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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 469 records · Page 26Linked to original sources
PubMed1995

Hemoglobin-induced lipid peroxidation in the retina: a possible mechanism for macular degeneration.

To investigate a possible link between subretinal hemorrhage and macular degeneration, oxyhemoglobin (HbO2) or methemoglobin (metHb) was incubated with retinal homogenate and unsaturated phospholipid peroxidation was monitored by (a) assay of thiobarbituric acid-reactive substances (TBARS), (b) luminescence originating from an energy transfer of lipid-degraded products to rose bengal, and (c) the decrease in composition of highly unsaturated fatty acids of phospholipids. TBARS formation and rose bengal luminescence in the case of metHb-induced lipid peroxidation were about 1.5 times greater than those in HbO2-induced lipid peroxidation. alpha-Tocopherol, a lipid-soluble antioxidant, and docosahexaenoic acid, a major unsaturated fatty acid, were slightly more rapidly decomposed after a 60-min incubation with metHb than with HbO2 at the same concentration. Atomic absorption analysis revealed that an equal concentration of iron was released from both HbO2 and metHb during incubation with retinal homogenates. The released iron may promote microsomal phospholipid peroxidation in the presence of endogenous ascorbate or NADPH-dependent cytochrome P-450 reductase because ascorbate oxidase and p-chloromercuribenzoic acid (an inhibitor of sulfhydryl enzymes) inhibited metHb- or HbO2-induced lipid peroxidation. MetHb-induced lipid peroxidation in retina was inhibited by KCN or NaN3, which binds to FeIII of metHb. KCN or NaN3 had no effect on HbO2-induced lipid peroxidation, because conversion of HbO2 to metHb, which can proceed in HbO2 incubated with phospholipid liposome, did not occur in retinal homogenates. It is concluded that metHb induces peroxidation of retinal unsaturated phospholipids (1) directly and (2) by releasing iron.

Animals↗
PubMed1995

Powerful hepatoprotective and hepatotoxic plant oligostilbenes, isolated from the Oriental medicinal plant Vitis coignetiae (Vitaceae).

The methanol extract of the Oriental medicinal plant Vitis coignetiae (Vitaceae) showed hepatoprotective activity in the in vitro assay method using primary cultured rat hepatocytes. Activity-guided fractionation of the extract afforded epsilon-viniferin as an active principle. The protective effect of epsilon-viniferin against mice carbon tetrachloride-induced hepatic injury in mice was shown by serum enzyme assay as well as by pathological examination. In addition to epsilon-viniferin, plant oligostilbenes, ampelopsins A, C, F and the mixture of vitisin A and cis-vitisin A were also present in the extract. Among them, ampelopsin C and the mixture of vitisin A and cis-vitisin A were found to be powerful hepatotoxins.

Animals↗
PubMed1995

Tumor necrosis factor-alpha and the failing human heart.

Tumor necrosis factor-alpha (TNF alpha) is a proinflammatory cytokine with negative inotropic effects. Recently, elevated levels of TNF alpha have been identified in patients with advanced heart failure. Although the clinical significance of this finding is unclear at present, there is increasing evidence that this cytokine may play a primary pathophysiologic role in the development and pathogenesis of heart failure in humans. Indeed, many of the clinical hallmarks of heart failure, including left ventricular dysfunction, cardiomyopathy, and pulmonary edema can be explained by the known biological effects of TNF alpha in humans. The present review will summarize recent evidence with regard to the biological role for TNF alpha in the adult mammalian heart, as well as summarize the increasing body of clinical information that implicates this cytokine in the pathophysiology of heart failure.

Adult↗
PubMed1995

Expression of estrogen receptor in diseased human prostate assessed by non-radioactive in situ hybridization and immunohistochemistry.

To understand the role of estrogen in the pathogenesis of benign prostatic hyperplasia, expressions of estrogen receptor (ER) mRNA and ER protein by in situ hybridization and by immunohistochemistry, respectively, were investigated in human prostatic tissues. In non-malignant region, ER mRNA and ER protein were found in cytoplasm and nucleus, respectively, of stromal cells, but not in glandular epithelial and basal cells. In benign regions, ER mRNA/ER protein positive cells were found in fibromyoadenomatous and myoadenomatous hyperplasia, but not in adenomatous hyperplasia. A striking feature was periacinar arrangement of ER mRNA/ER protein positive stromal cells in all prostate carcinoma treated with androgen withdrawal. The ER mRNA/ER protein positive cells were immunohistochemically identified as fibroblasts, myoblasts, and smooth muscle cells. These results indicate that stromal cells are the primary target of estrogen in prostate, and that androgen withdrawal upregulates the expression of ER gene.

Aged↗
PubMed1995

Intra-arterial chemotherapy with cisplatin followed by radical radiotherapy for locally advanced cervical cancer.

Locally advanced cervical cancer has a dismal prognosis, with a high local failure rate and a poor survival rate. To improve the cure rate for advanced carcinoma of the cervix, we initiated a study of intra-arterial (I-A) chemotherapy with cisplatin via the uterine artery prior to definitive radiotherapy. I-A chemotherapy via the internal iliac artery has been used to treat advanced cervical cancer; however, access by way of the uterine artery has not been tested for this purpose. Thirty-four patients with central tumor > or = 5 cm in anteroposterior diameter observed on CT scans were treated with I-A chemotherapy. I-A chemotherapy consisted of unilateral catheterization of the uterine artery using 120 mg/m2 cisplatin. After assessment of I-A chemotherapy, all but 3 patients were treated with a combination of whole-pelvis external irradiation and intracavitary irradiation. The 3 patients underwent external radiotherapy alone. Twenty-seven of 34 patients treated were evaluable for response to I-A chemotherapy. Eleven patients (41%) experienced a partial response. Seventy-six percent of the 34 patients treated with I-A chemotherapy followed by radiotherapy exhibited a complete response by the end of treatment. Toxicity was well tolerated and no death due to treatment occurred. The 2- and 5-year actuarial survival rates were 64 and 55%, respectively. The crude incidences of pelvic recurrence and distant metastasis observed at a median follow-up of 54 months were both 47%. This study for locally advanced cervical cancer suggests there is benefit to be derived from our I-A chemotherapy followed by radical radiotherapy.

Adult↗
PubMed1995

Surgical approach for maintaining nonischemic conditions of the liver in acute hepatic vein obstruction.

To establish a possible surgical approach for preventing warm ischemic injury to the liver followed by hepatic vein occlusion (HVO), the hepatic hemodynamics and energy metabolism were investigated in an acute canine HVO model with and without hepatic arterial blood flow. Arterial blood ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate) and adenylate energy charge potential (ECP = [ATP + 1/2 ADP]/[ATP+ADP+AMP]) of the liver tissue were measured during and after 60 min of HVO. In the group with hepatic arterial blood flow, in which arterial blood was drained by hepatofugal portal flow via the venovenous bypass, total hepatic blood flow, portal vein pressure, ECP, and AKBR were maintained at almost normal level after the termination of HVO, resulting in the survival of all animals for 3 days or longer. By contrast, in the group without hepatic arterial blood flow (warm ischemic group), total hepatic blood flow was maintained at less than 60% of preischemic value, and portal vein pressure gradually increased up to twice the preischemic value. ECP decreased from 0.81 +/- 0.06 to 0.71 +/- 0.07 along with increasing portal venous pressure, and AKBR also decreased from 1.23 +/- 0.12 to 0.63 +/- 0.23, resulting in no survival longer 6 hr. It was concluded that hepatic arterial blood flow during HVO, if drained as hepatofugal portal flow, could maintain nonischemic conditions in the liver, despite vena cava obstruction, by providing an alternate outflow via reversed flow in the portal vein.

Animals↗
PubMed1995

Determination of (+)- and (-)-nicardipine concentrations in human serum and their correlation with the antihypertensive effect after oral administration of racemic nicardipine.

Serum (+)- and (-)-nicardipine concentrations were determined after oral administration of racemic nicardipine, and the relationship between the concentration of each enantiomer and the percentage change in blood pressure was investigated. Serum concentrations of (+) and (-)-nicardipine were assayed separately by a method combining high-performance liquid chromatography (HPLC) with gas chromatography - mass spectrometry (GS-MS). Linear relationships were found with serum concentrations of 0.25-80 mg x ml(-1) for both enantiomers of nicardipine with correlation coefficients of greater than 0.999. A single oral dose of 40 mg racemic nicardipine was given to 15 patients with essential hypertension. Serum (+)-nicardipine concentration was 2-3 times higher than the concentration of (-)-nicardipine 1, 2, and 3 after drug administration. The logarithmically transformed value of the serum (+)-nicardipine concentration was inversely correlated with the percentage change in systolic blood pressure, the correlation being statistically significant 1 and 2 h after drug administration, and also inversely correlated with the percentage change in diastolic blood pressure 1, 2 and 3 h after drug administration. However, the logarithmically transformed value of serum (-)-nicardipine showed no significant correlations with the percentage change in either systolic or diastolic blood pressure.

Administration, Oral↗
PubMed1995

Force-inhibiting effect of okadaic acid on skinned rat uterus permeabilized with alpha-toxin.

Effects of okadai acid (OA) on contractile force in rat uterine uterine muscles permeabilized with alpha-toxin were examined. (1) Contractile force activated by Ca2+(10(-6.5) M to 10(-4.4) M) was suppressed by relatively low concentrations of OA (30 to 300 nM). The suppressed force was further decreased after washed out of OA. (2)Addition of 10 microM OA enhanced force. Whereas, the increased tension level fell to less than the control level after washed out of OA. (3)Okadaic acid methyl ester (methyl okadaate), an OA derivative without protein phosphatase inhibition, did not affect contraction. These results suggest that the force-inhibiting effect of OA is a result of interference with contractile elements through inhibition of protein phosphatases (PPs) activity.

Animals↗
PubMed1995

Effects of Na(+)-H+ exchange blocker amiloride on left ventricular remodeling after anterior myocardial infarction in rats.

We investigated the effects of amiloride, a Na(+)-H+ exchange blocker, on ventricular remodeling in an infarcted rat model. In the amiloride group, the left descending coronary artery was ligated and rats were given amiloride (1 mg/kg/day, n = 11) in their drinking water for 4 weeks. In the control group, rats were given water for 4 weeks (n = 8) after myocardial infarction. The rats were killed on day 28. Both the ratio of heart weight to body weight and that of left ventricular weight to body weight were significantly less in the amiloride group (p < 0.05). The diameter of a myocardial fiber in the region adjacent to the operated area was significantly reduced in the amiloride group compared with the control group (p < 0.05). Left ventricular cavity dimension was significantly smaller in the amiloride group than that in control group (p < 0.05). Our findings suggest that amiloride prevents ventricular remodeling after myocardial infarction.

Amiloride↗
PubMed1995

Analysis of bone marrow and peripheral blood immunoregulatory lymphocytes in patients with myelodysplastic syndrome.

The cell surface phenotype of immunoregulatory lymphocytes in bone marrow (BM) and peripheral blood (PB) in myelodysplastic syndrome (MDS), a stem cell disorder, was analyzed. Mononuclear cells from 25 patients with refractory anemia (RA) and nine with RA with an excess of blasts (RAEB) were characterized by two-color flow cytometry using various monoclonal antibodies. No significant change of CD3+, CD4+, and CD8+ cells in PB, but a decrease of the percent of positive cells for CD8++ among the total lymphocyte (%CD8++) was noticed in RA patients. On the other hand, in BM of RA patients, a decrease in the number of CD4+ cells, but not CD8++ cells, was noted. In RAEB patients, the absolute numbers of CD3+, CD4+, CD8+, and CD8++ cells in BM were decreased; however, the ratio of these lymphocytes was not changed. No change was observed among the CD4+ subsets in PB of RA or RAEB patients. In BM, a decrease in percentage of CD4+CD45RA+ (%CD4+CD45RA+; naive cell) and increases in CD4+CD45RO+ (%CD4+CD45RO+; memory cell) and CD4+CD29+ (%CD4+CD29+; helper/inducer) among CD4+ cells were found in both RA and RAEB patients. Analysis of the CD8++ subset showed an increased number of CD8++CD11a+ cells (activated CTL) in both BM and PB of RA patients, but not of RAEB patients. Furthermore, increments in CD56+ and CD16+ cells among CD3- cells (natural killer; NK cells) were seen in RA patients but not in RAEB patients. It remains unclear whether lymphocytes in MDS patients were involved in the abnormal (MDS) clones, but our results regarding the increments of CD8++CD11a+ and NK cells in RA patients suggest that the mechanism of immune surveillance against the abnormal MDS clones was activated in these RA patients, but not in RAEB patients. Further investigation is required to clarify the functions of these immunoregulatory lymphocytes in MDS patients.

Adult↗
PubMed1995

Release of superoxide radicals by mouse macrophages stimulated by oxidative modification of glycated low density lipoproteins.

Diabetic patients have high levels of glycated LDL. Although glycated LDLs are implicated in the development of atherosclerosis in such patients, convincing data are lacking. We observed release of superoxide radicals (O2-) from mouse resident peritoneal macrophages stimulated by an oxidized/glycated LDL by using a highly sensitive and specific chemiluminescence method. Oxidized/glycated LDL was achieved by an addition of low concentration of Fe3+ to glycated LDL. Macrophages took up an appreciable amount of the glycated LDL oxidized by iron, leading to the development of foam cells, while they did not take up untreated glycated LDL or the native LDL. These observations clearly indicate that the oxidized/glycated LDL reacts well with macrophages. Since an oxidation of glycated LDL may occur in vivo, the oxidized/glycated LDL might play an important role in atherogenesis.

Adenosine Diphosphate↗
PubMed1995

Splenic metastasis from lung cancer.

Splenic metastasis from lung cancer is a rare clinical event, most often diagnosed at the time of autopsy. We report 2 cases of splenic metastasis with a primary lung cancer. The first case was a 76-year-old man presenting with a recurrent solitary splenic metastasis 14 months after surgical removal of a squamous cell carcinoma of the lung. The second patient was a 72-year-old woman who had a poorly differentiated carcinoma of the lung and multiple abdominal metastasis. We also investigated 267 autopsy cases of lung cancer from 1975 to 1992. Histologically, there were 73 cases of squamous cell carcinoma, 123 adenocarcinoma, 29 large cell carcinoma, 36 small cell carcinoma, and 7 other miscellaneous tumours. The number of splenic metastasis from lung cancer in these cases was 15 (5.6%). Splenic metastasis from a primary cancer of the left lung was more frequent than that from the right lung. Nine of 15 splenic metastases were smaller than 1 cm in size. Splenic metastasis was associated with liver and pancreas metastasis. All 15 autopsy cases with splenic metastasis from lung cancer had other abdominal organ metastasis. Our analysis indicates that a solitary splenic metastasis is rare. Selection of a suitable therapeutic approach is important.

Aged↗
PubMed1995

Direct measurement of superoxide-dependent chemiluminescence from rat skin following UV-dependent fluoroquinolone-induced dermatitis.

Fluoroquinolones are widely used for the treatment of bacterial infection. However, some members of the group cause UV-dependent dermatitis. Therefore, animal models are required to screen and predict if a derivative is likely to cause photodermatitis. Under anaesthesia, the hair on the dorsal side of rats was shaved, then a fluoroquinolone derivative, Y-26611 or ofloxacin was administered subcutaneously (SC) followed by irradiation of a 3 cm diameter circular area of the skin with UV-B(ultraviolet-B) for 45 min. Peak photodermatitis was observed 24 h after irradiation in Y-2611-treated skin. Leucocyte infiltration into the skin, mostly polymorphonuclear leucocytes, was verified by histological techniques. O2.- radical generated by activated leucocytes was detected directly from the skin by SC application of a sensitive O2.- -dependent luminescence reagent, MCLA. O2.- -dependent photon emission (chemiluminescence) from the skin was amplified by phorbol myristate acetate and was markedly suppressed by superoxide dismutase. This is the first report of direct detection of chemiluminescence from the skin of a living animal.

4-Quinolones↗
PubMed1995

Influence of occlusal force and mandibular position on tooth contacts in lateral excursive movements.

The diagnosis and treatment of occlusal disharmonies requires an understanding of the variables that affect occluding tooth contacts. Quantitative recordings of tooth contacts and near tooth contacts are necessary for detailed analysis of occlusion. In this study, different thicknesses of registration strips were used to assess the influence of occlusal force and mandibular position on tooth contacts and clearance. This assessment was made for nonworking side molars and working side premolars. There was a significant decrease in clearance with increased occlusal force on both the nonworking and the working sides. A significant increase of clearance was noted as the mandible moved to the most lateral position on the nonworking side. These results indicate that the variables of occlusal force and mandibular position represent potential sources of disparity in the recording of tooth contacts. These variables should be considered when occlusal examination procedures are conducted.

Adult↗
PubMed1995

Detection of O2- generation and neutrophil accumulation in rat lungs after acute necrotizing pancreatitis.

BACKGROUND: Polymorphonuclear neutrophils (PMNs) and PMN-derived superoxide anions (O2-) have been found to mediate acute respiratory distress syndrome (ARDS). But the evidence has been obtained only indirectly, (for example, by treatment with free radical scavengers or by measuring lipid peroxides). METHODS: We used chemiluminescence technique to measure O2- generation directly from the surface of rat lungs with necrotizing pancreatitis. Myeloperoxidase activity in the lung tissue was measured by a new chemiluminescence method to quantitate pulmonary neutrophil sequestration. RESULTS: Transient bursts of chemiluminescence that reflected O2- generation were observed at the lung surface 3 to 5 hours after necrotizing pancreatitis was induced. No O2- dependent chemiluminescence was detected at the lung surfaces of the neutropenic rat made by pretreatment with polyclonal antineutrophil antibody. Myeloperoxidase activity was significantly high (mean, 1690 cell numbers/mg wet tissue) in the necrotizing pancreatitis rat lung (p < 0.005). CONCLUSIONS: These data confirmed that activated neutrophils and neutrophil-derived superoxide anions were implicated in lung injury after acute severe pancreatitis.

Acute Disease↗
PubMed1995

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome) in two Japanese siblings.

We report on two Japanese siblings (one female and one male) with PEHO syndrome (progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy). They showed profound generalized hypotonia early in infancy and developed infantile spasms with hypsarrhythmia within the first year of life. Abnormal eye movement and visual failure with optic atrophy were also observed early in infancy. Psychomotor development was arrested and serial neuroradiological studies showed slight progressive brain atrophy, dominantly of the brainstem. This is the first case report of PEHO syndrome, other than those dealing with the Finnish population.

Brain↗
PubMed1995

The effect of a probiotic on faecal and liver lipid classes in rats.

The effect of a probiotic composed of Bacillus, Lactobacillus, Streptococcus, Saccharomyces and Candida species (each at 10(7-8) colony-forming units (cfu)/g rice bran), given at a level of 150 g/kg diet for 6 weeks, on lipid metabolism was examined in the faeces, serum and liver of male rats. Liver weight decreased 35% in the rats fed on a high-fat, high-cholesterol diet containing the probiotic. Total cholesterol concentration in the serum was significantly lower in the probiotic group than in the control group throughout the experimental period in rats fed on the high-fat, high-cholesterol diet, and HDL-cholesterol concentration was significantly higher (P < 0.05) in the probiotic group than in the control group which was fed for the 6 week experimental period on a basal diet. The serum VLDL+IDL+LDL cholesterol concentration in the probiotic groups were reduced compared with those of the corresponding control groups. The probiotic groups fed on the high-fat, high-cholesterol diet and the basal diet had lower hepatic cholesterol concentrations than did the corresponding control groups (P < 0.05). Hydroxymethylglutaryl coenzyme A reductase (NADPH) (EC 1.1.1.34) activity in the liver was lower in rats fed on the high-fat, high cholesterol diet with the probiotic. The neutral and acidic steroid concentrations in faeces were higher in the probiotic group than in the control group fed on the high-fat, high-cholesterol diet. Escherichia coli decreased and Bifidobacterium and Eubacterium increased in the faecal microflora of rats fed on the dietary probiotic. Lactobacillus in the probiotic groups was higher than that in the control groups. The present study shows that the probiotic promotes Bifidobacterium and Eubacterium in the faecal microflora, and reduces cholesterol levels in the serum and liver of rats.

Animals↗