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Biomedical subjects

M Hori

Publications and source records attributed to M Hori.

At least 145 records · Page 8Linked to original sources

Nasal natural killer cell lymphoma in a post-renal transplant patient.

Posttransplant lymphoproliferative disorders in organ allograft recipients are most commonly of B-cell origin and only occasionally of T-cell origin. We present here a case of nasal natural killer cell lymphoma associated with Epstein-Barr virus that occurred in a recipient of a renal transplant 4 years posttransplantation. Immunohistochemically, the lymphoma cells showed CD2-, surface CD3-, cytoplasmic CD3E+, CD56+, CD57-, CD16-, and CD43+ phenotype. Analyses of T-cell receptor beta and gamma genes showed germ line configurations. EBER-1 was detectable in the lymphoma cells. The patient was diagnosed as having natural killer cell lymphoma and was treated with six courses of combination chemotherapy for non-Hodgkin's lymphoma He has been in remission for more than 3 years thereafter. To the best of our knowledge, this is the first report of a posttransplant NK cell lymphoma associated with Epstein-Barr virus.

Adult↗

Use of echocardiography for predicting myocardial viability in patients with reperfused anterior wall myocardial infarction.

Dobutamine stress echocardiography (DSE), myocardial contrast echocardiography (MCE), and ultrasonic tissue characterization with integrated backscatter are useful methods for assessing myocardial viability in acute myocardial infarction. In this study, we compared the potential of 3 methods for predicting myocardial viability in 38 patients with reperfused anterior wall acute myocardial infarction. We performed MCE shortly after coronary reperfusion with an intracoronary injection of microbubbles. We recorded 2-dimensional integrated backscatter images at rest and, then, performed low-dose (10 microg/kg/min) DSE 3 days later. In integrated backscatter images, we placed the region of interest in the midwall of the myocardial segment to reconstruct the cyclic variation of myocardial integrated backscatter. The myocardial segment was judged viable when it showed active contraction 3 months later. Among 74 segments analyzed, 34 were judged viable. Presence of contractile response during DSE predicted segmental viability with 91% sensitivity and 78% specificity. Intense and homogenous contrast enhancement with MCE predicted viability with 82% sensitivity and 73% specificity. The presence of synchronous contraction of cyclic variation predicted myocardial viability with 79% sensitivity and 83% specificity. There were no differences in sensitivity and specificity among the 3 methods. Thus, MCE and ultrasonic tissue characterization can predict myocardial viability as accurately as DSE in patients with acute myocardial infarction. The logistics of the methods may determine clinical application.

Angioplasty, Balloon, Coronary↗

Antiplatelet drugs attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes.

The intima-media thickness of the carotid artery has been established as a surrogate of definite atherosclerosis in subjects with high risk of vascular events. This study was done to evaluate the effectiveness of long-term antiplatelet therapy in attenuating progression of the intima-media thickness of the carotid artery of subjects with type 2 diabetes. Subjects who had an intima-media thickness over the threshold of the normal subjects but showed no symptoms of vascular events were randomly divided into groups given antiplatelet drugs [ticlopidine (n = 34) or a small dose of aspirin (n = 40)] or no drugs (n = 74). For the follow-up period (3.0+/-0.06 years), the subjects not given antiplatelet drugs showed a significantly higher progression of intima-media thickness (0.067+/-0.009 mm/year) than those given ticlopidine (0.034+/-0.013 mm/year) or aspirin (0.033+/-0.010 mm/year). Stepwise multivariant regression analysis showed that long-term administration of ticlopidine or aspirin significantly reduced the progression of intima-media thickness of diabetic subjects by 0.041 mm/year or 0.032 mm/ year, respectively. These data indicated that despite differences of their pharmacological mechanisms, antiplatelet drugs could attenuate the progression of intima-media thickness of the carotid artery wall of asymptomatic type 2 diabetics who had early-stage carotid atherosclerosis.

Aged↗

Nifedipine-induced coronary vasodilation in ischemic hearts is attributable to bradykinin- and NO-dependent mechanisms in dogs.

BACKGROUND: Dihydropyridine calcium channel blockers protect endothelial cells against ischemia and reperfusion injury, suggesting that nifedipine may increase the in vivo cardiac NO level and thus coronary blood flow (CBF) in ischemic hearts. We tested this hypothesis. METHODS AND RESULTS: In open-chest dogs, coronary perfusion pressure (CPP) was reduced in the left anterior descending coronary artery so that CBF decreased to one third of the control level, and thereafter CPP was maintained constant (103+/-8 to 43+/-3 mm Hg, n=9). We obtained fractional shortening (FS) and lactate extraction ratio (LER) as indices of regional myocardial contraction and metabolism. Both FS (26.4+/-2.1% to 6.7+/-2.0%, n=9, P<0.001) and LER (32+/-6% to -37+/-5%, n=9, P<0.001) showed a decrease when CPP was reduced. After intracoronary infusion of nifedipine (4 microgram. kg(-1). min(-1)), CBF increased from 30+/-1 to 48+/-4 mL. 100 g(-1). min(-1) (P<0.01) without a change of CPP (n=9). Both FS (14.0+/-1.9%, n=9) and LER (-9+/-7%, n=9) also increased (P<0.01). Nifedipine increased the difference in the level of metabolites of NO (nitrate+nitrite; 9+/-3 to 25+/-5 nmol/mL, n=9, P<0.01) and bradykinin (22+/-5 to 58+/-4 pmol/mL, n=9, P<0.01) between coronary venous and arterial blood. L-NAME (an NO synthase inhibitor) or HOE-140 (a bradykinin receptor antagonist) attenuated (P<0.05) the increase in CBF (29+/-3 and 35+/-2 mL. 100 g(-1). min(-1), n=5 each), FS (4.8+/-0.6% and 6.9+/-1.7%, n=5 each), LER (-47+/-8% and -35+/-9%, n=5 each), and nitrate+nitrite (3+/-2 and 8+/-4 nmol/mL, n=5 each) due to nifedipine infusion. CONCLUSIONS: These results indicate that the calcium channel blocker nifedipine mediates coronary vasodilation and improves myocardial ischemia through both bradykinin/NO-dependent and -independent mechanisms.

Animals↗

T2-weighted MR imaging for focal hepatic lesion detection: supplementary value of breath-hold imaging with half-Fourier single-shot fast spin-echo and multishot spin-echo echoplanar sequences.

The purpose of our study was to evaluate the supplementary value of breath-hold fat-suppressed T2-weighted magnetic resonance (MR) imaging with half-Fourier single-shot fast spin-echo (SE) or multishot SE echoplanar (EP) sequences combined with respiratory-triggered fat-suppressed fast SE T2-weighted MR imaging for detection and characterization of focal hepatic lesions. MR images in 42 patients with 82 solid, malignant and 77 nonsolid, benign lesions were analyzed. Image review was conducted on a segment-by-segment basis; in all, 333 liver segments were reviewed separately for solid and nonsolid lesions by three independent radiologists. For solid lesions, observer performance with receiver-operating-characteristic (ROC) analysis in one radiologist and specificity in another significantly improved after adding single-shot fast SE images. For nonsolid lesions, observer performance with ROC analysis in one radiologist and specificity in another significantly improved after adding single-shot fast SE images. Combining breath-hold half-Fourier single-shot fast SE imaging with respiratory-triggered fast SE imaging may be recommended for improved detection and characterization of focal hepatic lesions. J. Magn. Reson. Imaging 2000;12:444-452.

Adipose Tissue↗

Assessment of hypermethylated DNA in two promoter regions of the estrogen receptor alpha gene in human endometrial diseases.

OBJECTIVE: DNA methylation in the promoter regions of many genes is associated with the regulation of gene expression. We examined the frequency of DNA hypermethylation at two nucleotide positions, the proximal promoter region (PPR) in exon 1 and the distal promoter region (DPR) in exon 1', of the estrogen receptor alpha (ERalpha) gene in 111 cases of various human endometrial diseases. METHODS: The degree of hypermethylation of PPR and DPR was examined by semi-quantitative competitive polymerase chain reaction assay using restriction enzymes (HpaII, NotI, and SacII). RESULTS: Endometrial tissues in the proliferative phase obtained from patients with leiomyomas and/or adenomyosis and no significant hormonal abnormalities did not show hypermethylation at the HpaII cleavage position of DPR. In 6 of 16 (37.5%) cases of simple endometrial hyperplasia, the PPR was hypermethylated, whereas in cases of atypical endometrial hyperplasia and endometrioid adenocarcinoma the frequencies were extremely low. Hypermethylation of these promoter regions did not correlate with lack of ERalpha protein in the 46 cases that were analyzed by enzyme immunoassay. CONCLUSIONS: ERalpha gene transcription from the distal promoter, rather than from the proximal promoter, is predominant in the proliferative phase of the normal menstrual cycle, because the PPR, but not the DPR, is frequently hypermethylated under those conditions. Conversely, ERalpha gene transcription from the proximal promoter is predominant in precancerous lesions such as atypical hyperplasia and endometrial cancer. However, hypermethylation at the promoter sites we examined was not related to the loss of ERalpha protein in endometrial disease.

Adult↗

Estimation of the area at risk in myocardial infarction of rats by means of I-123 beta-methyliodophenyl pentadecanoic acid imaging.

Clinical investigations have suggested that the defects in SPECT images of a free fatty acid analog, I-123 beta-methyliodophenyl pentadecanoic acid (BMIPP) may indicate the ischemic risk area. To elucidate whether I-123 BMIPP can indicate the area at risk of ischemia, ex-vivo autoradiography was performed in rats whose left coronary artery was occluded for 60 min and then reperfused. I-123 BMIPP was injected at the acute stage (n = 10), or the subacute stage (7 days after reperfusion; n = 9). Infarction and the area at risk were identified by triphenyl tetrazolium chloride staining and injection of methylene blue during religation just before sacrifice, respectively. The BMIPP uptake in the risk area was significantly lower than that in the remote area at the acute (risk, 53.7+/-23.3% of the uptake at right ventricle, mean +/- SD; remote, 109.3+/-11.8%; p < 0.01) and subacute (risk, 52.5+/-11.5%; remote, 97.9+/-14.3%; p < 0.01) stages. In addition, the area with reduced uptake of I-123 BMIPP showed a significant correlation with the area at risk both at the acute (r = 0.98, p < 0.01) and subacute (r = 0.92, p < 0.01) stages. In conclusion, the area at risk can be evaluated by I-123 BMIPP both at the acute and subacute stages.

Animals↗

Changes in perfusion and fatty acid metabolism of rat heart with autoimmune myocarditis.

To elucidate the change in perfusion and aerobic metabolism in myocarditis, tissue counting and dual tracer ex vivo autoradiography with Tl-201 and a free fatty acid analog, I-123- or I-125-labeled (p-iodophenyl)-methyl-pentadecanoic acid (BMIPP), were performed in rats with myocarditis induced by immunization with cardiac myosin. Inflammatory damage was classified histologically. At the acute stage (2-4 weeks after the antigen-injection), total heart uptakes of Tl and BMIPP and the ratio (BMIPP/Tl) were significantly reduced in myocarditis rats (N = 15) compared with the controls (N = 12). Myocardial distribution of Tl and BMIPP was not homogeneous. Relative uptake of Tl and BMIPP (N = 9, 128 regions) was gradually decreased with the extent of inflammation, and the regional BMIPP/Tl was smaller than the control. At the subacute stage (7 weeks after the antigen-injection), total Tl uptake in myocarditis rats (N = 5) recovered to the control level (N = 4), but that of BMIPP was still significantly lower than the control. BMIPP/Tl was still significantly lower in myocarditis. Myocardial distribution of Tl and BMIPP recovered to be more homogeneous. Relative uptake of Tl and BMIPP (N = 6, 78 regions) still gradually but significantly decreased with the extent of inflammation. Regional BMIPP/Tl was still depressed in myocarditis. These results indicate that myocardial perfusion and aerobic metabolism were discrepant and heterogeneously suppressed with severe inflammation during the acute stages, but the difference decreases with time. Examination with Tl-201 and BMIPP may provide information about the severity of myocarditis.

Animals↗

Characteristics of myocardial 18F-fluorodeoxyglucose positron emission computed tomography in dilated cardiomyopathy and ischemic cardiomyopathy.

Myocardial 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) has been used to assess myocardial ischemia and viability, but few studies have conducted on FDG-PET for dilated cardiomyopathy (DCM). We investigated myocardial FDG uptake in patients with DCM in comparison with ischemic cardiomyopathy (ICM). Twenty-four patients with heart failure were included in this study. Fourteen of them were diagnosed as DCM and the other 10 were ICM. All of them underwent myocardial FDG-PET at fasting and after glucose loading the same day. FDG uptake was quantified by the ratio of the counts at the heart to those at the liver (H/L ratio). Left ventricular (LV) function was measured by echocardiography. We classified FDG distribution patterns in the myocardium in the fasting state into 3 types (faint uptake, regional uptake and diffuse uptake). In DCM patients, 5 had faint uptake, 7 had regional uptake, and the other 2 had diffuse uptake. On the other hand, all ICM patient had regional uptake (p < 0.05). In DCM, there were no significant relationships between the patterns and LV functions. On the other hand, there were close correlation between the H/L ratio after glucose loading and the left ventricular ejection fraction (r = 0.680, p < 0.01). The changes in PET images caused by glucose loading were classified into 2 types (non-reversing and reversing patterns). DCM significantly showed a non-reversing pattern (86%, 12 of 14 patients) whereas ICM showed mainly a reversing pattern (70%, 7 of 10 patients; p < 0.05). In conclusion, myocardial FDG uptake after glucose loading may indicate a myocardial viable mass although FDG uptake at fasting was not evidently related to LV function. The change in the pattern of the FDG image from fasting to glucose loading may be useful in differentiating DCM from ICM.

Adult↗

The novel acute phase protein, IHRP, inhibits actin polymerization and phagocytosis of polymorphonuclear cells.

OBJECTIVE AND DESIGN: In the present study, the involvement of the binding of IHRP (inter-alpha-trypsin inhibitor family heavy chain-related protein) and actin in phagocyte activity was investigated. MATERIALS AND METHODS: The actin polymerization and the phagocytic activity of the polymorphonuclear (PMN) cells were studied in the presence of IHRP. RESULTS: IHRP inhibited the polymerization of actin and the phagocytic activity of the PMN cells. CONCLUSION: 1) IHRP may bind to actin released from the damaged cells and suppress its toxic action by preventing the formation of actin fibril. 2) IHRP may bind to cell surface actin on PMN cells and inhibit their phagocytic activities. 3) From these results, IHRP may act as an anti-inflammatory protein.

Actins↗

Two-dimensional thick-slice MR digital subtraction angiography for assessment of cerebrovascular occlusive diseases.

Although spatial resolution of current MR angiography is excellent, temporal resolution has remained unsatisfactory. We evaluated clinical applicability of 2D thick-slice, contrast-enhanced subtraction MR angiography (2D-MR digital subtraction angiography) with sub-second temporal resolution in cerebrovascular occlusive diseases. Twenty-five patients with cerebrovascular occlusive diseases (8 moyamoya diseases, 10 proximal internal carotid occlusions, and 2 sinus thromboses ) were studied with a 1.5-T MR unit. The MR digital subtraction angiography (MRDSA) was performed per 0.97 s continuously just after a bolus injection of 15 ml of gadolinium chelates up to 40 s in sagittal (covering hemisphere) or coronal planes. Subtraction images were generated at a workstation. We evaluated imaging quality and hemodynamic information of MRDSA in comparison with those of routine MR imaging, non-contrast MR angiography, and X-ray intra-arterial DSA. Major cerebral arteries, all of the venous sinuses, and most tributaries were clearly visualized with 2D MRDSA. Also, pure arterial phases were obtained in all cases. The MRDSA technique demonstrated prolonged circulation in sinus thromboses, distal patent lumen of proximal occlusion, and some collateral circulation. Such hemodynamic information was comparable to that of intra-arterial DSA. Two-dimensional thick-slice MRDSA with high temporal resolution has a unique ability to demonstrate cerebral hemodynamics equivalent to that of intra-arterial DSA and may play an important role for evaluation of cerebrovascular occlusive diseases.

Adult↗

Time-resolved two-dimensional thick-slice magnetic resonance digital subtraction angiography in assessing brain tumors.

The aim of this study was to evaluate clinical applicability of two-dimensional (2D) thick-slice, contrast-enhanced magnetic resonance digital subtraction angiography (MRDSA) with high temporal resolution in diagnosis of brain tumors. Forty-four patients with brain tumors including, 15 meningiomas, 8 gliomas, 6 metastatic tumors, 4 neuromas, and 2 hemangioblastomas, were studied with 2D MRDSA with frame rate approximately 1 s. Images were continuously obtained following the initiation of bolus injection of gadolinium chelates for 40 s and subtraction images were generated in a workstation. We evaluated visualization of normal cranial vessels on MRDSA and compared MRDSA and intra-arterial digital subtraction angiography (IADSA) with regard to hemodynamic information. Large cerebral arteries, all venous sinuses, and most tributaries were clearly visualized. A stain was present in hypervascular tumors including all 15 meningiomas and 2 hemangioblastomas on MRDSA. Presence of a stain demonstrated on MRDSA and that on IADSA coincided in 16 of 20 cases (Spearman rank correlation value was 0.85). The location, shape, and phase of the stain on MRDSA were similar to those on IADSA. Two-dimensional MRDSA with high temporal resolution has a unique ability to demonstrate cerebral hemodynamics, such as IADSA, and can play an important role in assessing brain tumors.

Adolescent↗

Resident macrophages activated by lipopolysaccharide suppress muscle tension and initiate inflammatory response in the gastrointestinal muscle layer.

A great number of macrophages is found to be evenly distributed in the muscle layer of the gastrointestinal tract. We investigated their effects on smooth muscle contraction and the initiation of immune reactions such as inflammatory responses. Macrophages were demonstrated by the uptake of FITC-dextran and their ultrastructural features were elucidated by electron microscopy. Muscle layers of rats' ilea were incubated with lipopolysaccharide (LPS) for 4-8 h and the force of smooth muscle contraction was measured. The induction effect of inducible nitric oxide synthase (iNOS) on macrophages was then checked by immunohistochemistry. The expression of major histocompatibility complex (MHC) class II was also examined. Macrophages in the muscle layer were confirmed as resident macrophages and were different from a population of dendritic cells. After incubation with LPS, macrophages began to express iNOS and produced NO, and it reduced smooth muscle contraction. iNOS-immunopositive cells increased in a time-dependent manner. Macrophages also began to express MHC class II. The total number of macrophages did not alter after incubation. Results indicate that resident macrophages in the muscle layer induced iNOS as an inflammatory reaction, affected smooth muscle contraction, and initiated immune response in the smooth muscle layer of the gastrointestinal tract, when activated by LPS.

Animals↗

Muscarinic stimulation does not induce rhoA/ROCK-mediated Ca2+ sensitization of the contractile element in chicken gizzard smooth muscle.

We have attempted to determine whether muscarinic stimulation induces RhoA/ROCK-mediated Ca2+ sensitization of contractions in chicken gizzard smooth muscles. rhoA is a small GTP-binding protein, and ROCK is a rhoA-associated coiled coil-forming serine/threonine kinase. The relationship between the cytosolic Ca2+ level ([Ca2+]i) and muscle force in the presence of a high K+ concentration was not different from that in the presence of carbachol. Verapamil inhibited muscle force in proportion to the decrease in [Ca2+]i in both the muscle stimulated with high K+ and that stimulated with carbachol. In addition, Y-27632 (10 microM), a ROCKs inhibitor, had no effect on the contractions. In the alpha-toxin-permeabilized muscles, Ca2+ induced a greater contraction in the presence of guanosine 5'-O-(3-thiotriphosphapte) (GTP[gamma-S]), whereas carbachol with GTP was not effective. The GTP[gamma-S]-induced Ca2+ sensitization was completely inhibited by Clostridium botulinum exoenzyme C3. Western blot analysis revealed both rhoA and ROCKII in the muscle extract. In addition, reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed the expression of both ROCKI and ROCKII mRNAs. These results suggest that Ca2+ sensitization in the chicken gizzard is elicited via a rhoA/ROCKs pathway, and that this pathway may be responsible for the augmentation of contraction by GTP[gamma-S] in the permeabilized muscles. If such a pathway does exist, however, carbachol-induced contraction may not be coupled to it, which explains the absence of Ca2+ sensitization in the intact chicken gizzard stimulated by carbachol.

Amides↗

Identification of 187 single nucleotide polymorphisms (SNPs) among 41 candidate genes for ischemic heart disease in the Japanese population.

To investigate whether common variants in the human genetic background are associated with pathogenesis of ischemic heart diseases, we systematically surveyed 41 possible candidate genes for single-nucleotide polymorphisms (SNPs) by directly sequencing 96 independent alleles at each locus, derived from 48 unrelated Japanese patients with myocardial infarction, including 25.8 kb 5' flanking regions, 56.8 kb exonic and 35.4 kb intronic sequences, and 1.8 kb 3' flanking regions. In this genomic DNA of nearly 120 kb, we identified 187 SNPs: 55 in 5' flanking regions, seven in 5' untranslated regions (UTRs), 52 in coding elements, 64 in introns, eight in 3' UTRs, and one in a 3' flanking region. Among the 52 coding SNPs, 26 were non-synonymous changes. Allelic frequencies of some of the polymorphisms were significantly different from those reported in European populations. For example, the Q506R substitution in the coagulation factor V gene, the so-called "Leiden mutation", has a reported frequency of 2.3% in Europeans, but we detected the Leiden mutation in none of the Japanese genomes that we investigated. The allelic frequencies of the -33A>G SNP in the thrombomodulin gene were also very different; this allele occurred at a 12% frequency in the Japanese patients that we examined, although it had been detected in none of 82 Caucasians reported previously. These data support the hypothesis that some SNPs are specific to particular ethnic groups.

3' Untranslated Regions↗

Local neurohumoral regulation in the transition to isolated diastolic heart failure in hypertensive heart disease: absence of AT1 receptor downregulation and 'overdrive' of the endothelin system.

OBJECTIVE: Although isolated diastolic heart failure with preserved left ventricular (LV) systolic function frequently occurs, regulation of local neurohumoral factors in the transition from diastolic dysfunction without signs of heart failure to diastolic failure, a target for therapeutic strategy, remains to be clarified, partly because of a lack of animal models. Our laboratory recently demonstrated that Dahl-Iwai salt-sensitive (Dahl-S) rats fed on a high-salt diet since 7 weeks of age develop hypertension followed by compensated LV hypertrophy at 13 weeks and transition to isolated diastolic heart failure at 19 weeks. METHODS: Gene expression of the components of the renin-angiotensin system, endothelin (ET) system and natriuretic peptide system in the left ventricle was investigated in the transition to isolated diastolic heart failure in this model. RESULTS: The compensated ventricular hypertrophy was associated with slight increases in angiotensin-converting enzyme (ACE) and angiotensin II type-1a (AT1a) receptor mRNA levels. Although preproET-1 (ppET-1) and ET-converting enzyme-1 (ECE-1) mRNA levels were not increased, mRNA levels of ET type-A (ETA) and ET type-B (ETB) receptors were increased. Atrial natriuretic peptide (ANP) mRNA level increased, but not brain natriuretic peptide (BNP) mRNA level. At the decompensated failing stage (at 19 weeks), ACE mRNA level further increased without downregulation of ATla receptor mRNA level. The mRNA levels of ppET-1 and ECE-1 increased with persistent upregulation of mRNA levels of ETA and ETB receptors, and immunohistochemical staining for ET-1 was found at endothelial cells and myocytes. BNP mRNA level increased with a further increase in ANP mRNA level. CONCLUSIONS: The transition to isolated diastolic heart failure in hypertrophied hearts was associated with preserved gene expression of the renin-angiotensin system and 'overdrive' of gene expression of the ET system. BNP gene expression is likely to be activated by the progression of diastolic failure rather than by LV hypertrophy alone.

Analysis of Variance↗