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Biomedical subjects

T Mura

Publications and source records attributed to T Mura.

At least 19 recordsLinked to original sources

Effect of lactational exposure to 1,2,3,4- tetrachlorodibenzo-p-dioxin on cytochrome P-450 1A1 mRNA in the neonatal rat liver: quantitative analysis by the competitive RT-PCR method.

BACKGROUND AND METHODS: The aim of this study was to assess the effect of lactational exposure to dioxins in neonates on the cytochrome P450 1A1 (CYP1A1) induction in the level of gene expression. Maternal rats were treated with a single dose of 50 or 100 micromol/kg 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD), a low potent congener of dioxins, on the first day post-partum (day 1). Induction of CYP1A1 mRNA expression was quantitatively analyzed by the competitive reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: The CYP1A1 mRNA was detectable at extremely low amounts in the liver of control neonates and mothers. The mRNA ratios of CYP1A1 to beta-actin in neonates were dose-dependently increased by the treatment of 1,2,3,4-TCDD of their mothers. Its peak occurred on day 6 and was sustained at the same level on day 10. Increases of the ratio with 100 micromol/kg 1,2,3,4-TCDD on day 2, 6 and 10 were 26-, 40- and 40-fold of the appropriate controls, respectively. These levels paralleled the activity of ethoxyresorufin-o-deethylase, representing CYP1A mediated monooxygenase. In the mother, the mRNA ratio was increased only to threefold of the control, 10 days after treatment. CONCLUSION: Current RT-PCR procedure enabled to assess both constitutive and induced levels of CYP1A1 mRNA in the neonatal rat livers. Although the dose of 1,2,3,4-TCDD selected in this study was about 5000 times higher than the daily intake of dioxins in breast-fed infants, CYP1A1 mRNA was highly induced for a longer period of time in neonatal rats receiving 1,2,3,4-TCDD via lactation than the treated maternal rats.

Actins↗

Adjuvant chemotherapy with a combination of mitoxantrone, methotrexate, 5-fluorouracil for node-positive breast cancer: phase II pilot study.

A phase II pilot study was carried out on 30 patients to ascertain the toxicity and efficacy of combination chemotherapy with mitoxantrone, methotrexate, 5-fluorouracil (NMF) in the adjuvant setting for axillary lymph node-positive breast cancer. The NMF regimen was mitoxantrone 10 mg/m2, methotrexate 40 mg/m2, and 5-fluorouracil 600 mg/m2 administered i.v. on day 1, repeated every 3-4 weeks for 6 cycles. The median nadir WBC count was 2,000/microl; grade 4 leukocytopenia occurred only in 1 patient. Nausea and vomiting appeared as grade 0 and 1 severity in 26/30 patients. Alopecia was extremely mild, appeared as grade 0 and 1 in 29/30 patients. The overall and relapse-free survival rates were 67.8% and 68.4% at the 82-month follow-up, respectively. The overall survival rate in premenopausal patients was significantly better than that in postmenopausal patients (P<0.05). NMF is a well-tolerated combination regimen, suitable as adjuvant chemotherapy for node-positive breast cancer.

Adolescent↗

Adenovirus-transferred HNF-3 gamma conserves some liver functions in primary cultured hepatocytes of adult rats.

Hepatocyte nuclear factor-3 (HNF-3) isoforms are key factors for regulation of gene expression and differentiation in hepatocytes. HNF-3gamma is abundantly expressed in the mature liver, but down-regulated in primary cultured hepatocytes, in which some other hepatic gene expressions are also decreased. In this study, the primary hepatocytes were infected with the recombinant adenovirus carrying HNF-3gamma gene (AxCAHNF3gamma), and this led to marked induction of the HNF-3gamma gene. As a result, the expressions of albumin, catalase, and ornithine transcarbamylase (OTC) genes were also recovered to significant levels in the AxCAHNF3gamma-infected hepatocytes. Moreover, hepatocyte proliferation stimulated by epidermal growth factor (EGF) and insulin was also inhibited by AxCAHNF3gamma infection. Our results demonstrate that the enforced expression of HNF-3gamma gene can lead to conservation of some original liver functions in the primary cultured hepatocytes accompanied by morphological differentiation and growth inhibition.

Adenoviridae↗

[Effect on 5'-deoxy-5-fluorouridine (5'-DFUR) of pyrimidine nucleoside phosphorylase (PyNPase), matrix metalloprotease and serum IAP values. Hokuriku Colorectal Cancer Chemotherapy Study Group].

PyNPase activity, MMPs activity and serum IAP values were measured in tumor tissues from colorectal cancer patients who had been divided into two groups, one given preoperative 5'-DFUR and the controls. PyNPase activity of the preoperative administration group was approximately equivalent to that of the controls. In the control group, correlations were assessed between PyNPase activity and activities of MMP1 and MMP3. To assess the effect of 5'-DFUR on the activity of MMPs, we divided patients into two groups, a high and a low PyNPase activity group. Although there was no correlation with MMPs activity of the preoperative administration group and the control group in the low PyNPase activity group, the activities of MMP1 and MMP9 of the control group were significantly higher in the high PyNPase activity group. Moreover, the serum IAP value of the administration group was significantly lower than that of the control group. These results indicated that PyNPase activity was thus suggested to be somehow related to MMPs activity and serum IAP values.

Adult↗

Cu, Zn superoxide dismutase in patients with dementia of the Alzheimer type.

Cu, Zn superoxide dismutase (SOD) levels in the serum, cerebrospinal fluid (CSF) and skin fibroblasts of patients with dementia of the Alzheimer type (DAT) were estimated using enzyme immunoassay. The SOD mRNA level in the skin fibroblasts was also determined by the Northern blot analysis. As compared with the age-matched control groups of neurological patients without dementia, the AD group consisting of patients with DAT at ages under 65 years of age as well as the SDAT group of patients with DAT at ages over 65 years of age showed no significant changes in serum or CSF SOD levels. However, the skin fibroblast SOD- and SOD mRNA levels, which were correlate each other, were significantly higher in the AD group (p < 0.05), while lower in the SDAT group (p < 0.05). These results suggest that the determination of the SOD level of skin fibroblast may be useful for diagnosis of DAT and that the abnormality of SOD may play an important role in developing DAT.

Alzheimer Disease↗

Effects of human neonatal serum on DNA synthesis in suckling and adult rat hepatocytes in primary culture.

The effect of human neonatal serum on DNA synthesis in suckling and adult rat hepatocytes in primary culture was investigated to characterize growth regulating factors of the liver in neonates and to confirm whether the stimulatory factor is human hepatocyte growth factor (hHGF). Neonatal serum stimulated DNA synthesis of both adult and suckling rat hepatocytes. The stimulatory effect was dose-dependent up to 20% in volume. The molecular weight of the stimulatory substance in neonatal serum was between 12,500 and 25,000, as estimated by gel filtration. Its activity was stable after heating at 56 degrees C for 20 min, but was lost after heating at 90 degrees C for 30 s, and easily passed through S- or heparin-Sepharose columns. The concentration of hHGF quantified by ELISA was too low to stimulate DNA synthesis in vitro. Biological and biochemical properties of the growth stimulatory activity in neonatal serum differed from that of hHGF. The presence of other growth factors in human neonatal serum for suckling and adult hepatocytes was suggested.

Animals↗

Iron-saturated lactoferrin as a co-mitogenic substance for neonatal rat hepatocytes in primary culture.

We studied the effect of lactoferrin on DNA synthesis in neonatal rat hepatocytes in primary culture to determine if this agent acts as a mitogen in human milk. Thymidine incorporation into the DNA of cultured hepatocytes stimulated by lactoferrin in the presence of insulin and human epidermal growth factor was examined. Iron-saturated lactoferrin increased DNA synthesis of neonatal hepatocytes by 1.5 times and this potency was the same as that of insulin. It significantly enhanced the stimulatory effect of human epidermal growth factor plus insulin; DNA synthesis under these conditions was seven times that of control. Iron-free lactoferrin did not affect DNA synthesis, nor did the exogenous addition of ferric ions. The enhancement of DNA synthesis by iron-saturated lactoferrin was significant for neonatal hepatocytes, but not for adult hepatocytes. These results suggest that iron-saturated lactoferrin, which itself had low mitogenic activity, is a co-mitogenic substance for neonatal hepatocytes in vitro.

Animals↗

Decreased superoxide dismutase activity in erythrocyte in Parkinson's disease.

Superoxide dismutase (SOD) activities in Parkinson's disease (PD) were significantly lower than those in controls, especially in a treated PD group. However, SOD activities in an untreated PD group did not decrease. There was a significant correlation between SOD activities and the duration of illness in the treated PD group (p < 0.05). There was a significant correlation between SOD activities and the present doses of L-DOPA/carbidopa in the treated PD group.

Aged↗

[A resected case of advanced gastric cancer with complete remission of liver metastasis by chronic daily administration of oral etoposide and UFT].

An advanced gastric cancer with liver metastasis was treated with the combination MMC, Etoposide and UFT. Etoposide was administered orally at 25-50 mg/day to the gastric cancer patient with liver metastasis. In operative findings, there was no liver and lymphoid node metastasis. The gastric tumor diminished in size and changed its characteristics due to the chemotherapy. In 19 months, no liver nor LN metastasis was observed by CT scan. Presently, the patient feels well and receives outpatient treatment.

Administration, Oral↗

Papillary carcinoma in ectopic thyroid detected by TJ-201 scintigraphy.

A 37-year-old man with papillary carcinoma in an ectopic thyroid is presented. Excisional biopsy revealed the cervical mass to be a metastasis from thyroid cancer. X-ray, ultrasonography, and computed tomography, however, failed to identify the primary tumor in the thyroid. Incidental TI-201 uptake was noted in the midline of the anterior neck, and a palpable nodule was discovered in this area. Fine needle aspiration cytology demonstrated Class V papillary adenocarcinoma, and subsequent surgery confirmed a papillary carcinoma in the ectopic thyroid. This case suggests the usefulness of TI-201 scintigraphy for the detection of ectopic thyroid malignancy.

Adenocarcinoma, Papillary↗

The effect of human milk on DNA synthesis of neonatal rat hepatocytes in primary culture.

We studied the effect of human milk on DNA synthesis of neonatal hepatocytes to elucidate the physiologic role of human milk in growth of the liver. Neonatal hepatocytes were isolated from 5-d-old rats and cultured in serum-free medium. Human milk stimulated DNA synthesis of these hepatocytes in a concentration-dependent manner. The stimulatory activity of 7.5% (vol/vol) human milk plus 0.1 mumol/L insulin was five times that of control and was almost the same as that of 20 micrograms/L human epidermal growth factor (hEGF) plus insulin. The effect of human milk was additive with treatment with hEGF and insulin. The milk associated with prolonged jaundice of infants was significantly more active than the milk that was not associated with jaundice, although the concentration of hEGF was not different between the two types of milk. The mitogenic activity of milk was heat-labile, inactivated by DTT and stable after treatment with trypsin. Three peaks of the activity were detected in milk by gel filtration and the fraction containing proteins of molecular weight between 36,000 and 76,000 showed the highest activity. Anti-hEGF antibody did not inhibit this activity completely. These results suggested the presence of mitogens other than hEGF or a more active form of hEGF in human milk. The milk associated with breast-milk jaundice exerts a different influence on cell growth and may affect maturation of the liver function related to bilirubin metabolism. The mitogenic activity of milk might be important for growth and development of the liver in infants.

Animals↗

Vitamin K absorption capacity and its association with vitamin K deficiency.

We measured plasma vitamin K concentrations in 194 5-day-old infants three hours after administration of a 4-mg dose of vitamin K (menaquinone-4, Kaytwo syrup, Eisai Co Ltd, Tokyo, Japan). We investigated association with other factors contributing to vitamin K deficiency. These plasma vitamin K concentrations varied greatly among the neonates from values below the limit of detection (2 ng/mL) to more than 1000 ng/mL. The vitamin K concentration was associated with nutritive vitamin K deficiency represented by plasma protein induced by vitamin K absence or antagonist-II (PIVKA-II) values. The wide variation in vitamin K absorption is considered to be one of the major causative factors in infantile vitamin K deficiency.

Administration, Oral↗

The significance of regional lymph node dissection in the surgical management of breast cancer.

The results of an analysis done on the regional lymph node metastases of 300 patients with operable breast cancer, who were treated in the Department of Surgery (II), Kanazawa University Hospital from 1973 to early 1988 are reported herein. It was found that the metastases of the axillary and internal mammary lymph nodes were closely related to the survival of patients, but they were hardly diagnosed before the operation. Only the dissection of these lymph nodes proved useful for providing the prognostic information. Moreover, in a retrospective study comparing the en bloc extended radical mastectomy versus the other types of mastectomy, the extended radical mastectomy was seen to greatly improve the survival of patients with 3 or less than 3 metastatic axillary lymph nodes. Thus, the extended radical mastectomy provides the maximum diagnostic and prognostic information, and gives the best chance of loco-regional control of the disease. The anterior chest deformity created by the extended radical mastectomy, however, should be avoided in those patients without internal mammary involvement. We therefore propose the modified extended mastectomy as a staging operation.

Adult↗

Apolipoprotein abnormalities in dementia.

The serum levels of apolipoprotein B, C-II and the ratio of apolipoprotein B/A-I were found to be significantly higher in multiinfarct dementia than in dementia of the Alzheimer type. The high serum levels of apolipoprotein B, C-II and the high ratio of apolipoprotein B/A-I may cause multiinfarct dementia. The large difference between the groups suggests that the serum levels of apolipoprotein B, C-II and the ratio of apolipoprotein B/A-I may be useful in differential diagnosis of these two kinds of dementia.

Aged↗

High-performance liquid chromatographic-fluorescence determination of human faecal bile acids.

A high-performance liquid chromatographic method with fluorescence detection has been developed for the determination of human faecal bile acids, especially free faecal bile acids. Faecal bile acids were extracted using an Amberlite XAD-2 column and then fractionated into four groups (free, glycine-conjugated, taurine-conjugated and sulphated bile acids) on a piperidinohydroxypropyl Sephadex LH-20 column. The free bile acid fraction and free bile acids obtained after enzymatic hydrolysis and/or solvolysis of the three other fractions were derivatized with 1-bromoacetylpyrene and dicyclohexyl-18-crown-6-ether. The derivatized bile acids were separated stepwise on a Shim-pack CLC-ODS column using acetonitrilemethanol-water (100:50:30) (A), (100:50:20) (B), and (100:50:0) (C) as mobile phases with changing automatically from A to C using a solvent changer. Calibration curves of bile acid standards were linear in the range between 20 and 400 pmole, when monitored at 370 nm (excitation) and 440 nm (emission). Percent recoveries of bile acids from human faecal samples were between 80 to 95%. The method is applicable to clinical use and is sensitive, reliable, and useful for the detailed determination of human faecal bile acids, especially of free faecal bile acids.

Adult↗

Lp(a) lipoprotein in cerebrovascular disease and dementia.

Lp(a) lipoprotein has been considered an independent risk factor in the development of coronary heart disease (CHD). We examined the role of Lp(a) in patients with cerebrovascular disease (CVD) and those with dementia. The Lp(a) concentration in patients with CHD, those with cerebral infarction due to a large artery occlusion and those with vascular dementia (VD) was significantly higher than that of age-matched control subjects. However, the Lp(a) concentration was not high in cerebral infarction due to a small artery occlusion, intracerebral hemorrhage and dementia of the Alzheimer type (DAT). The present results suggest that Lp(a) should cause VD as well as CVD, and that Lp(a) should be one of the indicators that distinguish VD from DAT.

Aged↗

Age- and sex-related profiles of serum primary and total bile acids in infants, children and adults.

The relation of age and sex to serum primary (PBA) and total bile acid (TBA) concentrations was evaluated by an enzymatic fluorometric microassay in healthy infants, children and adults. TBA concentrations were the highest in the 6-day-old group and 1-month-old group and seemed to switch to almost normal adult levels by the age of 4-6 years, which persisted throughout life, while PBA concentrations were predominant over a period of 3 days to 3 months after birth. No sex-related differences were observed from neonates to very old persons for any of serum bile acids. These results show that the bile acid metabolism in the liver and the enterohepatic circulation of bile acids are usually matured in infancy and that aging and sex may insignificantly affect serum bile acid metabolic profiles.

Adolescent↗