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Biomedical subjects

K Ando

Publications and source records attributed to K Ando.

At least 307 records · Page 17Linked to original sources
PubMed1995

Protective effects of prophylaxis with a protease inhibitor and a free radical scavenger against a temporary ischemia model of pancreatitis.

OBJECTIVE: To evaluate the protective effects of combined prophylaxis with 4-sulfamoylphenyl, 4-guanidinobenzoate methanesulfonate (E3123), potent new protease inhibitor, and superoxide dismutase (SOD), a free radical scavenger, against the multifactor-related pancreatic injuries that occur in acute pancreatitis. DESIGN: Controlled experimental study in rats with pancreatitis induced by a temporary ischemic model of pancreaticobiliary-duct (PBD) obstruction. SETTING: A university-affiliated hospital. EXPERIMENTAL SUBJECTS: Seventy-eight male Wistar rats, weighing approximately 300 g each. INTERVENTIONS: In 18 rats the PBD was occluded with a metal clip, and cerulein was infused for 30 minutes at an hourly rate of 0.2 microgram/kg. After 1 hour the metal clip was removed and the abdomen closed (PBD obstruction group). In 21 rats the same protocol was followed, but ischemia was induced by occlusion of celiac and caudate mesenteric arteries for 30 minutes (ischemia group). In 24 rats the same protocol was followed as for the ischemia group, but 1 hour before and throughout the experiment, E3123 was infused at an hourly rate of 5 mg/kg, and before occlusion of the PBD and immediately after release of the occlusions of the PBD and arteries, SOD, 1 mg/kg, was injected intravenously (treatment group). Fifteen rats underwent laparotomy and gentle manipulation of the pancreatobiliary duct and celiac and caudate mesenteric arteries only (control group). MAIN OUTCOME MEASURES: Serum amylase levels and pancreatic water and amylase levels, histologic changes in pancreas, subcellular amylase and cathepsin-B activities and in-vivo amylase and cathepsin-B outputs. RESULTS: Serum amylase levels and pancreatic water and amylase content were significantly (p < 0.05) reduced in the treatment group (mean [+/- standard error] 13 [2] U/mL, 77 [2] % of wet weight and 503 [56] U/mg of DNA respectively) compared with the ischemia group (25 [3] U/mL, 83 [2] % of wet weight and 731 [52] U/mg of DNA respectively). PBD obstruction and ischemia also caused a significant (p < 0.05) subcellular redistribution of cathepsin B from the lysosomal to the zymogen fraction and impaired output of amylase and cathepsin B into pancreatic juice, which was compensated for in the treatment group. CONCLUSIONS: Temporary pancreatic ischemia and oxygen-derived free radicals appear to play an important role in the pathogenesis of acute pancreatitis. E3123 and SOD may be useful in the prophylaxis of clinical pancreatitis.

Acute Disease↗
PubMed1995

Thoracoscopic resection of a localized visceropleural mesothelioma.

Herein we present a case report of a 46-year-old man with a localized visceropleural mesothelioma detected incidentally during a health examination. The patient underwent a thoracoscopic resection, and his postoperative course was uneventful. A thoracoscopic resection of peripheral localized nodules can be easily performed using thoracoscopic techniques, and this method should not be considered inferior to thoracotomy in terms of curability.

Endoscopy↗
PubMed1995

[Intraportal infusion of 5-FU and lipiodol-aclarubicin after hepatic resection for colorectal liver metastasis].

Fifty-five patients with hepatic metastasis from colorectal cancer underwent curative hepatic resection. Postoperative intraportal infusion of 5-fluorouracil (500mg per day) for 14 days from 21 postoperative days (POD) and lipiodol-aclarubicin (40mg) at 35 POD was carried out in twenty-eight patients for reducing the recurrence in the remnant liver and improving the prognosis. Twenty-seven patients had hepatectomy alone as controls. Intraportal infusion chemotherapy did not induce any hepatotoxicity and hematologic severe abnormalities. The cumulative survival rates for the infusion group and the control group, respectively, were 89.3% and 63.0% at 1 year; 55.2% and 43.3% at 2 year; 27.0% and 27.5% at 3 year. The survival rate for the infusion group was significantly higher than that for the control group at 1 year (p < 0.05). No difference of the recurrent rate in the remnant liver was found between the two groups. It is suggested that intraportal infusion chemotherapy after curative hepatic resection for colorectal liver metastasis might improve survival rate at the early postoperative period. Intraportal infusion chemotherapy could be an effective adjuvant therapy especially in the patients with bilateral and multiple hepatic metastasis.

Aclarubicin↗
PubMed1994

Quantitative RT-PCR assay detecting the transcriptional induction of vascular endothelial growth factor under hypoxia.

Quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay was used to examine the induction of vascular endothelial growth factor (VEGF) transcript in human osteosarcoma cells, MG-63, under hypoxic culture condition. Using this assay system, the expression of VEGF mRNA was estimated eight-fold higher when cells were cultured under hypoxic condition. Transcription level of hypoxanthine phosphoribosyl transferase (HPRT) mRNA was also examined as an internal control. HPRT mRNA level under hypoxia was reduced to one fourteenth. Secretion of VEGF into the cell culture medium was implied by its stimulating activity on the growth of mouse vascular endothelial cultured cells in vitro.

Aerobiosis↗
PubMed1994

Radioprotection by WR-151327 against the late normal tissue damage in mouse hind legs from gamma ray radiation.

PURPOSE: To evaluate the protective effect of WR-151327 on late radiation-induced damage to normal tissues in mice. METHODS AND MATERIALS: The right hind legs of mice with or without WR-151327 administration (400 mg/kg) were irradiated with 137Cs gamma rays. Leg contracture and skin shrinkage assays were performed at 380 days after irradiation. The mice were killed on day 400 postirradiation and histological sections of the legs were made. The thickness of the dermis, epidermis, and skin (dermis plus epidermis) was measured. The muscular area of the legs and the posterior knee angle between the femur and tibia were also measured. The left hind legs were similarly assessed as nonirradiated controls. Group means and standard deviations were calculated and dose-response curves were drawn for every endpoint. Then, the dose modifying factor (DMF) for each endpoint and the correlations among endpoints were determined. RESULTS: Late damage assayed by leg contracture and skin shrinkage progressed with increasing radiation dose. However, it was reduced by drug treatment. The significant effect was indicated for skin shrinkage by a DMF of 1.8 at 35%. The DMF for leg contracture was 1.3 at 6 mm. In the irradiated legs, epidermal hyperplasia and dermal fibrosis in the skin, muscular atrophy, and extension disturbance of the knee joint were observed. These changes progressed with increasing radiation dose. Skin damage assayed by the present endpoints was also reduced by drug treatment by DMFs of 1.4 to 1.7. However, DMFs for damage to the muscle and knee were not determined because no isoeffect was observed. There were good correlations between leg contracture or skin shrinkage and the other endpoints in both untreated and drug-treated mice. CONCLUSIONS: WR-151327 has the potential to protect against radiation-induced late normal tissue damage.

Animals↗
PubMed1994

Nature and origin of cerebrovascular nerves with substance P immunoreactivity in bats (Mammalia: Microchiroptera), with special reference to species differences.

Double staining immunohistochemistry was used to investigate the origin and projection of nerves with substance P (SP) immunoreactivity (-IR) in the walls of the major cerebral arteries in two microchiropteran species. In the greater horseshoe bat, most of the cerebral perivascular nerves with SP-IR did not exhibit calcitonin gene-related peptide (CGRP)-IR, but emitted bright immunofluorescence for vasoactive intestinal polypeptide (VIP). In this species, a large number of cell bodies with both SP- and VIP-IR were observed in many cranial ganglia along various branches of the facial and glossopharyngeal nerves. There were no cell bodies immunoreactive for either SP and VIP in the two sensory (trigeminal and upper cervical dorsal root), two sympathetic (superior cervical and stellate), or two vagal (superior and jugular) ganglia. In addition, several thick fiber bundles with both SP- and VIP-IR were present in the wall of the cerebral carotid artery, and descended progressively reaching as far as the middle part of the basilar artery (BA). These and other findings suggest that SP-immunoreactive nerves with VIP-IR but not CGRP-IR, which contribute to the rich innervation of the vertebrobasilar system in the greater horseshoe bat, originate from neurons with the same combination of peptide-IR in the major or local facial or glossopharyngeal parasympathetic ganglia, and enter the cranial cavity along the internal carotid artery. In the bent-winged bat, however, cerebral perivascular SP-immunoreactive nerves, as well as SP-immunoreactive neurons within the trigeminal and upper cervical dorsal root ganglia (uCDRG), showed neither CGRP-IR nor VIP-IR, and were mostly confined to the caudal BA and the vertebral artery (VA). These observations, in addition to the projection of this nerve type to the BA via the VA as fiber bundles, or through the meninges, indicate that the principal source of the cerebrovascular SP-immunoreactive innervation in this species is the uCDRG.

Animals↗
PubMed1994

Involvement of sialylated poly-N-acetyllactosaminyl sugar chains of band 3 glycoprotein on senescent erythrocytes in anti-band 3 autoantibody binding.

When young and senescent erythrocytes, separated from freshly collected human blood, were incubated with 125I-goat anti-human IgG, binding of the IgG to the senescent cells was three times as high as that to the young cells. The release of the radioactivity from the anti-human IgG-bound senescent cells was enhanced by incubation with band 3 oligosaccharides but not by those digested with endo-beta-galactosidase or neuraminidase. The senescent cells whose surface band 3 saccharide chains were cleaved by endo-beta-galactosidase or totally removed by N-glycosidase F showed decreased binding of the anti-human IgG. The radioactivity was effectively released from the anti-human IgG-bound senescent cells by digestion with endo-beta-galactosidase. The results suggest that senescent erythrocytes bind anti-band 3 autoantibody, and the antigenic sites on the cell surface are sialylated poly-N-acetyllactosaminyl sugar chains of band 3 glycoprotein.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1994

CTL access to tissue antigen is restricted in vivo.

MHC class I-restricted, hepatitis B surface Ag (HBsAg)-specific, CD8+ polyclonal CTL lines and clones cause a severe necroinflammatory liver disease when they are injected i.v. into transgenic mice that display widespread tissue expression of HBsAg. Surprisingly, the same CTLs fail to cause disease in any other HBsAg-positive tissue in these animals. However, the CTLs are highly cytopathic for HBsAg-positive renal tubules and choroid plexus epithelial cells when they are injected extravascularly, either beneath the kidney capsule or intracerebrally. Analysis of the microvascular anatomy of these tissues reveals that the hepatic sinusoid is characterized by a discontinuous endothelium and the absence of a basement membrane. In contrast, the vasculature of most other tissues displays a continuous endothelium and basement membrane; and the epithelial cells of many of these tissues are also surrounded by a separate basement membrane. These results suggest that viral, tumor, and normal self Ags expressed in the liver are readily accessible to class I-restricted T cells, whereas the vascular endothelium and/or the vascular and cellular basement membranes constitute an extremely effective barrier that precludes CTL access to tissue Ag at many other sites. Because class I-restricted Ag recognition occurs throughout the body in many natural diseases and disease models, the vascular barrier must be breached by other events before CTL access to endogenously synthesized epithelial Ag can occur.

Animals↗
PubMed1994

Accelerated bone marrow recovery from radiation damage in etoposide-pretreated mice.

PURPOSE: Etoposide inhibits the activity of Topoisomerase II, and possesses radiosensitizing effects on cultured cells. We showed that pretreatment of mice with etoposide 1 day before whole-body irradiation (WBI) had a protective effect against radiation-induced bone marrow death. The number of endogenous colony-forming units (CFU-S) surviving in WBI mice was significantly increased by pretreatment with etoposide. The purpose of the present study is to clarify mechanisms underlying the protective activity of etoposide against radiation-induced bone marrow damage. METHODS AND MATERIALS: The spleen colony-forming cells (CFU-S) of femoral marrow were assayed by the method of Till and McCulloch. The proliferative state of CFU-S was assessed using the technique of Hodgson. The reduction in exogenous CFU-S after hydroxyurea injection was used to determine the fraction size of S-phase in CFU-S. RESULTS: Etoposide pretreatment did not modify the cell survival parameters of exogeneous CFU-S when bone marrow cells were assayed immediately after WBI. Recovery of CFU-S in femoral marrow started earlier in mice receiving etoposide pretreatment than in the radiation alone group. Administration of hydroxyurea revealed that the accelerated recovery of CFU-S was due to an increased population of S phase cells, suggesting etoposide pretreatment shortened generation time of CFU-S. CONCLUSIONS: The mechanism for the radioprotection appears to be accelerated proliferation of survived bone marrow cells rather than a change in cellular sensitivity to radiation.

Animals↗
PubMed1994

[Role of electrolytes in the development and maintenance of hypertension].

Sodium (Na) intake is one of the important environmental factors influencing the development and maintenance of high blood pressure (BP). Patients with essential hypertension can be divided into two groups: "salt-sensitive" and "non-salt-sensitive", according to BP response to salt loading, suggesting the heterogeneity of salt sensitivity of BP. Salt-sensitive patients had greater increases in BP by salt loading, associated with greater Na retention. Although the precise mechanism for impaired renal Na handling in salt-sensitive patients is still unknown, the sympathetic nervous system in the kidney may play an important role in the decreased renal function of Na excretion and the increased salt sensitivity. Moreover, there are several pieces of evidence indicating that increased renal sympathetic nerve activity is intimately related to the abnormal central noradrenergic systems. In addition, the renin-angiotensin system, insulin, and so on, may modulate salt sensitivity of BP. Some ions influence the hypertensinogenic effect of Na: Chloride ion facilitates it, while potassium, calcium and magnesium antagonize it. Moreover, obesity and a stressful environment increase salt sensitivity of BP.

Blood Pressure↗
PubMed1994

The radiosensitivity of quiescent cell populations in murine solid tumors in irradiation with fast neutrons.

PURPOSE: We analyzed the characteristics of radiosensitivity and potentially lethal damage repair in the quiescent cell populations of murine SCC VII solid tumors irradiated with fast neutrons, in comparison with those irradiated with 10 MV X rays. METHODS AND MATERIALS: SCC VII tumor-bearing C3H/He mice were irradiated with 30 MeV fast neutrons or 10 MV X rays after receiving 10 injections of 5-bromo-2'-deoxyuridine (BUdR) to label all proliferating tumor cells. Immediately or 24 h after irradiation, the tumors were excised and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus frequency in cells without BUdR labeling was determined using immunofluorescence staining to BUdR. This micronucleus frequency was then used to calculate the surviving fraction of unlabeled cells from the regression line for the relation between micronucleus frequency and the surviving fraction of all tumor cells. Thus, a cell survival curve could be determined for the cells not labeled by BUdR, which can be regarded as the quiescent cells for all practical purposes. RESULTS: The difference in intrinsic radiosensitivity between all tumor and quiescent cells became smaller by using fast neutrons, compared with X rays, especially when large radiation doses were given. Potentially lethal damage repair by quiescent cells was less evident following irradiation with fast neutrons than with X rays, especially when large doses were delivered. CONCLUSION: By using fast neutrons in clinical radiotherapy, the radiosensitivity of solid tumors is thought to depend on their heterogeneity less critically than for X rays.

Animals↗
PubMed1994

Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice.

During hepatitis B virus (HBV) infection, distinct host-virus interactions may establish the patterns of viral clearance and persistence and the extent of virus-associated pathology. It is generally thought that HBV-specific class I-restricted cytotoxic T lymphocytes (CTLs) play a critical role in this process by destroying infected hepatocytes. This cytopathic mechanism, however, could be lethal if most of the hepatocytes are infected. In the current study, we demonstrate that class I-restricted HBV-specific CTLs profoundly suppress hepatocellular HBV gene expression in HBV transgenic mice by a noncytolytic process, the strength of which greatly exceeds the cytopathic effect of the CTLs in magnitude and duration. We also show that the regulatory effect of the CTLs is initially mediated by interferon gamma and tumor necrosis factor alpha, is delayed in onset, and becomes independent of these cytokines shortly after it begins. The data indicate that the anti-viral CTL response activates a complex regulatory cascade that inhibits hepatocellular HBV gene expression without killing the cell. The extent to which this mechanism contributes to viral clearance or viral persistence during HBV infection remains to be determined.

Animals↗
PubMed1994

Class I-restricted cytotoxic T lymphocytes are directly cytopathic for their target cells in vivo.

Although CD8-positive, class I-restricted CTL play a critical role in viral clearance and immunopathology in many model systems, they have not been shown to directly kill their target cells in vivo at the single cell level. Using a hepatitis B surface Ag transgenic mouse model of class I-restricted, CTL-mediated liver disease, we now demonstrate that CD8-positive, Ld-restricted hepatitis B surface Ag-specific CTL bind and kill their target cells in vivo by triggering them to undergo degenerative cytologic changes compatible with apoptosis. Unexpectedly, the data also indicate that the pathologic consequences of this direct, Ag-specific CTL effect are much less severe than the cytodestructive, Ag-nonspecific inflammatory response that they induce when they are activated by Ag recognition.

Animals↗
PubMed1994

Distribution and molecular forms of C-type natriuretic peptide in plasma and tissue of a dogfish, Triakis scyllia.

A radioimmunoassay (RIA) to measure C-type natriuretic peptide (CNP) of a dogfish, Triakis scyllia, was established, and plasma and tissue levels of CNP were measured. Molecular forms of CNP in plasma and tissues were also examined using a combination of the RIA and cation-exchange high-performance liquid chromatography (HPLC). The antibody used in the assay cross-reacted with all forms of Triakis CNP, as well as eel CNP, against which the antibody was raised. The antibody exhibited no cross-reaction with any atrial, brain (B-type), and ventricular natriuretic peptides examined and showed a weak cross-reaction with porcine CNP. The detection limit of this assay was 0.8 fmol/tube of Triakis CNP-22 which was used as standard. The CNP level in the Triakis plasma was 1.97 +/- 0.38 pmol/ml (n = 5) which far exceeded the physiological levels of any natriuretic peptides in other species. Among various tissues examined, the highest concentration of CNP was measured in the atrium, followed by the ventricle, brain, and pituitary. Low levels were detected in the kidney, liver, and digestive tracts. HPLC analyses revealed that the major form of CNP in the brain was CNP-22, while it was proCNP (CNP-115) in the heart. In contrast to other species from teleosts to mammals thus far examined, the majority of CNP in dogfish plasma was prohormone instead of processed, mature forms.

Animals↗
PubMed1994

Murine experimental autoimmune uveoretinitis induced by interphotoreceptor retinoid-binding protein and Klebsiella pneumoniae 03 lipopolysaccharide (K03-LPS): a relation between H-2 haplotype and EAU induction.

The pathogenicity of interphotoreceptor retinoid-binding protein (IRBP) in the mouse and H-2 restriction of IRBP-induced experimental autoimmune uveoretinitis (EAU) was tested by repeated immunization using Klebsiella pneumoniae 03 lipopolysaccharide (K03-LPS) as an adjuvant. It was shown that IRBP had a greater capacity to induce EAU than S-antigen. Based on the incidence of EAU induction using B10 congenic mice and other strains, the susceptibility to EAU was, at least in part, controlled by the I-Ak haplotype of the H-2 subregion. The results also indicated that non-major histocompatibility complex (MHC) genes play some role in disease susceptibility.

Animals↗
PubMed1994

A murine model for bone marrow metastasis established by an i.v. injection of C-1300 neuroblastoma in A/J mice.

A reproducible tumor model for bone marrow metastasis has been developed by an injection of murine C-1300 neuroblastoma (C-1300 NB) cells into the tail vein of syngeneic A/J mice. The animals died with liver metastases at 18-21 days after an injection of 10(5) tumor cells and often had bone marrow metastasis in the femur. N-methylformamide (NMF), a maturational agent, was administered to inhibit liver metastases and to extend survival in mice with advancing bone metastasis. Histological examination of bone marrow metastasis, demonstrated lesions varying from a few small colonies of C-1300 NB cells either in metaphysis or diaphysis to large foci replacing normal hematopoietic bone marrow, simultaneously invading epiphysis or cortex of bone as bone metastasis. This assay demonstrated the ability to detect neuroblastoma cells in the bone marrow histologically and could determine bone marrow TD50 by extraction of bone marrow cells after treatment with various doses of drug. Fifty per cent of mice injected with cyclophosphamide (CY) developed bone marrow metastasis without liver metastasis. Treatment with tamoxifen, an anti-calmodulin drug, suppressed tumor takes in the recipient mice with tamoxifen-dose-dependent fashion. This experimental system allows for investigations into the therapeutic response and biology of neuroblastoma metastases in the bone marrow.

Animals↗
PubMed1994

Conformation of bilirubin oxidase in native and denatured states.

The conformation of bilirubin oxidase (EC 1.3.3.5) from Myrothecium verrucaria was studied by circular dichroism (CD). The far-UV CD spectrum showed a single minimum at 215 nm and a maximum near 198 nm, suggesting the dominance of beta-sheets. There was another negative band at 187 nm that is absent from the spectra of model alpha-helix or beta-sheet. CD analysis by the method of Chang et al. agreed well with the estimates based on the Chou and Fasman sequence-predictive method, but the Provencher-Glöckner method of CD analysis agreed well with the sequence-predictive method of Garnier et al. At pH 12 the 215- and 187-nm bands completely disappeared and the protein was denatured. This denaturation was accompanied by the appearance of a large positive band at 250 nm, probably due to ionization of tyrosine residues. In 20 mM sodium dodecyl sulfate the magnitude of the 215-nm band increased, but the spectrum transformed to that of partial helices after heating at 100 degrees C. In 6 M guanidine hydrochloride the far-UV CD spectrum was monotonic and became more negative at the lower wavelength limit (near 212 nm), suggesting that the secondary structure of the protein was disrupted. However, the near-UV CD spectrum retained residual aromatic bands even after heating at 100 degrees C. Thus, our denaturation studies suggest that bilirubin oxidase has a rigid tertiary structure.

Amino Acid Sequence↗