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Biomedical subjects

M Ando

Publications and source records attributed to M Ando.

At least 469 records · Page 26Linked to original sources
PubMed1996

Apoptotic cell death following exposure to fluoride in rat alveolar macrophages.

Since inhaled fluoride is implicated in the acute respiratory failure, cytotoxic effects of fluoride on alveolar macrophages, primary target cells of inhaled toxicants, were investigated. The LC50 of sodium fluoride was estimated to be 0.41 mM, while 1 mM sodium chloride, bromide and iodide had virtually no effects on the viability of alveolar macrophages. Photomicroscopic observation revealed that nuclei of the fluoride-exposed alveolar macrophages were fragmented. The ladder formation was observed when DNA isolated from fluoride-exposed alveolar macrophages was electrophoresed in agarose gel. These results suggest that cytotoxicity of fluoride is associated with apoptosis in rat alveolar macrophages.

Animals↗
PubMed1996

Hereditary cerebellar ataxia with Leber's hereditary optic neuropathy mitochondrial DNA 11778 mutation.

We investigated a family with optic atrophy which occurred in childhood or early adulthood plus late-onset cerebellar ataxia. The magnetic resonance imaging in the proband revealed cerebellar atrophy. The proband and her brother were homoplasmic for the most common mitochondrial DNA (mtDNA) 11778 mutation associated with Leber's hereditary optic neuropathy (LHON). This study showed further evidence that central nervous system lesions can occur in cases of LHON mtDNA mutation.

Adult↗
PubMed1996

A novel enzyme system for the reduction of 3-oxo bile acids in human red blood cells.

7 alpha,12 alpha-Dihydroxy-3-oxo- and 3,7,12-trioxo-5 beta-cholanoic acids labeled with 18O atoms were incubated with human red blood cells, and the biotransformation products were separated and characterized by gas chromatography-mass spectrometry as the pentafluorobenzyl ester-trimethylsilyl and -dimethylethylsilyl ether derivatives with the negative ion chemical ionization mode. The reduced products, 3 beta,7 alpha,12 alpha-trihydroxy-5 beta-cholanoic acid for the former, and 3 alpha-hydroxylated dioxo bile acid together with 3 beta-hydroxylated 7,12-dioxo-5 beta-cholanoic acid for the latter, were identified as metabolites. When 3-oxo bile acid was incubated with human blood denatured at 70 degrees C for 2 min, no metabolites were formed. The enzymic reduction activity has been localized in the red blood cell fraction.

Bile Acids and Salts↗
PubMed1996

Interaction of 2,4,4'-trichloro-2'-hydroxydiphenyl ether with microsomal cytochrome P450-dependent monooxygenases in rat liver.

We studied the effects of 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan DP300) on the kinetics of the cytochrome P450 (P450)-dependent monooxygenases in rat liver microsomes. The activities of 7-ethoxyresorufin O-deethylase (EROD) and 7-pentoxyresorufin O-depentylase (PROD) in rat liver microsomes exposed to 3-methylcholanthrene (MC) and phenobarbital (PB) respectively, were substantially inhibited by Irgasan DP300. The inhibition profile of EROD was competitive, whereas that of PROD was noncompetitive; the Ki values from Hanes plots were 0.24 and 1.48 microM for EROD and PROD, respectively. Phenacetin O-deethylase (PCOD) and 4-nitrophenol hydroxylase (4NPH) activities in rats exposed to PB were also inhibited by Irgasan DP300, at Ki values lower than those for other microsomes. Irgasan DP300 slightly inhibited testosterone 6 beta-hydroxylase (TS6BH) activities in some microsomes. No effect of Irgasan DP300 on lauric acid omega-hydroxylase (LAOH) activity was evident in any microsomal preparations. These results indicated that Irgasan DP300 inhibits MC- and PB-inducible P450-dependent monoxygenase in vitro competitively or noncompetitively, and that the P450 enzymes of the CYP1A or CYP2B subfamily may contribute to Irgasan DP300 toxicity.

Animals↗
PubMed1996

Induction of tissue transglutaminase in rat superior cervical sympathetic ganglia following in vitro stimulation of retinoic acid.

The addition of retinoic acid (RA, 50 nM) to Dulbecco's modifed Eagle's medium containing 1.0 percent bovine serum albumin and 50 mu g/l of gentamicin markedly increased the activity of a Ca(2+) -dependent tissue transglutaminase (TGase) (ca. 3.2-fold), which stabilizes newly formed protein assemblies at the sites of synapses, in isolated rat superior cervical sympathetic ganglia (SCG), which is abundant in synapses, following in vitro aerobic incubation for 3 h at 37 degrees C. An isomer of RA, 13-cis-RA (50 nM), showed the same tendency but rather lesser magnitude (ca. 1.7-fold) in ganglionic TGase activation. Also, retinal (50 nM), a precursor of RA, had a little effect on TGase stimulation (ca. 1.5-fold) in SCG. The RA-induced enhancement of ganglionic TGase activity was completely eliminated in the presence of either actinomycin D (1.0 mu g/ml), a depressant of molecular transcriptional activity, or a potent inhibitor of protein synthesis, cycloheximide (10 mu g/ml). Kinetic analyses show that the stimulation of ganglionic TGase activity evoked by RA addition was associated with only an increase in V max value (ca. 3.3-fold) without change in Km value. Thus, the enzyme protein of TGase might be synthesized de novo in the ganglia in response to RA. The RA-induced activation effect of ganglionic TGase almost disappeared (ca. 1.3-fold) 1 week following denervation, by which time preganglionic cholinergic nerve terminals were degradated. In axotomized SCG, where sympathetic neurons were degenerated and reactive proliferation of glial cells was in progress, the RA-evoked increase in ganglionic TGase activity was attenuated (ca. 1.3-fold). These findings imply that some retinoids, especially RA effectively participate in the cholinergic potentiation of synaptic activity.

Animals↗
PubMed1996

Developmental and denervation changes in c-ret proto-oncogene expression in chick motoneurons.

Receptor tyrosine kinases (RTKs) play important roles in cellular differentiation, survival, and proliferation. To search for genes involved in the survival of motoneurons, we isolated the RTKs specifically expressed on them. We used RT-PCR, by which RNA was obtained from purified embryonic day 5 (E5) chick motoneurons, and screened by in situ hybridization. Of 17 RTK cDNA clones, c-ret expression gradually increased in the motoneurons of the spinal cord during development. Compared with the expression of the neurotrophin receptor, TrkC, that of c-ret was very high in motoneurons from around E17 to adulthood. The level of c-ret expression on the motoneurons was unaffected by deafferentation at E2, but changed after denervation at post-hatching day 2. The in situ hybridization signal for c-ret mRNA increased slightly at day 1, then decreased progressively up to day 8, and increased again 2 weeks after sciatic nerve denervation in the motoneurons of the lumbar spinal cord. There were also changes in the signal of the lesioned sciatic nerve. In the most distal part from the lesioned site, the signal for c-ret mRNA significantly increased from day 3 on after denervation. These results suggested that the c-ret gene may encode the receptor for a factor involved in motoneuron differentiation and the promotion of regeneration of injured peripheral nerves.

Amino Acid Sequence↗
PubMed1996

The receptor tyrosine kinase, Cek8, is transiently expressed on subtypes of motoneurons in the spinal cord during development.

Receptor tyrosine kinases (RTKs) play important roles in cellular proliferation, differentiation, and survival. We performed reverse transcriptase-polymerase chain reactions (RT-PCR) from enriched embryonic day 5 (E5) chick motoneurons by panning to identify RTKs involved in the early development of motoneuron. In situ hybridization revealed that Cek8, a member of the eph family, was specifically expressed on motoneurons at the brachial and lumbar segments of the spinal cord which innervate limb muscles, and disappeared after the naturally occurring cell death period (E6-E11). Immunohistochemistry using an anti-Cek8 monoclonal antibody showed the localization of Cek8 protein at the cell bodies and axonal fibers of motoneurons and muscles. The unique expression of Cek8 suggests its involvement in cellular survival or cell-cell interactions for specific subpopulations of developing motoneurons.

Amino Acid Sequence↗
PubMed1996

Pulmonary veno-occlusive disease accompanied by microangiopathic hemolytic anemia 1 year after a second bone marrow transplantation for acute lymphoblastic leukemia.

Although hepatic veno-occlusive disease (HVOD) is a common complication of allogenic bone marrow transplantation (BMT), pulmonary veno-occlusive disease (PVOD) is very rare. Only three cases have been described in the literature. We report the case of a 19-year-old woman who developed PVOD accompanied by microangiopathic hemolytic anemia (MAHA) and hemolytic uremic syndrome (HUS) 1 year after a second BMT for relapsed acute lymphoblastic leukemia (ALL). Autopsy examination revealed obstruction of the small pulmonary veins with edematous thickening of the intima. These findings are compatible with PVOD. Pulmonary GVHD and pulmonary aspergillosis were also observed. Various etiologic factors have been implicated in PVOD after BMT. We postulate that pulmonary GVHD and pulmonary infection including aspergillosis played an important role in the occurrence of both PVOD and HUS in our patient. Microangiopathic cytokines released in response to the GVHD and infection may damage the intima of microvessels that were previously injured by the two BMT. Despite appropriate therapy, the microangiopathic process was irreversible and the patient died. Thus, measures must be taken to prevent and treat PVOD after BMT.

Adolescent↗
PubMed1996

Predictive factors for postoperative cerebral complications in patients with thoracic aortic aneurysm.

OBJECTIVE: Perioperative factors affecting the outcomes of postoperative brain function in patients with thoracic aortic aneurysm were demonstrated. PATIENTS AND METHODS: From December 1977 to September 1994, 745 patients with thoracic aortic aneurysm underwent 846 operations. The mean age at surgery was 57.1 +/- 14.2 years old. Four hundred seventy-four patients had true aneurysm and 372 had aortic dissection. Two hundred forty-four patients underwent repair in the ascending aorta, 189 arch repair, 242 repair in the descending aorta. 79 replacement of the thoracoabdominal aorta, and 92 extra-anatomical bypass or thrombo-exclusion of the aorta. Conventional cardiopulmonary bypass was used in 297 patients, partial cardiopulmonary bypass through femoral access in 167, selective cerebral perfusion in 253, deep hypothermic circulatory arrest and retrograde cerebral perfusion in 50, temporary shunt in 29, and no circulatory support was applied in 50. Postoperative cerebral complications were divided into permanent cerebral dysfunction. RESULTS: The early mortality rate was 15.5% (131 patients). Incremental risk factors for hospital mortality were non-preexisting cardiac lesions, ruptured aneurysm, postoperative cerebral complications, sepsis, bleeding, low output syndrome and renal failure. Cerebral complications occurred in 81 patients (9.6%), involving 47 permanent and 34 transient sequelae. The early mortality rate in patients with postoperative brain damage was 42.0%. The etiologies of the brain damage diagnosed by computed tomography were embolism in 41 patients, cerebral hypoperfusion in 16 and unknown in 24. Incremental risk factors for postoperative cerebral complications were: operation early in the series advanced age at surgery, preoperative renal failure, aortic arch lesions, atherosclerotic aneurysm, aortic arch procedures and clamping of the aortic arch. CONCLUSIONS: Although there was an increased incidence of advanced age and complex lesions in patients with aortic aneurysm, an improvement in surgical results has recently been achieved using advanced diagnostic and surgical techniques.

Adult↗
PubMed1996

Surgery for aortic dissection with intimal tear in the transverse aortic arch.

OBJECTIVES: This study reports surgical experience of 72 cases of aortic dissection with intimal tear in the transverse aortic arch. METHODS: Of 325 patients with aortic dissection, 72 (22.2%) had a tear in the arch, including 27 with acute dissection and 45 with chronic dissection. Mean age at surgery was 60.8 +/- 14.1 years. The dissection was localized from the ascending aorta to the arch in 30 patients and extensive from the ascending aorta to the descending aorta in 42. Surgeries consisted of total arch replacement in 50 patients, hemiarch replacement in 20, and extra-anatomical bypass in 1. In the initial series, cardiopulmonary bypass for brain protection during arch procedures was selective cerebral perfusion (61 patients), but since July 1993 deep hypothermic circulatory arrest with retrograde cerebral perfusion was exclusively utilized (8 patients). RESULTS: Hospital mortality was 9.7%, 11.1% of the patients who had acute dissection and 8.8% with chronic dissection. There has been no mortality since February 1993. The mean follow-up period was 51 +/- 37 months, and there were 3 late deaths. The 5 and 10 year survival rate was 85.3 +/- 4.8 in all patients, 84.3 +/- 8.9% with acute dissection, and 85.5 +/- 5.7% with chronic dissection. The 5 and 10 year survival was 79.8 +/- 7.1 with extensive dissection, and 93.5 +/- 6.5% with localized dissection. During follow-up, 6 patients underwent subsequent aortic surgeries. The freedom from reoperation at 5 years and at 10 years was 91.4 +/- 4.8% and 65.6 +/- 14.4%, respectively. In patients with acute dissection it was 92.3 +/- 7.4% and 61.5 +/- 25.6% at 5 years and 10 years, while with chronic dissection it was 87.0 +/- 7.0% and 44.0 +/- 17.3% at 5 years and 10 years, respectively (n.s.). The freedom from subsequent reoperation for the aorta in all patients was 91.4 +/- 4.8% at 5 years and 10 years was 65.6 +/- 14.4%. With acute dissection it was 92.3 +/- 7.4% at 5 years and 61.5 +/- 25.6% at 10 years, while that with chronic dissection it was 91.3 +/- 5.9% and 65.7 +/- 16.8% at 5 years and 10 years respectively (n.s.). The freedom from all reoperations with extensive dissection at 5 years and 10 years was 86.6% +/- 7.2% and 34.2 +/- 17.3%, respectively, moreover, the freedom from reoperations with localized dissection at 5 and at 10 years was 90.0 +/- 9.5% (n.s.). However, the freedom from subsequent aorta reoperation with extensive dissection at 5 years and 10 years was 86.6 +/- 7.2% and 56.0 +/- 16.0%, respectively, while with localized dissection it was 100% at 10 years (P < 0.01). CONCLUSION: Early and late surgical result for arch dissection was satisfactory with a surgical principle of resecting the aortic segment that contains the initial intimal tear and graft replacement.

Acute Disease↗
PubMed1996

Enhanced scavenger receptor expression in monocyte-macrophages in dialysis patients.

The macrophage scavenger receptor (SR), which has two isoforms named type I and II, plays a leading role in the atherosclerotic process. To elucidate the mechanism of atherosclerosis in dialysis patients, SR expression was studied in monocyte-macrophages from thirteen dialysis patients and eight healthy controls. SR mRNA expression was examined in four hemodialysis patients and four controls matched for age and sex. Monocytes were allowed to differentiate into macrophages in in vitro cultures for seven days and SR type I and II mRNA expression were analyzed with the reverse transcription-polymerase chain reaction and quantitated using radiation densities of Southern blots. Only SR type I expression increased during differentiation and was accelerated by one or two days and enhanced after five days in patients, as compared to controls. To detect SR protein expression, uptake of fluorescently labeled acetylated low-density lipoprotein (Ac-LDL) was evaluated by flow cytometry. The mean fluorescence intensity of labeled cells was significantly higher in hemodialysis and continuous ambulatory peritoneal dialysis patients than in controls, although the number of SR-positive cells remained constant. In conclusion, SR expression is enhanced in macrophages from dialysis patients, probably by up-regulation of type I, which may contribute to the development of atherosclerosis in these patients.

Adult↗
PubMed1996

Effects of insulin-like growth factor-I on follicle growth, oocyte maturation, and ovarian steroidogenesis and plasminogen activator activity in the rabbit.

We examined the effects of insulin-like growth factor (IGF)-I on follicular growth, oocyte maturation, and ovarian steroidogenesis and plasminogen activator (PA) activity in vitro, using a perfused rabbit ovary preparation in order to determine whether the follicle-stimulating effects of growth hormone (GH) are mediated by IGF-I. The addition of IGF-I to the perfusate stimulated follicular growth and the resumption of meiosis in follicular oocytes in a dose-dependent manner. There was no significant difference in the production of progesterone by perfused rabbit ovaries between IGF-I-treated and control ovaries, whereas IGF-I increased the production of estradiol (E2) by perfused rabbit ovaries in a dose-dependent manner. The concomitant addition of a monoclonal antibody recognizing the type I IGF receptor, alpha IR-3, to the perfusate significantly blocked IGF-I-stimulated follicular growth, oocyte maturation, and E2 production. Intrafollicular PA activity increased significantly 4 h after exposure to 10 or 100 ng/ml of IGF-I and reached maximal levels at 6 h. The percentage increase in follicle diameter at 6 h after exposure to IGF-I was significantly correlated with the intrafollicular PA activity. Treatment with GH resulted in a 2.7-fold increase in intrafollicular levels of IGF-I mRNA. The binding of [125I]-IGF-I to rabbit ovarian membrane preparations was inhibited by unlabeled IGF-I and IGF-II in a concentration-dependent manner. The relative affinity of the IGF-I receptor for IGF-I, IGF-II, and insulin was typical of type I binding (IGF-I > IGF-II > insulin). Affinity cross-linking of ovarian membranes with [125I]-IGF-I revealed a radiolabeled band corresponding to a molecular weight of 135,000, the alpha subunit of the type I IGF receptor. This band was totally displaced by IGF-I and alpha IR-3. It was concluded that IGF-I stimulated follicular development, E2 production, and oocyte maturation by interacting with its specific receptor located in rabbit ovarian membranes.

Animals↗
PubMed1996

Acceptability of patients with brain metastases for clinical trials of chemotherapy for metastatic non-small-cell lung cancer.

This study was conducted to determine whether patients with brain metastases from non-small-cell lung cancer (NSCLC) should be included in clinical trials of chemotherapy. Patients with metastatic NSCLC and good performance status were studied. The survival of patients with brain metastases was compared with that of patients without brain metastases. Of 100 eligible patients, 22 had brain metastases at diagnosis. The median survival time was poorer in patients with brain metastases than in other patients with metastatic NSCLC (96.5 vs. 181.5 days). However, the difference in survival was not significant on univariate analysis (p = 0.106). Multivariate analysis confirmed that the prognostic value of brain metastases was limited in this sample (p = 0.129). There was little difference in survival curves during the first 8 weeks. Patients with brain metastases who have good performance status and minimal neurologic symptoms can be observed for approximately 8 weeks in clinical trials to determine their response to chemotherapy. However, it is doubtful that patients with brain metastases would be eligible for phase III trials, in which survival is an endpoint.

Adult↗
PubMed1996

Bradykinin generation triggered by Pseudomonas proteases facilitates invasion of the systemic circulation by Pseudomonas aeruginosa.

To elucidate the mechanism of bacterial exoprotease in promotion of the intravascular dissemination of Pseudomonas aeruginosa, we examined the possible involvement of bradykinin (whose generation is induced by pseudomonal proteases in septic foci) in the invasion by bacteria, and in access of bacterial toxins to systemic blood circulation. P. aeruginosa 621 (PA 621), which produces very little protease, was injected intraperitoneally into mice together with pseudomonal exoproteases (elastase/alkaline protease). Dissemination of bacteria from the peritoneal septic foci to the blood was assessed by counting viable bacteria in the blood and spleen by use of the colony-forming assay. The results showed that pseudomonal proteases markedly enhanced (10- to 100-fold) intravascular dissemination of bacteria in mice. This enhancement was induced not only by pseudomonal proteases but also by bradykinin. More importantly, the increased spread of PA 621 induced by pseudomonal protease and bradykinin was significantly augmented by the addition of kininase inhibitors, indicating the direct involvement of bradykinin in bacterial dissemination. Similarly, bradykinin caused effective dissemination of pseudomonal toxins such as endotoxin (lipopolysaccharide) and exotoxin A when the toxins were injected into the peritoneal cavity with bradykinin. Furthermore, the lethality of the infection with PA 621 was strongly enhanced by pseudomonal proteases given i.p. simultaneously with PA 621. On the basis of these results, it is strongly suggested that pseudomonal proteases as well as bradykinin generated in infectious foci are involved in facilitation of bacterial dissemination in vivo.

Animals↗
PubMed1996

Therapeutic drug monitoring in 21-day oral etoposide treatment for lung cancer.

We aimed to determine whether or not therapeutic drug monitoring is applicable to 21-day oral etoposide treatment for lung cancer. As the starting dose, a 25-mg capsule of etoposide was taken orally three times daily (75 mg/body). To achieve the target concentration range of 1.0 to 1.5 micrograms/ml, the dose was changed to two (50 mg/body) or four (100 mg/body) times a day from day 5, depending on the mean concentration obtained on days 3 and 4 (Cbefore). The mean concentration was calculated by use of a limited sampling model we constructed previously. Among 26 courses in 15 patients, two patients experienced grade 4 leukopenia plus neutropenia, and one of them died on day 20. Because nausea/emesis prevented the planned dose escalation in one patient, we excluded two courses of this patient from the pharmacokinetic analysis of dose modification. Among 5 courses with dose reduction, the Cbefore of 1.7 +/- 0.1 (microgram/ml, mean +/- SE) was decreased to 1.3 +/- 0.2 after day 5 (Cafter). Among 7 courses with dose escalation, the Cbefore of 0.9 +/- 0.0 was increased to the Cafter of 1.2 +/- 0.1. Among the remaining 12 courses without dose modification, the Cbefore and the Cafter were 1.2 +/- 0.0 and 1.3 +/- 0.1, respectively. Hematologic toxicities tended to correlate with the drug concentration. TDM is thus applicable to oral etoposide given according to this schedule, and a larger study is now needed to confirm that the therapeutic efficacy is improved by introducing TDM.

Administration, Oral↗
PubMed1996

Therapeutic drug monitoring of etoposide in a 14-day infusion for non-small-cell lung cancer.

We investigated whether a constant plasma concentration could be obtained by the individualized administration of low-dose, prolonged-infusional etoposide. Etoposide was infused for 14 days at 40 mg/m2/day initially in patients with inoperable non-small-cell lung cancer. The infusion rate was modified based upon the etoposide concentration at 24 h following the initiation of the infusion (C24) to achieve a target concentration of 1.5 microgram/ml. We postulated that severe toxicities could be avoided by maintaining the steady-state concentration at less than 2 microgram/ml, while antitumor activity could be expected if the steady-state concentration was maintained at more than 1 microgram/ml. In a total of 21 courses in 12 patients, the mean etoposide dose was 35+/-6 mg/m2 daily. The C24 was 1.8+/-0.4 microgram/ml and ranged from 1.1 to 2.9 microgram/ml. Following dose modification, the mean concentration from 96 to 336 h (C mean) was 1.6+/-0.2 microgram/ml and ranged from 1.2 to 2.0 microgram/ml. The toxicities were well-tolerated except for one patient with WHO grade 4 leukopenia and neutropenia who developed infectious complications. There were no treatment-related deaths. Following dose modification, the inter-patient variability was decreased successfully. Although this pharmacologically-guided method needs to be validated using more patients, it could be used for therapeutic drug monitoring.

Aged↗