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Biomedical subjects

K Ihara

Publications and source records attributed to K Ihara.

At least 37 records · Page 2Linked to original sources
PubMed2001

Low expression of p27(Kip1), a cyclin-dependent kinase inhibitor, is a marker of poor prognosis in synovial sarcoma.

BACKGROUND: Low expression of p27(kip1), a dominant cyclin-dependent kinase inhibitor involved in G1-S transition of the cell cycle, recently has been reported to be associated with aggressive tumor growth. It has been shown that active cell proliferation alludes to poor prognosis in patients with synovial sarcoma. However, to the authors' knowledge, little is known about the clinicopathologic significance of p27(kip1) in synovial sarcoma. METHODS: p27(kip1) expression was examined immunohistochemically in 55 cases of primary synovial sarcoma, and the relations between p27(kip1) expression and several cell proliferation markers, i.e., mitotic index (MI), Ki-67 labeling index (Ki-67 LI), and clinicopathologic parameters related to poor prognosis, were determined. Univariate and multivariate survival analyses were performed to evaluate the prognostic significance of p27(kip1) expression in synovial sarcomas. RESULTS: p27(kip1) labeling index (p27(kip1) LI) correlated inversely with MI (r = -0.44, P = 0.0007) and Ki-67 LI (r = -0.63, P < 0.0001). Of the clinicopathologic parameters examined, tumor necrosis (P = 0.019) and American Joint Committee on Cancer (AJCC) stage (P = 0.021) correlated significantly with p27(kip1) LI. Survival analysis showed that p27(kip1) LI was an independent prognostic factor for overall survival in patients with synovial sarcoma (P = 0.0031). CONCLUSIONS: The study results suggested that low expression of p27(kip1) may be useful as a marker of poor-prognosis synovial sarcoma.

Adolescent↗
PubMed2001

Vascular complication in free tissue transfer to the leg.

The lower-extremity free flap has a high incidence of vascular complication. A retrospective study of 70 free flap transplants in 70 patients (1987-2000) was conducted to investigate factors leading to vascular complication and free flap failure. The overall success rate was 92% (64 of 70 flaps); the incidence of vascular complications was 22% (16 of 70 flaps). Among 16 complicated flaps, 7 were transferred in severely crushed legs, and 4 were in multioperated legs attributable to chronic osteomyelitis. Venous thrombosis occurred in 12 flaps (86%). The success rate of the patients operated on at Yamaguchi University Hospital was higher (96%) than at other hospitals tested. The key factors contributing to improved outcome in free tissue transplantation in the leg were careful preoperative planning for highly traumatized legs and proper selection of the recipient vein and of the hospital at which immediate reexploration can be performed for vascular complicated flaps.

Adolescent↗
PubMed2001

Rapid detection of the 22q11.2 deletion with quantitative real-time PCR.

We report the detection of 22q11.2 deletions using TaqMan(TM)PCR-based gene dosage analysis of patients previously diagnosed by fluorescent in situ hybridization (FISH). We performed quantitative PCR of the UFD1L gene from this region and showed a 99.7% statistical correlation between the two methods. The advantages of this method over FISH include: (i) rapidity; (ii) ease; (iii) relatively low cost and; (iv) the small quantities of DNA needed.

Abnormalities, Multiple↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

Association of IFN-gamma and IFN regulatory factor 1 polymorphisms with childhood atopic asthma.

BACKGROUND: IFN-gamma and related molecules play important roles in the differentiation and function of TH2 cells. OBJECTIVE: We sought to determine whether IFNG and related genes contribute to any susceptibility to atopic asthma, a representative TH2-dominant disorder. METHODS: We investigated the association of IFNG (CA repeat polymorphism within the first intron), IRF1 (GT repeat polymorphism within the intron 7), IFNGR1 (Val 14 Met), and IFNGR2 (Gln 64 Arg) gene polymorphisms with atopic asthma in the Japanese child population. RESULTS: A significant association (P =.0018) was observed between IFNG gene polymorphism and atopic asthma. The tendency was more prominent in patients with age of onset of 3 years or younger (P =.0004) or patients with a family history of allergic diseases (P =.0038). Furthermore, there was a significant association between IRF1 gene whole-allele distribution and atopic asthma (P =.044). The tendency was more prominent in patients with onset at 3 years of age or less (P =.0058). On the other hand, IFNGR1 and IFNGR2 gene polymorphisms showed no association with atopic asthma. CONCLUSION: These results suggested that among IFNG and related genes, IFNG and IRF1 genes confer genetic susceptibility to atopic asthma in Japanese children.

Adolescent↗
PubMed2001

Enhancement of oxidative damage to cultured cells and Caenorhabditis elegans by mitochondrial electron transport inhibitors.

The mechanisms that lead to mitochondrial damage under oxidative stress conditions were examined in primary and cultured cells as well as in the nematode Caenorhabditis elegans (C. elegans) treated simultaneously with electron transport inhibitors and oxygen gas. Oxygen loading enhanced the damage of PC 12 cells by thenoyltrifluoroacetone (TTFA, a complex II inhibitor), but did not by rotenone (a complex I inhibitor), antimycin (a complex III inhibitor), and sodium azide (a complex IV inhibitor). In primary hepatocytes, the enhancement was observed with the addition of sodium azide and rotenone, but not by TTFA or antimycin. In the nematode, only rotenone and TTFA enhanced the sensitivity under hyperoxia. These results demonstrate that highly specific inhibitors of electron transport can induce oxygen hypersensitivity in cell levels such as PC 12 cells and primary hepatocytes, and animal level of C. elegans. In addition the cell damage is different dependent on cell type and organism.

Animals↗
PubMed2001

Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population.

OBJECTIVE: Systemic lupus erythematosus (SLE) in a multisystem autoimmune disorder characterized by multiorgan pathology and autoantibodies against a variety of autoantigens. The CD28 and CTLA-4 genes might be candidate genes for SLE, because costimulation signals from CD80/CD86 to CD28/CTLA-4 have been suggested to play an important role in the activation or inactivation of T lymphocytes. METHODS: We investigated three polymorphic regions within the CTLA-4 gene, a C/T base exchange in the promoter region -318 (CTLA-4 -318C/T), an A/G substitution in the exon 1 position 49 (CTLA-4 49A/G), an (AT)(n) repeat polymorphism in the 3' untranslated region of exon 4 [CTLA-4 3' (AT)(n)], and a CD28 gene polymorphism, a T/C substitution in the intron 3 position +17 (CD28 IVS3+17T/C), in SLE patients and controls. RESULTS: SLE patients had significantly higher frequencies of the CTLA-4 49G allele (P=0.003) and of the CTLA-4 (AT)(n) 106 bp allele (P=0.0008) than controls. We also found a strong linkage disequilibrium between the A allele of CTLA-4 49A/G and the 86 bp allele of CTLA-4 3' (AT)(n). On the contrary, no association was found between SLE and CTLA-4 -318C/T or CD28 IVS3 +17T/C. CONCLUSION: We conclude that the CTLA-4 gene appears to play a significant role in the development of SLE in the Japanese population.

Abatacept↗
PubMed2001

Inflammatory bowel disease-like colitis in glycogen storage disease type 1b.

Chronic inflammatory bowel disease (IBD)-like colitis is occasionally associated with glycogen storage disease-type 1b (GSD-1b). We describe a 17-year old boy with GSD-1b who developed an IBD-like colitis. Roentgenography and colonoscopy showed the lead-pipe appearance of the colon and circumferential ulcers. Histopathologic examination revealed nonspecific inflammation without granulomatous lesions. High-dose granulocyte-colony stimulating factor (G-CSF) and sulfasalazine led to the resolution of the colitis, although neutropenia continued. Besides this case, 10 published cases of GSD-1b and IBD-like colitis were reviewed. All cases had severe neutropenia and/or neutrophil dysfunction. The mean onset of bowel disease was 12.3 years of age. Seven cases required surgical treatment. All five patients with G-CSF/GM-CSF therapy showed clinical remission. These findings suggest that IBD-like colitis is a grave complication of GSD-1b and that recurrent enteric infections due to neutrophil deficiency may contribute to the development of this bowel disease.

Adolescent↗
PubMed2001

Physical growth and retinopathy in preterm infants: involvement of IGF-I and GH.

GH and IGF-I are important for physical growth. We measured serum levels of these factors in preterm infants. The study population (n = 81) was divided into three groups according to the gestational age. We evaluated differences in serum GH and IGF-I levels among groups with regard to physical growth and development of retinopathy of prematurity. Serum GH levels in extremely preterm infants born at <28 wk of gestational age were significantly higher than levels in those born between 28 and 34 wk at 1 and 2 mo of age. In contrast, serum IGF-I levels in extremely preterm infants remained low, whereas those in the other two groups gradually increased. Evaluation of the effects of GH and IGF-I on physical growth in very low birth weight infants (<1500 g) showed that IGF-I concentrations were positively related to physical growth for several months after birth, whereas no relationship was observed between GH and physical growth. Multivariate analysis demonstrated that high GH concentration at 1 mo of age was significantly associated with development of severe retinopathy of prematurity. In conclusion, persistent low serum IGF-I levels may explain the slow physical growth during neonatal life, and exposure of high GH may cause, at least in part, severe retinopathy of prematurity in preterm infants.

Disease Progression↗
PubMed2001

[Efficacy of radiofrequency catheter ablation in a patient with sinus node reentrant tachycardia].

We performed electrophysiological study and catheter ablation on a 62-year-old patient with supraventricular tachycardia(SVT). This SVT was reproducibly initiated and terminated by atrial stimulation during the electrophysiological testing. The P-wave morphology and atrial activation sequence of intracardiac electrograms were identical to those in normal sinus rhythm. SVT was terminated with carotid sinus massage that increased vagal tone, and for this reason, the reentry circuit of SVT could be localized in sinus node. On the basis of these findings, the SVT was diagnosed as sinus node re-entrant tachycardia and was successfully eliminated by radiofrequency catheter ablation. Radiofrequency catheter ablation would be effective in patients with sinus node reentrant tachycardia refractory to anti-arrhythmic drugs. It should, however, be performed with careful consideration to the influence of the sinus node.

Catheter Ablation↗
PubMed2001

Stereoselective pharmacokinetics and pharmacodynamics of organic nitrates in rats.

Plasma concentration and vasodilating effect after i.v. bolus injection of stereoisomeric organic nitrates were evaluated. Pharmacokinetics of mononitrates was analyzed with a linear one-compartment model. The apparent volumes of distribution were almost identical, but systemic clearances were different among stereoisomers. The concentration data after dinitrate administration could be described based on a two-compartment model with elimination only from the central compartment via metabolism to mononitrate, and then mononitrate-dependent metabolic clearance was estimated. In the vasodilation by mononitrate administered intravenously, the maximum effect was not observed. The reduction of mean arterial pressure from baseline level was related to plasma concentration with a log-linear model. The pharmacological effect following dinitrate dosing was analyzed by a sigmoidal Emax model assuming a simple additive effect of dinitrate and mononitrate. Although almost the same Hill's constant and maximum effect (Emax) values were estimated, the concentrations required to produce 50% of Emax (EC50) differed among stereoisomers. The clearance and EC50 values of stereoisomers with nitrate group at the exo position were generally higher than those with the same group at the endo position. This suggests that the stereostructure of organic nitrates controls the vasodilator potency and duration of action.

Animals↗
PubMed2000

Epstein-Barr virus (EBV) load and cytokine gene expression in activated T cells of chronic active EBV infection.

To identify the role of T cells in chronic active Epstein-Barr virus (EBV) infection, EBV and cytokine gene expression was quantified by use of real-time polymerase chain reaction (PCR) among 6 patients who fulfilled the diagnostic criteria for chronic active EBV infection. Four of these patients showed clonal expansion of EBV-infected T cells. Quantitative PCR for EBV DNA in peripheral blood of patients with symptomatic chronic active EBV infection showed higher copy numbers of virus (mean, 1.45 x 10(5) copies/mL) than were seen in blood from patients with infectious mononucleosis (3.08 x 10(3) copies/mL) or with EBV-associated hemophagocytosis (2.95 x 10(4) copies/mL). Fractionated CD3(+) HLA-DR(+) cells from patients with chronic active EBV infection contained higher copy numbers than did CD3(+) HLA-DR(-) cells. Quantitative PCR for cytokines revealed that interferon-gamma, interleukin (IL)-2, IL-10, and transforming growth factor-beta genes were expressed at higher levels in HLA-DR(+) than in HLA-DR(-) T cells. These results suggest that activated T cells in chronic active EBV infection expressed high levels of EBV DNA and both Th1 and Th2 cytokines. EBV-infected T cells may contribute to the unbalanced cytokine profiles of chronic mononucleosis.

Adolescent↗
PubMed2000

An open conformation of switch I revealed by the crystal structure of a Mg2+-free form of RHOA complexed with GDP. Implications for the GDP/GTP exchange mechanism.

Mg(2+) ions are essential for guanosine triphosphatase (GTPase) activity and play key roles in guanine nucleotide binding and preserving the structural integrity of GTP-binding proteins. We determined the crystal structure of a small GTPase RHOA complexed with GDP in the absence of Mg(2+) at 2.0-A resolution. Elimination of a Mg(2+) ion induces significant conformational changes in the switch I region that opens up the nucleotide-binding site. Similar structural changes have been observed in the switch regions of Ha-Ras bound to its guanine nucleotide exchange factor, Sos. This RHOA-GDP structure reveals an important regulatory role for Mg(2+) and suggests that guanine nucleotide exchange factor may utilize this feature of switch I to produce an open conformation in GDP/GTP exchange.

Binding Sites↗
PubMed2000

Genomic imprinting of insulin-like growth factor-2 in infant leukemia and childhood neuroblastoma.

BACKGROUND: Loss of imprinting (LOI) of insulin-like growth factor-2 (IGF-2) has been implicated in the pathogenesis of certain human cancers and tumor-predisposing overgrowth disorders, such as Beckwith-Wiedemann syndrome. In a previous study, the authors revealed that certain patients with childhood acute leukemia and neuroblastoma had had rapid somatic growth after birth, suggesting the involvement of growth factor(s) in tumorigenesis. In the current study, the authors examined whether relaxation of IGF-2 imprinting occurred in infant leukemia and childhood neuroblastoma. METHODS: The genomic DNA of infant leukemia, childhood neuroblastoma, and control individuals was amplified by polymerase chain reaction (PCR). Patients who had heterozygous genotype were selected as informative cases using Apa I polymorphism in exon 9 of the IGF-2 gene. Total RNA was isolated from informative cases, followed by cDNA synthesis. cDNA was amplified by PCR, and direct sequence was performed for determining allele specific transcription. RESULTS: Twenty of 22 infant leukemia blasts and all of 16 neuroblastoma cells showed normal monoallelic expression of IGF-2 as well as 23 controls. The height and weight of two acute lymphoblastic leukemia patients with LOI were within normal ranges for Japanese children. CONCLUSIONS: The current study revealed that the imprinting status of IGF-2 was generally maintained in infant leukemia and confirmed that it was maintained in childhood neuroblastoma. The results suggest that LOI of IGF-2 does not play a major role in the carcinogenesis of these diseases or in rapid physical growth of the patients.

Female↗
PubMed2000

Analysis of measles virus binding sites of the CD46 gene in patients with subacute sclerosing panencephalitis.

Measles virus (MV) binding sites of the CD46 gene were sequenced in patients with subacute sclerosing panencephalitis (SSPE) and in controls. There were 3 novel polymorphisms, including C/T at nucleotide position 38 (C/T38), G/A at position 176 (G/A176), and C/T at position 453 (C/T453), at allele frequencies of.97:.03, .99:.01, and.97:.03, respectively. The G/A176 polymorphism causes an Arg/Gln amino acid change within the essential binding sites of MV, whereas the C/A38 polymorphism causes a Ser/Phe change outside the MV binding sites. The C/T453 polymorphism does not produce an amino acid change. Two of the 40 SSPE patients and 2 of the 32 controls had both C/T38 and C/T453 polymorphisms in heterozygous patterns. One control subject, but no SSPE patients, had the G/A176 polymorphism in a heterozygous pattern. Thus, it is not likely that CD46 gene alteration has a role as a host susceptibility factor in the development of SSPE.

Adolescent↗