Search PubMed⌕ Search

Biomedical subjects

H Yamanaka

Publications and source records attributed to H Yamanaka.

At least 19 recordsLinked to original sources
PubMed1992

Transient activation of hepatic glycogenolysis by thrombin in perfused rat livers.

Thrombin, a peptide with native protease activity, caused a rapid (less than 1 min) increase in glycogenolysis of about 30%, assessed from rates of production of glucose+lactate+pyruvate, and in oxygen uptake in perfused rat liver. These increases were followed by a rapid return to basal values within 5 min. The effect of thrombin on glycogenolysis was dose-dependent and was maximal at perfusate concentrations around 1 U/ml. Interestingly, the effect of thrombin on glycogenolysis could be elicited only once in any given liver. The activation of glycogenolysis by thrombin was diminished nearly 50% by prior infusion of the protease inhibitor, diisopropyl fluorophosphate (10 microM), and over 90% when thrombin was treated with diisopropyl fluorophosphate prior to infusion. The stimulation of glycogenolysis by thrombin could be detected in isolated hepatocytes or in livers stored for 24 h in cold Euro-Collins solution, a treatment which destroys endothelial cells. Further, thrombin stimulated production of prostaglandin D2 from arachidonic acid in cultured hepatic endothelial but not Kupffer cells. The effect of thrombin on carbohydrate output was also blocked by a phospholipase A2 inhibitor (quinacrine, 50 microM) and by an inhibitor of the cyclooxygenase (indomethacin, 20 microM), suggesting the involvement of cyclooxygenase in the mechanism of action of thrombin. In support of this idea, the transient kinetics of stimulation of glycogenolysis by thrombin and arachidonic acid was nearly identical to release of thromboxane B2 (80-420 pg/ml) and prostaglandin D2 (300-900 pg/ml) from the perfused liver. Further, a second addition of thrombin failed to increase thromboxane and prostaglandin D2 release as well as carbohydrate production, supporting a causal link between these phenomena. Taken together, these data support the hypothesis that thrombin interacts with receptors in the liver, possibly on endothelial cells, leading to activation of phospholipase A2 and subsequent transient production of prostaglandins and thromboxanes. These mediators subsequently interact with receptors on parenchymal cells, leading to a transient stimulation of glycogenolysis.

Animals↗
PubMed1992

Significance of a new stratification of alkaline phosphatase and extent of disease in patients with prostate carcinoma with bone metastasis.

Bone is the most frequent site of metastatic prostate cancer and the prognosis of patients with bone metastasis is poor. The authors have investigated a semiquantitative system to evaluate bone metastatic lesions in terms of cancer-specific survival. Based on the extension of disease (EOD) grade proposed by Soloway and associates, a new EOD grading system obtained from bone scintigraphy alone and EOD score obtained from bone scintigraphy and alkaline phosphatase was studied in 164 patients with prostate cancer with metastatic bone involvement. In terms of a cancer-specific survival and prostate cancer death, both the new EOD grade and the EOD score were apparently superior to eight other items studied (age, medical score, gait disturbance, histologic grade, erythrocyte sedimentation rate, prostatic acid phosphatase, and alkaline phosphatase). Multivariate analysis revealed that the EOD score was better than the new EOD grade. This improvement was due to the elimination of false-positive or nonactive metastatic bone lesions on bone scintigraphy through the alkaline phosphatase evaluation.

Aged↗
PubMed1992

NADPH-cytochrome c (P-450) reductase has the activity of NADPH-linked aquacobalamin reductase in rat liver microsomes.

To elucidate the mammalian system for synthesis of cobalamin coenzymes, microsomal NADPH-linked aquacobalamin reductase was purified and characterized. The enzyme was purified about 534-fold over rat liver microsomal fraction in a yield of about 32%. The purified enzyme was homogeneous in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and had a monomeric molecular weight of 79,000. The purified aquacobalamin reductase showed a high specific activity (about 55 mumol/min per mg protein) of NADPH-cytochrome c (P-450) reductase. About 33% of the NADPH-cytochrome c reductase activity found in the microsomal fraction was recovered in the final purified preparation. The activity ratio of NADPH-cytochrome c reductase/NADPH-linked aquacobalamin reductase was about 5.0 through the purification steps, indicating that the rat liver microsomal NADPH-linked aquacobalamin reductase is the NADPH-cytochrome c reductase.

Animals↗
PubMed1992

Action of Escherichia coli heat-stable enterotoxin II on isolated sections of mouse ileum.

When Escherichia coli STII was applied to the serosa of the ileum at a concentration of 40 micrograms/ml, an acceleration of the spontaneous motility and a weak contraction were induced 2-3 min later. The induction was not affected by the addition of atropine (10(-6) M), but was abolished by the addition of papaverine (10(-4) M). When STII was applied to the mucosa, the acceleration of the spontaneous motility appeared 7-8 min later, but a contraction was not induced. These results suggest that STII acts directly on muscle cell of the ileum and enhances the spontaneous motility of the intestine.

Animals↗
PubMed1992

Correlation between the prostatic vein and vertebral venous system under various conditions.

In dogs, the venous blood from the prostate gland was observed under X-ray fluoroscopy to drain into the vertebral venous system under conditions of abdominal compression, the addition of various intraabdominal pressures, and occlusion of the inferior vena cava by a balloon catheter. Pressure in the inferior vena cava and abdominal cavity were measured simultaneously. The venous blood draining from the prostate gland started to flow from the inferior vena cava into the vertebral veins at more than 25 mmHg of intraabdominal pressure with the animal in the supine position. The average pressure of the inferior vena cava draining into the vertebral veins was 12.8 +/- 1.3 mmHg in the supine position and 21.1 +/- 2.7 mmHg in the standing position. The average intraabdominal pressures were 35.5 +/- 3.9 mmHg and 30.1 +/- 2.8 mmHg, respectively. Under conditions of abdominal compression and balloon occlusion of the inferior vena cava, the materials flowed into the vertebral venous system from various routes, such as the internal iliac vein, common iliac vein, and inferior vena cava. It was suggested that the inferior vena caval blood easily enters the vertebral venous system in the standing position by adding high intraabdominal pressure, and that the vertebral venous system may be useful for experimental study of drug administration in bone metastasis of prostate cancer.

Animals↗
PubMed1992

Inhibition of 3 alpha-hydroxysteroid oxidoreductase and 5 alpha-reductase activity by antiandrogens and indomethacin in the rat prostate.

We studied the effects of antiandrogens in vitro on inhibition of 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) and 5 alpha-reductase activities in the rat prostate. Kinetic and inhibition experiments were analyzed by thin layer chromatography. Cyproterone acetate (CA), chlormadinone acetate (CMA), and TZP-4238 (TZP), which is more potent than other antiandrogens, were used as inhibitors and were compared with indomethacin IND, which is a recognized 3 alpha-HSOR inhibitor. The IC50S of CA, CMA, IND, and TZP for 3 alpha-HSOR reductase in cytosol were about 5, 10, 10, and 100 microM, respectively, and inhibition was competitive. The IC50 of IND for 3 alpha-HSOR reductase in microsomes was 20 microM. The IC50S of other inhibitors were > 100 microM, and inhibition was noncompetitive. The IC50S of CA, CMA, IND, and TZP for 3 alpha-HSOR oxidase in cytosol were > 100 microM, and inhibition was competitive or noncompetitive. Inhibition of 3 alpha-HSOR oxidation was not observed in microsomes. The difference between these inhibition patterns suggests that there may be 4 isoenzymes in rat prostatic tissue. The IC50S of MK-906, CMA, and TZP for 5 alpha-reductase in prostate homogenate were about 0.01, 200, and 200 microM, respectively.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Lymphatic drainage of the prostate gland in canines.

Lymphography of the penis was performed in 3 canines, and direct intraprostatic injection of India ink was carried out in 8 canines to visualize lymphatic drainage of the prostate gland. In penile lymphography, the contrast medium drained in 2 directions: (1) lymphatic drainage into the external and common iliac lymph nodes through the superficial inguinal lymph nodes; (2) lymphatic drainage into the presacral lymph nodes along the urethra and posterior wall of the pelvis. Lymphatics of the prostate gland drained in 3 directions: (1) lymphatics from the prostate gland mainly drained along the prostatic and internal iliac vessels into the internal and common iliac lymph nodes, (2) lymphatics from the dorsal region near the urinary bladder drained along the ureter into the common iliac lymph nodes, and (3) lymphatics from the apex of the prostate gland drained along the posterior wall of the pelvis into the presacral lymph nodes. Prostate cancer developed at the apex is estimated to preferentially metastasize to the presacral lymph nodes, and drug injection into the penile lymphatics is considered to be a good route to treat metastases of lymph nodes in the pelvis.

Animals↗
PubMed1992

Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia.

The effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One- to 2-year-old beagle dogs were castrated and administered 75 mg/week of androstanediol (A-diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP-4238, 0.1 mg/kg/day of TZP-4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A-diol plus E2. Treatment with 0.5 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP-4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/kg/day of TZP-4238 decreased 5 alpha-reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP-4238 and CMA were effective in inhibiting the growth of hormone-induced canine BPH, and TZP-4238 was at least 5 times more potent than CMA. TZP-4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen-AR complex. TZP-4238 decreased 5 alpha-reductase activity by prevention of the androgen action described above.

Androstane-3,17-diol↗
PubMed1992

Potential role of HBGF (FGF) and TGF-beta on prostate growth.

We review in this paper the role of heparin-binding growth factor (HBGF*) or fibroblast growth factor (FGF*), rat prostate cancer cells produce TGF-beta, IGF-II* and OGF*. Of these growth factors, TGF-beta and unknown labile factor with 19 kDa are the most probable candidates responsible for osteoblastic bony metastasis of prostate cancer. In vitro experiments suggest that TGF-beta modulates cell detachment of prostate cancer cells together with nutritional factors. HBGF-dependent growth of the prostate tumor epithelial cells is free from inhibition by TGF-beta, whereas normal prostate epithelial cells are sensitive to TGF-beta inhibition. Transfection experiments suggest that HBGF-2 (basic FGF) might be closely related to the malignant growth of prostate cancer, in addition to tumor angiogenesis.

Animals↗
PubMed1992

Palliative radiotherapy of bone metastasis.

We analyzed the effects of radiotherapy on 226 sites of metastatic bone tumors from 1981 to 1984, and on 157 sites of bone metastases of prostate cancer from 1970 to 1988. The radiation effect on pain relief was recognized in about 90% of cases within the dose of 20Gy to 30Gy, and there were not many differences in these effects according to the original tumors or histological types. In prostate cancer, the sites which needed re-irradiation were not recognized within 6 months after irradiation, and only 12 out of 80 sites (15%) that could be observed after more than 6 months needed re-irradiation due to recurring pain. As more than 60% of the patients with prostate cancer who needed irradiation to control bone metastases died within a year, to get pain relief by irradiation immediately and safely was thought to be very useful from the viewpoint of useful life. One patient was irradiated on 16 sites and 2 of these 16 sites received 4 treatments of irradiation and the shortest interval was 10 months and the longest one was 18 months.

Bone Neoplasms↗
PubMed1992

Analysis of survival of prostate cancer patients in Japan and the U.S.A.

The prognosis of U.S.A. patients with prostate cancer based on reports from the American College of Surgeons and Roswell Park Cancer Institute was compared with that of Japanese in Nagasaki and Gunma. There was more than a 10% difference in survival rate between the two countries. Several clinical parameters were analyzed to determine the basis for this difference. In general, stage distribution, metastatic sites, bone pain and alkaline phosphatase in the USA patients with Stage D disease were more severe than in the Japanese patients. Moreover the prostate cancer death rate in the USA was higher than that in Japan. However, only the distribution of pathological grade in the USA was better than that in Japan. From these results, it is difficult to conclude that prostate cancer in the USA is more aggressive than in Japan. The possibility of selection bias in these studies is discussed.

Adenocarcinoma↗
PubMed1992

Accelerated purine nucleotide degradation by anaerobic but not by aerobic ergometer muscle exercise.

The exact conditions under which exercise causes purine nucleotide degradation are not well understood. We determined plasma hypoxanthine and uric acid levels serially in eight individuals during ergometer muscle exercise. When the load was increased gradually by 15 W/min, plasma hypoxanthine was elevated only after the status exceeded the anaerobic threshold (AT), as determined by analysis of expired gas. Nonstrenuous ergometer exercise, which kept the status continuously below the AT, induced neither blood lactic acid nor plasma hypoxanthine elevation. These results suggest that the AT is also the threshold for the acceleration of purine nucleotide degradation. Muscle exercise to a degree that does not exceed the AT does not cause major purine nucleotide degradation, and, therefore, is expected to be beneficial for patients with gout and/or hyperuricemia.

Adult↗
PubMed1992

Novel Ca2+ currents in mammalian CNS neurons.

Voltage-dependent Ca2+ currents (ICa) in neurons can be classified into T-, N- and L-types. In the CA1 pyramidal neurons freshly dissociated from rat hippocampus we found an additional tetrodotoxin (TTX)-sensitive Ca2+ current (termed 'TTX-ICa'). The TTX-ICa showed a heterogeneous distribution, preferentially in the dorsal site of CA1 region. Activation and inactivation processes of the TTX-ICa were highly potential-dependent, and the latter was fitted by a double exponential function. The TTX-ICa was activated at a threshold potential of about -55 mV and reached full activation at -30 mV. The steady-state inactivation of TTX-ICa could be fitted by a Boltzmann equation with a slope factor of 6.0 mV and a half-inactivation voltage of -72.5 mV. When the peak amplitudes of TTX-ICa were plotted as a function of extracellular Ca2+ concentration ([Ca2+]o), the current amplitude increased linearly without showing any saturation. The ratio of peak amplitude in the individual I-V relationships of Ca2+, Sr2+ and Ba2+ currents passing through the TTX-sensitive Ca(2+)-conducting channel was 1:0.33:0.05, although the current kinetics were much the same. TTX inhibited the TTX-ICa in time- and concentration-dependent manner without affecting the current kinetics. Lignocaine inhibited the TTX-ICa in a second in a concentration-dependent manner, with accelerating the inactivation process. The concentrations of half-inhibition (IC50) were 3.5 x 10(-9) M for TTX and 3.6 x 10(-4) M for lignocaine. Scorpion toxin prolonged the inactivation phase of TTX-ICa in a time- and concentration-dependent manner. In the toxin-treated neurons, both the slow time constant of inactivation (tau is) and its functional contribution to the total current increased with increasing the toxin concentration.

Animals↗
PubMed1992

Inhibition of mitochondrial respiration and oxygen-dependent hepatotoxicity by six structurally dissimilar peroxisomal proliferating agents.

The purpose of this study was to test the hypothesis that a variety of structurally dissimilar peroxisomal proliferators inhibited O2 uptake and caused O2-dependent hepatotoxicity in the perfused rat liver. Aspirin, valproate, ethylhexanol, clofibric acid, ciprofibrate and perfluorooctanoate were selected as a representative group of weak, moderate, and potent peroxisomal proliferators, respectively. All compounds studied inhibited state 3 but not state 4 rates of oxygen uptake in isolated mitochondria (perfluorooctanoate greater than ciprofibrate greater than ethylhexanol greater than clofibric acid greater than aspirin greater than valproate; half maximal inhibition occurred at concentrations ranging from 0.6 to 3.2 mM depending on the compound). Clofibric acid, ethylhexanol and aspirin inhibited oxygen uptake only in upstream, oxygen-rich periportal regions of the perfused liver lobule by 30-40%. Perfusion with the six agents studied caused release of lactate dehydrogenase into the effluent perfusate in a dose-dependent manner and caused damage predominantly in periportal regions of the lobule as reflected by trypan blue uptake. A strong correlation between the concentration of compound needed to inhibit respiration in isolated mitochondria and cause hepatotoxicity in the perfused liver was observed. We propose that peroxisomal proliferators accumulate in the liver due to their lipophilicity where they inhibit actively respiring mitochondria in periportal regions of the liver lobule and cause local toxicity.

Animals↗
PubMed1992

Chromaticity analysis of immunostained tumor specimens.

In order to evaluate the correlation between immunohistochemical and morphometric data on the same histological sections, we have developed a flexible color image analyzer (Microcomputer-Assisted Picture Processing System type II, MAPPS-II), and established an effective method to analyze the immunostained colorectal neoplasms based on the color recognition theory of human visual system. Colorectal adenomas and adenocarcinomas were stained with a monoclonal antibody C 12, which recognizes abnormal H antigen, using Avidin-Biotin method and diaminobenzidine (DAB, brown dye). Nuclei were stained with Hematoxylin (blue dye). Density and colorimetric analyses revealed two results: (A) Separation of immunostained brown area from blue nuclei was best performed by plotting the representative sample areas on a standard chromaticity diagram, which displays the hue and saturation of colors simulating color of human visual system. (B) After separation of immunostained areas, usual density analysis was useful for the assay of nuclear morphometric information. Using these programs, normal mucosa was negative for C 12, and showed low nuclear/cytoplasmic ratio (NCR). Adenoma was occasionally focally positive for C 12, and showed medium NCR. Carcinomas were C 12 positive, and showed high NCR. Our method permits nuclear counterstaining by hematoxylin instead of low contrast methyl green, which will widen the field of combined immunohistochemical and morphometric study.

Adenocarcinoma↗
PubMed1992

Cytochrome b5/cytochrome b5 reductase complex in rat liver microsomes has NADH-linked aquacobalamin reductase activity.

To study the mammalian system for synthesis of cobalamin coenzymes, rat liver microsomal NADH-linked aquacobalamin reductase was characterized. Microsomal NADH-linked aquacobalamin reductase, which was solubilized with 10 g/L sodium deoxycholate, showed identical elution behavior to NADH-cytochrome c reductase (cytochrome b5/cytochrome b5 reductase complex) on DEAE-Toyopearl 650 column chromatography. By mixing the purified cytochrome b5 with cytochrome b5 reductase, cob(II)alamin was immediately formed from aquacobalamin and NADH. These results provide evidence that the NADH-linked aquacobalamin reductase activity is derived from the cytochrome b5/cytochrome b5 reductase complex in rat liver microsomes. Some properties of the cytochrome b5/cytochrome b5 reductase complex in the form of NADH-linked aquacobalamin reductase were studied. The inhibition studies with cobalamin analogues suggested that hydrophobicity of the corrin ring of cobalamin molecule is involved in binding of cobalamin to the cytochrome b5/cytochrome b5 reductase complex.

Animals↗