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M Suga

Publications and source records attributed to M Suga.

At least 109 records · Page 6Linked to original sources
PubMed1997

Nitric oxide synthase activity in human lung cancer.

Nitric oxide synthases (NOS) exist in human tumor cell lines and solid tumor tissues, and it has been suggested that NO may play important roles in growth, progression or metastasis of tumors. We investigated the activity and distribution of NOS in a series of human cancer and normal lung tissues. Seventy-two primary lung cancer samples (44 cases of adenocarcinoma, 18 of squamous cell carcinoma, 4 of large cell carcinoma, 2 of small cell carcinoma, 2 of adenosquamous carcinoma, and 2 of carcinoids) and corresponding normal lung samples were obtained from surgically treated patients. In normal lung tissues, little NOS activity was observed with no correlation between the patient's age and NOS activity. The total NOS activities in lung adenocarcinoma samples were significantly higher than those in other types of lung cancers of normal lung samples (P < 0.05). Analysis by tumor grade of the adenocarcinoma samples revealed no significant difference of NOS activity between grades. TNM classification showed that, although T stage did not correlate with NOS activity, cancer tissues from patients with N2 disease tended to have lower activity than those from patients with NO or N1 disease. Immunohistochemical studies revealed that the intensity of NOS immunoreactivity correlated with NOS activity. These results suggest that NO may play an important role in the metabolism and behavior of lung cancers, especially adenocarcinoma.

Adult↗
PubMed1997

Nitric oxide generation from hydroxyurea via copper-catalyzed peroxidation and implications for pharmacological actions of hydroxyurea.

We investigated the generation of nitric oxide (NO) by H2O2-dependent peroxidation of hydroxyurea in the presence of copper-containing proteins such as Cu,Zn-superoxide dismutase (Cu,Zn-SOD) or ceruloplasmin as a catalyst. In the reaction mixture of hydroxyurea, CuZn-SOD, and H2O2, NO generation was identified by measuring the specific electron spin resonance (ESR) signal of 2-phenyl-4, 4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO). The ESR signal of the NO-hemoglobin adduct was also detected in human red blood cells during copper-catalyzed peroxidation of hydroxyurea. The NO production during peroxidation of hydroxyurea was quantified as NO2- formation, measured by using the Griess assay, the amount of NO2- was dependent on the concentrating of hydroxyurea of the reaction mixture. ESR spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) showed hydroxy radical (OH) generation in the reaction of H2O2 with either Cu,Zn-SOD or ceruloplasmin. Several OH scavengers, such as ethanol, thiourea, DMPO, and dimethylsulfoxide, and the metalchelating agent diethylenetriaminepentaacetic acid significantly inhibited NO generation from hydroxyurea. This indicates that NO release from hydroxyurea may be mediated by OH derived from the copper-catalyzed Fenton-like reaction. Incubation of hydroxyurea and Cu,Zn-SOD with xanthine oxidase and hypoxanthine in a system forming O2- -->H2O2 also resulted in appreciable NO production. These results suggest that NO production from hydroxyurea catalyzed by copper-containing proteins may be the molecular basis of the pharmacological and antitumor action of hydroxyurea.

Ceruloplasmin↗
PubMed1997

Late onset type I familial amyloidotic polyneuropathy: presentation of three autopsy cases in comparison with 19 autopsy cases of the ordinary type.

Clinicopathological features of three autopsy cases of extremely rare late onset type I familial amyloidotic polyneuropathy were presented and compared with 19 autopsy cases of the ordinary type. In the late onset cases, the ages at onset and at death were 27.5 and 24.5 years older, respectively, compared with the ordinary type. Also, duration of the total clinical course from onset to death was 3.7 years less than in the late onset cases. The degree of amyloid deposition was more marked in the heart of the late onset cases, causing prominent cardiac hypertrophy. It was also marked in the kidneys or thyroid of two cases, but slight to moderate in the peripheral or autonomic nervous tissues in all cases. Immunohistochemical investigation demonstrated the presence of transthyretin (TTR) as an amyloid precursor protein and of serum amyloid P-component in amyloid deposits in various organs and tissues of the late onset type. These findings, as well as serum levels of variant TTR, were similar to those of the ordinary type. These results suggest that there are some factors other than the amyloid precursor protein that effect the degree of amyloid deposition.

Adolescent↗
PubMed1997

Summer-type hypersensitivity pneumonitis outside Japan: a case report and the state of the art.

A 61-year-old Korean housewife developed dyspnoea, cough and weight loss in the summer of 1994. The case was diagnosed as definite summer-type hypersensitivity pneumonitis (SHP) according to the criteria proposed for hypersensitivity pneumonitis and for SHP. Her serum antibodies to Trichosporon were positive. Her symptoms were exacerbated after she returned home and Trichosporon was isolated from the patient's home, indicating Trichosporon as the causative antigen. This is the first confirmed case of SHP outside Japan. On the basis of our research in SHP to date, we propose that SHP occurs in other Asian countries and that the assay of anti-Trichosporon antibodies is useful for the diagnosis of the disease.

Alveolitis, Extrinsic Allergic↗
PubMed1997

Effects of pulmonary surfactant on macrophage migration: suppression of chemokinesis by surfactant phospholipid and enhancement of chemotaxis by surfactant protein.

We fractionated the bronchoalveolar lavage fluid (BALF) from normal rabbit lungs into several fractions by high speed centrifugation and ethanol-ether extraction. Random migration, chemokinesis and chemotaxis of freshly harvested alveolar macrophages (AM), 24 h cultured AM, and peritoneal exudate cells (PEC) were assayed in vitro using a modified, under agarose method and a blind well chemotactic chamber method. Freshly harvested AM demonstrated little random migration compared with PEC. However, when freshly harvested AM were pre-incubated in surfactant free medium for 24 h, the cells showed the same rate of migration as PEC. The increased migration of the 24 h cultured AM was partially suppressed by the presence of all BALF fractions containing high proportions of phospholipid. The inhibition by Fr-L (a fraction enriched in phospholipids) was reversed by normal serum, but not by heat-inactivated serum, cholesterol, synthetic dipalmitoyl phosphatidyl choline, or indomethacin. Fr-L markedly suppressed macrophage chemokinesis but did not affect on macrophage chemotaxis. Alternatively, Fr-P, a delipidated preparation of surfactant consisting mainly of protein, had no effect on macrophage chemokinesis but increased the chemotaxis of PEC to zymosan-activated serum. We conclude that surfactant phospholipid suppresses AM migration, while surfactant protein increases macrophage chemotaxis.

Animals↗
PubMed1997

Induction of nitric oxide synthesis and xanthine oxidase and their roles in the antimicrobial mechanism against Salmonella typhimurium infection in mice.

The role of superoxide anion (O2-) and nitric oxide (NO) in the host defense mechanism against Salmonella typhimurium (LT-2) was examined by focusing on xanthine oxidase (XO) as an O2(-)-generating system and on inducible NO synthase (iNOS). When ICR mice were infected with a 0.1 50% lethal dose (2 x 10(5) CFU) of S. typhimurium, bacterial growth in the liver reached a peak value 3 days after infection (10(4.32) CFU/g of liver) and decreased thereafter. XO activity in the liver became maximum at 7 days after infection; the value was 34.6 +/- 1.4 mU/g of liver at 7 days (compared with 11.0 +/- 1.3 mU/g of liver before infection). The time profile of NO production in the liver as determined by electron spin resonance spectroscopy was consistent with that of XO activity. Histological examination of infected liver showed the formation of multiple microabscesses with granulomatous lesions consisting of polymorphonuclear cells and mononuclear cells, and iNOS-expressing cells were localized in the confined areas of the microabscesses. When XO inhibitors such as allopurinol and 4-amino-6-hydroxypyrazolo[3,4-d]pyrimidine (AHPP) were administered to the infected mice, the mortality of the mice was significantly increased (10 of 21 and 11 of 20 for the allopurinol- and AHPP-treated groups, respectively, versus 2 of 20 for control mice), and bacterial growth was significantly enhanced. A similar exacerbation of the infection was obtained with N(omega)-monomethyl-L-arginine (L-NMMA) treatment of the mice. Of considerable importance is that granuloma formation in the liver was poorly developed by treatment with either XO inhibitors or L-NMMA. These results suggest that XO and NO play an important role in the antimicrobial mechanism against S. typhimurium in mice.

Allopurinol↗
PubMed1997

Effects of granulocyte and granulocyte-macrophage colony-stimulating factors in a neutropenic murine model of trichosporonosis.

We produced disseminated trichosporonosis in a neutropenic murine model with Trichosporon asahii, which was identified by DNA relatedness analysis. We then assessed the efficacy of granulocyte colony-stimulating factor (G-CSF) (30 to 100 microg/kg of body weight per day) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.8 to 2 microg/kg x day). The administration of G-CSF either before or after infection improved the survival rate from less than 25% up to 100% (P < 0.05). The effects of G-CSF on organ clearance and histological examinations were most remarkable in the lungs. The levels of tumor necrosis factor alpha (TNF-alpha) in bronchoalveolar lavage fluid (BALF) of neutropenic and G-CSF-pretreated mice were 60 +/- 6 ng/ml and 18 +/- 6 pg/ml, respectively, at 24 h after infection. Immunohistologically, alveolar macrophages proved to be the main source of TNF-alpha in BALF. GM-CSF increased neutrophil counts less significantly than did G-CSF and increased the lethality (P < 0.05) with a high level of TNF-alpha in BALF. Expecting to inhibit TNF-alpha, we administered anti-TNF-alpha intraperitoneally at the dose completely inhibiting TNF-alpha in plasma (2 x 10(4) U), but the TNF-alpha level in BALF and the lethality increased. Though the number of neutrophils at the early stage of infection appeared to be the most critical, the results suggest that other host defense mechanisms, such as TNF-alpha overproduction in the lungs, have an important role in the prognosis of trichosporonosis.

Animals↗
PubMed1997

Expression of apoptosis-related antigen on eosinophils in chronic eosinophilic pneumonia.

We examined the expression of apoptosis-related antigens Fas and bcl-2 on eosinophils from peripheral blood (PB) and bronchoalveolar lavage (BAL) in patients with chronic eosinophilic pneumonia (CEP). The expression of those antigens was assessed before and after culture with or without eosinophil chemotactic factors derived from an established T-cell line (STO-2-derived ECFs; ECF-PI5, 6, 7, 8, and 9), granulocyte-macrophage colony stimulating factor, and interleukin 5 (IL-5). We found that the expression of these antigens on eosinophils from PB increased after 24 h culture without any stimulation. In contrast, little or no change was observed even after 24 h culture in eosinophils from BAL. All STO2-derived ECFs and IL-5 suppressed Fas expression on eosinophils from PB. Furthermore, we found that eosinophils which were attracted by ECF-PI9 expressed Fas and bcl-2 more highly than those attracted by other ECFs and IL-5. Such a heterogeneous response of eosinophils to respective ECFs suggests the possibility of a heterogeneous population of eosinophils in patients with CEP.

Adult↗
PubMed1997

Surgery of gastric cancer in patients over 80 years old.

A retrospective study on postoperative complications and factors affecting prognosis was performed on elderly patients with gastric cancer. We studied the correlation of age, pathological depth, preoperative laboratory data, physical status, duration of surgery, volume of blood loss, blood transfusion, curability, and extent of lymph node dissection to postoperative complications and prognosis in 47 patients with gastric cancer over 80 years old. Preoperative function of lung and liver frequently showed abnormal data. Postoperative complications were noted in 47% of patients, especially in the pulmonary system, liver and heart. Curability and extent of lymph node dissection were the significant factor affecting survival. Some mortalities caused by initial malignancy were recognized in the conservative lymph node dissection in the stage I. The incidence of postoperative complications was not significantly different according to extent of lymph node dissection. Blood transfusion was the only significant factor for the incidence of postoperative complication. The most frequent cause of death was the initial malignancy. We recommend that a low grade lymph node dissection should not be readily chosen for elderly patients in early cases.

Aged↗
PubMed1997

Altered accessory cell function of alveolar macrophages: a possible mechanism for induction of Th2 secretory profile in idiopathic pulmonary fibrosis.

Alveolar macrophages (AMs) are considered to play a central role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Recent studies have revealed a predominance of the type-2 T-helper (Th2) cytokine pattern of inflammatory response in the pulmonary interstitium in IPF. The aim of the present study was to determine whether or not the altered accessory cell function of AMs could account for the Th2 pattern of chronic inflammation in IPF. The levels of various cytokines were measured in the supernatants of soluble anti-CD3 monoclonal antibody (MoAb)-stimulated T-cells, co-cultured with autologous AMs, by enzyme-linked immunosorbent assay (ELISA). Cells from six patients with IPF and from nine normal volunteers (five nonsmokers and four smokers) were examined. The inhibitory effect of interleukin (IL)-10 on the accessory cell function of AMs and the expression of CD80 and CD86 on AMs were also investigated. IL-4 and IL-5 levels were significantly higher in the co-cultures from patients with IPF than in those from normal volunteers. IL-2, interferon-gamma (IFN-gamma), and IL-10 production in these co-cultures did not differ. IL-10 suppressed T-cell proliferation in co-cultures with AMs from healthy volunteers (smokers and nonsmokers), but not with AMs from patients with IPF. Expression of CD80 and CD86 on AMs from these groups did not differ. Thus, the altered accessory cell function of alveolar macrophages from patients with idiopathic pulmonary fibrosis may possibly relate to the pattern of type-2 T-helper cytokine production in response to inflammation.

Adult↗
PubMed1997

Indication of chemoembolization therapy without gelatin sponge for hepatocellular carcinoma.

This study evaluated the effect of chemoembolization (C-LIP) consisting of ethiodized oil (Lipiodol Ultra Fluid; André Guerbet, Aulnay-sous-Bois, France) and epirubicin, without gelatin sponge on hepatocellular carcinoma (HCC), administered by hepatic arterial infusion. We analyzed the cases from two points of view: the local recurrence rate for hypervascular solitary small HCC (tumor size: < or =3 cm in diameter) and the cumulative survival rate for advanced HCC (stage VI according to the criteria of Liver Cancer Group of Japan) following C-LIP therapy. The C-LIP also was compared with transcather arterial embolization (TAE; C-LIP followed by gelatin sponge) and percutaneous ethanol injection therapy (PEIT). In the small HCC cases, the recurrence rate at 1 year after C-LIP was 77% (10 of 13 patients), while the local recurrence rate was 46% (six of 13 patients) at 6 months and 61% (eight of 13 patients) at 1 year. The local recurrence rate at 1 year was 29% (four of 14 patients) after TAE and 20% (three of 15 patients) after PEIT. These results showed that the effect of local anticancer therapy by C-LIP was not as potent as that of TAE or PEIT. In advanced HCC cases, the cumulative survival rate for 13 patients treated by C-LIP was 72% at 6 months, 36% at 1 year, and 14% at 2 years. However, the survival rates for 13 patients at 6 months, 1 year, and 2 years after TAE were 46%, 23%, and 8%, respectively. There was no difference between the C-LIP patients and TAE patients with regard to the pretreatment liver function. Three patients died within 2 months after the initial TAE. These deaths were mainly due to damage to the noncancerous liver parenchyma. Therapy with C-LIP alone was not appropriate for hypervascular solitary small HCCs, and additional treatment was necessary. We think C-LIP therapy should be selected instead of TAE for advanced HCCs to avoid severe parenchymal damage.

Aged↗
PubMed1997

Effects of a novel free radical scavenger, MCl-186, on ischemic brain damage in the rat distal middle cerebral artery occlusion model.

We investigated the effects of a free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCl-186), on infarct areas, neurological deficits and regional cerebral blood flow (rCBF), with use of a rat thrombotic distal middle cerebral artery (dMCA) occlusion model to elucidate its possible therapeutic effects on focal cerebral ischemia. In addition, we have attempted to measure 2-oxo-3-(phenylhydrazono)-butanoic acid (OPB), which is the major oxidation product of MCl-186, in the penumbral cortex of a thrombotic dMCA occlusion model. Postischemic treatment with MCl-186 (3 mg/kg) significantly (P < .05) decreased the size of the cerebral infarcts 1 day after dMCA occlusion. MCl-186 (3 mg/kg) significantly (P < .05) improved the neurological deficits 1 day after dMCA occlusion. On the contrary, MCl-186 had no effect on rCBF 1 day after dMCA occlusion. MCl-186 mainly reacted into OPB by peroxidation in rat brain homogenates. Furthermore, the increase in OPB content in the ischemic penumbral cortex tissue was confirmed after 90 min of MCl-186 perfusion. These results suggest that MCI-186 has a protective effect on brain ischemia by reacting with oxygen radicals and that oxygen radicals are closely related to postischemic brain injury.

Animals↗
PubMed1997

[Quality control and cytogenetic analysis of human pre-embryos fertilized and cultured in vitro].

For the purpose to evaluate in vitro culture conditions of human preembryos, the efficacy of conventional culture and co-culture systems on embryonic development and genetic disorders was studied. Firstly, the development of cultured mouse embryos grown in standard media (Whitten's, GPM, HFT and Ham F10) or in HFT medium with different helper cell layers was compared. Embryonic growth was substantially reduced during in vitro culture, demonstrably by impaired cell proliferation, compared with in vivo controls. In in vitro fertilization and culture condition, SCEs of blastocysts were significantly increased. Development in co-culture with the feeder layers was notably better than in standard media. These results suggest that human preembryos could be rescued by the use of helper cells. Increased developmental rates and the cell numbers of blastocysts were the most evident morphological features of human preembryos that developed in co-culture with uterine luminal epithelial cells. However mosaicism may be caused by in vitro culture conditions and its onset may indicate when a disturbance in the embryonic development has occurred. It is advisable to perform further research into the mechanism of feeder cell-embryo interaction for understanding the optimal conditions of embryonic development in vitro.

Animals↗
PubMed1997

[Idiopathic interstitial pneumonia associated with a high level of CA19-9 in serum and with CA19-9 in lung tissue].

A 65-year-old man was admitted to our hospital because of mild dyspnea. A chest roentgenogram showed diffuse reticulonodular shadows in both lung fields. The concentration of CA19-9 in serum was high. Pancreatic cancer and other diseases were considered as causes, but no definitive diagnosis could be made. An open-lung biopsy was done, and examination of a specimen resulted in the diagnosis of idiopathic interstitial pneumonia (chronic type). Immunohistochemical staining with anti-CA19-9 antibody was positive. The lumens of microscopic honeycomb structures and fibrotic areas were covered with flattened and cuboidal metaplastic epithelial cells, which stained positively for anti-CA19-9 antibody.

Aged↗
PubMed1997

Mechanisms accounting for granulomatous responses in hypersensitivity pneumonitis.

Hypersensitivity granuloma formation is an immunopathological feature of HP. It is induced by the T cell-mediated delayed-type hypersensitivity reaction to organic dusts or active chemicals invading the lung. Circulating, antigen-reactive, memory CD4+ T cells, generated by previous sensitization, migrate into lung parenchyma in response to chemokines such as RANTES. The T cells develop into either Th0, Th1, or Th2 effector depending upon the conditions in which they first encounter the antigens. The Th1 cells produce IL-2 and IFN-gamma. IFN-gamma can prime macrophages to transcribe and to secrete greater amounts of TNF and IL-1. The macrophages activated by TNF and IL-1 produce a wide range of biologically active mediators such as MAF, MCF, and MIF. These monokines attract young macrophages into the lesions, activate them, and young macrophages develop into mature macrophages, resulting in the hypersensitivity granuloma consisting of epithelioid cells and multinucleated giant cells. CD8+ T cells, the most predominant cell in the lesions of HP, may modulate the granuloma formation via the production of Th1-like or Th2-like cytokines.

Allergens↗
PubMed1996

Induction of interstitial pneumonia in autoimmune mice by intratracheal administration of superantigen staphylococcal enterotoxin B.

The pathogenesis of lung complications in autoimmune disease remains unclear. To examine whether superantigens participate in the development of interstitial pneumonia in autoimmune disease, we instilled the bacterial superantigen staphylococcal enterotoxin B (SEB) into the tracheas of autoimmune and nonautoimmune mice. The intratracheal administration of SEB resulted in the induction of interstitial pneumonia manifested by infiltration of mononuclear cells into the alveolar septal walls and into the periarterial space and an increase in pulmonary interstitial collagen fibers in the autoimmune mouse strains. In the nonautoimmune strains, AKR, but not BALB/c and B10BR, mice also developed interstitial pneumonia after the intratracheal administration of SEB, although the degree of severity was milder than that induced in three autoimmune mouse strains. Although the intratracheal administration of another bacterial superantigen staphylococcal enterotoxin A also induced interstitial pneumonia, protein A which is a staphylococcal product but not a superantigen induced no remarkable change in lungs of MRL-+/+ mice. Immunohistologic studies revealed that not only SEB-reactive Vbeta8+ T cells, but also SEB-nonreactive Vbeta6+ T cells infiltrated the pulmonary lesions of SEB-primed MRL-+/+ mice, although this may be a secondary reaction for the Vbeta6+ T cells. The results of in vitro restimulation of spleen cells from SEB-primed BALB/c and SEB-primed MRL-+/+ mice with SEB suggest that incomplete induction of tolerance after the intratracheal administration of SEB may be involved in the pathogenesis of interstitial pneumonia induced in autoimmune mice. These results suggest participation of superantigens in the development of interstitial pneumonia in patients with autoimmune disease and other lung diseases such as idiopathic pulmonary fibrosis.

Animals↗