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Biomedical subjects

K Tokunaga

Publications and source records attributed to K Tokunaga.

At least 127 records · Page 7Linked to original sources
PubMed2000

Ganglioglioma in a patient with Turcot syndrome. Case report.

A 33-year-old woman with Turcot syndrome harbored a brain tumor and colon cancer and had a familial history of this syndrome. On histological examination, the brain tumor was found to have large and diffusely scattered ganglion cells within a diffuse background of astrocytic cells in a fibrillary matrix. The tumor was diagnosed as a ganglioglioma. No germline mutation in the adenomatous polyposis coli gene was detected using a protein truncation assay. These findings indicate that this patient had brain tumor-polyposis syndrome Type 1 of Turcot syndrome. This is the first report of a ganglioglioma related to Turcot syndrome.

Adenomatous Polyposis Coli↗
PubMed2000

Relationship between eradication therapy and clarithromycin-resistant Helicobacter pylori in Japan.

Since clarithromycin is expected to be widely used to treat Helicobacter pylori infection in the near future, it is important to investigate the relationship between resistance to clarithromycin and the regimens of eradication therapy. We investigated: (1) the usefulness of susceptibility tests prior to eradication therapy, and (2) the rate of acquisition of H. pylori resistance to clarithromycin after treatment failure. Drug susceptibility tests to clarithromycin and amoxicillin were conducted by Dry Plate Test or E-test. The subjects in the first part of this study included 112 patients with H. pylori infection who received triple therapy with various combinations of drugs, including clarithromycin. The eradication rate in patients with clarithromycin-susceptible H. pylori was significantly higher than that in patients with clarithromycin-resistant H. pylori. The second part of this study included 21 patients in whom H. pylori was not eradicated by triple therapy and 12 patients in whom H. pylori was not eradicated with dual therapy including clarithromycin. Of the 33 patients showing non-eradication. 90.9% of those treated with dual therapy and 35.7% of those treated with triple therapy acquired secondary resistance of H. pylori to clarithromycin. We conclude that it is important to conduct drug susceptibility tests prior to treatment of H. pylori infection. Since the incidence of acquiring clarithromycin resistance was significantly higher in the patients showing non-eradication, it is important to choose a regimen with a higher eradication rate, such as triple therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Analysis of HLA-DRB1 polymorphism in the Gidra of Papua New Guinea.

The genetic structure of the Gidra-speaking population inhabiting 13 villages in Papua New Guinea was investigated, based on the analysis of HLA-DRB1 polymorphism. Nei's fixation indices (F(IS), F(IT), and F(ST)) showed that the Gidra villages were genetically differentiated. The genetic distances significantly correlated with the geographic distances among the 13 villages. Thus, it is likely that a low intervillage migration rate has been maintained since the Gidra community was established. Correspondence analysis revealed that the Gidra, who belong to non-Austronesian-speaking groups, are genetically located at the intermediate point between the Aboriginal Australian groups and the Austronesian-speaking groups. Moreover, the HLA-DRB1*0802 allele, which has been observed in only two Polynesian groups (Austronesian-speaking groups) of Oceanian populations, was also found in the Gidra. These results suggest that the admixture of Austronesian and indigenous non-Austronesian groups beyond the linguistic boundary occurred partly in Papua New Guinea before Austronesian groups spread to the Pacific.

Black People↗
PubMed2000

[A case of a scalp arteriovenous fistula associated with Rendu-Osler-Weber disease treated by direct percutaneous embolization].

We present a case of Rendu-Osler-Weber disease (hereditary hemorrhagic telangiectasia) accompanied by a scalp arteriovenous fistula, which was successfully treated by direct percutaneous embolization. A 51-year-old man, who had multiple vascular telangiectases and pulmonary arteriovenous fistulae, developed an enlarging pulsatile mass of the scalp anterior to the site of the previous craniotomy for a brain abscess in the right occipital lobe. Angiography demonstrated a high-flow arteriovenous fistula between the right superficial temporal artery and a varix. Percutaneous injection of pure ethyl alcohol was planned but seemed risky because of the major drainage being into the bilateral cavernous sinuses through the superior ophthalmic veins. A 24-gauge plastic needle was placed in the right superficial temporal artery just proximal to the fistula, and 0.7 ml of a mixture consisting of n-butyl cyanoacrylate and lipiodol in a ratio of 1:1 was injected. Then, the varix was directly punctured, and retention of the contrast medium was confirmed under manual compression by the placement of a circular ring. Embolization of the varix using 1.0 ml of 70% glucose solution and a subsequent 1.0 ml of pure ethyl alcohol was performed with compression, resulting in total occlusion of the fistula. The scalp mass resolved gradually and there was no evidence of recanalization. We conclude that direct percutaneous embolization is the first therapeutic choice for a scalp arteriovenous fistula with multiple shuntings associated with Rendu-Osler-Weber disease. Dangerous venous drainage should be eliminated before performing embolization with ethyl alcohol.

Arteriovenous Fistula↗
PubMed2000

[A study on the appropriate time point for the assessment of Helicobacter pylori eradication--evaluation from the re-positive rate of H. pylori after successful eradication and delayed decrease of 13C-urea breath test levels].

We attempted to evaluate the appropriate time point for the assessment of Helicobacter pylori eradication after treatment. One hundred and nine patients with gastroduodenal diseases were enrolled this study. All of them were received proton pomp inhibitor based triple therapy and diagnosed as eradication of H. pylori infection at initial assessment. They were followed up over six months. The diagnosis of H. pylori eradication was determined by rapid urease test, culture, histology and 13C-urea breath test (UBT), and the initial assessment of the eradication was performed on 31-90 days after finishing eradication therapy. Re-appearance rate of H. pylori after initial diagnosis of eradication was 4.6% (5/109), and the mean follow-up period of them was 16.3 months. The time period of initial assessment of eradication in these 5 patients were 35, 37, 42, 49 and 60 days after treatment, respectively. On the other hand, there were 6 patients who were diagnosed as failed of eradication therapy by 13C-UBT, and being success at following period. All of the 13C-UBT levels of these 6 patients were less than 10/1000 and were decreased within negative range subsequently. The time periods of initial diagnosis of these patients except one were within 2 months after treatment. It was concluded that the assessment time of H. pylori eradication should be performed over 2 months after eradication therapy.

Adult↗
PubMed1999

Molecular analyses of the possible RNA-binding protein gene located in the human leukocyte antigen (HLA)--DR subregion.

We have previously found the sequence having potential for encoding a new protein in the human leukocyte antigen (HLA) class II region. The predicted amino acid sequence showed a significant sequence homology to the Xenopus double-stranded RNA-binding protein (Xlrbp) and the human cellular protein bound to the transactivation response (TAR) of human immunodeficiency virus type-1 (HIV-1) RNA (TRBP). Reverse transcription-polymerase chain reaction (RT-PCR) with poly(A)(+) RNA prepared from human peripheral lymphocytes and direct sequencing analyses in this study showed that the transcripts of the gene encoding the putative RNA-binding protein occurred in human cells: the gene was provisionally named Homo sapiens RNA-binding protein (hsRBP). From the result of Southern blot analyses, it appears that multiple copies of hsRBP are present in the human genome. Together with the known cDNAs having a high sequence homology to hsRBP, the data presented here suggest that the multigene family of the double-stranded RNA-binding protein exists in the human genome.

Amino Acid Sequence↗
PubMed1999

Killer cell immunoglobulin receptors and T cell receptors bind peptide-major histocompatibility complex class I with distinct thermodynamic and kinetic properties.

Human natural killer cells and a subset of T cells express a repertoire of killer cell immunoglobulin receptors (KIRs) that recognize major histocompatibility complex (MHC) class I molecules. KIRs and T cell receptors (TCRs) bind in a peptide-dependent manner to overlapping regions of peptide-MHC class I complexes. KIRs with two immunoglobulin domains (KIR2Ds) recognize distinct subsets of HLA-C alleles. Here we use surface plasmon resonance to study the binding of soluble forms of KIR2DL1 and KIR2DL3 to several peptide-HLA-Cw7 complexes. KIR2DL3 bound to the HLA-Cw7 allele presenting the peptide RYRPGTVAL with a 1:1 stoichiometry and an affinity (K(d) approximately 7 microM at 25 degrees C) within the range of values measured for other cell-cell recognition molecules, including the TCR. Although KIR2DL1 is reported not to recognize the HLA-Cw7 allele in functional assays, it bound RYRPGTVAL/HLA-Cw7, albeit with a 10-20-fold lower affinity. TCR/peptide-MHC interactions are characterized by comparatively slow kinetics and unfavorable entropic changes (Willcox, B. E., Gao, G. F., Wyer, J. R. , Ladbury, J. E., Bell, J. I., Jakobsen, B. K., and van der Merwe, P. A. (1999) Immunity 10, 357-365), suggesting that binding is accompanied by conformational adjustments. In contrast, we show that KIR2DL3 binds RYRPGTVAL/HLA-Cw7 with fast kinetics and a favorable binding entropy, consistent with rigid body association. These results indicate that KIR/peptide-MHC class I interactions have properties typical of other cell-cell recognition molecules, and they highlight the unusual nature of TCR/peptide-MHC recognition.

Amino Acid Sequence↗
PubMed1999

Specific loss of chondromodulin-I gene expression in chondrosarcoma and the suppression of tumor angiogenesis and growth by its recombinant protein in vivo.

Chondromodulin-I (ChM-I) was previously identified as an angiogenesis inhibitor in cartilage. Here, we demonstrated that the level of ChM-I transcripts was substantially reduced to 100 or even less in the lower-grade chondrosarcomas, in articular cartilage or other benign cartilage tumors. We implanted human chondrosarcoma OUMS-27 cells into nude mice that reproducibly produced tumors with cartilaginous matrix. Tumor-induced angiogenesis was evident when the tumors were excised 30 days after implantation. However, the local administration of recombinant human ChM-I almost completely blocked vascular invasion and tumor growth in vivo. Moreover, ChM-I also inhibited the growth of HT-29 colon adenocarcinoma in vivo, implying its therapeutic potential for solid tumors.

Animals↗
PubMed1999

The cellular kinase binding motifs (PxxP and RR) in human immunodeficiency virus type 1 Nef protein are dispensable for producer-cell-dependent enhancement of viral entry.

We have recently demonstrated that human immunodeficiency virus type 1 (HIV-1) Nef is required for enhancing viral infectivity by increasing the efficiency of viral entry in a producer-cell-dependent manner, suggesting the possible involvement of a cellular factor(s) in the enhancement of viral entry. Moreover, it has been reported that a proline-rich (PxxP) motif and an Arg-Arg (RR) motif in HIV-1 Nef bind to the SH3 domain of the Src-family tyrosine kinase Hck and to a serine/threonine kinase, respectively. To address whether these cellular kinase binding motifs, PxxP and RR, could be involved in virus producer-cell-dependent enhancement of viral entry, we constructed two nef mutant proviral clones in which these motifs were mutated. The results show that the HIV-1 Nef PxxP motif, which significantly influenced viral infectivity, and the RR motif, which modestly affected viral infectivity, were both dispensable for enhanced viral entry, thus suggesting that another interaction of Nef with a cellular factor(s) is involved in the efficiency of viral entry.

Alanine↗
PubMed1999

Overlapping peptide-binding specificities of HLA-B27 and B39: evidence for a role of peptide supermotif in the pathogenesis of spondylarthropathies.

OBJECTIVE: Previous studies indicated the increase of HLA-B39 among HLA-B27 negative patients with spondylarthropathies (SpA). This study was performed to examine whether the natural ligands of HLA-B27 are capable of binding to HLA-B39. METHODS: Peptides were synthesized according to the sequences of known natural ligands of HLA-B27 or B39 and were tested for their binding to HLA-B*3901 and B*2705 by quantitative peptide binding assay, using a TAP-deficient RMA-S cell line transfected with human beta2-microglobulin and HLA class I heavy chain genes. RESULTS: Four of the 10 HLA-B27 binding peptides significantly bound to HLA-B*3901. All 4 peptides had hydrophobic/aromatic amino acids (Leu or Phe) at the C-terminus. In contrast, peptides with basic residues (Lys, Arg) or Tyr at the C-terminus did not bind to B*3901. In parallel experiments, 1 of the 2 natural ligands of HLA-B*3901 was found to bind to B*2705. CONCLUSION: A subset of natural HLA-B27 ligands was capable of binding to B*3901. In addition to Arg at position 2 (Arg2), hydrophobic/aromatic C-terminal residues, such as Leu or Phe, seemed to be crucial for the cross-specificity. These results suggested that HLA-B27 and B39 recognize overlapping peptide repertoires, supporting the hypothesis that the peptides presented by both of these class I antigens play a role in the pathogenesis of SpA.

Amino Acid Sequence↗
PubMed1999

Identification of the gene variations in human CD22.

CD22, a member of the immunoglobulin superfamily, is a B-cell transmembrane glycoprotein that acts as an accessory-signaling component of the B-cell antigen receptor (BCR). Recent evidence indicating the role of CD22 as a negative regulator of BCR signal transduction prompted us to test the possibility that genetic variations of human CD22 may be associated with autoimmune diseases. In this study, variation screening of the entire CD22 coding region was performed, and possible association with rheumatic diseases was tested, using the genomic DNA from 207 healthy Japanese individuals, 68 patients with systemic lupus erythematosus (SLE), and 119 patients with rheumatoid arthritis (RA). Through the variation screening, seven non-synonymous and four synonymous substitutions were identified. In addition, single base substitutions were found in two introns flanking exon-intron junctions. Among these variations, Q152E substitution within the second extracellular domain was observed with a marginally higher frequency in the patients with SLE (3/68, 4.4%) than that in healthy individuals (1/207, 0.5%) (P=0.048. SLE vs healthy individuals), although this difference was no longer significant after correction for the number of comparisons (Pc=0.62). No significant association was observed between any of the variations and RA. These findings indicate that a number of genetic variants are present in CD22, and suggest that CD22 could be considered a candidate for the susceptibility genes to autoimmune diseases.

Adolescent↗
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

Experimental study of intracisternal administration of tissue-type plasminogen activator followed by cerebrospinal fluid drainage in the ultra-early stage of subarachnoid haemorrhage.

This experimental study evaluated the effect of intrathecal injection of tissue-type plasminogen activator followed by cisternal drainage in the ultra-early stage of aneurysmal subarachnoid haemorrhage to prevent vasospasm. Twenty Japanese white rabbits were divided into five groups. Either tPA (groups A, B, and E) or saline (groups C and D) was injected intrathecally 1 hour (groups A, B, C, and D) or 21 hours (group E) after the intrathecal injection of blood. Cerebrospinal fluid was drained 2, 4, and 6 hours after the intrathecal injection of blood (groups A, C, and E). On day 4, the angiographic caliber of the basilar artery in each group was as follows (mean +/- SD): A, 85.9 +/- 5.0%; B, 74.6 +/- 5.3%; C, 69.1 +/- 2.7%; D, 64.0 +/- 4.9%; E, 80.2 +/- 2.7% (compared with baseline). In the two groups in which CSF was drained (groups A and C), fibrinolysis with tPA significantly suppressed vasospasm. In the two groups treated with tPA (groups A and B), cisternal drainage significantly suppressed vasospasm. In the two groups treated with saline (groups C and D), however, cisternal drainage did not suppress vasospasm. Examination of the series of CSF samples (groups A and C) showed that fibrinolysis with tPA effectively cleared clots early. In the two groups treated with tPA and CSF drainage (groups A and E), early removal of subarachnoid clots reduced the degree of vasospasm. Early fibrinolysis with tPA and early removal of subarachnoid clots by drainage is effective for preventing vasospasm.

Angiography, Digital Subtraction↗
PubMed1999

Association of diffuse panbronchiolitis with microsatellite polymorphism of the human interleukin 8 (IL-8) gene.

Diffuse panbronchiolitis (DPB) is a distinctive chronic inflammatory lung disease predominantly found in Asian populations. Although its etiology is unknown, DPB is considered to be a multifactorial disease of whose susceptibility is determined by genetic predisposition unique to Asians. We and others have previously reported that the B*5401 allele of the human leukocyte antigen (HLA)-B gene or a closely linked gene in the HLA region on 6p21.3 is one of the major genetic factors in susceptibility to this disease. However, the association with B*5401 is not absolute and the contribution of other genetic or environmental factors should also be considered. Here, four candidate genes that are postulated to play a role in the pathophysiology of DPB, namely, RON-kinase, CYP3A4, motilin, and interleukin (IL)-8, were chosen, and association studies between microsatellite markers at these loci and DPB were conducted. We demonstrated the presence of a specific allele at the IL-8 locus was associated with the disease (c2 = 9.13; P = 0.0025; corrected P [Pc] < 0.05). Although further studies are needed to examine whether neutrophil accumulation in the airways of patients with DPB is controlled by a possible genetic variation of IL-8 or other chemokine genes located in the region 4q12-q13, our data suggest that genes other than those of the HLA system may also contribute to a genetic predisposition to DPB.

Asian People↗
PubMed1999

Genetic variations on the Y chromosome in the Japanese population and implications for modern human Y chromosome lineage.

A polymorphism in the coding sequence of the SRY gene was found by single-strand conformation polymorphism (SSCP) and direct sequencing analysis. The new allele of the SRY gene, which is raised by a C-to-T transition in the 155th codon, was found in 24% of Honshu, 35% of Okinawan, and 51% of Korean males respectively, whereas it was not observed among 16 Caucasian and 18 Negroid males. A haplotype analysis of the Y chromosome was carried out in Japanese, Korean, Caucasian and Negroid populations, using a combination of the polymorphisms in SRY, DXYS5Y, DYS287, and DXYS241Y loci. The results indicated that the Y chromosomes can be classified into seven heplotypes (Ia, Ib, Ic, IIa, IIb, III, IV). However, of these seven, only four (Ia, IIa, III, IV) were observed in the Japanese population. Furthermore, the presumed haplotype C, Y1, YAP, (CA)14, from which haplotype III was probably derived, was not found in any populations in this study. The regional distribution of each haplotype revealed that type III is more frequently observed in Okinawa (16%) and in Korea (21%) than in Honshu (4.4%). The haplotype analysis of the Y chromosome may contribute to the exploration of the origin of Japanese and the relationship between east Asian populations.

DNA-Binding Proteins↗