Progressive vascular calcification in autoimmune polyglandular syndrome type I.
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Adult↗
Biomedical subjects
T Hara
Publications and source records attributed to T Hara.
Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population.
Co-stimulatory molecules of CD28, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and the newly identified inducible co-stimulator (ICOS) are expressed on cell surfaces and provide regulatory signals for T-cell activation. Their genes are candidate susceptibility genes for type 1 diabetes because they co-localize to Chromosome 2q33 with the IDDM12 locus. After determining the genomic structure and screening for polymorphisms of the ICOS gene, we performed association studies between newly identified polymorphisms of the ICOS gene, together with known polymorphisms of CD28 and CTLA-4 genes, and type 1 diabetes. The 49A/G dimorphism in exon 1 and the (AT)n in the 3' untranslated region of the CTLA-4 gene were significantly associated with type 1 diabetes. Evaluation of the CTLA-4 49A-3'(AT)n 86-bp haplotype frequency in patients and controls confirmed the results from the analysis of each polymorphic site. Dimorphism in intron 3 of the CD28 gene was associated with type 1 diabetes only in the early-onset group. In contrast, there was no association with the microsatellite polymorphisms in the ICOS gene or dimorphisms in the promotor region of CTLA-4. Of the three genes encoding co-stimulatory molecules, the CTLA-4 gene appears to confer risks for the development of type 1 diabetes.
Abatacept↗
Establishment and characterization of cell-free translation/glycosylation in insect cell (Spodoptera frugiperda 21) extract prepared with high pressure treatment.
A coupled cell-free translation/glycosylation system, prepared from Spodoptera frugiperda insect cells, was established and optimized for protein production and glycosylation efficiency. Both translation and glycosylation were stimulated by addition of Mg2+, K+, ATP, GTP, creatine kinase and creatine phosphate, suggesting that glycoprotein productivity is largely determined by translation efficiency. However, high concentrations of creatine phosphate significantly inhibited translation. Spermidine stimulated both translation and glycosylation, but glycosylation required higher concentrations of spermidine than translation. Furthermore, extracts prepared at a nitrogen pressure of 10 kg/cm2 with the Mini-Bomb cell disruption chamber had the highest glycoprotein productivity; and extracts prepared at the higher nitrogen pressure of 15 kg/cm2 retained glycosylation ability. While extracts prepared with the Potter-Elvehjem homogenizer could mediate translation, no glycosylation was achieved. This indicated that the posttranslational machinery might survive disruption by high pressure, but not by physical shearing force. This insect cell-free system was able to synthesize approximately 25 microg of glycosylated gp120/ml of reaction mixture.
Animals↗
Pressure distribution in the humeroradial joint and force transmission to the capitellum during rotation of the forearm: effects of the Sauvé-Kapandji procedure and incision of the interosseous membrane.
A biomechanical study was undertaken, using four fresh cadaveric arms, to evaluate the changes in pressure distribution in the humeroradial joint (H-R joint) during rotation of the forearm before and after the Sauvé-Kapandji procedure (S-K procedure) and also after incision of the interosseous membrane (IOM) following the S-K procedure. The pressure distribution was measured with a pressure-sensitive conductive rubber sensor while the forearm was rotated. Force transmitted to the capitellum was calculated from the measured pressure. In the intact specimens, pressure was concentrated on the medial side of the capitellum in pronation and on the posterolateral side in supination. The pattern of change after the S-K procedure and that after incision of the IOM following the S-K procedure were almost the same as that in the intact forearm. Although the force transmitted to the capitellum increased after the S-K procedure, there were no significant differences between the forces before and after the S-K procedure. However, the force increased significantly after incision of the IOM following the S-K procedure when the forearm was supinated more than 35 degrees, and it was concentrated on the posterior side of the capitellum. The IOM seemed to have an important axial load-bearing function in the forearm position supinated more than 35 degrees. The S-K procedure in patients suffering from distal radioulnar joint disorders with IOM injury is likely to induce H-R joint osteoarthritis, so it should be avoided in these patients.
Analysis of Variance↗
Effects of ovariectomy and/or dietary calcium deficiency on bone dynamics in the rat hard palate, mandible and proximal tibia.
The effects of ovariectomy and/or dietary calcium deficiency on bone dynamics were examined by comparing the histomorphometric changes in these bones. Five groups of rats were studied, (1) unoperated basal controls; (2) sham-operated, fed on a normal-calcium diet; (3) ovariectomized, fed on a normal-calcium diet; (4) sham-operated, fed on a calcium-deficient diet; (5) ovariectomized, fed on a calcium-deficient diet. The basal controls were killed at 6 weeks of age, and the remaining groups were killed at 18 weeks of age. The hard palate, mandible and proximal tibia were processed undemineralized for quantitative bone histomorphometry. Bone volume, eroded surface, osteoid surface and bone-formation ratio were calculated. A significant age-related increase in bone volume and a significant decrease in bone formation were observed in the hard palate and mandible, whereas no significant age-related increase in bone volume could be found in the tibia. In the hard palate, ovariectomy neither inhibited age-related increases in bone volume nor affected bone dynamics, while both the combined ovariectomy and dietary calcium deficiency and dietary calcium deficiency alone led to bone loss and increased bone turnover. In contrast, in the mandible and proximal tibia, ovariectomy alone as well as dietary calcium deficiency led to bone loss and increased bone turnover. Ovariectomy, therefore, produced no significant changes in the hard palate, but affected bone dynamics in the mandible and tibia. However, dietary calcium deficiency induced bone loss and increased bone turnover in the hard palate, mandible and proximal tibia, independently of ovariectomy.
Analysis of Variance↗
Successful spectacle correction for an ametropic amblyopic child with congenital auricular aplasia using a new spectacle-supporting apparatus.
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Amblyopia↗
Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver.
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is associated with the metabolism of lipid, glucose and energy. Beta-adrenergic receptors play an important role in the regulation of energy expenditure, in part, by stimulating lipid mobilization through lipolysis. METHODS: To assess whether it is common for the beta2-adrenergic receptor (B2AR) gene polymorphisms in codons 16 and 27 to play a role in the development of fatty liver, we investigated 251 unrelated healthy Japanese males who were drug-free and showed no signs of heavy drinking. RESULTS: The allelic frequency of B2AR gene mutation in codons 16 and 27 did not differ between obese subjects (BMI>25.0 kg/m(2), n=151) and non-obese subjects (BMI</=25.0 kg/m(2), n=100). The Gly16 homozygotes had a lower high-density lipoprotein cholesterol (HDL-C) level than the Arg16 homozygotes (1.50+/-0.4 vs. 1.32+/-0.3 mmol/l, p=0.014). However, no significant association with fatty liver was observed in the Gly16 allele frequency. The Gln27Glu27 heterozygotes showed higher concentrations of serum triglycerides (TG) than the Gln27Gln27 homozygotes (1.62+/-0.93 vs. 2.21+/-1.67 mmol/l, p=0.013). This correlation was also observed in all subjects regardless of weight classification. Univariate analysis indicated that subjects with the heterozygous Gln27Glu mutant alleles had a significantly higher prevalence of fatty liver vs. those without the mutation (Glu27 allele frequency, 0.07 vs. 0.12, p=0.047; odds ratio, 1.92; 95% confidence interval, 1.01-3.68). However, multivariate logistic regression models showed the prevalence of fatty liver to be significantly related to the homeostasis model assessment (HOMA) index, BMI, triglyceride and HDL-cholesterol. CONCLUSIONS: These results suggest that the amino-terminal polymorphisms of the beta2-adrenergic receptor gene in codon 27 were associated with hypertryglyceridemia and independent of obesity, and thereby could be involved in the molecular pathogenesis of fatty liver.
Adult↗
Association of the Pro90Ser CD36 mutation with elevated free fatty acid concentrations but not with insulin resistance syndrome in Japanese.
BACKGROUND: CD36 deficiency is reportedly an underlying factor about insulin resistance, defective fatty acid metabolism and hypertriglyceridemia in spontaneously hypertensive rat (SHR), and may be involved in the pathogenesis of insulin resistance and hyperlipidemia in humans. METHODS: We examined 831 adults undergoing health screening. The majority (780) was Pro90 homozygous for the CD36 gene product, but 51 displayed a CD36 mutation (2 homozygous and 49 heterozygous for Ser90). This is the major mutation site involved in CD36 deficiency in Japanese. RESULTS: Among parameters related to insulin resistance, there were no differences in body mass index (BMI), HDL cholesterol, total cholesterol, triglycerides, insulin and insulin resistance index (HOMA IR), or blood pressure between 91 normal subjects (45 male and 46 female) randomly selected from the 780 Pro90 homozygotes and the 51 (29 male and 22 females) CD36-deficient subjects (Ser90 homozygote and Pro90Ser heterozygote). Free fatty acid concentrations, however, were higher in Ser90 CD36 subjects than in Pro90 control subjects. CONCLUSIONS: The CD36Pro90Ser mutation is not necessarily related to the insulin resistance syndrome, but is associated with high free fatty acid concentrations in Japanese.
Adult↗
Physiological and morphometric analyses of neuropathy in sucrose-fed OLETF rats.
To investigate the characteristic features of diabetic neuropathy in type 2 diabetes mellitus, Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human type 2 diabetes mellitus, and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were fed with or without sucrose and/or an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl] acetic acid (TAT), for 24 weeks, and physiological, biochemical and morphological assessments were performed. Sucrose administration caused remarkable hyperglycemia in OLETF rats but not in LETO rats. Sucrose-fed OLETF rats demonstrated delayed nerve conduction velocity, decreased coefficient of variation of R-R interval, reduced sciatic nerve blood flow, increased platelet aggregation activity, a lower concentration of erythrocyte 2,3-diphosphoglycerate, and decreased Na+/K+-ATPase activity in sciatic nerves, compared with the non-sucrose-fed OLETF and LETO rats. TAT prevented all these deficits except hyperglycemia. Sorbitol and fructose accumulation and myo-inositol depletion in tail nerves of sucrose-fed OLETF rats were ameliorated by TAT. Myelinated fiber size and density in sural nerves of sucrose-fed OLETF rats were decreased and increased, respectively, compared with non-sucrose-fed OLETF and LETO rats. These morphological abnormalities were normalized by TAT. These observations suggest that the sucrose-fed OLETF rat developed diabetic neuropathy not only electrophysiologically but also histologically, and that an aldose reductase inhibitor, TAT, possesses therapeutic value for the treatment of diabetic neuropathy.
2,3-Diphosphoglycerate↗
Functional analyses of cord blood natural killer cells and T cells: a distinctive interleukin-18 response.
OBJECTIVE: To search for the functional property of cord blood (CB) cells, the effects of interleukin-18 (IL-18) on interferon-gamma (IFN-gamma) production of T cells or natural killer (NK) cells were compared between CB and adult peripheral blood (PB). MATERIALS AND METHODS: T cells, CD45RA(+) T cells, and NK cells were purified from CB and adult PB mononuclear cells using magnetic beads or a cell sorter. After stimulation with or without IL-18 in the presence of IL-12 for 48 hours (NK cells) or 72 hours (T cells or CD45RA(+) T cells), IFN-gamma concentration was measured in each subset. Although IL-18 induced significant IFN-gamma production from both CB and adult PB T cells in the presence of IL-12, the IFN-gamma levels from CB T cells were lower than those from adult PB T cells. However, CD45RA(+) T cells from CB and from adult PB produced similar levels of IFN-gamma after stimulation with IL-18 + IL-12. On the other hand, CB NK cells exhibited higher IFN-gamma production and CD69 expression than adult PB NK cells after stimulation with IL-18 + IL-12. Cytolytic activity of CB NK cells increased to a level comparable to that of adult PB NK cells after the same IL-18/IL-12 stimulation. CONCLUSIONS: These results suggest that a low response of CB T cells to IL-18 is due to a higher proportion of naive (CD45RA(+)) T cells in CB, which may be one of the factors responsible for the neonatal immaturity of the immune system as well as the low incidence of graft-vs-host disease in patients receiving CB stem cell transplantation. On the other hand, a high response of CB NK cells to IL-18 may contribute to the host defense during the neonatal period and antitumor effects in CB stem cell transplantation.
Adult↗
Optimal incision sites to obtain an astigmatism-free cornea after cataract surgery with a 3.2 mm sutureless incision.
PURPOSE: To determine the optimal incision to eliminate astigmatism after cataract extraction. SETTING: Hara Eye Hospital, Utsunomiya, Japan. METHODS: Patients having cataract extraction through a 3.2 mm corneal limbal incision without limbal sutures were divided into 2 groups. Group 1 comprised 98 eyes of 80 patients without preoperative astigmatism and Group 2, 72 eyes of 62 patients with no astigmatism postoperatively. In Group 1, the incisions that caused postoperative corneal changes were retrospectively evaluated. In Group 2, the types of incisions that induced an astigmatism-free cornea postoperatively were retrospectively studied. Patients were examined preoperatively and 6 months postoperatively. RESULTS: In Group 1, 23 of 40 eyes (57.5%) with an incision between 9 and 12 o'clock (BENT incision) and 10 of 58 eyes (17.2%) with an incision at 12 o'clock remained astigmatism free postoperatively (P <.0001). One eye (2.5%) with a BENT incision and 17 (29.3%) with a 12 o'clock incision had astigmatism greater than 1.0 diopter (D) postoperatively (P <.001). In Group 2, 72 eyes had less than 1.2 D of preoperative astigmatism. No eye with more than 1.2 D of astigmatism was astigmatism free postoperatively, even when the incision was made at the steepest meridian. CONCLUSIONS: The results indicate that to reduce astigmatism in eyes with preoperative astigmatism of 0.5 D or more, a limbal 3.2 mm BENT incision should be placed at 10:30 o'clock. To prevent astigmatism postoperatively, the incision should be placed at the steepest meridian in eyes with preoperative astigmatism greater than 0.5 D; for preoperative astigmatism greater than 1.2 D, a 3.2 mm incision at the corneal limbus is insufficient and a wider incision or an additional incision is required.
Aged↗
Moyamoya syndrome with spherocytosis: effect of splenectomy on strokes.
A 3-year-old male patient with hereditary spherocytosis who developed moyamoya syndrome, presenting hemiplegia, and slurred speech is reported. Transient ischemic attacks occurred repeatedly with hemolytic crises. Magnetic resonance imaging and angiography revealed bilateral occlusion of the internal carotid and middle cerebral arteries with the formation of moyamoya vessels and multiple infarctions in the basal ganglia. Although splenectomy can increase the risk of stroke, no stroke occurred after splenectomy. On aspirin and dipyridamole therapy the patient has been free of neurologic deficits and progression of the vasculopathy for 5 years. This rare observation suggests that anemic hypoxia more greatly contributes to the progression of moyamoya syndrome than postsplenectomy thrombocytosis or reduced deformability of spherocytes.
Aspirin↗
Multiple cerebral arteriovenous fistulas and malformations in the neonate.
Multiple cerebral arteriovenous fistulas with malformations in the fetus or neonate are rare. Here we describe a patient who had these lesions with pulmonary stenosis, resulting in severe brain atrophy in utero and intractable heart failure after birth. The pathophysiology of this patient is discussed in hemodynamic terms.
Abnormalities, Multiple↗
Abnormal aluminium metabolism in two siblings with progressive CNS calcification.
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Aluminum↗
Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-gamma gene into lung cancer.
CD40-CD40 ligand (CD40L) interaction is an important costimulatory signaling pathway in the crosstalk between T cells and antigen-presenting cells. This receptor-ligand system is known to be essential in eliciting strong cellular immunity. Here we demonstrate that murine lung cancer cells (3LLSA) transduced with the CD40L gene (3LLSA-CD40L) were rejected in syngeneic C57BL/6 mice, but grew in CD40-deficient mice to the same extent as control tumor cells. Immunohistochemical study showed that inflammatory cells, including CD4+, CD8+ T cells and NK cells, infiltrated into the inoculated 3LLSA-CD40L tumor tissue. Inoculation of 3LLSA-CD40L cells into mice resulted in the induction of 3LLSA-specific cytotoxic T-cell immunity, and the growth of parental 3LLSA tumors was inhibited when 3LLSA cells were inoculated into C57BL/6 mice mixed with 3LLSA-CD40L cells or when they were rechallenged 4 weeks after 3LLSA-CD40L cells were rejected. Furthermore, co-inoculation of interferon (IFN)-gamma-transduced cells (3LLSA-IFNgamma) with 3LLSA-CD40L cells enhanced the antitumor immunity efficiently in vivo. These results indicate that the in vivo priming with CD40L- and IFN-gamma gene-transduced lung cancer cells is a promising strategy for inducing antitumor immunity in the treatment of lung cancer.
Animals↗
Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies.
Factors influencing the outcome for 39 children with haematological malignancy who were subjected to a cord blood transplantation (CBT) from genotypically HLA-mismatched unrelated donors were analysed. This retrospective study included 21 children with acute lymphoblastic leukaemia, 15 with acute myelogenous leukaemia and one each with chronic myelogenous leukaemia, refractory anaemia with myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukaemia (JMML). Those subjected to CBT during the first or second complete remission (CR) and MDS without blasts were assigned to the standard-risk (SR) group (n = 16). Patients in third or subsequent remission, relapse or partial remission with refractory leukaemia at the time of CBT were considered to be in advanced phase, and placed in the high-risk (HR) group (n = 11). JMML and the second CR after a relapse (n = 8), or bone marrow failure after a rejection (n = 3), following haematopoietic stem cell transplantation (HSCT) in the first CR were included in the high-risk group. Kaplan-Meier estimates for neutrophil and platelet recovery were 83.7 +/- 12.2 at d 60 and 55.4 +/- 16.6% at d 100 respectively. The incidence of grades II-VI acute graft-versus-host disease was 58.5 +/- 16.8%. The Kaplan-Meier estimate for 3-year event-free survival (EFS) was 49.2 +/- 16.6. From multivariate analysis, the most important factor influencing EFS was disease status at CBT: SR patients had a 3-year EFS of 75.0 +/- 21.6%, compared with 29.6 +/- 20.6% for those with HR disease (P = 0.013, RR 4.746, 95% CI 1.382-16.298). These data confirm that HLA-mismatched, unrelated CBT is a feasible procedure to cure a significant proportion of children with leukaemia, especially if conducted in a favourable phase of the disease.
Adolescent↗
High expression of platelet-derived growth factor and transforming growth factor-beta 1 in blast cells from patients with Down Syndrome suffering from transient myeloproliferative disorder and organ fibrosis.
To determine whether platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF-beta 1) are involved in organ fibrosis in patients with transient myeloproliferative disorder (TMD) in Down syndrome, the expression of PDGF and TGF-beta 1 mRNA in blast cells of TMD was investigated using real-time quantitative reverse transcription polymerase chain reaction. Blasts and liver tissue from TMD patients with hepatic fibrosis showed a significantly elevated expression of PDGF gene. The expression of TGF-beta 1 gene was higher in TMD and acute megakaryoblastic leukaemia than in the control group. These results suggest that PDGF in combination with TGF-beta 1 plays a role in organ fibrosis of TMD.
Adolescent↗
A thiol proteinase inhibitor, E-64-d, corrects the abnormalities in concanavalin A cap formation and the lysosomal enzyme activity in leucocytes from patients with Chediak-Higashi syndrome by reversing the down-regulated protein kinase C activity.
We have reported previously that the abnormally down-regulated protein kinase C (PKC) causes cellular dysfunction observed in natural killer (NK) cells, polymorphonuclear leucocytes (PMNs) and fibroblasts from beige mouse, an animal model of Chediak-Higashi syndrome (CHS). Here we show that the abnormal down-regulation of PKC activity also occurs in Epstein-Barr (EB) virus-transformed cell lines from CHS patients. When CHS cell lines were stimulated with concanavalin A (Con A) for 20 min, the membrane-bound PKC activity declined markedly, whereas that in control cell lines increased. We found that E-64-d, which protects PKC from calpain-mediated proteolysis, reversed the declined PKC activity and corrected the increased Con A cap formation to almost normal levels in CHS cell lines. We confirmed that the dysregulation of PKC activity also occurred in peripheral blood mononuclear leucocytes (PBMC) from CHS patients and that E-64-d corrected both the declined PKC activity and increased Con A cap formation. E-64-d also corrected the reduced lysosomal elastase and cathepsin G activity in CHS cell lines. In contrast, chelerythrin, a specific inhibitor of PKC, and C2-ceramide, which promotes PKC breakdown induced by calpain, increased Con A cap formation and inhibited both elastase and cathepsin G activity in normal cell lines. Moreover, we found that ceramide production in CHS cell lines increased significantly after Con A stimulation, which coincides with our previous observation in fibroblasts from CHS mice. These results suggest an association between ceramide-induced PKC down-regulation and the cellular dysfunctions in CHS.
Calpain↗