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Biomedical subjects

K Kashiwase

Publications and source records attributed to K Kashiwase.

At least 19 recordsLinked to original sources
PubMed2005

Serial changes in plasma brain natriuretic peptide concentration at the infarct and non-infarct sites in patients with left ventricular remodelling after myocardial infarction.

OBJECTIVES: To clarify the role of infarct and non-infarct sites on left ventricular (LV) remodelling after myocardial infarction by measuring brain natriuretic peptide (BNP) from each site. METHODS AND RESULTS: BNP from the aorta and the anterior interventricular vein (AIV) was measured in 45 patients with first anterior myocardial infarction at one, six, and 18 months. The LV was significantly dilated (> 10 ml/m(2) of end diastolic volume from one to 18 months) in 20 patients (remodelling (R) group) but not in 25 others (non-remodelling (NR) group). Patient characteristics and LV functions did not differ significantly at one month but plasma BNP concentration was higher in group R than in group NR (336 (288) v 116 (106) pg/ml, p < 0.01), predicting the degree of LV dilatation. The difference in BNP concentration between the aortic root and AIV (DeltaBNP), reflecting BNP secreted from the infarct site, did not differ at one month. In both groups BNP and DeltaBNP significantly decreased from one to six months (p < 0.05) and decreased from six months to 18 months, but the change was not significant. BNP and DeltaBNP were significantly higher in group R than in group NR after six months, when LV dilatation was not evident in both groups. CONCLUSION: Enhanced BNP secretion at one month in the non-infarct and infarct ventricular sites predicts subsequent LV dilatation (that is, remodelling). The slower process of LV remodelling decreased BNP secretion at both sites. Thus, BNP concentration should be useful for monitoring ventricular remodelling after infarction.

Cardiomyopathy, Dilated↗
PubMed2002

Polymorphisms in TNFA and TNFR2 affect outcome of unrelated bone marrow transplantation.

Effects of polymorphisms in TNFA and TNFR2 on the outcome of 462 cases of unrelated bone marrow transplantation (uBMT) were studied retrospectively. Four alleles of TNFA (U01-U04) distinguished by polymorphism in the upstream region, -1031 (T/C), -863 (C/A) and -857 (C/T), and two alleles of TNFR2 (196M/196R) distinguished by polymorphism at codon 196 were determined. Transplantation involving TNFA-U02- and/or U03-positive donors and/or recipients resulted in a higher incidence of graft-versus-host disease (GVHD) of grade III-IV (P < 0.05 for donor type, P < 0.01 for recipient type) and a lower relapse rate than that involving TNFA-U01 homozygous recipients and/or donors (P < 0.025 for donor type, P < 0.01 for recipient type). These results include the HLA mismatching effect due to linkage disequilibirium of TNFA with HLA loci. However, the effects were also observed in HLA-A, -B and -DRB1 allele-matched transplantation. Transplantation from TNFR2-196R-positive donors exhibited a higher incidence of severe GVHD (P < 0.05) and tendency for a lower relapse rate than that from TNFR2-196M homozygous donors. TNFR2-196R of recipient origin had no effect on GVHD but increased the relapse rate (P < 0.025). These results suggest that TNFA and TNFR2 typings are helpful for predicting uBMT outcome and for preventing severe complications at an early stage.

Adult↗
PubMed2002

Association of HLA-A*3303-B*4403-DRB1*1302 haplotype, but not of TNFA promoter and NKp30 polymorphism, with postherpetic neuralgia (PHN) in the Japanese population.

Herpes zoster is a common disease caused by reactivation of the varicella zoster virus (VZV). In a small number of herpes zoster patients, pain persists beyond 4 weeks or more after healing of vesicular eruptions; this condition is termed postherpetic neuralgia (PHN). Positive associations of human histocompatibility leukocyte antigens (HLA) class I antigens, A33 and B44, with PHN in the Japanese population have been reported. Our hypothesis is that susceptibility genes to PHN might exist in the HLA region and the study objective is to further examine possible associations of genes in HLA class I, II and III regions, HLA-A, -B, -DRB1, tumor necrosis factor alpha (TNFA) promoter, and a natural killer cell activating receptor, NKp30 polymorphisms with PHN. Although TNFA or NKp30 in the class III region had been considered as a candidate locus, we found no associations of TNFA promoter or NKp30 polymorphisms with PHN in this study. We demonstrated that HLA-A*3303, -B*4403 and -DRB1*1302 alleles were significantly associated with PHN (P = 0.0007 for A*3303, P = 0.001 for B*4403 and P = 0.001 for DRB1*1302). The frequency of the HLA-A*3303-B*4403-DRB1*1302 haplotype was also significantly higher in the PHN patients than in the healthy controls (P = 0.0039). Our results suggest that this haplotype might be related to the pathogenesis of PHN.

Adult↗
PubMed2001

Wide distribution of the MICA-MICB null haplotype in East Asians.

Stress-inducible MICA (MHC class I chain-related A) is known to bind to NKG2D, which is one of the natural killer (NK) cell receptors, and plays a role in immune surveillance. We have reported that a MICA-MICB null haplotype is in linkage disequilibrium with HLA-B*4801 in the Japanese population. In the haplotype, an approximately 100-kb deletion, including the entire MICA gene, was observed and MICB possessed a premature stop codon. In this study, a multiplex polymerase chain reaction (PCR) method was developed for detecting the MICA deletion. MICB alleles were typed by PCR-single-strand conformation polymorphism (SSCP) method and direct sequencing. The frequency of the MICA-MICB null haplotype was 3.7% on the average, and was strongly associated with HLA-B48 in seven East Asian populations. It was presumed that the stop codon of MICB gene generated after the large-scale deletion. The wide distribution of the null haplotype at polymorphic frequencies suggests that the haplotype has been conservatively maintained because of some selective advantage.

Alleles↗
PubMed2001

Allele frequency of HLA-B39 in the Japanese population and identification of a novel B39 allele, B*3923.

A new HLA-B39 allele, B*3923, was found in the Japanese population. Compared with B*39022, the new allele had a single point mutation at position 503 in exon 3 with an amino acid substitution, Gln144Arg. To determine B39 allele frequency in Japanese, 275 B39-positive samples from 3277 Japanese individuals were examined by polymerase chain reaction using microtitre plate hydribization (PCR-MPH) and single-strand conformation polymorphism (PCR-SSCP). The frequency of B*3923 was estimated to be 0.4% in B39 alleles of the Japanese population. B*3923 was found in samples from four Japanese individuals, all of whom have DRB1*1406.

Asian People↗
PubMed2001

Polymorphisms in the coding region of mtDNA and effects on clinical outcome of unrelated bone marrow transplantation.

The entire protein-coding region was divided into 45 fragments, separately amplified and analyzed for polymorphism by the PCR-SSCP (single-strand conformation polymorphism) method. The effect of polymorphism mismatching on the clinical outcome of unrelated bone marrow transplantation was studied to clarify whether products from mtDNA become minor antigens. Variability in PCR-SSCP pattern combinations of the 45 fragments suggests that each individual has a different polymorphism combination in the protein-coding region if all the coding regions were compared at the nucleotide sequence level. Nonsynonymous polymorphisms were found at relatively high frequency in MTATP8 and MTND3. Both the polymorphisms with and without substitution matched the peptide-binding motifs of HLA-A*0201. The effects of the polymorphism matching were retrospectively analyzed in 340 recipients transplanted with HLA-A, -B, -DRB1 allele-matched bone marrow from unrelated donors. There were no effects of polymorphism matching on the incidence of acute GVHD and cumulative disease-free survival. These results suggest that polymorphisms which generate peptides, with and without substitutions, that bind the same HLA molecule hardly influence GVHD because the difference between the HLA-peptide complexes is minute.

Bone Marrow Transplantation↗
PubMed2001

E variants found in Japanese and c antigenicity alteration without substitution in the second extracellular loop.

BACKGROUND: The molecular basis of E variants in the Japanese population is poorly understood. In this study, molecular analysis of E variants detected in Japanese by serologic methods was carried out. STUDY DESIGN AND METHODS: E variants from healthy Japanese blood donors were screened by serologic analysis using E MoAbs. Fifteen E variant samples were divided into three types--EFM, EKH, and EKK-on the basis of patterns of reactivity with five distinct E antibodies. The entire coding region of the Rh cDNAs from the E variant samples was analyzed by sequencing. RESULTS: Although the Rh cDNA sequences of the three types were different from each other, those of the EFM-type variants (RHEFM) had a partial DNA exchange in exon 5 between the RHCE and RHD genes, generating an RHcE variant (Gln233Glu, Met238Val). The cDNA of EKH-type variants (RHEKH) exhibited a point mutation (G461C) in exon 3 of the RHcE allele that resulted in an Arg154Thr substitution in the third external loop of the RhcE peptide. The EKK-type variant (RHEKK) carried a hybrid gene structure characterized by replacement of exons 1-3 (or 2-3) of the RHCE gene with those of the RHD gene. The RHD gene of a person possessing an E variant of the EKK type was also a hybrid gene, D-cE(2-3)-D or cE(1-3)-D (RHDKK). The E variants of types EKH and EKK showed weak c antigenicity. CONCLUSION: In serologic screening of 140,723 Japanese blood donors, 15 were found to possess E variants (0.011%). A new RHCE variant, RHEKH, was identified. On the basis of the variants found in this study, the c antigenicity seemed to be determined not only by Pro-103 but also by the structure of the third extracellular loop or the amino acids contained in it.

Amino Acid Substitution↗
PubMed2000

Identification of a novel HLA-B46 allele, B*4602, in Japanese.

The B*4602 was identified in a healthy Japanese donor. The B46 variant antigen differed serologically from B46. The nucleotide sequence of B*4602 differed from that of B*4601 by a single base (from A to G) at position 293 in exon 2. The substitution changed the amino acid Asp at position 74 to Gly. The gene frequency of B*4602 in the Japanese population is extremely low. The presumed haplotype of B*4602 was HLA-A2-Cw1-B*4602-DRB1*09. This is the first report of polymorphism of the B46 antigen.

Alleles↗
PubMed2000

Generation of HLA-DRB1*1501-restricted p190 minor bcr-abl (e1a2)-specific CD4+ T lymphocytes.

A small population of cells in acute lymphoblastic leukaemia is characterized by a specific translocation of the c-abl oncogene on chromosome 9 to the break point cluster lesion (bcr) on chromosome 22, t(9; 22)(q34; q11) (e1a2). Theoretically, the junction-spanning sequences of oncogene fusion proteins might be ideal targets for immunotherapy because these are not present in normal cells. In this study, we show for the first time that in vitro immunization with a 17-mer e1a2 peptide representing the p190 minor bcr-abl fusion protein resulted in HLA-DRB1*1501-restricted peptide-specific proliferative CD4+ T lymphocytes, using peptide-pulsed monocyte-derived dendritic cells as the antigen-presenting cells.

CD4-Positive T-Lymphocytes↗
PubMed2000

Polymorphisms of RhD(Va) and a new RhD(Va)-like variant found in Japanese individuals.

BACKGROUND AND OBJECTIVES: Red cell type RhD(Va) lacks epD1 and 5 and is encoded by hybrid RHD-CE(5)-D alleles. We analyzed RhD(Va) and RhD(Va)-like samples in Japanese blood donors. MATERIALS AND METHODS: Ten RhD(Va) samples lacked epD1 and 5 and 3 RhD(Va)-like variants also lacked, epD2 and a part of 6/7. We identified the full-length nucleotide sequences of the complementary DNA (cDNA) synthesized from 4 samples: 3 of type D(Va) and the 4th a D(Va)-like variant. RESULTS: Although their sequences differed from each other, all the substitutions were exclusively in exon 5. Three D(Va) samples had hybrid RHD-CE(5)-D alleles, but the D(Va)-like variant had a unique nucleotide substitution with a single amino acid change, E233K. Exon 5 of the genomic DNA from all 13 samples was analyzed by sequencing. No other sequences were identified. CONCLUSION: All RhD(Va) and RhD(Va)-like variants had the substitution for E233. E233 seems to be a determinant of epD1 and 5. A new category of RhD variant, DYO, was identified.

Amino Acid Substitution↗
PubMed1999

MIC-A polymorphism in Japanese and a MIC-A-MIC-B null haplotype.

A polymorphic gene, MIC-A, is one of the MIC family of genes which is composed of a group of homologous genes interspersed in the class III and class I regions of the major histocompatibility complex. MIC-A is located 46 kilobases (kb) centromeric of HLA-B, and is preferentially expressed in the epithelial cells and intestinal mucosa. Recently, MIC-A and the closely related MIC-B were reported as the molecules that conferred specificity in the recognition by the Vdelta1gammadeltaT cells. In the present study, polymorphic exons 2, 3, and 4 of the MIC-A gene were analyzed using the polymerase chain reaction-single-strand conformation polymorphism method. The number of patterns found in exons 2, 3, and 4 were 5, 6, and 4, respectively, in 114 healthy Japanese subjects. Eight MIC-A alleles were observed in Japanese individuals, among which one, tentatively named MIC-AMW, has not previously been reported. There was a strong linkage disequilibrium between MIC-A and HLA-B loci: each MIC-A allele showed strong association with a particular HLA-B group. In contrast, B*3901 showed association with multiple MIC-A alleles. Furthermore, the existence of a MIC-A-MIC-B null haplotype, which is associated with HLA-B*4801, was identified. In this haplotype, a large-scale deletion (of approximately 100 kb) including the entire MIC-A gene was indicated and the MIC-B gene possessed a stop codon.

Alleles↗
PubMed1999

Diversity of HLA-B17 alleles and haplotypes in East Asians and a novel Cw6 allele (Cw*0604) associated with B*5701.

The distribution of HLA-B17 alleles and their association with HLA-A, -C and -DRB1 alleles were investigated in seven East Asian populations Japanese, South Korean, Chinese-Korean, Man, Northern Han, Mongolian and Buryat populations). The B17 alleles were identified from genomic DNA using group-specific polymerase chain reaction (PCR) followed by hybridization with sequence-specific oligonucleotide probes (SSOP). In all of these East Asian populations, except Japanese and Chinese-Koreans, B*5701 was detected and strongly associated with A*0101, Cw*0602 and DRB1*0701. In contrast, B*5801 was detected in all the seven populations and strongly associated with A*3303, Cw*0302, DRB1*0301 and DRB1*1302. The A*3303-Cw*0302-B*5801-DRB1*1302 haplotype was observed in South Korean, Chinese-Korean, Buryat and Japanese populations, while A*3303-Cw*0302-B*5801-DRB1*0301 was predominantly observed in the Mongolian population. A similar haplotype, A*0101-Cw*0302-B*5801-DRB1*1302, was observed in the Buryat population. A novel Cw6 allele, Cw*0604, was identified in the Man population. This Cw allele was observed on the haplotype A*0101-B*5701-DRB1*0701. Thus, we confirmed, at the sequence level, that the common haplotypes carrying B*5701 and B*5801 have been conserved and shared in East Asian populations.

Alleles↗
PubMed1999

Splice acceptor site mutation of the transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome.

Expression of histocompatibility leukocyte antigen (HLA) class I molecules on the cell surface depends on the heterodimer of the transporter associated with antigen processing 1 and 2 (TAP1 and TAP2), which transport peptides cleaved by proteasome to the class I molecules. Defects in the TAP2 protein have been reported in two families with HLA class I deficiency, the so-called bare lymphocyte syndrome (BLS) type I. We have, to our knowledge, identified for the first time a splice site mutation in the TAP1 gene of another BLS patient. In addition, class I heavy chains (HCs) did not form the normal complex with tapasin in the endoplasmic reticulum (ER) of the cells of our patient.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

[DNA typing methods of HLA].

Human leukocyte antigens (HLA) are a group of cell membrane proteins encoded by the HLA gene complex on the short arm of the chromosome 6, with a high degrees of polymorphism, and a total of about 650 alleles have been identified at HLA-A, B, C and DR loci up to now, which regulate the immune response by self/not-self discrimination. A number of DNA-based typing methods using specific primers, specific probes or restriction enzymes have been developed. In HLA allele typing, a few methods which are simple in handling and able to determine the alleles automatically, have been available.

Base Sequence↗
PubMed1998

Guillain-Barré and Fisher's syndromes subsequent to Campylobacter jejuni enteritis are associated with HLA-B54 and Cw1 independent of anti-ganglioside antibodies.

The frequencies of human leukocyte antigens (HLA)-class I (A, B and Cw) were determined serologically and those of HLA-class II (DRB1 and DQB1) at the genomic level in 35 Japanese patients with Guillain-Barré syndrome (GBS), 58 with Fisher's syndrome (FS), and 112 healthy controls. HLA-B54 and -Cw1 antigens were found in GBS and FS patients from whom Campylobacter jejuni had been isolated more often than found in the healthy controls. No HLA types were related to GBS or FS as a whole, except for the B54 antigen which often was significant in the entire GBS group. This relation, however, may depend on the high population of C. jejuni-isolate patients in our GBS group. There were no relationships between the frequencies of HLA types and the presence of serum IgG antibodies to GM1, GQ1b, GD1a, or GalNAc-GD1a. Our findings suggest that HLA types are associated with the onset of GBS and FS after C. jejuni enteritis and that the HLA types in distinct GBS and FS subgroups of a single etiological origin need to be examined.

Antibodies↗
PubMed1998

Dendritic cells stimulate the expansion of bcr-abl specific CD8+ T cells with cytotoxic activity against leukemic cells from patients with chronic myeloid leukemia.

The role of T lymphocytes in the control of chronic myeloid leukemia (CML) after bone marrow transplantations has been clearly shown. This effect closely correlates with graft-versus-host disease (GVHD). A specific graft-versus-leukemia (GVL) effect separate from GVHD has been postulated but has been difficult to show. One possible target for specific GVL activity is the bcr-abl fusion protein characteristic of CML. We have investigated the use of normal peptide-pulsed dendritic cells for the generation of cytotoxic, bcr-abl-specific T cells from normal donors. T cells (CD3+, CD8+, TCR alpha beta+, and NK receptor-negative) generated from a normal donor (HLA A24, B52, B59, Cw1) after stimulation with autologous dendritic cells, primed with a 16 mer peptide spanning the b3a2 breakpoint of bcr-abl, lysed CML cells from the peripheral blood of seven patients with CML with the b3a2 breakpoint. CML cells from four patients with only the b2a2 breakpoint were not lysed. Phytohemagglutinin (PHA) blasts derived from peripheral blood of patients with CML were not lysed, suggesting that cytotoxicity was not due to alloreactivity. Blocking experiments with anti-HLA-A,B,C indicated that cytotoxicity was dependent on recognition of major histocompatibility complex (MHC) class I molecules, although cytotoxicity was not MHC-restricted because not all patients shared HLA types with the T-cell donor. Specificity for bcr-abl and absence of alloreactivity was confirmed by the presence of lytic activity against autologous and allogeneic class I HLA-A matched monocytes pulsed with the 16 mer bcr-abl fusion peptide, but not against unpulsed monocytes or monocytes pulsed with other peptides. These results show that bcr-abl-specific T cells with marked cytotoxic activity against CML cells can be generated and amplified from normal donor peripheral blood. Recognition of HLA molecules is essential for cytotoxicity but strict HLA identity is not required.

Antigens↗