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Biomedical subjects

M Ando

Publications and source records attributed to M Ando.

At least 325 records · Page 18Linked to original sources
PubMed1998

A phase I trial of docetaxel and 5-day continuous infusion of 5-fluorouracil in patients with advanced or recurrent breast cancer.

To determine the maximum-tolerated doses (MTDs), the dose-limiting toxicities (DLTs) and the recommended doses for further trials of docetaxel in combination with a 5-day continuous infusion of 5-fluorouracil (5-FU) in advanced or recurrent breast cancer patients who had been treated previously with at least one chemotherapeutic regimen, patients were treated with docetaxel as a 1-h infusion on day 1 followed by 5-FU as a continuous infusion on days 1 through 5 every 3-4 weeks. Three or six patients were assessed at the following escalating dose levels of docetaxel/5-FU per day: 40/150, 40/300, 50/300, 50/500 and 60/500 mg m(-2). Nineteen patients entered this trial, of whom 18 could be assessed for adverse event and therapeutic efficacy. The DLTs were neutropenia and diarrhoea. The MTDs were 60 mg m(-2) of docetaxel on day 1 and 500 mg m(-2) per day of 5-day continuous infusion of 5-FU. One of 18 patients achieved a complete response and eight achieved partial response (over all response rate: 50%). The recommended doses of docetaxel and 5-day continuous infusion of 5-FU for a phase II trial are 50 mg m(-2) and 500 mg m(-2) per day every 3 or 4 weeks.

Adult↗
PubMed1998

Investigation into thiol conjugation of transthyretin in hereditary transthyretin amyloidosis.

BACKGROUND: For all forms of amyloidosis, the amyloid-generating mechanism is unknown. Familial amyloidotic polyneuropathy type I is caused by a variant transthyretin (TTR Met-30). As electrospray ionization mass spectrometry (ESI-MS) discloses both thiol-conjugated and -unconjugated forms of wild-type and variant TTR, we wanted to investigate the relationship between TTR conjugation and clinically overt amyloid disease. METHODS: Plasma from 35 individuals (12 symptomatic TTR Met-30 carriers, nine asymptomatic and 14 healthy control subjects) were analysed using ESI-MS. RESULTS: The total TTR concentration was significantly lower in symptomatic TTR Met-30 carriers than in control subjects. An increased percentage of conjugated TTR Met-30 was found in symptomatic carriers compared with asymptomatic, whereas the percentage conjugated wild-type TTR was similar for control subjects, asymptomatic and symptomatic TTR Met-30 carriers. CONCLUSION: The finding of a decreased ratio of unconjugated to conjugated TTR Met-30 in plasma samples from symptomatic TTR Met-30 carriers indicates that thiol conjugation of TTR could be involved in amyloid formation.

Adult↗
PubMed1998

Morphological alteration of cultured tracheobronchial epithelial cells is accompanied by the expression of chemokines, MCP-1 and CINC/gro, in rats.

Morphologically altered epithelial cells are generally observed in fibrotic lung conditions and have been reported to produce several cytokines. To examine the relationship between morphological changes of the tracheobronchial epithelial cells (TBECs) and their chemokine production, we investigated, (1) the mRNA expression and protein secretion of monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant/gro (CINC/gro), (2) morphological changes by electron microscopy, and (3) cytokeratin (CK) expression, using a primary culture system of rat TBECs. The constitutive secretion of MCP-1 in the culture supernatant of TBECs increased in a time-dependent manner, whereas the CINC/gro secretion was not changed. These results were consistent with the chemokines' mRNA expression observed by in situ hybridization. The constitutive secretions of MCP-1 and CINC/gro were inhibited partially but significantly by dexamethasone. With the extension of the culture period, the morphology of the TBECs became flat and spindle in shape, similar to squamous metaplasia, as observed on electron microscopy, and with strong expression of CK 14. Sequential staining using immunocytochemistry and in situ hybridization revealed the coexpression of MCP-1 mRNA and CK 14. These data indicate a significant relationship between the morphological squamoid alteration and the constitutive expression of MCP-1 but not of CINC/gro. It is thought that the squamous metaplasia of TBECs may accompany the alteration of cytokine production and play an important role in chronic lung inflammation.

Animals↗
PubMed1998

Endoscopic and pathological manifestations of the gastrointestinal tract in familial amyloidotic polyneuropathy type I (Met30).

OBJECTIVES: To evaluate the characteristic changes in the gastrointestinal tract in familial amyloidotic polyneuropathy (FAP) (Met30), both fibre gastroscopy and colonoscopy studies were performed in FAP (Met30) patients. Microscopic changes were also examined in autopsied and biopsied materials from patients with FAP, and compared with data from autopsied samples from patients with AL amyloidosis, and secondary amyloidosis patients. DESIGN: Endoscopic and histopathological study. SETTING: Kumamoto University Hospital, Kumamoto, Japan. SUBJECTS: Nine patients with FAP (Met30) underwent fibre gastroscopy and colonoscopy. Six autopsied and 23 biopsied gastrointestinal samples from FAP patients, four from autopsied amyloidosis (including two myeloma associated form), and two from autopsied secondary amyloidosis patients were examined for histopathological study. MAIN OUTCOME MEASURES: Fibre gastroscopy and colonoscopy were employed for macroscopic study. Congo red and H-E staining were performed for histopathological study. Macroscopic changes in the gastrointestinal tract and microscopic differences in the amyloid distribution pattern were compared between the different types of amyloidosis. RESULTS: Fibre gastroscopy and colonoscopy for nine FAP patients revealed that four showed a fine granular appearance in the duodenum, three showed lack of lustre, and two showed mucosal friability in the gastrointestinal tract; however, no macroscopic abnormality was observed in four other FAP patients. Histopathological examination of tissue from FAP patients revealed that, although a small amount of amyloid was recognized in the submucosa perivascular layer, a significant amount of amyloid was seen in and around the nerves of the gastrointestinal tract, but very little in Auerbach's nerve plexus. In total, the amount of deposited amyloid in the tissues was small compared with that in other types of systemic amyloidosis, such as AL and secondary amyloidosis. CONCLUSION: These results suggest that the major reason why FAP patients show such severe gastrointestinal symptoms, compared with other types of systemic amyloidosis, may be because of the deposition of a significant amount of amyloid in the nerves in the gastrointestinal tract.

Adult↗
PubMed1998

Acute myocardial infarction and increased soluble intercellular adhesion molecule-1: a marker of vascular inflammation and a risk of early restenosis?

BACKGROUND: Plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been shown to predict activities of inflammatory disorders and malignancies. However, it is unknown whether the plasma level of sICAM-1 is increased in patients with acute myocardial infarction (AMI) with coronary intervention and whether the levels have any diagnostic or predictive values for vascular disease activity in patients with AMI. METHODS: We prospectively observed the time course of the plasma sICAM-1 levels in 20 patients with AMI whose infarct-related coronary artery was successfully recanalized by emergency balloon angioplasty. sICAM-1 was measured by enzyme-linked immunoassay. RESULTS: At admission, 48 hours, 1 week, and 2 weeks after angioplasty, sICAM-1 levels were significantly elevated in patients who had early (3 weeks) restenosis develop compared with those who did not (p < 0.05). At the other time points examined, there was a tendency of higher sICAM-1 levels in patients with than without restenosis (0.06 < p < 0.09). The relation of sICAM-1 levels and total white blood cell counts, neutrophil counts, or numbers of diseased major coronary artery branches was not statistically significant. CONCLUSIONS: A persistent increase in plasma sICAM-1 levels may indirectly implicate vascular inflammation, which could predict the risk of early coronary restenosis after emergency angioplasty in patients with AMI. Hence, measurements of sICAM-1 in patients with AMI would serve as a potentially useful predictor of the risk of early postangioplasty restenosis.

Adult↗
PubMed1998

Changes in rat liver cytochrome P450 enzymes by atrazine and simazine treatment.

1. We examined the effect of two chloro-s-triazines (atrazine and simazine) on hepatic microsomal cytochrome P450 enzymes in rat. Rats were treated intraperitoneally with atrazine or simazine daily for 3 days with 100, 200 and 400 mumol/kg. 2. Among the P450-dependent monooxygenase activities, testosterone 2 alpha-hydroxylase (T2AH) activity in rat, which is associated with CYP2C11, was significantly decreased at all doses of atrazine and simazine. The levels relative to control activities were 59-46 and 60-32% respectively. Similarly, oestradiol 2-hydroxylase (ED2H) activity was also significantly decreased by 28-51% by atrazine and simazine at all doses. However, no change in CYP2C11 protein level by either chloro-s-triazine was observed. K(m) for T2AH was significantly increased only by simazine (200 mumol/kg), whereas the Vmax and Cl(int) for T2AH were significantly decreased by atrazine and simazine at all doses. 3. 7-Ethoxyresorufin O-deethylase (EROD), 7-methoxyresorufin O-demethylase (MROD) and 7-pentoxyresorufin O-depentylase (PROD) activities were significantly increased by 1.4-1.6-, 1.7-3.2- and 1.5-2.2-fold respectively, by both chloro-s-triazines at 200 or 400 mumol/kg. Lauric acid omega-hydroxylase (LAOH) was also increased by 1.4-fold by simazine at 200 and 400 mumol/kg. Immunoblotting showed that only simazine induces CYP1A2 and CYP4A1/2 protein expression. 4. The activities of 7-ethoxycoumarin O-deethylase (ECOD), bufuralol 1'-hydroxylase (BF1'H), chlorzoxazone 6-hydroxylase (CZ6H), testosterone 6 beta-hydroxylase (T6BH) and testosterone 7 alpha-hydroxylase (T7AH) were not affected by either chloro-s-triazine. 5. These results suggest that the pattern of changes in P450 isoforms by chloro-s-triazines differs between atrazine and simazine, that these herbicides change the constitutive and/or male specific P450 isoform(s) in rat liver, and that these changes closely relate to the toxicity of chloro-s-triazines.

Animals↗
PubMed1998

Changes in hepatic cytochrome P450 enzymes by cis- and trans-1,2-dichloroethylenes in rat.

1. We examined the effect of cis- and trans-1,2-dichloroethylenes (DCEs) on hepatic microsomal cytochrome P450 (P450) enzymes in the male and female rat. Rats were treated intraperitoneally with 7.5 mmol/kg cis- or trans-1,2-DCE daily for 4 days. 2. Among the hepatic microsomal P450-dependent monooxygenase activities tested, testosterone 2 alpha-hydroxylase (T2AH) activity in the male rat, which is associated with CYP2C11, was decreased by both cis- and trans-1,2-DCE isomers. The levels to control activities were 53 and 63% respectively. Furthermore, immunoblotting showed that both isomers significantly reduced the CYP2C11/6 protein level in liver microsomes from the male. The levels of testosterone 6 beta-hydroxylase (T6BH) activity and CYP3A2/1 protein in the male rat were reduced by cis-1,2-DCE but not trans-1,2-DCE. 3. cis-1,2-DCE decreased ethoxycoumarin O-deethylase (ECOD), benzyloxyresorufin O-debenzylase (BROD), chlorzoxazone 6-hydroxylase (CZ6H) and testosterone 7 alpha-hydroxylase (T7AH) activities in the male rat by 29, 28, 34 and 27% respectively. On the other hand, trans-1,2-DCE significantly increased 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD) activities in the male rat 1.4- and 1.9-fold respectively. Immunoblotting showed that cis-1,2-DCE reduced CYP1A1/2 and CYP2B1/2 protein levels, whereas trans-1,2-DCE increased CYP1A1/2 and CYP2B1/2 protein levels in the male rat. 4. The activities of other P450-dependent monooxygenases, namely benzphetamine N-demethylase (BZND), aminopyrine N-demethylase (APND), erythromycin N-demethylase (EMND) and lauric acid omega-hydroxylase (LAOH), in the male rat were hardly affected by either 1,2-DCE isomer. In the female rat there were no apparent changes in P450-dependent monooxygenase activities upon treatment with the 1,2-DCE isomers. 5. These results suggest that 1,2-DCEs mainly affect male-specific P450 isoforms in the rat liver and that these changes may relate to the toxicity of 1,2-DCEs.

Animals↗
PubMed1998

Clinical characteristics of patients with metastatic breast cancer with complete remission following systemic treatment.

BACKGROUND: Patients with metastatic breast cancer (MBC) have variable clinical courses. The purpose was to describe the clinical characteristics of MBC patients with complete remissions (CR) following systemic treatment. METHODS: We analyzed 315 consecutive MBC patients treated with several types of systemic treatments at the National Cancer Center Hospital between January 1988 and December 1993. RESULTS: The median survival time (MST) and median progression-free survival were 28.0 and 17.1 months, respectively. Forty patients were defined as 'first-CR' following initial or second-line systemic treatment and the majority of them had a good performance status, low number of metastatic sites and low incidence of liver involvement. Nine of 40 patients with first-CR continued progression-free 5 years after beginning systemic treatments. The major sites of metastasis were the lung and bone and there were no cases with liver metastasis. Five patients received standard doxorubicin-containing combination chemotherapy with or without tamoxifen. Two of these nine patients remain progression free in first-CR. Three of them remained in first-CR after 5 years and died of progressive breast cancer and two others died of unrelated causes. Two patients relapsed after obtaining a first-CR for at least 5 years and remain alive with active metastatic disease. The MST and median progression-free survival of nine patients were 10.6 and 9.0 years, respectively. These nine patients represented 22.5% of all first-CR patients and 3.2% of the total patients. CONCLUSIONS: Although MBC is commonly recognized to be an incurable disease, a small percentage of patients clearly are alive and progression free for prolonged periods after initiation of systemic treatments.

Adult↗
PubMed1998

Mushroom worker's lung resulting from indoor cultivation of Pleurotus osteatus.

Indoor cultivation of oyster mushroom Pleurotus osteatus lead to an outbreak of extrinsic allergic alveolitis in two workers. High titer of indirect fluorescent antibody and positive precipitins against basidiospores of P. osteatus were demonstrated in sera of the patients. Mushroom workers should protect themselves from the basidiospores, being aware of their pathogenicity.

Adult↗
PubMed1998

I-123 uptake in nonfunctional struma ovarii.

A case of nonfunctional struma ovarii preoperatively diagnosed by scintigraphy of the pelvis using I-123 NaI is reported. US, CT, and MRI revealed a multilobulated mass composed of cystic and solid components. CT showed cystic components with slightly high density and MRI showed various signal intensities on T1- and T2-weighted images. I-123-scintigraphy of the pelvis showed uptake in the pelvic mass. Microscopic examination revealed the histologic appearance of thyroid tissue accompanied by follicular adenoma. I-123 scintigraphy of the pelvis was useful for reaching the correct preoperative diagnosis in this patient with nonfunctional struma ovarii.

Adenoma↗
PubMed1998

Nitric oxide and interstitial lung disease.

The role and significance of nitric oxide (NO) and its intermediates on interstitial lung diseases are discussed. NO itself has protective roles against lung injury; however, NO is converted to peroxynitrite through the reaction with the superoxide anion at the inflammation foci, resulting in various destructive effects against lung parenchyma. Increased production of NO and peroxynitrite play an important role in oxidative injury and remodeling associated with interstitial lung diseases.

Anti-Inflammatory Agents↗
PubMed1998

Significant correlation of nitric oxide synthase activity and p53 gene mutation in stage I lung adenocarcinoma.

Nitric oxide (NO) and its derivatives can directly cause DNA damage and mutation in vitro and may play a role in the multistage carcinogenic process. It has been reported that NO induces mutation in the p53 tumor suppressor gene; we therefore analyzed the relationship between NO synthase (NOS) activity and p53 gene status in early-stage lung adenocarcinoma. Surgical samples were classified into two categories: 14 lung adenocarcinomas with high NOS activity (>25 pmol/min/g tissue, category A), and 16 with low NOS activity (<25 pmol/min/g tissue, category B). A yeast functional assay for p53 mutations disclosed a red colony that corresponded to a mutation in the p53 gene in 8 cases (57.1%) in category A and 3 cases (18.8%) in category B, the frequency being significantly higher in the former (P<0.05). A p53 DNA sequence analysis revealed that 5 of the 8 p53 mutation-positive samples in category A had a G:C-to-T:A transversion, which is reported to be a major target of NO. The mechanism of carcinogenesis of adenocarcinoma is not fully understood, but these results suggest that an excess of endogenously formed NO may induce a p53 gene mutation containing mainly G:C-to-T:A transversion in the early stage of lung adenocarcinoma. Our results suggest that NO has potential mutagenic and carcinogenic activity, and may play important roles in human lung adenocarcinoma.

Adenocarcinoma↗
PubMed1998

Surgical treatment for aortic regurgitation caused by Takayasu's arteritis.

Aortic regurgitation (AR) caused by Takayasu's arteritis is relatively rare. We investigated the surgical results in patients with AR caused by Takayasu's arteritis. Between 1978 and December 1997, 65 patients (5 males, 60 females) with AR secondary to Takayasu's arteritis underwent surgery. The patients' ages ranged from 19 to 70 years (mean, 48 years). Takayasu's arteritis was diagnosed by clinical examination confirmed by intraoperative pathological examination of the aortic wall. The surgical procedures for AR were aortic valve replacement in 45 patients, Bentall-type operation in 19, and remodeling in 1. Four (6.2%) patients died during the hospital stay. The follow-up period ranged from 3 to 227 months (mean, 111 months). Eleven patients died during the follow-up period, and the actuarial survival rate was 87% at 5 years and 75% at 10 years. The incidence of prosthetic valve detachment was 4.6% (3/65). Three patients required a composite graft replacement. No prosthetic valve detachment was noted in 96% of the patients at 5 years and in 94% at 10 years. Preoperative steroid administration to treat inflammation and its postoperative use to control inflammation may be important in the treatment of these patients.

Adult↗
PubMed1998

Seasonal chronic cough with sputum eosinophilia caused by Trichosporon cutaneum (Trichosporon asahii).

The case of a 46-year-old man with a chronic cough with sputum eosinophilia (atopic cough) caused by Trichosporon cutaneum serotype II (Trichosporon asahii) is reported. The diagnosis was made with the inhalation challenge test with T. asahii antigen. He was admitted for the diagnosis and treatment of a severe nonproductive cough in the summer season. Although his sputum contained 13% eosinophils of nucleated cells, he did not have bronchial hyperresponsiveness to methacholine or a heightened bronchomotor tone. Bronchodilator therapy was not effective for his cough. His symptoms worsened on returning home, suggesting the existence of some etiologic agent in his house. A high titer of serum anti-Trichosporon antibody was detected and antigen provocation test with the Trichosporon extract was positive: the development of a cough 6 h later and a decrease in the cough threshold to inhaled capsaicin 48 h later (7.85 microM from 31.3 microM prechallenge). This is the first report on a chronic cough with sputum eosinophilia induced by T. cutaneum (T. asahii).

Chronic Disease↗
PubMed1998

Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice.

Erythromycin (EM) is an antibiotic with potent antiinflammatory effects that is used for treating chronic lower respiratory tract infections. It has been shown that free radicals, such as the superoxide anion and nitric oxide (NO), are pathogenic molecules in viral disease. Much attention has been given to a critical role of NO in the pathologic events of various inflammatory diseases. In the present study, we evaluated the effects of EM on influenza-virus-induced pneumonia in mice infected with a lethal dose of influenza virus A/Kumamoto/Y5/67 (H2N2). The administration of EM at a dose of 3.3 mg/kg/d (intraperitoneally, from Days 1 to 6 after infection), significantly improved the survival rate of mice infected with influenza virus, and the survival rate of the virus-infected mice at Day 20 after infection increased in a dose-dependent fashion with EM administered to the animals, from 14% among controls to 42% among animals given EM at 1.0 mg/kg/d and 57% among those given EM at 3.3 mg/kg/d. The induction of interferon-gamma (IFN-gamma) in the mouse lung was inhibited by EM treatment on Day 6 after infection. Simultaneously, the number of inflammatory cells recovered in lung lavage fluid 6 d after virus infection was significantly reduced by the treatment with EM. The EM treatment resulted in a dose-dependent decrease in the level of nitrite/nitrate (metabolites of NO) in the serum and the NO synthase (NOS)-inducting potential in the lungs of the virus-infected mice. These results indicate that EM may have substantial therapeutic value for various acute inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting inflammatory-cell responses and suppressing NO overproduction in the lung.

Animals↗
PubMed1998

Improvement of survival in patients with diffuse panbronchiolitis treated with low-dose erythromycin.

Diffuse panbronchiolitis (DPB) is a chronic inflammatory disease of the airways with a high rate of mortality despite treatment with a combination of antibiotics and the use of supportive therapy such as oxygen administration. Low-dose erythromycin therapy (EM) (400 to 600 mg/d) has been found to improve the survival of patients with DPB, and most patients with DPB in Japan have been treated with this erythromycin regime since 1984. The purpose of this study was to evaluate the effects of treatment with erythromycin on the survival rate of patients with DPB in Japan. We compared the survival rates of 498 patients with DPB after dividing them into three groups according to the date of their first medical examination (Group a: 1970-1979, Group b: 1980-1984, Group c: 1985-1990). DPB had been diagnosed in these patients using the criteria of the Ministry of the Health and Welfare Diffuse Lung Disease Committee (MHW-DLDC), which includes chronic productive cough, shortness of breath, presence of roentgenologically smoldering symmetrical granular shadows in the middle and lower lung fields, limitation of airflow without decrease in DLCO, elevated serum cold hemagglutinin titers, and/or narrowing bronchiolus with infiltration of lymphocytes and foamy alveolar macrophages. These patients were registered in the DPB research group of the Ministry of Health and Welfare (MHW). Survival rates were statistically compared using the generalized-Wilcoxon test. The survival rate of Group c was significantly higher than that of Groups a (p < 0.0001) and b (p < 0. 0001). In Group c, eight of 87 patients died; five died in the EM nontreated subgroup (n = 24), and three died in the EM-treated subgroup (n = 63). There was a significant difference in the survival rates between the two subgroups in Group c (p < 0.001). Treatment with EM was associated with a significant improvement in the rate of survival of patients with DPB. The efficacy of EM treatment increased the survival rate of patients with DPB, which was more significant in the older than in the younger patients.

Adult↗
PubMed1998

Allergen exposure induces the expression of endothelial adhesion molecules in passively sensitized human bronchus: time course and the role of cytokines.

To study the mechanisms contributing to the recruitment of a selective leukocyte subset in allergic inflammation involving the airways as may occur in asthma, we examined whether allergic exposure induces the expression of cell adhesion molecules (CAMs) on the bronchial endothelium of passively sensitized human bronchi. Human bronchial tissue obtained from patients undergoing lung cancer surgery was passively sensitized with serum from patients with atopic asthma who were sensitive to house dust mite. We incubated the tissues for 30, 120, 240, and 480 min in the presence or absence of the dust mite allergen. The tissues were stained immunohistochemically for intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule 1 (VCAM-1). ICAM-1 was constitutively expressed in both the epithelium and endothelium in all tissues but after allergen stimulation significantly increased at 240 and 480 min. E-selectin expression also existed constitutively and increased significantly at 120 and 240 min with allergen exposure. The constitutive expression of VCAM-1 was less than that of ICAM-1 and E-selectin. Following allergen exposure, VCAM-1 expression increased significantly at 30, 120, 240, and 480 min, and at 480 min reached an almost 3.5-fold increase from baseline expression. The TNF-alpha level in the supernatants significantly increased at 120 min after allergen stimulation, and the interleukin (IL)-1beta level increased in 4 of 15 samples. We also examined the induction of CAMs by TNF-alpha, IL-1beta, and IL-4 on human bronchial tissue. TNF-alpha and IL-1beta increased the expression of ICAM-1, E-selectin, and VCAM-1, whereas IL-4 induced only that of VCAM-1. In addition, neutralizing antibody against TNF-alpha and IL-1beta partially blocked the upregulation of CAMs on passively sensitized bronchial tissue after allergen exposure. Thus, both an IgE-dependent allergic response and selected cytokines are able to upregulate endothelial CAMs in human bronchial tissue. These observations provide further evidence that leukocyte infiltration into the site of allergic inflammation as occurs in atopic asthma is in part regulated by the expression of ICAM-1, VCAM-1, and E-selectin.

Adult↗