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Biomedical subjects

M Haga

Publications and source records attributed to M Haga.

At least 73 records · Page 4Linked to original sources

Isolation of bilobalide and ginkgolide A from Ginkgo biloba L. shorten the sleeping time induced in mice by anesthetics.

The leaves of Ginkgo biloba L. and aqueous extract from them shortened the sleeping time induced in mice by anesthetics (hexobarbital, alpha-chloralose and urethane, i.p.). Two characteristic terpenoids in G. biloba, bilobalide and ginkgolide A, significantly shortened the sleeping time induced by anesthetics. A toxic substance, 4-O-methylpyridoxine (MPN), responsible for "gin-nan food poisoning" isolated from the seed of G. biloba, was not detected from the extract of the leaves of G. biloba. Therefore, the Ginkgo biloba extract has no toxicities for MPN.

Anesthetics↗

Effect of phosphatidylcholine and cholesterol on pH-sensitive liposomes.

We previously reported that liposomes composed of phosphatidylethanolamine (PE) and fatty acid exhibited pH-dependent leakage, aggregation and fusion (N. Hazemoto, M. Harada, N. Komatubara, M. Haga and Y. Kato, Chem. Pharm. Bull., 38, 748 (1990)). In this study, we have examined the effects of phosphatidylcholine (PC) and cholesterol (Chol) on the pH-sensitivity of liposomes. Contents-leakage from liposomes was always accompanied by a change in light-scattering, suggesting that aggregation or fusion of liposomes causes the leakage. The pH-sensitivity was observed only when liposomes contained less than 32 mol% of PC. The leakage vs. pH curves shifted to the more acidic regions as the PC content of the liposomes increased, but the maximum leakage (%) did not change. The effect of cholesterol on the pH-sensitivity depended on the PC/PE ratio of the liposomes. Addition of cholesterol to PC/PE/oleic acid (OA) liposomes system induced two effects, that is, aggregation of liposomes via the reduction in PC content and the stabilization of the liposomal membrane. It was shown that pH-sensitivity can be controlled by addition of the appropriate amount of PC and/or Chol to liposomal lipids.

Cholesterol↗

[Studies on the constituents of edible and medicinal plants. IV. Determination of 4-O-methylpyridoxine in serum of the patient with gin-nan food poisoning].

The serum 4-O-methylpyridoxine (MPN) levels in a 21 months-old patient with gin-nan food poisoning were determined by HPLC. The blood of the patient was taken at 8.5 and 15.5 h after taking about 50 ginkgo albumens. After deproteinization of the serum, the supernatant was pretreated with Sep-pak C18 cartridge and was applied to HPLC. HPLC was performed with a Hibar LiChrosorb RP-18 (4.0 mm i.d. x 250 mm, 7 microns) using a fluorescence detector (wave length of excitation and fluorescence; 290 and 400 nm, respectively). The serum MPN level was determined by the absolute calibration method. The determination limit of MPN in the serum was 0.05 micrograms/ml. The serum MPN concentration was 0.09 micrograms/ml at 8.5 h after taking ginkgo seeds, and was less than the determination limit of MPN (0.05 micrograms/ml) at 15.5 h. MPN, isolated from the seed of Ginkgo biloba L., is responsible for "gin-nan food poisoning," and its cardinal symptoms are mainly tonic and/or clonic convulsions and loss of consciousness. Infants are particularly vulnerable. This method may be available for proving the gin-nan food poisoning, chemically.

Chromatography, High Pressure Liquid↗

Reproduction of progressive retinal degeneration (bright blindness) in sheep by administration of ptaquiloside contained in bracken.

The process of occurrence of bright blindness, progressive retinal degeneration (PRD), in sheep was observed using two Suffolk ram lambs fed on a diet containing bracken powder. The first sign of the bright blindness was detected 4 months after the start of experiment. Based on these preliminary results, the amount of bracken powder necessary to induce PRD was estimated (experiment I). In the following experiment, ptaquiloside (PT), a norsesquiterpene glucoside of the illudane type isolated from bracken, which is a bracken carcinogen and a causative principle of cattle bracken poisoning was administered to two Suffolk ram lambs. It was clearly demonstrated in this experiment (experiment II) that PT present in bracken is also a causative principle of PRD.

Animal Feed↗

[Extensive bowel infarction caused by intraaortic balloon pumping].

Two cases of an extensive bowel infarction occurred during Intraaortic Balloon Pumping (IABP) are reported. In the first, an acute myocardial infarction was seen suddenly on the seventh postoperative day following arterial reconstruction of the right lower leg and his condition required IABP support. Five day after beginning of IABP, severe symptoms suggesting peritonitis appeared, and laparotomy revealed an extensive infarction of small bowel and sigmoid colon. In the second, the patient required IABP support for weaning from cardiopulmonary bypass after completion of coronary artery bypass grafting. A severe peritonitis was caused by an extensive infarction of small and large intestine during two days of IABP support. Cholesterol emboli were found in the small bowel arteries of the case 1 at microscopic examinations of the autopsy specimen. Both patients died of cardiopulmonary failure and renal failure respectively, though necrotic intestine were resected. Circulatory support using IABP should not be selected, when a patient has severe arteriosclerotic lesions of the aorta.

Angina, Unstable↗

[A concomitant operation of aorto-coronary bypass graft and lung cancer: report of a case].

A case of a 66-year-old man with ischemic heart disease and lung cancer is reported. Chest roentgenogram revealed an irregular 2.8 x 2.0 cm mass in the right upper lobe. Coronary angiography showed 75-90% stenosis of the left anterior descending artery, and these lesions was suspected to cause perioperative myocardial infarction. A concomitant operation of aorto-coronary bypass graft and right upper lobectomy was performed through median sternotomy. A concomitant operation must be considered to be definitive and ideally preferable in selected cases.

Aged↗

Structure and antitumor activity of a branched (1----3)-beta-D-glucan from the alkaline extract of Amanita muscaria.

A beta-(1----6)-branched (1----3)-beta-D-glucan(AM-ASN) was isolated from the alkaline extract of the fruiting bodies of Amanita muscaria. AM-ASN had [alpha]D - 11 degrees in 0.5 M sodium hydroxide. Its estimated molecular weight was 95,000 in this alkaline solution and 260,000 in a neutral solution. The branches in the glucan were primarily single, (1----6)-linked D-glucopyranosyl groups, two for every seven residues in the (1----3)-linked main chain. AM-ASN exhibited significant antitumor activity against Sarcoma 180 in mice, and a mixture of AM-ASN with mitomycin C was more effective against the tumor than mitomycin C only.

Amanita↗

Enantiomeric difference in percutaneous penetration of propranolol through rat excised skin.

The percutaneous penetration of R-(+)- and S-(-)-propranolol (PL) through rat excised skin was investigated in vitro. The flux of S-(-)-PL after application to normal skin was high compared with that of R-(+)-PL. On the other hand, in damaged rat skin, the flux of R-(+)-PL was almost equivalent to that of S-(-)-PL. It is suggested that there is an enantiomeric difference between S-(-)- and R-(+)-PL in terms of penetration through rat stratum corneum.

Animals↗

Studies on the constituents of edible and medicinal plants. III. Effects of seven limonoids on the sleeping time induced in mice by anesthetics.

Effects of seven limonoids, obakunone (1), 7 alpha-obakunol (2), 7 beta-obakunol (3), limonin (4), 7 alpha-limonol (5), 7 beta-limonol (6) and nomilin (7), on the sleeping time induced in mice by anesthetics were assayed. All the limonoids, except for 2, shortened the sleeping time induced by alpha-chloralose and urethane. 7 gave the highest reduction rate of sleeping time, and the order of the reduction rate of sleeping time was as follows; 7 > 1 and 3 > 4, 5 and 6. As the chemical structures of these compounds are similar to each other, the relationship between the structure and the effects of limonoids on sleeping time was discussed.

Animals↗

Cardiac abnormalities in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of cardiac abnormalities in patients with systemic lupus erythematosus. DESIGN: Prospective survey. SETTING: Rheumatic diseases unit of a university hospital. PATIENTS: Volunteer sample comprising 83% of patients with systemic lupus erythematosus followed annually in the rheumatic disease unit (93 patients; mean age 46 +/- 13 years; female 79, male 14). These patients were age-matched with 16 female control volunteers (mean age 43 +/- 5 years) recruited from hospital staff. INTERVENTIONS: Electrocardiograms, two-dimensional echocardiograms and radionuclide angiograms were performed in patients and controls. Anticardiolipin antibodies were measured by enzyme-linked immunosorbent assay in the systemic lupus erythematosus patients. MAIN RESULTS: At least one cardiac abnormality was detected in 44 of 93 systemic lupus erythematosus patients (47%). These abnormalities included: aortic valve thickening 12%; mitral valve thickening, prolapse, vegetations or stenosis 23%; left ventricular segmental dysfunction 4%; left ventricular global hypokinesis 4%; right ventricular hypokinesis 4%; left ventricular hypertrophy 14%; left ventricular diastolic dysfunction 16%; and pericardial effusion 2%. Three of the 16 controls (19%) had cardiac abnormalities consisting of mitral valve prolapse (one), right ventricular hypokinesis (one) and pericardial effusion (one). Cardiac abnormalities were more common in the systemic lupus erythematosus group compared with controls (47% versus 19%, P less than 0.05). Raised anticardiolipin antibodies were specific (88%) but not sensitive (33%) for the presence of cardiac abnormalities in systemic lupus erythematosus patients. Renal disease and prednisone therapy were more common in systemic lupus erythematosus patients with cardiac involvement than in such patients without evidence of cardiac disease (40% versus 16%, P = 0.03; and 81% versus 59%, P = 0.04, respectively). CONCLUSIONS: Cardiac abnormalities can be identified noninvasively in 47% of patients with systemic lupus erythematosus.

Adult↗

Protease-catalyzed peptide synthesis in frozen aqueous systems: the "freeze-concentration model".

Freezing of the aqueous reaction mixtures can cause dramatically increased peptide yields in protease-catalyzed kinetically controlled peptide synthesis reactions. The "Freeze-concentration model" which implies that the enzymic reaction within a macroscopically frozen system takes place in an unfrozen liquid phase is presented as a reasonable basis for the understanding of the effect of freezing. It is shown that L-amino acid esters are effective nucleophiles in alpha-chymotrypsin-catalyzed acyl transfer reactions when these are performed in frozen state.

Amino Acid Sequence↗

The clinical course of Felty's syndrome compared to matched controls.

In a cohort of 919 patients with definite or classic rheumatoid arthritis followed prospectively since 1966, we identified 36 patients with Felty's syndrome (FS). Their clinical course was compared to that of 72 matched controls from the same cohort. Patients with FS had more extraarticular features and more infections than control patients. The presence of joint erosions, serial Lansbury indices, and death rates were similar in both groups. Cardiovascular disease was the commonest cause of death in both groups, accounting for 32% of all deaths. Sepsis accounted for 10% of deaths in the group with FS and 13% of deaths in the controls.

Adolescent↗

Hypoglycemic effect of intestinally administered monosaccharide-modified insulin derivatives in rats.

The effect of the modification of insulin (INS) with p-succinylamidophenyl (SA)-alpha-D-glucopyranoside (SAPG), SA-alpha-D-mannopyranoside and SA-alpha-L-arabinopyranoside on the enzymatic degradation and the hypoglycemic effect in rats was studied. When SAPG-INS was administered intraintestinally in the absence of bile and pancreatic juice, blood glucose level decreased to 56% of initial value. Other monosaccharide derivatives were less effective than SAPG-INS. The digestion of monosaccharide derivatives by pepsin and chymotrypsin indicated that the resistance of insulin to enzymatic degradation was increased by its modification with monosaccharide. One possibility for the hypoglycemic effect of SAPG-INS could be the increased resistance of insulin to enzymatic degradation as a result of its modification with monosaccharide.

Animals↗

An improved chemiluminescence-based liposome immunoassay involving apoenzyme.

An improved liposome immunoassay system (LIS) combining the chemiluminescence-based LIS with an apoenzyme reactivation immunoassay system (ARIS) was developed. A low-molecular-weight co-factor, FAD (flavin adenine dinucleotide), was incorporated into liposomes instead of the high-molecular-weight enzyme GOD (glucose oxidase). FAD released from liposomes by cytolysin-hapten conjugates bound to Apo-GOD and regenerated GOD. The system allowed detection of 10 pM digoxin, the model analyte and was linear over 10 pM to 13 nM digoxin. This sensitivity was about 300 times higher than that of the homogeneous system using GOD-containing liposomes and 30 times higher than that of the heterogeneous system which we reported previously. The time required for incubation during the detection of digoxin was reduced from 20 to 3 h.

Apoenzymes↗

Effects of preparing and ligand-binding methods of small unilamellar liposomes on their blood elimination and tissue distribution in rats.

The effects of two methods of preparing small unilamellar vesicles (SUV) (detergent removal or sonication) on their in vivo elimination and tissue distribution was investigated in rats. The SUV prepared by either method had the same size distribution and lipid composition (egg yolk phosphatidylcholine/cholesterol/dipalmitoyl phosphatidylethanolamine or palmitic acid = 20/10/0.3, molar ratio). Three types of SUV made by either method were prepared. These contained one of three different surface ligand-binding functional groups (N-hydroxysuccinimide ester of palmitic acid, NHSP; glutaraldehyde-phosphatidylethanolamine, GA-PE; N-[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine, MPB-PE). SUV prepared by detergent removal were eliminated slowly from the circulation, and exhibited a low liver uptake and little leakage of [3H]inulin. There was no significant difference in elimination of the NHSP-SUV, GA-SUV or MPB-SUV prepared by detergent removal and their tissue distribution was similar. In contrast, the sonicated SUV were eliminated from the circulation much more rapidly mainly by liver uptake. The leakage of [3H]inulin from sonicated SUV into urine was relatively large. When sonicated control-SUV were prepared in the presence of the antioxidant, alpha-tocopherol (alpha-T-SUV), which reduces lipid peroxidation during sonication, the alpha-T-SUV were eliminated slowly with only a low liver uptake. Our results indicate that the rapid elimination and greater liver uptake of sonicated SUV is partly due to lipid peroxidation during preparation. These findings have relevance to the use of liposomes as a drug delivery system.

Animals↗

pH-sensitive liposomes composed of phosphatidylethanolamine and fatty acid.

pH-induced destabilization, aggregation and fusion of liposomes composed of phosphatidylethanolamine (PE) and various fatty acid were studied. Destabilization was examined as a fluorescent change caused by leakage of coencapsulated aminonaphthalene-3,6,8-trisulfonic acid (ANTS) and N,N-p-xylylenebispyridinium bromide (DPX). Fusion was monitored by two different methods, that is, intermixing assay of internal aqueous contents of liposomes, and lipid dilution assay of liposomes labeled with fluorescent phospholipids. Contents leakage from liposomes was observed by lowering the pH, and pH where the leakage began depended on fatty acid used. Fifty percent leakage of contents from PE liposomes containing alpha-hydroxypalmitic acid or alpha-hydroxy-stearic acid was observed at pH 5.5, that from liposomes containing stearic acid or palmitic acid was observed at pH 6.5-6.7, and that from ricinoleic acid at pH 7.2. Aggregation and fusion of the respective liposomes also occurred at a similar pH region. These results were interpreted by the notion that the protonation of the fatty acid triggers a series of pH-sensitive events. The liposomes developed in this study may be useful as a drug carrier which could release the contents in response to pH changes in their environment.

Chemical Phenomena↗