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Biomedical subjects

K Ando

Publications and source records attributed to K Ando.

At least 145 records · Page 8Linked to original sources
PubMed1999

Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy.

PURPOSE: The irradiation system and biophysical characteristics of carbon beams are examined regarding radiation therapy. METHODS AND MATERIALS: An irradiation system was developed for heavy-ion radiotherapy. Wobbler magnets and a scatterer were used for flattening the radiation field. A patient-positioning system using X ray and image intensifiers was also installed in the irradiation system. The depth-dose distributions of the carbon beams were modified to make a spread-out Bragg peak, which was designed based on the biophysical characteristics of monoenergetic beams. A dosimetry system for heavy-ion radiotherapy was established to deliver heavy-ion doses safely to the patients according to the treatment planning. A carbon beam of 80 keV/microm in the spread-out Bragg peak was found to be equivalent in biological responses to the neutron beam that is produced at cyclotron facility in National Institute Radiological Sciences (NIRS) by bombarding 30-MeV deuteron beam on beryllium target. The fractionation schedule of the NIRS neutron therapy was adapted for the first clinical trials using carbon beams. RESULTS: Carbon beams, 290, 350, and 400 MeV/u, were used for a clinical trial from June of 1994. Over 300 patients have already been treated by this irradiation system by the end of 1997.

Calibration↗
PubMed1999

In vivo disturbance of hematopoiesis in mice persistently infected with murine cytomegalovirus: impairment of stromal cell function.

Although the pathogenic effects of a primary cytomegalovirus (CMV) infection on hematopoiesis has been largely investigated so far, the effects of a persistent or latent infection have yet to be elucidated. The effects of persistent CMV infection on hematopoiesis thus were examined using BALB/c mice at 4 weeks postinfection with 0. 2 LD50 of murine CMV (MCMV) infection as a persistent infection model. The parameters of constitutive hematopoiesis of MCMV persistently infected mice were completely identical to those of the control. However, the inductive hematopoiesis, examined by the autologous marrow reconstitution after 5-fluorouracil administration, was significantly impaired in the MCMV persistently infected mice (P < 0.05). In a colony-forming unit-spleen assay and a long-term bone marrow culture system, a decreased capacity of bone marrow stromal cells to support hematopoiesis was observed in the MCMV-infected mice in comparison with the controls. The existence of MCMV DNA in the adherent cells of long-term bone marrow culture from the MCMV-infected mice were confirmed by a polymerase chain reaction but not in the nonadherent cells. Furthermore, the increased expression level of tumor necrosis factor-alpha by stromal cells was also observed by semiquantitative reverse transcriptase-polymerase chain reaction. These results therefore strongly suggest that MCMV remains to infect the stromal cells while also inhibiting inductive hematopoiesis through the impairment of the stromal cell functions in the MCMV persistently infected mice.

Animals↗
PubMed1999

Correlation of unilateral thoracoscopic lung volume reduction with improvement in lung function and exercise performance in patients with severe pulmonary emphysema.

This study was conducted to investigate the correlation of thoracoscopic lung volume reduction to changes in pulmonary function and exercise performance in patients with pulmonary emphysema. Unilateral thoracoscopic lung volume reduction treatment was performed in 30 patients with severe pulmonary emphysema. If large bullae were present, they were excised using an endoscopic stapling device, and the emphysematous pleura was contracted by neodymium:yttrium-aluminium-garnet laser to reduce the volume of nonfunctional lung air space. Pulmonary function and incremental exercise tests were performed before and at least 3 months after treatment. Follow-up functional evaluation showed a highly significant improvement in the forced expiratory volume in 1s (FEV1), forced vital capacity, static compliance, and maximal oxygen uptake. The functional residual capacity as measured by the gas dilution method (FRCgas), was unchanged; however, it was found to be decreased significantly when measured by body plethysmograph (FRCbox). Positive correlations existed between the reduction in FRCbox and the increase in FEV1 (r = 0.586, P = 0.0042) and maximal oxygen uptake (r = 0.550, P = 0.018). Pulmonary ventilation and exercise ability in patients with pulmonary emphysema were improved in a volume-dependent manner by thoracoscopic lung volume reduction. These findings indicate that patients with a preoperative trapped gas volume level exceeding 11 would be ideal candidates for thoracoscopic lung volume reduction.

Aged↗
PubMed1999

Medial prefrontal cortex is involved in the discriminative stimulus effects of nicotine in rats.

RATIONALE: Central nicotinic receptors have been reported to be involved in the discriminative stimulus (DS) effects of nicotine. OBJECTIVES: The purpose of the present study was to investigate the role of the medial prefrontal cortex (mPFC) and the medial habenular nucleus (mHb) in the DS effects of nicotine. METHODS: Substitution tests with nicotine administered into mPFC and mHb were conducted in rats trained to discriminate nicotine (0.5 mg/kg, SC) from saline in a two-lever, food reinforced, operant task. RESULTS: Nicotine (40 microg) administered into mPFC substituted for nicotine (0.5 mg/kg, SC), whereas nicotine administered into mHb did not. CONCLUSIONS: Together with our previous study indicating that the nucleus accumbens and the ventral tegmental area are partially involved in the DS effects of nicotine, the present study suggests that mPFC is primarily involved in the DS effects of nicotine.

Animals↗
PubMed1999

Effects of monoclonal antibodies directed at cell surface molecules on murine experimental autoimmune uveoretinitis.

BACKGROUND: To elucidate the immunopathogenic mechanism of endogenous uveitis, the effects of monoclonal antibodies to molecules involved in the immune response were studied in murine experimental autoimmune uveoretinitis (EAU). METHODS: Monoclonal antibodies to CD4, CD8, Ia(k), Ia(d), lymphocyte function-associated antigen-1 (LFA-1), and intercellular adhesion molecule-1 (ICAM-1) were used in this study. The monoclonal antibodies were added in the culture of lymph node cells from B10.BR mice(H-2(K)) immunized with interphotoreceptor retinoid-binding protein (IRBP) and the inhibition of proliferative response was measured. In vivo, IRBP-immunized mice were treated with a high dose of the antibody, and the EAU induction was examined both clinically and pathologically. RESULTS: Proliferative response of IRBP-sensitized lymph node cells was inhibited strongly by anti-CD4 or anti-LFA-1 monoclonal antibody and moderately by anti-Ia(k) or anti-ICAM-1 monoclonal antibody. In contrast, no inhibitory effect of anti-CD8 or anti-Ia(d) monoclonal antibody was observed. In vivo treatment with anti-CD4 monoclonal antibody inhibited development of EAU in a dose-dependent manner, while in vivo treatment with other monoclonal antibodies did not cause significant suppression of EAU. CONCLUSIONS: CD4, Ia, LFA-1, and ICAM-1 molecules play important roles in the antigen-specific immune response of lymphocytes. However, in in vivo treatment with monoclonal antibodies to these molecules, only anti-CD4 monoclonal antibody had a strong inhibitory effect on the development of EAU.

Animals↗
PubMed1999

Elevated intracellular IFN-gamma levels in circulating CD8+ lymphocytes in patients with fulminant hepatitis.

BACKGROUND/AIMS: Fulminant hepatitis usually takes a rapidly progressive course, terminating in death within a short period. Experimental studies have demonstrated that immunological mechanisms play an important role, especially those involving virus-specific CD8+ cytotoxic T lymphocytes and their production of interferon-gamma (IFN-gamma). However, there are no immunological markers for prediction of the development of fulminant hepatitis in man. METHODS: Peripheral blood lymphocytes from four patients with fulminant hepatitis, six with acute hepatitis and 11 healthy volunteers as normal controls were analyzed. Intracellular IFN-gamma production in both CD8 positive and negative T lymphocytes was assessed by flow cytometry. RESULTS: Populations of CD8+ IFN-gamma+ T lymphocytes were significantly increased in patients with fulminant hepatitis, as compared with those with acute hepatitis and normal controls. Production of IFN-gamma in CD8+ T lymphocytes of patients with fulminant hepatitis was also elevated, furthermore significantly correlating with the prothrombin time (r=-0.64, p<0.01). CONCLUSIONS: The capacity for IFN-gamma production by CD8+ lymphocytes is up-regulated in fulminant hepatitis, and this may be important for the development of fulminant hepatitis.

Adult↗
PubMed1999

Light mask 500 lux treatment for delayed sleep phase syndrome.

1. Bright light exposure has been demonstrated as an effective treatment for circadian rhythm sleep disorders. Recent studies suggest that more moderate intensities of light might affect endogenous rhythms. A light mask treatment, using light applied through eyelids during sleep, was tested for Delayed Sleep Phase Syndrome. 2. The active light group (n = 5) received 500 lux light for 3 hours prior to awakening for 12 days. The placebo light group (n = 5) received 0.1 lux light with the same timing. Circadian rhythm phase was assessed from core body temperature and urinary 6-sulfatoxymelatonin measurements. The SIGH-SAD-SR mood scale was administered to assess mood. 3. There were slight trends toward a phase advance of the body temperature rhythm and a phase delay of the melatonin rhythm, and both groups reported anti-depressant benefits. However, no statistically significant effects of 500 lux light mask treatment were demonstrated compared with the placebo-light treatment. 4. More extensive studies will be required to clarify the factors of dose-response and phase-response.

Adult↗
PubMed1999

Rapid ex vivo expansion of human umbilical cord hematopoietic progenitors using a novel culture system.

Cell numbers limit the widespread clinical use of cord blood (CB) for gene therapy and marrow replacement in adults; a simple and effective method for ex vivo expansion of CB primitive progenitor cells (PPC) is required. Recently, the combination of thrombopoietin (TPO) and Flk-2/Flt-3 ligand (FL-2) was reported to support slow proliferation of CB-PPC in stroma-free liquid culture. We established a novel culture system in which the murine stromal cell line HESS-5 dramatically supports the rapid expansion of cryopreserved CB-PPC in synergy with TPO/FL-2. Furthermore, while HESS-5 cells directly adhered to human progenitors during culture, the cultured human cells could easily be harvested without contamination by HESS-5 cells. Within 7 days of culture, a 100-fold increase in CD34bright/CD38dim cells was obtained in serum-containing culture. When HESS-5 cells were physically separated from human progenitor cells in the presence of TPO/FL-2, synergy was blocked, suggesting that HESS-5 cells support proliferation of PPC by direct cell-to-cell interaction. The hematopoietic-supportive effects of this xenogeneic coculture system were then assessed in a very short-term (5 days) serum-free culture. Expansion was further enhanced by addition of stem cell factor (SCF) or interleukin-3 (IL-3). As a result, a 50- to 100-fold increase in CD34bright/CD38dim cells was noted. Colony-forming units in culture (CFU-C) and mixed colonies (CFU-GEMM) were enhanced by 10- to 30-fold and 10- to 20-fold, respectively. Moreover, generation of long-term-culture-initiating cells (LTC-IC) from CD34bright/CD38dim cells was amplified by 25-fold. The severe-combined immunodeficient (SCID) mouse-repopulating cell (SRC) assay confirmed extensive ability of the expanded cells to reconstitute long-term hematopoiesis. These results indicate that this xenogeneic coculture system, in combination with human cytokines, can rapidly generate PPC from cryopreserved CB.

Animals↗
PubMed1999

Preparation and properties of novel gramicidin S analogs possessing a tri-, tetra- or pentamethylene bridge between ornithine side chains.

Gramicidin S (GS) analogs in which the Ndelta atoms of the two Orn side chains are linked by an oligomethylene bridge [-(CH2)n-; n=3-5] were prepared via the bis(p-nitrobenzenesulfonyl) derivative [Orn(NBS)2,2']GS. For comparison the nonbridged secondary amino group-containing analog [Orn(Me)2,2']GS was also prepared. 1H NMR and CD spectral analysis indicated that these analogs adopt the same beta-sheet conformation as GS. The antimicrobial activities of these analogs were very similar, but were slightly dependent on the bridge chain length, the trimethylene-bridged analog being the most potent.

Anti-Bacterial Agents↗
PubMed1999

Convenient preparation of [Orn(Tfa)2]- and [Orn(Boc)2, Orn(Tfa)2]gramicidin S, versatile unsymmetrically protected derivatives of gramicidin S.

Treatment of gramicidin S (GS) with trifluoroacetic anhydride afforded a derivative in which only one of the two Orn side chains was trifluoroacetylated in 72% yield, furnishing the first efficient method for the preparation of a monoprotected derivative of GS. The mono(Tfa) derivative [Orn(Tfa)2']GS was treated with di-tert-butyl dicarbonate to yield dually protected derivative [Orn(Boc)2,Orn(Tfa)2']GS from which another monoprotected derivative [Orn(Boc)2]GS was prepared in high yield. These unsymmetrically protected GS derivatives are versatile starting materials for the preparation of various other GS derivatives. As an example of application of the unsymmetrically protected derivatives, a dimeric GS derivative was prepared via a singly p-nitrobenzenesulfonyl(NBS)-activated derivative [Orn(Boc)2,Orn(NBS)2']GS.

Amino Acid Sequence↗
PubMed1999

Inflammatory pseudotumor of the liver in a patient with chronic hepatitis C: difficulty in differentiating it from hepatocellular carcinoma.

A case of an inflammatory pseudotumor of the liver in a 75-year-old female with chronic hepatitis C whose radiologic features simulated that of hepatocellular carcinoma (HCC) is presented. On imaging studies, hypervascularity by CO2 ultrasound (US) angiography, enhancement at an early phase and isodensity at a late phase by incremental dynamic computed tomography (CT), perfusion defect by CT during arteriography (CTAP), and clinical background of hepatitis C virus (HCV) infection strongly suggested HCC. A US-guided needle biopsy revealed a mainly diffuse and polyclonal proliferation of lymphocytes positive for leukocyte common antigen (pan-lymphocyte cells), L-26 (B cell lymphocytes), and UCHL-1 (T cell lymphocytes), negative for both kappa and lambda light chains and sparsely distributed neutrophils and histiocytes. No lymphoid follicles were observed. The liver tissue around this tumor showed chronic hepatitis with mild activity and mild fibrosis. These histopathologic findings suggested that the diagnosis of inflammatory pseudotumor of the liver was tenable. As it is difficult to differentiate between inflammatory pseudotumor of the liver and HCC by imaging studies alone, supplemental biopsy, where possible, should be obtained when diagnostic imaging of tumors suggesting HCC is carried out. We emphasize that histopathology is a true gold standard in the diagnosis of this disease.

Aged↗
PubMed1999

Involvement of fibrinolytic factors in mid trimester amniotic fluid with development of severe early-onset preeclampsia.

Impaired placental development is a well-known pathogenesis in preeclampsia. The present study was undertaken to elucidate the involvement of fibrinolytic factors in amniotic fluid in midtrimester with development of severe early-onset preeclampsia. Amniotic fluid was obtained by amniocentesis at 15 to 18 weeks of gestation. All specimens were retrospectively identified according to the hospital records as coming from gestations that later had severe early-onset preeclampsia (severe preeclamptic group, n = 9) or gestations with normal outcomes (control group, n = 73). Fibrinolytic factors such as tissue plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and t-PA-PAI-1 complex (PAI-C) of specimens were measured by enzyme-linked immunoassay. In the control group, concentrations of t-PA as well as PAI-1 in amniotic fluid remained at similar levels from 15 to 18 weeks, although PAI-1 levels were more than 10 times higher compared with t-PA levels. Levels of t-PA and PAI-1 in the severe preeclamptic group were not different from those of the control group. PAI-C levels gradually decreased from 15 through 18 weeks of gestation in the control group. PAI-C levels of the severe preeclamptic group were significantly lower than those of the control group (55.5 +/- 18.0% versus control; mean +/- standard deviation [SD], p <0.001). PAI-C, as the most specific indicator of the early stage of fibrinolytic activities, showed lower levels in midtrimester amniotic fluid in the severe preeclamptic group, suggesting fibrinolytic activities of amniotic fluid may have a significant role in the development of severe early-onset preeclampsia via impaired placental development in the latent stage of preeclampsia.

Adult↗
PubMed1999

Accelerated reoxygenation of a murine fibrosarcoma after carbon-ion radiation.

PURPOSE: Reoxygenation of a murine tumour after irradiation with carbon ions was investigated and compared to that after gamma-rays. MATERIALS AND METHODS: NFSa fibrosarcoma cells were transplanted into the right hind legs of syngeneic C3H male mice. Conditioning irradiation with either 290 MeV/u carbon ions or 137-Cs gamma-rays was delivered to the tumours at 8 mm diameter. At given times after irradiation the leg tumours, either clamped or not, received test doses of photons. Differences in tumour growth delay between the clamped and non-clamped tumours were interpreted in terms of reoxygenation. A lung-colony assay was used to obtain cell-survival curves. RESULTS: The oxygen enhancement ratio in the NFSa tumour for 74 keV microm(-1) carbon ions was 1.6 while that for gamma-rays was 3.4. The NFSa tumours reoxygenated 4 days after 30 Gy of gamma-ray irradiation, but reoxygenated as early as 1 day after 16 Gy of carbon ions. Reoxygenation after gamma-rays shortened to 1 day when the tumours were initially clamped for the conditioning irradiation. CONCLUSIONS: The fraction of surviving oxic cells in the NFSa tumours is larger after irradiation with carbon ions than with gamma-rays, resulting in accelerated reoxygenation.

Animals↗
PubMed1999

Measurements of the equivalent whole-body dose during radiation therapy by cytogenetic methods.

Estimates of equivalent whole-body dose following partial body exposure can be performed using different biophysical models. Calculations should be compared with biodosimetry data, but measurements are complicated by mitotic selection induced in target cells after localized irradiation. In this paper we measured chromosomal aberrations in peripheral blood lymphocytes during radiotherapy, and estimated the equivalent whole-body dose absorbed, by using the novel technique of interphase chromosome painting. Premature chromosome condensation was induced in stimulated lymphocytes by incubation in calyculin A, and slides were hybridized in situ with whole-chromosome DNA probes specific for human chromosomes 2 and 4. Reciprocal exchanges were used to estimate the equivalent whole-body dose, based on individual pre-treatment in vitro calibration curves. Equivalent whole-body dose increased as a function of the number of fractions, and reached a plateau at high fraction numbers. Chromosomal aberration yields were dependent on field size, tumour position and concurrent chemotherapy. Results suggest that interphase chromosome painting is a simple technique able to give a reliable estimate of the equivalent whole-body dose absorbed during therapeutic partial-body irradiation.

Aged↗
PubMed1999

IL-12 induces specific cytotoxicity against regenerating hepatocytes in vivo.

Although impaired liver regeneration is thought to be a major cause of death in patients with fulminant hepatitis, the mechanisms are not well defined. Since IL-12 synthesis has been reported to be up-regulated in murine hepatitis virus infection, we studied the influence of continuous IL-12 stimulation on murine liver regeneration using flow cytometric and functional analyses. In non-hepatectomized mice, interestingly, the number of hepatic NK cells was significantly decreased on day 7, after six IL-12 injections, and day 14, after 13 IL-12 injections. The number of hepatic NKT cells was markedly increased on day 7 and day 14 of daily IL-12 treatment. The cytotoxic activity of hepatic lymphocytes against both YAC-1 and p815 cells was enhanced on day 2, after single IL-12 injection, and day 7, after six IL-12 injections. In contrast, hepatic lymphocytes isolated 24 h after partial hepatectomy with IL-12 pretreatment did not show any cytolytic activity against either YAC-1 cells or p815 cells. However, continuous IL-12 stimulation resulted in a significantly higher serum alanine aminotransferase (sALT) level 24 h after the partial hepatectomy as compared with sALT levels in mice subjected to either partial hepatectomy or IL-12 pretreatment alone. On the other hand, the expression of hepatic TNF-alpha mRNA was markedly enhanced by continuous IL-12 stimulation even 24 h after partial hepatectomy, as compared with that in non-treated mice and hepatectomy alone. Simultaneous administration of anti-tumor necrosis factor (TNF)-alpha mAb completely inhibited IL-12-induced in vivo enhancement of liver damage after partial hepatectomy. In conclusion, IL-12 induces the specific cytolytic activity against regenerating hepatocytes in vivo mainly through the enhancement of TNF-alpha synthesis.

Animals↗
PubMed1999

Immunopathogenesis of hepatic fibrosis in chronic liver injury induced by repeatedly administered concanavalin A.

Liver fibrosis is commonly observed in chronic liver disease. However, the immunological mechanisms underlying hepatic fibrosis due to chronic inflammation are not well defined, mainly because suitable experimental models have not been established. We have found that weekly i.v. administration of concanavalin A (Con A) in BALB/c mice brought about a striking alanine aminotransferase increase, resulting in piecemeal necrosis with bridging fibrosis in the parenchyma. Using this fibrosis model, we demonstrated the kinetics of cytokine mRNA expression in liver. Transforming growth factor (TGF)-beta1, TGF-alpha, basic fibroblast growth factor (bFGF) and hepatocyte growth factor mRNAs were up-regulated after each Con A administration. Furthermore, either anti-IFN-gamma, anti-tumor necrosis factor (TNF)-alpha or anti-TGF-beta mAb given together with Con A markedly inhibited the development of hepatic fibrosis. Treatment with either anti-IFN-gamma or anti-TNF-alpha mAb also completely prevented hepatic injury; in contrast, treatment with anti-TGF-beta mAb did not. The treatment with anti-TGF-beta mAb did not affect the levels of hepatic mRNAs for either IFN-gamma or TNF-alpha after Con A injection. Treatment with either anti-IFN-gamma or anti-TNF-alpha did not affect the expression levels of TGF-beta in the liver. In conclusion, the continuous presence of both severe liver damage and up-regulation of TGF-beta synthesis is necessary to induce hepatic fibrosis in this model.

Alanine Transaminase↗
PubMed1999

Primary low-grade lymphoma of mucosa-associated lymphoid tissue of the urinary bladder: a case report with special reference to the use of ancillary diagnostic studies.

We report a case of primary low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type of the urinary bladder. The patient, a 77-year-old woman, presented with a sense of urinary retention. An intravenous pyelogram and cystoscopy revealed a wide-based submucosal mass measuring 3 cm in the left wall of the urinary bladder. Histological findings of the tissue obtained by transurethral resection (TUR) showed a dense, monomorphic atypical lymphoid (centrocyte-like) infiltrate with reactive lymph follicles in the subepithelial tissue. Monocytoid and plasmacytoid features were readily evident in a population of these cells. Lymphoepithelial lesions involving the urothelium were also noticed in some areas. These features were strongly suggestive of primary low-grade lymphoma of the MALT type. The diagnosis was confirmed by immunohistochemical and flow cytometric studies, both of which showed a clear immunoglobulin restriction to lambda light chain and also by polymerase chain reaction-based assay using a formalin-fixed paraffin-embedded TUR tissue sample, which showed a clonal Ig heavy-chain gene rearrangement. Clinical staging procedures revealed that the tumor was localized in the urinary bladder. The patient has not received chemotherapy and is alive and well with no evidence of recurrence, 3 years after TUR. This case demonstrates that these ancillary tests are worth performing for confirmation of B-cell clonality in TUR tissue samples showing dense B-lymphocytic infiltration.

Aged↗