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S Hishinuma

Publications and source records attributed to S Hishinuma.

35 records · Page 2Linked to original sources
PubMed1993

Novel regulation of muscarinic receptors and their coupling with G proteins in smooth muscle: transient resensitization during desensitizing process.

1. Muscarinic stimulation of the smooth muscle of guinea-pig taenia caeci was produced with 10(-4) M carbachol for 15 s, 30 s, 1 min, 2 min and 30 min, and the time course of developing desensitization was studied by measuring the muscle contractility and the binding characteristics of muscarinic receptors. 2. The contractile response to carbachol was analyzed using dose-response curves. The response to 10(-7) M carbachol was reduced by treatment for 15 s with 10(-4) M carbachol (fast desensitization), but recovered partially after 30 s treatment and completely after 1 min treatment (resensitization). Contractility was reduced again after 2 min and 30 min treatment (re-desensitization). 3. The affinity of carbachol for muscarinic receptors was changed by the carbachol treatment in a manner similar to the contractility. Thus, the affinity was reduced at 15 s, restored slightly at 30 s and completely at 1 and 2 min, and was reduced again at 30 min. 4. 5'-Guanylylimidodiphosphate (GppNHp), a non-hydrolysable analogue of guanosine triphosphate (GTP) reduced the affinity of muscarinic receptors for carbachol via guanine nucleotide-binding regulatory proteins (G proteins). A similar effect was observed in tissues desensitized by 15 s carbachol treatment. This effect disappeared after 30 s, recovered completely after 1 and 2 min, and disappeared again after 30 min carbachol treatment. 5. Neither the dissociation constant (Kd value) nor the maximal binding (Bmax) of [3H]-quinuclidinyl benzilate ([3H]-QNB) to muscarinic receptors were changed by the carbachol treatment. 6. These results indicate that the whole process of desensitization, resensitization and re-desensitization are related to changes in the binding ability of muscarinic receptors, in their coupling with G proteins and in the post-receptor steps of the signal transduction. We emphasize that the desensitizing process involves an early transient phase of resensitization that could be caused by restoration of both the affinity of carbachol for muscarinic receptors and their coupling with G proteins. This novel resensitization mechanism may have some physiological significance for cellular homoeostasis by modulating cellular responsiveness transiently or even in an oscillatory manner during the process of desensitization.

Animals↗
PubMed1992

Haloperidol differentiates smooth muscle contractions induced by release of intracellularly stored Ca and by influx of extracellular Ca.

1. The effects of haloperidol on smooth muscle contraction induced by carbachol, histamine, high K or caffeine in the presence or absence of extracellular Ca were investigated. 2. In the presence of extracellular Ca, the maximal contraction induced by carbachol was reduced by haloperidol, while that by histamine or high K was much less affected. 3. In Ca-free solution, contraction induced by histamine was extremely reduced by haloperidol, while that by carbachol was not affected. 4. These results suggest that haloperidol selectively inhibited signal transduction processes from activation of muscarinic acetylcholine receptors to influx of extracellular Ca and from activation of histamine H1-receptors to release of intracellularly stored Ca. 5. Caffeine-induced contraction in Ca-free solution was markedly potentiated by haloperidol, although haloperidol did not elicit contraction in Ca-free solution by itself. 6. These results suggest that haloperidol increased the sensitivity of Ca-induced Ca release channels to caffeine.

Animals↗
PubMed1991

Blockade by the local anaesthetic, tetracaine, of desensitization of Ca-induced Ca release after muscarinic stimulation in smooth muscle.

1. Desensitization of contractile responses dependent on release of intracellularly stored Ca elicited by carbachol, histamine or caffeine was measured after desensitizing treatment with carbachol or histamine in the presence or absence of local anaesthetics in Ca-free solution containing 2 mM EGTA in the smooth muscle of guinea-pig taenia caecum. 2. Histamine-induced homologous desensitization was inhibited by tetracaine and procainamide. Dibucaine did not exert an inhibitory effect on the desensitization. This is consistent with our previous findings concerning the effects of local anaesthetics on the desensitization of histamine H1-receptors measured under normal physiological conditions. 3. Carbachol induced a functional change of intracellular Ca stores which resulted in heterologous desensitization. Tetracaine completely blocked carbachol-induced desensitization of the caffeine-elicited contraction, but in the case of carbachol-induced desensitization of carbachol- and histamine-elicited contractions, this blocking effect of tetracaine was very weak and absent, respectively. The other local anaesthetics used did not affect the desensitization. These results suggest that the Ca-induced and inositol trisphosphate-induced Ca release mechanisms were both desensitized by carbachol and that the desensitization of the Ca-induced Ca release mechanism was selectively blocked by tetracaine.

Animals↗
PubMed1991

Breast cancer developing after chemotherapy for osteosarcoma: a case report.

A 24-year-old patient who developed breast cancer 16 years after chemotherapy for osteosarcoma is presented. She had no family history of cancer. She had also not had radiotherapy. She had been given chemotherapy consisting of VAOMT (vincristine 10.2 mg, cyclophosphamide 900 mg, mitomycin C 15.2 mg, chromomycin A3 25.8 mg) pre- and post-operatively in the treatment of her osteosarcoma. Careful long-term follow-up is required after treatment of malignant neoplasms because there is a possibility of developing a second malignancy.

Adult↗
PubMed1990

[Clinical evaluation and problem of intra-arterial infusion chemotherapy of liver metastasis from digestive organ cancer].

Intra-arterial infusion chemotherapy using an implantable reservoir was used for 22 patients with liver metastasis from September 1986 to March 1990. The material consisted of 8 subjects with gastric cancer and 14 with colorectal cancer. One had metastasis in one lobe (H1), 10 had a few scattered metastases in both lobes (H2) and 11 had numerous metastases in both lobes (H3). In 5 cases, a reservoir was implanted to prevent the recurrence after hepatectomy. Infusion catheter was placed in the proper hepatic artery in 5 cases via the gastroduodenal artery at laparotomy and it was carried out subcutaneously via the femoral artery in 17 cases. In all cases intra-arterial infusion of 5-FU was continuously administered followed by intermittent one shot injection of ADM. The clinical effectiveness of the therapy was well evaluated. One-year cumulative survival rate of all cases by Kaplan-Meier method was 55% and that of H2 cases was 78%. No recurrence was noted in post hepatectomy cases. Eight cases (36.3%) showed remarkable complications, which made it impossible to continue intra-arterial infusion chemotherapy: hepatic artery occlusion (3 cases), infection (2 cases), abdominal pain (1 case), hematoma in the implanted site (1 case) and dislocation of the infusion catheter (1 case). From the present study, it is considered that intra-arterial infusion chemotherapy is a useful procedure for the control of liver metastasis. Regimens for improved chemotherapy and the maintenance of more useful and safer catheters should therefore be investigated for further development of the therapeutical estimation.

Colorectal Neoplasms↗
PubMed1990

[An esophageal cancer with a renal metastasis that was detected and resected as the only focus of recurrence].

Reported is the case of an esophageal cancer presenting a renal metastasis, which was detected and resected as the only recurrent focus. The patient was a 62-year-old male. Five months after an esophagectomy, a left renal mass was detected by abdominal computerized tomography, and a rise in the SCC antigen. The urinary cytology suggested a renal metastasis of the esophageal cancer. Thus, chemotherapy and irradiation was performed, followed by a resection. The histology of the resected mass showed a squamous cell carcinoma, similar to the findings at the primary site. A renal metastasis of an esophageal carcinoma usually is latent, but not rarely found on postmortem examination. A nephrectomy for a renal metastasis of an esophageal cancer is rare, and only 8 cases are reported in the literature.

Antigens, Neoplasm↗
PubMed1989

Short-term desensitization of phosphatidylinositol turnover via muscarinic acetylcholine receptors and histamine H1-receptors in smooth muscle.

Smooth muscle of guinea-pig taenia caecum was desensitized by treatment with 10(-4)M carbachol or 10(-4)M histamine for 30 min in Ca-free solution containing 2mM EGTA. Phosphatidylinositol turnover stimulated by carbachol was not reduced by desensitization with either carbachol or histamine, while the turnover stimulated by histamine was reduced by desensitization with histamine, but not with carbachol. These results are consistent with our previous report (1) that heterologous desensitization induced by carbachol occurs at intracellular Ca stores and homologous desensitization by histamine occurs at H1 receptors.

Animals↗
PubMed1988

Short-term desensitization of guinea-pig taenia caecum induced by carbachol occurs at intracellular Ca stores and that by histamine at H1-receptors.

1. In Ca-free solution, the contractile response of guinea-pig taenia caecum to 10(-4) M carbachol was mediated through muscarinic receptors and was reduced time-dependently by desensitization with 10(-4) M carbachol, but not 10(-4) M histamine. On the other hand, the response to 10(-4) M histamine was shown to be mediated through H1-receptors and to be reduced time-dependently by desensitization with either 10(-4) M histamine or 10(-4) M carbachol. 2. The maximal K+ contraction was not changed by desensitization with carbachol or histamine. Thus, contractile proteins and voltage-dependent Ca channels maintain their normal functions. 3. To study the coupling of Ca channel activity in cell surface membrane to receptor activation, the contractile responses elicited by carbachol and histamine added simultaneously with Ca to Ca-free solution were measured. The response elicited by carbachol plus Ca was not changed by desensitization with carbachol, while that elicited by histamine plus Ca was reduced by desensitization with histamine. These results show that desensitization by carbachol occurs at a post-receptor site, whereas that induced by histamine occurs at H1-receptors. 4. After desensitization with carbachol, but not histamine, the contractile response to 5 x 10(-2) M caffeine in Ca-free solution was significantly reduced. 5. These results show that short-term desensitization of guinea-pig taenia caecum by carbachol is heterologous and occurs at intracellular Ca stores, while that induced by histamine is homologous and occurs at histamine H1-receptors.

Animals↗
PubMed1987

Effects of local anaesthetics on short-term desensitization of guinea-pig taenia caecum to histamine.

1 Short-term desensitization to histamine was induced by incubating guinea-pig taenia caecum with 10(-4)M histamine for 30 min (desensitizing incubation) in normal Locke-Ringer solution or Ca-free Locke-Ringer solution containing 0.2 mM EGTA. This desensitization was measured as a reduction of the maximal contractile response. 2 The effects of the presence of local anaesthetics during the desensitizing incubation were examined. Results showed that tetracaine, procaine, procainamide, oxybuprocaine and lignocaine inhibited the desensitization, whereas dibucaine, benzocaine and mepivacaine did not. 3 The inhibitory effects of these drugs on the desensitization were not correlated with their lipid solubility nor with the potency of their known effects, such as membrane stabilization, Ca channel blockade, calmodulin antagonism, or inhibition of C-kinase. 4 It is concluded that the inhibitory effects of local anaesthetics on the desensitization are not due to their non-specific membrane-stabilizing effects per se, but to some other action.

Anesthetics, Local↗
PubMed1985

[Tumor markers of pancreatic cancer].

To determine the clinical usefulness for diagnosis and monitoring of pancreatic tumor markers, serum levels of CA 19-9 (RIA; less than or equal to 37U/ml), POA (EIA; less than 11 U/ml), CEA (EIA; less than or equal to 4.4 ng/ml) and TPA (RIA; less than or equal to 110 U/ml) were measured in 57 patients with pancreatic cancer and 25 patients with benign diseases of the pancreas. Frequencies of elevation for pancreatic cancers were 73.9% for CA 19-9, 69.2% for POA, 48.9% for CEA and 73.2% for TPA. Furthermore, the frequencies of elevation at relatively early stages of pancreatic cancer were not high. It was therefore thought that these markers were unsuitable for early diagnosis of pancreatic cancers. Although serum levels of CA 19-9 and POA in cases of pancreatic cancer were distributed up to on extremely high level, those for benign diseases of the pancreas were located up to twice the values of the cut-off levels. Therefore, these two markers seem promising for differentiating preoperatively between pancreatic cancer and benign diseases of the pancreas. CA 19-9 and POA were also useful for monitoring the recurrence of pancreatic cancer. In particular, patients with high preoperative levels seem good candidates for postoperative monitoring.

Antigens, Neoplasm↗
PubMed1985

[Diagnostic usefulness of serum levels of pancreatic oncofetal antigen (POA) and CA 19-9 in pancreatic cancers: monitoring of postoperative recurrences].

Serum levels of POA (EIA; less than 11.0 U/ml) and CA 19-9 (RIA; less than or equal to 37 U/ml) were measured in 54 patients with pancreatic cancer and 19 patients with benign diseases of the pancreas. Although serum CA 19-9 and POA were elevated in 72.7% and 69.4% of patients with pancreatic cancer, respectively, patients in relatively early stage showed low percent of elevation. Therefore, these markers are unsuitable for early diagnosis of pancreatic cancers. However, these markers seem promising in differentiating preoperatively between pancreatic cancer and benign disease of the pancreas. These markers are also useful for monitoring the recurrence of pancreatic cancers. Of particular, patients with preoperatively high level seem good candidates for postoperative monitoring.

Antigens, Neoplasm↗
PubMedDate not supplied

5-fluorouracil sensitivity and dihydropyrimidine dehydrogenase activity in advanced gastric cancer.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. Several studies have demonstrated the clinical importance of DPD in cancer patients, suggesting that the efficacy of 5-FU may be related to DPD activity in tumor tissue. In the present study, DPD activity and chemosensitivity to 5-FU were evaluated in advanced gastric cancer. MATERIALS AND METHODS: Thirty-four gastric cancers from 32 patients were studied and chemosensitivity to 5-FU was evaluated by histoculture drug response assay. RESULTS AND CONCLUSION: DPD activity and tumor inhibition of 5-FU among all cases showed no significant correlation, but among 14 histologically differentiated cases significant correlation was observed. DPD activity may be useful in determining the 5-FU sensitivity of differentiated gastric cancer.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Significance of para-aortic lymph node dissection in patients with advanced and recurrent gastric cancer.

Among 243 patients who underwent radical gastrectomy for advanced gastric cancer, 19 patients underwent radical gastrectomy with extended lymphadenectomy including cancer-positive para-aortic lymph nodes. Their prognosis was unexpectedly good, with a mean postoperative survival time of 24.1 months and a 2-year-survival rate of 42.4 percent. Another 4 patients developed para-aortic lymph node recurrence detected by computed tomographic scan during a follow-up examination. These 4 patients were treated with macroscopic curative dissection of the para-aortic lymph nodes. Although 2 of the 4 patients died within 6 months after re-operation, the prognosis of the other two patients was rather good when treated with active combination chemotherapy consisting of 5-fluorouracil, adriamycin and cisplatin. Dissection of para-aortic lymph nodes is considered of valuable in the treatment of advanced gastric cancer, and dissection of the para-aortic lymph node recurrence may also be valid when combined with potent chemotherapy.

Adult↗