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Biomedical subjects

Y Moriya

Publications and source records attributed to Y Moriya.

At least 19 recordsLinked to original sources

Correlation between pain and dysfunction and intra-articular adhesions in patients with internal derangement of the temporomandibular joint.

The correlation between pain and dysfunction scores obtained by questionnaire and an adhesions index obtained via arthroscopic inspection was investigated in 28 patients with internal derangements (closed lock) of the temporomandibular joint (TMJ). A weak correlation was found between pain scores and the adhesions index. However, joint noise had a negative correlation with both severity and distribution of adhesions in the TMJ. A weak, but statistically significant, negative correlation also was found between the degree of interincisal opening and the adhesions index. This study indicates that intra-articular adhesions are one of the factors contributing to limited mouth opening in patients with closed lock, but that they do not cause TMJ pain.

Adult

Efficacy of oral administration of live herpes simplex virus type 1 as a vaccine.

Mice given herpes simplex virus type 1 (HSV-1) (Miyama +GC strain) intragastrically via a stainless-steel cannula were rendered immune to subsequent lethal intraperitoneal (i.p.) challenge with HSV-1. The orally administered HSV-1 was completely inactivated in the stomach within a few minutes of inoculation. However, systemic immunity was established 14 days after oral inoculation with the virus and retained for up to 6 months. The mechanisms of establishing systemic immunity were investigated by means of adoptive transfer comparisons. When splenic cells from HSV-1-immunized mice were transplanted into nonimmunized mice, all of the recipient mice survived after a lethal i.p. challenge with the virus. Immunity was not established in antithymocyte serum-treated mice or by transfer of serum from immunized to nonimmunized mice. In addition, all HSV-1-immunized mice died after lethal challenge with HSV-2 and influenza virus A. These findings suggest that the immunity was virus specific, with T lymphocytes playing a major role in its establishment. The present study therefore supports the possibility of oral immunization with live HSV-1 as a vaccine.

Administration, Oral

Aminopeptidase activity of an antitumor antibiotic, C-1027.

An antitumor antibiotic C-1027, a complex protein consisting of an apoprotein and a non-covalently bound chromophore, showed some aminopeptidase activity, 1/15 (on the basis of activity per mg protein) that of porcine kidney enzyme [E.C. 3.4.11.2] by use of L-phenylalanyl 4-methyl-coumaryl-7-amide as the substrate. Neither the apoprotein alone nor the chromophore alone were active. Amastatin and bestatin but not leupeptin inhibited the activity. The enzyme activity of the holo-antibiotic, as opposed to that of the porcine kidney enzyme, was readily lost by UV irradiation, indicating that the intact structure of the chromophore was needed to maintain the native conformation of the holo-antibiotic. The cytotoxicity of the holo-antibiotic, but not that of the chromophore, to Ehrlich carcinoma cells in vitro was reduced to 1/5 by 1 microgram/ml of amastatin which alone had no effect on cell growth. The porcine aminopeptidase was not cytotoxic at all even at higher concentrations (higher enzyme activities/ml). Amastatin possibly occupied the catalytic domain of the holo-antibiotic, interfering with the binding of the holo-antibiotic with some cell-surface protein(s). Amastatin did not inhibit the holo-antibiotic to cleave isolated DNA.

Aminoglycosides

Heparin stimulates the collagen synthesis in mineralized cultures of the osteoblast-like cell line, MC3T3-E1.

We found that heparin induced an increase in collagen synthesis in MC3T3-E1 cells cultured for 15 and 30 days. Northern blots showed that the effect of heparin on the collagen synthesis was mediated through the mRNA expression of type I collagen (day 15). Although heparin stimulated collagen synthesis over and above that stimulated by the transforming growth factor (TGF)-beta, heparin did not stimulate TGF-beta binding. This study indicates that heparin has special tasks both in bone formation and resorption, since it has the ability to form and degrade collagen. We suggest that heparin assists the regulation of collagen metabolism at bone resorption sites.

Animals

[A case of fibromuscular dysplasia associated with intra- and extracranial multiple aneurysms].

A case of fibromuscular dysplasia (FMD) with intra- and extracranial multiple aneurysms is reported. A 42-year-old woman was admitted to Kagawa Central Hospital with severe headache and stiffness of the neck. CT scan showed subarachnoid hemorrhage predominantly in the left side of the basal cisterns and hydrocephalus. Angiography at admission revealed marked stenosis and dilatation of the extracranial major arteries and multiple aneurysms in the lt. PCA, lt. ICA, bil. VA, and the lt. renal artery. String-of-beads appearance was also seen in the branches of the lt. external carotid artery. During the operation, the PCA aneurysm which has been diagnosed as the ruptured one, was found to arise from the posterior communicating artery itself. It was thus a so-called true posterior communicating aneurysm. The aneurysm was trapped by clipping the artery on both the ICA and the PCA sides. The giant aneurysm of the lt. ICA was successfully treated by lt. STA-MCA anastomosis and ligation of the lt. ICA. Postoperative angiography demonstrated no visualization of the aneurysm and total occlusion at the origin of the lt. VA that had been patent preoperatively. On histological examination, intimal and medial hyperplasia was seen in the aneurysmal wall and occipital artery biopsied at operation. There has been no report of FMD associated with multiple and very rare posterior communicating aneurysms. Wide involvement of vascular change and advance of arterial occlusion noted by serial angiography indicates that FMD is a disease in which pathology would be progressive in some cases.

Adult

Platelet-activating factor stimulates production of prostaglandin E2 in murine osteoblast-like cell line MC3T3-E1.

We found that platelet-activating factor (PAF) stimulated the production of prostaglandin (PG) E2 in MC3T3-E1 cells in a time- and dose-dependent manner. 1.0 microM PAF gave a maximal stimulation of PGE2 production by MC3T3-E1 cells after a 4 hr PAF-treatment. Furthermore, the PAF-induced PGE2 production was abolished by the pre-treatment of the cells with a PAF receptor antagonist, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phospho(N,N,N-trimethyl)hexanolamine, which occupied the same receptor site as PAF. These results suggest that PAF stimulates the PGE2 synthesis through a PAF receptor mediated pathway. Possibly PAF modulates bone metabolism by stimulating PGE2 synthesis.

Animals

Analysis of antitumor effects of OK-432 against syngeneic mouse fibrosarcoma: combination effect of OK-432 and recombinant lymphokines.

OK-432, a streptococcal preparation with potent biological response modifying activities, had the ability to cure mice bearing BAMC-1 (fibrosarcoma) ascites when it was injected intraperitoneally five times, 2, 4, 6, 8, and 10 days after the tumor inoculation. Previously, it was shown that the OK-432 injection on day 2 was indispensable since only a minimal antitumor effect was obtained when an inflammation-inducing agent such as thioglycolate instead of OK-432 was injected on day 2, followed by four OK-432 injections on days 4, 6, 8 and 10. In the present study, the injection of OK-432 on day 2 and a subsequent injection of either IL-2 or IFN-gamma on day 4 or 6 showed a significant antitumor effect, achieving a complete cure in approximately 50% of mice treated, although none of the mice could be cured by a single injection of either OK-432, IL-2, or IFN-gamma on day 2. Interestingly, however, the mice treated with an injection of a lymphokine (IL-2 or IFN-gamma) on day 2 followed by OK-432 on day 4 were not cured either. Peritoneal cells on day 12 in mice treated with OK-432 and either of the lymphokines contained pantropic killer cells, which were Thy-1+ and asialo GM1+ (AsGM1+). Moreover, the antitumor effect of the combined treatment was abolished when mice were pre-treated with anti-AsGM1. No significant antitumor effect was observed in athymic nu/nu mice. Together with our previous findings, these results indicate that lymphokines induced by OK-432 administration may account for some of its therapeutic effects and that these lymphokines may also facilitate the subsequent induction of specific killer cells. These results warrant further investigation on possible effective therapeutic protocols with the combined use of OK-432 and lymphokines.

Animals

Inhibition of pinocytosis by hygrolidin family antibiotics: possible correlation with their selective effects on oncogene-expressed cells.

A fermentation broth of Streptomyces sp. SIPI-A4-0044 inhibited in vitro growth of src or ras oncogene-expressed (onc+) cells more strongly than that of oncogene-unexpressed (onc-) counterparts. The active components were isolated and identified as hygrolidin family antibiotics (HGL). In mixed cultures consisting of onc+ and onc- cells, at an appropriate ratio, HGL showed selective toxicity to focus like structures of onc+ cells, leaving monolayer areas of onc- cells little damaged. HGL rapidly inhibited pinocytosis, or the influx of neutral red into the cells, at concentrations partially inhibitory to the cell growth. In contrast, HGL only slightly inhibited the influx of 2-deoxyglucose, nucleosides and leucine and the syntheses of DNA, RNA and protein even at high concentrations. Upon prolonged exposure to sublethal concentrations of HGL, onc- cells but not onc+ cells recovered pinocytotic activity and resumed growth.

Animals

Adjuvant hepatic intra-arterial chemotherapy after potentially curative hepatectomy for liver metastases from colorectal cancer: a pilot study.

The site most at risk of recurrence after hepatectomy is the remaining liver. Therefore a study was conducted of the use of hepatic intra-arterial and oral chemotherapy for colorectal metastases to prevent intrahepatic recurrence. Our regimen consisted of intra-arterial 5-fluorouracil (5-FU), mitomycin C (MMC) and oral 1-hexylcarbamoyl-5-fluorouracil (HCFU). Sixteen patients were treated. Median total dose of 5-FU was 8.1 g, MMC was 43 mg, and HCFU was 54 g, respectively. Median follow-up period was 21 months. The recurrence rate of the remaining liver was 31%. With respect to the number of hepatic metastases, there was no recurrence in patients with a single deposit. On the other hand, the intrahepatic recurrence rate of patients with multiple deposits was 45%. Of six patients with more than five hepatic deposits, however, only one patient had developed recurrent disease in the liver. Chemical sclerosing cholangitis (19%) was the most serious complication. Consequently, we propose that a prospective randomized trial should be carried out to establish the effects of this type of adjuvant chemotherapy to reduce possible recurrences in the remaining liver.

Adult

Screening of antibiotics preferentially active against ras oncogene-expressed cells.

During the course of in vitro screening of agents which are preferentially active against ras oncogene-expressed cells, a new anthracycline (identified as 2-demethylsteffimycin D) and a heptaene (possibly a new member of partricins) were isolated from microbial fermentation broths. Among known compounds tested, 5-fluorouracil, 5-fluorodeoxyuridine and oxanosine showed high selectivity towards ras oncogene-expressed cells.

Animals

Serious chemical sclerosing cholangitis associated with hepatic arterial 5FU and MMC chemotherapy.

A case of iatrogenic sclerosing cholangitis secondary to hepatic intra-arterial 5-fluorouracil (5FU) and Mitomycin C (MMC) chemotherapy is described. When any unexplained elevation of liver function results in alkaline phosphatase and bilirubin level, chemotherapy should be discontinued, and further examination carried out using ultrasonography, transhepatic cholangiography and endoscopic retrograde cholangio-pancreatography (ERCP). Although percutaneous transhepatic biliary drainage has been effective in some cases, in our case, the clinical course was irreversible and the patient died of hepatic failure and gastrointestinal bleeding. When clinical signs of hepatic dysfunction occur in the absence of tumor progression, iatrogenic sclerosing cholangitis must be suspected.

Adult

[Results of prophylactic intra-arterial infusion chemotherapy after hepatic resection in colorectal metastases].

Fourteen colorectal cancer patients with metastatic liver metastases who received prophylactic intra-arterial infusion chemotherapy (IAIC) after curative resection for liver metastases at the National Cancer Center Hospital from May 1987 to December 1989 were reviewed. 5-fluorouracil (5-FU) (15 mg/kg) and mitomycin C (MMC) (0.1 mg/kg) were infused through implantable ports weekly or every two weeks. Five patients (35.7%) developed recurrent tumors in the residual liver during 3-12 months after hepatic resection. The se five patients had more than two metastatic lesions in the liver at hepatectomy. Four patients with solitary metastatic tumor had no recurrent liver diseases. The most serious complication was sclerosing cholangitis which occurred in two patients (14%) in this series. Both cases needed drainage PTCD, but one of them died from gastro-intestinal bleeding due to hepatic failure and the other from pneumonia. These two cases showed no recurrent liver cancers.

Administration, Oral

[Change of beta-actin gene expression during culture on osteoblast-like cell line, MC3T3-E1].

Multiple forms of actin (alpha, beta, and gamma-actin) have been found in a variety of mammalian cell lines and tissues by the use of high resolution, two-dimensional gel electrophoresis. alpha-Actin is found only in differentiated muscle cells, and its synthesis is induced during myogenesis in culture, beta- and gamma-actin isotypes are the principal components of microfilaments, structures believed to be involved in cellular morphogenesis, motility, and mitosis. Recent studies have shown that mammalian actin mRNA levels are modulated in response to changes in cell shape and during cell differentiation in vitro. On the other hand, Kodama et al. isolated clone MC3T3-E1 cells from newborn mouse calvaria, which have retained the ability to produce and mineralize a bone-like ground substance after many serial passages. Thus clone is useful for studying osteoblast differentiation as well as the mechanism of calcification. It is demonstrated that bone cells assume a stellate morphology after some hormone treatment and these changes were clearly associated with altered reorganization of the microfillaments which resulted in an enhanced osteoblast phenotype. We have now examined the effect of culture day on expression of beta-actin gene in MC3T3-E1 cells and found that expression of beta-actin gene reduced with culture days. These alternative on the expression of actin gene suggest that beta-actin may be involved in bone remodeling in vivo.

Actins

Significance of lateral node dissection for advanced rectal carcinoma at or below the peritoneal reflection.

Two hundred thirty two patients with rectal cancer at or below the peritoneal reflection, who underwent extended systematic lymphadenectomy, especially lateral node dissection, were reviewed with respect to survival rate, degree of surgical technique, and mode of recurrence. On the basis of the extent of lateral node spread, two types of lateral node dissection were performed, consisting of preservation of internal iliac vessels (conventional) and en bloc excision of these vessels (extended). The overall disease-free five-year survival rate was 69.4 percent in all patients--75.8 percent for those who underwent extended resection and 67.4 percent for those who underwent conventional resection an excellent survival rate of 49 percent of patients with lateral node metastasis was obtained. The analysis was carried out with regard to prognostic factors such as number of node metastases, obesity index, mode of recurrence, etc. We would recommend that systemic lymphadenectomy with lateral node dissection be performed for advanced rectal cancer at or below the peritoneal reflection.

Adenocarcinoma

Induction by herbimycin A of contact inhibition in v-src-expressed cells.

Herbimycin A, an inhibitor of pp60src tyrosin kinase, caused src oncogene-expressed cells to become sensitive to contact inhibition, but did not affect ras oncogene-expressed cells. The cell lines tested were temperature sensitive v-src- and temperature sensitive v-ras-integrated nontransformed rat kidney cell line (NRK) (srctsNRK and rastsNRK, respectively) and a wild-type v-src-integrated NIH3T3 (src3T3). srctsNRK cells in densely populated cultures (plated at 1.25 x 10(4) cells/cm2), grown at 33 degrees C in the presence of 0.45 micrograms/ml of herbimycin A, ceased the cell cycle at the G0-G1 stage within 2 days, and the cells showed normal morphology. Upon removal of herbimycin A, the quiescent cells resumed the cell cycle in concert with morphological alteration from 'normal' to 'transformed', and proceeded through the S and M stages successively in a synchronized manner. Cells in the late S stage, compared with those in other stages of the cell cycle, were more sensitive to the killing effect of 5-fluorodeoxyuridine. Such synchronism of the cell cycle was not observed with sparsely populated cultures (2.5 x 10(3) cells/cm2); the cells resumed their asynchronous growth after removal of herbimycin A, although their morphology returned to 'transformed' as in the experiment with the densely populated cultures. The induction by herbimycin A of contact inhibition in densely populated cultures was also observed with src3T3 (grown at 37 degrees C) but not with rastsNRK (grown at 33 degrees C).

Animals