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Biomedical subjects

K Miyata

Publications and source records attributed to K Miyata.

At least 253 records · Page 14Linked to original sources

Growth retardation in rats whose growth hormone gene expression was suppressed by antisense RNA transgene.

We produced four transgenic founder rats (F0) by introducing into rat embryos a fusion gene, which consisted of rat growth hormone (GH) promoter containing with four copies of thyroid hormone response element (TRE) and antisense cDNA sequences for rat GH. This transgene promoter directed 2.8-fold stimulation of CAT gene expression in transfected GH3 rat pituitary tumor cells compared with the rat GH promoter alone. Two of four transgenic rats expressed antisense RNA in the pituitary. Transgenic offspring (F1) from each founder rat exhibited dwarfism at as early as 3-4 weeks of age, and they exhibited approximately 70-85% reduced growth rate compared with their nontransgenic littermates over 56 weeks of observation. Plasma rat GH concentration was approximately 40-50% lower in transgenic F1 rats compared to their nontransgenic littermates. In these experiments, the pituitary hormone expression controlled in a complex manner was shown to be repressed by the antisense RNA transgene. Furthermore, the suppression of gene expression could be achieved by antisense RNA transgene in the rat as well.

Animals↗

Comparison of portal pressure with intravascular esophageal variceal pressure (IEVP) directly measured with a flexible indwelling needle.

Intravascular esophageal variceal pressure (IEVP) was measured using a flexible indwelling needle and compared with wedged hepatic venous pressure (WHVP) in 38 patients with liver cirrhosis. There was a high correlation between IEVP and WHVP; the former was lower than the latter, indicating the presence of a pressure gradient. Bleeders with a history of esophageal variceal rupture showed higher IEVP value than non-bleeders without a history of rupture, even though no difference in WHVP was observed. IEVP in the post-endoscopic injection sclerotherapy (EIS) group, even in those with endoscopic findings of large varices, was lower than that in the untreated groups. These results suggest that IEVP is a factor in the hemodynamics of patients with portal hypertension and that its measurement may be helpful in elucidating the pathophysiology of esophageal varices.

Blood Pressure Determination↗

Quantification of human splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 1).

Positron emission tomography (PET) by means of a dynamic state method and H2(15)O was performed to quantify splenic blood flow in 20 patients who had no hepatic functional disorders. Non-linear regression analysis was applied to determine splenic blood flow. In calculating arterial input function for the spleen, our original exponential method was used to facilitate computerization. Mean splenic blood flow per 100 g of spleen (SBF) was 168.0 ml/min/100 g with a standard error (SE) of 12.4 ml/min. The mean spleen-blood partition coefficient for water (rho) was 0.767 with a SE of 0.020. Significant correlations were noted between the values for SBF obtained by the exponential method and linear method in which individual increasing values for arterial 15O concentration were used rectilinearly (r = 0.96, p < 0.005) and also between the values for rho obtained by the two methods (r = 0.95, p < 0.005). In order to validate the application of a one compartment model to an organ with a large blood volume such as the spleen, a further experiment was performed with a water flow model simulating splenic circulation. We succeeded in quantifying regional splenic blood flow by PET. It was thought that the quantification of splenic blood flow by our method would be beneficial in the study of splenic circulation, which is expected to be altered under conditions of portal hypertension, liver dysfunction and shock, etc.

Adult↗

Relationship between liver function and splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 2).

We measured splenic blood flow in 55 patients by means of quantitative splenic positron emission tomography (PET), a novel, dynamic state method with H2(15)O as a tracer. Twenty-four of the 55 patients suffered from liver cirrhosis (LC), 25 showed no evidence of cirrhosis (NR) and 6 patients were diagnosed as having chronic hepatitis (CH). Splenic blood flow per 100 g weight of the spleen (SBF) was significantly correlated with splenic volume (r = -0.39, p < 0.005). The indocyanine green retention test at 15 min (r = -0.39, p < 0.005) and the hepaplastin test (r = 0.37, p < 0.025) also correlated significantly with SBF. The means and 95% confidence intervals for the LC, CH, and NR groups were 117.5 ml/min/100 g (96.6-138.4), 102.5 ml/min/100 g (60.6-144.4), and 160.3 ml/min/100 g (139.8-180.8), respectively. The differences in SBF between these 3 groups were significant (p < 0.01). We conclude that regional splenic blood flow is not proportionate to splenic volume, although the splenic volume does increase with the progressive chronic changes observed in hepatic diseases.

Adult↗

Difference in regional hepatic blood flow in liver segments--non-invasive measurement of regional hepatic arterial and portal blood flow in human by positron emission tomography with H2(15)O.

Organ blood flow can be quantitatively measured by positron emission tomography (PET). As the liver has dual blood supplies, arterial and portal, regional hepatic blood flow had not been measured quantitatively. However, we succeeded in simultaneously measuring both regional hepatic arterial and portal blood flow by PET in non-stressed patients. Mean regional portal hepatic blood flow in patients with normal liver and cirrhotic liver was 57.5 and 36.7 ml/minutes/100 g, respectively. Mean regional arterial blood flow was 42.5 and 30.7 ml/minutes/100 g, respectively. A significant difference between regional portal hepatic blood flows in normal and cirrhotic patients was noted. Mean regional portal hepatic blood flow in the lateral, medial, anterior, and posterior segments of the liver was 29.8, 43.4, 50.0, and 40.9 ml/minutes/100 g, respectively. Mean regional arterial blood flow in each liver segment was 37.6, 30.0, 28.2, and 31.6 ml/minutes/100 g, respectively. A significant difference between regional portal hepatic blood flows in lateral and anterior segment was noted. The p value was less than 0.025 and the 95% confidence interval of the difference between means was from -20.2 to -2.7 ml/minutes/100 g by ANOVA. These results showed that regional hepatic blood flow is not the same in all the liver segments.

Adult↗

Antisecretory effects of a novel and long-lasting histamine H2-receptor antagonist, YM-14471, in rats and dogs.

We investigated some properties of YM-14471 (2-2(-[2-(diaminomethyleneamino)thiazol-4-yl]methylthio)ethy l-5-[3- (diethylamino)propyl]-6-methyl-pyrimidine-4-one trihydrochloride), a new H2-receptor antagonist, in comparison with those of famotidine, cimetidine and omeprazole. In guinea pig atria, famotidine and cimetidine produced a competitive dose-dependent displacement of histamine-induced tachycardia. In contrast, low concentrations of YM-14471 showed competitive inhibition of tachycardia, whereas high concentrations were irreversible or slowly dissociable. In pylorus-ligated rats, intravenous YM-14471, famotidine and cimetidine dose-dependently inhibited basal gastric secretion with ED50 values of 0.04, 0.43 and 31.2 mg/kg, respectively. ED50 values for oral YM-14471, famotidine, cimetidine and omeprazole were 0.81, 0.42, 28.9 and 7.7 mg/kg when given at 1 hr before ligation, and 5.7, 26.7, 1639.5 and 18.6 mg/kg at 5 hr before ligation. In anesthetized dogs, intravenous YM-14471, famotidine, cimetidine and omeprazole also dose-dependently inhibited histamine (160 micrograms/kg.hr)-induced acid secretion with ED50 values of 13.7, 8.7, 333.3 and 65.3 micrograms/kg, respectively. In Heidenhain pouch dogs, YM-14471 inhibited histamine (40 micrograms/kg.hr)-induced acid secretion by both intravenous (0.02 mg/kg) and oral administration (0.3 mg/kg). Moreover, the inhibitory effect of YM-14471 was more prolonged than those of famotidine and cimetidine by either route, and it was as long as that of omeprazole dosed orally. These results suggest that YM-14471 is an irreversible or slowly dissociable H2-receptor antagonist, and has long antisecretory effect.

Animals↗

Histamine H2-receptor plays only a minor role in histamine-induced wheal response in the squirrel monkey and guinea pig.

We examined the contribution of the histamine H2-receptor to the histamine-induced wheal response in squirrel monkeys and guinea pigs. Intradermal injection of histamine, 2-pyridylethylamine (a selective H1-agonist), and dimaprit (a selective H2-agonist) dose-dependently induced the wheal response in squirrel monkeys and guinea pigs, although the reaction to dimaprit was much weaker than that to the other agonists. Chlorpheniramine dose-dependently depressed the wheal response in squirrel monkeys and guinea pigs at doses of 0.03-1 mg/kg and 0.03-3 mg/kg, p.o., respectively. However, famotidine, ranitidine and cimetidine had no effect at doses up to 30, 100 and 300 mg/kg, p.o. in guinea pigs and up to 1, 10 and 400 mg/kg, p.o. in squirrel monkeys, respectively. Cimetidine (3-300 mg/kg, p.o.) dose-dependently potentiated the inhibitory effects of chlorpheniramine (0.1 mg/kg, p.o.) in guinea pigs, but had no effects in squirrel monkeys. Famotidine and ranitidine did not alter the response to chlorpheniramine in either animal. These results suggest that the histamine H2-receptor plays only a minor role in the histamine-induced wheal response in squirrel monkeys and guinea pigs.

Animals↗

[Cryopreservation of transgenic mouse embryos by ultrarapid freezing].

Two transgenic mice lines were produced by introducing the rat GH antisense transgene and the chicken beta-actin promoter/firefly luciferase hybrid gene in our laboratory. We cryopreserved the transgenic embryos, obtained by fertilization in vitro with the sperm of hemizygous males for the transgene, by the ultrarapid freezing. The survival rates of cryopreserved 2-cell embryos were high (> 70%) at thawing in both lines and 53% and 16% of cryopreserved 2-cell embryos, respectively, developed to live young after transferring to oviducts of recipients. Each transgene was detected at about 40% of the live young from two transgenic lines. These results indicated that the cryopreservation of embryos by ultrarapid freezing was valuable for sustaining transgenic mouse lines without genetic contaminations.

Animals↗

[Inhibitory activity of urinary macromolecule upon calcium oxalate crystal aggregation using an aggregometer].

We studied inhibitory activity of urinary macromolecule upon the calcium oxalate crystal aggregation using an aggregometer. We have developed an aggregometric assay method to measure the anti-aggregation ratio of calcium oxalate crystals in vitro. The macromolecular fraction of urine with a molecular weight above 5,000 was isolated by PD-10 (Sephadex G-25M, Pharmacia) and made up to three-fold by Centriprep Concentrator (Amicon). The urinary macromolecular substances of recurrent calcium stone formers showed much less inhibitory activity than those of healthy controls. There were no significant relationships between the anti-aggregation activity and the concentration of urinary proteins and other parameters concerning with stone diseases. It was speculated that some proteins, molecular weight about 10,000-30,000, might inhibit the aggregation vigorously based on the result of gel filtration (Superrose 12 HR, 20/50, Pharmacia) technique used in a healthy man's 24 hours urine. Thus, it supports that some urinary macromolecules are important during the phase of aggregation of calcium oxalate crystals, and that the feeble activity to present the aggregation may be one of the cause of calcium oxalate stone formation.

Adult↗

[Clinical effects of granisetron and methylprednisolone against nausea, vomiting and anorexia induced by cisplatin].

We investigated the usefulness of concurrent therapy of granisetron with methylprednisolone sodium for on nausea, vomiting and anorexia induced by chemotherapy, including cisplatin, in patients with oral cancer. Group A: 10 patients who were on concurrent therapy of granisetron (3.0 mg/body) with methylprednisolone sodium (750 mg/body) (19 courses). Group B: 13 patients who were given coktail therapy of methylprednisolone sodium (750 mg/body) as the base drug plus metoclopramide (46.7 mg/body on average) and domperidone (82.9 mg/body on average) (21 courses). Efficacy rates for nausea, vomiting and anorexia were 89.4%, 100% and 100% in group A, and 33.3%, 47.6% and 42.9% in group B, respectively. Statistical significance was found with nausea, vomiting and anorexia (p < 0.01). The results suggest usefulness of concurrent therapy of granisetron with methylpredonisolone sodium for cisplatin-induced nausea, vomiting and anorexia.

Adult↗

Asymptomatic primary biliary cirrhosis in HTLV-I-associated myelopathy.

A 54-yr-old woman was admitted for complaints of slowly progressive gait and bladder disturbance, and HTLV-I-associated myelopathy (HAM/TSP) was diagnosed by positive antibodies to HTLV-I, both in her serum and cerebrospinal fluid. In the course of a diagnostic evaluation, she was found to have asymptomatic primary biliary cirrhosis. In immunohistochemistry, a fair number of her hepatocyte nuclei stained strongly positive for HTLV-I core protein, suggesting that HTLV-I may infect hepatocytes. The present case demonstrates that the spectrum of HTLV-I infection may be broad, and suggests the relationship between HTLV-I-associated myelopathy and primary biliary cirrhosis by autoimmune process.

Female↗

[New membrane filter (PORETEC) method for ocular diagnostic cytopathology].

We describe a new membrane filter (PORETEC) technique for processing cytopathologic fluid specimens. This procedure provides excellent cytologic preparations because there is no background staining and only a small amount of fluid specimen is necessary, as there is little cell loss. We compared the number of cells collected by the membrane filter technique with that collected by cytocentrifugation using conjunctival brush cytology specimens from 6 subjects. The number of cells obtained by the new method was significantly higher than that obtained by the cytocentrifugation technique. This method was very useful for ocular fluid specimens such as aqueous humor, vitreous specimens, and scrapings from the cornea and conjunctiva. We showed some examples of these specimens including immunocytochemical staining done by this method. We confirm that this is valuable for diagnostic cytopathologic study of various fluid specimens in ophthalmology.

Adult↗

[Damage to cultured corneal endothelium caused by ultrasound during phacoemulsification].

An experimental study was performed to estimate the degree of corneal endothelial damage caused by ultrasound during phacoemulsification. Cultured corneal endothelium prepared from bovine eyes was exposed to ultrasound. Dead cell rates were determined by counting the number of cells positively stained by trypan blue under various conditions of ultrasonic radiation. Dead cell rate increased from 13 +/- 2% to 39 +/- 4% (n = 5, Mean +/- S.D.) as ultrasonic duration was prolonged from 15 seconds to 45 seconds. Dead cell rate increased from 6 +/- 1% to 39 +/- 4% as ultrasonic power increased from 60% to 100%. Dead cell rate increased from 8 +/- 1% to 44 +/- 11% as the distance of the phaco tip decreased from 7 mm to 4 mm. Dead cell rate increased from 4 +/- 2% to 35 +/- 7% as the angle of the phaco tip increased from 30 degrees to 90 degrees. We confirmed that endothelial damage depended on ultrasonic duration, ultrasonic power, the distance of the phaco tip, and the angle of the phaco tip. We suggest that the endothelium is damaged mainly by shock waves emanating from the phaco tip.

Animals↗

[Establishment and characterization of a cell line (H-1) from squamous cell carcinoma of human gingiva--effect of temperature].

We established a cell line (H-1) from human oral cancer. It was derived from a biopsy specimen of squamous cell carcinoma in the lower gingiva of a japanese man. The cell line has now been growing in vitro for more than 86 passages. The cells had an epithelial morphology and grew as adherent monolayers. PAS stain was positive and activity of ALP also was positive. They had a doubling time of 37 hours and colony formation of 32%. Chromosomal numbers ranged from 49 to 75 and the modal number was 61. The cell line was tumorigenic in nude mice, its histologic examination showed identification with that from the original tumor. The cells were sensitive to hyperthermia.

Animals↗

[Intermittent intra-arterial infusion chemotherapy of 5-FU and carboplatin for unresectable liver metastases].

Intermittent intra-arterial infusion chemotherapy (5-FU: 500 mg and carboplatin; 100 mg per week) using an implantable access was performed for 19 patients with unresectable liver metastasis of colon cancer (17 cases) and gastric cancer (2 cases). Survival time ranged from 12 to 641 days, and the average was 281.4 days with 50% survival at 276 days. Of 19 cases, one access was infected, two cases had catheter obstruction, and two cases had nausea and vomiting.

Antineoplastic Combined Chemotherapy Protocols↗

[Recurrence and survival rate of advanced gastric cancer after preoperative intraarterial EAP I injection therapy].

In our department, curative operations were performed for 32 patients with advanced gastric cancer from April 1989 to August 1990. Preoperative intra-arterial injection therapy with etoposide (100 mg), pirarubicin (20 mg) and cisplatin (20 mg) was given 18 patients. Recurrence and survival rate were investigated. The survival rate of patients with preoperative intra-arterial injection therapy 45 months after operation was 59.2%, while that of patients without preoperative intra-arterial injection therapy was 75.8%. There were no significant differences between these two groups. Three lymph node recurrences were seen in patients with preoperative intra-arterial injection therapy (recurrence rate, 16.7%). Four recurrences were observed in patients without preoperative injection therapy (peritoneal dissemination 2, liver 1, local 1; recurrence rate, 28.6%). We earlier reported that preoperative intra-arterial cisplatin (40 or 60 mg) injection therapy may reduce the incidence of lymph node recurrence and liver metastasis but may not be effective to prevent postoperative peritoneal recurrence, while no peritoneal dissemination was observed in patients with preoperative intra-arterial EAP I injection therapy. Thus, it was concluded that further study of combination and dose of anti-cancer drug may improve effectiveness of preoperative intra-arterial injection therapy for gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of complete response by intermittent intra-arterial injection of 5-fluorouracil and carboplatin for liver metastases due to pancreatic cancer].

A 53-year-old woman with multiple liver metastases after pancreato-duodenectomy for pancreas cancer was inserted with a catheter from the left subclavian artery to the proper hepatic artery and an access was placed under the thoracic skin. Using this system, she was injected with 500 mg of 5-fluorouracil and 50 mg of carboplatin once a week. After about 7 months, liver metastases disappeared on ultrasonography and computed tomography scan. The patient is still free from recurrence after about 2 years from the initial chemotherapy. This result suggested that intermittent intra-arterial infusion of 5-fluorouracil and carboplatin is effective for liver metastases of pancreatic cancer, after curative resection of a primary tumor.

Adenocarcinoma↗