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Biomedical subjects

T Shibuya

Publications and source records attributed to T Shibuya.

At least 55 records · Page 3Linked to original sources
PubMed1999

Interferon-gamma prevents apoptosis in Epstein-Barr virus-infected natural killer cell leukemia in an autocrine fashion.

The significant function of cytokines includes maintenance of cell survival as well as induction of cell differentiation and/or proliferation. We demonstrate here that interferon-gamma (IFN-gamma) plays a role for progression of Epstein-Barr virus (EBV)-infected natural killer cell leukemia (NK leukemia) through maintaining cell survival. NK leukemia cells obtained from 7 patients had clonal episomal forms of EBV, indicating that the leukemic cells were of clonal origin. Although normal NK cells constitutively expressed Bcl-2, the EBV-infected NK leukemia cells lacked endogenous Bcl-2 expression and were hypersensitive to apoptosis in vitro. The addition of IFN-gamma to the culture significantly inhibited their spontaneous apoptosis without inducing cell proliferation or upregulation of Bcl-2. The NK leukemia cells constitutively secreted IFN-gamma, and the patients' sera contained a high concentration of IFN-gamma, levels that were high enough to prevent NK leukemia cells from apoptosis. Bcl-XL was not involved in the IFN-gamma-induced NK leukemia cell survival. These data suggest that the acquisition of IFN-gamma-mediated autocrine survival signals, other than Bcl-2 or BCL-XL, might be important for the development of EBV-infected NK leukemia.

Adolescent↗
PubMed1999

Importance of metabolic monitoring systems as an early prognostic indicator in severe head injured patients.

We have analyzed and evaluated what is the best metabolic monitoring system to determine the prognosis for maintenance of neurological function in severe head injured patients. Acute subdural hematoma (ASDH) was recognized in fifteen of 22 patients and cerebral contusion in seven in this series. Intracranial pressure (ICP), jugular venous pH and jugular bulb venous oxygen saturation (SjO2) were continuously monitored as soon as possible following stabilization. The measurement of cerebral blood flow (CBF) was carried out using a stable Xenon-computerized tomography (Xe-CT). After measuring CBF, 3% carbon dioxide (CO2) loading was conducted to determine CO2 responses (delta CBF/delta CO2). In patients who died (D), jugular venous pH showed evidence of acidosis (6.3-7.2) with delta CBF/delta CO2 < 1 and cerebral metabolic rate of oxygen (CMRO2) < 1.21 within several hours of the trauma. On the other hand, arterial pH was shown to be within the normal range. In vegetative state (VS) and severe disability (SD) patients, jugular venous pH was shown to be within normal range, with delta CBF/delta CO2 < 1 and 1.44 < CMRO2 < 1.79. In all of moderate disability (MD) and good recovery (GR) patients, jugular venous pH was shown to be within the normal range, with delta CBF/delta CO2 > 1 and 1.65 < CMRO2 < 1.85. These results suggest that jugular venous pH, CO2 response and CMRO2, were useful as early prognostic indicators in the maintenance of neurological function.

Acidosis↗
PubMed1999

A case of posterior cerebral artery aneurysm associated with idiopathic bilateral internal carotid artery occlusion: case report.

BACKGROUND: Aneurysms of the posterior circulation are challenging lesions to neurosurgeons, despite improvements in microsurgical techniques and advances in skull base approaches. We present a rare case of a posterior cerebral artery (PCA)-posterior communicating artery (PcomA) junction aneurysm associated with bilateral internal carotid artery (ICA) occlusion successfully treated with an endovascular procedure. CASE DESCRIPTION: A 57-year-old female presented with sudden onset of severe headache and loss of consciousness. CT scan showed diffuse subarachnoid hemorrhage and acute hydrocephalus. The patient developed severe neurogenic pulmonary edema and shock. Although her neurogenic pulmonary edema did not resolve, she recovered from shock. However, her general condition was so critical and her vital signs so unstable, that direct surgery under general anesthesia was considered too risky. A cerebral angiogram showed complete occlusion of both internal carotid arteries without any Moyamoya vessels. A saccular aneurysm located at the right PCA-PcomA junction was seen. To obliterate the aneurysm and prevent rerupture, the patient underwent coil embolization via an endovascular approach under sedation with local anesthesia. The balloon remodeling technique was useful to prevent occlusion of parent arteries. Finally, four interlocking detachable coils (IDC) with a total length of 44 cm were used to completely obliterate the aneurysm using the balloon remodeling technique. The patient made a full recovery after treatment and the aneurysm remained obliterated 2 years after coil embolization. CONCLUSIONS: We emphasize the advantages of the endovascular approach for the patient in critical condition. We believe that this is the first report of a PCA-Pcom junction aneurysm associated with bilateral ICA occlusion without moyamoya disease.

Aneurysm, Ruptured↗
PubMed1999

Multiple autoimmune haemopoietic disorders and insidious clonal proliferation of large granular lymphocytes.

We report a patient with clonal proliferation of CD3+8+TCRalphabeta+ large granular lymphocytes (LGL) presenting multiple episodes of autoimmune cytopenia, including autoimmune neutropenia, idiopathic thrombocytopenic purpura, autoimmune haemolytic anaemia, and pure red cell aplasia. Each disorder appeared separately or as a combination during an 11-year clinical course. The increase of blood CD3+8+TCRalphabeta+ LGL was detected 6 years after the initial diagnosis of cytopenia, but the absolute number of LGL cells was always < 1.0 x 109/l. LGL cells were of monoclonal origin and had a chromosomal abnormality. LGL cells transiently responded to cyclosporine A therapy, which was also effective on all of these autoimmune cytopenias. Accordingly, an undetectable level of proliferation of a clonal LGL population could cause various autoimmune haemopoietic disorders.

Adolescent↗
PubMed1999

Characterization of the ptr6(+) gene in fission yeast: a possible involvement of a transcriptional coactivator TAF in nucleocytoplasmic transport of mRNA.

Transport of mRNA from the nucleus to the cytoplasm is one of the important steps in gene expression in eukaryotic cells. To elucidate a mechanism of mRNA export, we identified a novel ptr [poly(A)+ RNA transport] mutation, ptr6, which causes accumulation of mRNA in the nucleus and inhibition of growth at the nonpermissive temperature. The ptr6(+) gene was found to encode an essential protein of 393 amino acids, which shares significant homology in amino acid sequence with yTAFII67 of budding yeast Saccharomyces cerevisiae and human hTAFII55, a subunit of the general transcription factor complex TFIID. A Ptr6p-GFP fusion protein is localized in the nucleus, suggesting that Ptr6p functions there. Northern blot analysis using probes for 10 distinct mRNAs showed that the amount of tbp+ mRNA encoding the TATA-binding protein is increased five- to sixfold, whereas amounts of others are rapidly decreased at the nonpermissive temperature in ptr6-1. ptr6 has no defects in nuclear import of an NLS-GFP fusion protein. These results suggest that Ptr6p required for mRNA transport is a Schizosaccharomyces pombe homologue of yTAFII67 and hTAFII55. This is the first report suggesting that a TAF is involved in the nucleocytoplasmic transport of mRNA in addition to the transcription of the protein-coding genes.

Cell Nucleus↗
PubMed1999

Inhibition of microtubule assembly by HPC-1/syntaxin 1A, an exocytosis relating protein.

HPC-1/syntaxin 1A (HPC-1), which has been identified as a presynaptic membrane protein, is believed to regulate the synaptic exocytosis as a component of t-SNARE. The distribution of the protein, however, is not restricted to the synaptic terminal, but it has been found to locate on the axonal membrane. When the expression of HPC-1 was suppressed, neurite sprouting was enhanced in cultured neurons. These findings suggest that HPC-1 possesses other functions than the regulation of the membrane fusion in neurotransmitter release. Rather it may also participate in the morphogenesis of neurons through membrane fusion, and possibly through cytoskeleton. HPC-1 has a sequence resemble to the assembly promoting sequence of heat stable MAPs in residues 89-106, suggesting that it can bind tubulin and be involved in microtubule system. Thus, both the tubulin binding property and the effect on microtubule assembly of HPC-1 were examined in vitro using a mutated HPC-1 lacking the C-terminal transmembrane region (HPC-deltaTM), which was overexpressed in E. coli. Affinity column chromatography showed that tubulin was found to bind HPC-1 directly. Synthetic peptide which corresponds to the residues 89-106 competitively inhibited the tubulin-HPC-1 binding, indicating that the sequence is responsible for the tubulin binding. In addition, chemical cross-linking with EDC revealed that one HPC-1 molecule can bind per one monomeric tubulin molecule. Light scattering measurement of microtubule polymerization showed that HPC-1 decreased the rate of the pure tubulin polymerization. Direct observation of single microtubules under dark-field microscopy showed that the growth rate of microtubule decreased by HPC-1. After shortening stopped, microtubules often spent attenuate phases, in which neither growing nor shortening was detected. When another mutant HPC-1 which is composed of residues 1-97 and lacks tubulin binding activity was used, however, the suppression of microtubule polymerization was not observed. These results suggest that HPC-1 is a potent regulator of microtubule polymerization, which directly bind tubulin subunit and decrease the polymerization activity.

Amino Acid Sequence↗
PubMed1999

Primary biliary cirrhosis associated with membranous glomerulonephritis.

A 33-year-old woman was admitted to our department for evaluation of liver dysfunction and proteinuria. A liver biopsy specimen showed ductular proliferation and moderate portal fibrosis indicating stage II primary biliary cirrhosis. A renal biopsy specimen showed mild to moderate mesangial cell proliferation without crescent formation or interstitial nephritis. Immunofluorescent staining revealed deposition of immunoglobulin G (IgG), third component of complement (C3), and Clq on glomerular basement membranes. The findings indicated stage I membranous glomerulonephritis. Administration of ursodesoxycholic acid together with prednisolone, azathioprine, and dipyridamole decreased proteinuria and improved cholestatic liver dysfunction.

Adult↗
PubMed1999

Association of polymorphism in the NeuroD/BETA2 gene with type 1 diabetes in the Japanese.

NeuroD/BETA2, a transcription factor of the insulin gene, also plays an important role in the development of pancreatic beta-cells. Recently, the NeuroD/BETA2 gene has been mapped to the long arm of human chromosome 2 (2q32) where the IDDM7 gene has previously been mapped, implying its involvement in diabetes. To identify mutations in the NeuroD/BETA2 gene that may predispose patients to develop diabetes, we studied the gene in 50 Japanese subjects with diabetes (4 with type 1 and 46 with type 2) by the polymerase chain reaction (PCR) followed by single-strand conformation polymorphism and sequencing analyses. Further analysis was performed in 392 Japanese subjects (60 with type 1 and 158 with type 2 diabetes and 174 healthy control subjects) by mismatch PCR restriction fragment length polymorphism. We found a DNA polymorphism of the NeuroD/BETA2 gene. A nucleotide G-to-A transition results in the substitution of alanine to threonine at codon 45 (Ala45Thr). The frequencies of heterozygotes for the Ala45Thr variant were 9.8% in the control subjects, 9.5% in the patients with type 2 diabetes, and 25.0% in the patients with type 1 diabetes, a significant difference (P = 0.006). Because the variant of the NeuroD/BETA2 gene (Ala45Thr) is associated with type 1 but not type 2 diabetes, it may be implicated in the loss of pancreatic beta-cells in type 1 diabetes.

Adult↗
PubMed1999

Development and evaluation of LIPODEET, a new long-acting formulation of N, N-diethyl-m-toluamide (DEET) for the prevention of schistosomiasis.

N, N-diethyl-m-toluamide (DEET) is a common and fairly safe active ingredient in many insect repellents. Our recent studies showed that when applied to the skin, DEET has a potent anti-parasitic effect against Schistosoma mansoni. However, the beneficial effects of DEET lasted only for a few minutes, presumably due to its rapid absorption through the skin. In this study, we evaluated different carrier formulations that prolong the activity of DEET in the skin. Among the various formulations analyzed, DEET incorporated into liposomes (LIPODEET) appeared to prolong the activity of DEET for more than 48 hr after a single application. Furthermore, LIPODEET was found to be minimally absorbed through the skin and loss due to washing off was limited. These findings thus suggest LIPODEET is a safe and long-acting formulation of DEET that is quite effective against schistosomiasis.

Animals↗
PubMed1999

[Myelodysplastic syndrome after autologous peripheral blood stem cell transplantation for adult acute myelogenous leukemia].

A 65-year-old woman was admitted to our hospital with arthritis and agranulocytosis. She had given a diagnosis of acute myelogenous leukemia (FAB classification M1) a year ago and treated with 3 cycles of cytarabine and anthracycline or etoposide for 4 months, achieving complete remission state. Her bone marrow aspirate revealed normocellularity with normal karyotype (46, XX [20]) without apparent dysplastic feature at this time. She received autologous peripheral blood stem cell transplantation subsequently after conditioning regimen consisted of granulocyte colony-stimulating factor, busulfan, Ara-C and etoposide. Three months later, she started to manifest low grade fever, polyarthralgia and agranulocytosis and she admitted to our hospital after nine months. Bone marrow aspirate revealed marked hypocellularity with dysplastic features in three series of hematopoietic cells. Arthritis was dramatically improved after administration of prednisolone, but low granulocyte count continued. Bone marrow aspirate revealed karyotypic abnormality with monosomy 7 and we diagnosed her as myelodysplastic syndrome. Chemotherapy-induced myelodysplasia has been reported so far. This case would represent secondary myelodysplastic syndrome after chemotherapy. We could not clarify the etiology for polyarthritis but could be one of the paraneoplastic syndrome. We should note subsequent occurrence of myelodysplasia when planning treatment schedule.

Aged↗
PubMed1999

Partial hepatectomy strongly increased the mutagenicity of N-ethyl-N-nitrosourea in MutaMouse liver.

The relationship between cell proliferation and mutagenesis can be investigated in vivo due to the advent of transgenic animal mutation assays. In these assays, slowly proliferating tissues, such as mammary gland and liver, that are exposed to mutagens generally have longer manifestation times for mutations and lower mutant frequencies. This may be because the cells have enough time prior to cell division to repair DNA damage. We carried out this study using the MutaMouse positive selection system to investigate the effect of a high rate of cell proliferation induced by partial hepatectomy (PH) on mutation induction. We used a 2 x 2 experimental design for PH (or no PH) and 50 mg/kg N-ethyl-N-nitrosourea (ENU) (or phosphate buffer), with the chemical injected 16-19 hr after PH. In the non-ENU groups, the mean MF was slightly but not significantly higher in the PH group than in the non-PH group. In the ENU non-PH group, the MF was also slightly but not significantly increased. In the ENU PH group, in contrast, the mean MF was 7 times the mean MF of the group that received either treatment alone. These results strongly support the hypothesis that ENU induced pre-mutational DNA lesions in liver are completely repaired prior to cell division, and PH increases the mutagen-induced MF by reducing the amount of time available for such repair.

Animals↗
PubMed1999

Effects of O (6)-alkylguanine-DNA alkyltransferase deficiency in Escherichia coli as the host for the detection of mutations in lacI transgenic mice.

Transgenic mice are widely used to detect gene mutations in vivo induced by a variety of chemicals. It is known, however, that no mutagenicity of methyl methanesulfonate (MMS) is detected in epididymal sperm in various transgenic mice assays, although MMS induces the dominant lethal and specific locus mutations in male mice. To investigate the issue of whether unrepaired lesions in DNA of mature sperm can be transformed into mutations during replication of the lambda phage in Escherichia coli cells, we developed an E. coli strain YG5152, which is a derivative of strain SCS-8 but is deficient in the genes encoding O (6)-alkylguanine-DNA alkyltransferases. When lambda LIZalpha phages were treated with MMS or N-ethyl-N-nitrosourea (ENU) in vitro and infected to the E. coli strains, the mutant frequencies of lacI were markedly higher in strain YG5152 than in strain SCS-8. When Big Blue(trade mark) mice were treated with MMS (160 mg/kg) or ENU (125 or 250 mg/kg) and the phages rescued from mature sperm were infected to the strains, the mutation frequency (MF) of phages from ENU-treated mice at a dose of 250 mg/kg in strain YG5152 was about two times higher than that in strain SCS-8. However, no increase in the MF was observed in the MMS-treated mice even in strain YG5152. These results suggest that, although strain YG5152 efficiently detects ex vivo mutations caused by mutagenic alkyl adducts formed by MMS in lambda phage DNA, no detectable levels of mutagenic methyl adducts are present in mature sperm of MMS-treated mice. Possible reasons for this lack of mutagenicity of MMS in mature sperm using transgenic mice assays are discussed.

Animals↗
PubMed1999

[An early phase II study of autologous peripheral blood stem cell transplantation for acute myelogenous leukemia in first remission. Japan Blood Cell Transplantation Study Group].

We performed a multicenter, an early phase II clinical trial to evaluate the feasibility, safety and efficacy of myeloablative therapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of acute myelogenous leukemia (AML) in first remission. A total of 105 patients were enrolled in the study, and 56 patients in first complete remission received auto-PBSCT. The median age was 44 years. Of the 56 patients, 34 (60.7%) had M2 or M3 AML by the French-American-British Classification system. The median concentration of infused CD34+ cells was 2.3 x 10(6)/kg by recipient body weight. Median days to reach an absolute neutrophil count > 500/microliter and a platelet count > 20000/microliter were 14 and 16, respectively. The median disease-free survival rate was estimated to be 62.0% at a median follow-up time of 534 days. Although the study enrolled a small number of patients and the follow-up period was relatively short, the preliminary results were encouraging and indicated that myeloablative chemotherapy with auto-PBSCT is feasible and can be performed safely as a post-remission therapy for AML. A prospective randomized clinical trial of auto-PBSCT versus standard chemotherapy alone will be necessary to assess the efficacy of high-dose therapy facilitated by auto-PBSCT as a post-remission therapy for AML.

Adolescent↗
PubMed1999

[Results and problems of thymectomy in myasthenia gravis over 65 years old].

From June 1975 to March 1999, 300 cases of myasthenia gravis (MG) have undergone thymectomy. Twenty-eight patients over 65 years old were examined, focusing on the relationship between clinical appearances and microscopic findings of the thymuses. Among these cases, six were classified as ocular type (one case with thymoma) and 22 generalized type (eight cases with thymoma). According to the thymoma registering stages defined by Masaoka and colleagues, those nine cases with thymoma associated with stages I (n = 7), II (n = 1) and III (n = 1), respectively. The case of stage III (74 year old female) died four years and eight months after surgery. The case of stage II died of old age two years after the surgery. Complete remission was achieved in two cases of stage I. The follicular hyperplasia were seen in eight cases, and all resulted in improvement. Nine cases with no particular findings of thymuses classified into four ocular type and five generalized type including one fulminating type. Post-operative course of all these cases were uneventful. Although one recurrent of the thymoma and one death of the tumor were observed, post-operative outcomes of these elderly patients were generally satisfactory. We concluded that there is an operative indication of thymectomy for MG of even elderly patients, if no particular findings were recognized in the thymus.

Aged↗
PubMed1998

Diagnostic value of plasma thrombin-antithrombin III complex and D-dimer concentration in patients with varicose veins for exclusion of deep-vein thrombosis.

The aim of this study was to evaluate the usefulness of determining plasma D-dimer (DD) and thrombin-antithrombin III complex (TAT) levels in the diagnostic workup for the screening of deep-venous thrombosis (DVT) among varicose vein patients. One hundred forty consecutive patients being treated for DVT or varicose veins underwent color-flow duplex scanning, and 25 patients had DVT and the remaining 115 had primary varicose veins. When DD and TAT were analyzed statistically in combination, it was determined that the combination of either positive DD (cutoff level 1.0 microg/ml) or positive TAT (cutoff level 3.0 microg/l) had a sensitivity of 100% for DVT with a specificity, positive predictive value, and negative predictive value of 79%, 51%, and 100%, respectively. This study demonstrates plasma levels of DD (less than 1.0 microg/ml) and TAT (less than 3.0 microg/l) in combination to be useful for the exclusion of DVT among patients with varicose veins. Patients with negative hematological data may safely undergo surgical treatment for varicose veins without further evaluation such as duplex scanning or contrast venography.

Antithrombin III↗
PubMed1998

New ferromagnetic bone cement for local hyperthermia.

We have developed a ferromagnetic bone cement as a thermoseed to generate heat by hysteresis loss under an alternate magnetic field. This material resembles bioactive bone cement in composition, with a portion of the bioactive glass ceramic component replaced by magnetite (Fe3O4) powder. The temperature of this thermoseed rises in proportion to the weight ratio of magnetite powder, the volume of the thermoseed, and the intensity of the magnetic field. The heat-generating ability of this thermoseed implanted into rabbit and human cadaver tibiae was investigated by applying a magnetic field with a maximum of 300 Oe and 100 kHz. In this system, it is very easy to increase the temperature of the thermoseed in bone beyond 50 degrees C by adjusting the above-mentioned control factors. When the temperature of the thermoseed in rabbit tibiae was maintained at 50 to 60 degrees C, the temperature at the interface between the bone and muscle (cortical surface) surrounding the material rose to 43 to 45 degrees C; but at a 10-mm distance from the thermoseed in the medullary canal, the temperature did not exceed 40 degrees C. These results demonstrate that ferromagnetic bone cement may be applicable for the hyperthermic treatment of bone tumors.

Animals↗
PubMed1998

Inhalation of diesel exhaust enhances allergen-related eosinophil recruitment and airway hyperresponsiveness in mice.

We have previously shown that intratracheal instillation of suspension of diesel exhaust particles enhances allergen-related eosinophilic airway inflammation, airway hyperresponsiveness, and local expression of interleukin (IL)-5 and granulocyte macrophage-colony stimulating factor (GM-CSF) in mice. The present study was designed to elucidate the effects of daily inhalation of diesel exhaust (DE) on the allergen-related respiratory disease. ICR mice were exposed for 40 weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 with aerosol allergen challenges (1% ovalbumin in isotonic saline for 6 min) at 3-week intervals during the last 24 weeks of exposures. Exposure to DE enhanced allergen-related eosinophil recruitment to the submucosal layers of the airways and to the bronchoalveolar space, and increased protein levels of GM-CSF and IL-5 in the lung in a dose-dependent manner compared to exposure to clean air. There were strong correlations between the number of eosinophils in bronchoalveolar lavage (BAL) fluid and IL-5 concentrations in BAL supernatants and lung tissue supernatants. In addition, the increases in eosinophil recruitment and local cytokine expression were accompanied by goblet cell proliferation in the bronchial epithelium and airway hyperresponsiveness to inhaled acetylcholine. In contrast, the control mice exposed for 40 weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 without allergen provocation showed no eosinophil recruitment to the submucosal layers of the airways nor to the bronchoalveolar space and few goblet cells in the bronchial epithelium. The present study provides experimental evidence that daily inhalation of DE can enhance allergen-related respiratory diseases such as allergic asthma. This effect may be mediated by the enhanced local expression of IL-5 and GM-CSF. Increased ambient levels of DE may be implicated in the increasing prevalence of bronchial asthma in recent years.

Administration, Inhalation↗