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Biomedical subjects

T Masui

Publications and source records attributed to T Masui.

At least 109 records · Page 6Linked to original sources

Establishment and characterization of an epithelial cell line with quasi-normal chromosomes from a tubular adenoma of a familial polyposis coli patient.

An epithelial cell line designated FPCK-1 has been established from a tubular adenoma developing in a male familial polyposis coli (FPC) patient. The FPCK-1 cells grow very slowly with abundant mucus production and have been maintained stably for 3 years in culture. No growth was evident either in soft agar or nude mice. FPCK-1 cells present a normal male karyotype and do not show loss of specific loci on chromosomes 5, 17, 18, and 22 which have been reported to be lost frequently in human colon carcinomas. The cells have neither a point mutation on codon 12 of K-ras gene nor gene amplification of myc, c-H-ras, and/or c-K-ras genes. These results thus suggest the existence of hitherto unknown causative event(s) underlying adenoma development in FPC patients. The FPCK-1 cell line should prove useful for further analytical investigation of the multiple steps involved in human colon carcinogenesis.

Adenoma↗

Myocardial infarction: assessment with an intravascular MR contrast medium. Work in progress.

The effect of a new intravascular magnetic resonance (MR) contrast medium (gadolinium diethylenetriaminepentaacetic acid [DTPA] polylysine) was evaluated in acute, subacute, and chronic myocardial infarctions in rats. Signal intensity (SI) was measured before and after intravenous administration of Gd-DTPA polylysine. Before administration of contrast material, chronic infarctions had lower SI than normal myocardium. With Gd-DTPA polylysine, three zones were identified in acute and subacute stages of myocardial infarction, but in the chronic stage, images demonstrated two zones. In acute and subacute infarctions, Gd-DTPA polylysine produced greater enhancement (over 60 minutes) in the peri-infarction zone than in the normal or infarcted myocardium. In chronic infarctions, Gd-DTPA polylysine had no discernible effect on the SI of the central infarction zone. Overall, it caused no significant hemodynamic effects. MR imaging with Gd-DTPA polylysine produced differential tissue enhancement in myocardial infarctions, which varied according to the age of the infarction.

Animals↗

Right and left lung perfusion: in vitro and in vivo validation with oblique-angle, velocity-encoded cine MR imaging.

Quantification of pulmonary flow is clinically important in the evaluation of both congenital and acquired heart disease. Velocity-encoded cine magnetic resonance (MR) is a promising technique for measuring velocity and volume of blood flow. The authors report validation of the accuracy of velocity-encoded cine MR for measurement of oblique-angle flow in vitro, with use of a constant-flow phantom, and in vivo, with nine healthy volunteers in whom velocities were measured separately in the main, right, and left pulmonary arteries. Findings at MR were compared with findings at Doppler echocardiography. Velocity measurements in a flow phantom with cine MR correlated well with direct measurements at Doppler echocardiography. Velocity-encoded cine MR enabled accurate and reproducible measurement of absolute blood flow in healthy subjects. Oblique-gradient flow encoding (ie, flow-encoding direction coinciding with the true direction of flow) was the method of choice for velocity measurements in the right and left pulmonary arteries.

Adult↗

Occlusive and reperfused myocardial infarcts: MR imaging differentiation with nonionic Gd-DTPA-BMA.

To increase the time during which effective contrast exists between normal and infarcted myocardium, a high dose (0.6 mmol/kg) of the nonionic contrast medium gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd-DTPA-BMA) was used to distinguish between occlusive and reperfused myocardial infarctions in rats. After administration of Gd-DTPA-BMA, there was clear and persistent demarcation of both occlusive and reperfused infarcts on T1-weighted MR images. In occlusive infarcts, normal, infarcted, and periinfarcted myocardium could be identified. High signal intensity was evident for 60 minutes in a band straddling the border between infarcted and normal myocardium, namely, the periinfarction zone. In the reperfused infarct, normal and infarcted myocardium could be identified. The reperfused zone was immediately enhanced after injection of Gd-DTPA-BMA. A differential pattern of enhancement between occlusive and reperfused myocardial infarcts was evident for 1 hour. Thus, Gd-DTPA-BMA has the potential to allow (a) depiction of occlusive and reperfused acute myocardial infarcts, (b) documentation of reperfusion of myocardial infarction, and (c) distinction between occlusive and reperfused infarction.

Animals↗

Abnormalities of the pulmonary veins: evaluation with MR imaging and comparison with cardiac angiography and echocardiography.

Seventy-seven patients underwent T1-weighted spin-echo magnetic resonance (MR) imaging. Group 1 (n = 56) consisted of patients with various types of congenital heart disease but normal pulmonary veins. Group 2 (n = 22) consisted of patients with the following conditions: partial anomalous pulmonary venous connection (n = 11), total anomalous pulmonary venous connection (n = 5), cor triatriatum (n = 4), or pulmonary vein stenosis (n = 2). In group 1, the sites of connections of all four pulmonary veins were identified with MR imaging in 88% of cases; the connections of at least three pulmonary veins were seen in all patients. In group 2, the prospective detection rate of pulmonary venous abnormalities with MR imaging was 95%. The prospective detection rates of pulmonary venous abnormalities with cardiac angiography (n = 13) and echo-cardiography (n = 13) were 69% and 38%, respectively. This study indicates that MR imaging can accurately demonstrate the normal pulmonary veins and abnormalities of the pulmonary veins.

Adolescent↗

Mechanistic analysis of multistage carcinogenesis in the rat prostate.

A new rat model of prostatic carcinomas has been developed using F344 rats and 3,2'-dimethyl-4-aminobiphenyl (DMAB). Immunohistochemical and biochemical investigation using polyclonal antibodies against DMAB-modified DNA showed DMAB-DNA adducts to be formed in all parts of the prostate including the seminal vesicles. DMAB normally induces in situ carcinomas limited to the ventral prostate. However, when it is given together with and followed by testosterone propionate (TP), invasive adenocarcinomas, some of which demonstrated metastatic growth in other organs, arose from the dorsolateral and anterior prostate and seminal vesicles, indicating that exogenous testosterone can exert strong enhancing effects on chemically induced carcinogenesis in these lobes of the rat prostate. Sequential observation has indicated that atypical hyperplasias are premalignant lesions and that testosterone plays a key role in the promotion and progression stages of prostate tumor development. By analogy, it is suggested that testosterone may exert equivalent influence on progression of prostate neoplasia in man. In the present studies low incidences of mutations were detected in p53 or K-ras genes in noninvasive and invasive rat prostate carcinomas induced by DMAB.

Animals↗

Transformation of rat bladder epithelial cells by introduction of a single oncogene.

Malignant transformation of cells in vitro requires the action of cooperating oncogenes. However, the action of a single activated oncogene, if placed under a strong constitutive promoter, is sufficient to transform in vitro established cells. We have investigated the role of cooperating oncogenes in the transformation of normal rat bladder epithelial cells. Effects of polyoma middle T, v-Ha-ras or activated rat c-Ha-ras, independently or in combination with v-myc on in vitro and in vivo behavior of rat bladder epithelial cells were studied. Introduction of polyoma middle T alone, c-Ha-ras or in some cases v-myc into "normal" rat bladder epithelial cells was sufficient for full malignant transformation of these cells. In addition, introduction of polyoma middle T, activated c-Ha-ras or v-myc transformed cells into nude mice, resulted in development of highly invasive adenocarcinomas. These results indicate that full malignant transformation of normal rat bladder epithelial cells did not require the action of introduced cooperating oncogenes.

Adenocarcinoma↗

Point mutation in codons 12 and 61 of the Ha-ras gene in rat urinary bladder carcinomas induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.

Male F344 rats were fed N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) for up to 4 wk, then were given the basal diets (Prolab 3200 or AIN-76A) with or without 5% sodium saccharin for up to 100 wk. Eleven transitional cell carcinomas (TCCs), one undifferentiated carcinoma, and two sarcomas of the urinary bladder were examined for the expression of ras gene product, p21, by immunohistochemical staining and western blot analysis. Point mutation in codons 12 or 61 of the Ha-ras genes amplified by polymerase chain reaction was examined by a slot-blot screening procedure using allele-specific oligonucleotide probes. Immunohistochemical staining showed enhanced immunoreactivity with the antibody to ras p21 in seven TCCs and one undifferentiated carcinoma. Western blot analysis showed faster migration of the p21 band in 6 of 11 TCCs. Oligonucleotide hybridization revealed the point mutation in codon 12 of Ha-ras gene (GGA----GTA in 1 TCC) and in codon 61 (CAA----CGA in 5 TCCs and CAA----CTA in 1 TCC). Two mutations in codons 12 and 61 coexisted in one tumor, which were found to be present in different Ha-ras alleles. The incidence of Ha-ras gene mutations were similar in groups treated with (3 of 6) or without (3 of 8) sodium saccharin. These results suggest the involvement of activated Ha-ras gene in rat urinary bladder carcinogenesis induced by FANFT.

Animals↗

Effects of different types of diet and sodium saccharin on proliferation at the limiting ridge of the rat forestomach.

Sodium saccharin, at high doses in the diet, has been reported to cause hyperplasia of the forestomach (squamous portion of stomach), at the limiting ridge in F344 rats, in addition to its potential to induce proliferative effects on the urinary bladder epithelium. We have characterized this hyperplasia of the squamous epithelium of the forestomach at the limiting ridge in F344 and Sprague-Dawley rats given various doses of sodium saccharin for 4 to 95 wk. With increasing doses of sodium saccharin, the limiting ridge of the forestomach showed dose-related morphological changes: basal-cell hyperplasia, early papillary hyperplasia with basal-cell hyperplasia and papillary hyperplasia. Calcium saccharin in Prolab diet caused hyperplasia of the forestomach at the limiting ridge, similar to that caused by sodium saccharin. The severity of hyperplasia was influenced by the type of diet and by the strain of rats. AIN-76A diet without added sodium saccharin caused basal-cell hyperplasia in F344 rats, whereas Prolab, Purina and NIH-07 diets without added sodium saccharin had little or no effect on the forestomach. The effect of AIN-76A diet alone persisted through 95 wk of feeding without any evidence of tumour formation. In Sprague-Dawley rats, which appeared more sensitive to effects on the forestomach than F344 rats, Prolab 3200 and Purina diets without sodium saccharin caused basal-cell hyperplasia in more than half of the treated rats. The forestomach hyperplasia associated with AIN-76A or saccharin administration appears to be mild, limited in extent to the limiting ridge, and not associated with carcinogenesis.

Animal Feed↗

Comparative sequential changes in serum and biliary levels of bile acid components after a single dose of D-galactosamine or partial hepatectomy in the rat.

In order to characterize changes in bile acid profile during liver cell damage and regeneration, levels of bile acids in serum and bile were determined by high performance liquid chromatography (HPLC) in F344 rats treated with a single dose of D-galactosamine (galactosamine, 300 mg/kg, i.p.) or subjected to two-thirds partial hepatectomy (PH). In the serum, galactosamine caused elevation of conjugated bile acids such as taurocholic acid (TCA) and tauro-beta-muricholic acid (T beta MCA) at the 24 and 48-h time points, whereas unconjugated bile acids including cholic acid (CA) at 24 h and hyodeoxycholic acid (HDCA) at 48 h were increased after PH. In the bile, elevation of TCA showed most remarkable elevation at the 24-h time point in the galactosamine-treated group. All components of biliary bile acids showed rapid decreases from 24 to 48 h. The results demonstrated that while liver tissue damaged by galactosamine is able to conjugate bile acids it allows leakage into the blood stream. In contrast, the results for rats subjected to PH indicated that liver cells during DNA synthesis are not capable of conjugating all free bile acids with taurine although a similar leakage occurs. It is concluded that obvious elevation of serum TCA or CA and biliary T beta MCA could be a useful indicator of hepatocellular proliferation.

Animals↗

Influences of diet and strain on the proliferative effect on the rat urinary bladder induced by sodium saccharin.

Rats were fed sodium saccharin as 5 or 7.5% of the diet by weight, and proliferation of the bladder epithelium was assessed by autoradiography, histology, and scanning electron microscopy. In Experiment 1, male F344 rats, 5 weeks old, were placed on a diet of 0, 5, or 7.5% NaS mixed in Prolab 3200, NIH-07, or AIN-76A diet for 4 or 10 weeks. In Experiment 2, 5-week-old F344 rats or 4-week-old Sprague-Dawley rats were fed 0, 5, or 7.5% NaS in Prolab 3200 or Purina 5002 diet for 10 weeks. In Experiment 1, at both the 4- and 10-week intervals, NaS had a greater effect on the urothelium when administered in the Prolab diet compared to the NIH diet, and there was little response with the AIN diet. Eight of 10 rats fed 7.5% NaS in Prolab 3200 for 4 or 10 weeks had bladders with simple or nodular hyperplasia, and eight of nine bladders contained abnormal surface features visible by scanning electron microscopy. At 10 weeks for control animals, the average labeling index following [3H]thymidine incorporation into bladder epithelium was approximately 0.05%. For rats fed 7.5% NaS diets, the labeling index was 0.43% for Prolab, 0.14% for NIH-07, and 0.04% for AIN-76A. In Experiment 2, the response to NaS was considerably greater in F344 rats than in Sprague-Dawley rats fed the same diet, and for both strains, the response to NaS was greater in Prolab than in Purina diets. In conclusion, the proliferative effect of NaS on male rat urinary bladder depended on rat strain as well as on type of diet.

Animals↗

Long-term feeding study of N,N'-diphenyl-p-phenylenediamine in F344 rats.

Groups of 50 F344 rats of each sex were fed a diet containing 0.5 or 2% of N,N'-diphenyl-p-phenylenediamine (DPPD) for 104 weeks and were killed 8 weeks after the cessation of DPPD administration. DPPD-treated rats of both sexes showed a dose-dependent reduction in body weight gain, but no lower survival rate, when compared with untreated control rats. Blood and urine analysis showed no remarkable changes due to the treatment. Calcium deposition in the kidney of males was the only significant histological change relating to the treatment. Tumors were found in many organs of all groups, but a significant increase of tumor induction in DPPD-treated groups was not observed.

Administration, Oral↗

Strong promoting activity by uracil on urinary bladder carcinogenesis and a possible inhibitory effect on thyroid tumorigenesis in rats initiated with N-methyl-N-nitrosourea.

Uracil has been shown to cause a strong proliferative response in the urinary bladder epithelium of rats and mice through calculus formation and, consequently, acts as a strong promoter in bladder carcinogenesis. In this study, we examined the effect of uracil on two-stage carcinogenesis in various organs using N-methyl-N-nitrosourea (MNU) as the initiator. F344 rats were injected i.p. with MNU twice weekly for 4 weeks and then given diet containing 3.0% uracil for 20 weeks. Uracil induced urinary bladder carcinomas in all rats pretreated with MNU, and it decreased the combined incidence of adenomas and carcinomas in the thyroid. Although not significant, uracil decreased the incidence of adenomas in the lung and increased that of lymphomas of the thymus. A possible influence of a significantly decreased body weight gain caused by uracil treatment on the reduced tumor incidence in the thyroid and lung is discussed. The present data demonstrate the strong promotion activity of uracil for urinary bladder carcinogenesis, and suggest a possible inhibitory effect on thyroid carcinogenesis.

Adenocarcinoma↗

Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes.

The majority of human lung cancers arise from bronchial epithelial cells. The normal pseudostratified bronchial epithelium is composed of basal, mucous, and ciliated cells. This multi-differentiated epithelium usually responds to xenobiotics and physical injury by undergoing basal cell hyperplasia, mucous cell hyperplasia, and squamous metaplasia. One step of the multistage process of carcinogenesis is thought to involve aberrations in control of the squamous metaplastic processes. Decreased responsiveness to regulators of terminal squamous differentiation may confer a selective clonal expansion advantage to an initiated cell. We studied the effects of endogenous [e.g., transforming growth factor beta 1 (TGF-beta 1) and serum] and exogenous [e.g., 12-O-tetradecanoyl-13-phorbol-acetate (TPA), tobacco smoke condensate, and aldehydes] modifiers of normal human bronchial epithelial (NHBE) cell in a serum-free culture system. NHBE cells are growth inhibited by all of these compounds and induced to undergo squamous differentiation by TGF-beta 1 or TPA. In contrast, lung carcinoma cell lines are relatively resistant to inducers of terminal squamous differentiation which may provide them with a selective growth advantage. Chemical agents and activated protooncogenes (ras,raf,myc) altered the response to endogenous and exogenous inducers of squamous differentiation and caused extended cellular lifespan, aneuploidy, and/or tumorigenicity. The data suggest a close relationship between dysregulation of terminal differentiation pathways and neoplastic transformation of human bronchial epithelial cells.

Bronchi↗

Modifying effects of concomitant treatment with butylated hydroxyanisole or butylated hydroxytoluene on N,N-dibutylnitrosamine-induced liver, forestomach and urinary bladder carcinogenesis in F344 male rats.

The modifying effects of concomitant antioxidant treatment on N,N-dibutylnitrosamine (DBN)-induced carcinogenesis were investigated. Male F344 rats were given 0.05% DBN in their drinking water for 16 weeks, and simultaneously administered powder diet containing 2.0% butylated hydroxyanisole (BHA) or 0.7% butylated hydroxytoluene (BHT) for 16 weeks. Control animals received drinking water containing 0.05% DBN without antioxidant treatment. The final incidences of hepatocellular carcinomas were 100, 100 and 40% in the DBN plus BHA, DBN plus BHT and DBN treated groups, respectively, the difference being significant (P less than 0.001). Lung metastases were only observed in the DBN plus BHT group and DBN plus BHA group (50%, P less than 0.001; 7%, respectively). The incidence of papillary or nodular hyperplasia of the urinary bladder in the DBN plus BHA group was significantly higher than that of the control (P less than 0.05). Furthermore, esophageal carcinomas and papillomas were observed in all DBN treated groups, with no inter-group significant variation in yield. On the other hand, combination of DBN treatment with BHA or BHT significantly reduced the resultant incidences of forestomach hyperplasia. The results clearly demonstrated that concomitant administration of antioxidants, and in particular BHT, can modify DBN carcinogenesis.

Animals↗

Detergent and ion-pair extraction of bile acids in liver tissue for analysis by fast atom bombardment mass spectrometry.

Methods for detergent and ion-pair extraction and group separation of bile salts in liver tissue using decyltrimethylammonium bromide (DTMAB), Lipidex 1000 and octadecyl-bonded silica were studied. Samples of rat liver were homogenized in 0.1 M DTMAB and the supernatants were diluted to 0.03 M DTMAB and passed through a column of Lipidex 1000/Sep-Pak C18. After washing with water, the bile salts were eluted with 70% aqueous methanol. The recovery of endogenous bile acids labelled with 14C in vivo was quantitative. Part of the extracted lipids and remaining DTMAB was removed by a second extraction on Sep-Pak C18, resulting in 84% recovery of bile acids in an extract suitable for analysis by fast atom bombardment mass spectrometry. The amount of extract required for this analysis corresponded to 5-10 mg of rat liver tissue. The ion-pairs of unconjugated and conjugated mono-, di- and trihydroxy bile acids could be separated into groups by reversed-phase chromatography on mu Bondapak C18 prior to mass spectrometric analysis.

Animals↗

Internal representations and the conceptual operation of color in pure alexia with color naming defects.

This research examined the structure of internal representation and the conceptual operation of color in two pure alexic cases (Case I and Case II) with color naming defects. Experiment I investigated the structure of the internal representation of different kinds of colors using a similarity judgment task. Experiment II examined categorical judgments of perceived colors using a two-alternative-forced choice task. Experiment III tested the classification of perceived colors using a color sorting task. The performance of Case I essentially fell within the normal range while the results of Case II showed some impairment in the conceptual operation of color. Analysis of the responses obtained from these experiments indicated that the color naming defects in Case I can be explained in terms of visual-verbal disconnection. However, the naming defects in Case II reflect disfunction in some other higher cortical processes coupled with visual-verbal disconnection.

Color Perception↗

Effects of urinary crystals induced by acetazolamide, uracil, and diethylene glycol on urinary bladder carcinogenesis in N-butyl-N-(4-hydroxybutyl)nitrosamine-initiated rats.

In order to examine the promoting effect of urinary crystals on urinary bladder carcinogenesis, acetazolamide, uracil, and diethylene glycol, all of which have been reported to cause urinary crystals or calculi, were administered to male F344 rats for 32 weeks after pretreatment with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks. A marked increase in urinary crystals was observed in acetazolamide-treated rats and a slight increase in crystals was observed in uracil- and diethylene glycol-treated rats. Histological examination of the urinary bladder revealed that the BBN-acetazolamide treatment resulted in a higher incidence of carcinoma than BBN-control. Uracil and diethylene glycol did not cause any significant difference compared to the control. Promoting effects by urinary crystals were not clearly shown in the present experiment and, therefore, urinary crystals appear to play a very limited role, if any, in urinary bladder carcinogenesis.

Acetazolamide↗