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Biomedical subjects

S Yano

Publications and source records attributed to S Yano.

At least 469 records · Page 26Linked to original sources

[Clinical studies of intermittent hepatic arterial occlusion with infusion chemotherapy for unresectable hepatocellular carcinoma associated with arterioportal or arteriovenous shunts].

Intermittent hepatic artery occlusion combined with infusion chemotherapy is a newly devised methodology. A double lumen balloon catheter was surgically inserted into the hepatic artery. Through the catheter, fluorouracil (5-Fu) was continuously infused and mitomycin (MMC) or adriamycin (ADM) was injected in one-shot at the time of blood flow occlusion. This new methodology was performed in 19 patients who had unresectable hepatocellular carcinoma. Although five of 19 cases had arterioportal (A-P) or arteriovenous (A-V) shunts, four of them also responded well and objective anti-tumor effects resulted. In addition, complications associated with A-P or A-V shunts such as bleeding from the digestive tract due to portal hypertension were well managed by this new methodology.

Aged↗

Persistent hyperkalaemia in vitamin B12 unresponsive methylmalonic acidaemia.

Persistent hyperkalaemia was found in a patient with vitamin B12 unresponsive methylmalonic acidaemia associated with hyperuricaemia. At 3 years and 8 months of age, a serum potassium level of 6.8 mmol L-1 was found when blood gas measurement was normal. One year later azotaemia was noted. At the age of 5 years, renal function studies disclosed hyperaldosteronism, decreased creatinine clearance, reduction of the reabsorption of sodium at distal diluting segments and inadequate concentration of urine at the collecting ducts. The reduction of the reabsorption of sodium, which may have resulted in decreased potassium excretion, and the decrease in glomerular filtration rate, together with the superimposed excess intake of potassium, appeared to be responsible for the hyperkalaemia. Dietary potassium restriction was effective in suppressing the hyperkalaemia.

Child↗

Effect of eicosapentaenoic acid ethyl ester on proteinuria of streptozotocin-induced diabetes mellitus in rats.

Streptozotocin (45 mg/kg) was intravenously administered to 7-week-old Wistar rats through their tail veins. After 11 days, the rats were divided into two groups. One group was fed a lipid-free diet (90%, w/w) plus lard (8%) and safflower oil (2%) for four weeks (Diet 1 group, n = 12). The other group was fed in the same way, except that safflower oil was replaced by 90% pure eicosapentaenoic acid (EPA) ethyl ester (Diet 2 group, n = 13). Twenty-four-hour urine was collected just before the diets started and during the experiment at 7-day intervals. In the second and third week, the levels of proteinuria were significantly lower in the Diet 2 group than they were in the Diet 1 group. There was no significant difference in the levels of creatinine, urea nitrogen, or lipids in plasma or in body weights between the two groups after four weeks on the diets. Because Diet 2 reduced proteinuria of diabetic rats compared to Diet 1, an EPA-rich diet may retard the development of diabetic nephropathy.

Animals↗

Urinary excretion of PGI2/3-M and recent N-6/3 fatty acid intake.

Epidemiological studies were performed in a Japanese fishing village when catches of fish were highest and in a Japanese farming village with usual fish consumption. Intake of eicosapentaenoic, docosahexaenoic and also arachidonic acid were significantly higher in the fishing village during the 3 days of the study than in the farming village. The correlation between eicosapentaenoic acid intake on the day when urine was collected and excretion of delta 17-2,3-dinor-6-keto-prostaglandin F1 alpha, the main urinary metabolite of prostaglandin I3, was highly significant, whereas there was no correlation between arachidonic or linoleic acid intake and excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha, the main urinary metabolite of prostaglandin I2. We suggest that the arachidonic acid pool for prostaglandin I2 production is not quickly influenced by dietary linoleic or arachidonic acid because of a large pool size of arachidonic acid and a slow conversion of linoleic acid to arachidonic acid, while prostaglandin I3 formation is directly related to the intake of eicosapentaenoic acid.

6-Ketoprostaglandin F1 alpha↗

Molecular cloning and characterization of MACIF, an inhibitor of membrane channel formation of complement.

Human erythrocytes contain a membrane protein, MACIF, which inhibits the formation of a membrane attack complex (MAC) of complement. We have cloned and sequenced the complementary DNA of MACIF messenger RNA. The amino acid sequence predicted from its nucleotide sequence consists of 128 amino acids. The amino-terminal 25 residues may correspond to a signal peptide. The carboxy-terminal sequence confirmed that MACIF is a glycosylphosphatidylinositol (GPI)-anchored protein. The amino acid sequence of MACIF was partially determined by established techniques for protein chemistry and the resultant sequence was consistent with that predicted from the nucleotide sequence. The results of sequence analyses also suggested that asparagine at the 18th position was N-glycosylated. When mRNA obtained from the MACIF cDNA clone with SP6 RNA polymerase was microinjected into Xenopus oocytes, the oocytes synthesized a product which exhibited MACIF activity and reacted with anti-MACIF antibody. Comparison of the predicted sequence revealed significant homology with mouse Ly-6 antigens.

Amino Acid Sequence↗

Morphological localization of a major lysosomal membrane glycoprotein in the endocytic membrane system.

We have raised specific polyclonal immunoglobulin G (IgG) against a major lysosomal membrane sialoglycoprotein (LGP107) taken from rat liver and have prepared a conjugate of its Fab' fragment with horseradish peroxidase (HRP-anti LGP107 Fab') as a probe for the subcellular antigen. Electron immunocytochemistry in primary cultured rat hepatocytes showed that LGP107 resided primarily within lysosomes and was associated with luminal amorphous materials as well as limiting membranes. In addition, LGP107 was shown to be substantially distributed throughout the endocytic vacuolar system. The glycoprotein was found clustered in coated pits at the cell surface and localized along the surrounding membranes in endocytic vesicles. When cultured cells were exposed to HRP-anti LGP107 Fab', the antibody which was bound to its antigen within the coated pits was internalized via a system of endocytic vesicles and transported to lysosomes. During 20 min of incubation at 37 degrees C, the HRP tracer appeared at an early stage in small vesicles and moved progressively to larger vesicles, including multivesicular bodies. After 1 h, the tracer could be clearly seen in lysosomes heterogeneous in shape and size. The existence of LGP107 in endocytic compartments and the uptake of anti LGP107 antibody by hepatocytes were not blocked by prior treatment of the cells with cycloheximide and excess amounts of anti LGP107 IgG. These data suggest that LGP107 circulates between the cell surface and lysosomes through the endocytic membrane traffic in hepatocytes.

Animals↗

Biochemical analysis of the movement of a major lysosomal membrane glycoprotein in the endocytic membrane system.

HRP-anti LGP107Fab' and 125I-anti LGP107IgG were used as probes to study the movement of LGP107 in the endocytic membrane transport system in primary cultured hepatocytes of rats. Following the addition of HRP-anti LGP107Fab' to the culture medium, the transfer of the antibody conjugate from the cell surface of lysosomes was examined by cell fractionation on Percoll density gradients. The HRP tracer showed a bimodal subcellular distribution, in plasma membrane and lysosomal fractions. The amount of HRP found in the lysosomal fractions became larger as the period of cell incubation was increased. The rate of HRP accumulation in lysosomes was 0.13% of the administered load per hour per 10(6) cells. When cells were given 125I-anti LGP107 IgG, the antibody was not stored but was rapidly degraded in the lysosomes. The uptake of 125I-IgG by the cells, which was assessed by measuring the TCA-soluble radiolabeled degradation products released into the medium, increased proportionally to the administered concentration of the antibody and to the incubation time. The rate of uptake of the polyvalent 125I-IgG was comparable to that for the uptake of the monovalent HRP-Fab', and remained unchanged even after long exposure of the cells to a saturating concentration of the polyvalent IgG. This uptake process continued for many hours in the cells exposed to the protein synthesis inhibitor, cycloheximide. These results suggest that there is a continuous circulation of LGP107 between the cell surface and lysosomes in hepatocytes.

Animals↗

Favorable effects of fish oil concentrate on risk factors for thrombosis in renal allograft recipients.

The incidence of thromboembolic complications in renal allograft recipients is very high. Since fish oil has antithrombotic properties, we administered 18 capsules of fish oil concentrate (1.5 g of eicosapentaenoic acid, EPA, and 0.7 g of docosahexaenoic acid) per day to 14 renal allograft recipients for 6 months. Another group of recipients served as controls. In the treated group the levels of EPA and docosahexaenoic acid in erythrocyte membrane lipids increased significantly after the fish oil treatment. Red blood cell filterability significantly increased in the treated group compared with the case of the control group. Epinephrine-induced platelet aggregation increased significantly in the control group, and this change was significantly different from that of the treated group (almost a null change). At the end of the study, the ratio of the main urinary metabolite of prostacyclin I2/3 to the metabolite of thromboxane A2/3 was significantly higher in the treated group than in the control group. In conclusion, we suggest that fish oil concentrate may favorably affect risk factors for thromboembolic complications in renal allograft recipients.

Adult↗

Involvement of metabolites in the inhibitory effects of 2-(4-ethyl-1-piperazinyl)-4-phenylquinoline dimaleate (AD-2646), a new quinoline derivative, on gastric acid secretion. A comparison with tricyclic antidepressants.

AD-2646, 2-(4-ethyl-1-piperazinyl)-4-phenylquinoline dimaleate, is a new quinoline derivative with similar pharmacological properties to tricyclic antidepressants. Its effects on stimulated gastric acid secretion were examined in the perfused stomach of anesthetized rats and compared with those of imipramine or trimipramine. Inhibitory effects of AD-2646, imipramine or trimipramine on 2-deoxy-D-glucose (2-DG)-induced gastric acid secretion were more prominent after intraduodenal application than after subcutaneous application. However, the potency of inhibition by AD-2876 (an active metabolite of AD-2646) of 2-DG-induced gastric acid secretion was not dependent on the route of administration. When applied subcutaneously, AD-2646 did not change gastric acid secretion stimulated by bethanechol (BeCh) or evoked by electrical stimulation of the vagus nerve. When applied intraduodenally, AD-2646 produced a moderate decrease in gastric acid secretion stimulated by BeCh. In contrast, imipramine decreased the BeCh-induced gastric acid secretion when applied subcutaneously, but not intraduodenally. In cobalt chloride-treated rats, inhibitory effects of intraduodenal AD-2646 and imipramine on 2-DG-induced gastric acid secretion were reduced, probably owing to the decreased formation of metabolites. It is suggested that subcutaneous AD-2646 inhibited 2-DG-induced gastric acid secretion mainly via centrally mediated mechanisms and intraduodenal AD-2646 reduced it at least partly via peripherally mediated mechanisms as well as via centrally mediated mechanisms, and that the inhibition was more prominent after intraduodenal application than after subcutaneous application probably because of greater efficiency in the formation of the active metabolites.

Animals↗

Antiulcer activities of glycyrrhetinic acid derivatives in experimental gastric lesion models.

Glycyrrhetinic acid (Ia) and eighteen related derivatives were examined for antiulcer activity using stress-induced gastric lesions (restraint plus water immersion at 25 degrees C) in mice and rats as screening tests. Among the compounds tested, dihemiphthalate derivatives of 18 alpha- or 18 beta-olean-12-ene-3 beta,30-diol (IV, IIId), 18 beta-olean-9(11)12-diene-3 beta,30-diol (VIc), and olean-11,13(18)-diene-3 beta,30-diol (VIIc) showed potent inhibition of gastric lesion formation at a dose of 12 or 25 mg/kg (p.o.); carbenoxolone sodium (Ib) significantly suppressed the lesion formation at a dose of 500 mg/kg (p.o.). Further evaluation of the antiulcer activity was carried out mainly for compound IIId. Compound IIId (p.o.) prevented the formation of indomethacin-induced or 0.6 N HCl-induced gastric lesions; the latter antiulcer effect was noted even in the combined treatment with indomethacin, suggesting that the effect occurs independently of endogenous prostaglandins. In contrast, compound IIId had no preventive effect against Shay rat ulcer when intragastrically (i.g.) administered; further, no antisecretory effect was seen by i.g. application in pylorus-ligated rats. Administration of compound IIId for 2 weeks accelerated the healing rate of acetic acid-induced gastric ulcer in rats. No significant change in urine excretion was observed after its consecutive administration for 3 d. These results suggest that dihemiphthalate derivatives (IIId, IV, VIc, VIIc) may produce a strong antiulcer activity, probably by strengthening some gastric mucosal defensive mechanism.

Animals↗

Long-term angiographic follow-up results in patients undergoing percutaneous transluminal coronary angioplasty.

Long-term effects following percutaneous transluminal coronary angioplasty (PTCA) were examined using follow-up coronary angiography (CAG) in 49 lesions in cases in which the procedure was considered to be successful. Follow-up CAG was performed 2-5 times (average, 2.7 times) per patient during a period of 1 year to 3 years and 7 months (average, 1 year and 10 months). The luminal diameter of the PTCA sites was expressed as the percentage of the value immediately after the procedure. Narrowing by 10% or more was observed in 17 lesions 3-8 months after PTCA but in only 4 lesions on the final CAG. The luminal diameter of the PTCA site was significantly greater (p less than 0.05) 2 years after PTCA in comparison to the findings after 1 year. These results suggest excellent long-term effects at the PTCA site.

Angioplasty, Balloon, Coronary↗

Inhibitory effect of intravenous GABA antagonists on gastric acid secretion stimulated by secretagogues in rats.

Effect of intravenous administration of GABA antagonists on gastric acid secretion in perfused stomachs was studied in rats anesthetized with urethane. Bethanechol (BeCh)-stimulated acid secretion was definitely inhibited by bicuculline, a GABA antagonist, and strychnine, a glycine antagonist, but not by picrotoxin and pentylenetetrazol, GABA antagonists. The inhibitory effect of bicuculline and strychnine was accompanied by vigorous convulsions. Only the bicuculline-induced inhibition was still seen in d-tubocurarine paralyzed rats, and it was abolished in spinal rats. 2-Deoxy-D-glucose (2-DG)-stimulated acid secretion was apparently depressed by all the GABA antagonists of bicuculline, picrotoxin and pentylenetetrazol. The inhibitory effect of picrotoxin, but not bicuculline, on the 2-DG stimulation was still elicited in spinal rats. Inhibition of acid secretion stimulated by pentobarbital, a centrally acting secretagogue, was produced by picrotoxin and pentylenetetrazol in spinal rats. These findings suggest that bicuculline acts centrally to inhibit acid secretion stimulated both peripherally by BeCh and centrally by 2-DG, besides nonspecific mechanisms due to convulsions, and the action would be directed to centers which are implicated in stimulation of the sympatho-adrenomedullary system; picrotoxin and pentylenetetrazol also act centrally to inhibit 2-DG- or pentobarbital-stimulated acid secretion through depression of the central vagal tone which leads to inhibition of gastric acid secretion.

Animals↗

Immortalization of rat spleen and thymus T cells by human T-cell leukemia virus type I.

Co-cultivation of thymus and spleen cells of Fisher and Lewis rats with lethally irradiated MT-2 cells harboring human T-cell leukemia virus type I (HTLV-I) resulted in the establishment of lymphoid cell lines, FIRT-1, FIRS-1, LERT-1, and LERS-1, respectively. Cells of these cell lines had rat T-cell characters as demonstrated by the positive reaction to monoclonal antibodies (MAbs) to rat T cell antigens (Thy 1 and pan T). They lacked surface immunoglobulins and strongly expressed rat interleukin-2 receptor antigen (Tac) and Ia antigen. Karyotypic analysis revealed that they had the normal rat karyotype in early cultures, but showed marked aneuploidy after long cultivation. None of them expressed HTLV gag proteins (p19 and p24) or virus particles, but they contained HTLV-I proviral DNA monoclonally and weakly expressed pX gene products (p40x). They were not transplantable into syngeneic newborn rats.

Animals↗

Platelet activating factor induced gastric damage in rats: participation of increased gastric vascular permeability.

Pharmacological factors involved in the injurious effect of platelet activating factor (PAF) on the gastric mucosa were studied in the acid (0.15 N HCI)-perfused stomachs of anesthetized rats. PAF infusion (100 ng/kg/min for 20 min, i.v.) induced distinct bleeding in the acid perfusate in proportion to mucosal lesions. Preceding the bleeding, a remarkable increase in mucosal vascular permeability was observed on dye-leakage assessment. Inhibition of the gastric bleeding and the dye leakage was achieved by pretreatment of the animals with CV-3988, a PAF antagonist, and hydrocortisone acetate, in contrast to the aggravation by caffeic acid. These results suggested the importance of mucosal vascular permeability in PAF-induced gastric mucosal lesions.

Animals↗

Effects of carbenoxolone and prostaglandin E2 on transmucosal potential difference in the rat stomach.

The effects of prostaglandins (PGs), carbenoxolone and some pharmacological agents on the gastric transmucosal potential difference (PD) were examined under ethanol challenge in anesthetized rats. The PD reduction induced by indomethacin + ethanol (20%) was clearly prevented by PGE2 or carbenoxolone, as well as by isoproterenol or i.v. NaHCO3 infusion. The degree of the protection and recovery of the PD change with carbenoxolone (3 mg/kg, i.g.) were found to be much greater than in the case of PGE2 (100 micrograms/kg, i.g.). The importance of gastric mucus was suggested in comparison with bicarbonate secretion and mucosal blood flow.

Animals↗

Comparison of the increment in plasma eicosapentaenoate concentrations by fish oil intake between young and middle-aged volunteers.

The effect of age on eicosapentaenoic acid (20:5 n-3; EPA) incorporation into plasma lipids was investigated in young volunteers (8 males, 19 +/- 1 yr) and middle-aged volunteers (6 males, 53 +/- 7 yr). They were asked to take 5.4 g fish oil per day for one week. The increment in EPA in the cholesteryl ester fraction after the supplementation was significantly greater in the middle-aged group (delta = 1.69%) than in the young group (delta = 0.44%) (p less than 0.05). The food intake analyzed for 3 consecutive days just before the supplementation revealed that the young group took more linoleate (17 vs. 10 g) than the middle-aged group. There was a significant inverse correlation between the increment in EPA in the cholesteryl ester fraction after the supplementation and daily linoleate intake among all the volunteers combined (r = -0.63, p less than 0.02). The higher increment in EPA in cholesteryl ester in the middle-aged group might be due to less intake of linoleate and not due to the difference in age itself.

Administration, Oral↗

[Improvement of airway hyperreactivity in bronchial asthma patients with short disease duration treated with anti-allergic agents].

We treated bronchial asthma patients with anti-allergic agents for more than three months, and examined their effects on the airway hyperreactivity in 15 cases; five were short cases (disease duration was less than one year from the onset) and 10 were long cases (disease duration was more than one year). A significant improvement in airway hyperreactivity to histamine inhalation was observed in all five short cases. In 4 out of 5 short cases, the threshold of histamine concentration reached to the normal level of 10,000 micrograms/ml. On the other hand, the significant improvement was observed only in 2 out of 10 cases. We suggested that in "short asthma cases" the airway hyperreactivity could improve with the use of anti-allergic agents in a relatively short period and at a high rate.

Adult↗

Autocytotoxic cells in rheumatoid synovial fluids.

The possibility that patients with rheumatoid arthritis (RA) might have autocytotoxic activity in the joints was investigated using a 51Cr release assay. Peripheral blood lymphocytes (PBL) and synovial fluid (SF) lymphocytes from 9 patients with active RA were tested for cytotoxic activity against autologous PBL stimulated with pokeweed mitogen (PWM). In 5 of 9 patients, lymphocytes isolated from the SF showed cytotoxic activity against autologous PWM-blasts, whereas none of PBL showed autocytotoxic activity. Unstimulated PBL were resistant to lysis by SF cytotoxic cells. The autocytotoxic cells in RA SF may have relevance to immunoregulatory activity in the diseased area.

Adult↗