[A case of Budd-Chiari syndrome associated with anti-phospholipid syndrome].
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Adult↗
Biomedical subjects
H Ikeda
Publications and source records attributed to H Ikeda.
[Pharmacological effects of a thiazolidinedione derivative, pioglitazone].
Pioglitazone, a thiazolidinedione derivative, was developed from our basic research on diabetic animal models and our chemical research on lipid-lowering agents. In clinical studies, pioglitazone at doses of 15-45 mg/man/day produced 1.0-1.6% reduction in HbA1c for 6 months. Moreover, pioglitazone produced about 14% reduction in plasma triglyceride levels and 4-11% increase in HDL-cholesterol(HDL-C) levels without the significant changes in total cholesterol and LDL-C levels. Although the exact molecular mechanism of reducing insulin resistance still remains obscure, pioglitazone normalizes abnormalities in the cellular insulin signal transduction. This effect seems to be due to the inhibitory action of pioglitazone on TNF-alpha production, which is one of the factors responsible for insulin resistance. Pioglitazone is a potent agonist for the peroxisome proliferator activated receptor(PPAR)-gamma, that is related to differentiation of adipocytes, and the relationship between TNF-alpha production and PPAR-gamma has been reported. Therefore, the agonistic activity of pioglitazone on PPAR-gamma may be involved in the mechanism for reducing insulin resistance. Recently, it was demonstrated that pioglitazone is also an agonist of PPAR-alpha, which plays a central role in lipid metabolism through enhancing the synthesis of apo AI, apo AII and reverse cholesterol transporters, such as fatty acid transporter molecules, and SR-B1 and ABCA1 reverse cholesterol transport receptors. Therefore, these findings suggest that pioglitazone has a benefit for prevention of both diabetic micro-angiopathy and macro-angiopathy.
Animals↗
[A case of squamous cell carcinoma of the oral floor showing a complete response to oral administration of UFT].
A 73-year-old male with squamous cell carcinoma of the oral floor (T1N0M0), who had not consented to radical treatment was treated with UFT by oral administration alone. After commencement of the administration, tumor remission was observed at 2 weeks and disappeared clinically at 8 weeks. The total period of oral administration of UFT was twenty-three months, and the total dose was 186.5 g as tegafur. Major adverse effects were pigmentation of hands and liver dysfunction. He remains under observation, and there is no evidence of tumor recurrence.
Administration, Oral↗
[Evaluation of venous system with 3D-CTA--from the viewpoint of treatment to cerebral aneurysm].
BACKGROUND AND PURPOSE: Recently, many reports have suggested that cerebral aneurysms can be treated under diagnoses based only on the information obtained from three-dimensional CT angiography (3D-CTA). However, these reports have mainly emphasized the excellence of the stereoscopic images of aneurysms and the relationships with the arteries, and almost never discuss the venous information. The present study used 3D-CTA images to evaluate potential problems in the venous system which may affect the pterional approach. PATIENTS AND TECHNIQUE: This study included 500 sides of 250 patients who underwent screening for cerebrovascular diseases by 3D-CTA. The voxel-transmission method was used for 3D reconstruction. 3D-CTA images in axial stereoscopic views were mainly evaluated, with views in other directions. RESULTS: The variations of the superficial middle cerebral vein draining the sphenoparietal sinus and cavernous sinus were related to the operative view to assess the potential for venous damage. Potential locations of venous damage to the basal vein include the veins of the first segment draining from the frontal base, the direct communication of the basal vein with the sphenoparietal sinus or cavernous sinus, and the veins of the first segment which independently form the uncal vein draining the sphenoparietal sinus or cavernous sinus. CONCLUSION: 3D-CTA demonstrates the venous system and the spatial relationships with other structures clearly. Such information will help neurosurgeons to construct a better and safer microdissection plan, which will preserve the venous system and help prevent postoperative neurological deficits.
Brain↗
[Antibiotic management guidelines in trauma and critical care].
Many patients with severe illness or conditions like multiple trauma and severe burns are vulnerable to infection due to their depressed immune function. In addition, most patients in the intensive care unit are at increased risk of developing ventilator-associated pneumonia and catheter-related sepsis. A basic concept of antibiotic use in these guidelines is to diagnose infection and identify the pathogenic microorganism as soon as possible. We should not start inadequate empirical antimicrobial therapy in cases of undetermined infection focus or pathogen because it may increase the risk of development of antibiotic-resistant bacteria and opportunistic infections. Antibiotic use should be planned deliberately from the time of admission in patients hospitalized long time. Prophylactic antibiotic use should be restricted to a specific diagnosis or an exceptional condition. The antibiotic choice should be determined based on data on antibiotic-resistant bacteria in the ward of a trauma center.
Anti-Bacterial Agents↗
Fractionated stereotactic radiotherapy of brain metastases from renal cell carcinoma.
PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for brain metastases from renal cell carcinoma (RCC). METHODS AND MATERIALS: From May 1983 to September 1998, 35 patients with brain metastases from RCC underwent radiotherapy at the National Cancer Center Hospital, Tokyo; 10 patients treated initially with FSRT (FSRT group); 11 with surgery followed by conventional radiotherapy (S/CR group); and 14 with conventional radiotherapy (CR group). Survival and local control rates were determined for patients who had an ECOG performance status of 0-2. RESULTS: Overall median survival rate was 18 months, and actuarial 1- and 2-year survival rates were 57.6% and 31.0%, respectively. Median survival rates were 25.6 months for the FSRT group, 18.7 months for the S/CR group, and 4.3 months for the CR group. Significant prognostic factors associated with survival were age less than 60 years and good performance status. In patients treated with FSRT, imaging studies revealed that 21 of 24 tumors (88%) were locally controlled during a median follow-up time of 5.2 months (range 0.5-68). Actuarial 1- and 2-year local control rates were 89.6% and 55.2%, respectively. No patient suffered from acute or late complications during and following FSRT. CONCLUSIONS: FSRT offers better tumor control and prolonged survival over the S/CR or CR groups, and should be considered as primary treatment for brain metastases from RCC. Patients under 60-years-old and those with a good performance status at the beginning of radiotherapy had a better prognosis.
Brain Neoplasms↗
Thrombopoietin and interleukin-2 induce association of CRK with STAT5.
Crk (Crk I and II) proteins and closely related CrkL are adapters which are commonly involved in various signaling processes in various cells, and these proteins share many ligands. Whether they have redundant or distinct physiologic roles is unclear. By coprecipitation and far Western blotting analysis, we demonstrate that Crk (I/II) binds to tyrosine phosphorylated STAT5 in cells stimulated by cytokines such as thrombopoietin (TPO) and interleukin-2 (IL-2). The association did not require nuclear elements and can be observed in primary cells as this was also demonstrated in TPO-stimulated platelets. Using a beta-casein promoter STAT5 binding site as a probe, we have also demonstrated that CrkL (a close relative of Crk) antiserum, but not Crk antiserum, supershifted the STAT5-DNA complex by an electrophoretic mobility shift assay, suggesting that CrkL, but not Crk, is the major component of the complex. Thus, Crk and CrkL may have distinct roles in the regulation of STAT5.
Base Sequence↗
Hypercholesterolemia inhibits angiogenesis in response to hindlimb ischemia: nitric oxide-dependent mechanism.
BACKGROUND: Endothelium-derived nitric oxide (EDNO) plays an important role in the regulation of angiogenesis, whereas hypercholesterolemia (HC) impairs EDNO release. We examined the hypothesis that HC may inhibit ischemia-induced angiogenesis by inhibition of EDNO in a rat model of unilateral hindlimb ischemia and that oral L-arginine supplementation, a substrate for NO synthase, may prevent HC-related impairment of angiogenesis. METHODS AND RESULTS: Male Sprague-Dawley rats were fed (A) standard diet (control), (B) 2% high-cholesterol diet (HC group), or (C) high-cholesterol diet with oral L-arginine (2.25% in drinking water) (HC+L-arg group). At 2 weeks of the dietary intervention, unilateral limb ischemia was surgically induced in all animals. Dietary HC groups (B and C) revealed elevated total and LDL cholesterol levels compared with control animals. Laser Doppler blood flow analyses showed significant decreases in the ischemic/normal limb blood flow ratio in the HC group compared with controls (P:<0.05) when followed up until 4 weeks after surgery. Selective angiography and immunohistochemical analyses in the ischemic limb at postoperative day 14 revealed significantly lower angiographic scores (P:<0.01) and capillary densities (P:<0.01) in the HC group than controls, which were associated with decreased tissue contents of NO(x) and cGMP. Oral L-arginine supplementation (HC+L-arg) significantly improved all parameters of the laser Doppler blood perfusion ratio, angiographic scores, and capillary densities (P:<0.01 versus HC group), which were accompanied by significant elevations in serum L-arginine levels and tissue NO(x) and cGMP contents. CONCLUSIONS: Collateral vessel formation and angiogenesis in response to hindlimb ischemia were significantly attenuated in rats with dietary HC. The mechanism may be related to the reduced NO bioactivity in the ischemic tissues. Augmentation of the tissue NO activity by oral L-arginine supplementation restored the impaired angiogenesis in HC.
Administration, Oral↗
Lysophosphatidic acid enhances collagen gel contraction by hepatic stellate cells: association with rho-kinase.
We studied the effect of lysophosphatidic acid (LPA) on collagen gel contraction by cultured rat hepatic stellate cells (HSCs) in association with the function of Rho-kinase, one of the target molecules of small GTPase Rho. Binding studies showed a single class-binding site of LPA on HSCs. LPA enhanced the contraction of a collagen lattice seeded with HSCs. LPA increased the number of HSCs with polygonal morphology that contained actin stress fibers, and enhanced the phosphorylation of myosin light chain and the assembly of focal adhesion kinase and RhoA around fibronectin-coated beads seeded on HSCs. The electric cell-substrate impedance sensor system showed that LPA enhanced adhesion of HSC to extracellular substrate. All the effects of LPA were suppressed by Y-27632, Rho-kinase inhibitor. These data support the notion that LPA is involved in modulating HSC morphology, its attachment to surrounding extracellular matrix and its contraction by a mechanism involving Rho-kinase.
Actins↗
Comparison of sensitivity to ultraviolet B irradiation between human lymphocytes and hematopoietic stem cells.
To investigate the clinical applicability of prophylaxis of post-transplant graft-versus-host disease by UV-B irradiation of stem cell preparations, the UV-B sensitivities of human lymphocytes and primitive hematopoietic progenitors were compared. The mononuclear cell fractions (MNC) derived from human cord blood and granulocyte-colony-stimulating factor-mobilized peripheral blood were used. After UV-B irradiation, lymphocyte proliferation ability, hematopoietic colony-forming cells, and apoptotic cells were analyzed. At a dose of 33 J/m(2), significant differences were observed in the residual percentages of hematopoietic progenitors and lymphocyte functions [ANOVA, F (5,46) = 19.4; P <.0001], and the difference between CFU-C (85.2% + 24.0%; n = 8) and MLR (12.7% + 12. 6%; n = 10) was significant (P <.0001). There were no significant differences in the residual percentages of CFU-C, HPP-CFC, and LTC-IC. Percentages of annexin V-positive cells in the total MNC and the CD34(+) cell population in MNC after UV-B irradiation were 69.8% and 18.7%, respectively. In conclusion, there was a range of UV-B doses over which T lymphocytes were inactivated but hematopoietic progenitors, including HPP-CFC and LTC-IC, were preserved.
Annexin A5↗
Evidence for an energy scale for quasiparticle dispersion in Bi2Sr2CaCu2O8
Quasiparticle dispersion in Bi2Sr2CaCu2O8 is investigated with improved angular resolution as a function of temperature and doping. Unlike the linear dispersion predicted by the band calculation, the data show a sharp break in dispersion at 50+/-15 meV binding energy where the velocity changes by a factor of 2 or more. This change provides an energy scale in the quasiparticle self-energy. This break in dispersion is evident at and away from the d-wave node line, but the magnitude of the dispersion change decreases with temperature and with increasing doping.
Journal Article↗
The external radiotherapy with three-dimensional conformal boost after the neoadjuvant androgen suppression for patients with locally advanced prostatic carcinoma.
PURPOSE: To analyze the results in patients with locally advanced prostatic carcinoma treated by hormonal therapy followed by external radiotherapy using three-dimensional conformal radiation therapy (3D-CRT) boost. METHODS AND MATERIALS: From 1987 to 1995, 46 patients with histologically proven locally advanced adenocarcinoma of the prostate were treated with 3D-CRT at the National Cancer Center Hospital, Tokyo. The neoadjuvant androgen suppression started immediately after the diagnosis followed by radical radiation therapy, according to the prospective protocol. They were treated with photons of 6-14 MV for wide fields and the boost, of which a multiple-leaf collimator of 2-cm width was available. The boosted dose was delivered with the rotational 3D-CRT, after the delivery of whole pelvis 4-field box from a dose of 40-46 Gy up to 66 Gy. The planning target volume encompassed 1 cm outside throughout the clinical target volume, and the prostate and the seminal vesicles were included in the boost field. RESULTS: The 3D-CRT boost treatment completed as planned in all 46 patients. The median follow-up for all the patients was 60 months (range, 5-120 months). Nineteen of 46 patients died. Of these, 11 patients died of the intercurrent diseases. For all 46 patients, the 5- and 8-year overall survival rates were 61.3% and 42.4%, and the 5- and 8-year cause-specific survival rates were 82.4% and 64.4%, respectively. The prostate-specific antigen (PSA) relapse-free rates for 5- and 8-year were 64.6% and 52.5%, and the clinical local control rates for 5 and 8 years were 75.3% and 69.9%, respectively. The preradiation therapy PSA and the Gleason score were the factors that significantly associated with PSA relapse-free survival. Sixteen of 46 patients (35%) showed at least one form of late toxicities. Of these, 3 patients experienced late complications of Grade 3 (urinary, 2, proctitis, 1). CONCLUSION: The treatment results were fairly good and were consistent with those in Western countries, indicating that this study shows the preliminary status of 3D-CRT for the locally advanced prostate cancer in Japan. Preradiation therapy PSA seems to be a significant predictor of PSA relapse-free survival (p = 0.004) after neoadjuvant androgen suppression.
Adenocarcinoma↗
A HER2/NEU-derived peptide, a K(d)-restricted murine tumor rejection antigen, induces HER2-specific HLA-A2402-restricted CD8(+) cytotoxic T lymphocytes.
We have identified an H-2K(d)-binding peptide, HER2p780 (PYVSRLLGI), derived from murine HER2/neu (HER2), that can induce HER2-specific murine cytotoxic T lymphocytes (CTL). Weekly vaccination of BALB/c mice by syngeneic dendritic cells pulsed with HER2p780 peptide, entirely common to murine and human HER2, suppressed growth of pretransplanted HER2-expressing syngeneic tumors. A HER2-expressing human cancer cell line SKOV3 transfected with murine H-2K(d) cDNA could also be lysed by HER2p780-specific murine CTLs, indicating that human HER2-expressing cancer cells can process and present the cognate peptide in the context of H-2K(d). Since H-2K(d) and HLA-A2402 molecules have similar anchor motifs, the possibility of inducing HER2-specific CTL activity with HER2p780 in HLA-A2402 individuals was examined. CD8(+) CTL clones specific for HER2-expressing cancer cell lines were established from peripheral blood lymphocytes with HLA-A2402 by repeatedly sensitizing with peptide-pulsed autologous dendritic cells as well as peripheral blood mononuclear cells. Detailed analysis of their specificity revealed that the cytotoxicity of CTL clones is specific for the cognate peptide with HLA-A2402 restriction. The results suggest that HER2p780 is a unique peptide that may function as a tumor rejection antigen peptide in HLA-A2402 individuals, as it was directly proven here to function in a murine tumor system.
Animals↗
Tumor bulk as a prognostic factor for the management of localized aggressive non-Hodgkin's lymphoma: a survey of the Japan Lymphoma Radiation Therapy Group.
PURPOSE: To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL). METHODS AND MATERIALS: The survey was carried out at 25 radiation oncology institutions in Japan in 1998. The 5-year event-free (EFS) and overall survival rates (OAS) were calculated, and univariate and multivariate analyses were done to identify which of the following factors, namely, gender, age, performance status (PS), serum lactate dehydrogenase (LDH) level, Stage (I vs. II), tumor bulk (maximum diameter), and treatment, were significant from the viewpoint of prognosis. RESULTS: A total of 1141 patients with Stage I and II NHL were treated by the Japanese Lymphoma Radiation Therapy Group between 1988 and 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate- and high-grade lymphomas in working formulation, constituted the core of this study. Primary tumors arose mainly from extranodal organs (71%) in the head and neck (Waldeyer's ring: 36% and sinonasal cavities: 9%). The factors associated with poorer prognosis were age over 60 years old (p < 0. 0001), radiation therapy alone (p < 0.0001), PS = 2-4 (p = 0.0011), (sex male, p = 0.0078), a bulky tumor more than 6 cm in maximum diameter (p = 0.0088), elevated LDH (p = 0.0117), and stage II (p = 0.0642). A median dose of 42 Gy was delivered mainly to the involved fields. Short-course chemotherapy was provided in 549 (70%) patients. The 5-year OAS and EFS rates for all patients were 71% and 67%, respectively. According to the stage-modified International Prognostic Index, the 5-year EFS of the patients with risk factors from 0 to 1 was 76%, 61% for patients with two risk factors, and 26% for patients with three or more risk factors. CONCLUSION: Extranodal presentation, especially Waldeyer's ring and sinonasal cavities, is encountered more frequently in Japan than in Western countries. Tumor bulk is an important prognostic factor in patients with localized aggressive extranodal NHL. Short course chemotherapy followed by radiation therapy was associated with prolonged survival in patients with localized aggressive NHLs of extranodal origin and 0-1 risk factor.
Adult↗
A rat model for human T lymphocyte virus type I-associated myeloneuropathy. down-regulation of bcl-2 expression and increase in sensitivity to TNF-alpha of the spinal oligodendrocytes.
We reported that the tumor necrosis factor-alpha (TNF-alpha) expression and apoptotic death of oligodendrocytes appeared to be a major pathogenesis of the demyelination of spinal cords of Wistar-King-Aptekman-Hokudai (WKAH) rats with human T lymphocyte virus type I (HTLV-I) infection, HAM rats. In the present study, we examined the sensitivity to TNF-alpha-induced cell death of in vitro-separated oligodendrocytes from HTLV-I-infected WKAH rats. Although the number of non-viable oligodendrocytes increased by adding recombinant TNF-alpha, in a dose-dependent manner, in both HTLV-I-infected and uninfected control rats, oligodendrocytes from the infected rats were more susceptible to TNF-alpha. In situ detection of DNA fragmentation showed apoptotic death of oligodendrocytes. The expression of bcl-2, an anti-apoptotic gene, was strongly down-regulated in oligodendrocytes of the infected rats but not in the control rats. We suggest that the down-regulation of bcl-2 expression in the oligodendrocytes of the HTLV-I-infected rats may increase the susceptibility to TNF-alpha-induced apoptosis of oligodendrocytes, the result being development of HTLV-I-induced myeloneuropathy in rats.
Animals↗
UvrA and UvrB suppress illegitimate recombination: synergistic action with RecQ helicase.
Illegitimate recombination is a major cause of genetic instability in prokaryotes as well as in eukaryotes. This recombination usually occurs at a low frequency, but it is greatly enhanced by UV irradiation or other environmental stresses. DNA damages produced by these environmental stresses are thought to induce DNA double-strand breaks, leading to illegitimate recombination. In this paper we show that UV-induced illegitimate recombination is enhanced by mutations of nucleotide excision repair genes, uvrA or uvrB, and partially by uvrC mutation, but not by uvrD mutation. Unexpectedly, the recombination was enhanced by the uvrA uvrB double mutation even without UV irradiation, but the uvrB uvrC double mutation has not shown this effect, suggesting that illegitimate recombination is mostly suppressed by UvrA and UvrB. Moreover, illegitimate recombination was synergistically enhanced by the recQ uvrA double mutation. In addition, overproduction of the UvrA protein suppressed the hyperrecombination phenotype of the recQ or uvrB mutant, but it did not affect the UV-sensitive phenotype of the uvrB mutant. We concluded that the UvrAB complex suppresses illegitimate recombination in a pathway shared with RecQ helicase. In addition, UvrA protein alone can suppress illegitimate recombination in the pathway, in which RecQ helicase and UvrAB complex work. Possible functions of the proteins involved in these pathways are also discussed.
Adenosine Triphosphatases↗
Preferential infection of neuronal and astroglia cells by Akabane virus in primary cultures of fetal bovine brain.
Akabane virus is a member of the genus Bunyavirus; it is pathogenic for ruminants and transmitted by arthropod vectors. Infection of adult cattle and sheep causes a transient viremia without obvious clinical signs, while infection of pregnant animals often causes fetal abnormalities including hydranencephaly, poliomyelitis and arthrogryposis. Infectious virus or viral antigens is present in the brain, spinal cord and skeletal muscle of infected fetuses. To understand the interaction between Akabane virus and bovine brain cells, we investigated the viral tropism using primary cultures of fetal bovine brain. The cultured neuronal cells, astroglia cells and microglia cells were distinguished by cell type specific antisera. Akabane virus was found to infect neuronal cells and astroglia cells, which led to degenerative death. No microglia cells were found infected. In some brain cultures, we observed different sensitivities of the cells to two Akabane virus strains: an attenuated strain infected and spread more readily than wild type virus. This difference was not observed in a hamster fibroblast cell line. Both viral and host determinants might be involved in the different susceptibility of brain cells to Akabane virus infection.
Animals↗
Specific c-kit mutations in sinonasal natural killer/T-cell lymphoma in China and Japan.
Sinonasal lymphoma is one of the constituents of lethal midline granuloma, which is a clinical term for progressive, destructive lesions affecting the midline of the face. The majority of sinonasal lymphomas, especially those showing polymorphous patterns of proliferation and thus termed polymorphic reticulosis, recently were categorized as sinonasal natural killer/T-cell lymphomas. They are more prevalent in Asia than Europe or North America and are associated with EBV infection. Twenty-three cases with sinonasal natural killer/T-cell lymphomas were collected from two high-incidence regions: Beijing, China (14 cases) and Osaka, Japan (9 cases). c-kit mutations were analyzed on paraffin-embedded specimens by PCR-single-strand conformation polymorphism followed by direct sequencing; the c-kit proto-oncogene encodes a receptor of tyrosine kinase, which plays an important role in the regulation of normal and neoplastic hematopoiesis by the interaction with its specific ligand, termed stem cell factor. Twelve single nucleotide substitution mutations were seen in 23 cases. Ten of 14 Chinese cases (71.4%) had mutations at exon 11 or exon 17, whereas only two of nine Japanese cases (22.2%) had mutations, showing a significant difference in frequency between Chinese and Japanese cases. Furthermore, seven of eight mutations (92%) in exon 17 occurred at codon 825 and three of four mutations (75%) in exon 11 occurred at codon 561. Such a specificity has not been reported before, and these results, taken together, suggest that location-specific differences in etiological factors cause specific mutations in c-kit gene.
Adolescent↗