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Y Sakiyama

Publications and source records attributed to Y Sakiyama.

At least 19 recordsLinked to original sources
PubMed2003

Interstitial lung disease associated with juvenile dermatomyositis: clinical features and efficacy of cyclosporin A.

OBJECTIVES: Interstitial lung disease (ILD) is a rare complication of juvenile dermatomyositis (JDM). The aim of this study was to clarify the clinical features of JDM-associated ILD and to evaluate the efficacy of cyclosporin A (CSA). METHODS: We reviewed clinical records of 10 cases of JDM that were admitted to Hokkaido University Hospital between April 1990 and March 2001. RESULTS: Five cases were complicated with ILD, three with interstitial pneumonia and two with bronchiolitis obliterans organizing pneumonia. ILD was associated with active JDM and progressed despite corticosteroid therapy. Testing for anti-Jo-1 antibody was negative in all cases. Respiratory symptoms were initially noticed in only one case. In the other cases, ILD was first detected by routine examination of chest X-ray. All the cases received CSA (3-5 mg/kg/day) in combination with prednisolone. One patient died of respiratory failure, but the others responded well to treatment with CSA. CONCLUSION: ILD should be evaluated carefully in all cases of JDM regardless of respiratory symptoms. CSA is a choice for steroid-resistant cases of JDM-associated ILD.

Adolescent↗
PubMed2002

Autosomal-dominant hypoplastic form of amelogenesis imperfecta caused by an enamelin gene mutation at the exon-intron boundary.

Amelogenesis imperfecta (AI) is currently classified into 14 distinct subtypes based on various phenotypic criteria; however, the gene responsible for each phenotype has not been defined. We performed molecular genetic studies on a Japanese family with a possible autosomal-dominant form of AI. Previous studies have mapped an autosomal-dominant human AI locus to chromosome 4q11-q21, where two candidate genes, ameloblastin and enamelin, are located. We studied AI patients in this family, focusing on these genes, and found a mutation in the enamelin gene. The mutation detected was a heterozygous, single-G deletion within a series of 7 G residues at the exon 9-intron 9 boundary of the enamelin gene. The mutation was detected only in AI patients in the family and was not detected in other unaffected family members or control individuals. The male proband and his brother showed hypoplastic enamel in both their deciduous and permanent teeth, and their father showed local hypoplastic defects in the enamel of his permanent teeth. The clinical phenotype of these patients is similar to that of the first report of AI caused by an enamelin gene mutation. Thus, heterogeneous mutations in the enamelin gene are responsible for an autosomal-dominant hypoplastic form of AI.

Amelogenesis Imperfecta↗
PubMed2001

Age-related changes of dopamine D1-like and D2-like receptor binding in the F344/N rat striatum revealed by positron emission tomography and in vitro receptor autoradiography.

To clarify age-related changes in dopamine D1-like and D2-like receptor binding in the striatum, positron emission tomography (PET) and in vitro receptor autoradiography (in vitro ARG) were performed using F344/N rats of various ages (6, 12, 18, and 24 months). In the PET study, [11C]SCH23390 and [11C]raclopride were used to image dopamine D1-like receptors and dopamine D2-like receptors, respectively, while [3H]SCH23390 and [3H]raclopride were used for the in vitro ARG study. With PET, we calculated the binding potential (= k3/k4, Bmax/Kd) of [11C]SCH23390 and [11C]raclopride in the striatum according to the curve fitting (CF) and the Logan plot (LP) methods. The binding potential of [11C]SCH23390 in the striatum demonstrated significant decrease as a function of age (max. decrease -26%) by the LP method, while this was not observed in the data analyzed by the CF method. In contrast, the binding potential of [11C]raclopride in the striatum decreased significantly with age by both the CF (max. decrease -28%) and the LP (max. decrease -36%) methods. However, no significant difference by either method was observed in rats between 6 and 12 months old using either ligand. In the in vitro ARG study, the specific binding (fmol/mg tissue) of [3H]SCH23390 and [3H]raclopride in the striatum were determined. Both [3H]SCH23390 and [3H]raclopride binding declined considerably with age as noted by comparing 12, 18, and 24-month-old rats against those 6 months old (max. decrease -29% and -31%, respectively). The substantial difference in binding shown in 12-month-olds in comparison with 6-month-olds using either ligand with in vitro ARG was in contrast with the PET results. These distinctions between the PET and the in vitro ARG studies may be attributed to the receptor microenvironment created under these experimental conditions. The results indicate that PET with LP analysis is useful in obtaining age-related changes of D1-like and D2-like receptor binding in the striatum of living rats.

Aging↗
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

T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the restoration of ADA activity resulted from the reversion of an inherited mutation.

Inherited deficiency of adenosine deaminase (ADA) results in one of the autosomal recessive forms of severe combined immunodeficiency. This report discusses 2 patients with ADA deficiency from different families, in whom a possible reverse mutation had occurred. The novel mutations were identified in the ADA gene from the patients, and both their parents were revealed to be carriers. Unexpectedly, established patient T-cell lines, not B-cell lines, showed half-normal levels of ADA enzyme activity. Reevaluation of the mutations in these T-cell lines indicated that one of the inherited ADA gene mutations was reverted in both patients. At least one of the patients seemed to possess the revertant cells in vivo; however, the mutant cells might have overcome the revertant after receiving ADA enzyme replacement therapy. These findings may have significant implications regarding the prospects for stem cell gene therapy for ADA deficiency.

Adenosine Deaminase↗
PubMed2001

Spontaneous in vivo reversion of an inherited mutation in the Wiskott-Aldrich syndrome.

The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease, arising from mutations of the WAS-protein (WASP) gene. Previously, we have reported that mononuclear cells from WAS patients showed lack/reduced of the intracellular WASP (WASP(dim)) by flow cytometric analysis, and analysis of WASP by flow cytometry (FCM-WASP) was useful for WAS diagnosis. In this study, we report a WAS patient who showed the unique pattern of FCM-WASP. The patient had the small population of normal expression of WASP (WASP(bright)) mononuclear cells together with the major WASP(dim) population. The WASP(bright) cells were detected in T cells, not in B cells or in monocytes. Surprisingly, the molecular studies of the WASP(bright) cells revealed that the inherited mutation of WASP gene was reversed to normal. His mother was proved as a WAS carrier, and HLA studies and microsatellite polymorphic studies proved that the WASP(bright) cells were derived from the patient himself. Therefore, we concluded that the WASP(bright) cells were resulted from spontaneous in vivo reversion of the inherited mutation. Furthermore, the scanning electron microscopic studies indicated that WASP-positive cells from the patient restored the dense microvillus surface projections that were hardly observed in the WASP(dim) cells. This case might have significant implications regarding the prospects of the future gene therapy for WAS patients.

Adult↗
PubMed2001

Molecular basis for paradoxical carriers of adenosine deaminase (ADA) deficiency that show extremely low levels of ADA activity in peripheral blood cells without immunodeficiency.

Adenosine deaminase (ADA) deficiency causes an autosomal recessive form of severe combined immunodeficiency and also less severe phenotypes, depending to a large degree on genotype. In general, ADA activity in cells of carriers is approximately half-normal. Unexpectedly, healthy first-degree relatives of two unrelated ADA-deficient severe combined immunodeficient patients (mother and brother in family I; mother in family II) had only 1-2% of normal ADA activity in PBMC, lower than has previously been found in PBMC of healthy individuals with so-called "partial ADA deficiency." The level of deoxyadenosine nucleotides in erythrocytes of these paradoxical carriers was slightly elevated, but much lower than levels found in immunodeficient patients with ADA deficiency. ADA activity in EBV-lymphoblastoid cell lines (LCL) and T cell lines established from these carriers was 10-20% of normal. Each of these carriers possessed two mutated ADA alleles. Expression of cloned mutant ADA cDNAs in an ADA-deletion strain of Escherichia coli indicated that the novel mutations G239S and M310T were responsible for the residual ADA activity. ADA activity in EBV-LCL extracts of the paradoxical carriers was much more labile than ADA from normal EBV-LCL. Immunoblotting suggested that this lability was due to denaturation rather than to degradation of the mutant protein. These results further define the threshold level of ADA activity necessary for sustaining immune function.

Adenosine Deaminase↗
PubMed2001

Gene-transferred oligoclonal T cells predominantly persist in peripheral blood from an adenosine deaminase-deficient patient during gene therapy.

Adenosine deaminase (ADA) deficiency is the primary cause of severe combined immunodeficiency disease and has become a focus for developing innovative approaches to gene therapy. We previously described successful treatment of a Japanese ADA-deficient patient by periodic infusions of genetically modified autologous T lymphocytes transduced with a retroviral vector containing human ADA cDNA. In order to investigate whether polyclonality was restored by the gene therapy and whether the gene-transduced T lymphocytes persisted in the peripheral blood of the patient, we analyzed the T cell clonotype using a T cell receptor-specific RT-PCR/SSCP method. Oligoclonal T cell expansion was observed in every Vbeta family, and the expanded T cell clones were stable throughout the periodic gene therapy. Some of these T cell clones are likely carrying the vector, since they were identical to the clones selected by G418 resistance. Therefore, although it is uncertain when oligoclonal T cells started to expand and what percentage of the oligoclones carries the vector, the peripheral blood of the patient administered the gene therapy included oligoclonal T cells, some of which were identical to the ADA-gene-transduced clones.

Adenosine Deaminase↗
PubMed2001

[Considerable supplement on the central cusp in the lower second molar].

The central cusp, one of morphological anomalies of tooth, is a supernumerary tubercle found principally in the center of the occlusal surface of a molar. Most central cusps reported are observed in the premolar, but very few studies are available on the central cusp in molar, especially in the lower second molar. In the present study, the central cusp on either side of the lower second molar were reported and discussed according to the previous investigation as a supplement on this subject.

Adolescent↗
PubMed2000

Determination of carrier status for the Wiskott-Aldrich syndrome by flow cytometric analysis of Wiskott-Aldrich syndrome protein expression in peripheral blood mononuclear cells.

The Wiskott-Aldrich syndrome (WAS) is caused by defects in the WAS protein (WASP) gene on the X chromosome. Previous study disclosed that flow cytometric analysis of intracellular WASP expression (FCM-WASP analysis) in lymphocytes was useful for the diagnosis of WAS patients. Lymphocytes from all WAS patients showed WASPdim instead of WASPbright. Here we report that FCM-WASP analysis in monocytes could be a useful tool for the WAS carrier diagnosis. Monocytes from all nine WAS carriers showed varied population of WASPdim together with WASPbright. None of control individuals possessed the WASPdim population. In contrast, lymphocytes from all the carriers except two lacked the WASPdim population. The difference of the WASPdim population in monocytes and lymphocytes observed in WAS carriers suggests that WASP plays a more critical role in the development of lymphocytes than in that of monocytes. The present studies suggest that a skewed X-chromosomal inactivation pattern observed in WAS carrier peripheral blood cells is not fixed at the hemopoietic stem cell level but progresses after the lineage commitment.

Female↗
PubMed2000

Rapid tyrosine phosphorylation and activation of Bruton's tyrosine/Tec kinases in platelets induced by collagen binding or CD32 cross-linking.

Stimulation of the platelet nonintegrin collagen receptor, glycoprotein VI, evokes a signaling response similar to that induced by antigen receptor activation in B and T lymphocytes. A key transducer of the lymphocyte signaling pathways is the Bruton's tyrosine kinase (Btk)/Tec kinase family, which connects receptors to the elevation of intracellular-free calcium levels. An important signaling function for Btk in collagen-induced platelet activation in vitro was recently demonstrated by other researchers using Btk-deficient platelets from patients with X-linked agammaglobulinemia (XLA). Since Btk-deficiency does not induce an overt platelet-based bleeding disorder in vivo, collagen receptor responses may include other Btk/Tec kinase family members in normal platelets. Both Btk and Tec had increased tyrosine following stimulation of collagen receptors or CD32 cross-linking. Data from kinetic analyses and inhibitor studies and the use of phosphopeptide-specific antibodies recognizing 2 Btk regulatory phosphorylated tyrosine residues suggest a mechanism for coordinate recruitment of Btk and Tec through the immunoreceptor tyrosine-based activation motif, Src family kinases, and phosphatidylinositol 3-kinase. In XLA platelets, collagen treatment increased tyrosine phosphorylation of Tec and several other signaling proteins, including Lyn, Fyb, Slp-76, and the Wiskott-Aldrich syndrome protein. This indicates that important elements of the collagen signaling pathway proximal and distal to Btk and Tec are preserved despite the lack of functional Btk. The results are consistent with the conclusion that activation of Tec may sustain XLA platelet function in vivo, while some in vitro assays of nonintegrin collagen receptor signaling through the Btk/Tec kinase family reflect the additive dosage of the transducers. (Blood. 2000;95:1663-1670)

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2000

Improved dysgammaglobulinaemia in congenital rubella syndrome after immunoglobulin therapy: correlation with CD154 expression.

UNLABELLED: A boy with congenital rubella syndrome developed dysgammaglobulinaemia with elevated serum levels of IgM. CD154 was not induced on his peripheral blood mononuclear cells when rubella virus RNA was detected in his throat swabs and peripheral blood by reverse transcriptase polymerase chain reaction. Following intravenous immunoglobulin therapy, improvement of immunoglobulin abnormalities, disappearance of rubella virus and normalisation of CD154 expression were demonstrated. CONCLUSION: These findings implicate the efficacy of intravenous immunoglobulin therapy for dysgammaglobulinaemia in congenital rubella syndrome and a role of CD154 for a prolonged virus infection.

Antibodies, Viral↗
PubMed2000

Characterization of the gammac chain among 27 unrelated Japanese patients with X-linked severe combined immunodeficiency (X-SCID).

X-linked severe combined immunodeficiency (X-SCID) is a rare fatal disease that is caused by mutations in the gene encoding the gammac chain. In this study, 27 unrelated Japanese patients with X-SCID were examined in terms of their genetic mutations and surface expression of the gammac chain. Among 25 patients examined, excluding two patients with large deletions, 23 different mutations were identified in the IL2RG gene, including 10 novel mutations. One patient bearing an extracellular mutation and all three of the patients bearing intracellular mutations after exon 7 expressed the gammac chain on the cell surface. Overall, 84% of patients lacked surface expression of the gammac chain leading to a diagnosis of X-SCID.

Antibodies, Monoclonal↗
PubMed2000

A PET study of adenosine A1 receptor in anesthetized monkey brain.

We demonstrated the distribution of adenosine A1 receptors in the anesthetized monkey brain with positron emission tomography (PET) using [(11)C]KF15372 ([1-propyl-(11)C]8-dicyclopropylmethyl-1, 3-dipropylxanthine). [(11)C]KF15372 was injected intravenously. The regional standardized uptake values and the distribution volume were calculated. We also investigated the effect of carrier on the uptake and regional brain distribution of [(11)C]KF15372. The use of [(11)C]KF15372 with dynamic PET scanning could be an appropriate method to analyze the regional binding potential of adenosine A1 receptors in living brain.

Anesthesia↗
PubMed2000

Genetic studies of three Japanese patients with p22-phox-deficient chronic granulomatous disease: detection of a possible common mutant CYBA allele in Japan and a genotype-phenotype correlation in these patients.

Chronic granulomatous disease (CGD) is a disorder caused by defects in the NADPH oxidase responsible for superoxide generation in phagocytes. Cytochrome b558, an essential component of this enzyme, is a heterodimer formed by a 91 kDa glycoprotein (gp91-phox) and a 22 kDa polypeptide (p22-phox). Mutations in the p22-phox gene (CYBA) locus in 16q24 result in one of the rare autosomal recessive forms of CGD. We performed mutation analysis in three female CGD patients suspected of having this form of the disease and found two novel mutations in CYBA. Whereas patient 1 with severe phenotype had a homozygous nonsense mutation in exon 1 (C-35 --> T, Gln-3 --> stop), patients 2 and 3 with mild phenotype shared the same homozygous missense mutation in exon 2 (G-98 --> A, Gly-24 --> Arg). None of the parents of patients 2 and 3 is related. Therefore, this mutation could be a hot-spot or a common mutation in the Japanese population. Patients 2 and 3, but not patient 1, were demonstrated to have detectable p22-phox expression and significant granulocyte respiratory burst (ROB) activity. In this study, we were able to demonstrate an excellent correlation between genotype, p22-phox expression, ROB activity and clinical phenotype in these patients.

Adult↗