Search PubMed⌕ Search

Biomedical subjects

Y Isobe

Publications and source records attributed to Y Isobe.

At least 109 records · Page 6Linked to original sources

Long-term survival of grafted cells, dopamine synthesis/release, synaptic connections, and functional recovery after transplantation of fetal nigral cells in rats with unilateral 6-OHDA lesions in the nigrostriatal dopamine pathway.

In animal models of hemi-Parkinson's disease, survival of grafted nigral cells, their synaptic connections, dopamine (DA) synthesis/release, and recovery from motor disturbances were investigated, and these were compared among 3 groups of animals raised for 3 months, 1 year and 2 years after the transplantation. Fetal nigral DAergic cell suspensions were transplanted in the ipsilateral caudate nucleus of rats with unilateral 6-OHDA lesions in the nigrostriatal DA pathway. Motor disturbances, assessed by methamphetamine-induced rotation, recovered partly in the 2nd week, significantly in the 4th week after the grafting, and remained stable thereafter. Many tyrosine hydroxylase (TH)-positive cells were detected along the grafting tracks. The number of TH-positive cells was similar in the 3 groups of animals. These TH-positive cells made synaptic connections in the host caudate. By in vivo microdialysis measurement, extracellular DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) around the grafted sites recovered to 30-100% of those of controls. No significant differences were observed in the concentration of DA, DOPAC and HVA among 3 groups of animals. They also responded to methamphetamine loading though the magnitudes were smaller. Using a TH cDNA probe, TH-positive cells were found to express TH mRNA in in situ hybridization-autoradiographic analysis. Data indicate that grafted fetal DAergic cells survive, synthesize and release DA, make synaptic connections in the host brain and ameliorate motor disturbances for over 2 years. There were no differences in these parameters among the 3 groups of animals, and no untoward side effects were observed even at 2 years after the grafting. Thus it was confirmed that the grafting of neuronal cells into the brain is a promising approach to restore disturbed function.

Animals↗

Spermine-like functions of N1, N12-bis(ethyl)spermine: stimulation of protein synthesis and cell growth and inhibition of gastric ulceration.

The spermine analogue N1, N12-bis(ethyl)spermine (BESPM) could mimic the functions of spermine in the following aspects: 1) BESPM could stimulate globin and ornithine decarboxylase synthesis in a rabbit reticulocyte cell-free system; 2) the addition of BESPM to the culture medium could recover cell growth of polyamine-deficient bovine lymphocytes; 3) spermidine uptake by bovine lymphocytes was inhibited by BESPM and spermine to a comparable degree; and 4) stress-induced gastric ulceration was inhibited by subcutaneous administration of BESPM. Since BESPM was less toxic than spermine for mice, BESPM or its derivatives may be useful for diseases which can be cured by polyamines.

Animals↗

H2-receptor antagonism by a novel compound IT-066 assessed from [14C]aminopyrine accumulation in rabbit parietal cells.

The H2-receptor antagonistic activities and properties of IT-066 were investigated in rabbit isolated gastric mucosal cell and were compared with those of famotidine and cimetidine. IT-066 inhibited dose dependently the histamine-stimulated [14C]aminopyrine ([14C]AP) accumulation in parietal cells. The antagonism was unsurmountable. The inhibitory action of IT-066 was enhanced by lengthening of its incubation time with the cells. IT-066 following 30 min preincubation with the parietal cells showed 32 and 1560 times the activity of famotidine and cimetidine, respectively, as an inhibitor of [14C]AP accumulation. The inhibitory activity of IT-066 on the histamine effect remained after repeated washing of the cells while with famotidine and cimetidine the response to histamine was restored after washout of the drugs from the cells. These data indicate that the antagonism of IT-066 on histamine H2-receptors is high and is unsurmountable in the isolated parietal cell model.

Aminopyrine↗

Effect of salvianolic acid A, a depside from roots of Salvia miltiorrhiza, on gastric H+,K(+)-ATPase.

Salvianolic acid A, a depside from the roots of Salvia miltiorrhiza, inhibited pig gastric H+,K(+)-ATPase and pNPPase with 50% inhibition values (IC50) of 5.2 x 10(-7) M and 1.7 x 10(-6) M, respectively. Kinetic studies revealed that the inhibition patterns induced by salvianolic acid A were competitive with respect to ATP and noncompetitive with respect to K+. Salvianolic acid A (25 mg/kg, i.p.) significantly inhibited acid secretion in pylorus-ligated rats. At the same dose it also showed a significant reduction in the formation of gastric lesion induced by water immersion and restraint stress. These results suggest that salvianolic acid A shows antisecretory and antiulcer activity by inhibiting the gastric H+,K(+)-ATPase.

Adenosine Triphosphatases↗

Inhibition of gastric H+, K(+)-ATPase by chalcone derivatives, xanthoangelol and 4-hydroxyderricin, from Angelica keiskei Koidzumi.

Two chalcone derivatives, xanthoangelol (1) and 4-hydroxyderricin (II) isolated from Angelica keiskei Koidzumi, inhibited pig gastric H+, K(+)-ATPase with IC50 values of 1.8 and 3.3 microM, respectively. The inhibition by I or II was competitive with respect to ATP and was non-competitive with respect to K+ I and II also inhibited K+, stimulated p-nitrophenyl phosphatase, with IC50 values of 1.3 and 3.5 microM, respectively. Proton transport in-vitro was inhibited by I or II, in a dose-dependent manner, 1 at 100 mg kg-1, i.p. significantly inhibited acid secretion and the formation of stress-induced gastric lesions. These results suggest that the antisecretory effect of 1 is due to the inhibition of gastric H+, K(+)-ATPase.

4-Nitrophenylphosphatase↗

Effects of the new H2-receptor antagonist 3-amino-4-[4- [4- (1-piperidinomethyl)-2-pyridyloxy]-cis-2-butenylamino]-3-cyclobutene-1, 2- dione hydrochloride on gastric acid secretion and ulceration.

The effect of 3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis- 2-butenylamino]-3-cyclobutene-1,2-dione hydrochloride (IT-066), a new H2-receptor antagonist, on gastric acid secretion and on various experimental ulcers was investigated. IT-066 showed very potent and long lasting antisecretory action in pylorus ligated rats. The inhibitory potency of IT-066 given subcutaneously for gastric acid secretion was 1285 and 44 times higher than for cimetidine and famotidine, respectively. The duration of the inhibitory action of IT-066 was significantly longer than that of famotidine and cimetidine. In pylorus ligated rats, IT-066 showed almost 20 times higher potency than omeprazole with intraduodenal administration, and almost the same duration of action as omeprazole with one tenth the dose in oral administration. IT-066 showed a powerful protective effect on various experimental ulcer models. The potency of IT-066 administered subcutaneously was significantly higher compared with that of cimetidine, famotidine and omeprazole. IT-066 given orally also showed a more powerful antiulcer effect than cimetidine and omeprazole, and was comparable with that of famotidine in restraint and water immersion stress and cold-stress plus indometacin induced ulcer models in rats. These results suggest that IT-066 has powerful and long lasting antisecretory and antiulcer effects and is a useful antisecretory drug for treatment of peptic ulcer diseases.

Animals↗

Antisecretory and antilesional effect of a new histamine H2-receptor antagonist, IT-066, in rats.

The effects of a new histamine H2-receptor antagonist, IT-066 (3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2-++ +butenylamino]- 3-cyclobutene-1,2-dione hydrochloride), were investigated on the secretagogue-induced acid secretion in vivo and in vitro, and on experimental gastric and duodenal lesion in rats. IT-066 (10-60 micrograms/kg) given i.v. inhibited histamine-stimulated acid secretion dose-dependently in gastric lumen-perfused rats, and the inhibitory effect was observed for about 12 hr. Famotidine (FMD) (10-60 micrograms/kg i.v.) also had an antisecretory effect, but the acid secretion recovered to the control level 4 hr after the administration. Cold stress plus indomethacin-induced lesion was significantly inhibited by IT-066 and FMD given i.v. 30 min before the cold stress plus indomethacin treatment. IT-066 given 7 hr before the cold stress plus indomethacin treatment also inhibited lesion formation significantly, but such antilesional effect was not observed with FMD. In the rat isolated gastric mucosal sheet, IT-066 inhibited histamine-stimulated acid secretion dose-dependently and noncompetitively; its action was produced via a unique mechanism. The inhibitory effect of IT-066 remained after washing of the mucosa, and became more potent time-dependently. The inhibitory effects of FMD and cimetidine were not observed after washing the mucosa. These data suggest that IT-066 has a potent and long lasting antisecretory effect in vivo and in vitro, and that these properties are responsible for the long lasting antilesional action.

Animals↗

[The suppressive effect of intravenous fluconazole against endogenous candida endophthalmitis in rabbits].

The therapeutic effect of intravenous fluconazole against endogenous candida endophthalmitis was investigated in rabbits. Twelve albino rabbits and a candida strain isolated from the human vitreous were used. Endogenous candida endophthalmitis was made by intravenous inoculation of 8 x 10(5) candida albicans spores in rabbits. In the first of two series of experiments, three rabbits out of six were injected intravenously with 5 mg/kg.b.w. of fluconazole at 30 minutes, 1 day and 2 days after inoculation. Another three control rabbits received no medication. The clinical course of the eyes was observed for a week and the viable cell numbers of candida in the eye were counted at 7 days after inoculation. Three rabbits treated with fluconazole developed no ocular lesions and no candida spores whatsoever were isolated from the eyes. In contrast, three rabbits in the control group developed bilateral chorioretinitis and candida albicans was isolated from each of 6 eyes. In the second series, three out of six rabbits were injected intravenously of the same dose of fluconazole as described above for four days starting at 3 days after inoculation, when chorioretinitis was first observed. No medication was given to another three rabbits as a control. All six rabbits in this series developed chorioretinitis similarly and candida spores were isolated from all eyes at 7 days after inoculation. These results show that intravenous fluconazole is effective in the prevention of the endogenous candida endophthalmitis in rabbits but ineffective for these short term therapeutic applications after onset.

Animals↗

[Surgical and preoperative treatment of soft tissue sarcoma].

Preoperative therapy effects, resected margin and local radicality were investigated in 40 cases of soft tissue sarcoma in which preoperative therapy (mainly radiation therapy) had been given. The results indicated that there was no effect upon prognosis due to postponement of surgery in order to perform preoperative treatment. In cases in which radiation therapy was used for preoperative treatment, even when a surgical margin resulted with in a tumor, no recurrence was found. However, histologically there was concern that some portion of the living tumor cell in marginal area of the tumor might have remained. Thus, at the present stage in cases having undergone initial treatment, radiation limited to the specific area of the resected margin causing non-curative margin should be given. If combined with preoperative radiation therapy, surgical intervention involving "wide margin" can be considered radical. On the other hand, cases having undergone surgery before and receiving preoperative therapy that show good response nevertheless show numerous recurrences. These recurrences, however, invariably occur outside of the irradiated area, and may be attributed to the fact that tumor cell dissemination from the earlier surgery was not within the radiation field. Hence, it was considered that the area for radiation in the case of a recurrence should extend well beyond the scar area.

Combined Modality Therapy↗

[An evaluation of MR imaging of soft-tissue masses in extremities].

We evaluated 22 soft-tissue masses in the extremities using magnetic resonance (MR) imaging. The twenty-two cases consist of 14 benign lesions and 8 malignant lesions. MR imaging is available to provide the representation of the extent of the masses, though characteristic diagnosis of them could not be identified. We think that there are more advantages to using MR imaging rather than computed tomography (CT) in the evaluation of soft-tissue masses in extremities.

Adolescent↗

[Pleuroperitoneal shunt for malignant pleural effusions].

The malignant pleural effusion was introduced into the abdominal cavity by the manual compression of a pleuroperitoneal shunt tube, which was indwelt in the subcutaneous tissue of the lateral chest under local anesthesia. Seven patients having malignant pleural effusion, due to lung cancer in 4 and breast cancer in 3, were used as subjects. This technique caused no serious complications. Retention of pleural effusion was markedly reduced in all of the 7 patients. Three patients, whose performance status (P.S.) was preoperatively determined to be 3 or 2, could be discharged during early periods. This technique seemed to be highly feasible in these patients, but not in those having P.S. of 4. Since peritoneal dissemination of the tumor was seen in 1 of 3 patients examined by autopsy, there is a possibility that this technique might have contributed to spread and scattering of tumor cells in the peritoneal cavity. These results suggested that this technique is useful therapeutic means for the treatment of patients in whom hospitalization is necessary due to the presence of malignant pleural effusion, while this technique involves the risk of artificial induction of peritoneal dissemination of tumor cells. Therefore, the application of this technique should be decided based on the prognosis of each patient.

Aged↗

Thermal salivation in rats, anesthetized with barbiturates, chloralose, urethane and ketamine.

1. The relationship between thermal salivation (TS) and thermoregulation was studied in anesthetized rats. 2. Of the 6 anesthetics used, ketamine-anesthetized rats secreted the largest amount of saliva. Salivation, however, was thermal and not induced by ketamine itself. 3. Ketamine-anesthetized rats readily secreted saliva at core temperatures less than 40 degrees C but TS was remarkably enhanced by hyperthermia of 40-42.5 degrees C. 4. The equilibrium phase in the triphasic heat response of core temperature was a consequence of equilibrium between heat gain and heat loss by salivation.

Anesthetics↗

Curative resection of multiple gastrinomas aided by selective arterial secretin injection test and intraoperative secretin test.

Recently a number of surgeons have recommended radical resection of gastrinomas in Zollinger-Ellison syndrome (ZES). We have developed a useful technique for preoperative localization of gastrinomas--the selective arterial secretin injection test (SASI)--and we recommend an intraoperative secretin test (IOS) for deciding the radicality of resection of gastrinomas. Here the results of SASI and IOS tests in 11 patients with ZES are examined and compared with the results of other techniques. The SASI test localized gastrinomas in all of the patients, while the sensitivity of ultrasonography, computed tomography, arteriography, or portal venous blood samplings was between 1/11 and 5/11. On the basis of the results of the SASI test, radical resection of gastrinoma was performed in four patients (three pancreatoduodenectomies and one extirpation). After pancreatoduodenectomy, immunohistologic study of the specimen revealed multiple microgastrinomas and lymph node metastases in two patients and the coexistence of a microgastrinoma and a gastinoma in one patient. The IOS test was useful in the estimation of the advisability of radicality, and in two patients total gastrectomy was not performed because of the results of the IOS test. These four patients are well and have returned to work, and their serum gastrin levels are below 35 pg/mL. Thus we believe SASI and IOS tests are helpful for planning curative resection of gastrinomas.

Adolescent↗

Measurements of auditory and somatically evoked magnetic fields and localization of their dipole sources.

We have measured neuromagnetic fields evoked by auditory and somatic stimulations using a SQUID. Responses of the auditory evoked field (AEF) have two peaks at about 100 and 180 ms after the onset of tone burst stimulus. Responses of the somatically evoked field (SEF) have two peaks at about 80 and 160 ms after the stimulus of current pulse. Magnetic field data measured at various positions of the lateral side of the head have been used to calculate parameters of an equivalent current dipole source based on a least-squares fit. The determined source locations indicate the auditory cortex for the AEF and the primary somatosensory cortex for the SEF, in agreement with anatomical structures obtained from NMR images. A simulation study has been done to estimate errors in the calculated dipole parameters due to the field noise. For typical measurement conditions of a signal-to-noise ratio of approximately 5 and measurement points of approximately 40, location errors of the order of 5 mm are estimated.

Auditory Cortex↗

Effect of polyamine related tetraamines on anti-ulcerogenic activity and anti-H+,K+-ATPase activity.

The relationship between the structure of polyamine related tetraamines and their anti-ulcerogenic activity in rats was studied. Among the tetraamines tested, linear tetraamines had stronger anti-ulcerogenic activity in both restraint stress-induced gastric ulceration and ulceration in pylorus-ligated rats. Macrocyclic tetraamines and polycyclotetraamines had less anti-ulcerogenic activity. Correlation was detected between the inhibitory effect of tetraamines on gastric secretion in pylorus-ligated rats and their inhibitory effect on H+,K+-ATPase activity in rat gastric mucosa. Thermine and spermine were the most effective in these two inhibitions. Thus, it is suggested that primary aminogroups are important in both anti-ulcerogenic activity and anti-H+,K+-ATPase activity.

Adenosine Triphosphatases↗