Biomedical subjects

T Hayashi

Publications and source records attributed to T Hayashi.

At least 109 records · Page 6Linked to original sources

PubMed2003

Conservation of the syntenies between porcine chromosome 7 and human chromosomes 6, 14 and 15 demonstrated by radiation hybrid mapping and linkage analysis.

Comparative mapping studies facilitate the identification of genes located in quantitative trait locus (QTL) regions in domestic animals by utilizing information from the human genome. Radiation hybrid (RH) mapping is effective for this purpose because of its high resolution in ordered gene mapping on chromosomes. We constructed an RH map of pig chromosome 7, by adding 23 markers associated with genes. This RH map clearly demonstrated the mosaic of homology between pig chromosome 7 (SSC7) and human chromosomes 6, 14 and 15 at a 'gene' level, and was confirmed by linkage analysis. Clarification of the homology of SSC7 to human chromosomes will contribute to the elucidation of the gene(s) responsible for QTL detected on this chromosome.

Animals↗

PubMed2003

Significance of HTLV-1 proviral load quantification by real-time PCR as a surrogate marker for HTLV-1-infected cell count.

We developed a real-time (RT) PCR quantitative assay to measure the level of the integrated viral genome of HTLV-1 in host peripheral blood-mononuclear cells (PB-MNC) from healthy carriers and patients with adult T-cell leukemia (ATL). All of the clinical specimens were serologically and molecularly characterized by enzyme-linked immunosorbent assay (ELISA) and Southern blot hybridization (SBH) analyses. The assay system for quantifying the proviral copy level was sensitive, accurate, and reproducible over a wide range of density from 100 to 0.1% with a coefficient of variation (%) of 4.5 to 9.6. The proviral load of the healthy carriers and patients with ATL was 301 +/- 339 copies per 10(4) MNC (3 +/- 3.4%) on average and varied depending on the ATL cell number and the SBH band-status of single or multiple bands. In ATL cases with multiple bands detected by SBH analysis, their ATL cells were shown to harbor multiple copies within one ATL cell, so that the corrected copy number interpolated by the band number in SBH was closely equivalent to the expected ATL cell number in PB, corresponding to the virus-infected cell burden. The proviral load in healthy carriers ranged from 0.1 to 15% of PB-MNC, and, in combination with the fraction (%) of ATL-like flower cells defined by PB smear morphology, enabled carriers to be subgrouped into three categories. This result indicates that the detection of proviral load by(RT) PCR is sufficient and relevant to monitor the infected cell number in the PB and to evaluate the HTLV-1 pathologic status.

Biomarkers↗

PubMed2003

Interleukin-4-expressing plasmid DNA inhibits reovirus type-2-triggered autoimmune insulitis in DBA/1 J suckling mice.

In this study we have examined the effect of systemic administration of T helper (Th) 2 cytokines on reovirus type-2 (Reo-2)-triggered Th1-mediated autoimmune insulitis with impaired glucose tolerance (IGT) in DBA/1J suckling mice. We have demonstrated clearly that the systemic administration of both interleukin (IL)-4-expressing plasmid DNA (pIL-4) and recombinant IL-4 (rIL-4) inhibited the development of insulitis with IGT in a dose dependent manner as compared to untreated groups in Reo-2-infected DBA/1J suckling mice. The inhibitory effects of IL-4 on the development of insulitis with IGT and the advantages of pIL-4 as compared to rIL-4 in this model are discussed.

Animals↗

PubMed2003

Less sensitivity for late airway inflammation in males than females in BALB/c mice.

Several studies have investigated allergic airway inflammation, a T helper 2 (Th2)-type immune response, using a mouse model of asthma. At present, however, no reports have described sex differences in the sensitivity of late airway inflammation (LAI). The LAI induced by ovalbumin in adult BALB/c mice was compared in males and females or sham-operated males and castrated males. The males showed less severe bronchial-bronchiolar inflammation with infiltration of eosinophils and lymphocytes and lower content of such cells in bronchoalveolar fluid than the females. Moreover, interleukin-4 (IL-4) mRNA expression levels in splenic cells were lower in the males than in the females. Castrated males performed like the females. Moreover, when compared with the sham-operated males, the castrated males showed lower testosterone levels in the blood. The present results suggest that less sensitivity for LAI in the males may be because of the decreased Th2 cell responses compared with the females. Moreover the testosterone, at least in part, may be responsible for the decreased Th2 cell responses in males in vivo.

Animals↗

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 antibodies to intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 on cytokine mRNA expression in reovirus type-2-triggered autoimmune insulitis in suckling DBA/1 mice.

Interleukin (IL)-12 in the presence of IL-18 induces T helper (Th) 1 dominated systemic immune reactions, such as those that occur in autoimmune insulitis in suckling mice infected with reovirus type-2 (Reo-2). The role of intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 on the induction of cytokines responsible for Reo-2-triggered insulitis with impaired glucose tolerance (IGT) was examined. One-day-old DBA/1 mice infected with Reo-2 intraperitoneally (i.p.) were treated i.p. with monoclonal antibodies (mAbs) against ICAM-1 and LFA-1 (ICAM-1/LFA-1) at 5 days post-infection (d.p.i.). At 10 d.p.i., the administration of the mAbs was seen to have prevented the development of insulitis with IGT. This was associated with a decrease in the mRNA expression for IL-12(p40) and IL-18 by splenic cells. The present study suggests that ICAM-1/LFA-1 may be required for the differentiation of Th0 cells to Th1 cells, which mediate insulitis with IGT in Reo-2-infected suckling mice.

Animals↗

PubMed2003

Covered expandable metallic stent placement for hemostasis of colonic bleeding caused by invasion of gallbladder carcinoma.

A 72-year-old Japanese man was admitted to our hospital complaining of right upper-quadrant abdominal pain, blood in his stool, and symptoms of anemia. On physical examination a hard mass, about 6 cm in diameter, was palpable in the right upper quadrant of the abdomen. Computed tomography revealed a gallbladder carcinoma which had invaded the transverse colon, with liver metastasis. We diagnosed gallbladder carcinoma, stage IVB. Colonoscopy was performed for persistent blood in the stools. This revealed an elevated lesion which appeared to be an invasion of gallbladder carcinoma, with diffuse bleeding from the right-side of the transverse colon. It proved difficult to stop this bleeding by ordinary therapeutic endoscopy. In order to achieve hemostasis we therefore inserted a covered Ultraflex metallic stent to compress the tumor. After stent placement, blood was no longer seen in the patient's stools, he became able to eat soft food and was discharged. This treatment was uninvasive and effective. Covered stent placement appears to be a new and useful method in the management of bleeding from malignant gastrointestinal tumors.

Aged↗

PubMed2003

Similar effects of cocaine and immobilization stress on the levels of heat-shock proteins and stress-activated protein kinases in the rat hippocampus, and on swimming behaviors: the contribution of dopamine and benzodiazepine receptors.

Cocaine (COC) has been reported to cause effects similar to physiological stressors in the brain neuroendocrinal system, including heat-shock protein (HSP) expression, although these effects have not been elucidated in detail. In the present study, we examined the effects of repeated (4 days) treatments with cocaine hydrochloride (35 mg/kg, i.p.) and 10 min immobilization stress (IM) on the distribution of HSP (HSP27, HSP60, HSP70, HSC70) and stress-activated protein kinase (SAPK) (SAPKalpha, SAPKbeta, SAPKgamma) immunoreactive nerve cells (positive cells) in the rat hippocampus. The swimming behaviors of the rats in the forced swimming test were also examined. In both COC and IM groups, an early enhancement (5 h time point) of hippocampal HSP (HSP27, HSP60, HSP70, HSC70) and SAPK (SAPKbeta, SAPKgamma) positive cells was observed, whereas a recovery (SAPKs) or attenuation (HSP60 and HSC70) was observed at the 24 h time point. In both groups, a depression of the swimming behaviors (attenuation in the activity counts and time until immobility) below the control level was observed at the 5 h point, but a recovery was observed at the 24 h time point. At the 48 h time point, all parameters returned to the control level. These alterations in the levels of HSPs and SAPKs, and the swimming behaviors were similar to those observed in the stress (IM) group, and were characteristic in that all of these alterations were attenuated by the benzodiazepine inverse agonist, Ro 15-4513 (5 mg/kg, i.p.), and the dopamine D1 receptor antagonist, SCH23390 (0.5 mg/kg, i.p.), which was not observed in the groups treated with another stressor-like drug (bicuculline).

Animals↗

PubMed2003

Argon plasma coagulation for successful treatment of early gastric cancer with intramucosal invasion.

BACKGROUND: In recent years, there has been an increasing number of cases of early gastric cancer (T1, NX) with intramucosal invasion, which are untreatable by surgical or endoscopic mucosal resection (EMR) because of their high risk. Currently, no adequate treatment is available for such patients. AIM: The main objective of this study was to evaluate whether argon plasma coagulation (APC) is an effective and safe modality for treating early gastric cancer untreatable by surgical resection or EMR. METHODS: The study group comprised 20 men and seven women diagnosed with gastric cancer with intramucosal invasion who were considered poor candidates for surgical resection or EMR due to risk factors such as severe cardiac failure or thrombocytopenia. Irradiation conditions for APC treatment were determined using swine gastric mucosa. We used an argon gas flow of 2 l/min at a power setting of 60 W and a maximum irradiation time of 15 s/cm(2). The follow up period of the 27 patients ranged from 18 to 49 months (median 30 months). RESULTS: All lesions were irradiated easily, including areas anatomically difficult for EMR such as the gastric cardia or the posterior wall of the upper gastric body. In 26 of 27 patients (96%) there was no evidence of recurrence during the follow up period (median 30 months). One patient showed recurrence six months after the treatment but was successfully retreated. No serious complications were found in any of the 27 patients but three patients (11%) experienced a feeling of abdominal fullness. INTERPRETATION: APC is a safe and effective modality for treatment of early gastric cancer with intramucosal invasion untreatable by surgical resection or EMR. However, further observations are necessary to determine the long term prognosis of patients undergoing this treatment.

Adenocarcinoma↗

PubMed2003

Angiotensin II receptor blockade prevents microangiopathy and preserves diastolic function in the diabetic rat heart.

BACKGROUND: Cardiac microangiopathy may be involved in the development of heart failure in diabetes mellitus. OBJECTIVE: To evaluate the effect of angiotensin II receptor blockade on cardiac function and fine structures in diabetes. METHODS: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 30), a model of spontaneously developing diabetes mellitus, and their diabetes resistant counterparts (n = 20) were used. At 30 weeks of age, when the OLETF rats show hyperglycaemic obesity with hyperinsulinaemia, the animals were divided into two groups and given candesartan, an angiotensin II receptor blocker, 0.2 mg/kg/day, or vehicle for six weeks. Capillary density was evaluated in the left ventricular myocardium by electron microscopy, matrix metalloproteinase (MMP) activity by zymography, and cytokines by reverse transcriptase polymerase chain reaction. RESULTS: Compared with the control rats, the OLETF rats at 36 weeks showed decreased peak negative dP/dt (mean (SD): 2350 (250) v 3492 (286) mm Hg/s) and increased cardiomyocyte diameter (24.3 (0.6) v 18.9 (0.6) microm) (both p < 0.05). Thickening of the capillary basement membranes and decreased capillary density were observed. Angiotensin receptor blockade improved almost all the haemodynamic variables, and the histological findings became similar to those of the controls. Angiotensin receptor blockade also activated MMP-2 and prevented an increase of inflammatory cytokines, especially interleukin (IL)-1beta and IL-6, in the diabetic heart. CONCLUSIONS: Angiotensin II receptor blockade preserved left ventricular diastolic function. It was also potent at improving cardiomyocyte diameter and the thickening of the capillary basement membrane, increasing MMP-2 activity, and decreasing inflammatory cytokines. With all these changes, candesartan could contribute to cardioprotection in diabetes mellitus.

Angiotensin II↗

PubMed2003

QT dispersion and left ventricular morphology in patients with hypertrophic cardiomyopathy.

OBJECTIVE: To evaluate the relation between QT variables and disproportion of left ventricular wall hypertrophy in patients with hypertrophic cardiomyopathy. DESIGN: Retrospective analysis of the results of echocardiography and electrocardiography. SETTING: University hospital (tertiary referral centre). PATIENTS: 70 patients with hypertrophic cardiomyopathy were divided into four groups according to the distribution of left ventricular wall hypertrophy on cross sectional echocardiography: group A--hypertrophy confined to the interventricular septum; group B--hypertrophy confined to the interventricular septum and left ventricular anterior wall; group C--hypertrophy confined to the interventricular septum, left ventricular anterior wall, and lateral free wall; group D--hypertrophy involving all portions of the left ventricle. MAIN OUTCOME MEASURES: QT intervals and QT dispersion in precordial six lead ECGs. RESULTS: There were no significant differences in the maximum left ventricular wall thickness among the four groups, and maximum and minimum QTc intervals also did not differ. QTc dispersion was increased significantly in groups A and B compared with groups C and D. Dispersions of the interval from the J point to the end of the T wave (JTc dispersions) in groups A and B were also increased significantly compared with groups C and D. By linear regression analysis, QTc and JTc dispersions correlated with the ratio of the interventricular septal thickness to left ventricular posterior wall thickness (p = 0.0152 and p = 0.0075, respectively). CONCLUSIONS: QT dispersion may be affected by not only electrical inhomogeneity but also by morphological inhomogeneity of the left ventricle in patients with hypertrophic cardiomyopathy.

Adult↗

PubMed2003

A case of solitary pulmonary lymphangioma.

Solitary pulmonary lymphangiomas are rare benign lesions thought to result from the development of abnormally proliferating lymphatic vessels. This report describes a case of solitary pulmonary lymphangioma resected under video assisted thoracoscopic surgery and diagnosed using histological and immunohistochemical investigations.

Female↗

PubMed2003

Elucidation of correspondence between swine chromosome 4 and human chromosome 1 by assigning 27 genes to the ImpRH map, and development of microsatellites in the proximity of 14 genes.

Loci affecting swine intramuscular fat content, backfat thickness, carcass weight, and daily weight gain were assigned to regions of swine chromosome (SSC) 4, which were shown to correspond to human chromosome (HSA) 1p22--> q25 by ZOO-FISH, bidirectional chromosome painting, as well as by the linkage map of genes. In order to select candidate genes responsible for the above traits from the human genome database, precise correspondence between SSC4 and HSA1 is a prerequisite. In the present study, 27 genes, PTGFR, GBP1, GBP2, GFI1, GCLM, ABCD3, EXTL2, KCNA3, ADORA3, KCND3, WNT2B, NRAS, SYCP1, PTGFRN, IGSF2, NOTCH2, S100A10, SHC1, SSR2, LMNA, CCT3, CD5L, PEA15, FCER1G, EAT2, DDR2, and LAMB3, located in the HSA1 region corresponding to SSC4 or possibly SSC4, were assigned to the IMpRH map. The alignment of genes from centromere to telomere in the SSC4 q arm is basically conserved in HSA1p22-->q25 with the direction from the q arm to the p arm, which is in good agreement with results from linkage mapping. In addition, the present study first demonstrated that WNT2B residing in the middle of the HSA1 region was assigned to SSC18 with a high lod score (> 5), and that at least three intrachromosomal rearrangements occurred in the region in the process of swine and human evolution. PTGFR, and LAMB3 localized at both ends of the HSA1 region were assigned to SSC6 and SSC9, respectively, which is consistent with regional correspondence reported earlier. In the course of the above analysis, microsatellite markers were developed in the proximity of eleven genes localized on SSC4, and three genes on other swine chromosomes.

Animals↗

PubMed2003

Construction of a high-resolution comparative gene map between swine chromosome region 6q11-->q21 and human chromosome 19 q-arm by RH mapping of 51 genes.

A comprehensive and comparative map was constructed for the porcine chromosome (SSC) 6q11-->q21 region, where the gene(s) responsible for the maldevelopment of embryos are localized using swine populations of the National Institute of Animal Industry, Japan (NIAI). Since the chromosomal region corresponds to a region of human chromosome (HSA) 19q13.1-->q13.3 based on bi-directional chromosome painting, primer pairs were designed from porcine cDNA sequences identified, on a sequence comparison basis, as being transcripts from genes orthologous to those in the HSA region. Fifty-one genes were successfully assigned to a swine radiation hybrid (RH) map with LOD scores greater than 6. ERF and PSMD8 genes were assigned to SSC4 and SSC1, respectively. The remaining 49 genes were assigned to SSC6, demonstrating that the synteny between the SSC6 and HSA19 chromosomal regions is essentially conserved, therefore confirming, the results of bi-directional chromosome painting. However, when examined precisely, rearrangements have apparently occurred within the region of conserved synteny. For the ERF and PSMD8 genes assigned to SSCs other than SSC6, additional mapping using somatic cell hybrid (SCH) panels was performed to confirm the results of RH-mapping.

Animals↗

PubMed2003

Synthetic CpG oligodeoxynucleotides accelerate the development of lupus nephritis during preactive phase in NZB x NZWF1 mice.

The effect of synthetic CpG-oligodeoxynucleotides (CpG-ODN) on the development of lupus nephritis during preactive phase (within seven months of age) in autoimmune lupus NZB x NZWF1 (B/WF1) mice was examined. Treatment of CpG-ODN was started at the age of 2.75 months and continued until 6.25 months. Overt disease began at the age of six months and progressed linearly at the age of 6.75 months in CpG-ODN-treated, but not control ODN-treated (control) groups. Also compared to control group, CpG-ODN-treated mice exhibited a severe glomerulonephritis (GN), with prominent deposits of IgG2a and C3, which paralleled increased titre of IgG2a type anti-nuclear antibody in the blood. Among several cytokines (interleukin, IL-6, IL-4, IL-1alpha, IL-10, interferon-gamma and tumor necrosis factor-alpha) in blood, IL-6 production paralleled the development of lupus nephritis. The present study suggests that CpG-ODN may enhance IL-6 production. The role of IL-6 in the development of GN will be discussed.

Adjuvants, Immunologic↗

PubMed2003

Thickness of the roof of the glenoid fossa and condylar bone change: a CT study.

OBJECTIVES: The aim of this study is to investigate the relationship between the thickness of the roof of the glenoid fossa in the temporomandibular joint (TMJ) and the existence and types of condylar bone change. MATERIALS AND METHODS: Helical CT was used to measure the thickness of the roof of the glenoid fossa at its thinnest part in 37 orthodontic patients with temporomandibular disorders. Condylar bone changes were classified into four types: no bone change (24 joints); flattening (19 joints); osteophyte formation (13 joints); and erosion (18 joints). RESULTS: The roof of the glenoid fossa was significantly thicker in joints with bone change than in joints with no bone change (Mann-Whitney U-test, P<0.05). There was also a significant difference in relation to the type of condylar bone change: the thickness of the roof of the glenoid fossa in the erosion group was significantly greater than in the no bone change (P<0.01), flattening (P<0.05) and osteophyte formation (P<0.05) groups (Kruskal-Wallis and Games-Howell tests). CONCLUSION: Compensative bone formation in the roof of the glenoid fossa might help to withstand the increased stress in the TMJ accompanying condylar bone change, especially erosion.

Adolescent↗

PubMed2003

A study of volumetric visualization and quantitative evaluation of bone trabeculae in helical CT.

OBJECTIVES: The aim of this study was to investigate the reliability of quantitative evaluation of bone trabeculae by helical CT. METHODS: Ten specimens of human cadaver mandibular condyles were examined using both micro-CT and helical CT, and volume rendered three-dimensional (3D) images were obtained from the CT data. Micro-CT was used as the reference standard. From the micro-CT data images, bone trabeculae in each condyle were extracted by image processing and their volumes were calculated automatically. From the helical CT data images, the cortical bone was manually removed and bone trabeculae in each condyle were extracted using opacity curve and colour mapping thresholds. The optimal cut-off CT value that resulted in a similar volume of bone trabeculae obtained from helical CT and micro-CT data was investigated. RESULTS: The optimal cut-off CT value to assess the volume of bone trabeculae accurately on 3D images obtained with helical CT data was found to be 200 Hounsfield units. CONCLUSIONS: This study suggests that quantitative evaluation of bone trabeculae using helical CT might be a valid and useful method.

Aged↗

PubMed2003

Central role of defective apoptosis in autoimmunity.

Lymphocyte development, selection and education represent tightly controlled immune processes that normally prevent autoimmunity. Lymphocyte development likely induces cellular selection through apoptosis to remove potentially autoreactive cells. Dysregulated apoptosis, both interrupted as well as accelerated apoptosis, are now demonstrated as central defects in diverse murine autoimmune disease. In murine models of autoimmune lupus, mutations in cell death receptor Fas (CD95) and its ligand, FasL (CD95 L), have been identified. These errors create a lymphoid system resistant to apoptosis. In contrast, select lymphoid subpopulations of maturing autoimmune prone non-obese diabetic mice have identifiable and pathogenic T cells with both in vivo and in vitro heightened apoptosis after drug interventions. In part, these defects are due to faulty activation of transcription factors such as nuclear factor-kappaB (NF-kappaB) that normally protect against apoptotic death. The genetic basis of interrupted NF-kappaB in pathogenic memory T cells in diabetes is attributable to a developmentally controlled gene defect in an essential subunit of the proteasome. No specific gene in most common forms of human autoimmune disease has yet been identified. Functional assays from diverse laboratories repeatedly demonstrate heightened apoptosis in multiple cellular signaling pathways for cell death, suggesting a common theme in disease causality.

Animals↗