analysis of 59 variant transcripts of Escherichia coli tRNA(Glu) with glutamyl-tRNA synthetase (GluRS), the U11.A24 base-pair, the U13.G22..A46 base-triple, and the lack of residue 47 (delta47) were found to serve as major determinants for tRNA(Glu) identity. This is the first system for which major identity determinants are reported to be clustered in the "augmented D helix", consisting of the D stem with some neighboring residues and the variable loop. Other identity determinants are U34, U35, C36 and A37 in the anticodon loop, and G1.C72 and U2.A71 in the acceptor stem. Phosphate-group protection by GluRS from ethylnitrosourea was observed most strongly for the minor groove side of D-stem helix, indicating that GluRs tightly binds to the D stem for recognition, on the minor groove side, of the potent identity-determinant groups of the U11.A24 and U13.G22 base-pairs. A46 is not involved in direct recognition by GluRS; the U13.G22..A46 base-triple is required probably for formation of the structural features that are recognized by GluRS. In this context, the essential role of characteristic delta47 in tRNA(Glu) identity may be to maintain the U13.G22..A46 base-triple.

Anticodon↗

Dual-tracer autoradiography with thallium-201 and iodine-125-metaiodobenzylguanidine in experimental myocardial infarction of rat.

UNLABELLED: Dual-isotope scintigraphic studies with 201Tl and radioiodinated metaiodobenzylguanidine (MIBG) suggest that acute myocardial infarction causes extensive regional myocardial denervation beyond the infarcted area. We therefore investigated the histopathological and biochemical significance of the discrepancy between 201Tl and 125I-MIBG distribution determined by dual-tracer autoradiography in experimental myocardial infarction. METHODS: Left coronary arteries of 12 male Wistar rats were ligated for 30 min followed by reperfusion. Dual-tracer autoradiography of infarcted heart sections was performed with 201Tl and [125I]MIBG 4 hr or 2 days after coronary reperfusion, followed by immunohistochemical staining with myoglobin monoclonal antibody to determine the area of myocardial infarction. Ultrastructural alterations and myocardial norepinephrine (NE) content in the region determined by dual-tracer autoradiography and myglobin immunostaining were studied. RESULTS: Thirty-minute coronary ligation with 4-hr reperfusion produced myocardial infarction associated with discrepant region in the peri-infarcted myocardium characterized by decreased [125I]MIBG uptake and normal 201Tl distribution (discrepant region), as determined by dual-tracer autoradiography. In the discrepant region, which disappeared after 2 days, the nerve terminals showed loss of granular cores, with normal structures between normal myocytes. The mean myocardial NE level in the discrepant region was significantly lower than that in the nonischemic region (255.2 +/- 85.9 versus 549.5 +/- 82.5 ng/mg). CONCLUSION: The uptake discrepancy of 201Tl and [125I]MIBG observed in the infarcted heart represents a transient functional denervation of the regional cardiac sympathetic nerve terminals in the noninfarcted myocardium.

3-Iodobenzylguanidine↗

Assessment of fatty acid uptake in ischemic heart disease without myocardial infarction.

UNLABELLED: To assess the clinical value of 123I fatty acid analog, 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) was imaged at rest in coronary patients without prior myocardial infarction. The BMIPP findings were compared with various clinical parameters. METHODS: Thirty-one patients with ischemic heart disease (19 with unstable angina, 12 with stable angina), without myocardial infarction underwent BMIPP SPECT at rest, coronary arteriography, rest/stress thallium SPECT and left ventriculography exams. RESULTS: Regional decrease of BMIPP was seen in 63% of the myocardial areas at risk, whereas regional perfusion decrease at rest was observed only in 35% (p < 0.01). The BMIPP decrease was more often seen in the unstable group (79%) than stable group (38%) (p < 0.01). Stress-induced ischemia was seen in 77% of segments with decreased BMIPP uptake in unstable group and in 57% in the stable group. Frequency and severity of BMIPP abnormality increased with the severity of stress-induced ischemia (p < 0.005) and the severity of coronary artery stenosis (p < 0.005). In addition, regional BMIPP abnormality was related to severity of wall motion abnormalities (p < 0.005). While 67% of segments with a wall motion abnormality showed BMIPP decrease, 36% with normal wall motion also showed BMIPP decrease (p < 0.01). CONCLUSION: Abnormal fatty acid metabolism was often observed at rest in patients with ischemic heart disease without history of myocardial infarction, and the abnormalities were related to severe myocardial ischemia and regional wall motion abnormalities.

Aged↗

Regional abnormality of iodine-123-MIBG in diabetic hearts.

UNLABELLED: Autonomic neuropathy along with cardiac denervation is one of the prognostic factors of diabetic patients. The aim of this study was to establish qualitative and quantitative assessment of diabetic cardiac denervation using [123I]metaiodobenzylguanidine (MIBG). METHODS: The study population consisted of 31 diabetic patients and 12 control subjects (C). Diabetic patients were classified into the following three groups according to their presentation of neuropathy: NO, without neuropathy; N1, mild neuropathy; N2, severe neuropathy. All subjects underwent triple-phase MIBG scanning, including dynamic planar imaging as well as early and delayed planar and SPECT imaging. Myocardial uptake ratios of MIBG and heart-to-mediastinum count ratios (H/M) were calculated as global uptake indices. Inferior-to-anterior count ratios and coefficients of variation were calculated as regional distribution indices. The washout rate of the inferior wall and whole myocardium were also studied. RESULTS: MIBG abnormalities were obvious in the inferior wall, which gradually spread to the adjacent segments. All indices of regional uptake showed a significant difference (p < 0.01) among the groups, while only the H/M of the late image showed significant differences in the two global uptake indices (p = 0.02). the washout rate of the inferior wall was enhanced with neuropathy. CONCLUSION: Diabetic neuropathy involves an MIBG abnormality in its early stages. Since this abnormality occurs in the inferior segment, an inferior-to-anterior count ratio, an index of regional MIBG uptake could be suitable for the evaluation of this condition because of its superior sensitivity.

3-Iodobenzylguanidine↗

A three-dimensional structure model of the complex of glutamyl-tRNA synthetase and its cognate tRNA.

A docking model of glutamyl-tRNA synthetase (GluRS) and tRNAGlu was constructed, on the basis of the distinguished similarity between the X-ray crystallographic three-dimensional structures of the N-terminal halves of the Thermus thermophilus GluRS in the free state and the Escherichia coli glutaminyl-tRNA synthetase in a complex with tRNAGln. The modeled structure is energetically favorable and is also well consistent with the results of site-directed mutagenesis studies. The model indicates that the GluRS-specific insertions 2 and 3 fit and bind to the acceptor stem and the D arm, respectively, of the cognate tRNA without affecting other contacts. In particular, insertion 3 strongly interacts with the two D-stem base pairs that are essential for the tRNA-GluRS recognition.

Anticodon↗

Assessment of coronary vasodilator reserve by N-13 ammonia PET using the microsphere method and Patlak plot analysis.

UNLABELLED: Noninvasive quantification of regional myocardial blood flow (MBF) has been successfully achieved with N-13 ammonia. The microsphere method as a simple method for quantifying regional myocardial blood flow was reevaluated in comparison with Patlak graphical analysis. In addition coronary vasodilator reserve (CVR) was estimated by both methods. METHODS: Dynamic N-13 ammonia PET studies were performed in 10 healthy volunteers and 10 patients with coronary artery disease at baseline and after dipyridamole infusion (0.56 mg/kg). MBF was estimated by the microsphere method at various times and by Patlak graphical analysis. In order to reduce the noise level in the microsphere method, MBF estimates were also performed after data in 10-40 seconds were averaged. RESULTS: In the studies on normal subjects MBF (ml/min/g) determined by the microsphere method significantly differs from time to time. However, MBF determined by the modified microsphere method [with average (Extraction fraction) x MBF values obtained between 100 and 120 sec] linearly correlated well with MBF by Patlak graphical analysis (r = 0.97, slope = 0.98, intercept = 0.20). In the studies on patients with coronary artery disease a good agreement of the MBF estimates was also observed (r = 0.97, slope = 0.98, intercept = 0.22). In the studies on the normal subjects and patients with coronary artery disease, CVR obtained by the modified microsphere method after correcting the overestimated MBF values also correlated well with that by Patlak graphical analysis (r = 0.90, slope = 1.14, intercept = -0.15, and r = 0.92, slope = 0.82, intercept = 0.25, respectively). CONCLUSION: The modified microsphere method is a very simple and reliable approach for quantifying MBF with N-13 ammonia PET which is comparable to Patlak graphical analysis. It also makes possible CVR assessment as accurate as Patlak graphical analysis.

Adult↗

Origin of posterior pituitary high intensity on T1-weighted magnetic resonance imaging. Immunohistochemical, electron microscopic, and magnetic resonance studies of posterior pituitary lobe of dehydrated rabbits.

RATIONALE AND OBJECTIVES: To investigate the origin of posterior pituitary high intensity (PPHI) seen on T1-weighted magnetic resonance (MR) images. METHODS: Six rabbits, including four rabbits deprived of drinking water for 4 days and two control rabbits, were examined by MR imaging. Plasma vasopressin levels were sequentially measured by radioimmunoassay. Pituitary glands were immunostained with guinea pig anti-rabbit vasopressin antibody, and ultrathin sections of Epon/Araldite-embedded specimens were observed with a transmission electron microscope. RESULTS: In control rabbits, PPHI was noted on T1-weighted MR images, and the posterior pituitary lobe was positively immunostained with anti-vasopressin antibody. At the ultrastructural level, nerve terminals contained numerous neurosecretory granules bearing vasopressin. Conversely, plasma vasopressin levels gradually increased and PPHI was absent in 4-day dehydrated rabbits. The posterior lobe was scarcely stained with anti-vasopressin antibody, and neurosecretory granules were rarely observed. However, a number of small dispersed vesicles, possibly derived from the fragmentation of neurosecretory granule envelopes, were seen in the nerve terminal. CONCLUSIONS: Posterior pituitary high signal seen on T1-weighted MR images is attributed to neurosecretory granules bearing vasopressin.

Animals↗

Cardiac accumulation of 125I-labeled monoclonal antibody to atrial natriuretic peptide in a rat model of myocardial infarction.

Atrial natriuretic peptide (ANP) may be an important factor in myocardial infarction and subsequent congestive heart failure. In the failing heart, ANP is expressed in both the atrium and the ventricle. ANP has now been localized with 125I-labeled monoclonal antibodies (MAbs) in vivo in a rat model of myocardial infarction. Myocardial infarction was produced in 3-month-old Wistar rats by ligating the left anterior coronary artery. Two MAbs to rat alpha-ANP accumulated in the infarcted left ventricles of treated rats to a significantly greater extent (p < 0.01) than in the noninfarcted left ventricles of control rats. However, an irrelevant MAb also accumulated to a significantly greater extent in infarcted myocardium than in control myocardium. Thus, the accumulation of the two MAbs to ANP in infarcted tissue seems to be nonspecific and may be due to increased permeability of the injured myocardium.

Animals↗

[Usefulness of 123I-MIBG and 123I-BMIPP myocardial scintigraphy for detecting coronary artery disease and for evaluating left ventricular function].

We evaluated the diagnostic value of 123I-metaiodobenzylguanidine (MIBG) and 123I-labeled beta-methyliodophenyl pentadecanoic acid (BMIPP) myocardial SPECTs for evaluating coronary artery disease and left ventricular function, in comparison with the diagnostic value of 201Tl (Tl) SPECT. For forty-nine patients with coronary artery disease, resting MIBG and BMIPP SPECTs were performed to detect coronary artery stenosis, compared with the diagnostic value of exercise Tl. Left ventricular ejection fraction and regional wall motion were compared with the total US (TUS) and regional US (RUS) of resting MIBG and BMIPP SPECTs, and in turn, compared with resting Tl SPECT. The sensitivity of resting BMIPP SPECT for detecting coronary artery stenosis was lower, and the specificity of resting MIBG SPECT was lower than the other two methods. The accuracy of resting MIBG SPECT for evaluating coronary lesions was nearly the same as the accuracy of exercise Tl, but higher than that of BMIPP SPECT. Left ventricular ejection fraction was well correlated with TUS of resting MIBG SPECT (r = 0.80), resting BMIPP SPECT (r = 0.77), and resting Tl SPECT (r = 0.68). Regional wall motion was most correlated with RUS of resting BMIPP SPECT, compared with that of resting Tl and MIBG SPECTs. These data suggest that resting MIBG SPECT is useful for detecting coronary artery disease and that resting BMIPP SPECT is valuable in evaluating regional left ventricular function.

3-Iodobenzylguanidine↗

Effect of inhaled furosemide on lung clearance of technetium-99m-DTPA.

UNLABELLED: The diuretic furosemide has been reported to have a protective effect on allergic asthmatic reactions. This study was performed to investigate the effect of aerosolized furosemide on the lung clearance of 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA). METHODS: Pulmonary clearance rates of 99mTc-DTPA were measured by a computerized gamma camera with and without the inhalation of aerosol furosemide in 6 nonsmoking normal volunteers (Group 1), 7 smokers without pulmonary disease (Group 2) and 11 patients with asthma (Group 3). RESULTS: None of the six normal volunteers showed significant effects of inhaled furosemide on the 99mTc-DTPA clearance rates. Three of seven smokers presented an accelerated 99mTc-DTPA clearance by inhaled furosemide and the other four showed no significant change of 99mTc-DTPA clearance by furosemide inhalation. However, in 10 of 11 patients with asthma, there was significant suppression of 99mTc-DTPA clearance by furosemide inhalation. CONCLUSION: Asthmatics possess a furosemide-sensitive mechanism. Pulmonary aerosol scintigraphy with 99mTc-DTPA will be useful in predicting the effect of inhaled furosemide therapy.

Administration, Inhalation↗