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Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 793 records · Page 44Linked to original sources
PubMed1988

Inhibitory effect of tamoxifen on diethylstilbestrol-promoted hepatic tumorigenesis in male rats and its possible mechanism of action.

Male Sprague-Dawley rats were given a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg body weight). Two weeks later the rats were divided into 4 groups; DEN-C group rats were given no further treatment; DEN-DES group rats were fed diethylstilbestrol (DES, 0.5 mg/day); DEN-TMX group rats were given tamoxifen (TMX, 1.0 mg/day) orally; DEN-DES TMX group rats were fed both DES and TMX for 8 months. Rats of the DEN-DES group developed grossly visible hepatic tumors. On the other hand, tumor development was significantly inhibited in rats of the DEN-DES TMX group. Total area of gamma-glutamyl transpeptidase-positive lesions and the mean area per lesion were significantly larger in rats of the DEN-DES group than those of the DEN-C, DEN-TMX or DEN-DES-TMX group. Estrogen receptor (ER) content of liver cytosol assayed by enzyme immunoassay (EIA) was significantly greater in rats of the DEN-DES group than in those of the DEN-C group and smaller in rats of the DEN-TMX and DEN-DES TMX group than in the DEN-C group. On the contrary, ER content of liver nuclei was significantly greater in rats of the DEN-TMX and DEN-DES TMX group than in those of the DEN-C or DEN-DES group. These results suggest that the promotive action of DES and the inhibitory action of TMX on DES-promoted hepatic tumorigenesis are, at least in part, mediated by ER in the rat.

Animals↗
PubMed1988

Expression of oncogenes in human liver disease.

To elucidate the role of oncogene expression in hepatocarcinogenesis, we examined the expression of 8 cellular oncogenes by dot blot and/or northern blot analysis in neoplastic, cirrhotic and non-cirrhotic human liver tissues obtained at surgery. Significantly higher levels of c-myc gene expression were observed in tissues of hepatocellular carcinoma (HCC) and adjacent cirrhotic tissues than in apparently normal liver tissues or those of chronic hepatitis (normal-chronic hepatitis). There was a tendency to higher c-myc mRNA levels in HCC than in liver cirrhosis. However, when tumorous and adjacent cirrhotic tissues from the same patient were compared, c-myc mRNA levels were not consistently higher in HCC. No significant differences in mRNA levels of c-fos, N-myc, N-ras, Ha-ras, c-erbA, c-erbB and c-abl were observed among the HCC, cirrhosis and normal-chronic hepatitis groups. Although the significance of increased c-myc gene expression in liver cirrhosis and HCC is still not known, it is conceivable that the persistent elevation of c-myc gene expression in cirrhosis contributes to the development of HCC.

Carcinoma, Hepatocellular↗
PubMed1988

Differentiation of Na+-K+ pump in rat proximal tubule is modulated by Na+-H+ exchanger.

This study examines the effect of in vivo modulation of Na+-H+ exchange activity on the development of Na+-K+-ATPase in rat kidney proximal convoluted tubule (PCT) segments. To stimulate Na+-H+ exchanger (major entry pathway for Na in PCT), weanling rats were fed NH4Cl for 4 days to induce metabolic acidosis (MA). In vehicle (Vh)-fed rats PCT Na+-K+-ATPase activity (pmol Pi.mm tubule-1.h-1 +/- SE) increased from 481 +/- 78 at 16 days to 1,122 +/- 119 at 20 days. In 20-day-old chronic MA rats, PCT Na+-K+-ATPase activity was 1,717 +/- 109, i.e., significantly higher (P less than 0.01) relative to controls. Chronic MA had no effect on PCT Mg ATPase activity and on Na+-K+-ATPase in the medullary thick ascending limb (MTAL). To inhibit the Na+-H+ exchanger, weanling rats received amiloride (30 micrograms.100 g body wt-1.day-1) via osmotic minipump for 4 days. In Vh-treated rats PCT Na+-K+-ATPase increased from 481 +/- 78 at 16 days to 1,428 +/- 81 at 20 days. In rats given chronic amiloride, PCT Na+-K+-ATPase was significantly lower (858 +/- 75) at 20 days relative to controls but PCT Mg ATPase and MTAL Na+-K+-ATPase activity was the same as in controls. Chronic MA and amiloride had no significant effect on PCT Na+-K+-ATPase activity in adult rats. Acute MA and acute amiloride injection had no significant effect on PCT Na+-K+-ATPase in weanling rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1988

Use of experimental models to study the development of renal function.

By use of animal experiments it has been demonstrated that renal cells are immature at birth. Membrane transport is quantitatively and qualitatively different. The control of fluid and electrolyte balance is therefore different in infancy. The increased filtered load at birth as well as hormones will induce tubule maturation. The use of animal experiments will in the future give an insight into how external factors influence growth and maturation.

Animals↗
PubMed1988

The role of interstitial collagens in cleft formation of mouse embryonic submandibular gland during initial branching.

An interstitial collagenase was purified from the explant medium of bovine dental pulp and was shown to degrade collagens I and III but not IV and V. The enzyme halted cleft initiation in the epithelium of 12-day mouse embryonic submandibular glands in vitro, indicating the active involvement of interstitial collagens in the branching morphogenesis. Transmission electron microscopic observation of the intact 12-day gland without any clefts showed the scattered localization of a few collagen fibrils at the epithelial-mesenchymal interface of the bulb and also revealed the presence of numerous microfibrils around the stalk. Collagen bundles were regularly seen close to the wavy basal lamina at the bottom of clefts of the intact 13-day gland and 12-day gland cultured for 17 h under normal conditions. Mesenchymal cells were found in the clefts together with the frequent localization of peripheral nerve fibres and capillary endothelial cells. The collagen bundles were more often observed in the 12-day gland cultured in the presence of bovine dental pulp collagenase inhibitor, which had been shown to enhance cleft formation. In contrast, collagen fibrils were rarely found at the epithelial-mesenchymal interface of the 12-day gland cultured in the presence of Clostridial or bovine dental pulp collagenase. The findings indicated that the formation of interstitial collagen bundles is essential to form clefts in the epithelium both in vivo and in vitro.

Animals↗
PubMed1988

A case of subclavian steal syndrome with a specific form of obstruction of the right proximal subclavian artery.

We experienced a case of subclavian steal syndrome (SSS) with a specific form of obstruction of the right proximal subclavian artery. The patient was a 44-year-old man who complained of numbness of the right hand. Right carotid-subclavian artery anastomosis was performed under general anesthesia. The obstructed segment was a fibrous cord, 3.5 cm in length and 2.0 mm in diameter. Postoperatively, the patient was free from the symptom. In the Japanese literature, 73 cases of SSS were reported from 1965 to 1986, and the etiology was mentioned in 64 cases. In 28 cases the cause was aortitis syndrome (43.8%), in 22 cases arteriosclerosis (34.4%), in 13 cases congenital malformation (20.3%), and in 1 case iatrogenic lesion (1.6%). These data indicated that SSS caused by congenital malformation was not so rare as previously believed. Of 13 cases with congenital malformation, our case and 3 other cases had similar aspect in clinical features. All 4 patients were middle-aged men (aged 34, 26, 45 and 44 years) with a fibrous cord at the proximal portion of the right subclavian artery. None had any other cardiovascular anomalies.

Adult↗
PubMed1988

[Effects of cadralazine on the respiration, circulation, kidney, autonomic nervous system, digestive system, blood and so on].

The general pharmacological effects of cadralazine and its major metabolite ISF 2405 were studied by comparing them with those of hydralazine. Cadralazine at 3.0 mg/kg, i.v., increased respiratory movement and heart rate and decreased blood pressure in cats. Cadralazine at 3.0 mg/kg, i.v., inhibited the hypertensive response induced by adrenaline, but showed little effect on the hypotensive response induced by acetylcholine in cats. Cadralazine and ISF 2405 at 10(-4) g/ml had negative chronotropic effects on isolated guinea-pig atria. The drug at 2.5 mg/kg, p.o., inhibited the passage of BaSO4 in the gastrointestinal tract in mice. The drug at 5.0 mg/kg, i.d. or more inhibited gastric secretion in rats. Cadralazine, except at higher doses, had little effect on spontaneous gastric motility and uterine spontaneous movement in rats. Cadralazine at 2.5 mg/kg, p.o., or more reduced or tended to reduce urine volume and urinary excretion of electrolytes. The drug showed little effect on coagulation and osmotic fragility in blood cell in rats nor on hemolysis and platelet aggregation in rabbits. ISF 2405, however, showed slight or moderate influence on hemolysis at concentrations as high as 0.01-1.0%. Cadralazine at 5.0 mg/kg, p.o. or more antagonized carrageenin-induced hind paw edema in rats. In conclusion, these effects of cadralazine were found to be qualitatively identical with those of hydralazine.

Animals↗
PubMed1988

Modification by chemical stimuli of temporal difference in the onset of inspiratory activity between vagal (superior laryngeal) or hypoglossal and phrenic nerves of the rat.

Temporal differences in the onset of inspiratory activities between the efferent vagal (superior laryngeal, Xsl) or hypoglossal (XII) and phrenic (Phr) nerves were measured at various levels of chemical stimuli in the halothane-anesthetized, vagotomized, and artificially ventilated rat. The onset of Xsl (XII) inspiratory activities always preceded the abrupt start of the Phr discharge. Hyperoxic hypocapnia due to hyperventilation delayed the start of inspiratory activity (reduction in respiratory frequency) and shortened the difference in onset time between the cranial (Xsl, XII) and Phr nerve discharges (Td). During respiratory stimulation due to asphyxia (progressive hypoxia and hypercapnia), the start of Xsl (XII) inspiratory activity became progressively earlier than that of Phr discharge, which extremely prolonged the Td. Severe asphyxia, however, retarded the start of inspiratory activities with accompanying long Td and slow respiratory frequency. The early but gradually augmenting inspiratory activity of the Xsl (XII) nerve was always followed by large bursts synchronized with Phr discharges during altered chemical stimuli. The termination of inspiratory activity, which occurred simultaneously in the three respiratory nerves, was not significantly affected by changes in chemical stimuli except for extreme hypocapnia. The results indicate that changes in chemical stimuli not only alter the start of inspiratory activity but also influence the transition from the initial slow onset to the final synchronized inspiratory activity in the Xsl (XII) nerve. The apparent dissociation of the onset time between the Xsl (XII) and Phr nerve discharges shows that the temporal aspect of the brain stem process(es) for starting inspiratory activities may not be determined from the trajectory of Phr discharges only.

Animals↗
PubMed1988

Arterial to end-tidal PCO2 difference varies with different ventilatory conditions during steady state hypercapnia in the rat.

To estimate the influence of ventilatory conditions on the CO2 equilibration between the alveolar gas and arterial blood during steady state hypercapnia, we measured arterial and end-tidal PCO2 (PaCO2, PETCO2) of the anesthetized rat under the following three conditions: spontaneously breathing with CO2 inhalation, artificial respiration with gas mixture containing CO2, and artificial respiration with reduced ventilatory volume (hypoventilation). In each ventilatory condition, PaCO2 correlated linearly with PETCO2. However, in spontaneously breathing animals, the PaCO2-PETCO2 difference which was positive in a control condition (without CO2 inhalation) became negative during CO2 inhalation. The mean (+/- S.D.) difference was -3.6 +/- 1.5 mmHg (n = 9, p less than 0.001) at the PETCO2 range from 72 to 77 mmHg. During artificial respiration with constant ventilatory volume, initial positive PaCO2-PETCO2 difference approached zero when CO2 was administered into inspiratory gas. In both ventilatory conditions the slope of the PETCO2-PaCO2 relation line was less than 1.0, whereas the PaCO2-PETCO2 difference remained positive when PCO2 level was increased with reducing the ventilatory volume (accumulation of endogenous CO2). These observations suggest that for a given increase in PCO2 by administration of exogenous CO2, the extent to which PaCO2 increases is smaller than that of PETCO2. This peculiar relationship together with changes in breathing pattern during CO2 inhalation likely results in "negative" PaCO2-PETCO2 difference in the spontaneously breathing animal. We conclude that the PaCO2-PETCO2 difference, either as positive or negative values, depends upon both the level of PCO2 and the ventilatory condition to increase PCO2.

Animals↗
PubMed1988

Delayed ventilatory response to CO2 after carbonic anhydrase inhibition with acetazolamide administration in the anesthetized rat.

In order to estimate to what extent the stimulatory action of CO2 on ventilation is mediated by the formation of H+, we studied effects on the temporal profile of ventilatory response to CO2 of carbonic anhydrase (CA) inhibition with acetazolamide in the halothane anesthetized spontaneously breathing rat. Since hydration reaction of CO2 yielding H+ is delayed by CA inhibition, the time courses of changes in tidal volume (VT), respiratory frequency (f), and minute ventilation (VE) in response to a stepwise increase in end-tidal PCO2 (delta PETCO2 15 mmHg) were compared before (control state) and after i.v. injection of acetazolamide (50 mg/kg) in the hyperoxic condition. In the control state, an increase in VT was significantly slower than that in f, and the mean response half-times (T1/2) for the increase in VT, f, and VE were 50.6, 18.1, and 31.0 s, respectively. After acetazolamide administration, responses to CO2, especially f-response and consequently VE-response became much slower, and the T1/2 for VT, f, and VE were 67.9, 55.0, and 63.0 s, respectively. The delay in VT-response was not statistically significant. The magnitude of increase in VE in the steady state hypercapnic stimulation was almost the same before and after acetazolamide administration. The results suggest that a rapid increase in f during CO2 inhalation occurs predominantly through an increase in H+ produced by hydration of CO2 with CA, whereas VT-response may occur without involvement of this process. The different time courses of VT- and f-responses and possible effects of molecular CO2 and/or H+ on the regulatory mechanisms for ventilatory pattern were discussed.

Acetazolamide↗
PubMed1988

[Portal blood level of carcinoembryonic antigen (CEA) in colorectal cancer: correlation between tumor CEA content and immunohistochemical staining].

From tumors obtained from 87 patients with colorectal cancer during operation, portal blood levels of carcinoembryonic antigen (CEA) in drainage vein were measured and evaluated, according to the disease stage and histology, in comparison with cancerous tissue CEA in the extracts of surgical specimens and immunohistochemical analyses graded according to localization patterns and immunoreactivity; thereby trying to clarify a mechanism for the elevation of peripheral CEA levels. Mean value of portal CEA was higher than that of peripheral CEA at each stage of diseases, with a marked elevation by operative procedures. Although no significant correlation was observed between CEA contents of cancerous tissue (ng/g wet weight) and peripheral CEA levels, a close correlation was observed between portal CEA levels and cancerous CEA contents. A high CEA value was noted in moderately differentiated adenocarcinoma, according to cell differentiation (p less than 0.05). High portal CEA level was recognized in those with stain of cytoplasm and stroma, besides cancerous tissue CEA content, by means of immunopathochemical localization pattern, but a more significantly elevated CEA level was observed in those with the cancer pathologically infiltrating over muscle layers. The present study suggests that the route of CEA transfer from tumor to portal blood can be an important contributing factor to the control of peripheral CEA level.

Carcinoembryonic Antigen↗
PubMed1988

[The expression of c-myc, c-fms, c-sis oncogenes in the trophoblast of normal pregnancy and trophoblastic disease].

Recently it has been suggested that proto-oncogene plays a role not only in cellular proliferation, development and differentiation, but also in neoplastic transformation. We now show the expression and its localization of c-myc, c-fms and c-sis proto-oncogenes in human developing chorionic tissue and fresh surgical specimens of mole and choriocarcinoma with the method of Northern blotting and In-situ hybridization. The 2.4kb c-myc transcript has been localized to the cytotrophoblast in early placenta and also localized to the C and S typed trophoblastic cells in mole and choriocarcinoma. The 4.0kb c-fms transcript has been localized to the syncytiotrophoblast, especially the highly differentiated syncytiotrophoblast in the second and third trimesters and S typed trophoblastic cells in mole and choriocarcinoma. Moreover, the 4.0kb c-sis transcript has been localized to the cytotrophoblast in early placenta, but not detected in mole or choriocarcinoma. First, these results suggest that the stage and site specific expression of c-myc, c-fms and c-sis proto-oncogenes are clearly related to the proliferation, development and differentiation of normal trophoblastic cells. Second, the expression of c-myc, c-fms proto-oncogenes may be of particular importance in the tumorigenesis and progression of trophoblastic disease.

Blotting, Northern↗