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Biomedical subjects

Hideyuki Murata

Publications and source records attributed to Hideyuki Murata.

15 recordsLinked to original sources

Donor-derived cells and human graft-versus-host disease of the skin.

Graft-versus-host disease (GvHD)-induced apoptosis of the skin targets both epidermal keratinocytes and dermal endothelial cells. We studied the donor-versus-recipient origin of GvHD of these target cells in skin of 18 sex-mismatched hematopoietic stem-cell transplant (HSCT) recipients. Combining XY fluorescence in situ hybridization (FISH) and double immunostaining, and further 3D tissue Z-stack analysis, we found keratinocytes and endothelial cells of donor origin, but only in patients with GvHD. Using terminal dUTP nick-end labeling (TUNEL) assay on sister sections, we found a correlation between the numbers of chimeric and apoptotic epidermal and endothelial cells. Moreover, donor-derived cells were more numerous and preferentially distributed in the areas of severe GvHD damage in biopsies performed early in the course of GvHD, whereas they were less numerous and found in the whole epidermis in late biopsies. Because donor-derived cells were found at the site and at the time of maximum tissue damage, they could contribute to epidermal and microvessel repair.

Biopsy↗

Mixed germinoma and choriocarcinoma in the intramedullary spinal cord: case report and review of the literature.

Primary germinomas in the spinal cord are very rare with only 15 cases published previously. In this case a 22-year-old woman with urinary incontinence, lumbago, and bilateral leg pain and weakness was found to have a solid tumor in the conus medullaris between the L1 and L2 vertebral bodies. Serum HCG was elevated without pregnancy. The pathological diagnosis was mixed germinoma and choriocarcinoma of the intramedullary spinal cord. She received craninospinal irradiation and three courses of chemotherapy and is currently asymptomatic with no evidence of recurrence and metastasis 22 months after surgery. To our knowledge, this is the first case report of a patient with a primary mixed germinoma and choriocarcinoma of the intramedullary spinal cord. The previous 15 cases of primary spinal cord germinoma have been reviewed for comparison.

Adult↗

T cell receptor BV gene repertoire of lymphocytes in bronchoalveolar lavage fluid of polymyositis/dermatomyositis patients with interstitial pneumonitis.

We analyzed the T cell receptor (TCR) repertoire of bronchoalveolar lavage fluid (BALF) lymphocytes from polymyositis (PM) and dermatomyositis (DM) patients with interstitial pneumonitis (IP) to elucidate the pathogenic mechanisms of IP in these disorders. Samples from 2 PM patients, 1 DM patient and 3 healthy controls were used. RNA was isolated from BALF, cDNAs were synthesized, and family PCR and Southern blot analysis were performed by primers specific for TCR BV1-25 and TCR BC to determine TCR repertoire. We examined single-strand conformation polymorphism (SSCP) to evaluate T cell clonality. The CDR3 region of TCR BV genes in BALF T cells were determined by DNA sequencer. Our examination showed that TCR repertoire of T cells in BALF was heterogeneous both in patients with PM/DM and control subjects. SSCP analysis demonstrated an increased number of accumulated T cell clones in BALF of three PM/DM patients, but not in the healthy subjects and the junctional sequence analysis showed the presence of conserved amino acid motifs (RGS, GLA, LQG, SGG, DRG, GTS, TSGR, GGS, GQA, GAG, GTG) in the TCR-CDR3 region of BALF lymphocytes from PM/DM patients, which were not detected in the control. Our findings suggest that T cells in BALF may recognize the restricted antigen and accumulate via antigen-driven stimulation, suggesting that T cells may play a crucial role in the development of IP in patients with PM/DM.

Adult↗

[Adjuvant chemotherapy with TS-1 for head and neck cancer--side effect of two-week application followed by one-week rest regimen].

Multimodality therapy incorporated with radiotherapy, surgery and chemotherapy are used in the treatment of head and neck cancer in order to improve the local control and survival rate. TS-1, a newly developed oral antitumor agent which could achieve the same therapeutic concentration as that of 5-FU under continuous and intravenous treatment, has been used as adjuvant therapy for carcinomas in recent years. We presented our experience applying a new regimen of TS-1 and its side effects. TS-1 has been applied for head and neck carcinomas since 2001. The oral application of TS-1 has been used in 32 cases of head and neck cancer in our department since 2003, and the agent has been applied in 22 of 32 cases as adjuvant therapy. The primary sites of malignancy included hypopharyngx (7 cases), larynx (6 cases), maxillary sinus (2 cases), oropharynx (2 cases), oral cavity (4 cases), submandibular gland (1 case) and one case in which the primary site was unknown. A regimen of four-week application followed by two-week rest had been used in 6 cases in the first part of this trial. However, a high frequency of blood toxicity was found from the third week, requiring alteration of the protocol. Thus, a new regimen of two-week application followed by one week rest was thereafter used in the other 16 cases. Blood toxicity was found in 66.7% of those cases receiving a four-week application followed by two-week rest regimen. In the 16 cases receiving the two-week application followed by one-week rest regimen, only one case showed grade 2 leucopenia while continuous application for more than eight weeks was possible in 9 cases. Mild macrocytic anemia was found in some of these cases, however none of which required any necessary interruption of the treatment. Side effects other than blood toxicity, such as edema or pigmentation of lower limbs, erythema of skin and diarrhea, were found in the other cases, requiring suspension of the treatment. But the subsequent application was possible after a break or decreasing the dosage. We concluded that the new regimen of two-week application followed by one-week rest is less likely to be interrupted by the side effects and is safer to be used outpatiently, compared with the four-week application followed by two-week rest.

Administration, Oral↗

Glucose-6-phosphate isomerase variants play a key role in the generation of anti-GPI antibodies: possible mechanism of autoantibody production.

Glucose-6-phosphate isomerase (GPI), recognized as an autoantigen in the K/BxN arthritis model, is a ubiquitous cytoplasmic enzyme. Anti-GPI antibodies (Abs) are also detected in the serum of patients with arthritic diseases including rheumatoid arthritis (RA). So far, 24 GPI variants have been reported and most of these variants relate to non-spherocytic hemolytic disease. To understand the mechanisms of anti-GPI Ab production, cDNAs from peripheral blood mononuclear cells of subjects with or without anti-GPI Abs were cloned and sequenced. We identified 39 new GPI variants (57-1596 bp). The frequency of GPI variants in healthy control subjects (HS) with anti-GPI Abs (27/73, 31.5%) was significantly higher than that in anti-GPI Ab-negative HS (5/78, 6.4%, p < 0.001). The frequency of GPI variants in anti-GPI Ab-positive RA patients (22/77, 28.6%) was more significantly higher than in anti-GPI Ab-negative patients (1/63, 1.6%, p < 0.0001). Our results suggest that GPI variants may play a crucial role in the production of autoantibodies against ubiquitous GPI autoantigens.

Arthritis, Rheumatoid↗

Reiter's syndrome following intravesical bacille biliE de Calmette-GuErin treatment for superficial bladder carcinoma: report of six cases.

We report the cases of six patients who developed acute Reiter's syndrome following intravesical bacille biliE de Calmette-GuErin (BCG) immunotherapy for superficial bladder cancer. After the third to eighth BCG intravesical injection, the patients developed conjunctivitis, aseptic urethritis, and polyarthritis consistent with a diagnosis of Reiter's syndrome. HLA-B27 antigen was negative in five of the patients examined. Two of the patients responded to nonsteroidal anti-inflammatory drugs for polyarthritis, and the other four responded to steroids (prednisolone 5-10 mg/day). The frequent use of intracavitary BCG may increase the incidence of BCG-induced Reiter's syndrome. Further analysis of the relationship between HLA-B and -DR alleles and arthritis should shed light on the mechanism of BCG-induced Reiter's syndrome.

Journal Article↗

Polymorphisms of IL-1 beta gene in Japanese patients with Sjögren's syndrome and systemic lupus erythematosus.

OBJECTIVE: Interleukin (IL)-1 beta is a proinflammatory cytokine involved in various immune responses. Five polymorphisms in the IL-1 beta gene have been described, and relationships between these polymorphisms and some autoimmune diseases have been reported. Evidence suggests that IL-1 beta may be involved in the destruction of salivary and lacrimal glands in Sjögren's syndrome (SS). We evaluated the significance of IL-1 beta gene polymorphisms in SS. METHODS: Blood samples were taken from 101 patients with SS, 103 patients with systemic lupus erythematosus (SLE, excluding those with secondary SS), and 106 healthy volunteers. Each polymorphism of the IL-1 beta gene was analyzed by polymerase chain reaction (PCR) amplification of the polymorphic site, followed by site-specific restriction digestion. Genotype frequencies of each polymorphism in SS patients were compared with those of the controls and SLE patients, and differences between primary and secondary SS patients were also compared. RESULTS: Genotypes CC, TT, and AA in positions -511, -31, and 3877, respectively, were significantly less frequent in SS patients than controls or patients with SLE. No significant differences were found in genotype frequencies of any of the polymorphisms between patients with primary SS and secondary SS. CONCLUSION: IL-1 beta gene polymorphisms may affect susceptibility to SS, but not SLE.

DNA↗

Expression of tristetraprolin (G0S24) mRNA, a regulator of tumor necrosis factor-alpha production, in synovial tissues of patients with rheumatoid arthritis.

OBJECTIVE: To determine the significance of tristetraprolin (TTP) gene expression in synovial tissues of patients with rheumatoid arthritis (RA). METHODS: Gene expression was examined in synovial tissue and peripheral blood lymphocytes of a patient with RA by differential display-polymerase chain reaction (PCR). One of the identified genes, TTP, was selected for further analysis. cDNA was prepared from synovial tissues of 22 patients with RA and 22 with osteoarthritis (OA). Expression of TTP and tumor necrosis factor-a (TNF-a) genes was measured by TaqMan real-time semiquantification PCR. In RA samples, expression of TTP mRNA was compared with TNF-a mRNA, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and steroid and/or disease modifying antirheumatic drug use. RESULTS: Expression of TTP gene was significantly higher in synovial tissues of RA patients than in OA. There was no apparent relationship between expression of TTP and TNF-a genes. TTP gene expression had a tendency to be inversely correlated with serum CRP, measured immediately before surgery. In addition, CRP was higher in patients with a low TTP/TNF-a gene expression ratio (p = 0.0071, Spearman rank correlation). CONCLUSION: A low TTP/TNF-a gene expression ratio could indicate failure of RA patients to produce adequate amounts of TTP in response to increased TNF-a production. Inappropriate TTP production may be one factor that contributes to higher RA disease activity.

Arthritis, Rheumatoid↗

Mannose binding lectin gene polymorphism in patients with type I diabetes.

Our purpose was to investigate a possible relationship between occurrence of type I diabetes and polymorphism of the mannose binding lectin gene. Polymorphism of codon 54 of the mannose binding lectin (MBL) gene, whose presence of the minority allele leads to significant reduction of serum MBL concentration, was investigated in 128 Japanese patients with type I diabetes and 78 healthy volunteers by restriction fragment length polymorphism method. Frequencies of the minority allele were compared between the patient group and the control group. Frequency of the minority allele was 24.2% in the patient group and 19.9% in the control group. The probability of being heterozygous or homozygous for the minority allele was 41.4% in the patient group and 33.3% in the control group. Patients with DRB1*0405-DQB1*0401 and/or DRB1*0901-DQB1*0303 haplotypes, the two major type I diabetes-prone human leukocyte antigen haplotypes, showed a slightly higher probability of being heterozygous or homozygous for allele B of the MBL gene. Possession of the minority allele of the MBL gene may be a minor risk factor for having type I diabetes.

Age of Onset↗

T cell receptor repertoire of T cells in the kidneys of patients with lupus nephritis.

OBJECTIVE: To determine the role of T cells in the pathogenesis of lupus nephritis (LN). METHODS: Renal biopsy specimens from 12 patients with systemic lupus erythematosus were used for the experiments. We analyzed T cell receptor (TCR) Vbeta1-20 family genes on intrarenal T cells and on peripheral blood lymphocytes (PBLs) by nested reverse transcriptase-polymerase chain reaction (PCR) and Southern blot analysis. Nucleotide sequence was determined in the third complementarity-determining region of the TCR Vbeta gene in expanded T cells. Messenger RNA (mRNA) expression levels of Th1 and Th2 cytokines on infiltrating T cells were measured by nested PCR. RESULTS: The repertoire of TCR Vbeta in intrarenal T cells was relatively restricted compared with that in PBLs. The TCR Vbeta8 and TCR Vbeta20 genes were preferentially expressed in 6 of 12 patients (50%) and the TCR Vbeta9 and TCR Vbeta14 genes were expressed in 5 of 12 patients (42%). Junctional sequences of complementary DNA encoding the TCR Vbeta8 and TCR Vbeta20 genes in intrarenal T cells showed oligoclonal expansion, indicating antigen-driven stimulation. Interleukin-4 (IL-4) and IL-10 mRNA were highly expressed on intrarenal T cells, while interferon-gamma mRNA was not detected. CONCLUSION: Our findings suggest that T cells infiltrating the kidneys of patients with LN may recognize restricted epitopes on antigens and function as Th2-type T cells.

Adolescent↗

Spinal tuberculosis: report of an atypical presentation.

A 24-year-old woman was treated by the authors for an atypical form of spinal tuberculosis. The patient had simultaneous involvement of T1, T7, and the right ilium. At the T7 level, the anterior and posterior vertebral elements were involved. These findings closely mimicked spinal malignancies. There was no evidence of pulmonary tuberculosis. A biopsy confirmed tuberculosis and the patient was treated successfully with antituberculosis therapy. It is important to be aware that spinal tuberculosis can mimic spinal malignancy.

Adult↗

Cadmium exposure decreases androgen-dependent metabolism of acetohexamide in liver microsomes of male rats through its testicular toxicity.

Administration of cadmium (Cd) at a dose of 1.23 mg/kg (2.0 mg/kg as CdCl(2)) markedly decreased the activity of an enzyme (acetohexamide reductase) catalysing the ketone-reduction of acetohexamide, an oral antidiabetic drug, in liver microsomes of male rats. However, the decreased enzyme activity was increased by repeated treatment with testosterone propionate (TP). When male rats were castrated and TP was given to the castrated ones, a similar decrease and increase, as described above, were observed in the microsomal enzyme activity. Cd exposure to male rats induced haemorrhage and atrophy of the testes and significantly diminished serum testosterone levels. There was no possibility that Cd accumulated in liver microsomes of male rats causing direct inhibition of the microsomal enzyme activity. We conclude that Cd exposure decreases androgen-dependent metabolism of acetohexamide in liver microsomes of male rats through its testicular toxicity. Cd exposure had no effect on acetohexamide reductase activity in liver cytosol of male rats.

Acetohexamide↗

Indications for surgery in intestinal Behçet's disease.

BACKGROUND/AIMS: As advances in steroids and immunosuppressants made medical treatment first-line therapy for Behçet's disease, the criteria for elective surgery became unclear. The aim of this paper is to establish surgical criteria for Behçet's. METHODOLOGY: We reviewed the medical records of 8 consecutive Japanese patients who were diagnosed with intestinal Behçet's at Tsukuba University Hospital between 1976 and 2001. Records were examined for medical treatment including dose of steroids, and surgical treatment including length of resected intestine, incidence of recurrence, and the form and site of recurrence. RESULTS: Elective surgery was performed in cases where the preoperative steroid administration could not be reduced to under 40mg/day, once steroids exceeded 40mg/day to control symptoms and inflammation. Cases with emergency operations (perforated cases), the preoperative doses of steroids were not so high (0, 0, 10, 20mg/day). In all cases, the post-surgical steroid dose was reduced under 20mg/day. Three cases showed recurrence after surgery within 2 years. These cases also had an increase in steroid dosage at the time of recurrence, but have been controlled medically so far. CONCLUSIONS: Surgery should be strongly considered when the steroid dose exceeds 40mg/day.

Adolescent↗