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T Miyahara

Publications and source records attributed to T Miyahara.

At least 73 records · Page 4Linked to original sources

Twin helical undulator beamline for soft X-ray spectroscopy at SPring-8.

A very high resolution soft X-ray beamline, BL25SU, has been designed and is under construction at SPring-8. Completely right or left circularly polarized light is supplied on a common axis of a newly designed twin helical undulator. A helicity modulation up to 10 Hz can be performed using five kicker magnets. The fundamental radiation covers the region 0.5-3 keV. Higher-order radiation is rather weak on the axis. A monochromator with varied-line-spacing plane gratings is installed to cover the region below 1.5 keV. A very high resolution beyond 10(4) is expected for the whole energy region.

Journal Article↗

Association of high-altitude pulmonary edema with the major histocompatibility complex.

BACKGROUND: A constitutional susceptibility has been suggested in the development of high-altitude pulmonary edema (HAPE) because HAPE generally affects healthy young people, some of whom suffer recurrent episodes. We examined whether immunogenetic susceptibility is present in HAPE-susceptible subjects. METHODS AND RESULTS: The frequencies of human leukocyte antigen (HLA) alleles in 28 male and 2 female subjects with a history of HAPE were compared with those in 100 healthy volunteers. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically. The pulmonary hemodynamics on admission to the hospital and the ventilatory response to hypoxia and hypercapnia were retrospectively examined in 10 of the HAPE-susceptible subjects. HLA-DR6 was positive in 14 (46.7%) of the subjects with HAPE but only 16.0% of the control subjects (P=.0005), and HLA-DQ4 was positive in 12 (40.0%) of the subjects with HAPE but only 10.0% of the control subjects (P=.0001). HLA-DR6 or HLA-DQ4 was positive in 8 (100%) of the subjects with recurrent HAPE. The pulmonary arterial pressure on admission of the HLA-DR6-positive subjects with HAPE was significantly higher than that of the HLA-DR6-negative subjects with HAPE. CONCLUSIONS: There were significant associations of HAPE with HLA-DR6 and HLA-DQ4 and of pulmonary hypertension with HLA-DR6. An immunogenetic susceptibility, which is associated with HLA class II alleles located within the major histocompatibility complex, may underlie the development of HAPE, at least in some of its forms.

Adolescent↗

Lecithinized superoxide dismutase attenuates phorbol myristate acetate-induced injury in isolated dog lung.

Lecithinized superoxide dismutase, a lecithin derivative bound to recombinant human CuZn superoxide dismutase, has a higher affinity for cells such as polymorphonuclear leukocytes and endothelial cells than recombinant human CuZn superoxide dismutase has. We determined the protective effects of lecithinized superoxide dismutase on the increased microvascular permeability induced by phorbol myristate acetate (PMA) in isolated dog lungs. Microvascular permeability was assessed by the capillary filtration coefficient (Kf,c) and solvent drag reflection coefficient (sigma(f)). PMA (13.3 microg) increased microvascular permeability, as evidenced by an increase in Kf,c and the small sigma(f) value. Lecithinized superoxide dismutase at both low (4800 U) and high doses (48,000 U) inhibited the PMA-induced increase in Kf,c, but only the high dose of lecithinized superoxide dismutase attenuated the decrease in sigma(f). Recombinant human CuZn superoxide dismutase did not affect the PMA-induced increase in vascular permeability at either a low (4800 U) or a high dose (48,000 U). These findings suggest that lecithinized superoxide dismutase has a protective effect against oxygen radical-induced lung injury in isolated dog lungs.

Animals↗

An open-label dose comparison study of ondansetron for the prevention of emesis associated with chemotherapy prior to bone marrow transplantation.

Nausea and vomiting are significant side effects in bone marrow transplant (BMT) patients who receive high-dose preparative regimens. Higher than conventional ondansetron doses and continuous infusion might improve emetic control, because of the high doses and combinations of chemotherapy (CT) used in this setting. Our objective was to conduct a prospective, randomized study comparing two different administration methods of high-dose ondansetron during a BMT preparative regimen in breast cancer patients. Patients were eligible if they were nonpregnant women over 18 but under 65 years of age, undergoing highly emetogenic CT in preparation for autologous BMT. All patients received ondansetron as an intermittent (INT = 24 mg i.v. q 12 h/day) or continuous intravenous infusion (CIV = 8 mg i.v. loading dose followed by a continuous infusion of 2 mg/h per day). A total of 66 patients were enrolled in the study (n = 34, INT; n = 32, CIV). There was no statistical difference between treatment groups in the worst grade of emesis for the entire study period (P = 0.49). Greater than 90% of all patients were graded as failures (> or = 5 emetic episodes or need for rescue antiemetics). Complete control (no vomiting episodes) and complete plus major control (1-2 emetic episodes) per day ranged from 8% to 85% and 11% to 91%, respectively. There was no significant difference between the treatment arms in: grade of emesis, episodes of vomiting and retching, nausea scores, and mean number of rescue medications administered. There were no differences in efficacy when high-dose ondansetron was given as CIV or INT for the control of nausea and vomiting in breast cancer patients undergoing high-dose CT for autologous BMT. Ondansetron alone was not adequate to provide sustained control of CT-induced nausea and vomiting over the entire 5-day study period. A combination of antiemetics targeting various mechanisms of CT-induced nausea and vomiting may be necessary to improve response rates.

Adult↗

Inflammatory cytokines in BAL fluid and pulmonary hemodynamics in high-altitude pulmonary edema.

To evaluate the pathogenesis of high-altitude pulmonary edema (HAPE), we performed bronchoalveolar lavage (BAL) and pulmonary hemodynamic studies in seven patients with HAPE at its early stage. We measured cell counts, biochemical contents, and concentrations of pro-inflammatory cytokines including interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha and of anti-inflammatory cytokines including IL-1 receptor antagonist (ra) and IL-10 in the BAL fluid (BALF). All patients showed increased counts for total cells, alveolar macrophages, neutrophils and lymphocytes, and markedly elevated concentrations of proteins, lactate dehydrogenase, IL-1beta, IL-6, IL-8, TNF-alpha and IL-1ra. The levels of IL-1alpha and IL-10 were not increased. Patients also showed pulmonary hypertension with normal wedge pressure. Both the driving pressure obtained as pulmonary arterial pressure minus wedge pressure and the PaO2 under room air were significantly correlated with the concentrations of IL-6 and TNF-alpha in the BALF. These findings suggest that the inflammatory cytokines play a role at the early stage of HAPE and might be related to pulmonary hypertension.

Adult↗

In oesophageal squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis.

Vascular endothelial growth factor (VEGF) affects malignant tumours by promoting angiogenesis. The tumour-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on oesophageal carcinoma and the connection between VEGF and p53. One hundred and nine resected oesophageal squamous cell carcinomas were examined. VEGF expression was analysed by immunohistochemical staining. Sixty-five tumours (59.6%, 65 out of 109) were classified as VEGF positive. A significant correlation was found between the VEGF expression and both the depth of invasion (P = 0.0001) and lymph node metastasis (P < 0.0001). With regard to p53, we compared the expression of VEGF with the mutation of p53, examined using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing in tumour samples obtained from 36 patients who we have reported previously. The VEGF expression was significantly correlated to p53 mutation (P = 0.0291). To evaluate the angiogenesis, microvascular density (MVD) was counted, and endothelial cells were stained immunohistochemically using anti-CD34 monoclonal antibody against 29 cases with invasion limited to the submucosal layer. The average MVD had a tendency to correlate to VEGF expression (P = 0.1626). The prognoses of patients with VEGF-positive primary tumours were significantly worse than for those with VEGF-negative primary tumours (P = 0.0077). We have assumed that VEGF contributes to aggressive characteristics in oesophageal carcinomas and that VEGF expression might be affected by p53 status.

Carcinoma, Squamous Cell↗

Activation of microvascular endothelial cells in active ulcerative colitis and detection of inducible nitric oxide synthase.

Endothelial nitric oxide (NO) synthase (NOS) that is expressed constitutively on microvascular endothelium is believed to be essential to systemic and/or local vascular integrity. Endothelial cells (ECs) were reported to express inducible NOS (iNOS) under some conditions iNOS expression indicates vascular activation. In this study we examined microvascular activation using ECs obtained from patients with ulcerative colitis (UC). We cultured ECs from the mesenteries of surgical UC patients and assayed NOS activity by NADPH-diaphorase cytochemistry and immunocytochemistry with an anti-iNOS antibody. Strong NOS activity was demonstrated on the cells from UC patients (5/5), whereas no activity was detected on the cells from cancer patients and human umbilical vein endothelial cells (HUVEC 0/5, 0/5). Strong iNOS activity was detected by immunoreaction, and large amounts of NO generated were detected by the conversion from [14C]arginine to [14C]citrulline (HUVEC 624+/-376 vs. EC-UC 1,492+/-233 dpm). These results suggest the possibility that ECs express spontaneous and continuous iNOS in active UC. They indicate a close relationship of vascular activation with the pathogenesis of UC.

Adult↗

Specific immunoadsorbent for myasthenia gravis treatment: development of synthetic peptide designed to remove antiacetylcholine receptor antibody.

We have developed Medisorba MG, a new immunoadsorbent column for myasthenia gravis (MG). The alpha 183-200 segment of the Torpedo Californica acetylcholine receptor (AChR) is recognized as the acetylcholine binding site by the blocking antibody, which is one of the anti-AChR antibodies involved in the pathogenesis of MG. As a specific affinity ligand to remove the blocking antibody, Torpedo alpha 183-200 was synthesized and immobilized covalently to porous cellulose beads. This immunoadsorbent showed specific removal of the blocking antibody without reducing IgG and albumin levels significantly in clinical evaluation and in vitro study. Clinical improvement was found in 78% of the cases, and no adverse effects were observed in any case. The Medisorba MG column has been confirmed as a useful device for the treatment of MG.

Acetylcholine↗

Pharmacokinetic evaluation of amphotericin B in lung tissue: lung lymph distribution after intravenous injection and airspace distribution after aerosolization and inhalation of amphotericin B.

We have studied the pharmacokinetics of amphotericin B (AmB) in lung lymph circulation and bronchial-wash fluid after intravenous infusion and inhalation, respectively. For two experiments with awake sheep, we used lung lymph fistulas and tracheotomy. In experiment 1, AmB concentrations in plasma and lung lymph after intravenous infusion of AmB (1 mg/kg of body weight) over 1.5 h were measured. The mean peak in plasma level was 756.0 +/- 188.8 ng/ml at 3 h after the start of infusion, and the level then decreased gradually to 194.8 +/- 28.9 ng/ml at 24 h. The stable and maximal levels in lung lymph last 5 to 9 h after the start of AmB infusion. The concentrations in lung lymph after 9 h were slightly higher than those in plasma. Thus, the lung lymph-to-plasma ratio of AmB concentrations increased gradually during infusion, and the ratio was more than 1.0 after the end of infusion, suggesting that AmB could be easily moved from plasma to pulmonary interstitium and/or lung lymph circulation. In another experiment, 5 or 30 mg of aerosol AmB was inhaled, and the concentration of AmB in the bronchial-wash fluid was determined by bronchoalveolar lavage. The peak AmB concentration in the fluid was observed at 0.5 h. After that, AmB was slowly eliminated over 24 h. The area under the concentration-time curve for 30 mg of inhaled AmB was higher than that for 5 mg, but maximum concentrations of AmB in serum for 5 and 30 mg were almost similar. These observations identify the pharmacokinetic characteristics of AmB in the lung and may provide a new insight into the strategy for clinical treatment of fungal pneumonia.

Administration, Inhalation↗

The effect of Kampo formulae on bone resorption in vitro and in vivo. I. Active constituents of Tsu-kan-gan.

Four water extracts of Kampo formulae (Yi-kkan-sen, Dai-ho-in-gan, Ni-chi-gan, Tsu-kan-gan) were screened for their inhibitory activities on bone resorption induced by parathyroid hormone (PTH) in organ culture using neonatal mouse parietal bones. Among the Kampo formulae, Tsu-kan-gan (TKG) showed the most potent inhibitory activity. We further fractionated the TKG water extract by monitoring the inhibitory activity on bone resorption stimulated by PTH in vitro. The MeOH fraction of the water extract inhibited PTH-stimulated bone resorption, and its inhibitory activity was more potent than those of other fractions. The MeOH fraction was then subjected to Sephadex LH-20 column chromatography to give fractions I, II and III, which were examined for bone resorption activity. Fraction I inhibited PTH-stimulated bone resorption, and its inhibitory activity was more potent than those of the other fractions. Upon oral administration of the three fractions (100 mg/kg/d) to ovariectomized (OVX) mice, fractions I and III prevented the decrease of bone mineral density (BMD) of the lumbar vertebra. Eleven compounds isolated from the MeOH fraction were examined for their inhibitory effect on PTH-stimulated bone resorption. Among them, berberine (1), syringin (3), limonin (4) and mangiferin (10) showed a significant inhibitory effect on bone resorption. In the formation assay of osteoclast-like cells, these compounds decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs). The inhibitory effect of TKG on bone resorption may be at least partly due to the inhibitory action of these compounds.

Animals↗

Antiosteoporotic activity of the stems of Sambucus sieboldiana.

We previously found that a methanolic extract of the stems of Sambucus sieboldiana inhibited bone resorption in organ culture. In this study, we further fractionated the methanol extract guided by the activity towards bone resorption stimulated by parathyroid hormone (PTH) in vitro. The ethyl acetate fraction (EtOAc Fr.) of the methanolic extract inhibited PTH-stimulated bone resorption of neonatal mouse bones, and the inhibitory activity was more potent than those of other fractions. Oral administration of the EtOAc Fr. (50 and 100 mg/kg/d) to ovariectomized (OVX) rat prevented the decrease in bone mineral density (BMD) of the lumbar (L2-4) vertebra, indicating that the EtOAc Fr. is effective in vivo. Furthermore, the EtOAc Fr. (50, 100 and 150 mg/kg/d) decreased the serum calcium level elevated in low calcium dietary rats. The phenolic constituents of the EtOAc fraction were examined for their inhibitory effect on bone resorption stimulated by PTH in neonatal mouse bone. Among them, vanillic acid, vanillin and coniferyl alcohol showed significant inhibitory effects on bone resorption. Of the compounds examined, vanillic acid was found to have a significant inhibitory effect on the decrease of BMD in OVX mice. Therefore, the EtOAc Fr. of S. sieboldiana showed a suppressive effect on bone resorption in vitro and in vivo. In addition, the inhibitory effects of the EtOAc Fr. on bone resorption may be at least partly due to the inhibitory action of vanillic acid.

Acetates↗

[A clinical comparison of orthodox myringoplasty and a simple method with fibrin glue].

Orthodox myringoplasty was clinically compared with a simple method with fibrin glue which rapidly came into wide use after the report of Yuasa in 1989. In Okayama Saiseikai General Hospital, orthodox myringoplasty was performed in 109 ears from September 1988 to November 1995, and the simple method with fibrin glue was performed in 84 ears from May 1991 to November 1995. The results showed that 90.8% of all eardrum perforations treated by orthodox myringoplasty and 79.8% of all eardrum perforations treated by the simple fibrin glue method were successfully closed. The rate of closure with each method was low in patients with large perforations. Generally speaking the hearing prognosis with each method, hearing improvement was observed right after the operation, and the improved hearing became stable about six months later. The difference in hearing prognosis was investigated in patients with small or large perforations. In patients with large perforations, the improved hearing slightly worsened a year after treatment by orthodox myringoplasty. These results show that the simple method with fibrin glue had the advantage of good hearing prognosis over orthodox myringoplasty, while it was inferior in the rate of closure of large eardrum perforations. It was considered that a simple fibrin glue method should be devised to prevent reperforation and should be used for patients with large perforations.

Adolescent↗

Pharmacokinetic characteristics of the novel anticancer agent CPT-11 and its active metabolite in plasma and lung lymph fluid following intravenous administration to sheep.

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11, 100286-90-6) is one of the most promising novel anticancer agents, especially for lung cancer. 7-Ethyl-10-hydroxycamptothecin (SN-38), an active metabolic of CPT-11, has much stronger cytotoxicity than CPT-11. The present study was designed to evaluate the distribution and behavior of CPT-11 and SN-38 in lung lymph circulation following intravenous infusion. Awake sheep with chronically instrumented lung lymph fistulas were prepared. The concentrations of CPT-11 and SN-38 in plasma and lung lymph fluid were measured after intravenous infusion of 100 mg/body of CPT-11 for 90 min. SN-38 constantly showed higher lymph to plasma concentration ratios than those of CPT-11, and the % area under the curve (AUC) ratio of SN-38/CPT-11 in lymph fluid was significantly higher than that in plasma. These data indicated that SN-38 distributed in lung tissue moved more easily into lung lymph fluid than CPT-11, and might be more rapidly metabolized in lung tissue than plasma. CPT-11 may have favorable therapeutic effects on intrathoracic malignancies such as lung cancer and lymph metastasis.

Animals↗

Autoimmune pancreatitis as a new clinical entity. Three cases of autoimmune pancreatitis with effective steroid therapy.

The most common forms of chronic pancreatitis are related to alcohol ingestion, whereas the entity of non-alcohol-associated (idiopathic) pancreatitis is poorly understood. Autoimmunity has been suggested as a possible etiologic factor of idiopathic chronic pancreatitis. A total of 362 Japanese patients underwent endoscopic retrograde pancreatography (ERP) for suspected pancreatic disease, and 161 were diagnosed with chronic pancreatitis. Among them, we found three cases (1.86% incidence) of unique chronic pancreatitis, in which ERP revealed diffuse narrowing of the main pancreatic duct with an irregular wall. We diagnosed these three patients as having pancreatitis associated with an autoimmune mechanism morphologically and biochemically and started them on steroid therapy. The characteristics of the these three patients were as follows: hypergammaglobulinemia, eosinophilia, ultrasonography showing hypoehoic diffuse swelling in the pancreas (sausage-like appearance), ERP showing diffuse narrowing of the main pancreatic duct with irregular like thumbprint-like marks, reversible exocrine insufficiency, and positive anti-carbonic anhydrase II antibody. After one month of the treatment with steroids, pancreatitis dramatically improved morphologically and enzymatically. Here we describe these cases of the suspected autoimmune chronic pancreatitis. We must recognize the concept and the features of autoimmune pancreatitis in order to avoid unnecessary surgery as pancreatic cancer.

Aged↗

Genetic alterations in patients with esophageal cancer with short- and long-term survival rates after curative esophagectomy.

OBJECTIVE: The objective of this study was to ascertain the exact relation between specific oncogenes and long- and short-term survival rates in patients with esophageal cancer. SUMMARY BACKGROUND DATA: Recent developments in molecular biology have shown that several oncogenes and suppressor genes are involved in the development of esophageal cancer. However, the role of these genes still is unknown. METHODS: The clinical outcome of 84 cases of R0-resected esophageal carcinomas (from 1986-1993) and the molecular and biologic characteristics of these tumors were studied. The patients studied were divided into three groups, which were designated as follows: shortest term survivors (up to 6 months), short-term survivors (7-12 months), and long-term survivors (>5 years). These groups included 23, 17, and 44 subjects, respectively. For the genomic analysis, CyclinD1, int-2, murine double minute 2 (MDM2), retinoblastoma, p53, adenomatous polyposis coli (APC), deleted in colorectal carcinoma (DCC), and human papillomavirus were studied in these patients. The regrowth capability of primary cultures and the clinicopathologic characteristics of these patients also were analyzed. RESULTS: The CyclinD1 and int-2 genes, which are located in the 11q13 chromosome, and the MDM2 gene were related to short survival. However, the p53 mutation and human papillomavirus infection were not related to short-term survival. The average ratio of genomic abnormalities to genes examined was higher in the shortest and short-term survival groups than in the long-term survival group. Regrowth capability in primary cultures also was related to short-term survival. Among the long-term survival patients, 7 (16%) of 44 cases suffered further cancer after esophagectomy. CONCLUSIONS: These results suggest that the 11q13 amplicon and MDM2 may play an important role in the progression of esophageal cancer, and an accumulation of genomic abnormalities may result in poor prognosis. Careful follow-up testing for double cancer is needed in long-term survivors of esophageal cancer.

Chromosome Aberrations↗

Possible application of transmitted laser light for the assessment of human pulpal vitality.

The purpose of this study was to determine whether use of transmitted laser light would enable a better assessment of human pulpal vitality than back-scattered light does (LDF: laser Doppler flowmetry). The experiments were carried out on ten upper central incisors in six subjects aged 23-28 years; five of the teeth were vital with no restoration, and five were non-vital. For use with transmitted laser light, the fibers within the probe of a conventional LDF apparatus were used, one for transmitting light onto the buccal surface, the other for receiving it at the palatal surface of the same tooth. For LDF, the probe was fixed at the buccal surface. Blood flow was measured at three different locations on each experimental tooth: the incisal third, the center and the cervical third of the tooth crown. In non-vital teeth, 1) output signals with transmitted laser light all registered zero, and no oscillation could be seen in recordings from any location on the tooth, but 2) LDF signals were above zero, there were regular oscillations related to heart rate, and passive increases in blood flow (corresponding to blood pressure increases) were recorded from both the center and the cervical third of the tooth, indicating that LDF registered blood flow of non-pulpal origin. In vital teeth, LDF signals were significantly higher than in non-vital teeth at each location on the tooth. At the central site on vital teeth, the output signals for transmitted laser light were about twice those seen with LDF, and passive blood flow changes corresponding to blood pressure increases were more clearly observed. These results indicated that transmitted laser light would be useful for the assessment of tooth pulp vitality both because the blood flow signals did not include flow of non-pulpal origin, and because its output signals and response to blood flow changes were clear and could easily be monitored.

Dental Pulp↗