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Biomedical subjects

M Tada

Publications and source records attributed to M Tada.

At least 235 records · Page 13Linked to original sources
PubMed1996

Distribution of inflammation and atrophy in the stomach of Helicobacter pylori-positive and -negative patients with chronic gastritis.

OBJECTIVES: To investigate the extent of inflammation and atrophy in the stomach of Helicobacter pylori-positive and -negative patients with chronic gastritis. METHODS: Endoscopy with biopsies from the lesser curvatures of the antrum, angulus, middle body, and the greater curvature of the middle body of the stomach was performed in 59 patients with histologically confirmed chronic gastritis. The extent of atrophic gastritis was assessed endoscopically as well histologically. H. pylori status was assessed by histology as well as enzyme-linked immunosorbent assay. The histological severity of chronic and acute inflammation, glandular atrophy, and intestinal metaplasia was assessed according to the Sydney system. RESULTS: In H. pylori-positive patients, H. pylori was evenly distributed throughout the stomach when the extent of atrophic gastritis was limited to the antrum and the lesser curvature of the body, but disappeared from the antrum of patients with more extensive atrophic gastritis. The severity of acute and chronic inflammation at the greater curvature of the body increased with the extension of atrophic gastritis. In H. pylori-negative patients, the severity of chronic inflammation at the greater curvature of the body was significantly higher in patients with extensive atrophic gastritis than in those with a lesser extent of atrophic gastritis. CONCLUSION: At the greater curvature of the body, the development of atrophy is closely associated with the increase in the severity of inflammation, which is more marked in H. pylori-positive patients.

Adolescent↗
PubMed1996

A nitric oxide donor reverses myocardial injury in rabbits with acute hypercholesterolemia.

We evaluated the propagation of myocardial injury in a model of coronary artery occlusion and reperfusion in control and hypercholesterolemic rabbits. This was done by examining the differences in the infarct size and in the extent of leukocyte accumulation resulting from coronary artery occlusion (30 min) followed by reperfusion (2 or 48 hr) in rabbits fed 1% cholesterol for 4 days vs. controls not fed cholesterol. There was no significant difference in the infarct size in the 2-hr (45.7 +/- 6.7%, n = 8) vs. 48-hr (48.8 +/- 5.8%, n = 9) models of reperfusion in control rabbits. However, infarct size in the cholesterol-fed rabbits at 2 hr (64.0 +/- 4.1%, n = 6) or 48 hr (72.3 +/- 3.0%, n = 8) of reperfusion significantly exceeded that in the corresponding controls (P < .05). The infarct in cholesterol-fed rabbits at 2 hr of reperfusion was smaller than that at 48 hr of reperfusion, but not significantly. Treatment with S-nitroso-N-acetylpenicillamine, a nitric oxide donor, effectively reduced the size of infarct in the cholesterol-fed rabbits. However, treatment with N-acetylpenicillamine had no infarct-limiting effect. When we evaluated the extent of leukocyte accumulation in the ischemic myocardium, as assessed by myeloperoxidase activity, a positive correlation was observed between myeloperoxidase activity and infarct size at 48 hr of reperfusion. Results indicate that the propagation of myocardial ischemia and reperfusion injury in acutely hypercholesterolemic rabbits differed from that in controls. An exogenous nitric oxide donor effectively reduced the size of infarct associated with the reduction in the accumulation of leukocytes 48 hr after reperfusion, which suggests that a reduction in the production of endogenous nitric oxide during ischemia and reperfusion may aggravate the severity of myocardial injury in acutely hypercholesterolemic rabbits.

Animals↗
PubMed1996

[Hepatic intra-arterial 5-fluorouracil and CDDP administration in patients with colorectal cancer metastasis to the liver].

Eleven patients with hepatic metastasis from colorectal cancer were treated by combined chemotherapy with 5-FU and CDDP. Metastatic tumor was not resected or incompletely removed in all cases. 5-FU (180 mg/m2/day) as a 7-day continuous hepatic arterial infusion (HAI) with CDDP (10 approximately 20 mg/2 weeks) or intermittent high dose 5-FU HAI (1,000 mg/m2/5 h) with CDDP (10 approximately 20 mg/2 weeks) was administered, followed by a one-week rest. The overall response rate was 63.8%. There was a significant prolongation in overall survival compared with controls. Drug-related toxicity was observed in 10 cases (91.0%), but nothing serious. Survival can be prolonged with almost normal quality of the life in patients with colorectal liver metastasis.

Adult↗
PubMed1996

Re-evaluation of myocardial FDG uptake in hyperglycemia.

UNLABELLED: Myocardial [18F] fluorodeoxyglucose (FDG) uptake depends on several metabolic variables in vivo. The effect of different levels of experimentally induced hyperglycemia on myocardial FDG uptake was examined. METHODS: FDG uptake was studied in young Donryu rats 1 hr after intravenous injection under various pretreatments that increased serum glucose levels. Serum samples were analyzed for glucose, insulin and free fatty acids. Myocardial distribution of FDG was examined with autoradiography. RESULTS: Administration of glucose (n = 42), triiodothyronine (n = 7), epinephrine (n = 7), dehydroascorbic acid (n = 5) and 4 mg streptozotocin (Szt, n = 10) increased glucose levels to 120-200 mg/dl. Dexamethasone (Dex, n = 34) and 6 mg Szt (n = 6) increased glucose levels to 200-450 mg/dl. Myocardial FDG uptake increased proportionately with increases in serum glucose level up to 200 mg/dl. In severe hyperglycemia (serum glucose: 200-450 mg/dl), however, the FDG uptake decreased and did not correlate with blood glucose level. A study of fractional FDG uptake calibrated by the arterial FDG curve confirmed the same results. Heterogeneous distribution of FDG was observed in the myocardium, both in fasting and in severe hyperglycemic conditions. The pattern of FDG uptake by skeletal muscles was similar to that of the myocardium, although the uptake was lower than that in the myocardium. Changes in insulin and free fatty acids levels could not explain the FDG uptake pattern in severe hyperglycemia. Blood FDG uptake level remained constant regardless of glucose level. CONCLUSION: Hyperglycemia induced a biphasic pattern of myocardial FDG uptake, common with skeletal muscles. The understanding of myocardial FDG uptake characteristics and their dependence on blood glucose is helpful in interpreting myocardial FDG-PET images.

Animals↗
PubMed1996

Clinicopathological study of choroid plexus tumors: immunohistochemical features and evaluation of proliferative potential by PCNA and Ki-67 immunostaining.

This report concerns the retrospective immunohistochemical characterization and evaluation of the proliferative potential of eight choroid plexus tumors (CPTs) that included six cases of choroid plexus papilloma (CPP), one of whom had a recurrence, and two cases of choroid plexus carcinoma (CPC). Antibodies to prealbumin, glial fibrillary acidic protein (GFAP), vimentin, keratin, and carcinoembryonic antigen (CEA) were used to determine the immunohistochemical features of interest. The proliferative potential was evaluated with antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67. Antibody binding was visualized by the avidin-biotin-peroxidase complex (ABC) method. Immunoreactivity was scored on a-to 4+ scale, and in the case of PCNA and Ki-67, expected as staining index (SI). All seven CPP specimens were immunostained for prealbumin, but not for CEA. Expression of GFAP, vimentin and keratin varied from one CPP case to another. Both CPCs expressed CEA, but not prealbumin, GFAP and keratin; one of them was vimentin-positive. As determined by immunostaining for Ki-67, the proliferative potential was lower in the CPPs than in the CPCs. Among the former, the highest Ki-67 SI was seen in the primary lesion of a recurring papilloma. On the other hand, immunostaining for PCNA gave less consistent SI values. Our results show that immunohistochemical assays for prealbumin and CEA expression are of significant value for the differential diagnosis of CPPs and CPCs, and that high Ki-67 SI values may serve as an indicator of CPP recurrence, even if the primary lesion is benign.

Adult↗
PubMed1996

[Early gastric cancer].

In the therapy for early gastric cancer, Endoscopic diagnosis is essential. When early gastric cancer is diagnosed within certain range, it is possible to be cured without surgery only endoscopic therapy. Indication for now endoscopic therapy is limited lesion which is well differentiated adenocarcinoma not more than 2 cm in size with mucosal infiltration but no ulceration. In the endoscopic therapy, it is important to detect serial multiple occurrence of early gastric cancer and recurrence of residual cancerous lesion. For these problems, annual endoscopic examination is needed.

Adenocarcinoma↗
PubMed1996

Effect of cadmium injury on growth and migration of cultured human vascular endothelial cells.

The effect of cadmium chloride (CdCl2) on the cell proliferation and migration of cultured human umbilical vein endothelial cells (HUVECs) was quantitatively analyzed. The HUVEC viable cell count decreased dose-dependently after exposure to Cd (cadmium chloride, 10 nM-1 mM). Morphologic examination by phase-contrast microscopy revealed severe damaging effects of Cd at higher concentrations. The cytotoxic effect of Cd (10 microM-1 mM) on DNA synthesis was also concentration-dependent. When the distance endothelial cells grew out from the scraped edge of a monolayer was measured, HUVEC outgrowth was found to be inhibited by Cd (1.0 microM-1.0 mM) in a dose-dependent manner. These findings suggest that HUVEC cell proliferation and migration are susceptible to Cd cytotoxicity, and that this may be involved in the pathogenesis of atherosclerosis.

Cadmium Chloride↗
PubMed1996

Copper enhances EDNO (endothelium-derived nitric oxide) activity by cultured human vascular endothelial cells.

The effect of copper sulfate (Cu) on viable cell number, endothelium-derived nitric oxide (EDNO), and nitric oxide synthase (NOS) in cultured human umbilical vascular endothelial cells (HUVEC) was investigated. The viable cell number was not affected by the addition of Cu (1.0-500.0 microM). To assess the effect of EDNO by HUVEC, platelet aggregation experiments were performed, using cuvettes lined with HUVEC. Thrombin (0.05 units/ml)-induced platelet aggregation was markedly inhibited in the presence of HUVEC compared with aggregation in the absence of HUVEC. The HUVEC-dependent anti-platelet aggregatory effect was slightly reduced when HUVEC were pretreated with indomethacin (IND; 1.0 micro M), an inhibitor of the cyclo-oxygenase pathway. However, the thrombin-induced platelet aggregation in the presence of HUVEC pretreated with IND was smaller than that in the absence of HUVEC, which is dependent on EDNO. The anti-platelet aggregatory effect of HUVEC pretreated with IND was increased dose-dependently by 48-hour pretreatment of HUVEC with Cu (1.0-100.0 microM). To assess the effect of Cu on NOS, HUVEC were stained with NOS/NADPH diaphorase. However, there were no significant differences in the NOS-positive HUVEC cell count between cells without Cu and those with various concentrations of Cu. These findings suggest that Cu stimulates the activity of EDNO, which action may be dependent on Cu decreasing EDNO-oxidative damage.

Cell Survival↗
PubMed1996

Cadmium injures tube formation by cultured human vascular endothelial cells.

The effect of cadmium chloride (Cd; CdCl2) on the tube formation by cultured human umbilical vascular endothelial cells (HUVEC) was examined. HUVEC were collected by enzymatic digestion with collagenase. Tube formation was studied by culturing the cells on a gelled basement membrane matrix (Matrigel). Treatment of HUVEC with 0.1 microM-1.0 mM Cd for 24 hours inhibited tube formation dose-dependently. The cadmium concentration inhibiting tube formation by 50% relative to untreated cells was about 150 microM. The length of tube formation decreased time-dependently with 150 microM Cd. The treatment of HUVEC by 50 nM of beta-phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, increased tube formation. However, the inhibitory effect of Cd on tube formation was not affected by the addition of PMA. The pretreatment of the Matrigel by Cd inhibited tube formation similarly to the results of Cd treatment. These findings suggest that Cd inhibits the formation of a capillary network by HUVEC, and that the Cd-inhibitory effect on tube formation may have been dependent in this study on the degeneration of Matrigel by Cd.

Cadmium Chloride↗
PubMed1996

Methylmercury modulation of monocyte chemotactic protein-1 mRNA expression in human peripheral blood mononuclear cells.

The effect of methylmercury (MeHg; CH3HgCl) on the gene expression of monocyte chemotactic protein-1 (MCP-1) by human peripheral blood mononuclear cells (PBMC) was examined. PBMC were exposed with or without thrombin (1 U/ml) or MeHg (0.3 or 3.0 microM) for 24 hours. The total RNA was reverse transcribed and then amplified by the method of reverse transcriptase-polymerase chain reaction (RT-PCR). Thrombin enhanced MCP-1 mRNA expression in PBMC. MeHg inhibited thrombin-stimulated MCP-1 mRNA expression in a dose dependent manner. These findings suggest that MeHg affects the atherosclerotic process by changing MCP-1 mRNA expression in PBMC.

Chemokine CCL2↗
PubMed1995

Effect of methylmercury (CH3HgCl) injury on nitric oxide synthase (NOS) activity in cultured human umbilical vascular endothelial cells.

The effects of methylmercury (CH3HgCl; MeHg) on the production of nitric oxide (NO) and the activity of the enzyme, nitric oxide synthase (NOS), in cultured human umbilical vascular endothelial cells (HUVEC) were examined. To assess the production of NO by HUVEC, platelet aggregation experiments were performed using cuvettes lined with HUVEC. Thrombin (0.05 U/ml)-induced platelet aggregation was inhibited in HUVEC pretreated with indomethacin (1 microM), an inhibitor of the cyclo-oxygenase pathway. The anti-platelet aggregatory effect of HUVEC treated with indomethacin was decreased dose-dependently by 48-h pretreatment with MeHg (0.5-2 microM). The effect of MeHg on the NADPH diaphorase staining of NOS in HUVEC showed dose-dependent cytotoxicity in regard to NOS activity. These findings suggest that MeHg inhibits the production of NO by HUVEC, an action which may be dependent on the cytotoxic effect exerted by MeHg on NOS activity.

Blood Platelets↗
PubMed1995

Inactivation of glutathione peroxidase by nitric oxide. Implication for cytotoxicity.

S-nitro-N-acetyl-DL-penicillamine (SNAP), a nitric oxide (NO) donor, inactivated bovine glutathione peroxidase (GPx) in a dose- and time-dependent manner. The IC50 of SNAP for GPx was 2 microM at 1 h of incubation and was 20% of the IC50 for another thiol enzyme, glyceraldehyde-3-phosphate dehydrogenase, in which a specific cysteine residue is known to be nitrosylated. Incubation of the inactivated GPx with 5 mM dithiothreitol within 1 h restored about 50% of activity of the start of the SNAP incubation. A longer exposure to NO donors, however, irreversibly inactivated the enzyme. The similarity of the inactivation with SNAP and reactivation with dithiothreitol of GPx to that of glyceraldehyde-3-phosphate dehydrogenase, suggested that NO released from SNAP modified a cysteine-like essential residue on GPx. When U937 cells were incubated with 100 microM SNAP for 1 h, a significant decrease in GPx activity was observed although the change was less dramatic than that with the purified enzyme, and intracellular peroxide levels increased as judged by flow cytometric analysis using a peroxide-sensitive dye. Other major antioxidative enzymes, copper/zinc superoxide dismutase, manganese superoxide dismutase, and catalase, were not affected by SNAP, which suggested that the increased accumulation of peroxides in SNAP-treated cells was due to inhibition of GPx activity by NO. Moreover, stimulation with lipopolysaccharide significantly decreased intracellular GPx activity in RAW 264.7 cells, and this effect was blocked by NO synthase inhibitor N omega-methyl-L-arginine. This indicated that GPx was also inactivated by endogenous NO. This mechanism may at least in part explain the cytotoxic effects of NO on cells and NO-induced apoptotic cell death.

Animals↗
PubMed1995

Roles of alpha 1-adrenoceptor activity in the release of nitric oxide during ischemia of the canine heart.

The difference in end-products of the nitric oxide, i.e., nitrate-plus-nitrite, in the coronary arterial and venous blood was increased during coronary hypoperfusion of the canine heart (12.8 +/- 0.6 vs. 2.2 +/- 0.2 microM at the baseline). Norepinephrine from sympathetic nerve endings in the heart is released due to ischemic stress, however the relation of norepinephrine with nitric oxide is unknown during ischemia. Neither beta- or alpha 2-adrenoceptor antagonists attenuated the release of nitric oxide during coronary hypoperfusion. An intracoronary infusion of an alpha 1-adrenoceptor antagonist attenuated the release of nitric oxide during coronary hypoperfusion (5.3 +/- 0.4 microM), and the attenuation of alpha 1-adrenoceptor activity further decreased coronary blood flow during hypoperfusion. These findings suggest that alpha 1-adrenoceptor activity contributes to the mechanisms whereby nitric oxide is released from the ischemic myocardium.

Animals↗
PubMed1995

Plasma nitric oxide end products are increased in the ischemic canine heart.

Coronary arteriovenous difference in stable end-products of nitric oxide metabolism, nitrate and nitrite, was increased in ischemic canine hearts. In accordance with the reduction of coronary blood flow by 40, 67, 80 and 100%, the plasma nitrate+nitrite concentration increased from 3.2 +/- 0.6 to 8.7 +/- 1.3, 12.5 +/- 1.8, 15.9 +/- 2.7, and 20.2 +/- 2.3 microM, respectively. The plasma nitrate+nitrite concentrations were further elevated during reperfusion. Administration of NG-nitro-L-arginine methyl ester decreased the production of both nitrate+nitrite and coronary blood flow; the former was restored by the concomitant administration of L-arginine. These findings suggest that the increases in the nitric oxide production result from the action of nitric oxide synthase during myocardial ischemia and reperfusion, decreasing coronary vascular resistance and attenuating myocardial ischemia.

Animals↗
PubMed1995

Effects of partial hepatectomy on initiation of liver cell foci by 4-nitroquinoline 1-oxide, a non-hepatocarcinogen, and generation of DNA adducts in rats.

The influence of administration time after partial hepatectomy (PH) on liver cell foci induction and generation of DNA adducts by tritiated or non-tritiated 4-nitroquinoline 1-oxide (4NQO), a reported non-hepatocarcinogen, was investigated. With the use of the resistant hepatocyte model (Experiment I), 4NQO (20 mg/kg body wt. i.g.) was administered to 7-week-old male F344 rats at various times from 6 h before to 24 h after PH. Numbers and areas of glutathione S-transferase placental from (GST-P) positive liver cell foci gradually increased as the interval between PH and administration of 4NQO was prolonged to 24 h. In a 4NQO-DNA adduct study (Experiment II-a), adduct levels in the liver, pancreas and lung of partially hepatectomized rats were found to be appreciable 6-20 h after administration of 4NQO. In the adduct study (liver, pancreas and lung) after PH (Experiment II-b), 4NQO administration from the 0- to 18-h time points was associated with significantly marked elevation (P < 0.001-0.01) of adduct levels as compared to the carcinogen control value, while by 24 h the formation of adducts had again decreased significantly. The findings suggest that cell proliferation with effective DNA adduct levels is important for initiation of foci development.

4-Nitroquinoline-1-oxide↗
PubMed1995

Nucleolar segregation as an early marker for DNA damage; an experimental study in rats treated with 4-hydroxyaminoquinoline 1-oxide.

Male 6-week-old Sprague Dawley rats were given a single intravenous injection of 4-hydroxyaminoquinoline 1-oxide (4HAQO) at a dose of 20 mg/kg in order to produce ultrastructural changes as possible morphological biomarkers for toxicity. Immunohistochemically demonstrated formation of 4HAQO-DNA adduct was correlated with the changes found. Nucleolar alteration, demonstrable by electron microscopy as segregation of nucleolar components into granular and fibrillar compartments, was evident in cells of the target organs, exocrine pancreas and adrenocortex, but not of the non-target liver parenchyma. Sequential observation clarified that such alteration was highest in frequency 6 h and 4 h after 4HAQO administration in pancreatic acinar cells and adrenocortical cells respectively. Electron microscopically, apoptotic changes of acinar cells were evident 2 h after injection of 4HAQO. DNA adduct formation was consistently demonstrated in the same target organs showing nucleolar segregation, the highest frequency being noted 4 h after 4HAQO treatment in both pancreatic acinar cells and adrenocortical cells. Our results thus indicate an identity of the target cells for nucleolar segregation and 4HAQO-DNA adduct formation which correlates with 4HAQO-toxicity. We suggest that nucleolar segregation occurs subsequent to the generation of DNA damage.

4-Hydroxyaminoquinoline-1-oxide↗