[Four cases of paragonimiasis due to consumption of wild boar meat].
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Adult↗
Biomedical subjects
M Okuno
Publications and source records attributed to M Okuno.
Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group.
BACKGROUND: In patients with hepatocellular carcinoma (hepatoma), the rate of recurrent and second primary hepatomas is high despite surgical resection and percutaneous ethanol-injection therapy. We developed an acyclic retinoid, polyprenoic acid, that inhibits hepatocarcinogenesis in the laboratory and induces differentiation and apoptosis in cell lines derived from human hepatoma. In a randomized, controlled study, we tested whether the compound reduced the incidence of recurrent and second primary hepatomas after curative treatment. METHODS: We prospectively studied 89 patients who were free of disease after surgical resection of a primary hepatoma or the percutaneous injection of ethanol. We randomly assigned the patients to receive either polyprenoic acid (600 mg daily) or placebo for 12 months. We studied the remnant liver by ultrasonography every three months after randomization. The primary end point of the study was the appearance of a histologically confirmed recurrent or new hepatoma. RESULTS: Treatment with polyprenoic acid significantly reduced the incidence of recurrent or new hepatomas. After a median follow-up of 38 months, 12 patients in the polyprenoic acid group (27 percent) had recurrent or new hepatomas as compared with 22 patients in the placebo group (49 percent, P = 0.04). The most striking difference was in the groups that had second primary hepatomas--7 in the group receiving polyprenoic acid as compared with 20 in the placebo group (P = 0.04 by the log-rank test). Cox proportional-hazards analysis demonstrated that as an independent factor, polyprenoic acid reduced the occurrence of second primary hepatomas (adjusted relative risk, 0.31; 95 percent confidence interval, 0.12 to 0.78). CONCLUSIONS: Oral polyprenoic acid prevents second primary hepatomas after surgical resection of the original tumor or the percutaneous injection of ethanol.
Aged↗
Retinoic acid-stimulated liver stellate cells suppress the production of albumin from parenchymal cells via TGF-beta.
We studied a cell-cell interaction via transforming growth factor-beta (TGF-beta ) between liver stellate cells (SCs) and parenchymal cells (PCs) using co-cultures of rat primary SCs and PCs. Both TGF-beta added exogenously to the culture medium, and TGF-beta produced endogenously from SCs after stimulation with retinoic acid (RA), suppressed the production and secretion of albumin from PCs. This effect occurred at the translational level, but not at the transcriptional level; TGF-beta, as well as SC culture medium conditioned by RA, did not affect the albumin mRNA levels, but decreased the biosynthesis of [35-S]methionine-labeled albumin without altering its post-translational degradation rate. These results suggest that TGF-beta generated from SCs facilitates the development of liver cirrhosis not only by inducing the production of fibrotic components from SCs, but also by impairing the function of the surrounding PCs.
Albumins↗
Peptide YY-induced alteration of colonic electrolyte transport in the rat.
The effect of peptide YY (PYY) on active electrolyte transport in rat colon was studied under short-circuited conditions. PYY (10(-6) M) decreased the basal short-circuit current (Isc) in both the distal and proximal segments of the colon. The decrease in Isc induced by PYY in the distal colon was about 3 times larger than that in the proximal colon. The response to PYY was inhibited by diphenylamine 2-carboxylate, a specific blocker of the Cl-channel, but not by amiloride, a Na-channel blocker. Unidirectional flux measurements in the distal colon revealed that PYY increased the net Na and Cl absorption and decreased the serosal-to-mucosal Cl flux. PYY inhibited the neurally mediated secretory response to electrical field stimulation in a concentration-dependent manner. PYY was also shown to reduce the direct action of the cholinergic agonist bethanechol on the epithelium. These results suggest that PYY inhibits electrogenic Cl secretion and stimulates electroneutral NaCl absorption via both presynaptic and postsynaptic sites in the distal colon.
Amiloride↗
Impaired synthesis of retinol-binding protein and transthyretin in rat liver with bile duct obstruction.
To gain further insight into the protein metabolism in bile duct-obstruction, we examined the synthesis of retinol-binding protein (RBP) and transthyretin (TTR) in rats with common bile duct-ligation. In these rats, liver and plasma levels of RBP and TTR decreased markedly, whereas liver retinoid contents remained unchanged. Although there appeared no decrease in the total amount of RBP or TTR mRNA expressed in the liver, the subcellular distribution of these mRNAs changed from the membrane-bound polysome fraction to the membrane-unbound polysome fraction. This abnormal distribution recovered rapidly after biliary drainage, resulting in the subsequent recovery of the plasma RBP and TTR levels. These observations suggest that cholestasis inhibits the synthesis and secretion of RBP and TTR by disrupting the binding of their mRNAs to membrane-bound polysomes. Plasma levels of RBP and TTR might be sensitive indicators of the recovery of protein synthesis after biliary drainage in patients with obstructive biliary disorders.
Animals↗
Primary sclerosing cholangitis associated with increased peripheral eosinophils and serum IgE.
Symptoms of cholestasis, including epigastralgia, fever, and jaundice, with marked increases in peripheral eosinophils and serum IgE in a 20-year-old man are reported here. Endoscopic retrograde cholangio-pancreatography (ERCP) detected constrictions of the bile ducts, compatible with primary sclerosing cholangitis (PSC). The symptoms and blood parameters of liver dysfunction were associated with the degree of eosinophilia and high serum IgE levels. During corticosteroid therapy, all of these parameters improved, and morphologic improvements of the bile ducts were also observed. The pathogenesis of PSC may be explained, in part, by the concept of hypereosinophilic syndrome or allergic reaction.
Adult↗
Two effects of lysophosphatidic acid on Ca(2+)-movement in cultured bovine adrenal chromaffin cells.
We found that lysophosphatidic acid (LPA) exerted two effects on Ca(2+)-movement in cultured bovine adrenal chromaffin cells. At concentrations of above 10(-5) M, it induced slight, but significant 45Ca2+ influx, resulting in release of a small portion of stored catecholamine. At high concentrations it also significantly increased the intracellular Ca2+ concentration in Fura-2-loaded cells. At concentrations as low as 10(-7) M, it stimulated extracellular Na(+)-dependent 45Ca2+ efflux, possibly by increasing Na+/Ca2+ exchange. The maximal efflux of Ca2+ attained with 10(-5) M LPA was inhibited by tyrosine kinase inhibitors, but augmented by a protein kinase C inhibitor. These results suggest that LPA-induced Ca2+ efflux is controlled positively and negatively by mechanisms involving tyrosine kinase and protein kinase C, respectively.
Animals↗
Suppression of mouse skin papilloma by canthaxanthin and beta-carotene in vivo: possibility of the regression of tumorigenesis by carotenoids without conversion to retinoic acid.
Using mouse skin papilloma as a model system, we examined whether the antitumorigenic activity of carotenoids was related to their provitamin A activity. Oral administration of canthaxanthin (CX) or beta-carotene at 200 mg/kg/day for 14 days significantly reduced the cumulative size of papillomas induced on the skin by 9,10-dimethyl-1,2-benzanthracene (p < 0.05), after the accumulation of these carotenoids in the tumors. The levels of a protooncogene, c-myc, were simultaneously suppressed in papillomas in carotenoid-treated mice. Because CX cannot be converted metabolically to retinoids, these results suggested that CX directly inhibited the growth of papillomas. Neither the accumulation of retinoids nor the expression of a retinoic acid-inducible gene, retinoic acid receptor-beta, was found in papillomas of CX- and beta-carotene-treated mice, suggesting that, like CX, beta-carotene might exert the tumor-suppressing effect without being converted to retinoids. Thus a certain antitumorigenic activity of carotenoids appears not necessarily to require their provitamin A activity.
9,10-Dimethyl-1,2-benzanthracene↗
Suppressing effect of perilla oil on azoxymethane-induced foci of colonic aberrant crypts in rats.
We have investigated the modulatory effect of dietary perilla oil which is rich in the n-3 polyunsaturated fatty acid, alpha-linolenic acid, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats. Animals were given three weekly subcutaneous injections of AOM (15 mg/kg body weight) to induce ACE. The rats were fed a basal diet containing either 12% olive oil, 12% safflower oil, 12% perilla oil, 6% perilla oil plus 6% olive oil, or 3% perilla oil plus 9% olive oil for 5 weeks, starting 1 week before the first dosing of AOM. All rats were sacrificed 2 weeks after the last AOM injection. The amount of food consumed and body weight gain were identical among every dietary group. The frequency of ACF was significantly lower in the rats fed 12% perilla oil than in those fed 12% olive oil or 12% safflower oil (P < 0.01 and P < 0.05, respectively). The suppressive effect of perilla oil was dose-dependent, as the number of ACF was 20.7, 40.7 and 47.4% of those of the 12% olive oil-fed controls in rats fed 12% perilla oil, 6% perilla oil plus 6% olive oil and 3% perilla oil plus 9% olive oil, respectively. Perilla oil significantly reduced ras expression as well as the AgNORs count (cell proliferation biomarkers) in the colonic mucosa, as compared with olive oil or safflower oil (P < 0.01, respectively). Marked increases in n-3 polyunsaturated fatty acids in membrane phospholipid fractions and decreased PGE2 levels were observed in colonic mucosa of perilla oil-fed rats. These results suggest that perilla oil, even in small amounts, suppresses the development of aberrant crypt foci, and is therefore a possible preventive agent in the early stage of colon carcinogenesis.
Animals↗
Synergistic suppression of azoxymethane-induced foci of colonic aberrant crypts by the combination of beta-carotene and perilla oil in rats.
The modulating effect of the combined dietary feeding of beta-carotene and perilla oil, which is rich in alpha-linolenic acid, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in male F344 rats. Rats received oral administration of beta-carotene (0, 50 or 200 mg/kg body weight/day) and fed a basal diet containing either 12% olive oil, 3% perilla oil plus 9% olive oil, or 12% perilla oil. A dose-dependent suppressive effect of perilla oil was found. The numbers of ACF were 42.0 and 18.4% of those of the 12% olive oil-fed controls in the rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. The development of ACF was also reduced significantly by the addition of dietary beta-carotene in each of the oil-fed groups (P < 0.05, respectively). The suppression by the combination of beta-carotene and perilla oil was synergistic, as the numbers of ACF were 12.9 and 8.9% of those of the 12% olive oil-fed controls in beta-carotene-treated rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. beta-carotene plus perilla oil also suppressed the numbers of silver-stained nucleolar organizer regions and the expression of ras mRNA in the colonic mucosa (cell proliferation biomarkers). Following administration of beta-carotene, a significant increase in the concentration of intact beta-carotene molecules was found in the colonic mucosa, livers, and sera. However, no accumulation of retinoids was observed in the colonic mucosa, suggesting that the inhibitory effect may not be related to the provitamin A activity. These results suggest that the combination of beta-carotene and perilla oil may be useful in the prevention of colon cancer.
Administration, Oral↗
Oral supplementation with branched-chain amino acids improves transthyretin turnover in rats with carbon tetrachloride-induced liver cirrhosis.
The hypothesis that dietary branched-chain amino acid (BCAA) supplementation improves the impaired protein turnover in male Donryu rats with carbon tetrachloride-induced liver cirrhosis was tested. We supplemented cirrhotic rats orally for 2 wk with BCAA solution [26.67 mg BCAA/(100 g body weight . d)], a conventional amino acid mixture [4.25 mg BCAA/(100 g body weight . d)] or saline and fed these three groups the AIN76 basal diet to have similar intakes of total energy and total nitrogen. Normal rats without liver cirrhosis were fed the basal diet similar to the above (noncirrhotic controls). After supplementation, rats were fed intravenous transthyretin (thyroxine-binding prealbumin) doubly labeled with 125I-tyramine-cellobiose and 131I. Kinetic indices including production rate of transthyretin were analyzed from plasma transthyretin disappearance curves. Tissue sites of transthyretin degradation were assayed using a trapped ligand technique by measuring 125I-tyramine-cellobiose levels. The production rate of transthyretin was significantly lower in cirrhotic rats supplemented with saline (mean 25.46 X 10(-3) . h(-1)) compared with noncirrhotic controls (45.08 X 10(-3) . h(-1)) (P < 0.05). This was corrected by supplementing cirrhotic rats with BCAA (37.05 X 10(-3) . h(-1), P < 0.05) but not with conventional amino acid mixture (22.49 X 10(-3) . h(-1)). The accelerated degradation of transthyretin in muscles of cirrhotic rats was improved by BCAA (P < 0.05). In conclusion, dietary supplementation with BCAA improves the impaired transthyretin turnover in rats with liver cirrhosis.
Administration, Oral↗
Esophagomediastinal fistula as a complication of tuberculous mediastinal lymphadenitis.
In a 44-year-old female esophagomediastinal fistula was found secondary to tuberculous mediastinal lymphadenitis. Chest computed tomography revealed amorphous air collection in the subcarinal region of the mediastinum with mediastinal lymphadenopathy. Esophagography with gastrografin confirmed esophagomediastinal fistula. The patient was treated with antituberculous therapy with rifampicin, isoniazid, pyrazinamide and ethambutol, resulting in resolution of the esophagomediastinal fistula and mediastinal lymphadenopathy.
Adult↗
[Otorhinolaryngological medical care by the general practitioners in rural areas].
In the present study, a survey of otorhinolaryngological medical care by the general practitioner, including the relationship between general practitioners and otorhinolaryngologists in rural areas was carried out. A questionnaire for otorhinolaryngological medical care by the general practitioners was sent to 326 hospitals with less than 100 beds where non-otorhinolaryngological doctors who had graduated from Jichi Medical School were working. Of these hospitals 164 (50.4%) responded. Most respondents said that they had about 3 or 4 patients with otorhinolaryngological disease per month. The distance between most hospitals and the nearest otorhinolaryngologists was within one hour by available transportation facilities. About 70% of the respondents were provided with simple otorhinolaryngological instruments, such as an aural speculum, a nasal speculum and a head mirror. The most frequent otorhinolaryngological diseases which they treated were vertigo, allergic rhinitis and upper respiratory infection including acute tonsillitis and pharyngolaryngitis. Only 10 to 20% of the general practitioners had otorhinolaryngological training. We found several problems in otorhinolaryngological medical care in rural areas. Patients with otorhinolaryngological disease seek otorhinolaryngological care at the nearest medical facility where general practitioners with inadequate otorhinolaryngological experience examine patients with inadequate otorhinolaryngological instruments. Therefore, a close relationship between general practitioners and otorhinolaryngologists should be developed and the quality of otorhinolaryngological medical care should be raised in rural areas.
Hospitals↗
[Selective thermocoagulation of unresectable malignant tumors using radiofrequency].
Based on our experimental findings on porcine liver, we have been conducting a clinical trial of selective hyperthermia by radiofrequency (RF) capacitive heating with laparotomy for patients with unresectable malignant tumors. In 10 patients with malignant tumors (8 carcinoma of the pancreas, 2 carcinoma of the gallbladder), laparotomy and RF heating were performed after informed consent. The local heat coagulation was produced by heating equipment using 13.56 MHz radiofrequency produced by Omron Corporation, Japan. Four 2-cm electrode needles were placed in the tumor in a square array at intervals of 2.0 cm. Hyperthermia was given for 30 min with a controlled temperature of 50 degrees C in the RF field (2 x 2 x 2 cm3). That of the surrounding area was maintained at less than 40 degrees C. The calculated volume treated by RF ranged between (2 x 2 x 2 cm3) x 1 and (2 x 2 x 2 cm3) x 6. We followed all patients by computed tomographic (CT) scan 2 weeks after coagulation. Tumor markers in the blood were assayed before and 14 days after heating. Follow-up CT scans demonstrated that after the tumor mass had been heterogeneously enhanced, it changed to a homogeneous low-density area in 6 of 10 patients. The levels of tumor markers decreased to lower than the pre-treatment values in 9 of 10 patients. In all patients, the changes in CT scans and/or decrease in the markers were confirmed. Complications such as bleeding or abscess formation were not observed. It was suggested that the selective hyperthermia was safely produced by this equipment. The encouraging results in these patients justify further clinical trials.
Biomarkers, Tumor↗
[Concentration and fiber size of asbestos in lungs of residents living close to the serpentinite area].
Concentrations and fiber size distribution of asbestos in the lung tissue of 16 ( 8 males and 8 females) rural residents living close to the serpentinite area (neighboring group) were analyzed by low temperature ashing-analytical transmission electron microscopy, and were compared with those of 5 (5 males) rural and 53 (34 males and 19 females) urban residents living away from the serpentinite area (reference group). The results are as follows; 1. Pulmonary asbestos fibers were found in all rural residents. The types of asbestos fibers were chrysotile, amosite, crocidolite, actinolite, and tremolite. These findings were very similar to results for urban residents. 2. In males, the geometric mean concentration of actinolite-tremolite in the neighboring group (1.78 x 10(6) fibers/g dry lung) was significantly higher than those in the reference groups (rural: 0.32 x 10(6), urban: 0.31 x 10(6), p < 0.01). In females also, the geometric mean concentration of actinolite-tremolite in the neighboring group (0.59 x 10(6)) was significantly higher than that in the reference group (urban: 0.16 x 10(6), p < 0.05). There were no significant differences in the actinolite-tremolite concentrations between males and females in the neighboring group. 3. The serpentinite in this area have contained not only chrysotile but also both actinolite and tremolite. There was no significant relationship between actinolite-tremolite concentration and occupational history in the neighboring group. It is possible that actinolite and tremolite are liberated from the serpentinite to the atmosphere and inhaled by the residents near the serpentinite area which increases pulmonary actinolite-tremolite concentration. 4. The difference in the geometric mean concentration of chrysotile between the neighboring and the reference group was not statistically significant for both sexes, possibly due to the poor durability of chrysotile in the lung tissue. 5. There were no significant differences in the geometric mean of fiber length and diameter of actinolite-tremolite between the neighboring and the reference group.
Adolescent↗
Extrusion of microtubule doublet outer dense fibers 5-6 associating with fibrous sheath sliding in mouse sperm flagella.
Our previous experiments (Si and Okuno [1993a] Exp. Cell Res., 208:170-174) provided evidence that the fibrous sheath (FS) slid headward to middle piece in the activated mouse sperm flagellum when doublet microtubules together with their outer dense fibers (ODFs) extruded from the axoneme. Of the extruded doublet-ODFs, however, which one was responsible for the FS sliding remained unresolved. The present study demonstrated that the FS sliding and the order of doublet-ODFs extrusion in mouse sperm flagella were trypsin concentration dependent. Under the condition of mild trypsinization (0.1 micrograms/ml), only doublet-ODFs 4, 5-6 (doublet-ODFs 5 and 6 were always paired), and 7 extruded from the axoneme. Furthermore, the extrusion of doublet-ODFs 5-6 was identified to precede doublet-ODFs 4 and 7, and was considered the candidate responsible for FS sliding. In contrast, the high-concentration trypsinization (4 micrograms/ml) led to extrusion of doublet-ODFs 1, 2, and 9 following doublet-ODFs 4, 5-6, and 7. FS sliding, however, did not occur.
Animals↗
Regulatory mechanism of calcium efflux from cultured bovine adrenal chromaffin cells induced by extracellular ATP.
The effect of adenosine-5'-triphosphate (ATP) on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. ATP stimulated the efflux of 45Ca2+ from the cells in a concentration-dependent manner (0.01-1 mM). The 45Ca2+ efflux from the cells was also stimulated by adenosine-5'-O-(3-thiotriphosphate) (ATP-gamma s), alpha beta-methylene-ATP and adenosine-5'-diphosphate (ADP), but was not by adenosine-5'-monophosphate (AMP) and adenosine. The ATP-stimulated 45Ca2+ efflux was not affected by deprivation of the extracellular Ca2+ and Mg2+, but was dependent on the extracellular Na+ concentrations. ATP increased the influx of 22Na+ into the cells. These results indicate that ATP stimulates extracellular Na(+)-dependent 45Ca2+ efflux from cultured bovine adrenal chromaffin cells, probably through its stimulatory effect on membrane Na+/Ca2+ exchange.
Adenosine Triphosphate↗
Changes in the ratio of branched-chain to aromatic amino acids affect the secretion of albumin in cultured rat hepatocytes.
The effect of branched-chain amino acids (BCAAs) on the synthesis and secretion of albumin was studied in the primary cultures of rat hepatocytes. The changes in the normal BCAAs/aromatic amino acids (AAAs) ratio reduced the secretion of albumin without altering its mRNA levels. Protein-labeling and pulse-chase experiments showed that a low BCAAs/AAAs ratio reduced the biosynthesis, whereas a high ratio accelerated intracellular decay of albumin. These results suggest that normalization of the BCAAs/AAAs ratio improves albumin synthesis while the excess ratio may induce the degradation of albumin in the cells.
Amino Acids, Branched-Chain↗