Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 397 records · Page 22Linked to original sources

PubMed1998

Role of endogenous nitric oxide in ischaemia-reperfusion injury of rat gastric mucosa.

It has been suggested that endogenous nitric oxide may act as a protective factor for gastric mucosa since nitric oxide increases blood flow and may scavenge certain oxyradicals. We tested the hypothesis that nitric oxide protects rat gastric mucosa against ischaemia-reperfusion stress. Gastric ischaemia was induced by clamping the left gastric artery for 20 min. Rats were treated with two kinds of specific inhibitors of nitric oxide production, NG-nitro-L-arginine or NG-monomethyl-L-arginine. Gastric mucosal integrity was continuously monitored by measuring the blood-to-lumen clearance of [51chromium]-labelled ethylenediaminetetraacetic acid (EDTA) under control conditions, during ischaemia and after reperfusion. Oxidative stress in gastric mucosa was assessed by measuring dichlorofluorescein (DCF) fluorescence intensity before ischaemia and after reperfusion. Blockade of nitric oxide resulted in a significant increase in [51Cr]-EDTA clearance and DCF fluorescence intensity after reperfusion. These effects of nitric oxide inhibitors were attenuated by pretreatment with L-arginine. In conclusion, these findings support the hypothesis that endogenous nitric oxide acts as an important protective factor against ischaemia-reperfusion stress in rat gastric mucosa.

Animals↗

PubMed1998

Solitary rectal ulcer syndrome accompanied by submucosal invasive carcinoma.

We report a case of carcinoma in solitary rectal ulcer syndrome. The diagnosis was made by colonoscopic appearance and biopsy. A tumor measuring 0.9 x 0.6 cm was found in a resected solitary rectal ulcer. The lesion exhibited typical histological features of solitary rectal ulcer syndrome, with a well differentiated adenocarcinoma invading submucosal layers and some dysplastic glands. We believe that the adenocarcinoma represents a malignant transformation from solitary rectal ulcer syndrome, because similar to longstanding chronic idiopathic colitis, colorectal dysplasia and carcinoma may develop.

Adenocarcinoma↗

PubMed1998

[Antibody response of inactivated influenza vaccine in the elderly].

The antibody responses of 31 elderly persons (11 males and 20 females, mean 82.2 years) and 23 adults (mean 40.7 years) to inactivated influenza vaccine were studied. Participants were given twice the influenza vaccine containing A/Yamagata/32/89, A/Kitakyusyu/159/93, and B/ Mie/1/93. Serum specimens were obtained before vaccination, and 2 weeks and 3 months after the second vaccination. Antibody to influenza was determined by hemagglutination inhibition test (HI). The rates of fourfold or greater increases of HI antibody against the A/Yamagata, A/ Kitakyusyu, and B/Mie were 96.8%, 100%, and 74.2%, and there was no significant difference of the rates of fourfold or greater increases between elderly persons and adults. The rates of possession of HI antibody more than 128 in titer after vaccination were significantly higher than those of HI antibody before vaccination, and were maintained at high levels up to three months after the second vaccination. These results suggest that antibody response to the inactivated influenza vaccine is satisfactory in the elderly.

Adult↗

PubMed1998

Increased induction of apoptosis by a Sendai virus mutant is associated with attenuation of mouse pathogenicity.

An avirulent mutant of Sendai virus, Ohita-MVC11 (MVC11), was generated from a highly virulent field strain, Ohita-M1 (M1), through successive passages in LLC-MK2 cell cultures (M. Itoh, Y. Isegawa, H. Hotta, and M. Homma, J. Gen. Virol. 78:3207-3215, 1997). In LLC-MK2 cells, MVC11 induced a high degree of apoptotic cell death that was demonstrated by chromatin condensation of the nucleus and DNA fragmentation, and production of MVC11 declined markedly after prolonged culture. On the other hand, M1 did not induce prominent apoptosis and maintained high virus titers. In primary mouse pulmonary epithelial cell cultures, M1 replicated rather slowly to reach maximum level of virus production at 3 days postinfection, and high levels of virus production were maintained thereafter without causing apoptosis. In contrast, MVC11, which produced 20 times more progeny virus than M1 at 1 day postinfection, induced a high degree of apoptotic cell death before the virus replication cycle was completed. Accordingly, the production of progeny virus was strongly inhibited thereafter. In the lungs of mice infected with MVC11, virus antigens and signals of DNA fragmentation detected by the in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling technique colocalized in bronchial epithelial cells, clearly demonstrating that infection by MVC11 triggered apoptosis in vivo as well as in vitro. These results suggest the possibility that induction of apoptosis by MVC11 plays an important role in attenuation of mouse pathogenicity by restricting progeny virus production in the lung. The C protein was shown to have the capacity to induce apoptosis, and the increased level of the C protein in MVC11-infected cells was considered to account partly, if not entirely, for the induction of apoptosis.

Animals↗

PubMed1998

The various Sendai virus C proteins are not functionally equivalent and exert both positive and negative effects on viral RNA accumulation during the course of infection.

Recombinant Sendai viruses were prepared which cannot express their Cprime, C, or Cprime plus C proteins due to mutation of their respective start codons ([Cprime-minus], [C-minus] and [double mutant], respectively). The [Cprime-minus] and [C-minus] stocks were similar to that of wild-type (wt) virus in virus titer and plaque formation, whereas the double-mutant stock had a much-reduced PFU or 50% egg infective dose/particle ratio and produced very small plaques. Relative to the wt virus infection, the [Cprime-minus] and [C-minus] infections of BHK cells resulted in significantly greater accumulation of viral RNAs, consistent with the known inhibitory effects of the Cprime and C proteins. The double-mutant infection, in contrast, was delayed in its accumulation of viral RNAs; however, once accumulation started, overaccumulation quickly occurred, as in the single-mutant infections. Our results suggest that the Cprime and C proteins both provide a common positive function early in infection, so that only the double mutant undergoes delayed RNA accumulation and exhibits the highly debilitated phenotype. Later in infection, the same proteins appear to act as inhibitors of RNA accumulation. In infections of mice, [Cprime-minus] was found to be as virulent as wt virus whereas [C-minus] was highly attenuated. These results suggest that the Cprime and C proteins cannot be functionally equivalent, since C can replace Cprime for virulence in mice whereas Cprime cannot replace C.

Animals↗

PubMed1998

Role of gap junctions in inhibiting ischemia-reperfusion injury of rat gastric mucosa.

Gap junctional intercellular communication (GJIC) is known to be important in the maintenance of tissue homeostasis. However, the role of GJIC in gastric mucosa has not been well investigated. We tested the hypothesis that maintenance of GJIC protects rat gastric mucosa against ischemia-reperfusion (I/R) stress by using irsogladine, an activator of GJIC, and octanol, an inhibitor of GJIC. Intragastric perfusion with octanol before ischemia resulted in a significant increase in 51Cr-EDTA clearance after reperfusion. Intraduodenal pretreatment with irsogladine attenuated the increase in 51Cr-EDTA clearance produced by octanol in a dose-dependent manner. Epithelial gap junctions reacted with anticonnexin-32 monoclonal antibodies were not changed after I/R stress alone. Intragastric perfusion with octanol caused a significant reduction in immunoreactive connexin-32 spots, which was completely reversed by irsogladine. These results indicate that inhibition of GJIC weakens the barrier function of gastric mucosa and subsequently causes damage of the barrier function in combination with I/R. Facilitation of GJIC and maintenance of gap junctions protect gastric mucosal barrier functions by potentiating cellular integrity.

Animals↗

PubMed1998

Exogenous NO enhances hydrogen peroxide-mediated neutrophil adherence to cultured endothelial cells.

One important aspect of oxidant injury is the enhancement of neutrophil-endothelial adhesion by oxidants such as hydrogen peroxide. Recent studies suggest that nitric oxide (NO) can limit oxidant-mediated tissue injury, since inhibitors of endogenous NO synthesis often promote neutrophil-endothelial adhesion. However, less is known about the direct role of exogenous NO in modulating proadhesive effects of oxidants. The objective of this study was to examine how an NO donor modifies hydrogen peroxide-mediated adhesion of neutrophils to cultured endothelial cells. Human umbilical vein endothelial cell monolayers were exposed for 30 min to 0-0.1 mM hydrogen peroxide with or without the NO donor spermine-NONOate (SNO; 0-0.5 mM), and the adhesion of 51Cr-labeled polymorphonuclear neutrophils (PMNs) was measured in a static adhesion assay. PMN adherence was not altered by either peroxide (up to 0.1 mM) or SNO (up to 0.5 mM) alone but was significantly increased by over 300% by coadministration of both 0.1 mM peroxide and 0.5 mM SNO. This increase in adhesion with these two agents was correlated with an increase in the presentation of surface P-selectin but not intercellular adhesion molecule-1. Both PMN adhesion and P-selectin presentation were blocked by 0.1 mM desferrioxamine (an iron chelator) and 1 mM methionine (an oxyradical scavenger). WEB-2086, a platelet-activating factor-receptor antagonist (10 microM), also prevented PMN adhesion but not P-selectin expression. An antibody directed against either P-selectin or intercellular adhesion molecule-1 also blocked adhesion. These data indicate that NO may actually exacerbate rather than protect against the inflammatory effects of peroxide in some models of inflammation through the synthesis of platelet-activating factor and the mobilization of P-selectin.

Azepines↗

PubMed1998

Urinary excretion of podocytes reflects disease activity in children with glomerulonephritis.

The significance of the presence of podocytes in the urine was studied in various renal diseases in children. The podocytes were detected by immunofluorescence using monoclonal antibodies against the podocalyxin that is present on the surface of podocytes which serves as a glycocalyx. They were scored according to the numbers per partitioned area on cytospun urine sediments. Urine podocytes were absent in normal control, nonglomerular diseases such as urinary tract infection and nonglomerular hematuria, and glomerular, non-inflammatory diseases such as minimal change nephrotic syndrome and membranous nephropathy. Conversely, the excretion of podocytes in the urine were detected in various glomerular, inflammatory diseases. A significantly higher level of the podocyte score was found in the acute state of glomerular diseases which was defined as within 6 months after disease onset. Positive correlations were obtained between the presence of urinary podocytes and the histological features of active extracapillary changes and mesangial proliferation. Urinary podocytes were examined monthly for 12 months in 7 cases with IgA nephropathy and 2 cases with Henoch-Schönlein purpura nephritis, and a consistently higher urinary podocyte score was observed in the patients with histological progression. The scoring of urinary podocytes was found to be useful clinically, as a diagnostic tool for glomerular or nonglomerular diseases, inflammatory or noninflammatory diseases, a marker for the estimation of the severity of active glomerular injury and also as a predictor of disease progression.

Adolescent↗

PubMed1998

Inhibitory effects of TRK-530 on rat adjuvant arthritis.

TRK-530 is a novel bisphosphonate derivative. We examined the anti-inflammatory effects of TRK-530 on adjuvant arthritis (AA) rats. When TRK-530 at a dose of 2.5 mg/kg was administered for 2 weeks to AA rats, it inhibited destructive changes in arthritic joints such as paw edema, bone loss and joint degeneration. TRK-530 also inhibited splenomegaly and suppressed the increase in serum sialic acid which is measured as a systemic parameter of inflammation. To clarify the inhibitory mechanism of TRK-530, interleukin-1 (IL-1)-like activities of resident peritoneal macrophages in AA rats given TRK-530 were compared with those of control rats. We found that TRK-530 inhibited IL-1-like activity induced by bacterial lipopolysaccharide 6 weeks after administration when the IL-1-like activities of control rats were still at high levels. These findings suggest that TRK-530 exerts anti-inflammatory activities in AA rats.

Animals↗

PubMed1998

Studies on the role of adhesive proteins in maintaining pregnancy.

UNLABELLED: It is well known that maternal fibrinogen (Fg) and factor X III are essential for maintaining early pregnancy. We studied their role by analysis of clinical reports and immunohistochemical investigation. METHODS: (1) We analyzed the pregnancy cases of congenital afibrinogenemia and congenital factor X III deficiency. (2) Immunohistochemical staining of Fg, subunit A of factor X III (X IIIA) and fibronectin (Fn) were performed in the human implantation site, placenta, and endometrial cells cultured in serum-free medium. RESULTS: (1) Afibrinogenemia needed to be administrated Fg from 4 weeks' gestation (4 wG), and factor X III deficiency needed factor X III concentrate from 5 wG, in order to prevent abortion. (2) Implantation tissues: Fg, cellular X IIIA and Fn were present at the decidual stroma around invasive cytotrophoblasts at 5 wG. X IIIA-positive cells coincided with LN-5-positive macrophages. Placenta: Fg, cellular X IIIA and Fn were present in the decidual layer. Endometrial culture cells: Fn was secreted by spindle-like shaped cells. X IIIA was secreted by round-shaped cells. CONCLUSION: Maternal Fg and factor X III are essential just after 4-5 wG, and in that period they and Fn are present abundantly in decidual stroma around invasive cytotrophoblasts. It is concluded that when cytotrophoblasts invade endometrium maternal Fg, factor X III and Fn are concerned with cytotrophoblasts' anchoring as adhesive proteins.

Abortion, Spontaneous↗

PubMed1998

Deposition and clearance of inhaled 18FDG powder in patients with chronic obstructive pulmonary disease.

As freon is limited in its use as a generator for aerosol inhalation, powder particles are used as an alternative for inhalation therapy. The pulmonary deposition and clearance of inhaled powder particles was studied by positron emission tomography (PET) in ten patients with chronic obstructive pulmonary disease (COPD) and in five normal controls. The powder, 5 microm in mean diameter, was water soluble and labelled with 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG). Powder inhalation was done with single deep inspiration from residual volume to total lung capacity. The initial deposition ratio in the right or left lung field to total inhaled dose, measured by an anteroposterior rectilinear scan, did not differ between normals and COPD patients. Ratios of radioactivity detected within the central and peripheral regions (the central to peripheral ratio) measured by the PET scan was not significantly different between COPD patients (4.8+/-2.6, mean+/-SD) and normals (2.6+/-0.8, mean+/-SD). However, the regional powder deposition in peripheral lung fields measured by the PET scan was significantly more uneven in COPD patients than in normal patients. The clearance rate of 18FDG, defined as the retention ratio of 18FDG activity to the initially deposited 18FDG at 60 and 120 min after inhalation, in the trachea, large bronchi or peripheral lung fields measured by tomographic scan showed a wider variation in COPD patients than in normals. To conclude, inhaled powder tended to be deposited more centrally and was distributed more unevenly in the peripheral lung in chronic obstructive pulmonary disease patients than in normals. This could be a limitation of powder inhalation used for therapy in chronic obstructive pulmonary disease patients.

Administration, Inhalation↗

PubMed1998

Enantioselective synthesis of a key intermediate of 20(S)-camptothecin via an enzyme-catalyzed resolution.

The key intermediate of a 20(S)-camptothecin 1 synthesis was obtained in a highly enantioselective fashion using an enzyme-catalyzed resolution. A commercially available protease was found to exhibit the highest enantioselectivity with moderate activity, and (S)-ethyl 2-acetoxy-2-[6-(acetoxymethyl)-1,1-(ethylenedioxy)-5-oxo- 1,2,3,5-tetrahydroindolizin-7-yl]butanoate 7c of 98% e.e. was obtained as the remaining substrate.

Antineoplastic Agents↗

PubMed1998

A new scoring system to predict the efficacy of steroid therapy for patients with active myocarditis--a retrospective study.

The efficacy of steroid therapy for active myocarditis is controversial, so a new scoring system was constructed based on 6 clinical parameters: (1) the mode of onset of the disease; (2) complications of immune-related systemic disorders; (3) evidence of viral infection; (4) the population of infiltrating inflammatory cells; (5) the appearance of multinucleated giant cells in endomyocardial biopsy specimens; and (6) the duration of active myocarditis. Points from -2 to +2 were assigned to each parameter and the total score was calculated from the 6 parameters. Twenty-one patients with clinically suspected myocarditis, who had been admitted to hospital from 1987, were retrospectively analyzed by this scoring system. Sixteen patients were treated without corticosteroids at presentation, and 5 patients were treated by conventional methods with adjunctive use of corticosteroids. In 10 patients of the non-steroid group myocarditis improved and their mean score was -4.8 at presentation. In 6 patients of the non-steroid group, myocarditis and cardiac symptoms persisted after initial therapy, and their score at presentation was -0.8. In 2 patients of the steroid group myocarditis improved after initial therapy and their score was +2. In 2 other patients of the steroid group, myocarditis and cardiac symptoms persisted and their score was +3. Another patient of the steroid group died from congestive heart failure and his score was -5 at presentation. In 8 of 9 patients with persistent myocarditis, the secondary phase therapy was challenged. Seven patients were treated with corticosteroids and 6 patients improved. Their score at the secondary phase was +2.5. Overall, non-steroid conventional treatment was successful in patients with the scores from -5 to -4, and steroid therapy succeeded in patients with scores from 0 to +6. Although this is a retrospective study, this scoring system is able to predict the efficacy of steroid therapy in patients with clinically suspected active myocarditis.

Acute Disease↗

PubMed1998

[Functional neuropharmacology in the human brain using positron emission tomography: PET imaging of impaired cognitive performance induced by sedative antihistamines].

Antihistamines are the efficacious drugs to be used for the symptomatic relief of allergic diseases. The safety issue of antihistamines is of central importance because of their widespread use in current medical practice. Positron emission tomography (PET) was used to better understand the pharmacological effects of antihistamines on the central nervous system. The H1 receptor occupancy was examined in young male volunteers with [11C]-doxepin after the oral or intravenous administration of antihistamines. In other studies, the cognitive performance was also measured tachistoscopically before and after taking antihistamines. The H1 receptor occupancy in the human cortex caused by antihistamines is significantly correlated with the reported values of incidence of sleepiness in clinical trials, and the occupancy is well proportional to the impaired cognitive performance. To understand the brain mechanism of antihistamine-induced "sleepiness and impaired cognition", the regional cerebral blood flow (rCBF) during the task was measured using 3D-PET and H2(15)O before and after administration of d-chlorpheniramine. After its administration, the rCBF was significantly decreased on the bilateral middle temporal gyrus, midbrain and anterior cingulate. These findings suggest that H1 receptor blockade would be affected on the activity of the attention and cognitive system in the brain.

Animals↗

PubMed1998

Utility of measuring serum parathyroid hormone-related protein concentration in leukemic patients with hypercalcemia for assessing disease status.

OBJECTIVE: To evaluate serum parathyroid hormone-related protein (PTHrP) as a marker of hypercalcemia in leukemic patients. DESIGN AND METHODS: We measured the serum levels of PTHrP, lactate dehydrogenase (LDH) and calcium in three patients with hypercalcemia due to leukemia. RESULTS: Serum levels of PTHrP, LDH and calcium were elevated at admission in all patients, and these levels were reduced to within the normal range after chemotherapy. However, normalization of serum PTHrP concentration occurred more rapidly than normalization of serum LDH levels after chemotherapy. The increase in serum PTHrP concentration accompanied leukemic cell proliferation and preceded the increases in serum LDH and calcium. Serum LDH concentration increased, but serum PTHrP concentration did not after administration of granulocyte colony-stimulating factor. CONCLUSION: These findings suggest that serum PTHrP may be a more useful marker than serum LDH or calcium in assessing the status of leukemic patients with hypercalcemia.

Biomarkers↗

PubMed1998

Distribution of F4/80-positive cells in developing ovaries in the mouse.

The mature ovary contains a large number of macrophages. In the present study, the distribution of macrophages in murine ovaries at various developmental stages was immunohistochemically studied using a monoclonal antibody against F4/80, a highly specific antigen of murine macrophages. The results showed that definite F4/80-positive stains were hardly detectable in ovaries on day 0 after birth. On day 7, a few F4/ 80-positive cells could be identified between the developing follicles. The positive stains were irregular in shape and showed little physical contact with the primordial or primary follicles. By days 14 and 21, when the theca cell layers of growing follicles were developing, the positive cells had extended or elongated to surround the cell layer. On day 28, besides the presence of elongating positive cells surrounding the growing follicles, irregularly shaped F4/80-positive cells became apparent in the interstitium between the growing follicles and also in the capsular tissues. Thereafter, positive cells with stellate appearance were detected in the corpora lutea, which first developed around 6 weeks of age. Although the positive cells were homogenously distributed in the corpora lutea in virgin adults, only a few sporadic positive cells were found there in pregnant mice. However, the positive cells infiltrated into the corpora lutea again in the postpartum period. These results show that ovarian macrophages exhibit dramatical changes in their distribution from neonatal to postpartum periods.

Animals↗

PubMed1998

Retroperitoneal malignant fibrous histiocytoma causing variegated colonic lesions.

A 68-year-old man visited our hospital because of heartburn. A firm mass was palpated in the left upper abdominal quadrant. Ultrasonography and computed tomography revealed a large left sided retroperitoneal tumor. A barium enema examination showed shallow irregularly depressed or elevated lesions. Colonoscopy revealed an irregularly shaped ulcer and multiple submucosal masses suggesting invasion by an extrinsic malignant tumor. Although colonoscopic biopsy was negative, a resected tumor was histologically diagnosed as a malignant fibrous histiocytoma (MFH). When such varigated lesions are detected in the colon, MFH should be considered, and an attempt to sample the submucosal layer may be necessary.

Aged↗

PubMed1998

Mixed connective tissue disease with severe pulmonary hypertension and extensive subcutaneous calcification.

The results of the autopsy of a 38-year-old female with mixed connective tissue disease who had suffered from painful subcutaneous calcification in her buttocks and extremities for 14 years and died from rapidly progressive pulmonary hypertension are reported. On autopsy, her heart and lungs revealed changes of severe pulmonary hypertension with intimal thickening and plexiform lesions in the small pulmonary arteries which had resulted in the collapse of both lungs and caused marked dilatation and hypertrophy of the right ventricle of the heart. Microscopic examinations of the subcutaneous calcified tissues indicated that the calcification may have been caused by repeated panniculitis.

Adult↗