Biomedical subjects

Y Kasahara

Publications and source records attributed to Y Kasahara.

At least 19 recordsLinked to original sources

PubMed2006

Thermal conductivity of the pyrochlore superconductor KOs2O6: strong electron correlations and fully gapped superconductivity.

To elucidate the nature of the superconducting ground state of the geometrically frustrated pyrochlore KOs2O6 (Tc=9.6 K), the thermal conductivity was measured down to low temperatures (approximately Tc/100). We found that the quasiparticle mean free path is strikingly enhanced below a transition at Tp=7.8 K, indicating enormous electron inelastic scattering in the normal state. In magnetic fields, the conduction at T-->0 K is nearly constant up to approximately 0.4Hc2, in contrast with the rapid growth expected for superconductors with an anisotropic gap. This unambiguously indicates a fully gapped superconductivity, in contrast with previous studies. These results highlight that KOs2O6 is unique among superconductors with strong electron correlations.

Journal Article↗

PubMed2005

Characterization of cDNA and the genomic sequence encoding canine neural-cell adhesion molecule, CD56/N-CAM.

The neural-cell adhesion molecule, CD56/N-CAM is a member of the immunoglobulin superfamily expressed by various tissues and cells, including natural killer (NK) cells. Despite the importance of CD56 as a marker for identifying NK cells in circulating blood, canine CD56 has not been identified. In the present study, we identified the canine counterparts of the 140-kDa (CD56-140) and 120-kDa (CD56-120) isoforms of human DC56. Both of amino acid sequences encoded by the canine CD56-140 and -120 cDNA showed high homology with those of human (both 96% homology), having well-conserved domains (five immunoglobulin, two fibronectin type III, and transmembrane and intracellular or glycosylphosphatidylinositol-linked domain) among various species (human, mouse, and feline). We revealed that the transcripts of canine CD56-140 and -120 arise from alternative mRNA splicing from a single gene located on canine chromosome 5. Moreover, the mRNA encoding canine CD56-140 was expressed at high levels constitutively by nervous system and endocrine tissues as has shown in other animals.

Alternative Splicing↗

PubMed2005

Line nodes in the superconducting gap function of noncentrosymmetric CePt3Si.

The superconducting gap structure of recently discovered heavy fermion CePt(3)Si without spatial inversion symmetry was investigated by thermal transport measurements down to 40 mK. In zero field a residual T-linear term was clearly resolved as T --> 0, with a magnitude in good agreement with the value expected for a residual normal fluid with a nodal gap structure, together with a T2 dependence at high temperatures. With an applied magnetic field, the thermal conductivity grows rapidly, in dramatic contrast to fully gapped superconductors, and exhibits one-parameter scaling with T/sqrt[H]. These results place an important constraint on the order parameter symmetry; that is, CePt(3)Si is most likely to have line nodes.

Journal Article↗

PubMed2005

Thermal transport in the hidden-order state of URu2Si2.

We present a study of thermal conductivity in the normal state of the heavy-fermion superconductor URu2Si2. Ordering at 18 K leads to a steep increase in thermal conductivity and (in contrast with all other cases of magnetic ordering in heavy-fermion compounds) to an enhancement of the Lorenz number. By linking this observation to several other previously reported features, we conclude that most of the carriers disappear in the ordered state and this leads to a drastic increase in both the phononic and electronic mean free path.

Journal Article↗

PubMed2005

Selective expansion of CD16highCCR2- subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation.

Monocytes are composed of two distinct subpopulations in the peripheral blood as determined by their surface antigen expressions, profiles of cytokine production and functional roles played in vivo. We attempted to delineate the unique functional roles played by a minor CD16(high)CCR2(-) subpopulation of circulating monocytes. They produced significant levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, but very low levels of IL-10 upon in vitro stimulation. Characteristic profiles of cytokine production were confirmed by stimulating purified subpopulations of monocytes after cell sorting. It was noteworthy that freshly isolated CD16(high)CCR2(-) monocyte subpopulations produced significant levels of haem oxygenase (HO)-1, whereas the major CD16(low)CCR2(+) subpopulation produced little. These results were contrary to the generally accepted notion that the CD16(high)CCR2(-) monocyte subpopulation plays a predominantly proinflammatory role in vivo. The CD16(high)CCR2(-) subpopulation increased in Kawasaki disease and influenza virus infection. In accord with this, HO-1 mRNA expression by mononuclear cells was significantly increased in these illnesses. These results indicate that CD16(high)CCR2(-) subpopulations are of a distinct lineage from CD16(low)CCR2(+) monocytes. More importantly, they may represent a monocyte subpopulation with a unique functional role to regulate inflammation by producing HO-1 in steady state in vivo.

Acute Disease↗

PubMed2005

Association of clinical features with HLA in chronic pulmonary thromboembolism.

The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown and may be heterogeneous, because there are several ethnic differences in the clinical characteristics of CTEPH. Female predominance and a higher ratio of chronic to acute pulmonary thromboembolism have been reported in Japan as compared with the USA. Because such ethnic differences may be controlled by genetic factors, the current study investigated HLA polymorphisms in Japanese patients with CTEPH. HLA typing by serological and/or DNA typing methods was performed (for HLA-A, B, DPB1, DRB1) in 80 patients and 678 controls, and the association of clinical characteristics with HLA alleles was studied. The frequencies of HLA-B*5201 (40 versus 24%) and DPB1*0202 (19 versus 6%) were significantly higher in the patients. HLA-B*5201 positive patients showed a significant female predominance. Total pulmonary vascular resistance and mixed venous oxygen tension were better in the HLA-B*5201 positive patients. In contrast, cardiac index and gas exchange parameters were worse in the HLA-DPB1*0202 positive patients. In the patients carrying HLA-B*5201 and/or -DPB1*0202, the frequency of deep vein thrombosis was significantly lower than the other patients. These observations suggested that both the susceptibility and clinical characteristics of chronic thromboembolic pulmonary hypertension were controlled in part by the HLA-B and -DPB1 loci.

Adult↗

PubMed2005

Treatment with low-dose angiotensin-converting enzyme inhibitor (ACEI) plus angiotensin II receptor blocker (ARB) in pediatric patients with IgA nephropathy.

AIM: IgA nephropathy associated with heavy proteinuria is considered a more progressive form of this disease. In this report, we describe the favorable clinical effect of combination therapy with low doses of an angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) in the chronic stage of pediatric IgA nephropathy associated with heavy proteinuria. PATIENTS: We initially used ACEI for seven children with IgA nephropathy and heavy proteinuria who did not achieve remission with the routine treatment including steroids. RESULTS: With ACEI therapy alone, only three patients showed an antiproteinuric response. In one of the three patients, the proteinuria decreased by half, but was still over 1 g/day. In the other four patients, the proteinuria did not decrease. In these five patients, of whom one partial was a responder and four were non-responders for ACEI, ARB was added, and in marked contrast to ACEI therapy alone, the antiproteinuric effect was significantly augmented (p < 0.01). The antiproteinuric response induced by combination therapy was not accompanied by blood pressure changes. Urinary low-molecular protein and N-acetyl-beta-D-glucosaminidase (NAG) levels tended to decrease after both ACEI alone and combination therapy. CONCLUSION: These data indicate that inhibition therapy of the angiotensin system not only decreases proteinuria levels but also protects renal tubular cells. Moreover, there were no obvious side effects associated with this therapy during the follow-up period of our clinical trial. In conclusion, this report shows that the combination of low doses of ACEI and ARB might provide marked antiproteinuric and long-term renoprotective effects in pediatric IgA nephropathy, with this approach appearing to be both well-tolerated and safe.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2004

Molecular analysis of B-cell differentiation in selective or partial IgA deficiency.

Selective IgA deficiency is the most common form of primary immunodeficiency, the molecular basis of which is unknown. To investigate the cause of selective IgA deficiency, we examined what stage of B-cell differentiation was blocked. DNA and RNA were extracted from three Japanese patients with selective IgA deficiency and three with a partial IgA deficiency. In selective IgA deficiency patients, Ialpha germline transcript expression levels decreased and alpha circle transcripts were not detected. Stimulation with PMA and TGF-beta1 up-regulated Ialpha germline and alpha circle transcripts. In some patients, IgA secretion was induced by stimulation with anti-CD40, IL-4 and IL-10. In partial IgA deficiency patients, Ialpha germline, alpha circle transcripts and Calpha mature transcripts were detected in the absence of stimulation. Our findings suggest that the decreased expression level of Ialpha germline transcripts before a class switch might be critical for the pathogenesis of some patients with selective IgA deficiency. However, in patients with a partial IgA deficiency, B-cell differentiation might be disturbed after a class switch.

Adolescent↗

PubMed2004

Oligoclonal expansion of circulating and tissue-infiltrating CD8+ T cells with killer/effector phenotypes in juvenile dermatomyositis syndrome.

Although triggering by infectious agents and abnormal immune responses may play some role in the pathogenesis of juvenile dermatomyositis syndrome (JDMS), the precise mechanism of muscle destruction and vascular damage is largely unknown. In this study, we tried to elucidate the role of cytotoxic T cells in two patients with JDMS, who were diagnosed based on the characteristic symptoms, laboratory data, MRI findings and electromyographic patterns. Peripheral blood T cell phenotypes were determined by flow cytometry, using mAbs against specific T cell receptor (TCR) Vbetas. Complementarity-determining region3 (CDR3) size analysis was performed by gene scanning of CDR3 polymerase chain reaction (PCR) amplification products specific for each Vbeta. Subsequently, CDR3 nucleotide sequences were obtained after cloning of the predominant products. The distribution of lymphocytes infiltrating the muscle tissue was analysed by immunohistochemistry. In both patients examined, a unique combination of TCR Vbeta repertoires was increased within the CD8+ T cells. These subpopulations expressed a characteristic phenotype, indicating that they are memory/effector T cells with killer functions. At the same time, immunohistological and molecular biological examinations of the biopsied muscle samples revealed that identical CD8+ T cell clones with identical phenotypes/TCR Vbeta infiltrated within the inflammatory tissue, in particular around vessels. These findings indicate that oligoclonal expansion of CD8+ T cells plays a central role in the pathogenesis of muscle injury in the juvenile form of dermatomyositis syndrome and may provide a useful clinical parameter of disease activity and responsiveness to anti-inflammatory therapy.

Antigens, CD↗

PubMed2003

Essential Bacillus subtilis genes.

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximately 4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden-Meyerhof-Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

Bacillus subtilis↗

PubMed2002

Effect of Seihai-to, a Kampo medicine, in relapsing aspiration pneumonia--an open-label pilot study.

Two published case reports described palliation of disease after Seihai-to therapy for refractory aspiration pneumonia caused by recurrent laryngeal nerve paralysis and cerebrovascular disease. We undertook an open-label trial in patients with relapsing aspiration pneumonia. Fifteen patients with relapsing aspiration pneumonia were randomly divided into conventional therapy group (n = 8) or Seihai-to group (n = 7). In Seihai-to group, patients were treated with Seihai-to in addition to conventional therapy (Western medicines). Frequency of feverish days and antibiotics-use, CRP value and chest CT or X-ray findings were compared between the two groups during the study period of 16 weeks. In the Seihai-to group, the latency of swallowing reflex was measured in 6 patients before and after administration of Seihai-to. The mean values of fever index, CRP value and antibiotics-use in the Seihai-to group were decreased significantly, compared with those of the conventional therapy group. However, the latency of the swallowing reflex after 4 weeks of treatment was not significantly changed (p = 0.249), compared with the latency before administration of Seihai-to. No adverse reaction was observed in either group. Seihai-to was effective in reducing relapse of aspiration pneumonia in this small group. Seihai-to might not improve the swallowing reflex, but might instead improve a defense mechanism or excessive inflammation caused by pneumonia in the lower airway. Further evaluation of Seihai-to therapy for patients with aspiration pneumonia in a larger population is warranted.

Aged↗

PubMed2002

Inhibitory effects of Choto-san (Diao-teng-san), and hooks and stems of Uncaria sinensis on free radical-induced lysis of rat red blood cells.

The present study is designed to test our hypothesis that the ingestion of Uncaria sinensis (US), the main medicinal plant of Choto-san (Diao-teng-san, CS), would protect red blood cell (RBC) membrane from free radical-induced oxidation if polyphenolics in US could be absorbed and circulated in blood. When incubated with RBC suspension, Choto-san extract (CSE) and Uncaria sinensis extract (USE) exhibited strong protection for RBC membrane against hemolysis induced by 2,2-azo-bis (2-amidinopropane) dihydrochloride (AAPH), an azo free-radical initiator. The inhibitory effect was dose-dependent at concentrations of 50 to 1000 microg/mL. Ingestion of 200 mg of USE was associated with a significant decrease in susceptibility of RBC to hemolysis in rats. Furthermore, caffeic acid, an antioxidative hydroxycinnamic acid, was identified in rat plasma after administration of URE.

Amidines↗

PubMed2002

A comparative study between excess-dose users and regular-dose users of rhubarb contained in Kampo medicines.

With prolonged use of rhubarb-containing Kampo medicines, some patients come to ask for high-dose rhubarb because of deteriorated reactivity to rhubarb. We divided patients into two groups in terms of rhubarb-dose, and compared clinical backgrounds between regular-dose group and excess-dose group. Patients who were treated with rhubarb-containing Kampo extracts (manufactured prescriptions) or Kampo formulae (decoctions) for more than 12 months were enrolled. These two groups were compared for age, sex, shape of stool, abdominal symptoms, existence of hemorrhoids, Kampo diagnosis of abdomen, past stimulant laxative use, duration of stimulant laxative use before the first administration of rhubarb, duration of rhubarb use in our hospital, and initial existence of stimulant pain caused by taking stimulant laxatives for the first time. No significant difference was shown between the two groups in terms of age, duration of stimulant laxative-use before the first prescription of rhubarb, shape of stool, abdominal symptoms, existence of hemorrhoids, or duration of rhubarb-use. However, most patients in the regular-dose group had initial stimulant pain of the abdomen upon taking stimulant laxatives for the first time, but most patients in the excess-dose group did not (p < 0.001). All patients except one in the regular dose group had the sign of "umbilical region tenderness on pressure", but half of the excess-dose group did not have it (p = 0.041). Based on these findings, the absence of "initial stimulant pain" and the absence of "umbilical region tenderness on pressure" may predict increasing or excess use of rhubarb, and long-term use of rhubarb should be discouraged more strongly in the patients without these signs.

Cathartics↗

PubMed2002

Reduction of plasma triglyceride level and enhancement of plasma albumin concentration by Oren-gedoku-to administration.

Oren-gedoku-to (Huanglian-Jie-Du-Tang, OGT) has been used for the treatment of cerebrovascular disease, hypertension, gastritis and liver disease in Japan. The present study was to test whether ingestion of OGT extract (TJ-15) would affect the metabolism of fatty acids and the usual antioxidant molecule (such as albumin, uric acid and bilirubin) levels in human plasma. After the administration of TJ-15, plasma total cholesterol and the triglyceride level significantly decreased, and lipoprotein lipase mass increased. Significant enhancement of plasma albumin level and reduction of the total plasma protein level resulted in an increment of the albumin/globulin ratio. Plasma fibrinogen, an independent risk factor for cerebrovascular disease, declined considerably, but the reduction was not statistically significant. The findings of this study suggest that ingestion of TJ-15 improves the microcirculation through lipid and protein metabolisms, and is useful for the treatment of cerebral vascular attack in human.

Chromatography, High Pressure Liquid↗

PubMed2001

Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection.

Unusual Epstein-Barr virus (EBV) infection into T or natural killer cells plays a pivotal role in the pathogenesis of acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV). The precise frequency and localization of EBV genome in lymphocyte subpopulations especially within T-cell subpopulations are unclear in these EBV-related disorders. This study analyzed the frequency of EBV-infected cells in circulating lymphocyte subpopulations from 4 patients with acute EBV-HLH and 4 with CAEBV. EBV- encoded small RNA-1 in situ hybridization examination of peripheral blood lymphocytes showed a significantly higher frequency of EBV-infected cells of 1.0% to 13.4% in EBV-HLH and 1.6% to 25.6% in CAEBV, respectively. The patterns of EBV infection in lymphocyte subpopulations were quite different between acute EBV-HLH and CAEBV. EBV infection was predominant in CD8(+) T cells in all EBV-HLH patients, whereas the dominant EBV-infected cell populations were non-CD8(+) lymphocyte subpopulations in CAEBV patients. Phenotypical analysis revealed that EBV-infected cell populations from both EBV-HLH and CAEBV were activated. There was no predominance of any EBV substrain of latent membrane protein-1, EBV-associated nuclear antigen (EBNA)-1, and EBNA-2 genes between the 2 abnormal EBV-associated disorders, and self-limited acute infectious mononucleosis. These results showing differential virus-cell interactions between acute EBV-HLH and CAEBV indicated different pathogenic mechanisms against EBV infection between the 2 EBV-associated diseases, which accounts for the difference in clinical manifestations between the 2 diseases.

Acute Disease↗

PubMed2001

Molecular cloning and characterization of CHM1L, a novel membrane molecule similar to chondromodulin-I.

Chondromodulin-I (ChM-I) is a cartilage-specific glycoprotein that stimulates the growth of chondrocytes and inhibits the tube formation of endothelial cells. In the present study, we identified a novel ChM-I like molecule, designated ChM1L. Cloning of full length cDNAs of human, mouse, and rat ChM1L revealed that ChM1L encodes 317 amino acids novel type II transmembrane protein. ChM1L protein was expressed on the cell surface as N-glycosylated and non-N-glycosylated protein with molecular mass of 45 and 40 kDa, respectively. In adult mouse tissues, ChM1L mRNA was highly expressed in eye, skeletal muscle, and whole rib. The temporal pattern of ChM1L mRNA was examined using whole embryo at day 10 to 19 of gestation. After day 11, ChM1L mRNA was detected and its level was progressively elevated in association with development of mouse embryo. These data suggest that ChM1L is a novel membrane molecule which is similar to ChM-I that plays a regulatory role in eye, skeletal muscle, and development of embryo.

Amino Acid Sequence↗

PubMed2001

Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis.

Pulmonary arteries of patients with severe pulmonary hypertension (SPH) presenting in an idiopathic form (primary PH-PPH) or associated with congenital heart malformations or collagen vascular diseases show plexiform lesions. It is postulated that in lungs with SPH, endothelial cells in plexiform lesions express genes encoding for proteins involved in angiogenesis, in particular, vascular endothelial growth factor (VEGF) and those involved in VEGF receptor-2 (VEGFR-2) signalling. On immunohistochemistry and in situ hybridization, endothelial cells in the plexiform lesions expressed VEGF mRNA and protein and overexpressed the mRNA and protein of VEGFR-2, and the transcription factor subunits HIF-1alpha and HIF-1beta of hypoxia inducible factor, which are responsible for the hypoxia-dependent induction of VEGF. When compared with normal lungs, SPH lungs showed decreased expression of the kinases PI3 kinase and src, which, together with Akt, relay the signal transduction downstream of VEGFR-2. Because markers of angiogenesis are expressed in plexiform lesions in SPH, it is proposed that these lesions may form by a process of disordered angiogenesis.

Aryl Hydrocarbon Receptor Nuclear Translocator↗

PubMed2001

Anti-angiogenic therapy and radioimmunotherapy in colon cancer xenografts.

Angiogenesis is critical to the growth and metastatic process of malignant tumors. An endogenous estrogen metabolite, 2-methoxyestradiol (2-ME), displays anti-angiogenic and anti-tumorigenic effects. The purpose of this investigation was to determine whether exogenously administered 2-ME would enhance the efficacy of radioimmunotherapy (RIT). Experimental RIT with 4.63 MBq of 131I-A7, an IgG1 anti-colorectal monoclonal antibody, was conducted in mice xenografted with LS 180 human colon cancer cells. 2-ME suspended in 0.5% carboxymethylcellulose was administered daily at a dose of 75 mg/kg per day. 2-ME administration suppressed tumor growth and improved the efficacy of RIT in comparison to RIT alone. Tumor volumes on day 13, expressed as a ratio relative to the initial volume, were 12.7 +/- 2.95 in the nontreated control, 4.73 +/- 0.89 with 2-ME, 3.05 +/- 0.37 with RIT and 0.97 +/- 0.20 with RIT+2-ME. Immunohistochemistry of tumor sections stained with an antibody against factor VIII demonstrated a decrease in microvessel number within tumors treated with 2-ME (7.9 +/- 0.8/200x field) as compared with that in control tumors (29.9 +/- 2.5). Cell proliferation assay at increasing concentrations of 2-ME showed direct cytotoxicity of 2-ME in vitro at 5 microM and greater. In conclusion, 2-ME enhanced the efficacy of RIT with 131I-A7 via inhibition of angiogenesis within the xenografts. The direct cytotoxicity of 2-ME appears to have contributed to this improvement. Anti-angiogenic therapy may prolong the dormancy of microscopic metastases while RIT may exterminate this population of cells. Therefore, the combined treatment may improve the therapeutic outcome of patients with disseminated cancer.

2-Methoxyestradiol↗