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Biomedical subjects

Y Shirai

Publications and source records attributed to Y Shirai.

At least 217 records · Page 12Linked to original sources

Elevated levels of transforming growth factor beta messenger RNA and its polypeptide in human hepatocellular carcinoma.

Malignant cells in culture express elevated levels of transforming growth factor beta 1 (TGF-beta 1) mRNA and secrete an abundant amount of TGF-beta protein, but little is known about the production of TGF-beta in human malignant tissues in vivo. We estimated the levels of TGF-beta 1 mRNA expression by Northern hybridization and measured TGF-beta protein using a radioreceptor assay in tumor tissues surgically obtained from six patients with hepatocellular carcinoma (HCC). TGF-beta 1 mRNA was expressed at much higher levels in HCC tissues from all the cases compared with normal human liver, suggesting an association of the activated TGF-beta 1 gene transcription with hepatocarcinogenesis. The content of TGF-beta was 207 +/- 121 ng/g wet tissue in the HCC tissue, and it showed correlation with the level of TGF-beta 1 mRNA in the tissue (r = 0.69; P less than 0.05). An immunohistochemical study demonstrated that TGF-beta 1 staining could be observed in HCC cells. These observations suggest that human HCC strongly expresses TGF-beta 1 mRNA in vivo, leading to a high content of TGF-beta protein.

Aged↗

Prolongation of antipyretic action and reduction of gastric ulcerogenicity in the rat by controlled-release granules of bermoprofen, a new nonsteroidal anti-inflammatory drug.

While bermoprofen [(+-)-10,11-dihydro-alpha,8-dimethyl-11- oxodibenz[b,f]oxepin-2-acetic acid], a new nonsteroidal antiinflammatory drug (NSAID), has potent antipyretic and analgesic activities with a short biological half-life, it shows ulcerogenic activity as a side-effect like other nonsteroidal anti-inflammatory drugs. A bermoprofen preparation was specially designed to prolong its duration of action and to reduce its side effect. Immediate-release granules (IRGs) were prepared by coating particles of Nonpareil 103 with bermoprofen. The IRGs were also coated by spraying a film solution composed of ethylcellulose and hydroxypropylmethylcellulose (3:2), and, thereby, three kinds of retard-release granules (RRGs) were obtained with the coating amounts of 1.5, 2.5, and 4%. Peak plasma bermoprofen levels were seen 0.5, 1, 2, and 3 h after single oral administrations of IRG, RRG(1.5%), RRG (2.5%), and RRG(4%), respectively, in rats. The potency order in ulcerogenic activity was RRG(1.5%) greater than IRG greater than RRG(2.5%) greater than RRG(4%) after a single oral dosage in rats. Then, IRG and RRG(4%) were mixed (in the ratio 3:7, which was calculated from their simulated plasma bermoprofen profiles) in order to get fast onset and long duration of antipyretic action. These mixed granules [i.e., the sustained-release granules (SRGs)] exhibited a falt plasma bermoprofen profile, and longer lasting antipyretic and lower ulcerogenic activities in rats in comparison with IRG or bermoprofen. From these results, it is suggested that a bermoprofen SRG preparation has more durable therapeutic activity and lower side-effects as a NSAID.

Animals↗

[Clinicopathological study on rectal cancer after sphincter-saving operation in conjunction with preoperative radiation therapy].

In an attempt to clarify the effect of preoperative radiation on rectal cancer after sphincter-saving resection, radiation group (10 cases) and non-radiation group (22 cases) were studied clinicopathologically. A rate of local recurrence was 36.4% and 10.0% in radiation and non-radiation group, respectively. In cumulative 5-year-survival, non-radiation group showed 70.7%, however, all cases were alive in radiation group. Histological examination demonstrated that such factors predictive of local recurrence as depth of invasion a2, ew (distance between tumor invasion and surgical surface) less than 2 mm, have reduced in radiation group. As a result, it was shown that irradiation had an effect of lowering local recurrences even in cases with high risk factors of local recurrence prescribed above. On the contrary, AW (distance between tumor invasion and anal stump) and frequency of lymph node metastasis had no association with local recurrence, and have not changed favorably even after irradiation. It was also thought to be important to avoid radiation colitis as carefully as possible in radiation therapy for rectal cancer.

Combined Modality Therapy↗

Effects of phorbol ester on cell growth inhibition by transforming growth factor beta 1 in human hepatoma cell lines.

The effects of phorbol ester on cell growth inhibition by transforming growth factor beta 1 (TGF-beta 1) in human hepatoma cell lines, Mahlavu and PLC/PRF/5, were investigated. TGF-beta 1 (2.5 to 10 pM) alone could not inhibit the growth of Mahlavu cells, whereas in the presence of 12-O-tetradecanoyl phorbol 13-acetate (TPA) at 1 ng/ml, TGF-beta 1 could suppress their growth in a dose-dependent manner. The growth of PLC/PRF/5 cells could be inhibited by addition of TGF-beta 1 (2.5 to 10 pM) alone in a dose-dependent manner, and this action was not affected by TPA (1 ng/ml). The TGF-beta 1 inhibition induced by TPA in Mahlavu cells could not be cancelled by addition of protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) (10 microM) or staurosporin (1 nM). Thus, TPA could induce TGF-beta 1 inhibition of cell growth in Mahlavu cells which did not respond to TGF-beta 1 alone, and activation of protein kinase C does not seem to be behind this TPA action.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Norepinephrine-induced 1,2-diacylglycerol accumulation and change in its fatty acid composition in the isolated perfused rat heart.

Phosphoinositide hydrolysis is elicited by alpha-adrenoceptor stimulation in the myocardium, resulting in the generation of 1,2-diacylglycerol by the direct activation of phospholipase C. However, the physiological role of 1,2-diacylglycerol accumulation in the heart has been largely unexplored. Therefore, we studied the effects of norepinephrine on the accumulation of 1,2-diacylglycerol and its fatty acid composition, as well as its function in isolated perfused rat hearts. A 30 min perfusion with norepinephrine following a stabilization period of 25 min caused increases of 68% and 57% in 1,2-diacylglycerol levels in the heart at 10(-6) M and 5 x 10(-6) M, respectively, compared to controls. Analysis of its fatty acid composition showed a significant elevation in the percentages of 18:2 and 20:4 although the absolute amounts of these increases in fatty acids were relatively low when compared to the elevation in the total amount of 1,2-diacylglycerol. The change in contractility was not consistently related to an increase in 1,2-diacylglycerol. These results indicate that the increase in 1,2-diacylglycerol level in response to norepinephrine perfusion was accompanied by a change in fatty acid composition of 1,2-diacylglycerol.

Animals↗

Vascular abnormalities in congenital cutis laxa--report of two cases.

Two cases of Japanese girls with congenital cutis laxa associated with cardiovascular abnormalities are described. Case 1: A 12-year-old girl has been under our observation from the age of 6 months. Cardioangiogram revealed dilatation of the ascending aorta, meandering of the descending aorta and the coronary arteries, coiling of the carotid and innominate (brachiocephalic) arteries, and hypoplasia of the pulmonary arteries. Case 2: A 2.8/12-year-old girl died after our follow-up from the age of 3 months. The cause of death was congestive heart failure secondary to peripheral stenosis of the pulmonary arteries. In both cases, skin biopsy revealed a decreased number of elastic fibers and an increased amount of acidic mucopolysaccharides. The same histological features were observed in the pulmonary arteries and other arteries as well. Electron microscopic findings were diffuse thinning of elastic fibers and reduced elastic content. The high blood level of elastase (167.8 micrograms/l) in case 1 may cast a light on the unknown etiology of the disease.

Abnormalities, Multiple↗

1,2-diacylglycerol content in thoracic aorta of spontaneously hypertensive rats.

Phosphoinositide metabolism participates in the control of cell calcium homeostasis. Because a notable neutral lipid (1,2-diacylglycerol) is generated from phosphoinositide hydrolysis and is assumed to be a secondary messenger, we determined 1,2-diacylglycerol content and its fatty acid profiles in the thoracic aorta of spontaneously hypertensive rats (SHR) and compared it with those of normotensive Wistar-Kyoto (WKY) rats. After the aorta was exposed to 10(-5) M norepinephrine as a stimulant, 1,2-diacylglycerol content in SHR was significantly higher by 33% than in WKY rats at 4 weeks of age, whereas there was no difference in 1,2-diacylglycerol content between the two strains at 20 weeks of age. Before norepinephrine stimulation, there was no significant difference in 1,2-diacylglycerol level between the two strains at 4 weeks of age. Analysis on a gas chromatograph showed that 1,2-diacylglycerol was composed of similar molecular species of fatty acids in aortas obtained from SHR and WKY rats. On the other hand, the cholesterol content of aortas was higher in SHR than in WKY rats at 20 weeks of age, whereas the difference at 4 weeks was not significant. Phosphatidylcholine, phosphatidylethanolamine, and triglyceride showed no significant difference between the two strains. It is concluded that norepinephrine-induced 1,2-diacylglycerol production increases in the thoracic aorta of SHR before the development of hypertension.

Animals↗

Influence of specific gravity and food on movement of granules in the gastrointestinal tract of rats.

The suitability of rats as an animal model for estimating the bioavailability of controlled-release granules in humans was investigated. Non-disintegrating granules (diameter of 0.8 mm; specific gravity of 0.9-1.85) were used as a model preparation. Twenty granules were administered to fed rats, fasted rats and rats given soft food, and the number of granules remaining in the gastrointestinal tract was counted at suitable intervals. Granules with a specific gravity of 1.25 administered to fasted rats were rapidly emptied from the stomach with a 50% gastric emptying time of 1 h as compared with granules with a specific gravity of less than 1.0 or with a high specific gravity such as 1.85. The presence of food in the stomach reduced the emptying rate of granules. The mean transit time of granules through the small intestinal tract was not influenced by the specific gravity or the presence of food. The mean transit time was about 3 h. It was found that the transit profile of granules through the gastrointestinal tract in rats was similar to that of granules in humans. Accordingly, it is possible to use rats at the preformulation stage for estimating the bioavailability of controlled-release granules in humans.

Animals↗

[Clinical evaluation of second-look operations in colorectal cancer].

Second look operations in colorectal cancer after curative resection were undertaken for liver metastasis or local recurrence. In our 247 curative cases, 35 were operated for liver metastasis and 18 for local recurrence. In 35 cases of liver metastasis, 25 had local disease amenable to resection and one had palliative resection. Among 21 pelvic recurrences, 11 had curative re-resection and 2 had palliative resection. The survivors generally experienced relief from various clinical distress, and most of those previously employed could return to work. The actual 3-year survival rate is 51.9% in the group of resected liver metastasis, and 9 of 13 cases resected for local recurrence are alive without evidence of re-recurrence. In conclusion, selected patients with recurrence may recover and resume ordinary living with the second look operation.

Aged↗

[Studies of diagnosis of rectal cancer using MRI, CT and intrarectal ultrasonography].

Examination using MRI, CT and Intrarectal Ultrasonography (US) were performed in 186 patients with primary rectal cancer and 127 postoperative cases, in order to diagnose the depth of invasion, lymph node metastases and local recurrence. In the diagnosis of depth of invasion, intrarectal US was superior to MRI and CT for detailed diagnosis, and MRI was the best examination modality for detecting infiltration of other organs. Also, these were available for the diagnosis of lymph node metastases, and intrarectal US was superior to MRI and CT for detecting small lymph nodes. In the detection of local recurrence, MRI, CT guided biopsy and intrarectal US were useful, especially MRI was the best examination for the decision of re-resection.

Humans↗

Effect of the content of divinylbenzene in ion-exchange resins on the chromatographic separation of alpha-cyclodextrin and glucose.

In the chromatographic separation of alpha-cyclodextrin and glucose, the parameters relating to the adsorption equilibria and rate processes of the solutes were evaluated for the sodium forms of cation-exchange resins with contents of divinylbenzene (DVB) of 2, 4, 6 and 8%. By using these parameters, the chromatograms of the solutes were then calculated. It is concluded that the resin with 6% DVB is most suitable for the chromatographic separation of the solutes on a preparative scale.

Chromatography, Ion Exchange↗