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Biomedical subjects

K Otsubo

Publications and source records attributed to K Otsubo.

At least 73 records · Page 4Linked to original sources
PubMed1991

Leupeptin causes an accumulation of lipofuscin-like substances in liver cells of young rats.

Leupeptin, a thiol protease inhibitor, has previously been shown to cause a dense accumulation of substances resembling age pigment and called ceroid-lipofuscin, in brain cells of young rats. Thus far, however, attempts to produce age pigments in hepatocytes of normal young rats with protease inhibitor(s) have not been successful. The present study provides the first demonstration that leupeptin induces lipofuscin-like substances in normal young rat hepatocytes. Male Fischer-344 rats (age 4-6 weeks) were continuously infused with leupeptin or saline i.p. for 2 weeks by an osmotic minipump (dosage, 1-50 mg/100 g per day). Liver tissues were then examined by light, fluorescence and electron microscopy. Both hepatocytes and non-parenchymal cells of livers treated with leupeptin, but not saline, showed a dense accumulation of pigments which stained deeply with toluidine blue, were PAS-positive and were brightly autofluorescent. After UV excitation the pigments had an emission spectrum with a broad peak at 480-540 nm extending to 650 nm resembling the spectrum of age pigment from livers of normal aged rats. Electron microscopic examination revealed numerous lipofuscin-like deposits with heterogeneous morphology in the cytoplasm of both hepatocytes and non-parenchymal cells; lipid and myelin-like bodies were also present in hepatocytes. The results indicate that the perturbation of proteolytic activity in liver by leupeptin causes an accumulation of substances which by several criteria resemble lipofuscin. These results thus provide further support for the 'Protease Inhibitor Model of Lipofuscin Formation' as well as a potential experimental model for studying hepatocellular aging processes.

Aging↗
PubMed1991

Endoscopic management of shoulder pain in long-term haemodialysis patients.

In 48 shoulders of 29 patients receiving long-term haemodialysis and complaining of intolerable shoulder pain, endoscopic resection of the coracoacromial ligament was performed under local anaesthesia on an outpatient basis, using the Universal Subcutaneous Endoscope system. Predominant endoscopic findings were proliferation of the subacromial bursae and popping between the coracoacromial ligament and the rotator cuff. Amyloid originating from beta 2 microglobulin (beta 2-M) was demonstrated in 87% of the resected coracoacromial ligaments and 86% of the subacromial bursae. Resection of the coracoacromial ligament relieved the shoulder pain in all patients.

Adult↗
PubMed1991

Synthesis and antiulcer activity of optical isomers of 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]propionic acid (rebamipide).

The enantiomers of 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid [(+/-)-1, rebamipide, OPC-12759], a new antiulcer agent that enhances mucosal resistance, were synthesized from optically active alpha-amino acid derivatives of 2(1H)-quinolinone. The key intermediates, alpha-amino acid derivatives, were prepared by asymmetric synthesis and optical resolution. The (+)-1 was about 1.7 times as potent as the (-)-isomer in antiulcer activity against ethanol-induced gastric ulcers.

Alanine↗
PubMed1990

Parathyroid hormone-related protein in tumor tissues obtained from patients with humoral hypercalcemia of malignancy.

We assessed the relationship between the parathyroid hormone-related protein (PTHrP) and the development of humoral hypercalcemia of malignancy (i.e., hypercalcemia due to the production by solid tumors of hypercalcemic factors) by assaying tumor extracts from hypercalcemic and normocalcemic patients with cancer for immunoreactive PTHrP contents. Immunoreactive PTHrP was demonstrated in extracts of 21 of 22 tumor tissues obtained from 22 patients with humoral hypercalcemia of malignancy. Immunoreactive PTHrP was rarely seen in tumor tissue extracts obtained from 34 normocalcemic patients with cancer and two hypercalcemic patients with cancer with severe bone metastases. Gel filtration studies of tumor extracts revealed a molecular-size heterogeneity of immunoreactive PTHrP. These radioimmunoassay data indicate a close relationship between detection of PTHrP in tumor tissues and the development of humoral hypercalcemia of malignancy.

Adult↗
PubMed1990

Production of S-(+)-ibuprofen from a nitrile compound by Acinetobacter sp. strain AK226.

S-(+)-2-(4'-Isobutylphenyl)propionic acid [S-(+)-ibuprofen] was produced from racemic 2-(4'-isobutylphenyl)propionitrile (Ibu-CN) by an isolated bacterial strain, Acinetobacter sp. strain AK226. Ammonium acetate, acetonitrile, or n-butyronitrile as a carbon source in the culture medium was effective for bacterial growth and induction of this activity. The optimum pH of the reaction was around 8.0. S-(+)-Ibuprofen formed from Ibu-CN by resting cells was present in a 95% enantiomeric excess. Acinetobacter sp. strain AK226 appeared to possess a nitrilase for Ibu-CN because 2-(4'-isobutylphenyl)propionamide was not detected in the reaction mixture and 2-(4'-isobutylphenyl)propionamide was not hydrolyzed to S-(+)-ibuprofen. Since S-(+)-ibuprofen was preferentially produced while the R enantiomer of Ibu-CN was left almost intact over the time course of the reaction, the putative nitrilase appeared to be highly specific for the S enantiomer of Ibu-CN.

Acinetobacter↗
PubMed1990

Synthesis and antibacterial activity of the metabolites of 9-fluoro-6,7-dihydro-8-(4-hydroxy-1-piperidyl)-5-methyl-1-oxo-1H,5H- benzo[i,j]quinolizine-2-carboxylic acid (OPC-7251).

The metabolites of 9-fluoro-6,7-dihydro-8-(4-hydroxy-1-piperidyl)-5-methyl-1-oxo-1H,5H- benzo[i,j]quinolizine-2-carboxylic acid (OPC-7251) (1), which has a potent antibacterial activity against gram-positive bacteria, characteristically Propionibacterium acnes, were synthesized to confirm their structures and to examine their antibacterial activity. The structures of three major metabolites (2, 3a and 4) were identified by means of comparison with the synthetic compounds. The antibacterial activity of the metabolites (2, 3a and 4) was found to be lower than that of 1.

Anti-Bacterial Agents↗
PubMed1990

Efficacy of emetic and United State pharmacopoeia ipecac syrup in prevention of drug absorption.

The efficacy of both the emetic syrup prepared in the previous report and the United States Pharmacopoeia (USP) ipecac syrup concerning the prevention of drug absorption was investigated in 4 beagle dogs using a randomized and cross-over design. In order to control the intragastric pH of the beagle dogs, the administration of pentagastrin or hydrochloric acid (HCl)-glycine buffer (pH 1.5) was tested. The intragastric pH changed from 7.2 to 1.8 with the intramuscular administration of pentagastrin, but the primary emesis occurred more slowly. On the other hand, the HCl-glycine buffer (pH 1.5) gave the appropriate emesis. Therefore, the HCl-glycine buffer (pH 1.5) was used to control the intragastric pH of the beagle dogs. Acetaminophen (AcA), salicylic acid (SA) and kanamycin (KM) as markers were administered orally after conditioning the intragastric pH at 1.5. The emetic syrup or the USP ipecac syrup was then administered. The recovery rate of AcA and KM from vomit was 42-65%. The emetic syrup and the USP ipecac syrup significantly reduced the absorption of AcA from the calculation of pharmacokinetic parameters compared to the control syrup. It was observed that the absorption of cephaeline (CP) in the emetic syrup was less than that of CP in the USP ipecac syrup.

Absorption↗
PubMed1990

Estimation of the molecular volumes of the reaction products between beta-lactam antibiotics and aminoglycoside antibiotics, and those of the degradation products of beta-lactam antibiotics by isotachophoresis.

The correlative equations between the molecular volume and the qualitative indication (hR) for beta-lactam antibiotics, the reaction products between beta-lactam antibiotics and kanamycin, and the degradation products of beta-lactam antibiotics were hR = 0.32 + 0.080 VA2/3//Z/(N = 15, r = 0.972 for penicillins) and hR = 0.04 + 0.072 VA2/3//Z/(N = 12, r = 0.987 for cephems). Where VA is van der Waals volume (A3/molecule), hR is the relative step height in the isotachopherogram, and Z is the electric change, respectively. According to these equations, the molecular volumes of the reaction products between beta-lactam antibiotics and the other aminoglycoside antibiotics, and those of the degradation products of beta-lactam antibiotics can be estimated from the value of hR. Also according to the step height in the isotachopherogram, the reaction products or the degradation products may be estimated directly when the electric charge is known. It was confirmed that a molecule of aminoglycoside antibiotics reacted with a molecule of beta-lactam antibiotics. Therefore, the inactivation of aminoglycoside antibiotics is much greater than for beta-lactam antibiotics when the clinical doses of these antibiotic combinations are used.

Aminoglycosides↗
PubMed1989

Morphological, physiological and biochemical alterations in livers of rodents induced by protease inhibitors: a comparison with old livers.

A "Protease inhibitor model of aging" has been proposed primarily based on observations on brain tissues exposed to a thiol protease inhibitor, leupeptin (Ivy et al., 1984a). In order to validate this model in terms of a mechanism of cellular aging, as well as of lipofuscin formation in particular, attempts have been made to induce lipofuscin in hepatocytes in young rodent (rat and mouse) livers by continuous i.p. infusion of two different thiol protease inhibitors, leupeptin and E-64C. With doses of leupeptin higher than 1.0 mg/100g/day for 2 wks, a fine granular lipofuscin-like deposition with distinct yellowish-green fluorescence was induced in young rat hepatocytes. The deposition became greater in degree with increasing leupeptin doses. In Kupffer cells and other endothelial cells, fluorescent granules were also induced. In contrast to rat livers, lipofuscin-like pigments induced in hepatocytes in mice were much less, even with a higher dose (20 mg/100 g/day). E-64C also induced the accumulation of lipofuscin-like pigments at a dose of 5 mg/100 g/day, their characteristics being very similar to those induced by leupeptin, but the accumulation being smaller in degree. The fluorescence of leupeptin induced lipopigments was yellowish-green having a peak around 520 nm in emission profile, closely resembling that observed in old rat livers. The hepatobiliary transport functions such as biliary transport maximum (Tm) for sulfobromophthalain and the biliary recovery of iv injected ouabain which are known to decline with age tended to decline in young (6-wk-old) rats administered with leupeptin at a dose of 5 mg/100 g/day for 2 wks. On the other hand, dolichol concentration in leupeptin treated livers was not increased in comparison to control livers, whereas in old rat livers, the dolichol concentration was more than 2 times greater than in young livers. A clear-dose-dependent deposition of ceroid-lipofuscin induced in young rodent livers by protease inhibitors strongly suggests that the "Protease inhibitor model" is generally valid not only for the brain but for other tissues such as the liver, and for two different thiol protease inhibitors.

Aging↗
PubMed1989

Differences in the influence of diet on hepatic glutathione S-transferase activity and glutathione content between young and old C57 black female mice.

The effect of a protein-free diet (PFD) on hepatic activity of glutathione S-transferase (GST) and hepatic content of total glutathione (GSH) was examined in young (9-month-old), middle-aged (17-month-old) and old (27-month-old) C57BL/6CrS1c female mice. There were no significant differences in the control values of GSH or of enzyme activity for four of five substrates among young, middle-aged, and old animals fed normal diet (ND) only. Both GSH and GST activity were significantly decreased by the 7-day PFD in both young and old groups but the decrement was generally greater in old mice. After a 2-3-day refeeding of ND, young mouse enzyme activities were significantly higher than control (basal) values for all five substrates, whereas old mouse values were still significantly lower than corresponding control values. There was no overshooting of GSH levels after refeeding of ND in either young or old animals. This study indicates that an age difference in this detoxification system can be clearly demonstrated in the hepatic response to PFD feeding and especially to ND refeeding, despite the enzymes' stable basal activities with aging.

Aging↗
PubMed1989

Closed and continuous algae cultivation system for food production and gas exchange in CELSS.

In CELSS (Controlled Ecological Life Support System), utilization of photosynthetic algae is an effective means for obtaining food and oxygen at the same time. We have chosen Spirulina, a blue-green alga, and have studied possibilities of algae utilization. We have developed an advanced algae cultivation system, which is able to produce algae continuously in a closed condition. Major features of the new system are as follows. (1) In order to maintain homogeneous culture conditions, the cultivator was designed so as to cause a swirl on medium circulation. (2) Oxygen gas separation and carbon dioxide supply are conducted by a newly designed membrane module. (3) Algae mass and medium are separated by a specially designed harvester. (4) Cultivation conditions, such as pH, temperature, algae growth rate, light intensity and quantity of generated oxygen gas are controlled by a computer system and the data are automatically recorded. This equipment is a primary model for ground experiments in order to obtain some design data for space use. A feasibility of algae cultivation in a closed condition is discussed on the basis of data obtained by use of this new system.

Biomass↗
PubMed1989

Cross-linking and stereospecific structure of collagen in mineralized and nonmineralized skeletal tissues.

Molecular distributions of the intermolecular cross-links in fetal bovine bone type I collagen fibrils were quantitatively determined and compared with those of periodontal ligament. Results indicated that Hyl and Lys residues in the COOH-terminal nonhelical peptide portions (residues 16C) of both alpha 1 chains were quantitatively converted to aldehydes. These in turn stoichiometrically formed cross-links with residues Hyl-87 on both alpha 1 and alpha 2 chains of neighboring molecules. The ratio of cross-linked alpha 1 to alpha 2 chains was 3.5 to 1 indicating a stereospecific packing of collagen molecules in the fibrils similar manner to periodontal ligament collagen. It was found that there were few aldehyde derived cross-links in the NH2-terminal nonhelical portions of the bone type I collagen. The relative paucity of the cross-links in NH2-terminal region of bone collagens may favor mineralization.

Animals↗
PubMed1988

[In vitro activity of minocycline against Chlamydia trachomatis clinical isolates and clinical efficacy of minocycline to C. trachomatis associated nongonococcal urethritis].

The in vitro activity of minocycline (MINO) against Chlamydia trachomatis and its efficacy in the treatment of C. trachomatis-associated nongonococcal urethritis were investigated. Six isolates of C. trachomatis were inhibited at 0.06 micrograms/ml of MINO and 5 isolates at 0.03 micrograms/ml. All cases received oral MINO twice daily for 7 or more days in doses of 100 mg. In 5 of 31 cases, 2 g of spectinomycin was intramuscularly administrated together with MINO only once. C. trachomatis was eliminated in all cases tested. Excellent results were obtained in 26 cases (84%); urethral discharge and polymorphonuclear cells (PMN) disappeared or decreased to normal levels (3 cells/hpf or less) in these cases. Ureaplasma urealyticum was isolated from 8 cases, 7 of which became free of ureaplasmal infection. MINO seemed to be less effective on the decrease of PMN in the urethral smear in cases infected coincidentally with C. trachomatis and U. urealyticum than in cases infected with C. trachomatis alone. No subjective side effects were observed in any of the 31 cases studied. In conclusion, MINO was a useful antimicrobial agent for the treatment of C. trachomatis- and U. urealyticum-associated nongonococcal urethritis.

Adult↗
PubMed1987

Food production and gas exchange system using blue-green alga (Spirulina) for CELSS.

In order to reduce the cultivation area required for the growth of higher plants in space adoption of algae, which have a higher photosynthetic ability, seems very suitable for obtaining oxygen and food as a useful source of high quality protein. The preliminary cultivation experiment for determining optimum cultivation conditions and for obtaining the critical design parameters of the cultivator itself has been conducted. Spirulina was cultivated in the 6-liter medium containing sodium hydrogen carbonate solution and a cultivation temperature controlled using a thermostat. Generated oxygen gas was separated using a polypropyrene porous hollow fiber membrane module. Through this experiment, oxygen gas (at a concentration of more than 46%) at a rate of 100-150 ml per minute could be obtained.

Air Conditioning↗
PubMed1987

Preliminary experimental results of gas recycling subsystems except carbon dioxide concentration.

Oxygen concentration and separation is an essential factor for air recycling in a CELSS. Furthermore, if the value of the plant assimilatory quotient is not coincident with that of the animal respiratory quotient, the recovery of O2 from the concentrated CO2 through chemical methods will become necessary to balance the gas contents in a CELSS. Therefore, oxygen concentration and separation equipment using Salcomine and O2 recovery equipment, such as Sabatier and Bosch reactors, were experimentally developed and tested.

Air Conditioning↗
PubMed1987

Vapor compression distiller and membrane technology for water revitalization.

Water revitalization for a space station can consist of membrane filtration processes and a distillation process. Water recycling equipment using membrane filtration processes was manufactured for ground testing. It was assembled using commercially available components. Two systems for the distillation are studied; one is an absorption type thermopervaporation cell and the other is a vapor compression distiller. Absorption type thermopervaporation able to easily produce condensed water under zero gravity was investigated experimentally and through simulated calculation. The vapor compression distiller was studied experimentally and it offers significant energy savings for evaporation of water.

Absorption↗