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Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 1,225 records · Page 68Linked to original sources
PubMedDate not supplied

Bisbenzylisoquinoline alkaloids inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Bisbenzylisoquinoline alkaloids, cepharanthine, berbamine and isotetrandrine, were isolated from Stephania cepharantha Hayata. These compounds inhibit arachidonic acid-induced inflammation in mice. We have found that cepharanthine inhibits tumor promotion after topical application and oral administration in two-stage carcinogenesis in mouse skin. Furthermore, topical application of berbamine (2 mumol/mouse) and isotetrandrine (2 mumol/mouse) markedly suppressed the tumor-promoting effect of 12-O-tetradecanoylphorbol-13-acetate (1 microgram) in mouse skin initiated with 7,12-dimethylbenz[a]anthracene (50 micrograms), at a grade corresponding to that of cepharanthine.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Azaphilones inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mice.

Monascorubrin (an azaphilone derivative) was isolated from Monascus anka, 'Monascus pigment', a natural pigment of food additivies, was extracted from Monasucs spp., and chaetoviridin A, one of the azaphilones, was isolated from Chaetomium globosum var. flavo-viridae. Application of 1 microgram of 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoting agent, to the mouse ear resulted in induction of inflammation. Among monascorubrin and related compounds assayed, monascorubrin, chaetoviridin A and its related compounds inhibited the inflammatory activity of TPA in mice. The 50% inhibitory dose of these compounds for TPA-induced inflammation was 0.4-1.5 mumol. Furthermore, monascorubrin (2 mumol), chaetoviridin A (2 mumol) and Monascus pigment (1 mg) markedly suppressed the promoting effect of TPA (1 microgram) on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene (50 micrograms). It is assumed that the inhibition of tumor promotion by monascorubrin, chaetoviridin A and Monascus pigment is due to anti-inflammatory activity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Humulon, a bitter in the hop, inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Humulon, one of the bitters in the hop, was isolated from the female flowers of Humulus lupulus. This component has inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. At 1 mg/mouse, humulon inhibited markedly the tumor-promoting effect of TPA (1 microgram/mouse) on skin tumor formation following initiation with 7,12-dimethylbenz[a]anthracene (50 micrograms/mouse). Furthermore, humulon inhibited arachidonic acid-induced inflammatory ear edema in mice.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Platelet function tests in thrombotic cerebrovascular disorders.

A variety of platelet function tests were performed in patients with four forms of obstructive cerebrovascular disease (CVD); transient ischemic attacks (TIA), reversible ischemic neurological deficit (RIND), cerebral infarct, and cerebral embolism of cardiac source in rheumatic valvular heart disease (RVHD). Platelet studies included platelet aggregation induced by ADP and ristocetin, spontaneous platelet aggregation, von Willebrand factor (VIII:vWF), platelet aggregation enhancing factor (PAEF), and percentage of large platelets (megathrombocytes). Serial testing was carried out in acute stroke patients. The effect of aspirin therapy was also evaluated. A clear difference in results was observed between patients with cardiogenic embolism and those with other forms of CVD. In patients with TIA, RIND, and cerebral infarct, platelet aggregation, both induced and spontaneous, was enhanced along with elevation of plasma VIII:vWF and PAEF, and increased percentage of megathrombocytes. In patients with cardiogenic embolism, however, these studies were negative except for percent megathrombocytes. This value was increased in the embolic patients with RVHD in comparison with non-embolic patients with RVHD. Increase in platelet aggregation to ADP and percent megathrombocytes developed slowly over a week following stroke. Induced and spontaneous platelet aggregation, and percent megathrombocytes could be normalized with 600 mg aspirin p.o. These studies suggest that a systemic increase of hyperaggregable platelets and of plasma activators of platelet function exists in thrombotic CVD and may be related to its pathogenesis, while local hemodynamic factors may be more important in the thrombogenesis of cardiogenic embolism.

Adult↗
PubMedDate not supplied

Sequential observation of spontaneous endometrial adenocarcinoma development in Donryu rats.

Sequential observation of spontaneous endometrial adenocarcinoma development revealed a clear, hormone-dependent, histogenetic pathway in Donryu rats. The first histological changes of the uterine endometrium appeared in both the lining epithelium and uterine gland of the endometrium at 6 mo of age, along with the beginning of persistent estrus. These changes included areas of tall columnar epithelium and gland formation in the lining epithelium as well as metaplastic change in the uterine gland. At 8 mo of age, endometrial hyperplasias were found, with subsequent increase in both incidence and degree. At 8-10 mo of age, hyperplasias were all within the limit of grade ++. After 12 mo of age, however, severe hyperplasias (grade ) began to increase markedly, and adenocarcinomas developed at 15 mo of age. The findings thus suggest that uterine endometrial adenocarcinomas arise from hyperplastic lesions, which should therefore be regarded as preneoplastic, as in the human case. Sequential analysis of plasma gonad steroids also ascertained a link between the appearance of these lesions and an increased estrogen:progesterone ratio, suggesting that estrogen may play an important role in development of both hyperplastic and neoplastic lesions. In Fischer-344 rats used for comparative assessment of strain differences, neither advanced histological changes nor hormonal changes were evident.

Adenocarcinoma↗
PubMedDate not supplied

Immunohistochemical detection of 8-hydroxy-2'-deoxyguanosine in paraffin-embedded sections of rat liver after carbon tetrachloride treatment.

To test the applicability of an anti-8-hydroxy-2'-deoxyguanosine (8-OH-dG) antibody for immunohistochemistry using paraffin-embedded sections, carbon tetrachloride (CCl4)-induced rat liver injury was evaluated. Male rats were given a single dose of CCl4 and killed at 6 hr, 12 hr, 1, 2, 3, and 7 days thereafter. Severe centrilobular necrosis was evident at 1 day. At 2 days, moderate mononuclear cell infiltration was present in centrilobular necrotic regions. Infiltrating mononuclear cells, surrounding sinusoidal endothelial cells and hepatocytes were stained with anti-8-OH-dG antibody at 2 and 3 days. Formation of 8-OH-dG in DNA and 8-oxo-dGTPase mRNA expression were also increased at these time points, the amounts of malondialdehyde and 4-hydroxy-2-nonenal showed 2 peaks at 6 hr and 3 days. The findings suggest that the main contributory factor in the massive hepatic necrosis was increased lipid peroxidation, rather than excessive formation of 8-OH-dG, and that the observed increase in the latter was largely due to infiltrating mononuclear cells. The agreement between biochemical data and the results for immunohistochemical analysis confirms that the anti-8-OH-dG antibody is applicable for detection of cells targeted by free radicals in paraffin-embedded sections and also for investigation of the mechanisms of oxidative damage-related disease, including carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMedDate not supplied

Right ventricle of patients undergoing congenital cardiac surgery differentially expresses haem oxygenase-1 and heat shock protein 70 genes.

Reactive oxygen species are implicated in the pathogenesis of cardiac hypertrophy. Haem oxygenase-1 (HO-1), the rate-limiting enzyme in haem catabolism, is induced by oxidative stress and confers protection against oxidative tissue injuries. We used Northern blotting to examine expression of HO-1 and heat shock protein 70 (HSP70) in the hypertrophic cardiac muscle of eight patients (one infant and seven children) who underwent surgery for congenital heart disease. Levels of HO-1 and HSP70 mRNA were significantly increased in all specimens, but the orders of magnitude of the increases were different, suggesting that the genes expressing HO-1 and HSP70 are regulated separately.

Antioxidants↗
PubMedDate not supplied

The telmisartan renoprotective study from incipient nephropathy to overt nephropathy--rationale, study design, treatment plan and baseline characteristics of the incipient to overt: angiotensin II receptor blocker, telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) Study.

We planned the INNOVATION study to determine whether telmisartan, an angiotensin-2-receptor blocker, delays the progression of renal disease from incipient nephropathy to overt nephropathy in hypertensive or normotensive Japanese patients with type 2 diabetes mellitus. The INNOVATION study is a randomized, double-blind, placebo-controlled trial. Eligible patients must have incipient nephropathy (defined as a urinary albumin to creatinine ratio of 100-300 mg/g creatinine) and a serum creatinine concentration of < 1.5 mg/dl for men and < 1.3 mg/dl for women. Patients who need treatment with angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors are excluded. Eligible patients are randomly assigned to three groups: telmisartan titrated to 40 mg; telmisartan titrated to 80 mg; or placebo. The primary endpoint is the time from baseline visit to first detection of overt nephropathy (defined by a urinary albumin to creatinine ratio that is > 300 mg/g creatinine and 30% higher than the baseline on at least two consecutive visits). A total of 1855 patients have been enrolled from 160 study centres. In 527 randomized patients (28.4% of the enrolled patients), mean (SD) urinary albumin to creatinine ratio and serum creatinine concentration at baseline were 173.3 (47.2) mg/g creatinine and 0.78 (0.19) mg/dl. Sixty-eight per cent of the patients had hypertension at baseline. Mean (SD) systolic and diastolic blood pressures at baseline were 137.1 (14.6) and 77.5 (10.3) mmHg. The INNOVATION study will determine whether telmisartan, an angiotensin II receptor blocker, provides clinical benefits in hypertensive or normotensive patients with diabetes mellitus and diabetic nephropathy.

Aged↗
PubMedDate not supplied

Immune deficiency of cataract Shionogi (CTS) mouse. II. Impaired in vivo T cell-mediated immune response.

Our previous study demonstrated that cataract Shionogi (CTS) mice, an inbred strain related to non-obese diabetic (NOD) mice, are T lymphocytopenic and that their T cell-mediated in vitro reactions, such as proliferative responses of spleen cells to T cell mitogens and alloantigens or production of IL 2 and IL 2 receptors after stimulation of spleen cells with Con A, are greatly reduced. To confirm these in vitro characteristics, in vivo immune responses of CTS mice to T-dependent and T-independent antigens were compared with those of some reference strains including NOD mice. Antibody responses of CTS mice after one injection of a high dose (10(8)) or one or two injections of a low dose (10(5)) of sheep red blood cells (SRBC) were markedly lower than those of the reference strains. The decrease was particularly striking in the IgM antibody production at primary response to both high and low doses, and the IgG antibody production at the secondary response to low dose. Similar lower antibody production was observed in CTS mice against bovine serum albumin (BSA). Little production of IgE antibody was observed from 1 through 3 weeks after an injection of BSA plus Bordetella pertussis. IgG1 response was observed at high incidence but lower in titer than those in the reference strains. Unexpectedly, in spite of the poor antibody production to BSA, potent systemic sensitization for anaphylactic shock was easily established; incidence of lethal shock being comparable with those in the reference strains. This suggests that CTS mice are highly susceptible to the effector phase of active anaphylactic shock. Cell-mediated immunity was also impaired. Delayed type of hypersensitivity to SRBC was low, and the rejection of the skin graft from NOD mouse did not occur. In contrast to the reduced T cell-mediated responses, no difference was found between CTS and reference strains with regard to the antibody production to LPS, a T-independent antigen. These in vivo findings are consistent with the previous in vitro study.

Anaphylaxis↗
PubMedDate not supplied

Age-dependent difference in susceptibility to IgE antibody- and IgG1 antibody-mediated passive anaphylactic shock in the mouse.

The age dependence of the susceptibility to passive anaphylactic shock was studied in the mouse. Anti-BPO IgE monoclonal antibody produced potent systemic sensitization sufficient for provocation of lethal shock in most aged (6 to 10 months) CTS, DS and C57BL/6J mice but only in a very few young (1.5 to 2.5 months) mice. A similar trend was found in the NOD strain, though it was not as definite as in the above three strains. Age-dependent potentiation of the IgE antibody-mediated anaphylactic shock was not found in both sexes of five other strains, C3H/He, DBA/2, NON, BALB/c and B6D2F1. However, the potentiation became obvious even in these strains, when they were treated with Bordetella pertussis before the antigen challenge. Age-dependent potentiation was also clear with IgG1 antibody-mediated anaphylactic shock in DS females and NON males. In contrast, no age-dependent difference was seen for the shock induced by PAF which is estimated to be the main mediator for anaphylactic shock in the mouse. This suggests that the age-dependent potentiation of anaphylactic shock does not seem to be due to elevated susceptibility to the mediator but to its increased release. The sex-dependent differences was also studied and found to be particularly clear in the case of IgG1 antibody-mediated anaphylactic shock in young DS and aged NON mice.

Aging↗
PubMedDate not supplied

Establishment of an in vivo human myeloid leukemia model in the SCID mouse.

We succeeded in establishing a human myelogenous leukemia model in severe combined immunodeficient (SCID) mice by transplanting 2 x 10(7) ML-2 cells intraperitoneally (i.p.) with cyclophosphamide (CTX) pretreatment. Two months after transplantation, 9 of 10 mice developed leukemia and leukemia cells were detected in the peripheral blood (PB) and bone marrow (BM). The main findings at autopsy were peritoneal and pleural effusions and large tumor masses involving the peritoneal organs. However, successful transplantation required injection of a large number of cells. We therefore established a new cell line, ML-2S, from the PB of a mouse with ML-2 leukemia. Although only 2 x 10(6) ML-2S cells were inoculated, ML-2S induced the same pattern of leukemic dissemination reminiscent of the parent ML-2 cells. Compared to ML-2, progression of ML-2S was slow, suggesting that ML-2S is suitable as a leukemia model to study treatment. Furthermore, we confirmed that ML-2S cells are of human origin using isoenzyme analysis and also that ML-2S and ML-2 cells have the same phenotypic character by cell surface marker analysis.

Animals↗
PubMedDate not supplied

The non-surgical treatments of hepatocellular carcinomas in a patient with severe hemophilia A.

We recently treated a patient with multiple hepatocellular carcinomas (HCC) who had severe hemophilia A and thrombocytopenia secondary to cirrhosis. He was not a candidate for surgery because of his liver failure. Transcatheter arterial chemoembolization and percutaneous ethanol injection therapy were successfully performed without complications by maintaining factor VIII levels above 40%. We believe that the non-surgical treatment of HCC can be performed safely in patients with coagulation disorders, by the appropriate administration of coagulation factors, despite thrombocytopenia and/or elongation of the prothrombin time from cirrhosis.

Adult↗
PubMedDate not supplied

Noninvasive measurement of the electrical bioimpedance of breast tumors.

The purpose of this study was to evaluate the possibility of differential diagnosis of tumors, such as breast cancer, by measuring the mammary electrical bioimpedance via the skin surface noninvasively and by examining the relationship between the tissue structure of the breast and electrical bioimpedance. The mammary electrical bioimpedance was measured in 24 patients with breast cancer. Taking into account the measurement results and the distribution of the mammary glands and fatty tissue, a breast model with tumors was proposed. Based on this model, the distributions of the electric potential and electric field in the tissue were theoretically analyzed by the three-dimensional finite element method. In clinical cases, the Re values of the diseased breast were significantly larger than those of the contralateral healthy breast. In theoretical analysis based on the breast model, the Re value of mammary electrical bioimpedance varied due to the structure of the breast, that is, the ratio of fatty tissue to mammary gland and the presence of mammary tumors. The results of the measurement agreed with the theoretical analyses. These results suggest that differential diagnosis of breast tumors is possible by measuring the mammary electrical bioimpedance using noninvasive electrodes on the skin.

Adipose Tissue↗
PubMedDate not supplied

An autopsy case of multilocular cystic hepatocellular carcinoma without liver cirrhosis.

Although simple cysts, cystadenoma and cystadenocarcinoma of the liver have been well documented as hepatic cystic diseases, cystic hepatocellular carcinoma is a curious entity. Only 3 cases have been reported in the English literature. A 70-year-old man was admitted to Nagoya University Hospital for multiple liver tumors and a thrombus in the main trunk of the portal vein. A part of the tumors contained cystic components, and were diagnosed as hepatocellular carcinoma by needle biopsy. After giving informed consent, the patient was treated with several systemic chemotherapy using doxorubicin, fluorouracil, cyclophosphamide, cisplatin and oral anticancer agent UFT, a combination of uracil and tegafur, for almost 2 years. During this time, the tumors enlarged gradually, and also underwent cyst formation, the patients then died of biliary sepsis. Autopsy confirmed the diagnosis of multilocular cystic hepatocellular carcinoma without liver cirrhosis.

Aged↗
PubMedDate not supplied

A case of the development of two hepatocellular carcinomas and a cholangiocarcinoma with cirrhosis after elimination of serum hepatitis C virus RNA with interferon therapy.

A 64-year-old man who had exhibited abnormal transaminase levels for about 20 years was admitted to a hospital for the treatment of liver damage. Laboratory testing demonstrated that he was suffering from chronic hepatitis C, and a liver biopsy showed chronic active hepatitis with septal fibrosis. He was treated with interferon-alpha, and HCV-RNA became undetectable. Four years after the completion of interferon treatment, 3 lesions in the patient's liver were revealed by routine ultrasonography, and he was referred to Nagoya University Hospital for further examinations on November 1997. Radiographical examinations such as computed tomography and angiography demonstrated 2 hypervascular tumors (size: phi 35 mm and phi 20 mm) and 1 hypovascular tumor (phi 28 mm). Qualitative analysis for HCV-RNA by polymerase chain reaction method was negative. Partial hepatectomy was performed, and pathological examination of the tumors showed 2 moderately differentiated hepatocellular carcinomas and cholangiocarcinoma accompanied with liver cirrhosis. We propose that even patients with disappearance of HCV-RNA after interferon therapy, especially with liver cirrhosis or severe fibrosis, should be followed-up closely and examined at regular intervals because of the high risk of developing primary liver cancers.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

The micronucleus assay with mouse peripheral blood reticulocytes using acridine orange-coated slides with triethylenemelamine.

A micronucleus assay using mouse peripheral blood and supravital staining with acridine orange (AO) was validated by two laboratories on triethylenemelamine-treated mice. Dose- and time-dependent increases in micronucleated peripheral reticulocytes were observed. This new method can be used as an alternative to the conventional bone marrow micronucleus assay.

Acridine Orange↗
PubMedDate not supplied

Significance of postoperative irradiation for stage III lung cancer.

The significance of postoperative irradiation for stage III lung cancer was analyzed in 30 patients. Radiation was given to 15 of the patients and the remaining 15 did not receive any radiation therapy following surgical intervention. A total dose of 40 to 70 Gy was given to the radiation group with a fraction dose of 2 Gy five times a week using cobalt 60 gamma-ray or linac 10 MV X-ray. There was no significant difference of survival time between these two groups. However, in analyzing modes of operation, radiation seemed to improve the survival rate in patients who underwent curative or relatively curative operations (P = 0.1), while the patients who underwent non-curative operations did not receive any benefit from the postoperative irradiation. Some reasons for the ineffectiveness in cases of non-curative operation are discussed.

Adenocarcinoma↗