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Biomedical subjects

M Kurihara

Publications and source records attributed to M Kurihara.

At least 253 records · Page 14Linked to original sources

Lower number of atrial natriuretic peptide receptors in thymocytes and spleen cells of spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) have a much lower number of atrial natriuretic peptide (ANP) receptors in thymus and spleen from young and adult animals than age-matched normotensive controls. In spite of this low receptor concentration, the ANP-stimulated cyclic GMP response in isolated thymocytes and spleen cells from SHR was similar to that of normotensive control rats. Alterations in ANP receptor concentration in thymus and spleen of SHR may be related to the immune abnormalities described in these animals, and to the pathophysiology of genetic hypertension.

Animals↗

Chromosome abnormalities in malignant lymphoma in patients from Saitama.

Clonal chromosome abnormalities were found in 89 (97%) of 92 patients with non-Hodgkin's malignant lymphoma including immunologically determined 34 B- and 25 T-lymphomas; only 3 of 19 T-lymphoma patients examined had serum adult T-cell leukemia/lymphoma-associated antigen antibody. Association of 8q24 translocations with small non-cleaved cell (P less than 0.01) and that of t(14;18) (q32;q21) with follicular histology (P = 0.03) were significant. Several other abnormalities were also found to be correlated with histological or immunological phenotypes: trisomy 5 with diffuse, mixed cell lymphoma (P = 0.03); a break at 3q21 with diffuse, large cell lymphoma (P = 0.04); gain of chromosome 18 or X and rearrangements of 13q with immunoblastic lymphoma (P = 0.02, 0.03, and 0.03, respectively); and rearrangements of 7q with diffuse large cell histology (P = 0.02) and T-cell phenotype (P = 0.02). Multiple clones were more frequently seen in T-cell lymphoma than in B-cell lymphoma (P = 0.01). Structural changes of the long arm of chromosome 4 or 15 and a break in 6p21 were also associated with T-lymphoma (P = 0.03, respectively). Since the frequency of T-lymphoma is significantly higher and that of t(14;18) is significantly lower in the adult T-cell leukemia/lymphoma nonendemic area of Saitama in Japan than in Minnesota in the United States (P less than 0.01), factors affecting the lymphoma-genesis may be different or operating in different intensities in different areas.

Adolescent↗

Atrial natriuretic peptide receptors in sympathetic ganglia: biochemical response and alterations in genetically hypertensive rats.

High concentration of atrial natriuretic peptide (99-126) (ANP) receptors were localized by quantitative autoradiography in superior cervical and stellate ganglia from young and adult Wistar Kyoto (WKY) rats. ANP increased cyclic GMP formation in stellate ganglia from adult rats. Both young and adult spontaneously hypertensive rats (SHR) had a much lower number of ANP receptors in the sympathetic ganglia. In spite of low receptor concentration, the cyclic GMP response to ANP in SHR was unchanged. These results suggest the existence of physiologically active ANP receptors in the rat sympathetic ganglia. These receptors may also be involved in the pathophysiology of spontaneous hypertension.

Animals↗

Specific angiotensin II binding sites in the rat stellate and superior cervical ganglia.

Angiotensin II binding sites were localized and quantified in rat stellate and superior cervical ganglia by quantitative autoradiography using 125I-Sar1-angiotensin II as a ligand. Both ganglia possess a single class of angiotensin II binding sites. High concentrations of binding sites were localized in the areas rich in principal ganglion cells. These binding sites might mediate the facilitatory action of angiotensin II on the ganglionic transmission.

Angiotensin II↗

Atrial natriuretic peptide, ANP(99-126), receptors in rat thymocytes and spleen cells.

A single class of saturable, specific binding sites for the circulating form of atrial natriuretic peptides, ANP(99-126), was identified in rat thymus and spleen and in isolated thymocytes and spleen cells using quantitative autoradiographic techniques. In the thymus, the relative potency of ANP analogs to inhibit [125I] ANP(99-126) binding was ANP(99-126) = ANP(103-126) greater than ANP(111-126) greater than ANP(103-125). ANP(103-123) could not displace [125I]ANP(99-126) binding. Addition of ANP(99-126) stimulated the formation of cyclic GMP in isolated thymocytes and spleen cells in a dose-dependent manner. Our results indicate that immune cells have specific ANP receptors which could be coupled to guanylate cyclase activation and may play a role in the regulation of the immune response.

Animals↗

Localization and characterization of atrial natriuretic peptide binding sites in discrete areas of rat brain and pituitary gland by quantitative autoradiography.

Atrial natriuretic peptide [rat (r) ANP6-33 or ANP99-126] binding sites were localized in discrete areas of rat brain and pituitary gland using quantitative autoradiographic techniques. High numbers of rANP6-33 binding sites were concentrated in the circumventricular organs (the organon vasculosum laminae terminalis, organon subfornicalis, and area postrema) and selected hypothalamic nuclei (the nucleus supraopticus, nucleus preopticus medianus and nucleus paraventricularis). High binding was also present in the choroid plexus and the bulbi olfactorii (laminae medullaris interna). A relatively low number of rANP6-33 binding sites was observed in other olfactory, limbic and brainstem areas (the nucleus tractus solitarii, nucleus motoris dorsalis vagii and nucleus hypoglossi), the eminentia mediana and the pituitary gland (anterior and posterior lobes). High-affinity rANP6-33 binding sites were demonstrated in the organon subfornicalis and the area postrema after incubation of consecutive sections from individual rat brains with 125I-rANP6-33 in concentrations from 20 to 400 pM. rANP6-33 binding sites were concentrated in areas associated with angiotensin II and/or vasopressin, suggesting an interaction among these peptides in the central nervous system.

Animals↗

Localization of angiotensin II receptors along the anteroventral third ventricle area of the rat brain.

Autoradiographic techniques were utilized to localize and to quantify angiotensin II (ANG) binding sites in rat forebrain. Specific, localized ANG binding sites were demonstrated in midline sagittal sections, corresponding to the entire anteroventral third ventricle (AV3V) area, including the nucleus preopticus medianus and the subependymal area of the anterior third ventricle from the nucleus preopticus medianus to the organon vasculosum laminae terminalis. A continuous band of ANG receptors extended dorsally from the nucleus preopticus medianus along the subependymal area of the third ventricle to the organon subfornicalis. Scatchard analysis performed with consecutive sections from single animals revealed a single class of high-affinity ANG receptors in both the organon subfornicalis and the organon vasculosum laminae terminalis. In addition, ANG receptors were localized in areas anatomically and physiologically related to the AV3V area, including the nuclei paraventricularis and periventricularis and the eminentia mediana. These results support the idea that ANG may act as both a hormone and a neurotransmitter in the central regulation of fluid balance and cardiovascular function, and suggest that the circumventricular organs are the most likely sites for an interaction between the peripheral and central ANG systems.

Angiotensin II↗

Alterations in substance P binding in brain nuclei of spontaneously hypertensive rats.

Substance P binding sites were characterized in brain nuclei of young (4-wk-old) and adult (16-wk-old) spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats by quantitative autoradiography. Young SHR presented higher affinity constants (KA) than young WKY. The changes were restricted to the locus coeruleus, the area postrema, the dorsal motor nucleus of the vagus, and to discrete areas located in lobes 9 and 10 of the vermis cerebelli of SHR. There were no differences in the maximal binding capacity (Bmax) except in the nucleus ambiguus where the Bmax was lower than in WKY. Conversely, the number of substance P binding sites was higher in the locus coeruleus, the nucleus tegmentalis dorsalis, the nucleus ambiguus, the dorsal motor nucleus of the vagus, the hypoglossal nucleus, the inferior olivary nucleus, and lobes 9 and 10 of the vermis cerebelli of adult SHR when compared with adult WKY. Our results support the hypothesis of a role for brain substance P in blood pressure regulation and in genetic hypertension in rats.

Aging↗

Increased atrial natriuretic peptide binding sites in the rat subfornical organ after water deprivation.

Binding sites for rat atrial natriuretic peptide (99-126) were localized and quantified in the subfornical organ and choroid plexus of control and water-deprived rats. Brain sections were analyzed after incubation with 125I-rat atrial natriuretic peptide (99-126), autoradiography, computerized microdensitometry and comparison to 125I-standards. Higher numbers of atrial natriuretic peptide binding sites were present in both the subfornical organ and the choroid plexus after 4 days of water deprivation. Our results indicate a central role for atrial natriuretic peptide in the regulation of water balance.

Animals↗

[Randomized comparison of continuous and intermittent oral administration of 5'-deoxy-5-fluorouridine in the treatment of advanced gastric cancer; a phase II trial by the Multi-institutional Cooperative Study Group].

To investigate the optimal dosage schedule for 5'-deoxy-5-fluorouridine (5'-DFUR), a randomized comparative study was performed in patients with inoperable or advanced gastric cancer. Eight hundred mg/m2/day of 5'-DFUR was administered in the continuous administration group, while in the intermittent administration group 1,400 mg/m2/day was given for 4 days followed by 3 days with no medication in a one-week cycle, making the total dose 5,600 mg/m2/week in both regimens. In both groups, 5'-DFUR was administered for more than 4 weeks. Overall response rate was 14.3% (3/21) for both administration methods. The response rate for the primary site was 9.5% (2/21) in the continuous administration group, and 14.3% (3/21) in the intermittent group. As to toxicity, the incidence of diarrhea was 26.7% in the continuous group and 4.2% in the intermittent group. Although there was no significant difference between these two dosage schedules in efficacy and toxicity, the lower incidence of diarrhea suggested the clinical usefulness of the intermittent administration method. This result emphasized the need to further studies to investigate the most appropriate dosage schedule for fluorinated pyrimidine derivatives.

Administration, Oral↗

[UFT therapy of experimental gastric cancer in beagles induced by ENNG].

Therapeutic effects and dynamics of UFT were studied using beagles with ENNG-induced gastric cancers. Nine canine subjects confirmed to have gastric cancers by punch biopsy under gastrofiberscopy were divided into 3 group given 5 mg/kg/day of UFT for 101 days, 7.5 mg/kg/day for 67 days and 12 mg/kg/day for 45 days, respectively. Although the extent of macroscopic change revealed by gastrofiberscopy was minor, one of the dogs in the third group did show a Grade II b effect according to the criteria of Histopathological Effects on Cancer Tissues by Chemotherapy proposed by Oboshi and Shimozato. Animals were sacrificed by bleeding 4 hours after the last administration of anticancer agent and concentration of 5-FU and tegafur in the serum and each organ were determined. It was recognized that the concentration of anticancer agent in gastric cancer tissue was higher than that in neighboring normal gastric tissue.

Animals↗

[FO-152].

5'-O-(L-valyl)-5-fluorouridine hydrochloride (FO-152) is a derivative of 5-fluorouridine. In preclinical studies, FO-152 has demonstrated more favorable antitumor effect with greater therapeutic index compared with the parent compound, 5-fluorouridine. A phase I study was performed in 38 cases with advanced cancer. Myelosuppression was dose limiting, with leukopenia more pronounced than thrombocytopenia. Other side effects included mild hot feeling of the body during infusion and slight G.I. toxicities. Clinical responses were seen in patients with adenocarcinoma of the stomach, lung, etc. FO-152 has major advantages over 5-fluorouridine in terms of reduced toxicity. The recommended phase II dose for patients with solid tumors is 250 mg/m2 X 1, or 35 mg/m2 X 5 consecutive days with a 4-week rest, provided there is reversal of drug related myelosuppression.

Absorption↗

[Clinical evaluation on the usefulness and safety of norfloxacin in a twice-a-day regimen against upper respiratory tract infections].

Sixty-six patients with tonsillitis or pharyngolaryngitis received oral norfloxacin (NFLX) 200 mg b.i.d. or 300 mg b.i.d. for not less than 3 days in general at School of Medicine, Yokohama City University, and 6 related hospitals. The results are summarized as follows: 1. Ten patients were excluded from the study because 4 patients did not present at the follow-up visits, 4 patients did not follow the protocol and 2 patients had unclear infections. Thus, 56 patients were evaluated. 2. The fifty-six evaluable patients were classified as follows: Twenty patients were with tonsillitis and 36 were with pharyngolaryngitis. Thirty-eight patients were treated with 200 mg b.i.d. while 18 patients received 300 mg b.i.d. Thirty-two patients were male and 24 patients were female. Three patients were inpatients and 53 patients were outpatients. Most of patients were light or moderate cases, and the 26 patients had mild underlying disorders. 3. Clinical improvements were observed in 11 of 15 patients (73.3%) with tonsillitis and 25 of 30 patients (83.3%) with pharyngolaryngitis (80.0% overall) within 7 days administration. 4. Clinical improvements were observed in 15 of all 20 patients (75.0%) with tonsillitis and 30 of all 36 patients (83.3%) with pharyngolaryngitis (80.4% overall). 5. Bacteriologically, "eradication", "decrease" and "replacement" were observed in 6, 2 and 1 patients, respectively. 6. As for adverse effects, nausea and headache were observed in 1 patient and abnormal changes in laboratory findings were noted in 1 patient (slight elevations of GOT and GPT). 7. Oral NFLX 200 mg b.i.d. or 300 mg b.i.d. was as almost equally effective as 200 mg t.i.d. in tonsillitis or pharyngolaryngitis. Thus NFLX 200 mg b.i.d. or 300 mg b.i.d. appears to give sufficient clinical efficiency. 8. When antibacterial activity and serum half-life of NFLX are considered, twice daily administration was confirmed to be sufficiently effective in the clinical application.

Adolescent↗

Specific substance P binding sites in rat thymus and spleen: in vitro autoradiographic study.

Substance P binding sites were localized in rat thymus and spleen by incubation of tissue sections with [125I]Bolton-Hunter substance P, [3H]Ultrofilm autoradiography with image analysis coupled to computerized microdensitometry and comparison with 125I standards. The tissue localization of the binding sites was determined with emulsion autoradiography. A single type of specific, saturable, high affinity binding sites was found associated with the vasculature in the medulla of the thymus and the marginal sinus of the spleen, with a Kd of 0.10 and 0.14 nM, respectively. Of all the unlabeled tachykinins tested (substance P, physalaemin, substance K, eledoisin, kassinin, and neuromedin K) substance P was the most potent inhibitor of [125I]Bolton-Hunter substance P binding, with an IC50 of approximately 0.5 nM, indicating the presence of substance P-P binding sites. Our results support the hypothesis of a role for substance P in the modulation of the immune system.

Animals↗