Caspase requirement for the apoptotic death of WR19L-induced by FTY720.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
T Matsuda
Publications and source records attributed to T Matsuda.
Fas and Fas ligand in discordant xenogeneic antibody-dependent cell-mediated cytotoxicity.
Explore the source record for details and available documents.
Animals↗
Microstructural changes of bile canaliculi in canine liver: the effect of cold ischemia-reperfusion in orthotopic liver transplantation.
Explore the source record for details and available documents.
Actins↗
Small cell lung cancer accompanied by lactic acidosis and syndrome of inappropriate secretion of antidiuretic hormone.
Lactic acidosis is a rare complication in lung cancer. We report a case of lung cancer accompanied by both syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and lactic acidosis. A 70-year-old man was referred to our hospital for examination of a left hilar mass shadow on a chest X-ray film. Small cell lung cancer (SCLC) was demonstrated by brushing the bronchial mucosa of the left lower lobe bronchus. His laboratory data showed SIADH and lactic acidosis that were probably due to SCLC. Fluid restriction improved SIADH, and combination chemotherapy for SCLC improved the lactic acidosis although the tumor size did not change.
Acidosis, Lactic↗
Characterization of acellular dermal matrices (ADMs) prepared by two different methods.
The efficacy of acellular dermal matrix (ADM) in the treatment of full-thickness skin injuries as a dermal substitute depends on its low antigenicity, capacity for rapid vascularization, and stability as a dermal template. These properties will be determined largely by the final composition of the ADM. We have treated human skin with either Dispase followed by Triton X-100 detergent or NaCl followed by SDS detergent, cryosectioned the resulting ADMs, and then characterized them immunohistochemically. Staining for cell-associated antigens (HLA-ABC, HLA-DR, vimentin, desmin, talin), extracellular matrix components (chondroitin sulfate, fibronectin, laminin, vitronectin, hyaluronic acid), elastin, and collagen type VII was dramatically reduced or absent from ADMs prepared by both methods. However, significant amounts of elastin, keratan sulfate, laminin, and collagen types III and IV were still observed in both ADMs. Both methods of ADM preparation resulted in extensive extraction of both cellular and extracellular components of the skin but retention of the basic dermal architecture. In general, ADM prepared by the NaCl-SDS method retained larger amounts of each antigen than did that prepared by the Dispase-Triton method. This was most evident for laminin and type VII collagen but larger amounts of type IV collagen, fibronectin, desmin, elastin, and HLA-DR were also evident in the NaCl-SDS ADM.
Cytoskeletal Proteins↗
Bronchoalveolar lavage cell findings in three types of eosinophilic pneumonia: acute, chronic and drug-induced eosinophilic pneumonia.
There are clinically different types of eosinophilic pneumonia (EP) but no study to date has compared pulmonary inflammatory cells between different types of EP, such as acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP) and drug-induced eosinophilic pneumonia (drug-EP). The present study compared bronchoalveolar lavage fluid (BALF) cell findings to elucidate whether the profiles of the pulmonary inflammatory cells were different among the three types of EP. Clinical records of 28 patients with EP, consisting of eight AEP patients, 10 CEP patients and 10 drug-EP patients, were examined retrospectively. The differential cell counts, the CD4+/CD8+ ratio of lymphocytes, the percentage of HLA-DR+ in CD4+ and CD8+ lymphocytes, and the mean number of nuclear segmentations in cosinophils in BALF were compared among the three types of EP. The numbers of total cells, lymphocytes, neutrophils and eosinophils in BALF from patients with AEP were increased compared with those from normal subjects, and patients with CEP and drug-EP. The CD4+/CD8+ ratio of the BALF lymphocytes in patients with AEP, which exceeded 1.0 in all patients, was significantly higher than that in normal subjects. The percentages of HLA-DR+ cells in CD8+ lymphocytes in BALF from patients with CEP were significantly higher than those from patients with AEP and drug-EP. There was no significant difference in the mean number of nuclear segmentations in eosinophils in BALF among the three types of EP. The BALF cell findings in patients with EP showed some characteristics in accordance with type of EP. It is suggested that pulmonary neutrophils and lymphocytes, rather than eosinophils, may be related to the pathogenesis of the different types of EP.
Acute Disease↗
Intracellular calcium affects neutrophil chemoattractant expression by macrophages in rats with cerulein-induced pancreatitis.
Pancreatitis complicated with infection often results in the development of multiple organ failure. We investigated the role of altered intracellular calcium as a priming signal for cytokine-induced neutrophil chemoattractant expression in this process. Agents modulating cytosolic Ca2+ were utilized to study the in vivo and in vitro cytokine-induced neutrophil chemoattractant expression for macrophages in rats with cerulein-induced pancreatitis after intraperitoneal administration of lipopolysaccharide as a septic challenge. Pretreatment with the calcium channel blocker verapamil significantly reduced serum cytokine-induced neutrophil chemoattractant concentrations in rats with cerulein-induced pancreatitis after septic challenge. Lipopolysaccharide-stimulated in vitro cytokine-induced neutrophil chemoattractant (CINC) production by peritoneal macrophages was significantly enhanced by pretreatment with thapsigargin (an inhibitor of the endoplasmic reticulum-resident Ca2+-ATPase), but not by A23187 (a calcium-specific ionophore, extracellular Ca2+ influx). Pretreatment with U73122 (a phospholipase C inhibitor) inhibited lipopolysaccharide-stimulated but not basal cytokine-induced neutrophil chemoattractant production, while verapamil (a calcium channel blocker), TMB-8 (an inhibitor of calcium release from endoplasmic reticulum), and W7 (calmodulin antagonist) completely abrogated the chemoattractant production. Altered intracellular calcium, due to Ca2+ efflux from intracellular stores, may be involved in the "priming" of macrophages to release cytokine-induced neutrophil chemoattractant following triggering with lipopolysaccharide during acute cerulein pancreatitis.
Acute Disease↗
Dose-finding study of irinotecan and cisplatin plus concurrent radiotherapy for unresectable stage III non-small-cell lung cancer [seecomments].
Irinotecan hydrochloride (CPT-11) shows marked anti-tumour activity alone and in combination with cisplatin in non-small-cell lung cancer (NSCLC). It is necessary to investigate combined-modality therapy including novel effective anti-cancer agents to improve long-term survival of patients with unresectable stage III NSCLC. A phase I/II study of concurrent chemoradiotherapy with CPT-11 and cisplatin was conducted to determine the maximum tolerated dose (MTD) and efficacy in this group of patients. Thirteen previously untreated patients with unresectable stage IIIA/B NSCLC were enrolled and efficacy and toxicity was evaluated in 12 of them; one patient was ineligible. Chemotherapy was repeated every 4 weeks for three courses. Radiation therapy was started on day 2 of the first course of chemotherapy and 60 Gy in 30 fractions was given over 6 weeks. Four of six patients enrolled at level 1 completed the scheduled treatment. Another two received only one and two courses of chemotherapy as a result of persistent leucopenia and neutropenic fever respectively. Three of six patients given level 2 therapy completed the scheduled treatment. Another three received only one and two courses of chemotherapy, two refused treatment because of diarrhoea and one died of pneumonia. Radiation therapy was inadequate in these three patients. As the CPT-11 dose intensity in this trial was low, because of the necessity of omitting CPT-11 administration on days 8 and/or 15 as a result of leucopenia or diarrhoea, and the low radiation therapy completion rate, the trial was discontinued at level 2. Five patients at level 1 and three at level 2 showed partial responses, an overall response rate of 67%. Although neither MTD nor dose-limiting toxicity could be identified, chemotherapy with CPT-11 and cisplatin plus concurrent radiation therapy was deemed unacceptable. We are now conducting a phase I/II study of chemotherapy using CPT-11 as a single agent in combination with radiation therapy.
Adult↗
A partial involvement of histamine in ultrasonically nebulized distilled water-induced bronchoconstriction in guinea-pigs.
1. Inhalation of ultrasonically nebulized distilled water (UNDW) can induce bronchoconstriction only in asthmatics, but mechanisms of the response are not well known. We recently reported a guinea-pig model of UNDW-induced bronchoconstriction (UNDW-IB) in which UNDW induces bronchoconstriction when UNDW is inhaled 20 min after a challenge with aerosolized ovalbumin (OA) in passively sensitized, anaesthetized and artificially ventilated guinea-pigs. 2. To elucidate the role of histamine in the UNDW-IB, we examined the effects of antihistamines, diphenhydramine hydrochloride (DH) and chlorpheniramine maleate (CP), and measured histamine content in bronchoalveolar lavage fluid (BALF) in the animal model. 3. DH in doses of 0.1, 1.0 and 10 mg kg(-1) and CP in doses of 0.01, 0.1 and 1.0 mg kg(-1) administered intravenously 15 min after the OA challenge partially reduced the UNDW-IB at 1 and 2 min after the UNDW inhalation in a dose-dependent manner. Histamine content in BALF recovered 10 min after the UNDW inhalation following the OA provocation was significantly increased compared with that after saline inhalation and before the UNDW inhalation following the OA challenge. 4. Intravenous atropine in a dose of 0.5 mg kg(-1) or inhaled disodium cromoglycate in concentrations of 1 and 10 mg ml(-1) did not alter the UNDW-IB. 5. These results suggest that histamine is involved in part in the UNDW-IB in our animal model.
Administration, Inhalation↗
Successful treatment of Epstein-Barr virus-associated natural killer cell large granular lymphocytic leukaemia using allogeneic peripheral blood stem cell transplantation.
We report a case of natural killer cell large granular lymphocytic (NK-LGL) leukaemia successfully treated with allogeneic peripheral blood stem cell transplantation (allo-PBSCT). The peripheral blood (PB) revealed an abnormal expansion of LGL that were CD3-, CD16- and CD56+, and had natural killer activity. In situ EBER-1 hybridization of the PB mononuclear cells showed the presence of Epstein-Barr virus (EBV) in the LGL as well as in lymphocytes infiltrating the tonsils and colon. Southern blotting with an EBV-terminal repetitive sequence probe demonstrated clonal proliferation of EBV+ cells. The patient received allo-PBSCT from his HLA-matched sister with a conditioning regimen involving the use of cyclophosphamide and fractionated total body irradiation. The patient promptly recovered trilineage haematopoiesis without graft-versus-host disease, and has been in complete remission without therapy for 10 months since allo-PBSCT, suggesting that allo-PBSCT could eradicate the NK-LGL leukaemic cells.
Adolescent↗
Role of tachykinins in distilled water-induced bronchoconstriction in guinea-pigs.
BACKGROUND: An inhalation of ultrasonically nebulized distilled water (UNDW) induces bronchoconstriction only in asthmatics, but the mechanism underlying the response is not fully understood. We recently showed that bronchoconstriction occurs immediately after UNDW is inhaled 20min after an aerosolized antigen challenge in passively sensitized guinea-pigs. OBJECTIVE: This study was conducted to examine the role of tachykinins in this response. METHODS: Passively sensitized animals were anaesthetized and artificially ventilated, and changes in pressure at the airway opening (Pao) were measured as an overall index of airway narrowing. A tachykinin NK1 and NK2 dual receptor antagonist, FK224, and a tachykinin NK1 selective antagonist, FK888, were intravenously administered 15 min after the antigen challenge. The effects of capsaicin desensitization and a neutral endopeptidase inhibitor, phosphoramidon, were also examined. RESULTS: FK224 and FK888 significantly (P < 0.05 and P < 0.05, respectively) reduced the time course curve of the increase in Pao caused by UNDW inhalation in a dose-dependent manner. The percentage increase in Pao from the preantigen challenge value at 1 min after the UNDW inhalation was 267.4+/-17.1, 358.0+/-33.7 and 412.4+/-27.6% with 10 mg/kg of FK224, 1.0 mg/kg of FK224 and vehicle, respectively, (P<0.01 between 10 mg/kg of FK224 and vehicle) and the value was 254.4+/-48.5% with 10 mg/kg of FK888, 327.1+/-57.6% with 1.0 mg/kg of FK888 and 418.5+/-39.0% with vehicle, respectively (P < 0.05 between 10 mg/kg of FK888 and vehicle). The capsaicin desensitization, but not phosphoramidon, significantly reduced the UNDW-induced increase in Pao. CONCLUSION: These results suggest that tachykinins, at least substance P, are involved in a part of the UNDW-induced bronchoconstriction in our guinea-pig model.
Animals↗
Molecular studies of bronchial asthma, sarcoidosis and angiotensin converting enzyme inhibitor-induced cough.
The role of genetic factors was reviewed with respect to the pathophysiology of bronchial asthma, sarcoidosis and cough induced by angiotensin converting enzyme (ACE) inhibitor administration. The so-called 'atopy gene' in 11q13 is not linked to atopy but is associated with serum IgE levels. The beta2-adrenergic receptor gene on 5q32-33 was found to have polymorphism by Ban I and to be related to beta2-receptor function; a defect of a 2.3 kb allele is related to lowered sensitivity to beta2-agonists. This defect is also related to higher prevalence on non-atopic bronchial asthma. The occurrence of amino acid mutation (Arg16 to Gly) of beta2-receptors was lower and Gln27 to Glu mutation is extremely rare in the Japanese population compared with Caucasians. There is polymorphism of ACE genotypes among normal subjects and patients with sarcoidosis, II, ID and DD. The genotype is a significant determinant of serum ACE activity and may determine the prognosis of sarcoid patients. Genotype II has a higher incidence of coughing induced by ACE inhibitors.
Alleles↗
Involvement of calcineurin in Ca2+ paradox-like injury of cultured rat astrocytes.
The Ca2+/calmodulin-dependent phosphatase calcineurin may have physiological and pathological roles in neurons, but little is known about the roles of the enzyme in glial cells. We have previously reported that reperfusion of cultured astrocytes in Ca2+-containing medium after exposure to Ca2+-free medium caused Ca2+ influx followed by delayed cell death. In this study, we examined if calcineurin is involved in this Ca2+-mediated astrocytic injury. FK506, an inhibitor of calcineurin, protected cultured rat astrocytes against paradoxical Ca2+ challenge-induced injury in a dose-dependent manner (10(-10)-10(-8) M). Cyclosporin A at 1 microM mimicked the effect of FK506. Rapamycin (1 microM) did not affect astrocyte injury, but it blocked the protective effect of FK506. Deltamethrin (20 nM), another calcineurin inhibitor, had a similar protective effect, whereas okadaic acid did not. FK506 affected neither paradoxical Ca2+ challenge-induced increase in cytosolic Ca2+ level nor Na+-Ca2+ exchange activity in the cells, suggesting that the calcineurin is involved in processes downstream of increased cytosolic Ca2+ level. Immunochemical studies showed that both calcineurin A (probably the A beta2 isoform) and B subunits were expressed in the cells. It is concluded that calcineurin is present in cultured astrocytes and it has a pathological role in the cells.
Animals↗
Treatment of disseminated intravascular coagulation (DIC) with all-trans retinoic acid in an endotoxin-induced rat model.
Anticoagulant drugs such as heparin are often administered to patients with disseminated intravascular coagulation (DIC) who are also being treated for their underlying disease. The pathophysiology of DIC is so varied that treatment with medications other than anticoagulants may be useful. All-trans retinoic acid (ATRA), which is used for the treatment of acute promyelocytic leukemia (APL), improves DIC in APL. In vitro studies have reported that ATRA caused downregulation of tissue factor and upregulation of thrombomodulin (TM) on endothelial cells as well as APL cells. We examined the effect of ATRA in an endotoxin-induced rat DIC model. DIC was induced in male Wistar rats with a 4-h sustained infusion of endotoxin at a dose of 30 mg/kg. ATRA (20 mg/day) was given every day for 1 week before the injection of endotoxin. ATRA improved the increase in thrombin-antithrombin III (TAT) complex and D-dimer in this model. Fibrin deposition in renal glomeruli was inhibited by ATRA administration, with an increase in the intensity of immunohistochemical TM staining. These findings suggest that ATRA has beneficial effects in the endotoxin-induced rat DIC model. The mechanism may be an upregulation of TM expression on endothelial cells.
Animals↗
A spectrum of mutations induced by crotonaldehyde in shuttle vector plasmids propagated in human cells.
A spectrum of crotonaldehyde-induced mutations in the supF gene of the shuttle vector plasmid pMY189 replicated in human fibroblast cells was examined. Base sequence analysis of 104 plasmids with mutations in the supF gene revealed that the majority of the mutations were base substitutions (85%) and the rest were frameshifts (15%). A single base substitution was most frequently found (47%), while 25% had multiple base substitutions and interestingly 13% had tandem (adjacent two) base substitutions. Of the base substitution mutations, 50% were G:C-->T:A transversions and 23% were G:C-->A:T transitions. The mutations were not distributed randomly but were located at several hotspots, most of which were G:C base pairs in 5'-AAGG-3' (or 5'-CCTT-3') sequences. Production of propanodeoxyguanosine adducts may be related to such specificity in the mutation spectrum.
Aldehydes↗
Presence of a threshold for promoting effects of phenobarbital on diethylnitrosamine-induced hepatic foci in the rat.
The dose dependence of the hepatopromoting effects of phenobarbital (PB) was investigated in a rat liver medium-term bioassay (Ito test) to elucidate a practical threshold level. F344 rats were given a single i.p. injection of diethylnitrosamine (200 mg/kg body wt) and subjected to two-thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, PB at doses of 0, 1, 2, 4, 7.5, 15 or 500 p.p.m. in experiment 1 and 0, 0.01, 0.1 or 0.5 p.p.m. in experiment 2 were fed to the rats for 6 weeks. Experiment 3 was conducted to confirm previous data using the same medium-term bioassay, with PB at doses of 0, 1, 2, 4, 7.5, 15, 30, 60, 125, 250 or 500 p.p.m. fed to the rats. All surviving animals were killed at week 8 in these experiments and their livers were immunohistochemically examined for expression of glutathione S-transferase placental form (GST-P). Quantitative values for GST-P-positive foci in the liver were increased dose dependently in rats given 60-500 p.p.m. PB. However, those for doses in the range 1-7.5 p.p.m. demonstrated a decrease as compared with the control group (0 p.p.m.), with significant differences observed for 1 and 2 p.p.m.. The results for 15-30 and 0.01-0.5 p.p.m. were comparable with the control values. Examination of transforming growth factor-alpha (TGF-alpha)-positive foci also produced similar results to those for GST-P in experiment 1. Immunohistochemical staining of TGF-alpha and GST-P using serial liver sections demonstrated that the TGF-alpha-positive foci comprised a sub-population of the GST-P-positive lesions, being approximately 1/8-1/10th as common in livers of animals treated with PB. TGF-alpha-positive foci were almost always negative on immunostaining for TGF-beta. Western blotting for proteins CYP2B1, 2C6 and 3A2 revealed a good correlation between changes in GST-P-positive foci and CYP3A2 protein expression. The finding of inhibition effects at low doses of PB confirms the presence of a threshold level for promoting effects by PB on liver carcinogenesis in rats.
Animals↗
Synthesis of neoglycoconjugates containing deaminated neuraminic acid (KDN) using rat liver alpha2,6-sialyltransferase.
2-Keto-3-deoxy-D- glycero -D- galacto -nononic acid (KDN) was introduced into asialotransferrin and N -acetyllactosamine (LacNAc) from CMP-KDN by using rat liver Galbeta1-->4GlcNAc alpha2, 6-sialyltransferase to form KDN-transferrin and KDN-LacNAc. These structures contain terminal KDNalpha2-->6Gal-residues, a glycotope that has not yet been described in natural glycoconjugates. KDN was transferred to all four Gal residues in asialotransferrin by this enzyme. The incorporation efficiency of KDN from CMP-KDN into asialotransferrin was about half that of Neu5Ac from CMP-Neu5Ac, based on the V max/ K m values for these donor substrates, 0.0527 min-1and 0.119 min-1, respectively. The KDNalpha2-->6Gal linkage was resistant to exosialidase treatment, in contrast to the sensitivity of the Neu5Acalpha2-->6Gal linkage. Interestingly, Sambucus sieboldiana agglutinin (SSA) was shown to prefer KDN-transferrin to the corresponding Neu5Ac-transferrin, as estimated by slot-blot analysis. The use of an alpha2,6-sialyltransferase to synthesize neoglycoproteins containing KDN has not been previously reported. Their facile synthesis using CMP-KDN and sialyltransferases with different specificities offers new possibilities to study the function of neo-KDN-glycoconjugates, and to explore their use in glycotechnology.
Amino Sugars↗
Disintegration of lysosomes mediated by GTPgammaS-treated cytosol: possible involvement of phospholipases.
We showed previously that cytosol treated with guanosine 5'-O-(3-thiotriphosphate) (GTP-gammaS) disintegrated lysosomes in vitro [Sai, Y. et al. (1994) Biochem. Biophys. Res. Commun. 198, 869-877] in time-, temperature-, and dose-dependent manners. This also requires ATP, however, the latter can be substituted with deoxy-ATP, ADP, or ATPgammaS, suggesting no requirement of ATP hydrolysis. The lysis was inhibited by several chemical modifiers, including N-ethylmaleimide, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, and by various phospholipase inhibitors (trifluoperazine, p-bromophenacyl bromide, nordihydroguaiaretic acid, W-7, primaquine, compound 48/80, neomycin, and gentamicin), but not by ONO-RS-082, an inhibitor of phospholipase A2. The reaction was also inhibited by phospholipids (phosphatidylinositol, phosphatidylserine, phosphatidic acid, and phosphatidylcholine) and diacylglycerol. Among the phospholipase A2 hydrolysis products of phospholipids, unsaturated fatty acids (oleate, linoleate, and arachidonate) and lysophospholipid (lysophosphatidylcholine) by themselves broke lysosomes down directly, whereas saturated fatty acids (palmitate and stearate) had little effect. We found that GTPgammaS-stimulated cytosolic phospholipase A2 activity was highly sensitive to ONO-RS-082. These results suggest the participation of phospholipase(s), though not cytosolic phospholipase A2, in the GTPgammaS-dependent lysis of lysosomes.
Animals↗