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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 289 records · Page 16Linked to original sources
PubMed2000

Fractalkine-mediated endothelial cell injury by NK cells.

Endothelial cells (ECs) are primary targets of immunological attack, and their injury can lead to vasculopathy and organ dysfunction in vascular leak syndrome and in rejection of allografts or xenografts. A newly identified CX3C-chemokine, fractalkine, expressed on activated ECs plays an important role in leukocyte adhesion and migration. In this study we examined the functional roles of fractalkine on NK cell activity and NK cell-mediated endothelial cell injury. Freshly separated NK cells expressed the fractalkine receptor (CX3CR1) determined by FACS analysis and efficiently adhered to immobilized full-length fractalkine, but not to the truncated forms of the chemokine domain or mucin domain, suggesting that fractalkine functions as an adhesion molecule on the interaction between NK cells and ECs. Soluble fractalkine enhanced NK cell cytolytic activity against K562 target cells in a dose- and time-dependent manner. This enhancement correlated well with increased granular exocytosis from NK cells, which was completely inhibited by the G protein inhibitor, pertussis toxin. Transfection of fractalkine cDNA into ECV304 cells or HUVECs resulted in increased adhesion of NK cells and susceptibility to NK cell-mediated cytolysis compared with control transfection. Moreover, both enhanced adhesion and susceptibility of fractalkine-transfected cells were markedly suppressed by soluble fractalkine or anti-CX3CR1 Ab. Our results suggest that fractalkine plays an important role not only in the binding of NK cells to endothelial cells, but also in NK cell-mediated endothelium damage, which may result in vascular injury.

Adjuvants, Immunologic↗
PubMed2000

CX3C-chemokine, fractalkine-enhanced adhesion of THP-1 cells to endothelial cells through integrin-dependent and -independent mechanisms.

Leukocyte adhesion and trafficking at the endothelium requires both cellular adhesion molecules and chemotactic factors. A newly identified CX3C chemokine, fractalkine, expressed on activated endothelial cells, plays an important role in leukocyte adhesion and migration. We examined the functional effects of fractalkine on beta1 and beta2 integrin-mediated adhesion using a macrophage-like cell line, THP-1 cells. In this study, we report that THP-1 cells express mRNA encoding a receptor for fractalkine, CX3CR1, determined by Northern blotting. Scatchard analysis using fractalkine-SEAP (secreted form of placental alkaline phosphatase) chimeric proteins revealed that THP-1 cells express a single class of CX3CR1 with a dissociation constant of 30 pM and a mean expression of 440 sites per cell. THP-1 cells efficiently adhered, in a fractalkine-dependent manner, to full-length of fractalkine immobilized onto plastic and to the membrane-bound form of fractalkine expressed on ECV304 cells or TNF-alpha-activated HUVECs. Moreover, soluble-fractalkine enhanced adhesion of THP-1 cells to fibronectin and ICAM-1 in a dose-dependent manner. Pertussis toxin, an inhibitor of Gi, inhibited the fractalkine-mediated enhancement of THP-1 cell adhesion to fibronectin and ICAM-1. Finally, we found that soluble-fractalkine also enhanced adhesion of freshly separated monocytes to fibronectin and ICAM-1. These results indicate that fractalkine may induce firm adhesion between monocytes and endothelial cells not only through an intrinsic adhesion function itself, but also through activation of integrin avidity for their ligands.

Adjuvants, Immunologic↗
PubMed2000

Methylenetetrahydrofolate reductase polymorphism and risk of colorectal adenomas.

A homozygous mutation at bp 677 in the gene for the methylenetetrahydrofolate reductase (MTHFR) was previously shown to be associated with a decreased risk of colorectal cancer. We examined the relation between the MTHFR genetic polymorphism and risk of colorectal adenoma in Japanese men using 205 cases of colorectal adenomas and 220 controls of normal total colonoscopy. The homozygous mutation was not measurably associated with colorectal adenomas. The findings corroborate the lack of an association between the MTHFR genotype and colorectal adenomas, but do not deny the possibility that the genotype may be involved in the late stage of colorectal carcinogenesis.

Adenoma↗
PubMed2000

2-Methoxy-4-(2-phthalimidinyl)phenylsulfonyl chloride as a fluorescent labeling reagent for determination of phenols in high-performance liquid chromatography and application for determination of urinary phenol and p-cresol.

Highly sensitive fluorescent labeling reagents, 2-(alkyloxy)-4-(2-phthalimidinyl)phenylsulfonyl chlorides (alkyloxy = methoxy, ethoxy, and propoxy; MPS-Cl, EPS-Cl, and PPS-Cl, respectively), for determination of phenols by high-performance liquid chromatography (HPLC) have been developed. These reagents react with phenols in basic medium to produce the corresponding fluorescent sulfonyl esters. The maximum fluorescence wavelengths of the derivatives were 308 nm for excitation and 410 nm for emission. The peaks due to phenol labeled with MPS-Cl, EPS-Cl, and PPS-Cl eluted at 6.3, 8.8, and 12.8 min, respectively, on a reversed-phase column with isocratic elution of methanol/water (2:1, v/v), and the detection limits (signal-to-noise = 3) of the derivatives were 10, 12, and 17 fmol per injection, respectively. Among these reagents, MPS-Cl was advantageous because its derivatives had shorter retention times and higher sensitivities in HPLC. The efficiency of converting phenol to the fluorescent derivative by MPS-Cl was about 100%. When MPS-Cl was applied to the determination of urinary phenol and p-cresol by HPLC using p-ethylphenol as an internal standard, the derivatives were separated at retention times of 6.3, 8.7, and 12.3 min, respectively, under the HPLC conditions described above. The concentrations of phenol and p-cresol in normal human urine were 11.9-293.5 and 8.2-346.1 nmol/mg creatinine, respectively.

Chromatography, High Pressure Liquid↗
PubMed2000

Transcatheter arterial chemoembolization therapy using iodized oil for patients with unresectable hepatocellular carcinoma: evaluation of three kinds of regimens and analysis of prognostic factors.

BACKGROUND: The current study was conducted to evaluate retrospectively the effects of three kinds of regimens used in transcatheter arterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC) and patients' prognosis, and to analyze their prognostic factors. METHODS: The study population was comprised of 152 patients who were treated by TACE alone. Three kinds of regimens were used successively: doxorubicin hydrochloride (ADM) and mitomycin C mixed with iodized oil in 26 patients (ADMOS group), a combination of cisplatin (CDDP) solution and ADMOS in 70 patients (CDDP-ADMOS group), and CDDP powder and pirarubicin hydrochloride mixed with iodized oil in 56 patients (CTLS group). The CTLS group was comprised of patients with significantly worse background factors than the other two groups. RESULTS: The initial tumor response rate with a > 50% reduction was 12%, 23%, and 30%, respectively, in the ADMOS, CDDP-ADMOS, and CTLS groups. CTLS was significantly more effective than ADMOS (P < 0.05), and slightly but not significantly better than CDDP-ADMOS (P <0.1). The cumulative survival rates for the ADMOS, CDDP-ADMOS, and CTLS groups were 59.0%, 70.1%, and 72.0%, respectively, at 1 year; 0%, 16. 3%, and 29.8%, respectively, at 3 years; and 0%, 4.1%, and 16.8%, respectively, at 5 years, with median survival times of 448 days, 574 days, and 758 days, respectively. The CTLS group showed a slightly but not significantly better survival than the ADMOS and CDDP-ADMOS groups (P <0.1). Multivariate analysis indicated that the significantly important prognostic factors (in order) were extrahepatic metastasis followed by the TACE regimen, serum alpha-fetoprotein levels, and portal vein involvement and that CTLS was the best of the three regimens. CONCLUSIONS: Although TACE, using an effective regimen, improves clinical results, tumor factors appear to be more important when determining prognosis.

Adult↗
PubMed2000

Impaired glucose tolerance as a determinant of early deterioration of left ventricular diastolic function in middle-aged healthy subjects.

To clarify the determinants of an abnormal relaxation diastolic pattern assessed by Doppler echocardiography, 131 middle-aged healthy subjects were analyzed. By multivariate logistic regression analysis, fasting insulin levels (p = 0.0016) and peak glucose levels (p = 0.046) were independent predictors of an abnormal relaxation diastolic pattern 2 hours after 75 g OGTT.

Diastole↗
PubMed2000

Radiographic analysis of lumbar motion in relation to lumbosacral stability. Investigation of moderate and maximum motion.

STUDY DESIGN: This in vivo study was performed to examine active lumbar motion without any support. OBJECTIVES: To establish the behavior of segmental flexibility according to the degree of whole lumbar motion and to clarify the correlation between bony characteristics of the lumbosacral junction and stability in the segment. SUMMARY OF BACKGROUND DATA: In previous studies, the full mobility of the lumbar segments has been investigated. The details of motion commonly seen with the activities of daily living have not been clarified. It has been reported that the iliolumbar ligaments have an influence on lumbosacral stability and that the relative thickness of the transverse process of L5 could indicate the functional strength of the iliolumbar ligaments. However, the effects of the iliolumbar ligaments on the lumbosacral range of motion have not been studied in vivo. METHODS: Ninety adults, aged 20-39 years, were requested to perform motion commonly associated with activities of daily living, defined as moderate motions of the lumbar spine. The subjects then were asked to perform maximal motion of the lumbar spine. The segmental ranges of motion, segmental flexion, and extension at every level of the lumbar spine were calculated by using functional radiographs. The correlation between the relative thickness of the transverse process of L5 and the motion seen at the lumbosacral junction was also determined. RESULTS: The greatest segmental range of motion was found at L2-L3 in moderate motion and at L4-L5 in maximal motion. It shifted gradually from the upper to lower lumbar levels with the increase in total lumbar motion. With an increase in lumbar spine motion, maximum segmental flexion shifted from L2-L3 to L3-L4, then to L4-L5. Segmental extension changed only at L5-S1, increasing with total lumbar spine motion. There was an inverse statistical correlation between lumbosacral motion and relative thickness of the L5 transverse process. CONCLUSIONS: The greatest segmental flexibility induced by the moderate lumbar motion, usually seen with the activities of daily living, occurred more in the upper segments of the lumbar spine, especially in flexion. Further, the iliolumbar ligaments regulate lumbosacral motion especially flexion.

Activities of Daily Living↗
PubMed2000

Exercise-induced U-wave alterations as a marker of well-developed and well-functioning collateral vessels in patients with effort angina.

OBJECTIVES: We sought to determine whether exercise-induced U-wave alterations are observed in association with well-developed and well-functioning collateral vessels. BACKGROUND: Although exercise-induced electrocardiographic (ECG) U-wave alterations including negative and prominent U waves have been established as a marker of significant or critical narrowing of a major coronary artery, the relation between this finding and the degree of collateral development has not yet been determined. METHODS: Patients with stable effort angina were divided into two groups according to the presence (group A, n = 46) or absence (group B, n = 79) of exercise-induced either negative or prominent U waves in the precordial leads; the clinical profiles, coronary angiographic findings and also ischemic status during 60 s of coronary balloon occlusion were compared between the two groups. RESULTS: The incidence of severe angina (CCS [Canadian Cardiovascular Society] class III or IV) was higher (p < 0.05) in group A (52%) than in group B (32%) patients. Good collateral vessels (Rentrop grade 2 or 3) into the perfusion territory of the culprit vessel were observed more frequently (p < 0.05) in group A (70%) than in group B (43%) patients. Coronary balloon angioplasty was carried out in 23 patients of group A and 40 patients of group B. Both ischemic ST changes (52% vs. 85%) and angina (57% vs. 80%) during balloon inflation were less (p < 0.05) frequently observed in group A than in group B. The incidence of no apparent myocardial ischemia with ST deviation or angina during the balloon inflation was higher (p < 0.05) in group A (39%) than in group B (10%) patients. In the prediction of the absence of myocardial ischemia during balloon inflation by the presence of exercise-induced U-wave alterations, the sensitivity was 69% (9/13) and the specificity was 72% (36/50) in the study patients. CONCLUSIONS: Exercise-induced U-wave alterations are a marker for well-developed collateral circulation in patients with stable but severe effort angina. This finding is also highly predictive of the absence of myocardial ischemia during transient coronary balloon occlusion and possibly of low-risk for development of acute myocardial infarction or hemodynamic instability upon abrupt closure of the culprit coronary artery.

Angina Pectoris↗
PubMed2000

Genetic variants of IL-13 signalling and human asthma and atopy.

Asthma and atopy show epidemiological association and are biologically linked by T-helper type 2 (T(h)2) cytokine-driven inflammatory mechanisms. IL-4 operates through the IL-4 receptor (IL-4R, a heterodimer of IL-4Ralpha and either gammac or IL-13Ralpha1) and IL-13 operates through IL-13R (a heterodimer of IL-4Ralpha and IL-13Ralpha1) to promote IgE synthesis and IgE-based mucosal inflammation which typify atopy. Recent animal model data suggest that IL-13 is a central cytokine in promoting asthma, through the stimulation of bronchial epithelial mucus secretion and smooth muscle hyper-reactivity. We investigated the role of common genetic variants of IL-13 and IL-13Ralpha1 in human asthma, considering IgE levels. A novel variant of human IL-13, Gln110Arg, on chromosome 5q31, associated with asthma rather than IgE levels in case-control populations from Britain and Japan [peak odds ratio (OR) = 2.31, 95% CI 1.33-4.00]; the variant also predicted asthma and higher serum IL-13 levels in a general, Japanese paediatric population. Immunohistochemistry demonstrated that both subunits of IL-13R are prominently expressed in bronchial epithelium and smooth muscle from asthmatic subjects. Detailed molecular modelling analyses indicate that residue 110 of IL-13, the site of the charge-modifying variants Arg and Gln, is important in the internal constitution of the ligand and crucial in ligand-receptor interaction. A non-coding variant of IL-13Ralpha1, A1398G, on chromosome Xq13, associated primarily with high IgE levels (OR = 3. 38 in males, 1.10 in females) rather than asthma. Thus, certain variants of IL-13 signalling are likely to be important promoters of human asthma; detailed functional analysis of their actions is needed.

Adult↗
PubMed2000

Altered expression of Fhit in carcinoma and precarcinomatous lesions of the esophagus.

The FHIT gene, located at chromosome 3p14.2, is a tumor suppressor gene often involved in tumors resulting from exposure to environmental carcinogens. We studied 46 pairs of esophageal primary tumors and corresponding normal squamous mucosa specimens by molecular genetic and immunohistochemical methods to investigate the role of the FHIT gene in esophageal carcinoma. In addition, we studied several different types of lesions, such as carcinoma in situ or dysplasia by immunohistochemistry. Loss of heterozygosity at or around the FHIT gene was observed in 35 (76%) primary tumors. Immunohistochemical detection of Fhit protein in the primary tumors demonstrated that 14 (30%) were positive and 32 (70%) were negative. We observed concordance between loss of Fhit protein and loss of heterozygosity and between loss of Fhit protein and RNA abnormalities. Because the FHIT/FRA3B locus is susceptible to damage by environmental carcinogens, we investigated the correlation between Fhit expression and smoking or alcohol habits. In this relatively small study, the patients who were both heavy users of tobacco and alcohol showed a significantly higher frequency of loss of Fhit expression than those who were light users. Noncarcinomatous squamous epithelium showed positive Fhit reactivity in most cases; however, five showed negative Fhit reactivity. Interestingly, all of these five patients had habits of heavy use of tobacco and alcohol. Eight of 12 carcinomas in situ, 2 of 4 severe dysplasias, 4 of 8 moderate dysplasias, and 3 of 9 mild dysplastic lesions showed negative Fhit reactivity. These findings indicated that loss of Fhit expression may be an early event in the development of human esophageal carcinoma and may occur even in normal-appearing squamous epithelium in some patients heavily exposed to environmental carcinogens.

Acid Anhydride Hydrolases↗
PubMed2000

A one-step phosphorylation of D-aldohexoses and D-aldopentoses with inorganic cyclo-triphosphate.

The phosphorylation reaction by inorganic cyclo-triphosphate (P3m) having a six-membered ring was examined for D-aldohexoses and D-aldopentoses in aqueous solution. Similar to the process for D-glucose, D-galactose, D-xylose or D-allose were phosphorylated with P3m to give stereoselectively beta-D-galactopyranosyl 1-triphosphate, beta-D-xylopyranosyl 1-triphosphate or beta-D-allopyranosyl 1-triphosphate with maximum yields of 31.3, 32.5 or 32.1%, respectively. On the other hand, in the reaction of D-ribose, D-lyxose, D-mannose or D-arabinose with P3m, the yields of beta-D-ribopyranosyl 1-triphosphate, alpha-D-lyxopyranosyl 1-triphosphate, alpha-D-mannopyranosyl 1-triphosphate or alpha-D-arabinopyranosyl 1-triphosphate were 8.0, 16.5, 9.6 or 14.1%, respectively. The phosphorylation mechanism of D-aldopyranoses with P3m was also discussed.

Chromatography, High Pressure Liquid↗
PubMed2000

Small angle X-ray scattering studies on local structure of tobacco mosaic virus RNA in solution.

Effects of temperature and ionic strength (S) on the local structure of tobacco mosaic virus RNA in phosphate buffer solution are studied by analyzing the small-angle X-ray scattering (SAXS) curves. The root-mean-square radius of a cross-section of RNA chain was kept at 0.845+/-0.005 nm over a wide range of S from 0.2 to 0.003 at 20 degrees C, whereas it gradually diminished from 0.85 to 0.61 nm when the temperature is raised from 20 to 50 degrees C at S = 0.2. Nevertheless, all of SAXS curves reflecting the backbone structures were equally mimicked by theoretical ones of freely hinged rod (FHR) models, i.e. several straight rods joined with freely hinged joints in the form of a combination of the letter Y, if the constituent rod lengths in the models are adjusted. From these facts, it is suggested that the local structure of the RNA chain in aqueous solution is characterized by an essential feature that unpaired bases in the partially double-stranded helix are constantly far isolated from each other along the helix and the rod-like structure of the helix is preserved over a range of helical contents. Such a characteristic local structure of the chain is entirely collapsed in the formamide solution at 50 degrees C.

Buffers↗
PubMed2000

Acetylcholine- and ergonovine-induced coronary microvascular spasm reflected by increased coronary vascular resistance and myocardial lactate production.

Diagnosis of coronary microvascular spasm remains largely speculative because it has been mostly based on chest pain and electrocardiographic ST-segment shift with slow filling of contrast medium into the coronary artery. A patient with resting chest pain and normal coronary angiograms underwent provocative tests with intracoronary acetylcholine (ACh) and ergonovine. During the tests, coronary diameter and flow velocity in the left anterior descending (LAD) coronary artery were measured with quantitative coronary angiography and intracoronary Doppler guide wire, respectively. Vascular resistance of the LAD and lactate production were determined separately. With injections of 100 microg of ACh and 20 microg of ergonovine, chest pain occurred with ST-segment elevation in the precordial leads in the absence of epicardial coronary spasm. Coronary vascular resistance increased by 2.2- and 1.6-fold of the baseline value with ACh and ergonovine, respectively. Myocardial lactate production was noted during the ST-segment elevation. Coronary microvascular spasm was verified by the increment in coronary vascular resistance and myocardial lactate production with concomitant ST-segment elevation in the presence of normal coronary angiograms.

Acetylcholine↗
PubMed2000

Relation of transesophageal echocardiographic findings to subtypes of cerebral infarction in patients with atrial fibrillation.

BACKGROUND: Transesophageal echocardiography (TEE) has been used to identify the potential risk for cardiogenic embolism in patients with atrial fibrillation (AF). However, ischemic stroke in patients with AF is not always attributable to embolism. Identification of the risk of embolic versus atherothrombotic stroke should lead to the optimal individualized management of patients with AF. HYPOTHESIS: The goal of the study was to determine the relation between cortical infarction and perforating infarction and TEE findings in patients with AF. METHODS: We investigated the clinical usefulness of TEE in the risk stratification of clinical subtyping of the cerebral infarctions which were divided into two territories of the cortical branch (cortical infarction due to embolism) and deep perforators (perforating infarction due to atherothrombosis). Left atrial spontaneous echo contrast, peak flow velocity in the left atrial appendage, and generalized atherosclerosis as estimated by the intima-media wall thickness of the thoracic aorta were assessed by TEE in 118 consecutive patients with either paroxysmal (n = 44) or chronic (n = 74) AF. All patients underwent either brain computed tomography or magnetic resonance imaging. RESULTS: Cortical and perforating infarction was found in 39 and 18% of patients, respectively. The grade of spontaneous echo contrast was higher in patients with than in those without cortical infarction (p < 0.05). In contrast, patients with perforating infarction showed significant increase in the aortic wall thickness when compared with patients without perforating infarction (p < 0.05). In addition, multivariate logistic analysis revealed that spontaneous echo contrast was an independent predictor of cortical infarction, while intima-media wall thickness of the aorta, hypertension, and age were useful in predicting the risk of perforating infarction. CONCLUSIONS: Transesophageal echocardiography has a potential role in the risk stratification for cortical and perforating infarction in patients with AF.

Aged↗
PubMed2000

Semi-quantitative approach to estimating GFR by magnetic resonance imaging.

OBJECTIVE: The purpose of this study was to compare a semi-quantitative approach to estimating glomerular filtration rate (GFR) by magnetic resonance imaging with radionuclide calculation of GFR, and to investigate whether spin echo or gradient echo is more suitable for estimating GFR. METHODS AND PATIENTS: Fourteen kidneys of seven patients (GFR ranging from 26 to 57 ml/min) were studied. Spin echo and gradient echo sequences interleaving each other at every excitation were used. After intravenous injection of gadopentetate dimeglumine, serial scans were performed. The signal intensities measured in the regions of interest were converted to time-transverse relaxation rate changes for both spin echo (DeltaR2) and gradient echo (DeltaR2*). The areas under the time-DeltaR2 and time-DeltaR2* curves were calculated as a semi-quantitative index of GFR for both spin echo and gradient echo images, and the results were compared by GFR measured by radionuclide imaging. RESULTS: The semi-quantitative index of the GFR calculated from spin echo images showed a significant correlation with the GFR measured by radionuclide imaging (r=0.85, P<0.001). On the other hand, the semi-quantitative index of the GFR calculated from gradient echo images showed no such correlation (r=0.46, P=0.10). CONCLUSION: Spin echo sequences may be more suitable than gradient echo sequences for the evaluation of GFR.

Adult↗
PubMed2000

Metastatic colon carcinoma found within an inguinal hernia sac: report of a case.

We report herein the case of a patient in whom metastatic colon carcinoma was found within an inguinal hernia sac. According to Lejar's classification, colon carcinomas within inguinal hernias are categorized as intrasaccular- and saccular-type tumors. In our patient, asymptomatic transverse colon carcinoma was the primary lesion, and to the best of our knowledge, this is only the fourth case of such a saccular-type tumor to be reported in the literature. To date, 21 cases of intrasaccular tumors have been reported, and saccular-type tumors are considered to be an even rarer entity, unless the patients have obvious ascites, indicating peritonitis carcinomatosa. Histologic examination of the hernia sac is recommended for male patients of advanced age with an inguinal hernia, especially those who have previously undergone surgery for colorectal carcinoma.

Adenocarcinoma↗
PubMed2000

Characterization and expression of a Neurospora crassa ribosomal protein gene, crp-7.

We have isolated and characterized a Neurospora crassa cytoplasmic ribosomal protein gene, named crp-7, which is found upstream of the photolyase gene. The deduced amino-acid sequence of this gene is highly homologous to the YS25 ribosomal protein of Saccharomyces cerevisiae. The crp-7 ORF consists of two exons which are separated by a short intron. The deduced polypeptide contains 87 amino acid residues and has a calculated molecular weight of 9.7 kDa. RFLP mapping showed that the crp-7 gene is located on the right arm of linkage group I. Southern blot hybridization analyses indicated that there is only one copy of the crp-7 gene in the N. crassa genome. Transcriptional elements, the Dde box, the Taq box and the CG element, that have been identified in other N. crassa ribosomal protein genes are observed in the promoter region of the crp-7 gene. The crp-7 mRNA levels were low in conidia and highest in young mycelia during vegetative growth. The mRNA levels of four r-protein genes, including the crp-7 gene, as well as the tef-1 gene encoding translational elongation factor 1 alpha, were raised following the treatment of mycelia with a low concentration of cycloheximide. This indicates that the expression of r-protein genes is under the control of so-called super-induction.

Amino Acid Sequence↗