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Biomedical subjects

T Masaki

Publications and source records attributed to T Masaki.

At least 91 records · Page 5Linked to original sources
PubMed2000

Expression of rat uncoupling protein family mRNA levels by chronic treatment with thyroid hormone.

The present study was conducted to assess the effects of chronic treatment with triiodothyronine (T3) on mRNA expression of uncoupling protein (UCP) family in male Wistar King A rats. Subcutaneous injection of T3 (37 nmol/body weight 100 g) over 7 d increased mRNA expression of UCP1 in brown adipose tissue (BAT), UCP2 in white adipose tissue (WAT), and UCP3 in skeletal muscle (MSL) mRNA by 1.3, 1.7, and 2.0-fold, respectively. In contrast, the expression of ob gene mRNA in WAT and serum leptin level in the T3-treated rats decreased by 0.5-fold of the controls. These results suggest that T3 may increase UCP family expression independent of leptin action.

Adipose Tissue↗
PubMed2000

Hepatocellular carcinoma cell cycle: study of Long-Evans cinnamon rats.

Amplification found in a number of cyclin genes, especially in cyclin D and E, is an important event process that takes place in cancers, including hepatocellular carcinoma (HCC). The activities of a wide range of cell cycle-related kinases remain obscure in HCC. The purpose of the present study is to determine the cyclins and kinase activities of HCC in Long-Evans Cinnamon (LEC) rats. Cyclin D1, E, A, H, Cdk1(cyclin-dependent kinase; Cdc2), Cdk4, and Cdk6 protein levels were determined by Western blot analysis at different pathologic stages of liver tissues exhibiting HCC. Enzymatic activities of cyclin D1, E, A, Cdk4, Cdk6, Cdc2, Cdk7, and Wee1 kinase were measured by in-gel kinase assay. Protein levels and kinase activities of cyclin D1, E, Cdk4, cyclin A, and Wee1 increased proportionally with the development of HCC, especially in the transition process from chronic hepatitis to HCC. Although Cdc2 kinase activity was found to increase slightly from normal liver to chronic hepatitis, its activity remained unchanged in the process from chronic hepatitis to HCC. Cdk6 and Cdk7 activities remained unchanged in the process from normal liver to HCC. These data suggest that the increase in Cdc2 kinase may play a role in the process from normal liver to chronic hepatitis, whereas the predominant increase in cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 suggests involvement not only in the process from normal liver to chronic hepatitis, but also during transition into HCC.

Animals↗
PubMed2000

Involvement of APC and K-ras mutation in non-polypoid colorectal tumorigenesis.

The aim of this study was to clarify the role of APC and K-ras mutations in non-polypoid colorectal tumorigenesis. DNA from 63 adenomas (31 polypoid, 17 superficial elevated, 15 superficial depressed), 66 submucosally invasive carcinomas (47 polypoid, 19 non-polypoid) and 34 advanced carcinomas were examined for K-ras codon 12 point mutations and APC mutations in the mutation cluster region. K-ras mutation: the frequency in superficial depressed adenomas was lower than that in polypoid adenomas (0% vs 31%: P= 0.018). The frequency in non-polypoid carcinomas was lower than that in polypoid carcinomas (11% vs 56%: P = 0.0008), and was relatively low compared with that in polypoid adenomas (11% vs 31%). APC mutation: the frequency in superficial depressed adenomas was lower than that in polypoid adenomas (7% vs 43%: P = 0.016), and that in polypoid carcinomas was similar to that in non-polypoid carcinomas. Polypoid adenomas, polypoid carcinomas and advanced carcinomas had almost the same frequency. There may be some pathway other than the conventional adenoma-carcinoma sequence in development of non-polypoid carcinomas. The precursors of most non-polypoid carcinomas are considered to be de novo or superficial depressed adenomas. In this non-polypoid pathway, APC mutation seems to be requisite but K-ras mutation not. It is possible that new APC mutations are acquired after the development of superficial depressed adenomas.

Adenoma↗
PubMed2000

Effect of high ligation on the long-term result of patients with operable colon cancer, particularly those with limited nodal involvement.

OBJECTIVE: To find out what effect the extent of nodal dissection has on patients with operable colonic cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. PATIENTS: 564 consecutive patients who had potentially curative operations for colon cancer. Patients treated by limited nodal dissection, in which only pericolonic nodes were dissected, were excluded. MAIN OUTCOME MEASURES: Disease free survival classified by extent of nodal dissection. RESULTS: High ligation gave no significant advantage when patients were subgrouped according to degree of nodal involvement. However, number of patients with aggressive involvement (including intermediate or central nodes) was small. 511 patients (91%) had limited nodal involvement (no nodal involvement or nodal involvement confined to pericolonic nodes). High ligation of the vessels gave no advantage even with meticulous subgrouping according to age, site, and depth of invasion. CONCLUSION: Most patients with colonic cancer had limited nodal involvement. High ligation did not affect the long term results in these patients, so, less invasive low ligation should be considered. A larger study will be necessary to clarify the indications for low and high ligation for patients with aggressive nodal involvement.

Aged↗
PubMed2000

Clinical significance of MUC1 and MUC2 mucin and p53 protein expression in colorectal carcinoma.

BACKGROUND: Up-regulation of MUC1, down-regulation of MUC2 and p53 overexpression are seen in colorectal carcinomas. However, there have been few reports about the associations between MUC1, MUC2 and p53 expression and metastatic potential. The aim of this study was to investigate MUC1, MUC2 and p53 expression in colorectal carcinoma with special reference to regional and distant metastasis. METHODS: Eighty-six colorectal carcinomas were collected from patients undergoing tumor resection. Sections were used for MUC1, MUC2 and p53 immunostaining. Cancers were regarded as MUC1 or MUC2 positive when the positive cells were beyond 30% of cancer cells. Cancers with diffuse or nested patterns were regarded as having p53 overexpression. RESULTS: Of 86 cancers, 37 (43%) were MUC1 positive, 28 (33%) were MUC2 positive and 59 (69%) showed p53 overexpression. A difference was observed only in the frequency of MUC1 positivity with respect to depth of tumor invasion. Neither depth of tumor invasion nor histological differentiation had a positive correlation with MUC1, MUC2 and p53 overexpression. The frequency of MUC1 positive cells in Dukes' C and D tumors was significantly higher than that in Dukes' A and B tumors. The frequency of MUC1 positivity in tumors with hepatic involvement was significantly higher than that in tumors without hepatic involvement (100 vs 39%; p < 0.01). There was no difference in the frequency of MUC2 or p53 positivity in Dukes' stage or hepatic metastasis. MUC1 immunoreactivity of the surface was identical with that of the whole tumor in 81% (70/86) of carcinomas, MUC 2 in 87% and p53 in 100%. CONCLUSIONS: The results suggest that up-regulation of MUC1 is involved in the progression from the non-metastatic to the metastatic stage and that p53 abnormality is not directly involved in it. The data also imply that immunostaining of preoperative biopsy samples is useful for evaluating the immunoreactivity of the whole tumor.

Adult↗
PubMed2000

Small advanced colorectal cancers: clinicopathological characteristics and pathogenetic origin.

BACKGROUND: Recently, increasing numbers of small but deeply invading colorectal cancers have been detected. We conducted the present study to examine the hypothesis that these small advanced cancers are more biologically malignant than larger cancers and to elucidate their pathogenetic origin. METHODS: We analyzed the clinicopathological characteristics of 23 advanced cancers not exceeding 2 cm in diameter (Small-Ca) in comparison with 1117 advanced cancers larger than 2 cm (Large-Ca). We compared the frequency of K-ras mutation and the growth pattern (polypoid growth, PG; non-polypoid growth, NPG) between Small-Ca and 60 submucosal cancers not exceeding 2 cm in diameter (Early-Ca). RESULTS: Generally, Small-Ca showed less malignant characteristics than Large-Ca. However, Small-Ca with NPG pattern invaded more deeply and metastasized more frequently than those with PG pattern. In Small-Ca, all ulcerated lesions showed NPG pattern, whereas only 14% of protruded lesions did. In Early-Ca, 90% of non-polypoid lesions showed NPG pattern, whereas only 16% of polypoid lesions did. K-ras mutation was less frequent in ulcerated Small-Ca than in polypoid cancers (33 vs 57%). In Early-Ca, non-polypoid cancers showed a lower frequency of K-ras mutation than polypoid cancers (9% vs 46%). CONCLUSIONS: Small-Ca, in general, were less malignant clinicopathologically than Large-Ca; however, Small-Ca with NPG pattern showed a tendency to be more aggressive than those with PG pattern. The similarity of the K-ras mutation rate and growth pattern of ulcerated Small-Ca and non-polypoid Early-Ca suggests that the majority of ulcerated Small-Ca may originate from non-polypoid Early-Ca.

Aged↗
PubMed2000

The effects of aprotonin on platelets in vitro using whole blood flow cytometry.

UNLABELLED: We sought to evaluate the effects of aprotinin on the number and function of the platelet glycoprotein (GP) IIb-IIIa receptor and on the expression of P-selectin in vitro in order to gain insight into the potential mechanisms involved in the platelet-protective action of aprotinin during cardiopulmonary bypass. Aprotinin at 50 to 200 kallikrein inhibiting units/mL decreased the expression of activated GP IIb-IIIa complex in response to adenosine diphosphate or thrombin receptor activator peptide 6 in a dose-dependent manner in both citrated and heparinized whole blood experiments. Aprotinin inhibited adenosine diphosphate-induced platelet aggregation, but it exhibited no effect on the expression of GP IIIa and P-selectin. These results indicate that aprotinin interferes with the platelet fibrinogen receptor function during pharmacological activation. Reduced aggregability and platelet adhesion to fibrinogen adsorbed to synthetic surfaces in the presence of aprotinin may prevent platelet consumption during clinical cardiopulmonary bypass. This in vitro study demonstrates that aprotinin decreases the agonist-induced expression of activated GP IIb-IIIa receptors that play a major role in platelet aggregation and adhesion to biomaterial surfaces. IMPLICATIONS: This in vitro study demonstrates that aprotinin decreases the agonist-induced expression of activated glycoprotein IIb-IIIa receptors that play a major role in platelet aggregation and adhesion to biomaterial surfaces.

Adenosine Diphosphate↗
PubMed2000

The effects of heparin, protamine, and heparinase 1 on platelets in vitro using whole blood flow cytometry.

UNLABELLED: The effects of heparinization and the reversal of heparin activity on platelet function after cardiopulmonary bypass have not been well defined. Flow cytometry has become a convenient and powerful technique for characterizing platelets. We examined the expression of a secretion marker (P-selectin) and an aggregation marker (activated fibrinogen receptor GP IIb-IIIa) on normal platelets in response to heparin, heparinase 1, and protamine in vitro using whole blood flow cytometry. Unfractionated heparin increased adenosine diphosphate-induced expression of P-selectin and GP IIb-IIIa in a dose-dependent manner. Heparinase 1 alone decreased both markers of platelet activation. Protamine alone increased P-selectin expression but had no effect on GP IIb-IIIa expression. Heparinase 1 antagonized the stimulatory effect of heparin on both markers. In contrast, protamine antagonized the effect of heparin on GP IIb-IIIa expression but potentiated the effect of heparin on P-selectin expression. These in vitro observations suggest that 1) both heparin and its reversal agents affect platelet secretion and aggregation, and 2) heparinase 1 reverses heparin-induced platelet preactivation more effectively than protamine. IMPLICATIONS: This experimental in vitro study demonstrates that heparin and its reversal agents affect platelet secretion and aggregation.

Adult↗
PubMed2000

The endothelin family: an overview.

Endothelin (ET) is a potent vasoconstrictive peptide initially found in the conditioned medium of cultured endothelial cells (1). It comprises 21 amino acid residues including four cysteine residues. The four cysteine residues form two intramolecular disulfide bonds. No amino acid sequence similar to that of ET had been previously reported. Furthermore its pharmacological action was unique. When it was injected intravenously into rats, a sustained and long-lasting pressor response was observed, suggesting a role of ET in maintenance of blood pressure or generation of hypertension. For these reasons many investigators were interested in this peptide. However, numerous reports following publication of the first paper detailing study of ET revealed that the mechanism for maintenance of blood pressure was not so simple. Apart from this problem, many pharmacological studies revealed that ET was active not only in the cardiovascular system but also in noncardiovascular systems. Those results stimulated further the worldwide interest in ET.

Endothelins↗
PubMed2000

Endothelin-1-induced contraction of rat thoracic aorta depends on calcium entry through three types of calcium channel.

We have recently shown that endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and store-operated Ca2+ channel (SOCC). These channels can be pharmacologically discriminated using 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1-H-imidazoe l hydrochloride (SK&F 96365) (a blocker of NSCC-2 and SOCC) and (RS)-(3,4-dihydro-6,7-dimethoxyisoquinoline-1-gamma l)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]acetamide (LOE 908) (a blocker of NSCC-1 and NSCC-2). For our study we characterized Ca2+ channels involved in ET-1-induced contractions and increases in the intracellular free Ca2+ concentration ([Ca2+]i) using these blockers. Our results show that the response to lower concentrations of ET-1 involves only one Ca2+ channel which is sensitive to SK&F 96365 and LOE 908 (NSCC-2). In contrast, the response to higher concentrations of ET-1 involves two types of Ca2+ channel in addition to NSCC-2: one is sensitive to SK&F 96365 but resistant to LOE 908 (SOCC), and the other is resistant to SK&F 96365 but sensitive to LOE 908 (NSCC-1). Furthermore, the percentage contribution of Ca2+ entry through NSCC-1, NSCC-2 and SOCC is calculated to be 10%, 50-60% and 30-40%, respectively.

Acetamides↗
PubMed2000

Pharmacological properties of calcium entry channels in A7r5 cells activated by endothelin-1.

Using whole-cell recordings of patch-clamp and monitoring of the intracellular free calcium (Ca2+) concentration ([Ca2+]i), we characterized Ca2+ entry channels in A7r5 cells activated by endothelin-1 (ET-1). ET-1 activates three types of voltage-independent Ca2+ entry channels: two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and store-operated Ca2+ channel (SOCC). Furthermore, it was found that these channels can be discriminated pharmacologically using Ca2+ channel blockers such as 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1-H-imidazoe l hydrochloride (SK&F 96365) and (RS)-(3,4-dihydro-6,7-dimethoxyisoquinoline-1-gamma l)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxyphenyl)ethoxyl]acetamide (LOE 908). NSCC-1 is resistant to SK&F 96365 but sensitive to LOE 908, whereas NSCC-2 is sensitive to both drugs: SOCC is sensitive to SK&F 96365 but resistant to LOE 908. Using these channel blockers, we analyzed the Ca2+ entry channels involved in the ET-1-induced increase in [Ca2+]i of the cells. The increase induced by lower concentrations of ET-1 (< or = 0.1 nM) was unaffected by SK&F 96365 but it was abolished by LOE 908. In contrast, the increase caused by higher concentrations of ET-1 (> or = 1 nM) was suppressed by SK&F 96365 or LOE 908 to about 35% of controls, and abolished by combined treatment with SK&F 96365 and LOE 908. These results show that the increase in [Ca2+]i resulting from lower concentrations of ET-1 (< or = 0.1 nM) involves Ca2+ entry through only NSCC-1, whereas that resulting from higher concentrations of ET-1 involves Ca2+ entry through NSCC-1, NSCC-2 and SOCC, contributing 35%, 30% and 30%, respectively, to total Ca2+ entry.

Acetamides↗
PubMed2000

Retrospective radiographic analysis of nonpedunculated colorectal carcinomas with special reference to tumor doubling time and morphological change.

OBJECTIVE: Our aim was to characterize the development of nonpedunculated colorectal carcinomas by retrospective radiographic analysis, with special reference to tumor doubling time and morphological change. METHODS: Eleven colorectal carcinomas, which were observed for >6 months by barium enema examinations, were collected and retrospectively reviewed. There were five early and six advanced carcinomas, including submucosally invasive, superficial depressed carcinomas. RESULTS: Mean diameter of lesions at initial barium enema examination was 13.5 mm (early, 10.4 mm; advanced, 16.0 mm) and that at final barium enema examination was 30.9 mm (early, 18.2 mm; advanced, 41.5 mm). Initial morphology of the lesions was superficial in three, sessile in seven, and semipedunculated in 1. There was no pedunculated lesion. Macroscopic morphology of the five early carcinomas was superficial depressed (IIc) in two cases, mostly depressed but partly elevated (IIc+IIa) in one case, and superficial elevated with a depressed component (IIa+IIc) in two cases; all of the advanced carcinomas were of the ulcerated type. Mean doubling time was 6.8 months (early, 9.4 months; advanced, 4.7 months). Early carcinomas had significantly longer doubling times than advanced carcinomas (p = 0.017, Wilcoxon's text). The lesions with the longest doubling times were superficial depressed lesions. CONCLUSIONS: Early carcinomas have longer doubling times than advanced carcinomas. Most nonpedunculated colorectal carcinomas grow without significant morphological changes. Superficial depressed type tumors grow slowly, maintaining their macroscopic morphology.

Adult↗
PubMed2000

Inducible expression of LOX-1, a novel receptor for oxidized LDL, in macrophages and vascular smooth muscle cells.

Macrophages appear to take up oxidized low density lipoprotein (Ox-LDL) by multiple receptor-mediated pathways. This study, therefore, has been performed to determine if LOX-1, a novel receptor for Ox-LDL, which was identified in vascular endothelial cells, is also expressed in macrophages. Expression of LOX-1 can be induced after macrophage-like differentiation in human peripheral blood monocytes as well as THP-1 cells. Furthermore, expression of LOX-1 in macrophages is also upregulated by an inflammatory cytokine TNF-alpha, which was shown to be present in atherosclerotic arterial wall. Expression of this novel receptor LOX-1 may play an important role in Ox-LDL uptake and subsequent foam cell formation in macrophages.

Animals↗