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Biomedical subjects

T Naruse

Publications and source records attributed to T Naruse.

At least 19 recordsLinked to original sources
PubMed2005

HLA class II DPB1, DQA1, DQB1, and DRB1 genotypic associations with occupational allergic cough to Bunashimeji mushroom.

We previously reported that two-third of workers in a Bunashimeji mushroom (Hypsizigus marmoreus) farm complained of respiratory allergic symptoms, but one-third workers did not suffer from such symptoms even when working for a long period. CD4+ T-helper (Th) cells increased, and Th2/Th1 ratio increased in the allergic workers. To address these immunological backgrounds, we have investigated whether there is any relationship between mushroom allergy and human leukocyte antigen (HLA) class II alleles of DPB1, DQA1, DQB1, and DRB1 by using the polymerase chain reaction-restriction fragment length polymorphism (RFLP) and sequencing-based typing methods. We observed that the allele frequencies of DQA1*0103, DQB1*0601, and DRB1*0803 were significantly higher in the workers having no allergic symptoms than allergic workers (DQA1*0103: 57 vs 25%, DQB1*0601: 49 vs 14%, and DRB1*0803: 29 vs 0%). However, this phenomenon was not seen in workers producing another kind of mushroom, Honshimeji (Lyophyllum aggregatum). The HLA-DRB1*0803 allele alone, the DRB1*0803, DQA1*0103, DQB1*0601 haplotype, or both were negatively associated with allergy to Bunashimeji, and these alleles might be involved in the prevention of Bunashimeji mushroom-specific respiratory allergy.

Adult↗
PubMed2004

Association of polymorphic MHC microsatellites with GVHD, survival, and leukemia relapse in unrelated hematopoietic stem cell transplant donor/recipient pairs matched at five HLA loci.

In order to determine whether matching/mismatching for microsatellite polymorphism provides useful information on acute graft-vs-host disease (GVHD), survival, and leukemia relapse in hematopoietic stem cell (HSC) transplantation, we genotyped for polymorphisms at 13 microsatellite loci within the major histocompatibility complex (MHC) of 100 unrelated HSC transplant donor-recipient pairs who were matched at five classical human leukocyte antigen (HLA) loci. A high percentage of allele matching was obtained for five microsatellite loci, DQCARII (96%), MICA (93%), MIB (89%), C1-3-1 (93%), and D6S510 (97%), that are localized within 100 kb of the HLA-DR, HLA-DQ, HLA-B, HLA-C, or HLA-A locus. In contrast, the other eight microsatellites are located farther away from the HLA classical loci and have much lower percentages of allele matching [e.g. tumor necrosis factor a (TNFa) (73%), TNFd (74%), D6S273 (64%), C3-2-11 (46%), C5-3-1 (50%), C5-4-5 (63%), C5-2-7 (68%), and D6S265 (81%)]. Therefore, there were at least eight microsatellite markers with relatively high percentages of mismatches in the donor/recipient pairs with acute or chronic GVHD, poor graft survival, and leukemia relapse. However, there were no statistically significant associations between mismatched donor-recipient pairs at the 13 microsatellite loci and acute or chronic GVHD, graft survival, and leukemia relapse. Nevertheless, allele matching at the microsatellite TNFd locus near the TNFa gene was found by the Fisher's exact double-sided test to be significantly associated with decreased survival in the grade III/IV acute GVHD group. Overall, these results suggest that the matching of microsatellite polymorphisms within the HLA region, especially the ones farthest from the classical HLA loci, was not useful indicator for the outcome of HSC transplantation from unrelated donors. In this regard, the future determination of the genome-wide microsatellite genotypes in HLA-matched donor-recipient pairs, outside the MHC, may be a better possibility for identifying minor histocompatibility genes in linkage disequilibria with microsatellites as potential predictive markers for the occurrence of acute GVHD and survival rate in HSC transplantation.

Adolescent↗
PubMed2004

Molecular analysis of HLA allele frequencies and haplotypes in Baloch of Iran compared with related populations of Pakistan.

The extreme polymorphism in different loci of the human leukocyte antigen (HLA) system has been used as an invaluable tool for anthropological studies. Determination of HLA allele and haplotype frequencies in different ethnic groups is useful for population genetic analyses and the study of genetic relationships among them. In the present study, molecular analysis of HLA-A, -B, -C, -DQA1, -DQB1, and -DRB1 genes has been used to assign HLA allele and haplotype frequencies in 100 unrelated healthy individuals from the Baloch ethnic group of Iran. The results were compared with Baloch and other ethnic groups in the neighboring Pakistan. The results of this study showed that the most frequent HLA class I alleles were A*02011 (20.2%), B*4006 (11.1%), and C*04011 (28.6%). The most common HLA class II alleles were DQA1*0101/2 (42.5%), DQB1*0201 (32%), and DRB1*0301 (29%). Three-locus haplotype analysis revealed that A*11011-B*4006-C*15021 (5.8%) and DQA1*0501-DQB1*0201-DRB1*0301 (22.1%) were the most common HLA class I and II haplotypes, respectively, in this population. Neighbor-joining tree based on DA genetic distances and correspondence analysis according to HLA-A, -B, -DQB1, and -DRB1 allele frequencies showed that Baloch of Iran are genetically very close to Baloch and Brahui of Pakistan. This may reflect an admixture of Brahui and Baloch ethnic groups of Pakistan in the Balochistan province of Iran.

Alleles↗
PubMed2003

Lack of association of the interleukin-1 receptor antagonist gene with palmoplantar pustulosis in Japanese.

We analysed a polymorphism of the interleukin (IL)-1 receptor antagonist (IL1RN) gene in 93 Japanese patients with palmoplantar pustulosis (PPP). None of the IL1RN alleles was significantly increased in the patients compared with controls. Because PPP has been reported to be associated with the tumour necrosis factor (TNF) region, we examined the association between the TNF and IL1RN genes. There was a difference in IL1RN*2 positivity between patients with and without the AA genotype of the TNF gene. In contrast, such a difference was not found in controls. These data indicate a possible epistatic effect between TNF and IL1RN linked genes for susceptibility to the pathogenesis of PPP.

Adult↗
PubMed2002

Molecular diversity of the HLA-A*19 group of alleles in North Indians: possible oriental influence.

The present study aims to determine the genetic diversity of the HLA-A19 allelic family in the North Indian and Japanese populations. The HLA-A*19 group of alleles occurred at similar frequencies in North Indians and Japanese as in Caucasians. All the known serological splits of HLA-A19 were observed among the North Indians, i.e. A*33 (15.6%), A*32 (8.6%), A*31 (3.5%), A*30 (3%), A*29 (1.2%) and A*74 (0.77%), while only A*30 (0.7%), A*31 (17.6%) and A*33 (11.7%) were observed in the Japanese. High resolution analysis indicated that the A*29, A*30, A*31 and A*32 alleles were represented by only single subtypes among the North Indians while the HLA-A*33 group comprised two alleles, A*3301 (4.3%) and A*3303 (43.7%). All 15 of the HLA-A*33 positive samples from the Tamil population of South India were found to be A*3303. One novel subtype of A*33, A*3306 was also observed in the North Indian sample. Conversely, only one subtype each of A*30, A*31 and A*33 was encountered in the Japanese population, of which A*3101 and A*3303 were the most frequent (58.5% and 39%, respectively, among the HLA-A*19 group of alleles). All other subtypes of A19 were not found in the Japanese in the present study. The study suggests a significant amount of genetic admixture in the North Indian gene pool from other racial groups, with profound oriental influence.

Alleles↗
PubMed2001

A second susceptibility gene for developing rheumatoid arthritis in the human MHC is localized within a 70-kb interval telomeric of the TNF genes in the HLA class III region.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with a multifactorial genetic basis. However, pathogenic genes for RA other than the human leukocyte antigen (HLA)-DRB1 gene have yet to be identified. Here, we investigated whether there is a second susceptibility locus for RA within the human major histocompatibility complex using 18 microsatellite markers distributed from the centromeric (HSET) to the telomeric end (P5-15) of the 3.6-Mb HLA region. Statistical studies of associated alleles on each microsatellite locus showed that one pathogenic gene for RA in the HLA region is localized in the DRB1 gene, as expected. Further, a second susceptibility gene of RA was suggested to be present in the HLA class III region, narrowed to 70 kb, that is just telomeric of the TNF gene cluster (TNFA and LTA) and that is located between the microsatellites TNFa and C1-2-A. In this critical segment, four expressed genes have been thus far identified, NFKBIL1 (IkappaBL), ATP6G, BAT1, and MICB, all of which are candidate genes for determining susceptibility to RA. These results exclude the possibility of involvement of the TNFA genes (TNF-alpha) in the development of RA, which was suggested previously to be a strong candidate for RA in the class III region.

Alleles↗
PubMed2001

The association between HLA-A alleles and an Alu dimorphism near HLA-G.

The AluYb8 sequences are a subfamily of short interspersed Alu retroelements that have been amplified within the human genome during recent evolutionary time and are useful polymorphic markers for studies on the origin of human populations. We have identified a new member of the Yb8 subfamily, AluyHG, located between the HLA-H and -G genes and 88-kb telomeric of the highly polymorphic HLA-A gene within the alpha block of the major histocompatibility complex (MHC). The AluyHG element was characterised with a view to examining the association between AluyHG and HLA-A polymorphism and reconstructing the history of the MHC alpha block. A specific primer pair was designed for a simple PCR assay to detect the absence or presence (dimorphism) of the AluyHG element within the DNA samples prepared from a panel of 46 homozygous cell-lines containing complete or recombinant ancestral haplotypes (AH) of diverse ethnic origin and 92 Caucasoid and Asian subjects on which HLA-A typing was available. The AluyHG insertion was most strongly associated with HLA-A2 and, to a lesser degree with HLA-A1, -A3, -A11, and A-19. The gene frequency of the AluyHG insertion for 146 Caucasians and 94 Chinese-Han was 0.30 and 0.32 and there was no significant difference between the observed and expected frequencies. The results of the association studies and the phylogenetic analysis of HLA-A alleles suggest that the AluyHG sequence was integrated within the progenitor of HLA-A2, but has been transferred by recombination to other human ancestral populations. In this regard, the dimorphic AluyHG element is an important diagnostic marker for HLA association studies and could help in elucidating the evolution and functions of the MHC alpha block and polymorphism within and between ancestral haplotypes.

Alleles↗
PubMed2001

Molecular detection of tumor cells at diagnosis invading the bone marrow and peripheral blood of patients with aggressive or indolent lymphomas.

We studied tumor cell invasions of bone marrow and peripheral blood in patients with various types of advanced non-Hodgkin's lymphoma by amplifying complementarity determining region III using the polymerase chain reaction (PCR) method and developing patient-specific probes. After molecular engineering, we could detect tumor cells in bone marrow from seven of 11 cases and in peripheral blood from six of 11 cases, despite negative results in four cases studied morphologically. Indolent cases were more likely to yield positive results than aggressive cases. The reason may be different biological behaviors among the histological types.

Bone Marrow Neoplasms↗
PubMed2001

Identification of MICA alleles with a long Leu-repeat in the transmembrane region and no cytoplasmic tail due to a frameshift-deletion in exon 4.

MHC class I chain-related gene A (MICA) is located close to HLA-B gene and expressed in epithelial cells. The MICA gene is reported to be highly polymorphic as are the classical class I genes. To further assess the polymorphism in the MICA gene, we analyzed a total of 60 HLA-homozygous cells for the sequences spanning exons 2-6. In the analysis, four new MICA alleles were identified and six variations were recognized in exon 6. MICA*017, which was identified in three HLA-B57 homozygous cells (DBB, DEM and WIN), differed from MICA*002 in exon 3 and had a guanine deletion at the 3' end of exon 4. MICA*015 identified in an HLA-B45 homozygous cell (OMW) also had the same deletion that causes a frameshift mutation resulting in complete change of the transmembrane region and premature termination in the cytoplasmic tail; these alleles have a long hydrophobic leucine-rich region instead of the alanine repeat in the transmembrane region and terminate at the second position in the cytoplasmic domain. The frameshift deletion was found only in HLA-B45- or -B57-positive panels tested, suggesting a strong linkage disequilibrium between the deletion and B45 or B57. MICA*048, which was different in exon 5 from MICA*008, was identified in an HLA-B61 homozygous cell (TA21), while MICA*00901 identified in HLA-B51 homozygous cells (LUY and KT2) was distinguished from MICA*009 by exon 6.

Base Sequence↗
PubMed2001

Polymorphisms in the tumor necrosis factor (TNF) genes are associated with susceptibility to effects of ultraviolet-B radiation on induction of contact hypersensitivity.

We investigated the allelic distributions of single nucleotide polymorphisms (SNPs) of the TNFA, TNFB and IKBL genes, 3 microsatellites within the tumor necrosis factor (TNF) region of HLA locus, and the HLA phenotypes as well as the TLR4 gene in Chromosome 9 in 26 healthy Caucasian volunteers. These individuals were also assessed as ultraviolet B (UVB)-susceptible (S) or UVB-resistant (R). Our results identified 12 UVB-S and 14 UVB-R individuals. Attempts to correlate particular HLA-A, -B, -C, and -DR antigens with the UVB phenotypes failed. Similarly, attempts to correlate SNP at the NcoI-RFLP within intron 1 of the TNFB, IKBL and TLR4 gene with UVB phenotypes also failed. However, microsatellite analyses of TNFa, TNFc, and TNFd markers revealed a significant increase in the frequencies of TNFa2 in UVB-S individuals (P=0.00032) and of TNFd3 in UVB-R individuals (P=0.012). Moreover, DNA sequencing analyses of 5 SNPs of the TNFA promoter region revealed a significant increase in the frequency of the allele B of the TNFA gene (TNFApB) representing the nucleotide A at position -863 and C at position -1031 (P=0.015). Since it is known that TNFa2 and TNFApB is a high TNF-alpha responder, whereas TNFd3 is a TNF-alpha low responder, we propose that the TNF region of HLA contains polymorphic genes that confer susceptibility and resistance to the deleterious effects of UVB radiation on the induction of contact hypersensitivity. This proposal is consistent with previous reports that a unique microsatellite region of the Tnfa gene in mice contains alleles that dictate the UVB-dependent phenotypes in mice, and implicate TNF-alpha as the primary mediator of the immune-damaging effects of UVB radiation.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Reduced urinary excretion of intact osteopontin in patients with IgA nephropathy.

Osteopontin (OPN) is a phosphoprotein secreted by many cells of epithelial, mesenchymal, and hematopoietic origin. In the kidney, OPN is expressed in the renal tubules and collecting ducts and is excreted into the urine. A pathophysiologic role for urinary OPN has not been established. In this study, urinary excretion of OPN was analyzed in patients with primary glomerular diseases, including immunoglobulin A nephropathy (IgAN; n = 32), minimal change nephrotic syndrome (MCNS; n = 16), and membranous nephropathy (MN; n = 18). Compared with normal controls (n = 20), mean +/- SD of urinary OPN in IgAN patients was decreased significantly (21.4 +/- 6.2 versus 11.6 +/- 9.6 mg/g creatinine, P: < 0.001). In contrast, the levels of urinary OPN in patients with MCNS or MN did not differ significantly from normal values. Immunoblot analysis showed that OPN is present as a 55- to 60-kd molecule in normal urine. A 34-kd fragment of OPN was the major immunoreactive band in samples from IgAN patients. This fragment also was detectable in the urine from some patients with MCNS or MN but was absent in normal subjects. OPN has a thrombin-cleavage site near its central portion. Thrombin treatment of the urine from normal controls could result in 34-kd OPN fragments. Although the underlying mechanisms remain to be determined, these data provide evidence that secretion or processing (or both) of urinary OPN is altered in patients with IgAN.

Adult↗
PubMed2001

Serum factors attenuating the anti-tumor activity of 5-fluorouracil.

In sera of cachectic patients bearing advanced cancers, the concentration of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrotizing factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) have been reported to elevate. In this study, we investigated whether those cytokines influenced in vitro anti-tumor effect of 5-fluorouracil (5-FU) on a human colon tumor cell line, HCT-15. Pretreatment of HCT-15 cells with IL-1 beta, IL-6 or TNF-alpha did not affect the anti-tumor effect of 5-FU at various concentrations. However, IFN-gamma attenuated the anti-tumor effect of 5-FU at the concentrations of 0.1-10 IU/ml. An experiment with tritium thymidine showed that 0.1 IU/ml of IFN-gamma did not suppress the growth of HCT-15 cells. As low as 0.1 IU/ml of IFN-gamma attenuated the anti-tumor effect of 5-FU in another experimental system where HCT-15 cells were exposed to 0.1 IU/ml of IFN-gamma before and during the treatment with 5-FU. This system mimicked the clinical condition around in situ cancer cells. Treatment of HCT-15 cells with 0.1-10 IU/ml of IFN-gamma did not change their DNA histogram pattern. An immunoblotting with the antibodies to thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in HCT-15 cells revealed that 0.1-10 IU/ml of IFN-gamma enhanced their TS and DPD expressions. Results of the immunoblotting gave some explanation to attenuation in the sensitivity of HCT-15 cells to 5-FU.

Antimetabolites, Antineoplastic↗
PubMed2001

Platelet-activating factor antagonist, SM-12502, attenuates experimental glomerular thrombosis in rats.

Platelet-activating factor (PAF) is involved in many pathologic conditions through its potent proinflammatory and vasoactive effects. Using a specific PAF antagonist, SM-12502, we investigated the role of PAF in rat experimental glomerular thrombosis. In this model, sequential injections of nephrotoxic serum (NTS) and lipopolysaccharide (LPS) selectively induce glomerular fibrin deposition accompanied by neutrophil accumulation. SM-12502, when injected simultaneously with either NTS or LPS, strongly inhibited glomerular fibrin deposition in a dose-dependent manner. In contrast, neutrophil invasion was similar in both SM-12502-injected and uninjected rats, suggesting that the antithrombotic effect was not mediated by inhibition of neutrophil migration. However, serum myeloperoxidase activity, a marker of neutrophil activation, was significantly suppressed by treatment with SM-12502. From a previous finding supporting the indispensable role of neutrophils in this model and the current observations, SM-12502 is suggested to attenuate glomerular thrombosis by inhibiting neutrophil activation. Thus, the present findings suggest an involvement of PAF in this glomerular thrombosis model.

Animals↗
PubMed2001

Acquired hemophilia A in a patient with systemic lupus erythematosus.

A patient with systemic lupus erythematosus (SLE) developed acquired hemophilia A. The patient, a 24-year-old Japanese woman, was referred to our hospital because of uncontrollable bleeding following a tooth extraction. Laboratory examination revealed prolonged APTT (116 seconds), reduced factor VIII activity (2.8 %) and the presence of factor VIII inhibitor at a titer of 46.5 Bethesda units/ml. Transfusion of prothrombin complex concentrate and activated prothrombin complex concentrate followed by administration of prednisolone and cyclophosphamide successfully arrested bleeding and reduced the factor VIII inhibitor level. Acquired hemophilia A is a rare but lethal condition. Rapid diagnosis and introduction of adequate therapies are critical.

Adult↗
PubMed2001

Corticosteroid therapy in patients with IgA nephropathy and impaired renal function.

AIM: IgA nephropathy (IgAN) is a common type of primary glomerulonephritis that constitutes a major cause of end-stage renal disease. Oral and/or intravenous glucocorticoid therapy can protect against progression of IgAN in patients with preserved renal function. We evaluated steroid therapy in IgAN with established renal dysfunction. PATIENTS AND METHODS: We retrospectively analyzed the effect of methylprednisolone (MP) pulse therapy in 8 IgAN patients with serum creatinine concentrations (sCr) 2.76 +/- 1.32 mg/dl (mean +/- SD). In each patient renal function had progressively deteriorated in the 12 months preceding treatment, as indicated by negative slopes of 1/sCr plotted against time (regression coefficients). RESULTS: Regression coefficients during the 12 months following therapy improved significantly from -0.02333 +/- 0.00732 to -0.00036 +/- 0.00423 dl/mg/month, respectively. The mean difference in slope was 0.0230 +/- 0.0076 dl/mg/month (95% confidence interval, 0.0165 to 0.0295, p < 0.001). Proteinuria also significantly decreased from a mean urine protein/creatinine ratio of 2.57 +/- 1.12 before therapy to 1.12 +/- 0.84 6 months after therapy (p < 0.005). Other factors that might affect progression of renal dysfunction remained unchanged during the observation periods. CONCLUSION: Corticosteroids may attenuate progression of renal failure and delay the need for dialysis in this patient population, although a large randomized trial is necessary.

Administration, Oral↗
PubMed2001

[Ectopic calcification in patients with aplastic bone disease undergoing dialysis].

Aplastic bone disease (adynamic bone disease) has been attracted attention as the most frequent type of renal osteodystrophy in patients undergoing dialysis, and relatively low serum parathyroid hormone level is considered to be the major cause of aplastic bone disease. In aplastic bone disease, both the number of osteoblast and osteoclast are few and the speed of bone turnover is low, therefore, buffering action of bone for calcium and phosphorus is extremely disturbed. Hypercalcemia due to a prescription of large dose calcium carbonate and hyperphosphatemia derived by high protein diet in this occasion induce high serum calcium and phosphorus product level, and ectopic calcification is likely to occur. When ectopic calcification occur at artery it might develop ischemic change of visceral organ. Recently, the strong association between coronary arterial calcification and high serum calcium and phosphorus products is clarified by a method of electron-beam computed tomography. Based on these findings, high calcium and phosphorus product is now believed as a risk for poor patients' survival. Thus, we should pay attention to calcium and phosphorus product in patients suffering from aplastic bone disease.

English Abstract↗
PubMed2000

Number of glomeruli is increased in the kidney of transgenic mice expressing the truncated type II activin receptor.

Histological analyses of the kidney were performed in transgenic mice expressing the truncated type II activin receptor. In these mice, signaling through the activin receptor was attenuated. Size and wet weight of the kidneys were identical to those of normal mice. Histologically, the number of glomeruli was approximately 180% of that in normal mice. The sizes and shapes of the glomeruli were variable, but many of them were smaller than those in normal mice. Morphometrically, the total glomerular area was 130% of that of the normal mice. Abnormality of the epithelia in Bowman's capsule was observed and the number of tubular epithelial cells was increased in the transgenic mice. The serum levels of blood urea nitrogen, creatinine, and creatinine clearance were identical to those in normal mice. These results suggest that the action of activin or related ligands is critical for determination of the nephron number.

Activin Receptors, Type II↗