[Comparison of quantitative regional myocardial blood flow in patients with ischemic heart disease using dynamic positron emission tomography with coronary arterial regions].
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Biomedical subjects
Publications and source records attributed to Y Ono.
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Subcutaneous injection of N2-[N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a synthetic muramyl dipeptide derivative, favoured recovery of mice from experimental leukopenia induced by cyclophosphamide or by irradiation with X-rays. These effects were observed only when MDP-Lys(L18) treatment occurred after cyclophosphamide injection or X-ray irradiation. Prophylactic treatment resulted in neither preventive nor restorative efficacy on leukopenia. In contrast, glutathione was hardly effective on leukopenia in both models, irrespective of treatment timing. The restorative efficacy of muroctasin was found to be dose-dependent and to be attributable at least to its augmenting effect on colony-stimulating factor production, followed by the marked proliferation and differentiation of myeloblasts towards mature granulocytes in the bone marrow. These beneficial effects of MDP-Lys(L18) warrant further evaluation of its clinical usefulness.
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Three types of cDNA clone of the protein kinase C family termed delta, epsilon and zeta were newly identified by molecular cloning and sequence analysis. These members have a common structure that is closely related to, but clearly different from the other four known members of the family which have alpha-, beta I-, beta II- and gamma-sequences, although the zeta-cDNA available at present does not contain a complete reading frame for a protein kinase C molecule. The diverse heterogeneity of the enzyme seems to be an important factor in determining the mode of response of many tissues and cell types to a variety of external stimuli.
Elucidation of the complete sequences of four cDNA clones (alpha, beta I, beta II, and gamma) of the rat brain protein kinase C family has revealed their common structure composed of a single polypeptide chain with four constant (C1-C4) and five variable (V1-V5) regions. Although these sequences are highly homologous and closely related to one another V3-, V4-, and V5-regions of gamma-subspecies are slightly bigger than the corresponding regions of the other three subspecies. The first constant region, C1, contains a tandem repeat of cysteine-rich sequence (6, total 12 cysteine residues). The third constant region, C3, has an ATP-binding sequence which is found in many protein kinases. In adult rat whole brain, the relative activities of alpha-, beta I-, beta II-, and gamma-subspecies are roughly 16, 8, 55, and 21%, respectively. gamma-Subspecies is expressed after birth apparently only in the central nervous tissue, implying its role in the regulation of specific neuronal functions.
Complementary DNA (cDNA) clones encoding the regulatory subunit of the type I cAMP-dependent protein kinase (R-I) were isolated by screening of rat brain cDNA libraries. A 1.5-kilobase (kb) cDNA insert containing the entire coding region was sequenced and full amino acid sequence has been deduced from the nucleotide sequence. The clone encodes for a protein of 380 amino acids that shows 97% homology to the bovine R-I subunit. Northern blot analysis demonstrated two major mRNA species (2.8 and 4.4 kb in size) in rat brain and liver.
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Rat brain protein kinase C purified to apparent homogeneity [(1986) Biochem. Biophys. Res. Commun. 135, 636-643] was resolved into three distinct fractions, type I, II and III, upon chromatography on a hydroxyapatite column connected to high-performance liquid chromatography. Comparison of each fraction with the four subspecies of protein kinase C, that were separately expressed in COS cells transfected by the respective cDNAs, alpha, beta I, beta II and d gamma, identified the primary structures of these three fractions of protein kinase C. Type I corresponded to the enzyme encoded by the gamma-sequence; type II was a mixture of the two subspecies determined by the beta I- and beta II-sequences; and type III had the structure encoded by the alpha-sequence. The structures and properties of these subspecies of protein kinase C were similar to each other.
Two complementary DNA's, encoding the complete sequences of 671 and 673 amino acids for subspecies of rat brain protein kinase C, were expressed in COS 7 cells. The complementary DNA sequence analysis predicted that the two enzymes are derived from different ways of splicing and differ from each other only in the short ranges of their carboxyl-terminal regions. Both enzymes showed typical characteristics of protein kinase C that responded to Ca2+, phospholipid, and diacylglycerol. The enzymes showed practically identical physical and kinetic properties and were indistinguishable from one of the several subspecies of protein kinase C that occurs in rat brain but not in untransfected COS 7 cells. Partial analysis of the genomic structure confirmed that these two subspecies of protein kinase C resulted indeed from alternative splicing of a single gene.
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A possible involvement of oxytocin (OT) has been indicated in regulation of water and electrolyte metabolism, based on findings that the secretion of OT is increased by either water deprivation or sodium loading. However, to date, no informations have yet been obtained about the role of OT in hypertension. The present study was therefore undertaken to elucidate the role of OT for abnormalities of fluid and electrolyte metabolism in essential hypertension (EH) in comparison with normotensive subjects (NT). The major results were as follows. Plasma level of OT was 3.7 +/- 2.1 pg/ml (mean +/- SD) in EH, not significantly higher than that in NT (3.2 +/- 1.7 pg/ml). Plasma OT in low-renin EH (4.8 +/- 2.5 pg/ml) was significantly different from that in high-renin EH (2.9 +/- 1.4 pg/ml, p less than 0.05) and NT (p less than 0.05), but not in normal-renin EH (3.8 +/- 2.0 pg/ml). Plasma OT was inversely correlated with plasma renin activity (PRA) in EH (r = -0.384, p less than 0.01), but not in NT (r = 0.102). No significant correlation was found between plasma OT and plasma aldosterone concentration (PAC), plasma concentration of antidiuretic hormone (ADH), serum sodium and potassium, blood pressure and renal function in either EH or NT. I.m. injection of OT (0.04 IU/kg) increased significantly urinary excretions of sodium and potassium in EH and NT. However, the increment in sodium excretion was greater in low-renin EH than that in normal-renin EH (0.05 less than p less than 0.10), high-renin EH (p less than 0.05) and NT (p less than 0.05). PRA, PAC and ADH were significantly decreased after OT injection, but blood pressure, serum sodium and potassium were not altered in both EH and NT. I.v. administration of OT (0.1 approximately 0.2 IU/min) suppressed angiotensin II-induced increase of PAC and elevation of blood pressure in both EH and NT. The decrease in PAC by the OT administration was the greatest in low-renin EH. The reduction of blood pressure was significantly greater in EH than in NT (p less than 0.05). I.v. administration of hypertonic saline (5%) resulted in a significant increase of plasma OT in EH and NT, and the increment in OT was the greatest in low-renin EH. Serum sodium concentration was increased by the infusion, positively correlated with plasma OT in both EH (r = 0.458, p less than 0.05) and NT (r = 0.830, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
Human lymphocytes derived from regional lymph nodes adjacent to the primary gastric cancer were transformed with Epstein-Barr virus (EBV) to establish lymphoblastoid cell lines secreting human antibodies reactive with cell surface antigens expressed on the gastric cancer cells. The EBV transformation technique was applied to lymph node lymphocytes obtained from 4 gastric cancer patients. As a result of mass screening with the radioactive cell binding assay for the production of anti-gastric cancer related antibodies, one culture (TGc-106) among 1,400 microcultures was identified to secrete human antibody specifically reactive with an established human gastric cancer cell line as target (MKN-45). Furthermore, it was demonstrated with the autologous assay system by the histoimmunofluorescence method that cell surface antigens of autologous gastric cancer cells could be clearly defined with human antibody from one culture (TEb-079) out of 470 microcultures established from a gastric cancer patient (GCP-26); there was no reactivity against the surrounding normal cells constructing the gastric wall. The immunoglobulin class of the human antibodies produced both in TGc-106 and TEb-079 was determined from immunodiffusion tests to be IgM.
A prospective chemotherapeutic trial using combinations of three drugs consisting of three different protocols was performed in 24 patients with advanced transitional-cell carcinoma of the urothelial tract between April 1981 and August 1986. All patients had histologically proven transitional-cell carcinoma and bidimensionally measurable lesions. The protocol I (PPA) was a 5-day course of treatment with 20 mg/m2 cis-platinum and 5 mg/m2 peplomycin (a derivative of bleomycin) on days 1-5, and 25 mg/m2 adriamycin on day 1. Protocol II (CFMit) was a 10-day course with 3 mg/m2 mitomycin-C and 300 mg/m2 cyclophosphamide on day 1, and 180 mg/m2 5-fluorouracil on days 1-10. Protocol III (PAM) was a 1-day course comprising 60 mg/m2 cis-platinum, 30 mg/m2 adriamycin, and 40 mg/m2 methotrexate. In protocols I and III, the drugs were administered every 4-5 weeks, while in protocol II, the drugs were administered continuously without any interval. Of the 9 patients who received 1 to 5 PPA courses, only 3 patients showed a minor response. In the 10 patients who received 4 to 44 CFMit courses, 3 (33%) achieved partial remission for 1.5-22 months, and 3 had a minor response. Of the 5 patients receiving 3 to 7 PAM courses, 1 patient achieved partial remission for 5 months, and 1 had a minor response. Myelosuppression, nausea, vomiting, and anorexia were frequently observed in each protocol. Loss of hair was often observed in protocols I and III. Stomatitis and diarrhea were observed in protocol II. Three patients in protocol I, 4 patients in protocol II, and 1 patient in protocol III were unable to tolerate more courses of the regimen due to the severe side effects.