Search PubMed⌕ Search

Biomedical subjects

T Ariga

Publications and source records attributed to T Ariga.

At least 19 recordsLinked to original sources
PubMed2007

A novel missense mutation (p.P52R) in amelogenin gene causing X-linked amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a hereditary disease with abnormal dental enamel formation. Here we report a Japanese family with X-linked AI transmitted over at least four generations. Mutation analysis revealed a novel mutation (p.P52R) in exon 5 of the amelogenin gene. The mutation was detected as heterozygous in affected females and as hemizygous in their affected father. The affected sisters exhibited vertical ridges on the enamel surfaces, whereas the affected father had thin, smooth, yellowish enamel with distinct widening of inter-dental spaces. To study the pathological cause underlying the disease in this family, we synthesized the mutant amelogenin p.P52R protein and evaluated it in vitro. Furthermore, we studied differences in the chemical composition between normal and affected teeth by x-ray diffraction analysis and x-ray fluorescence analysis. We believe that these results will greatly aid our understanding of the pathogenesis of X-linked AI.

Amelogenesis Imperfecta↗
PubMed2005

Significance of eosinophilia after stem cell transplantation as a possible prognostic marker for favorable outcome.

Although eosinophilia after stem cell transplantation (SCT) has been addressed in recent reports, the significance of eosinophilia in disease outcome after SCT has not been well studied. In this study, we investigate the frequency of eosinophilia after SCT to determine its prognostic value. The subjects were 113 patients with malignant or nonmalignant diseases who underwent SCT treatment. In these patients, eosinophilia was detected in 44 cases (38.9%), on average 67.5 days after transplantation, and the mean maximum absolute eosinophil count was 840.5 x 10(6)/l. To study the basis of eosinophilia after SCT, various serum cytokine levels during SCT in patients both with and without eosinophilia were analyzed. Statistical analysis indicated that the overall patient survival rates improved in those with eosinophilia compared to those without eosinophilia (88.7 vs 43.0%, P=0.0034). In particular, in patients with malignant diseases, those with eosinophilia showed a higher event-free survival (81.1 vs 44.6%, P=0.0025) and a lower relapse rate (16.0 vs 43.0%, P=0.0287) than those without eosinophilia. In conclusion, we propose that eosinophilia after SCT could be a useful prognostic marker for determining favorable outcomes in patients with malignant diseases. The reasons for this good prognosis in SCT patients with eosinophilia are discussed.

Adolescent↗
PubMed2005

Molecular analysis of non-syndromic preaxial polydactyly: preaxial polydactyly type-IV and preaxial polydactyly type-I.

Human GLI3 gene mutations have been identified in several phenotypes of digital abnormality such as Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type-IV (PPD-IV) and postaxial polydactyly. However, the different phenotypes resulting from GLI3 mutations have not yet been properly defined. We have experienced two types of digital abnormality without other complicating developmental defects; a family with foot PPD-IV with syndactyly of the third and fourth fingers, and four sporadic cases with biphalangeal thumb polydactyly (PPD-I). The genes responsible for syndactyly of the third and fourth fingers (syndactyly type-I) and PPD-I have not yet been identified; we therefore examined the involvement of the GLI3 gene in these subtypes of digital abnormality. We found a non-sense mutation in the GLI3 gene in the family with foot PPD-IV accompanied with hand syndactyly of the third and fourth fingers, but no mutations were detected in the GLI3 gene in the four other cases with PPD-I alone. Thus, the phenotype of foot PPD-IV accompanied with hand syndactyly of the third and fourth fingers may result from a GLI3 mutation, whereas the PPD-I phenotype alone is not caused by GLI3 gene defect. These results will help to define the phenotypic spectrum of GLI3 morphopathies, which have been recently proposed.

Codon, Nonsense↗
PubMed2004

Q fever and lymphadenopathy: report of four new cases and review.

Coxiella burnetii, the causative agent of Q fever, is responsible for various clinical syndromes, but lymphadenitis has been described during Q fever in only three recent case reports. Four new cases of acute Q fever associated with lymphadenopathy are reported here, and these cases are discussed along with the three previously reported cases. Coxiella burnetii was isolated for the first time from a lymph node. Q fever should be considered an etiologic agent of lymphadenitis.

Adult↗
PubMed2004

The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride.

Allyl sulfides, e.g., diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), are principal constituents of garlic oil. In the present study, we investigated the in vivo effect of these sulfides on the phase I and phase II drug-metabolizing enzymes, and elucidated their structure-function relationship. A highly purified form of each sulfide (more than 99% purity) was administered i.p. as a bolus to rats at a concentration of 10 or 100 micromol/kg body weight for 14 consecutive days. As to the phase I enzymes, DAS (100 micromol/kg) slightly but significantly increased cytochrome P-450 (CYP) 2E1 activity (1.6-fold vs. control), whereas DADS and DATS did not affect it or the hepatic total CYP level or CYP1A1/2 activity. With respect to the phase II enzymes, DATS (10 micromol/kg) and DADS at a 10-fold higher dose (100 micromol/kg) significantly increased the activities of glutathione S-transferase, quinone reductase, and antioxidative enzyme glutathione peroxidase; whereas DAS did not. In the carbon tetrachloride (CCl4)-induced acute liver injury model of rats, either DATS (10 micromol/kg) or DADS (100 micromol/kg) significantly reduced the injury caused by the induction of phase II enzymes with CCl4. In conclusion, the sulfides affected both phase I and phase II enzymes, the former being stimulated by the monosulfide only and the latter, strongly by the trisulfide and weakly by the disulfide. Therefore, the polysulfide DATS may be one of the important factors in garlic oil that protects our body against the injury caused by radical molecules encountered in daily life.

Allyl Compounds↗
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↗
PubMed2002

[Thoracoscopic pericardial fenestration for persistent pericardial effusion after radiotherapy for esophageal cancer; report of a case].

We performed thoracoscopic pericardial fenestration for persistent pericardial effusion after radiotherapy for esophageal cancer. An 85-year-old man who had radiation therapy (70.2 Gy) for esophageal cancer was admitted for shortness of breath. Chest computed tomography showed a pericardial effusion. During the 6 months prior to this admission, the patient had undergone percutaneous pericardial drainage 3 times for cardiac tamponade. We performed thoracoscopic partial pericardiectomy with creation of a pleuropericardial window via one access port. Histopathologically, no malignant cells were found in either the resected pericardium or the pericardial effusion. Therefore, we believe the persistent pericardial effusion was secondary to radiotherapy. There was no recurrence of the pericardial effusion for 7 months postoperatively. In summary, thoracoscopic pericardial fenestration is useful in both the diagnosis and treatment of persistent pericardial effusion.

Aged↗
PubMed2001

Induction of hepatic tissue-type plasminogen activator and type 1 plasminogen activator-inhibitor gene expressions and appearance of their translation products in the bile following acute liver injury in rats.

BACKGROUND/AIMS: The plasminogen activator (PA)-plasmin system is primarily involved in fibrinolysis, but is also in the patho/physiological events in which breakdown of extracellular matrices is evoked topically. In this present study, we examined the expression of fibrinolytic factors, tissue-type PA (t-PA) and Type 1 PA inhibitor (PAI-1), in acute liver injury. METHODS: Acute liver injury was produced in rats by the intraperitoneal administration of carbon tetrachloride (CCl(4)). Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured to verify the hepatocellular damage. t-PA and PAI-1 gene expressions were measured by Northern blotting, and the cell type(s) expressing these genes was identified by in situ hybridization. t-PA and PAI-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: A single intraperitoneal administration of CCl(4) caused severe acute parenchymatous liver injury. Both t-PA and PAI-1 gene expressions were induced by the acute liver injury, and plasma t-PA and PAI-1 concentrations were also increased. In situ hybridization studies demonstrated that the hepatocytes were the cells expressing t-PA and PAI-1 genes during the acute liver injury. t-PA was also augmented in the bile, whereas PAI-1 was decreased there. CONCLUSIONS: t-PA and PAI-1 gene expressions are induced in the hepatocytes of rats with acute liver injury. These fibrinolytic factors induced by liver injury may play important roles in liver regeneration.

Animals↗
PubMed2001

IL-1beta down-regulates tissue-type plasminogen activator by up-regulating low-density lipoprotein receptor-related protein in AML 12 cells.

Interleukin-1 (IL-1) regulation of tPA in hepatocytes was studied in mouse hepatocyte line AML12. IL-1 induced transient accumulation of tPA mRNA as high as threefold by 2 h after the start of treatment. The cytokine also induced the mRNA for serum amyloid A, a typical acute-phase protein in mice, with more sustained kinetics in a time-dependent manner. In contrast to the induction of mRNA, tPA activity and protein levels in the harvested medium were dramatically diminished by IL-1. IL-1 stimulated the uptake of (125)I-tPA by AML 12. This uptake was inhibited by 39-kDa receptor-associated protein (RAP), but not by the sugar mannan. These results revealed that low-density lipoprotein receptor-related protein (LRP), which is known to be a receptor for tPA and to be blocked by RAP, was up-regulated by IL-1. We also demonstrated, for the first time, that IL-1 transiently increased the mRNA level of LRP threefold by 30 min after the start of IL-1 treatment of AML 12. The receptor-mediated endocytosis of tPA by hepatocytes may thus play a crucial role in the down-regulation of fibrinolysis during the acute-phase response.

Animals↗
PubMed2001

Recent studies on the roles of antiglycosphingolipids in the pathogenesis of neurological disorders.

Evidence is mounting to suggest a causal role of humoral immunity arising from antiglycosphingolipid (GSL) antibodies in a variety of neurological disorders. These disorders include the demyelinating and axonal forms of Guillain-Barre syndrome, multifocal motor neuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, and IgM paraproteinemia. Many claims have been made regarding other neurological disorders, which should be carefully scrutinized for their validity, based on several criteria proposed in this review. These criteria include 1) characterization of the causative antigens and immunoglobulins, 2) correlation of the pathological lesions and clinical manifestation of the antigens, 3) establishment of animal models using pure GSLs as the antigens, 4) immunopathogenic mechanisms of the neurodenerative process, 5) mechanisms for the malfunctioning of blood-nerve barrier and the ensuing leakage of circulating antibodies into peripheral nerve parenchyma, and 6) the roles of anti-GSL antibodies that may cause humorally mediated nerve dysfunction and injury as well as interference with ion channel function at the node of Ranvier, where carbohydrate epitopes are located. Finally, the origin of the anti-GSL antibodies is discussed in light of the recent circumstantial evidence pointing to a molecular mimicry mechanism with infectious agents. With a better understanding of the immunopathogenic mechanisms, it will then be possible to devise rational and effective diagnostic and therapeutic strategies for the treatment of these neurological disorders.

Antibodies↗
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

Characterization of high-affinity binding between gangliosides and amyloid beta-protein.

The binding specificities of amyloid beta-protein (A beta) such as A beta 1-40, A beta 1-42, A beta 40-1, A beta 1-38, A beta 25-35, and amyloid beta precursor protein (beta-APP) analogues for different glycosphingolipids were determined by surface plasmon resonance (SPR) using a liposome capture method. A beta 1-42, A beta 1-40, A beta 40-1, and A beta 1-38, but not A beta 25-35, bound to GM1 ganglioside in the following rank order: A beta 1-42 > A beta 40-1 > A beta 1-40 > A beta 1-38. The beta-APP analogues bound to GM1 ganglioside with a relatively lower affinity. Aged derivatives of A beta were found to have higher affinity to GM1 ganglioside than fresh or soluble derivatives. A beta 1-40 bound to a number of gangliosides with the following order of binding strength: GQ1b alpha > GT1a alpha > GQ1b > GT1b > GD3 > GD1a = GD1b > LM1 > GM1 > GM2 = GM3 > GM4. Neutral glycosphingolipids had a lower affinity for A beta 1-40 than gangliosides with the following order of binding strength: Gb4 > asialo-GM1 (GA1) > Gb3 > asialo-GM2 (GA2) = LacCer. The results seem to indicate that an alpha2,3NeuAc residue on the neutral oligosaccharide core is required for binding. In addition, the alpha2-6NeuAc residue linked to GalNAc contributes significantly to binding affinity for A beta.

Alzheimer Disease↗
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

Characterization of blood group ABO(H)-active gangliosides in type AB erythrocytes and structural analysis of type A-active ganglioside variants in type A human erythrocytes.

Several monosialogangliosides containing the type A-active epitope have been detected in type A erythrocytes on immunological analysis with a monoclonal antibody, and three of them were purified by repeated silica bead column chromatography and by scraping from the TLC plate. Two of these A-active gangliosides were characterized by methylation analysis by GC/MS, negative SIMS, MALDI-TOF/MS, proton nuclear magnetic resonance spectroscopy, and immunological assays, and their structures were concluded to be as follows. A-active ganglioside I:A-active ganglioside II:The reactivity of the purified gangliosides to the anti-A monoclonal antibodies (mAbs) exhibited enhancement after removal of the sialic acid. Therefore, the sialic residue has been shown to inhibit the binding to the terminal A-active epitope through the formation of an immune complex. To confirm the presence of A- (including S-A-I, -II and -III) and B-active gangliosides, the reactivity of anti-A and -B mAbs were investigated using total gangliosides from type A, -B and -AB erythrocytes on TLC plate. The results were that the gangliosides from types A and AB showed positive reaction to anti-A mAbs, whereas in the anti-B mAbs binding the gangliosides from types B and AB were positive. Thus, it revealed that A-active gangliosides were present in type A and -AB, and B-active gangliosides in types B and AB. As there was no difference in respective gangliosides on type AB erythrocytes of 22 individuals, both A- and B-active gangliosides are equally present in type AB erythrocytes. The biological significance of these A- and B-active ganglioside variants remains vague at present. As these molecules exhibit different reactivities to the anti-A mAbs, it is very likely that they can regulate the antigenicity of the A-epitope on the cell surface.

ABO Blood-Group System↗
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

Reciprocal regulation of tissue-type and urokinase-type plasminogen activators in the differentiation of murine preadipocyte line 3T3-L1 and the hormonal regulation of fibrinolytic factors in the mature adipocytes.

Adipose tissue expresses a variety of genes including tumor necrosis factor alpha and type-1 plasminogen activator inhibitor (PAI-1); and these factors, produced by adipocytes, may be associated with the risk of coronary events in obesity. In this study, we characterized the production of fibrinolytic factors including tissue-type plasminogen activator (tPA), urokinase-type PA (uPA), and PAI-1 in the differentiation of preadipocytes, and examined the hormonal regulation of these fibrinolytic factors in mature adipocytes. Mouse 3T3-L1 preadipocytes were employed as a model of adipocytes. Adipocyte differentiation was induced by insulin, dexamethasone, and 3-isobutyl-1-methyl xanthine (IBMX). alpha-Glycerophosphate dehydrogenase (GPDH) activity and glucose transporter 4 (GLUT4) mRNA, indices for adipocyte maturation, were induced on Day 4, and gradually increased. GPDH activity reached its maximum level on Day 14. The level of tPA, a major PA in preadipocytes, dramatically decreased with differentiation. On the other hand, that of uPA reciprocally increased. PAI-1 production was also dramatically induced concomitant with differentiation. In mature adipocytes, uPA production was dominant (25 microg/ml/24 h vs. 0.8 microg/ml/24 h for tPA). Total PA activity in the mature adipocytes was reduced by insulin or dexamethasone, but not by glucagon. Insulin, IBMX, and dexamethasone significantly decreased both uPA and tPA production, and increased PAI-1 production. Glucagon had no effect on the production of these fibrinolytic factors. Our results reveal that uPA is one of the markers for the differentiation of 3T3-L1 cells and that insulin, IBMX, and dexamethasone are potent regulators of the fibrinolytic activity in differentiated 3T3-L1 cells, reciprocally affecting PA and PAI-1 levels in them.

1-Methyl-3-isobutylxanthine↗
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↗