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Biomedical subjects

Y Hori

Publications and source records attributed to Y Hori.

At least 19 recordsLinked to original sources
PubMed2005

Familial aggregation and coaggregation of history of hypertension and stroke.

We attempted to evaluate familial aggregation and coaggregation of history of hypertension and stroke. Past and family history of hypertension and stroke for 83 089 probands and their relatives were obtained from a data set for the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Ministry of Education (JACC Study), which was initiated from 1988 to 1990. First, evaluation was performed for familial aggregation of each of two disorders using ordinal logistic regression of the generalized estimation equations (GEE) to account for dependence of observations within families. Secondly, in order to evaluate the familial congregation of the history of hypertension and stroke, a GEE-based multivariate probed predictive model was applied. After adjusting for the proband's age, level of obesity, smoking status, drinking status, habitation area, and the gender and type of the relatives, the estimated odds ratios for the intraindividual clustering and familial aggregation of the disease history showed statistically significant relationships. In addition, the history of the two disorders showed a significant relationship in terms of familial coaggregation independently of the aggregation of each disorder itself. Our results confirmed that hypertension and stroke coaggregate strongly within families through possible effects of genetic factors, which, alone or in conjunction with environmental factors, influence susceptibility to both hypertension and stroke.

Adult↗
PubMed2005

Insertion of a C in the exon 28 of integrin alphaIIb gene leading to a frameshift mutation is responsible for Glanzmann thrombasthenia in a Japanese case.

BACKGROUND: Glanzmann thrombasthenia (GT) is a hereditary bleeding disorder caused by a qualitative or quantitative defect in the integrin alphaIIbbeta3. OBJECTIVE: Our objective is to identify the gene mutation that resulted in GT. PATIENTS AND METHODS: The patient was a 66-year-old male with a history of frequent bleeding. The expression levels of the integrin proteins in the platelets were determined by flow cytometry and Western blot analysis. The sequences of genomic DNA and mRNA encoding for alphaIIb and beta3 were analyzed by the dye-terminator cycle sequencing method. For transfection experiments, expression vectors encoding for wild-type alphaIIb, mutated alphaIIb, beta3, green fluorescent protein (GFP) fusion wild-type alphaIIb, GFP fusion mutated alphaIIb and DsRed fusion beta3 were constructed. These vectors were transfected to COS-7 cells, and the expression levels were determined. RESULTS: The alphaIIb protein was remarkably reduced in the patient's platelets, and gene analysis showed that the patient possessed compound heterozygous mutations in the alphaIIb gene. One was a C --> G substitution at the splice acceptor site (- 3) of exon 26 (CAG -->GAG) and the other was the insertion of an additional C at the region including six C bases between 2911 and 2916 in exon 28 (InsC). Transfection experiments using COS-7 cells showed that alphaIIb containing InsC had expressed and formed a complex with beta3, but had not been transported to the Golgi apparatus. CONCLUSIONS: In the present study the novel mutation InsC, leading to a frameshift that affects the transmembrane domain and the cytoplasmic tail, was found to be responsible for GT.

Aged↗
PubMed2003

Association between weight fluctuation and fasting insulin concentration in Japanese men.

OBJECTIVE: To investigate whether long-term weight fluctuation is associated with the fasting serum insulin concentration. DESIGN AND SUBJECTS: Weight histories of 1932 male Japanese workers aged 40-59 y were analyzed in relation to their current fasting serum insulin concentration. MEASUREMENTS: Individual weight fluctuation was calculated by root mean square error (RMSE) along the linear regression line of weight measured at five to six different ages. RESULTS: The mean RMSE and fasting insulin concentration were 1.22 kg and 4.5 microU/ml, respectively. The multivariate adjusted insulin level became higher with the increase in weight fluctuation. Subanalysis stratified by current body mass index (BMI) showed that the multivariate adjusted insulin level in individuals in the top quartile of fluctuation was 4.3 microU/ml, against 3.9 microU/ml in those in the bottom quartile (P=0.018, analysis of covariance (ANCOVA)) in the normal weight subgroup with current BMI below 25 kg/m(2). In the overweight subgroup with BMI 25 kg/m(2) or above, the level was 6.9 microU/ml in individuals in the top quartile and 6.2 microU/ml in those in the bottom quartile (P=0.054, ANCOVA). CONCLUSION: The results suggest that weight fluctuation increases the risk of developing hyperinsulinemia. Prospective observations together with measurement of changes in adiposity are needed for confirmation.

Adult↗
PubMed2003

The metabolic syndrome is associated with elevated circulating C-reactive protein in healthy reference range, a systemic low-grade inflammatory state.

OBJECTIVE: To elucidate the underlying mechanisms between C-reactive protein (CRP) and cardiovascular disease, we examined the association of circulating CRP in healthy reference range (< or =1.0 mg/dl) measured by high-sensitive CRP assay with the metabolic syndrome (MS). DESIGN: Cross-sectional study of circulating CRP in adult men. SUBJECTS: A total of 3692 Japanese men aged 34-69 y. MEASUREMENTS: Serum CRP, total cholesterol, triglycerides, LDL-cholesterol, fasting glucose, fasting insulin, uric acid, systolic blood pressure, diastolic blood pressure, and body mass index (BMI). RESULTS: There was a statistically significant positive correlation between CRP and BMI (r=0.25), total cholesterol (r=0.096), triglycerides (r=0.22), LDL-cholesterol (r=0.12), fasting glucose (r=0.088), fasting insulin (r=0.17), uric acid (r=0.13), systolic blood pressure (r=0.12), and diastolic blood pressure (r=0.11), and a significant negative correlation of CRP with HDL-cholesterol (r=0.24). After adjusting for age, smoking, and all other components of MS, obesity, hypertriglyceridemia, hyper-LDL-cholesterolemia, diabetes, hyperinsulinemia, and hyperuricemia were significantly associated with both mildly (> or =0.06 mg/dl) and moderately (> or =0.11 mg/dl) elevated CRP. Compared with men who had no such components of the MS, those who had one, two, three, four, and five or more components were, respectively, 1.48, 1.84, 1.92, 3.42, and 4.17 times more likely to have mildly elevated CRP levels (trend P<0.001). As for moderately elevated CRP, the same association was observed. CONCLUSIONS: These results indicate that a variety of components of the MS are associated with elevated CRP levels in a systemic low-grade inflammatory state.

Adult↗
PubMed2003

Long-term body weight variability is associated with elevated C-reactive protein independent of current body mass index among Japanese men.

OBJECTIVE: To elucidate the effect of long-term weight variability on C-reactive protein (CRP) levels. DESIGN: Cross-sectional study of the circulating CRP. SUBJECTS: A total of 637 Japanese men aged 40-49 y in1997. MEASUREMENTS: Serum CRP levels, body mass index in 1997 (current BMI), the slope of weight on age (weight-slope) representing an individual's weight trend of direction and magnitude, and the root mean square error around the slope of weight on age (weight-RMSE) representing the weight fluctuation magnitude, as calculated by a simple linear regression model in which each value of the subject's five actual weights (aged 20, 25, 30 y, five years ago, and current) was a dependent variable and the subject's ages independent variables. RESULTS: After adjustment for age and confounders, including smoking and health status, the odds ratios of elevated CRP (> or =0.06 mg/dl) were 1.83 (95% CI: 1.25-2.69), 2.63 (1.69-4.11), and 10.31 (2.17-48.98) for upper normal-weight (BMI: 22-<25 kg/m(2)), overweight (25-<30), and obese (> or =30) persons, respectively, compared with lower normal-weight persons (18.5-<22). Adjusting for age, confounders, and current BMI, weight-slope was positively associated with CRP level especially among subjects with BMI> or =25 kg/m(2) (trend P<0.01), and weight-RMSE was positively associated with CRP level particularly among subjects with BMI <25 kg/m(2) (trend P<0.05). CONCLUSION: Our results suggest a state of low-grade systemic inflammation not only in overweight and obese persons, but also in normal-weight persons with large weight fluctuation, possibly explaining in part the positive association between weight fluctuation and CVD.

Adipose Tissue↗
PubMed2003

The accuracy of long-term recall of past body weight in Japanese adult men.

OBJECTIVE: To examine the influences of recall period, current body weight, weight gain and loss, and weight variability on the accuracy of long-term recall of past weight. DESIGN AND SUBJECTS: Comparison of recalled weights around 25 y old with weights measured at age 25y in health checkup records among 2453 Japanese men (age: 34-61 y). MEASUREMENTS: Deviations between reported and measured weights were examined as to the three indexes: actual error (reported-measured), percent error (actual error/measured x 100), and absolute value of the percent error. Weight variability was defined as (1) the coefficient of variation of weight (CV) and (2) the root mean square error around the slope of weight on age (RMSE). RESULTS: Recalled weight strongly correlated with measured weight (r=0.849). Correlation coefficients decreased as age or the elapsed time since age 25y increased. Recalled weight (mean=58.3 kg) was slightly greater than measured weight at age 25y (mean=57.0 kg, mean actual error=1.28 kg). Subjects with a current body mass index (BMI) of less than 28.6 kg/m(2) overestimated their past weights, whereas those with BM1 of 28.6 kg/m(2) or over underestimated it. Subjects with weight loss since age 25y underestimated their past weights, whereas those with stable weight or gain overestimated it. There were monotonic increases in the three indexes of deviation across the CV quartile categories. Concerning the effect RMSE, a similar trend was observed. CONCLUSION: These results indicate that past body weights over a long period seem to be recalled with good accuracy. However, it should be kept in mind when using recalled weight in an epidemiologic study that accuracy of recall is influenced by age or elapsed time, current BMI, weight gain and loss, and weight variability.

Adult↗
PubMed2003

Glanzmann's thrombasthenia due to a point mutation within intron 10 results in aberrant splicing of the beta3 gene.

Glanzmann's thrombasthenia (GT) is an hereditary bleeding disorder caused by a quantitative or qualitative defect in the integrin alphaIIbbeta3. We attempted to identify genetic defects responsible for a case of GT in Korea. The patient was a 6-year-old boy who had suffered from hemorrhage and purpura. The cDNAs of alphaIIb and beta3 were amplified by reverse transcription (RT)-PCR and were sequenced. RT-PCR of COS7 cells transfected with Exontrap vectors containing the beta3 genomic DNA fragments were performed to verify an aberrant splicing. Transient expression of alphaIIbbeta3 on transfected-COS7 cells was determined by flow cytometry, and the presence of alphaIIbbeta3 was confirmed by immunoprecipitation. We discovered an abnormality with the insertion of 38 bp between exon 10 and exon 11, including a stop codon, in beta3 cDNA. Sequence analysis of genomic DNA showed a point mutation, G-->T, at the position 29 107 of intron 10. RT-PCR analyses of COS7 cells transfected with Exontrap vector containing the mutant beta3 gene revealed that the point mutation at the position 29 107 of intron 10, G-->T, was responsible for an aberrant splicing in the beta3 gene. The transfection experiments and immunoprecipitation revealed the absence of alphaIIbbeta3 in the COS7 cells transfected with mutant gene. The mutation at the position 29 107 of intron 10, G-->T, in the beta3 genomic DNA was found to induce an aberrant splicing and to be responsible for GT in this patient.

Alternative Splicing↗
PubMed2003

Effect of basic fibroblast growth factor on vascularization in esophagus tissue engineering.

We carried out an experimental study to evaluate the effect of basic fibroblast growth factor (bFGF)-containing collagen gel on vascularization in esophageal tissue engineering. We compared an acellular collagen sponge scaffold and an acellular collagen gel scaffold in combination with bFGF using a canine model. The construct was implanted in the cervical esophagus and the regenerated tissue was evaluated one month after surgery. Histological analysis confirmed a significantly large amount of blood vessels in the bFGF-containing collagen gel group as compared to the collagen gel group without bFGF (bFGF (-)). However, in the collagen sponge groups, no difference was observed between the bFGF (+) group and the bFGF (-) group. These results showed that bFGF-containing collagen gel is suitable not only for an acellular scaffold for tissue engineering but also for an effective tropic factor vehicle in vivo.

Animals↗
PubMed2003

Immunohistochemical study of macrophage migration inhibitory factor in rat liver fibrosis induced by thioacetamide.

Macrophage migration inhibitory factor (MIF) is a molecule known to regulate macrophage accumulation at sites of inflammation. To elucidate the role of MIF in progression of liver fibrosis, the immunohistochemical localization of MIF and macrophages in the liver were examined. Male Wistar rats received thioacetamide (TA) injections (200 mg/kg, i.p.) for 1 or 6 weeks. In biochemical and histological tests, it was confirmed that liver fibrosis was induced. In immunohistochemical analyses, the expression of MIF protein was seen in hepatocytes in the areas extending out from the central veins to the portal tracts. In particular, at 6 weeks, immunoreactivity was detected in degenerated hepatocytes adjacent to the fibrotic areas but hardly observed in the fibrotic areas. On the other hand, a number of exudate macrophages stained by antibody ED1 were seen in the areas from the central veins to the portal tracts at 1 week and in the fibrotic areas at 6 weeks. Macrophages also showed a significant increase in number as compared with controls. These results revealed that there was a close relationship between the appearance of MIF expression and ED1-positive exudate macrophages in degenerated hepatocytes during the progression of TA-induced liver fibrosis.

Animals↗
PubMed2002

Inhibition of antigen-induced arthritis in guinea pigs by a selective LTB4 receptor antagonist LY293111Na.

OBJECTIVE AND DESIGN: To investigate the role of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) in the development and progression of antigen-induced arthritis (AIA) in guinea pigs and rats. METHODS: Arthritis was induced by injecting cationic amidated bovine serum albumin (aBSA) into the knee joint of immunized guinea pigs or rats. The effect of a potent and selective LTB4 receptor antagonist, LY29311INa (2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]-propoxy]-phenoxy]benzoic acid sodium salt) was compared with those of indomethacin and dexamethasone. The effect of LY293111Na on adjuvant arthritis in rats was also examined. RESULTS: LY293 111Na (5 to 50 mg/kg b.i.d.) significantly inhibited knee joint swelling and histopathological changes of AIA in guinea pigs, but not in rats. Especially its protective effect against bone and cartilage destruction was substantial. In contrast, the cyclooxygenase inhibitor indomethacin significantly inhibited AIA in rats, but slightly inhibited in guinea pigs, while dexamethasone markedly inhibited AIA in both guinea pigs and rats. Increases of LTB4 and myeloperoxidase (MPO) activity were observed in the knee joint tissue of AIA guinea pigs, and LY293111Na dose-dependently inhibited the increase of MPO activity. Moreover, in adjuvant arthritic rats, LY293111Na showed slight inhibitory effect, while indomethacin showed marked inhibition. CONCLUSIONS: LTB4 but not PGE2 appeared to play important roles as an effective mediator in joint, particularly in cartilage and bone destruction of AIA in guinea pigs probably by inducing polymorphonuclear leukocytes (PMNs) chemotaxis to the joint tissue. In contrast, PGE2 but not LTB4 is an important mediator of arthritis in rats.

Animals↗
PubMed2002

Evaluation of peripheral nerve regeneration across an 80-mm gap using a polyglycolic acid (PGA)--collagen nerve conduit filled with laminin-soaked collagen sponge in dogs.

We evaluated peripheral nerve regeneration using a novel artificial nerve conduit. The conduit was made of a polyglycolic acid(PGA) - collagen tube filled with laminin- soaked collagen sponge. We implanted this nerve conduit across an 80mm gap in the peroneal nerve of dogs. Histological observation 12 months after implantation showed numerous unmyelinated and myelinated nerve fibershad regenerated beyond the gap. Neurofilaments were widely observed immunohistochemically in the regenerated nerve segments. These findings indicated that newly regenerated axons had extended across the gap and connected into the distal nerve segments. Compound muscle action potentials(CMAPs) and somatosensory evoked potentials (SEPs) were recorded in all dogs. At 12 months, the CMAPs indicated complete recovery, while the SEPs showed incomplete but substantial recovery. Walking patterns had returned to near-normal 12 months after implantation. Use of this nerve conduit can lead to peripheral nerve elongation and favorable functional recovery across a wider nerve gap.

Absorbable Implants↗
PubMed2001

Effect of methylprednisolone on phospholipase A(2) activity and lung surfactant degradation in acute lung injury in rabbits.

Glucocorticoids are the most potent and widely used anti-inflammatory agents, but they are not particularly effective against early phase of acute respiratory distress syndrome. We investigated whether methylprednisolone, a synthetic glucocorticoid, could inhibit increase of phospholipase A(2) activity in the lung and lead to protection against a model of acute respiratory distress syndrome in rabbits. Infusion of oleic acid (0.1 ml/kg/h, i.v. for 2 h) provoked pulmonary hemorrhage and edema, protein leakage and massive neutrophil infiltration, resulted in severe hypoxemia and impaired lung compliance, accompanying the increase of phospholipase A(2) activity and interleukin-8, and degradation of surfactant in the bronchoalveolar lavage fluid. Infusion of methylprednisolone (60 mg/kg/h, i.v. for 30 min before the oleic acid and then 0.5 mg/kg/h, i.v. for 6 h) did not improve the above described lung injury induced by oleic acid, nor did it suppress phospholipase A(2) activity and degradation of surfactant in bronchoalveolar lavage fluid, while it strongly reduced interleukin-8 levels in both plasma and bronchoalveolar lavage fluid. We conclude that methylprednisolone did not attenuate oleic acid-induced acute lung injury and this can be explained partly by its failure to reduce the increase of phospholipase A(2) activity and the surfactant degradation in the lung, which might also account for its clinical ineffectiveness against early acute respiratory distress syndrome.

Animals↗
PubMed2001

Deterioration of axotomy-induced neurodegeneration by group IIA secretory phospholipase A2.

Phospholipase A2 (PLA2) is proposed to play a role in the repair of the ruptured membrane after axotomy. In neonatal rats, we examined the effect of Group IIA secretory PLA2 (sPLA2-IIA) on axotomy-induced cell death of motoneurons. sPLA2-IIA significantly induced death of axotomized motoneurons. Indoxam, a specific inhibitor for sPLA2-IIA, protected motoneurons from the sPLA2-IIA-induced deterioration. The present study indicated that sPLA2-IIA possessed neurotoxic effect rather than neuroprotective effect against facial nerve.

Animals↗
PubMed2001

Mice lacking histidine decarboxylase exhibit abnormal mast cells.

Histidine decarboxylase (HDC) synthesizes histamine from histidine in mammals. To evaluate the role of histamine, we generated HDC-deficient mice using a gene targeting method. The mice showed a histamine deficiency and lacked histamine-synthesizing activity from histidine. These HDC-deficient mice are viable and fertile but exhibit a decrease in the numbers of mast cells while the remaining mast cells show an altered morphology and reduced granular content. The amounts of mast cell granular proteases were tremendously reduced. The HDC-deficient mice provide a unique and promising model for studying the role of histamine in a broad range of normal and disease processes.

Alleles↗
PubMed2001

Warthin's tumor of parotid gland on Tc-99m pertechnetate scintigraphy with lemon juice stimulation: Tc-99m uptake, size, and pathologic correlation.

The aim of this study was to evaluate the usefulness of technetium-99m (Tc-99m) pertechnetate scintigraphy with lemon juice stimulation in the diagnosis of Warthin's tumor and its correlation with Tc-99m uptake, tumor size, and histologic subtype. Tc-99m pertechnetate scintigraphy before and after lemon juice stimulation and pathologic specimens of 34 Warthin's tumors and 47 non-Warthin's lesions were retrospectively evaluated. Tc-99m uptake of Warthin's tumors before and after stimulation was visually graded as follows: absent; indeterminate; low grade; definite; and strong. Tumor size was defined as maximum diameter of the tumor measured from the surgical specimen. Warthin's tumors were classified into three histologic subtypes according to the ratio of epithelial and lymphoid stromal components: predominant epithelial; intermediate; and low-grade epithelial types. Eighteen of 34 (53%) Warthin's tumors and one benign lymphoepithelial cyst showed higher uptake than that of the normal parotid gland on Tc-99m scintigraphy before lemon juice stimulation. Thirty-two of the 34 (94%) Warthin's tumors, one benign lymphoepithelial cyst, one pleomorphic adenoma, and one oncocytoma revealed higher uptake than that of the normal parotid gland on Tc-99m scintigraphy after lemon juice stimulation. The mean size was 37 mm in strong uptake Warthin's tumors, 24 mm in definite uptake tumors, 19 mm in low-grade uptake tumors, and 12 mm in low-grade uptake tumors excluding those tumors with large cystic component. There was a significant correlation between tumor size and degree of Tc-99m uptake after lemon juice stimulation. However, there was no correlation between histologic subtype and Tc-99m uptake, and histologic subtype and tumor size in Warthin's tumors. Our study concludes that Tc-99m pertechnetate scintigraphy with lemon juice stimulation is useful for the detection and diagnosis of Warthin's tumor. The degree of uptake in Warthin's tumor on Tc-99m scintigraphy with lemon juice stimulation depends mainly on tumor size and the presence of large cystic component in it.

Adenolymphoma↗
PubMed2001

Multiconnection of identical zinc finger: implication for DNA binding affinity and unit modulation of the three zinc finger domain.

Cys(2)-His(2)-type zinc finger proteins have a tandemly repeated array structure consisting of independent finger modules. They are expected to elevate the DNA binding affinity and specificity by increasing the number of finger modules. To investigate the relation between the number and the DNA binding affinity of the zinc finger, we have designed the two- to four-finger peptides by connecting the central zinc finger (finger 2) of Sp1 with the canonical linker sequence, Thr-Gly-Glu-Lys-Pro. Gel mobility shift assays reveal that the cognate three- and four-finger peptides, Sp1(zf222) and Sp1(zf2222), strongly bind to the predicted target sequences, but the two-finger peptide, Sp1(zf22), does not. Of special interest is the fact that the dissociation constant for Sp1(zf2222) binding to the target DNA is comparable to that for Sp1(zf222). The methylation interference, DNase I and hydroxyl radical footprintings, and circular permutation analyses demonstrate that Sp1(zf2222) binds to its target site with three successive zinc fingers and the binding of the fourth zinc finger is inhibited by DNA bending induced by the binding of the three-finger domain. The present results strongly indicate that the zinc finger protein binds to DNA by the three-finger domain as one binding unit. In addition, this information provides the basis for the design of a novel multifinger protein with high affinity and specificity for long DNA sequences, such as chromosomal DNAs.

Base Sequence↗
PubMed2001

Guide DNA technique reveals that the protein component of bacterial ribonuclease P is a modifier for substrate recognition.

We developed a guide DNA technique with which the cleavage efficiency of pre-tRNA substrate raised in the RNase P reaction. The 20-mer guide DNAs hybridizing to the upstream region of the cleaving site enhanced the cleavage reactions of RNA substrates by Escherichia coli RNase P. This guide DNA technique was also applicable to cleavage site selection by choosing the DNA-hybridizing site. Results showed that RNase P accepts DNA/RNA double-stranded 5'-leader region with high catalytic efficiency as well as single-stranded RNA region in pre-tRNAs as substrates, which suggests that the protein component of bacterial RNase P prefers bulky nucleotides. The protein component did not affect the normal 5'-processing reaction of pre-tRNAs, but enhanced the mis-cleaving (hyperprocessing) reactions of tRNA in non-cloverleaf folding. Our results suggested that the protein component of RNase P is a modifier for substrate recognition.

Bacterial Proteins↗