Search PubMed⌕ Search

Biomedical subjects

Y Fujimoto

Publications and source records attributed to Y Fujimoto.

At least 541 records · Page 30Linked to original sources

Stimulation of prostaglandin E2 synthesis by exogenous phospholipase A2 and C in rabbit kidney medulla slices.

We have investigated the effects of phospholipase A2 and C on the synthesis of prostaglandin E2 in rabbit kidney medulla and the release of fatty acids from the medulla slices. Exogenous phospholipase A2 [from Naja naja (Indian cobra) venom] and phospholipase C (from Clostridium welchii) stimulated prostaglandin E2 production in a dose-dependent manner. At the maximal effective concentrations (0.5 unit of phospholipase A2/ml, 2 units of phospholipase C/ml), phospholipase C increased prostaglandin E2 formation to the level observed with phospholipase A2. Phospholipase A2 enhanced the release only of unsaturated fatty acids, whereas phospholipase C stimulated the release of individual free fatty acids (C 16:0, C 18:0, C 18:1, C 18:2 and C 20:4). Moreover, p-bromophenacyl bromide inhibited phospholipase A2-stimulated prostaglandin E2 production and the release of fatty acids, but it had no influence on prostaglandin E2 formation and the release of fatty acids increased by phospholipase C, indicating that the stimulatory effect of phospholipase C is not mediated through the activation of endogenous phospholipase A2. These results suggest the presence of diacylglycerol lipase and monoacylglycerol lipase in the kidney and the importance of this pathway in prostaglandin synthesis by the kidney.

Acetophenones↗

Caffeic acid is a selective inhibitor for leukotriene biosynthesis.

.eukotrienes are significantly involved in immunoregulation and in a variety of diseases, including asthma, inflammation and various allergic conditions. They are initially biosynthesized by 5-lipoxygenase from arachidonic acid, which can also be metabolized to prostaglandin endoperoxide by cyclooxygenase. The specific inhibitors for 5-lipoxygenase would be useful not only as tools for investigating the regulation mechanism of leukotriene biosynthesis, but also as drugs for clinical use. Although recently a few selective inhibitors have been reported, most of them are difficult to obtain, since they are new compounds. We found that caffeic acid, which is one of the most common reagents, is a selective inhibitor for 5-lipoxygenase and therefore for leukotriene biosynthesis. The inhibitory effect of its methyl ester on 5-lipoxygenase (ID50 = 4.8 X 10(-7) M) was stronger than that of caffeic acid itself (ID50 = 3.7 X 10(-6) M). Caffeic acid inhibited 5-lipoxygenase in a non-competitive manner. Caffeic acid and its methyl ester did not inhibit prostaglandin synthase activity at all, at least up to 5 X 10(-4) M, but rather stimulate at higher doses. The biosynthesis of leukotriene C4 and D4 in mouse mast tumor cells was also inhibited completely with 10(-4) caffeic acid. Besides, caffeic acid had little effect on arachidonic acid metabolism in platelet at less than 1 X 10(-5) M, but at higher doses it showed a definite inhibitory effect, i.e., thromboxane B2, HHT (12(S)-hydroxy-5,8,10-heptadecatetraenoic acid) and 12-HETE (12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid) syntheses were inhibited 33, 40 and 80% at 1 X 10(-4) M, respectively. Platelet aggregation induced by arachidonic acid was also inhibited by caffeic acid at high dose, while platelet aggregation induced by ADP is not influenced by caffeic acid at all. The observations on caffeic acid and its derivatives may contribute to leukotriene research.

Animals↗

Synthesis of phosphotriester by DCC and its biological activities.

The synthesis of a phosphotriester, an inhibitor of acetylcholinesterase, was performed by the coupling reaction of diethylphosphate with various phenolic compounds using dicyclohexylcarbodiimide (DCC). All of the compounds synthesized inhibited housefly acetylcholinesterase activity. Derivatives including an electronegative part as a nitro group in the phenol ring showed strong inhibition towards housefly acetylcholinesterase, but those with hydrophobic derivatives of the phenol group, such as cresol, naphthol and biphenol, showed relatively low inhibition. In experiments with housefly, the value of LD50 for each chemical correlated with the I50 value for acetylcholinesterase except alpha-naphthyl diethylphosphate, beta-naphthyl diethylphosphate and p,p'-biphenyl diethylphosphate.

Acetylcholinesterase↗

Purification of a membrane-bound neutral endopeptidase from rat kidney and its activation by polyamines.

An endopeptidase which cleaves succinyl trialanine p-nitroanilide (Suc(Ala)3-pNA) into succinyl dialanine and alanine p-nitroanilide (Ala-pNA) was solubilized from a microsomal membrane fraction of rat kidney with Nonidet P-40 following treatment with 1 M KCl and Brij 35. The solubilized enzyme was purified to homogeneity by DEAE-Sephadex chromatography, Sepharose CL-6B gel filtration and sucrose gradient centrifugation. The final enzyme preparation had a specific activity of 1.69 mumol/min/mg protein, representing about 140-fold purification over the starting membrane. The enzyme hydrolyzes Suc(Ala)3-pNA with a Km value of 0.28 mM and a Vmax value of 1.3 mumol/min. The molecular weight of the undenatured enzyme was estimated to be 360,000 by gel filtration on a Sepharose CL-6B column and that of the denatured enzyme to be 92,000 by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, revealing the presence of a single polypeptide chain. The enzyme was markedly activated by polyamines, producing increases in the values of both Km and Vmax. Comparatively less activation was found in the presence of some monovalent cations and Ca2+. The activation by polyamines was inversely proportional to the concentration of monovalent cations, but Ca2+ and polyamines seemed to stimulate additively.

Aminopeptidases↗

Mammalian signal peptidase: partial purification and general characterization of the signal peptidase from microsomal membranes of porcine pancreas.

Signal peptidase has been enriched extensively from microsomal membranes of porcine pancreas. Microsomal membranes were washed with 1 M KCl and Brij 35, and then solubilized with 1% Nonidet P-40. The solubilized signal peptidase was purified by DEAE-cellulose chromatography and Sepharose CL-6B filtration. Cleavage of pre-human placental lactogen with the partially purified enzyme gave the mature form, whose NH2-terminus was identified as valine. The signal peptidase is heat-labile and approximately 90% of the enzymatic activity was lost at 60 degrees C within 1 min. The pH optimum of the activity was 7 to 8. Chymostatin and o-phenanthroline at concentrations of 2.5 mM inhibited the signal peptidase activity by 62% and 30%, respectively.

Amino Acid Sequence↗

High-frequency jet ventilation for differential lung ventilation.

High-frequency jet ventilation using a jet injector located at the right mainstem bronchus was superimposed on standard mechanical ventilation to ventilate the injured lung of a patient with unilateral massive atelectasis secondary to pulmonary hemorrhage. This technique of differential ventilation markedly improved arterial oxygenation in this patient and may prove to be a simpler modality of respiratory support in patients who have respiratory failure from unilateral lung disease.

Hemorrhage↗

Inhibition of prostaglandin synthesis in rabbit kidney medulla slices by antioxidants.

The inhibitory effects of NN'-diphenyl-p-phenylenediamine (DPPD), sodium diethyldithiocarbamate (SDDC) and 2,6-di-t-butylphenol (DTBP) on the generation of medullary prostaglandin E have been compared. DPPD (1 microM) and SDDC (1 mM) failed to inhibit arachidonic acid-induced stimulation of prostaglandin E synthesis, while DTBP (1 mM) inhibited it. This suggests that DPPD and SDDC inhibit prostaglandin formation by affecting a phospholipase pathway, and the inhibition of prostaglandin generation by DTBP occurs at the cyclooxygenase step.

Animals↗

A case of calcitonin producing adenoma of the thyroid.

A thyroid tumor about 4 cm in diameter was removed from a 53-year-old female. The clinical features were those of common thyroid adenomas, such as soft, smooth-surfaced and round contour of the tumor, no calcification and no lymph node metastasis. However, microscopically, the tumor was composed of compact cell nests rather similar to paraganglioma without any follicle formation. Histochemical examination revealed its C-cell nature, such as argyrophilia and calcitonin activity, although no amyloid deposit was demonstrated. Extremely high levels of calcitonin were found in the stored serum taken pre-operatively, but serum carcinoembryonic antigen levels were within normal limits. The calcitonin level dropped to the normal range soon after the operation, indicating the absence of residual tumorous tissues. Thus, the tumor behaves as an adenoma with a C-cell nature. Interestingly enough, the benign counterpart of medullary carcinoma of the thyroid seems to be quite rare in humans, and no similar tumors have ever been reported. Variations of C-cell tumors will be discussed in relation to their production and secretion of carcinoembryonic antigen.

Adenoma↗

[Chemotherapy of urothelial cancer with vincristine, mitomycin C, bleomycin, tegafur and OK-432].

A total of 24 patients with urothelial cancer were treated with a combination chemotherapy consisting of vincristine (1 mg, i.v., day 1), bleomycin (15 mg, or peplomycin, 10 mg, i.m. day 2), mitomycin-C (4 mg, i.v. day 3), tegafur (600-750 mg, p.o., every day) and OK-432 (2-4 KE, i.m., day 1, 3, 5). This one-week course was repeated for an average of 4.6 courses. Of these cases, 13 patients with early stage treated as adjuvant chemotherapy after radical operation showed strong suppressive effects against tumor recurrence or metastasis except 3 cases. However, in advanced cancer this regimen was less effective. Therefore, we modified this regimen: VCR 2mg and PEP, 10 mg on days 2, 4 and 6. This modified regimen was given to two patients and one showed partial response and I-A according to Karnofsky's criteria. Mild side effects such as slight leukopenia, fever up, gastrointestinal symptoms or alopecia were observed. These results suggest that this regimen could be used as an adjuvant chemotherapy after radical operation of urothelial malignancy for the purpose of protecting tumor recurrence or metastasis.

Aged↗

[A new B-cell alloantigen of the rat].

The major histocompatibility complex of the rat (RTl) is composed of at least five subregions. They are RTl-A,B,C,D and E regions. RTl-A,E and RTl-B,D regions encode class I and class II alloantigens, respectively. The RTl-C region encodes antigens which are similar to class I alloantigens and they are the homologue of mouse Qa-Tla antigens. A monoclonal antibody (X81-5C9) was produced against a rat B-cell leukemia, KNL-14. The KNL-14 cells were injected to a congenic rat, WKA. 1A(ACI). Spleen cells taken from the congenic rat were hybridized with mouse myeloma cell line P3.X63.Ag8.653. The monoclonal antibody lysed over 80% of nylon wool (N. W) adherent cells of lymph nodes, 25-30% of unseparated lymph node cells and/or spleen cells, and approximately 15-20% of peripheral blood lymphocytes of WKAH strain of rats. Only a portion (30-40%) of N. W. adherent cells of the peripheral blood lymphocytes was killed. Bone marrow cells, thymus cells and N. W. nonadherent cells were not lysed by the antibody. Macrophages, fetus, thymus and kidney homogenates could absorb the reactivity, whereas RBC, epidermal cells, brain, liver, testis could not absorb the cytotoxicity. A survey for the strain distribution of the antigen disclosed positive strains such as WKAH, W/Hok, LEJ, WKA. 1J (LEJ), ALB, WKA. 1B (ALB), BUF, BN, LEW, F344, W. 1L (F344) and KYN rats. The negative strains were NIG-III, WF, WKA. 1U WF), SDJ, W. 1U (SDJ), TO, W. 1T(TO), ACI, WKA. 1A(ACI), BDIX, WKA. 1DV1 (BDIX) and PVG/c rats. Immunochemically, the antibody precipitated antigens that gave two major bands on the SDS-PAGE. The heavy chain has an apparent molecular weight of 30 KD, which shifted to 33 KD under reducing conditions. The light chain has an apparent molecular weight of 12 KD. From these data a monoclonal antibody X81-5C9 is considered to detect a rat MHC (RTl) gene product which is different from the classic class I or class II cell surface antigens. It may be one of RTl-C antigens expressed mainly on B-cells. The characteristic feature of rat RTl-C antigens were discussed in relation to mouse Qa-Tla antigens.

Animals↗

Effect of transition metal ions on lipid peroxidation of rabbit renal cortical mitochondria.

Effect of transition metal ions on lipid peroxidation in rabbit renal cortical mitochondria was studied. The lipid peroxidation of mitochondria was promoted by the metal ions tested in the following order of intensity; Fe2+, Hg2+ and Cu2+. Sodium selenite inhibited Fe2+ or Hg2+-induced lipid peroxidation, but it had no influence on the lipid peroxidation stimulated by Cu2+. This result suggests that the mechanism of the stimulatory effect on lipid peroxidation of Cu2+ may be different from that of Fe2+ or Hg2+ in mitochondria.

Animals↗

[Surgical management of primary hyperparathyroidism].

We have experienced 186 patients with proven primary hyperparathyroidism operated on during past 16 years. In this series, 147 patients (79%) had adenoma, 24 patients (12.9%) had carcinoma and only 15 (8.1%) had hyperplasia. Because of a 92% of single gland involvement, the removal of an enlarged gland is adequate, if the remaining gland are grossly normal. Besides, interestingly enough, an incidence of parathyroid carcinoma is rather high in Japan, so that surgeons should be alert to recognize the parathyroid carcinoma on the basis of clinical and operative findings. In an effort to minimize recurrence, en bloc resection of the parathyroid carcinoma is important. When a patient with parathyroid carcinoma has a local recurrence or distant metastases, an aggressive surgical approach is recommended to alleviate hypercalcemic symptoms. The majority of patients with hyperplasia belong to multiple endocrine neoplasia, type 1. Recent development of the non-invasive diagnostic methods is remarkable. The last consecutive 31 patients underwent preoperative localization study by 201Thallium (201TI-CI) scanning and ultrasonography. 201TI-CI scanning gave the most accurate results and 100% correct localization was obtained when the parathyroid tumor was more than 1 g. However, it is noteworthy that the parathyroid tumor was less than 1 g in 64% of patients who had no evidence of generalized fibrous osteitis.

Adult↗