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Biomedical subjects

M Kurihara

Publications and source records attributed to M Kurihara.

369 records · Page 21Linked to original sources
PubMedDate not supplied

Quantitative distribution of angiotensin II binding sites in rat brain by autoradiography.

Angiotensin II binding sites were localized and quantified in individual brain nuclei from single rats by incubation of tissue sections with 1 nM 125I-[Sar1]-angiotensin II, [3H]-Ultrofilm autoradiography, computerized microdensitometry and comparison with 125I-standards. High angiotensin II binding was present in the circumventricular organs (organon vasculosum laminae terminalis, organon subfornicalis and area postrema), in selected hypothalamic nuclei (nuclei suprachiasmatis, periventricularis and paraventricularis) and in the nucleus tractus olfactorii lateralis, the nucleus preopticus medianus, the dorsal motor nucleus of the vagus and the nucleus tractus solitarii. High affinity (KA from 0.3 to 1.5 X 10(9) M-1) angiotensin II binding sites were demonstrated in the organon subfornicalis, the nucleus tractus solitarii and the area postrema after incubation of consecutive sections from single rat brains with 125I-[Sar1]-angiotensin II in concentrations from 100 pM to 5 nM. These results demonstrate and characterize brain binding sites for angiotensin II of variable high affinity binding both inside and outside the blood-brain barrier.

Angiotensin II↗
PubMedDate not supplied

Autoradiographic localization and characterization of angiotensin II binding sites in the spleen of rats and mice.

Specific binding sites for angiotensin II (Ang II) were localized in the red pulp of the spleen of rats and mice by quantitative autoradiography using 125I-Sar1-Ang II as a ligand. In the rat, the binding was saturable and specific, and the rank order for Ang II derivatives as competitors of 125I-Sar1-Ang II binding correlates well with their affinity for Ang II receptors in other tissues. Kinetic analysis in the rat spleen revealed a single class of binding sites with a KD of 1.11 nM and a Bmax value of 81.6 fmol/mg protein. Ang II binding sites were also localized on isolated rat spleen cells with similar affinity but with much lower Bmax, 9.75 fmol/mg protein. Ang II receptors were not detected in thymus sections from rats or mice, or on isolated rat thymocytes. The binding sites described here might represent a functional Ang II receptor with a role in the regulation of splenic volume and blood flow and in the modulation of the lymphocyte function.

Angiotensin II↗
PubMedDate not supplied

Adrenoleukomyeloneuropathy presenting as cerebellar ataxia in a young child: a probable variant of adrenoleukodystrophy.

A child aged 5 years 7 months was diagnosed as suffering from adrenoleukomyeloneuropathy (ALMN). The first sign was ataxia, and high intensity lesions were observed in the cerebellar hemispheres on T2-weighted brain MRI. His condition progressed rapidly to a vegetative state in 1 year. When aged 7 years 3 months adrenal insufficiency supervened and his skin turned dark. Rectal biopsy revealed linear cytoplasmic inclusions in macrophages in the rectal membrane. At the age of 8 years 2 months, an analysis of very long-chain fatty acids of sphingomycin in plasma led to the final diagnosis. At the age of 10 years, cerebellar and cerebral atrophy were prominent and diffuse high intensity lesions were noted in the cerebellum and cerebrum. An onset below 9 years of age has not previously been documented in ALMN.

Adrenoleukodystrophy↗
PubMedDate not supplied

Binding of angiotensin and atrial natriuretic peptide in brain of hypertensive rats.

Atrial natriuretic peptides, produced in the mammalian cardiac atrium, are released into the general circulation and may be actively involved in the control of blood pressure and in fluid homeostasis as antagonists of the peripheral angiotensin system. Certain cardiovascular effects of atrial natriuretic peptides may be centrally mediated, as binding sites for atrial natriuretic factor (8-33) (ANF) have been localized to the subfornical organ. This circumventricular structure lacks a blood-brain barrier and is therefore accessible to circulating peptides. It contains large numbers of angiotensin II (AII) binding sites, and has been suggested as the main central site of action for circulating AII in the regulation of blood pressure and fluid metabolism. Here we have studied binding sites for rat atrial natriuretic peptide(6-33) (rANP) and AII in the brains of spontaneously (genetic) hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto (WKY) rats, by quantitative autoradiography. Binding sites for both peptides were highly localized in the subfornical organ. The number of rANP binding sites was decreased in the subfornical organ of both young (4 weeks old) and adult (14 weeks old) SHR compared with age-matched normotensive controls. Conversely, the number of AII binding sites was higher in both young and adult SHR compared with WKY rats. Our results suggest a central role for rANP and AII in genetic hypertension; they may act as mutual antagonists in brain areas involved in control of blood pressure and fluid regulation.

Age Factors↗
PubMedDate not supplied

Pilot study of combined treatment with continuous infusion of 5-fluorouracil, mitomycin C, and cisplatin (FMP) in patients with inoperable advanced gastric cancer.

We investigated combined chemotherapy with 5-fluorouracil (600 mg/m2/day, day 1-5, c.i.v.), mitomycin-C (6 mg/m2, day 6), and cisplatin (60 mg/m2, day 7) for inoperable advanced gastric cancer, including those with poor performance status (PS). Overall response rates were 62.5% (20/32), 59.1% (12/22) for PS 0-2 and 70.0% (7/10) for PS 3-4. Median survival was 7.2 months, 8.7 for PS 0-2; and 6.3 for PS 3-4. There was no serious toxicity or any treatment-related death. This therapy is useful, even for poor PS.

Adult↗
PubMedDate not supplied

Phase 1/11 study of bi-weekly irinotecan plus cisplatin in the treatment of advanced gastric cancer.

OBJECTIVES: To conduct a phase I/II study of irinotecan with cisplatin to establish a recommended dose, and assess the safety, efficacy and feasibility of this regimen in unresectable advanced or recurrent gastric cancer. PATIENTS AND METHODS: In the phase I portion of the study, patients received a fixed dose of cisplatin (30 mg/m2) with escalating doses of irinotecan, ranging from 30 mg/m2 to 70 mg/m2, on days 1 and 15. In the phase II portion of the study, 40 patients were evaluated for response and safety at the recommended dose. RESULTS: Eighteen patients were enrolled in the phase I study. Dose-limiting toxicity (diarrhea and neutropenia) appeared at the irinotecan dose of 70 mg/m2. Therefore, the recommended irinotecan dose was 60 mg/m2. In the phase II study, 40 patients received cisplatin (30 mg/m2) plus irinotecan (60 mg/m2). Twenty-five out of 40 patients had received prior chemotherapy. The median number of cycles was 3.5. The response rate was 32.5% (13/40) overall, and 53.3% (8/15) in patients without prior chemotherapy. The median time to tumor progression (TTP) was 162 days. The median survival time was 288 days. Four patients (10%) developed grade 4 neutropenia and 3 patients (7.5%) developed grade 4 anemia. The only observed non-hematological toxicity at grade 3 or higher was diarrhea, seen in 2.5% (1/40) of the patients. CONCLUSION: Bi-weekly administration of irinotecan and cisplatin is safe and active for the management of unresectable advanced or recurrent gastric cancer.

Adult↗
PubMedDate not supplied

Effect of combination therapy with UFT plus cisplatin (UFTP) on the survival of mice in the experimental model for wide-spread metastasis in the peritoneal cavity of gastrointestinal cancer using colon 26 PMF-15 cells.

The prognosis of unresectable advanced gastric cancer patients, especially with wide-spread metastasis in the peritoneal cavity, is very poor. In such cases, only a few treatment methods are available, and chemotherapy as a systemic therapy is often selected. We recently devised an experimental model for wide-spread metastasis in the peritoneal cavity of gastrointestinal cancer, by intraperitoneally implanting colon 26 murine carcinoma PMF-15 cells. When the control mice were autopsied, a number of tumor nodules were formed in their mesenterium, pancreas, liver, etc. and pools of ascites were also occasionally seen. Using this model, oral UFT (combining tegafur and uracil at a molar ratio of 1:4) plus cisplatin (UFTP regimen) prolonged the survival of mice and maintained these mice in relatively better condition than with continuous infusion of 5-fluorouracil plus cisplatin (FP regimen). Since UFT can be used orally, patients receiving UFTP therapy are not required to stay in a hospital for long periods, but rather, are intermittently hospitalized for short periods of time. Better QOL and prolonged survival highlight the potential clinical usefulness of the UFTP therapy.

Animals↗