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T Ide

Publications and source records attributed to T Ide.

At least 163 records · Page 9Linked to original sources

[Telomere and telomerase associated genes].

Telomerase is a ribonucleoprotein, telomere specific reverse transcriptase, which contains some protein components and telomerase RNA components. Human telomerase RNA and some telomerase components have been identified but not completely. More recently, human telomerase catarytic subunits have been cloned, which are called hTRT or hEST2. The expression of hTRT in human cultured cells is well correlated with telomerase activity and immortality. Moreover, the expression of hTRT in cancer tissues is higher than that of normal tissues. These results suggested that hTRT and telomerase activity may be a powerful additional tool for cancer diagnosis.

DNA-Binding Proteins↗

Activity of hepatic fatty acid oxidation enzymes in rats fed alpha-linolenic acid.

The activity of hepatic fatty acid oxidation enzymes in rats fed linseed and perilla oils rich in alpha-linolenic acid (alpha-18:3) was compared to that in rats fed safflower oil rich in linoleic acid (18:2) and a saturated fat (palm oil). Palm and safflower oils were essentially devoid of alpha-18:3. The palmitoyl-CoA oxidation rates both in mitochondrial and peroxisomal pathways in liver homogenates were significantly higher in rats fed linseed oil than in those fed palm and safflower oils. Among rats fed diets containing palm oil, safflower oil, fat mixtures composed of safflower and perilla oils (2:1, w/w and 1:2, w/w), and perilla oil, mitochondrial and peroxisomal fatty oxidation rates increased with increasing dietary levels of perilla oil. Compared to palm and safflower oils, dietary alpha-18:3 either in the form of linseed or perilla oils profoundly increased the activity of carnitine palmitoyltransferase, acyl-CoA oxidase, 3-ketoacyl-CoA thiolase, and 2,4-dienoyl-CoA reductase. Smaller but significant increases by dietary alpha-18:3 of the activity of acyl-CoA dehydrogenase, enoyl-CoA hydratase, and delta 3, delta 2-enoyl-CoA isomerase were also observed. Unexpectedly, dietary alpha-18:3 greatly reduced the activity of 3-hydroxy-acyl-CoA dehydrogenase. Compared to palm oil, dietary polyunsaturated fats significantly reduced the activity of fatty acid synthetase and glucose-6-phosphate dehydrogenase to the same levels. The activity of pyruvate kinase was significantly higher in rats fed palm oil than in those fed polyunsaturated fats. The extent of reduction was more prominent with polyunsaturated fats containing alpha-18:3 than with safflower oil devoid of alpha-18:3. Thus, compared to linoleic acid and saturated fatty acids, dietary alpha-18:3 caused characteristic changes in the activity of hepatic enzymes in fatty acid and glucose metabolism in rats.

Adipose Tissue, Brown↗

Telomerase activity in human breast cancer and benign breast lesions: diagnostic applications in clinical specimens, including fine needle aspirates.

We analysed telomerase activity in normal, benign and malignant breast tissues and in fine needle aspirates by a PCR-based assay. The tissue samples we used in this assay consisted of 20 cryostat sections, 10 microns thick, from each breast biopsy. This method was used to obtain effective extraction from small samples and to confirm the histological identity of the specimen by microscopical examination of serial sections. Fifty-two of 71 breast carcinomas were positive for telomerase activity, and the intensity of this was strong in most cases, whereas all 6 samples of normal breast tissue and 17 of fibrocystic disease were negative and only 1 of 15 fibroadenomas was positive. Invasive ductal carcinomas were more frequently positive than invasive lobular carcinomas. There was no correlation of telomerase activity with tumour size or the occurrence of lymph node metastasis. Evaluation of our assay system showed that a signal of telomerase activity was detectable in extracts from single cryostat sections (< 1 mm2) of a cancer specimen and from as few as 4 cells of a human breast cancer cell line. On the basis of the above data, we applied this assay to fine needle aspirates of breast lesions. Ten of 15 aspirates which had been cytopathologically diagnosed as cancer were strongly positive, while 26 of 29 benign aspirates were totally negative and the remaining 3 showed only borderline activity. In 3 cases, the telomerase result could have helped establish a diagnosis when the cytological observations were inconclusive. Our results indicate that this sensitive assay could become a useful new modality for supplementing microscopic cytopathology in the detection of cancer cells in small tissue biopsies and fine needle aspirates.

Autoradiography↗

Telomerase activity in normal human epithelial cells.

Telomerase activity is found in most cancer tissues and many immortalized cell lines as well as in germ line cells but it is generally undetected in normal human somatic tissues. There is weak telomerase activity in some cell types of hematopoietic lineage in which a stem cell-like subpopulation may exist. Likewise, physiologically regenerating somatic tissues and organs such as skin, small intestine, and most other epithelia of the human body are supposed to contain similar cell lineages to maintain their renewal throughout the life span of individuals. It is therefore of interest whether telomerase activity is present in physiologically regenerating epithelial cells. Telomerase activity was detected, though very weakly, in cultured normal epidermal keratinocytes and at higher levels in a subpopulation that adhere rapidly on collagen IV-coated culture dishes. No telomerase activity was detected in a subpopulation that was less adherent on the coated dishes. The rapidly adherent subpopulation of keratinocytes was enriched in small proliferating cells with macrocolony forming potential. It was also passaged through more generations in culture, and expressed integrin beta 1 at higher levels than the less adherent subpopulation. Telomerase activity was similarly found in ectocervical keratinocytes as well as in simple endocervical epithelial cells. These findings provide the evidence of a telomerase-positive population among physiologically regenerating normal human epithelial cells. The identity of the telomerase-positive cells remains to be defined.

Base Sequence↗

An immunosuppressant, FK506, protects hippocampal neurons from forebrain ischemia in the mongolian gerbil.

We examined whether an immunosuppressant, FK506, inhibits delayed neuronal death in the gerbil hippocampal CA1 sector after 5-min forebrain ischemia. After reperfusion, gerbils were injected intravenously with FK506. Gerbils in the early injection group were injected with FK506 immediately after reperfusion, and gerbils in the delayed injection group were injected with FK506 1 or 2 h postischemia. The body temperature of the FK506-treated gerbils in the normothermic group was maintained at 37.5-38.0 degrees C for 2 h postischemia. In the chronic survival group, neuroprotection was assessed after recovery for 45 days. Seven or 45 days after reperfusion, neuronal density in the CA1 was assessed following perfusion fixation. FK506 ameliorated cell death in the CA1 in a dose-dependent manner in every group, although it showed a hypothermic effect. FK506 is neuroprotective against forebrain ischemia in gerbils.

Animals↗

Regulation of calcium release channel in sarcoplasmic reticulum.

In this review, we summarized the results obtained mainly by flux measurements through Ca2+ channel in HSR vesicles. The Ca2+ channel has a large pore which passes not only divalent cations such as Ca2+, Mg2+, and Ba2+ and monovalent cations such as Na+, K+, and Cs+, but also large ions such as choline and tris. The permeation rates of choline and glucose through the Ca2+ channel were measured quantitatively by the light scattering method. The slow permeation of such molecules may reflect the structure of pores since the permeation process is the rate-limiting step for such large molecules. Neutral molecules such as glucose became permeable in the presence of submolar KCl, which suggests that pore size of the channel becomes larger in KCl. The apparent permeation rates of Ca2+ and Mg2+ obtained from the flux measurement were the same, although their single-channel conductances were different. This discrepancy was explained by the fact that flux measurements reflects the open rate of the channel. Thus, complementarity between the flux measurement and single-channel recording was demonstrated. From the effects of K+ on the action of regulators on Ca2+ channel, it was suggested that the Ca2+ channel has many binding sites for activators and inhibitors. There are two kinds of Ca2+ binding sites for activation and inhibition. Activation sites for Ca2+, caffeine, and ATP are different and inhibition sites for Ca2+ and procaine are different. The binding sites for ruthenium red and Mg2+ are the same as the activation and/or inhibition sites for Ca2+. Ryanodine-treated Ca2+ channel became permeable to glucose even in the absence of KCl. The conformational state of the channel opened by ryanodine is different from that opened by Ca2+, caffeine, and ATP. The maximal flux rates of choline and glucose induced by ryanodine were smaller than those attained by caffeine and ATP. This result is consistent with the observation obtained by single-channel recording; the maximal value of single-channel conductance after ryanodine treatment becomes 40-50% of the value before the treatment. It is likely that the radius of the pore opened by ryanodine is smaller than that opened by Ca2+, caffeine, or ATP. The flexibility of the channel may be decreased in the open locked state induced by ryanodine. The Ca2+ response to open the channel by micromolar Ca2+ was lost when calsequestrin was released from the vesicles. It is possible that calsequestrin acts as an endogenous regulator of Ca2+ channel through triadin in excitation-contraction coupling.

Animals↗

Distribution of diaphragm blood flow during sevoflurane anaesthesia in dogs.

PURPOSE: The purpose of this study was to determine the effect of increasing the concentrations of sevoflurane anaesthesia on the distribution of diaphragm blood flow (Qdi) in ten dogs during mechanical ventilation. METHODS: Animals were divided into two groups, sevoflurane (n = 6) and time control (n = 4) groups. Blood flow to the crural and the costal diaphragm (Qcru, Qcost) was determined by the hydrogen clearance technique at 0, 0.5, 1.0 and 1.5 minimum alveolar concentration (MAC) of sevoflurane after a 30 min period of steady-state conditions. Cardiac output (CO) and the mean arterial blood pressure (MBP) were also measured. RESULTS: Sevoflurane anaesthesia caused a reduction in CO (L.min-1) from a control value of 1.51 +/- 0.21 to 1.38 +/- 0.1 (0.5 MAC), 1.09 +/- 0.15 (1.0 MAC) and 0.98 +/- 0.12 (1.5 MAC) (Mean +/- SD). Mean blood pressure, Qcru and Qcost also decreased with increasing depth of anaesthesia. In addition, the decrease of Qcru was greater than that of Qcost at all levels of MBP and CO. No change occurred in these variables in the time control group. CONCLUSION: Sevoflurane anaesthesia changes the distribution of Qdi with a greater reduction occurring in Qcru than in Qcost.

Anesthetics, Inhalation↗

Clinical and histopathological analysis of proliferative potentials of recurrent and non-recurrent meningiomas.

Proliferative potentials of meningiomas from 127 patients were examined immunohistochemically using the anti-Ki-67 monoclonal antibody, MIB-1, on paraffin sections, and the correlation among MIB-1 staining index (SI), histopathological finding, and clinical course of the disease was analyzed retrospectively. The mean MIB-1 SI of 50 male patients with meningioma was 5.5%, whereas that of 77 female patients was 2.7%. Higher MIB-1 SI were observed for younger patients. These age- and sex-related differences in MIB-1 SI were statistically significant. The patients were assigned to one of three groups: those with non-recurrent meningioma (n = 73); those with recurrent meningioma in whom the specimens obtained during the initial surgery were used to calculate the MIB-1 SI (n = 21); and those with recurrent meningioma for whom the specimens obtained during the surgery for recurrent tumors were used to calculate the MIB-1 SI (n = 33). The mean MIB-1 SI in these patients were 1.6%, 3.6%, and 8.8%, respectively, and there were statistically significant differences among these three groups. Statistical analyses reveal that meningiomas with a MIB-1 SI of 3% or more have a significantly high tendency for recurrence during the clinical courses, especially within the first 10-year follow-up periods. Moreover, there is statistically significant correlation between MIB-1 SI and recurrence in each Simpson's grade. The time interval to the next recurrence for recurrent meningiomas is associated with the proliferative potential represented by the MIB-1 SI, and a correlation equation has been proposed to predict the date of the next recurrence. Analyses on cellularity of meningiomas revealed no statistically significant difference in cellularity between non-recurrent and recurrent meningiomas. There was no statistically significant relationship between cellularity and MIB-1 SI of meningiomas. In conclusion, examination on proliferative potentials of meningiomas using MIB-1 SI is very important for biological and histopathological analyses and the prediction of future recurrence.

Adult↗

Glycosides of megastigmane and of the simple alcohols from Alangium premnifolium.

From the water-soluble fraction of a methanol extract of leaves of Alangium premnifolium, two new megastigmane glycosides, alangionosides N and O, along with three known megastigmane glycosides, dendranthemoside A and alangionosides A and B, were isolated. Shimaurinosides A and B, xylopyranosyl(1-->6)glucopyranosides of simple alcohols were also found to be constituents of the water-soluble fraction. Structures were determined by spectroscopic analyses.

Alcohols↗

Anti-HIV-1 activity of thiadiazole derivatives: structure-activity relationship, reverse transcriptase inhibition, and lipophilicity.

The structure-activity relationship of the non-nucleoside HIV-1-specific reverse transcriptase (RT) inhibitors 4-phenyl-1,2,5-thiadiazol-3-yl N,N-dialkylcarbamate (TDA) derivatives was investigated with respect to their anti-HIV-1 activity, RT inhibition, and lipophilicity. 4-Phenyl-1,2,5-thiadiazol-3-yl N,N-dimethylcarbamate inhibited HIV-1-induced cytopathic effect (CPE) by 50% at a concentration of 28.8 microM in MT-4 cells. The activity increased more than 100-fold when the hydrogens at the 2-position and the 6-position in phenyl moiety were substituted by chlorines. However, the derivative with a chlorine at the 4-position of phenyl moiety did not show any inhibition of HIV-1 replication at its non-toxic concentrations. All of the 4-(2,6-dichlorophenyl)-1,2,5-thiadiazol-3-yl N-methyl-N-alkylcarbamates proved inhibitory to HIV-1 replication in the nanomolar concentration range. The TDA derivatives that showed anti-HIV-1 activity also inhibited RT activity in an enzymatic assay. However, the TDA derivatives did not show any specific inhibition of a non-nucleoside RT inhibitor (NNRTI)-resistant mutant and its RT activity. When the TDA derivatives were examined for their inhibitory effect on HIV-1 replication in the presence of 50% human serum, the activity significantly decreased depending on-their lipophilicity.

Anti-HIV Agents↗

Development and exacerbation of oral lichen planus during and after interferon therapy for hepatitis C.

Oral lichen planus (OLP) is frequently seen in patients with hepatitis C virus (HCV) infection. To clarify the role of HCV in OLP pathogenesis, we investigated the occurrence and progression of oral lesions in chronic hepatitis C patients treated with interferon. Oral surgeons examined 24 hepatitis C patients (15 men, nine women; mean age 48.1 years) for oral lesions before, during and after interferon (IFN) treatment. OLP was observed in 16.7% (4/24). Two patients had OLP before treatment, one during and one after treatment. Those who developed OLP during or after treatment had neither improvement nor disappearance of OLP even when serum HCV RNA became negative. Leucoplakia was seen in four patients before treatment and oral cancer in one patient 6 months after completing treatment. OLP can occur, exacerbate and persist during IFN treatment for hepatitis C, even when serum HCV RNA becomes negative. The present study suggested that OLP pathogenesis in hepatitis C is due to host factors induced by HCV infection rather than direct HCV participation. Treating physicians should be aware of OLP occurrence or exacerbation by IFN treatment with hepatitis C patients, but IFN therapy is not necessarily contraindicated in these patients.

Adult↗

Evaluation of interferon treatment in cirrhotic patients with hepatitis C.

The aim of this study was to examine the effects of interferon on cirrhotic patients with hepatitis C and the incidence of adverse reactions. The subjects were 35 cirrhotic patients, and 29 chronic active hepatitis patients without cirrhosis (CAH) served as controls. The cirrhotic patients received 3 or 6 million units of human lymphoblastoid interferon daily for one or two weeks and then three times a week for 22 or 23 weeks, while the CAH patients received 6 million units daily for 2 weeks and then three times a week for 14 or 16 weeks. Discontinuation of interferon treatment or dose reduction was required in the 7 cirrhotic patients. The most frequent reason was thrombocytopenia. Dose reduction alone was necessary in two CAH patients. Five cirrhotic patients (14.3%) and nine CAH patients (31.0%) were classified as complete responders to interferon treatment. In all five complete responders with cirrhosis, the hepatitis C virus RNA level before treatment was less than 5 log copies/50 microliters. The results of this study confirm the beneficial effect of interferon in selected patients with cirrhosis on basis of pre-treatment virus levels and platelet count.

Base Sequence↗

Sequential interferon-alpha and beta treatment in patients with chronic hepatitis C.

To assess the effectiveness and side effects of sequential interferon (IFN)-alpha and beta treatment for patients with chronic hepatitis C, 25 patients were enrolled in a trial of this regimen. The patients were given 6 million units (MU) of natural human INF-beta daily for 2 weeks followed by 6 MU of natural human IFN-alpha three times a week for 10 to 22 weeks. Serum alanine aminotransferase (ALT) levels normalized for at least 24 weeks in 10 patients (40%), of whom 4 (40%) had no detectable serum hepatitis C virus (HCV) RNA. Three variables were significant in predicting a sustained response: a low serum HCV RNA level, a low Knodell's fibrosis score, and a low indocyanine green retention rate at 15 minutes. Elevated serum ALT and proteinurea were observed with IFN-beta treatment but these side effects were mild and disappeared when INF-beta treatment ended. While all patients completed the entire regimen, we concluded that sequential IFN-alpha and beta treatment provides no additional antiviral effects in chronic hepatitis C.

Alanine Transaminase↗

An experimental animal model of primary biliary cirrhosis induced by lipopolysaccharide and pyruvate dehydrogenase.

Previously, we found that the antibody titer belonging to the IgM class produced against the bacterial antigen (Lipid A) was elevated in sera from patients with primary biliary cirrhosis (PBC). On the other hand, the targets of the mitochondrial autoantibodies have been identified as being components of the pyruvate dehydrogenase complex (PDH). We tried to produce an experimental animal model for the investigation of the association between hepatic bile duct alteration and bacterial infection. Female C57/BL mice, aged 4 weeks, were used. An emulsion consisting of lipopolysaccharide (LPS) derived from Salmonella minnesota Re595, PDH, and Freund's adjuvant was prepared. This emulsion was subcutaneously injected on the back of the mice. The mice were divided into a control group (n = 5), a group given LPS (n = 5) alone, those given PDH alone (n = 5), and those given a combination of LPS and PDH (n = 5). The antigens were administered once a week every week with a maximum duration of administration of 24 weeks. The serum levels of IgM after 24 weeks in the LPS and LPS + PDH groups were 2.5 times higher than those in the control and PDH groups. The light microscopic findings of liver tissue revealed that infiltration of lymphocytes and plasma cells in the portal area, proliferation of the bile duct, and degeneration of the biliary epithelial cells were more prominent in the PDH and LPS + PDH groups than in the other groups. These results indicate that our animal model may be useful in investing the pathogenesis of PBC.

Animals↗

Transient ischemia depletes free ubiquitin in the gerbil hippocampal CA1 neurons.

We investigated ubiquitin immunoreactivity in the post-ischemic gerbil hippocampus using a panel of ubiquitin antibodies. Immunostaining for ubiquitin in the hippocampus was strongly dependent on the antibodies used. With rabbit polyclonal antibody U-5379, immunoreactivity disappeared from the hippocampus in the early reperfusion period and reappeared in the dentate granule cells and CA3 pyramidal cells but never in the CA1 pyramidal cells. In contrast, rat monoclonal antibody DF2 and mouse monoclonal antibody MAB1510 showed sustained immunoreactivity in the CA1 during the 48-hour reperfusion period. On the immunoblots of gerbil brain homogenates, three antibodies, U-5379, DF2 and MAB1510, exhibited similar specificities; all three labeled free ubiquitin most strongly. Immunoprecipitation disclosed that, under nondenaturing conditions, U-5379 bound exclusively free ubiquitin, whereas DF2 and MAB1510 had little affinity for free ubiquitin but appeared to have more affinity for conjugated ubiquitin. Immunoabsorption of these antibodies with free ubiquitin confirmed the above result. It is most likely that U-5379 recognized free ubiquitin in the tissue, whereas DF2 and MAB1510 recognized preferentially conjugated ubiquitin. Thus, transient ischemia depletes free ubiquitin but not conjugated ubiquitin in the CA1. This depletion may be caused by impaired conversion from conjugated to free ubiquitin and/or failure of de novo ubiquitin synthesis.

Animals↗

[Telomerase].

Telomerase is expected to be a powerful tool for cancer diagnosis and cancer chemotherapeutics because of its selective expression exclusively in various cancer tissues at a high frequency (90%) in human somatic tissues. Some precancerous tissues also express telomerase at a high frequency. Normal somatic tissues are mostly telomerase negative. Cancer cells die after a loss of telomerase activity.

Apoptosis↗

Stimulation of the activities of hepatic fatty acid oxidation enzymes by dietary fat rich in alpha-linolenic acid in rats.

The activities of hepatic fatty acid oxidation enzymes in rats fed perilla oil rich in alpha-linolenic acid (alpha-18:3) were compared with those fed saturated fats or safflower oil (the mixture of safflower oil and olive oil, 94:8, w/w) containing the same amount of polyunsaturated fatty acids with perilla oil exclusively as linoleic acid (18:2). When the rats were fed the diets containing 15% coconut, safflower, and perilla oils for 1 week, the rate of mitochondrial and peroxisomal oxidation of palmitoyl-CoA (16:0-CoA) in the liver homogenates was the highest in rats fed perilla oil. Among the rats fed the diets containing 15% palm, safflower, and perilla oils for 2 weeks, the rates of mitochondrial and peroxisomal oxidations of 16:0-, 18:2-, and alpha-18:3-CoAs were the highest in rats fed perilla oil, and the rate of oxidation of alpha-18:3-CoA by both pathways was higher than those of other acyl-CoAs in all groups. Dietary perilla oil relative to palm and safflower oils significantly increased the activities of carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, and 2,4-dienoyl-CoA reductase. The substrate specificity of carnitine palmitoyltransferase appeared to be responsible for differential rates of the mitochondrial oxidation of acyl-CoAs. The substrate specificity of acyl-CoA oxidase did not account for the preferential peroxisomal oxidation of alpha-18:3 relative to 18:2. The preferential mitochondrial and peroxisomal beta-oxidation of alpha-18:3-CoA relative to 16:0- and 18:2-CoAs was also confirmed in rats fed laboratory chow irrespective of the substrate/albumin ratios in the assay mixture. It was suggested that both substrate specificities and alterations in the activities of the enzymes in beta-oxidation pathway play a significant role in the regulation of the serum lipid concentrations in rats fed a diet rich in alpha-18:3.

Acyl-CoA Dehydrogenases↗