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Biomedical subjects

A Ohta

Publications and source records attributed to A Ohta.

At least 271 records · Page 15Linked to original sources
PubMed1987

Retinoid modulation of collagenase production by adherent human mononuclear cells in culture.

Previous observations have suggested that retinoids might be useful for the treatment of rheumatoid arthritis. In this study we examined the effects of various retinoids on collagenase production by adherent human peripheral blood mononuclear cells in culture. We have previously shown that these cells, consisting predominantly of monocyte-macrophages, actively synthesize and secrete collagenase upon stimulation with concanavalin A. The cells were incubated in serum free medium with all-trans-retinoic acid, 13-cis-retinoic acid, all-trans-retinal, or Ro 10-9359 (trimethylmethoxyphenyl retinoic acid ethyl ester) for up to 72 hours, and the collagenase activity was determined with [3H]proline labelled type I collagen as substrate. The incubation of mononuclear cells with all-trans-retinoic acid in the concentration range 10(-7)-10(-5) mol/l resulted in a dose dependent inhibition of the collagenase production. All-trans-retinal was also a potent inhibitor, whereas 13-cis-retinoic acid and Ro 10-9359 in a concentration of 10(-5) mol/l had a lesser effect. Control experiments indicated that the inhibition of collagenase production by all-trans-retinoic acid did not result from inhibition of total protein synthesis nor could it be explained by induction of an inhibitory molecule. These results indicate that retinoids with distinct structural features can inhibit collagenase production by monocyte-macrophages, and suggest a role for retinoids in the treatment of rheumatoid arthritis.

Cells, Cultured↗
PubMed1987

Effect of 5-(3-[4-(4-fluorophenyl)-1-piperazinyl]-propoxy)indan (BP-528) on benzodiazepine receptor bindings and gamma-aminobutyric acid release.

The action of a new type of anti-anxiety compound, 5-(3-[4-(4-fluorophenyl)-1-piperazinyl]-propoxy)indan (BP-528), was tested on benzodiazepine receptor bindings and on [3H]-GABA release. BP-528 did not alter [3H]-diazepam binding to rat cerebral cortical and hippocampal membranes either in the presence or absence of GABA; and the binding of [3H]-propyl-beta-carboline-3-carboxylate at low concentration (0.04 nM), which labels only the type I benzodiazepine receptor, was not changed by BP-528. BP-528 did not interact with the GABA-benzodiazepine receptor complex, which is related to the anti-anxiety activity of benzodiazepines. This compound affected neither GABA binding nor GABA uptake. Ten micromolar BP-528 depressed high K+-induced [3H]-GABA release from preloaded rat hippocampal slices. However, the same concentration of BP-528 also inhibited high K+-induced calcium uptake by rat cerebral cortical synaptosomes.

Animals↗
PubMed1987

Observing responses maintained by conditional discriminative stimuli.

In a conditional discrimination procedure, pigeons' observing responses were analyzed to examine whether two color stimuli (blue or red), conditionally related to whether each of two line stimuli (vertical or horizontal) accompanied reinforcement or nonreinforcement, functioned as conditioned reinforcers. If a variable-interval (VI) 10-s requirement was fulfilled, an observing response produced onset of a color stimulus. A little later, a line stimulus was presented independently of responding, added to the color stimulus to form a compound stimulus. If 55 s elapsed with a response not having occurred either through 55 s or after the variable-interval 10-s had timed out, one of the color-line compound stimuli was presented independently of responding. To control for sensory reinforcement effects and for earlier entrance to the later link, a simple discrimination procedure also was conducted in which reinforcement was not correlated with the color stimuli but with the line stimuli only. As in the conditional discrimination, the observing response also could produce earlier presentation of blue or red. The observing response occurred more frequently during the conditional discrimination than during the simple discrimination. The results were related to different theoretical accounts of conditioned reinforcement, particularly the information hypothesis.

Animals↗
PubMed1987

Adult Still's disease: review of 228 cases from the literature.

To clarify the clinical pictures of adult Still's disease, 228 cases reported in the past 15 years since Bywaters' first description were reviewed. These included our 9 new cases and an additional 25 cases from the Japanese literature, none of which had been described in previous English reviews. Most of the patients with long followup showed frequent recurrences. About one third developed deforming arthritis with ankylosis. There were 6 deaths. Of interest was the remarkably elevated levels of serum ferritin and prostaglandin E1 in some patients.

Adolescent↗
PubMed1987

Paraproteinemia in patients with scleredema. Clinical findings and serum effects on skin fibroblasts in vitro.

Four patients with paraproteinemia and scleredema were studied. Histologic features included marked thickening and fibrosis of the dermis and subcutis. Variable amounts of mucin deposits were detected in the interfibrillar spaces. Serum from one patient significantly stimulated collagen production in normal skin fibroblast cultures, whereas serum from another patient stimulated collagen production in autologous cell cultures. Moreover, serum from one patient stimulated the [35S]sulfate incorporation into the fibroblasts. Circulating serum factors, possibly related to the paraprotein, may enhance the synthesis of extracellular macromolecules by dermal fibroblasts in these patients, thus providing a mechanism for dermal fibrosis.

Aged↗
PubMed1986

Assay of phospholipase A2 activity of synaptic membranes using a phospholipid transfer protein: stimulation by depolarization.

A phospholipid transfer protein from bovine liver was used to transfer exogenous ([14C]linoleoylphosphatidylethanolamine [14C]linoleoyl PE) into synaptic membranes and synaptosomes without modifying the lipid compositions in order to study the intrinsic activity of phospholipase A2 of the preparations. Results were compared with the conventional method in which the substrate was simply dispersed with the enzyme preparations. Liberation of [14C]linoleic acid from [14C]linoleoyl PE-preloaded synaptic membranes by the transfer protein continued almost linearly over 60 min of incubation in the presence of Ca2+. The dose-response curve of Ca2+ for the activity of phospholipase A2 obtained in the present method was slightly shifted to the left in comparison with the conventional method: Ca2+ even at the concentration of 100 microM significantly enhanced the enzyme activity. Requirement of Ca2+ for the reaction is more specific in the present method than in the conventional one. When synaptosomes were prelabeled with [14C]linoleoyl PE by the transfer protein, the liberation of [14C]linoleic acid during the incubation at 37 degrees C increased linearly over 2 min. The liberation of [14C]linoleic acid was significantly enhanced in the presence of 56 mM KCl, 50 microM veratridine and 50 microM calcium ionophore A23187. These agents did not stimulate the reaction in the absence of Ca2+.

Animals↗
PubMed1986

Overproduction of proteins encoded by lambda replicon-integrated plasmid: effect of partial inactivation of cI repressor.

Composite plasmids containing the 7.2-kb fragment of bacteriophage lambda cI857cro27, essential for lambda DNA replication and its control, have been constructed. The plasmids contained, in addition, pBR322, a part of Co1E1, and the Escherichia coli pss gene, coding for phosphatidylserine synthase. When the plasmid-harboring cells were induced at different temperatures, the phosphatidylserine synthase production was maximum at 37 degrees C, and the specific activities at 37 degrees C continuously increased until the culture reached saturation. The results suggest that, when the cro gene is defective, only a transient temperature for inactivation of cI repressor provides both the increase in copy number of the plasmids and cellular activities that allow overproduction of the plasmid-encoded protein.

Bacteriophage lambda↗
PubMed1986

An unusual alimentary duplication cyst at the floor of the mouth--a proposal of new criteria for alimentary duplications.

In a 11-month-old boy, a cyst lined with non-keratinising stratified squamous epithelium and surrounded by striated muscle bundles with respiratory elements was found at the floor of the mouth. The cyst was excised without complications. As the cyst wall resembles the structure of the upper oesophagus, we think that this may be an alimentary duplication cyst, although it does not satisfy Lister's proposed criteria for alimentary duplications. To our knowledge, intraoral duplication cysts similar to the upper oesophageal tissue have not been reported previously. From the experience of this case, we propose new criteria for alimentary duplications.

Choristoma↗
PubMed1986

Membrane phospholipid synthesis in Escherichia coli: alteration by glycerol and physiological consequences in a pss mutant.

Escherichia coli mutants harboring the pss-1 allele (coding for a temperature-sensitive phosphatidylserine synthase) are temperature sensitive for growth and synthesize less phosphatidylethanolamine at higher temperatures, giving rise to abnormal membrane phospholipid compositions. To obtain information concerning the determinant for the phospholipid polar headgroup composition and the lethal factor in the defective membranes, we have examined the effect of increased supply of sn-glycerol 3-phosphate on the phospholipid synthesis and the growth ability of a pss-1 mutant. For this purpose, a pair of E. coli K-12 derivatives isogenic except for the pss-1 allele was constructed from strain BB26-36 to harbor the mutations related to glycerol metabolism (glpD3, glpR2, glpKi, and phoA8). Pulse- and uniform-labeling of phospholipids with 32P at 42 degrees C in a synthetic medium with (0.2%) or without glycerol showed that glycerol further lowered the temperature-sensitive formation of phosphatidylethanolamine, removed the phosphatidate and CDP-diacylglycerol accumulated in the absence of glycerol, and resulted in an increase in cardiolipin content in the pss-1 mutant. The phospholipid synthesis and contents in the pss+ strain were not significantly affected by glycerol. Glycerol in the medium markedly enhanced the growth defect of the pss-1 mutant, which was remediable by sucrose. The results indicate that the intracellular pool of sn-glycerol 3-phosphate is the limiting factor for acidic phospholipid synthesis in the pss-1 mutant, and cardiolipin unusually accumulated is injurious to the functional E. coli membranes. Possible determinants for the phospholipid composition of the wild-type E. coli cells are also discussed on the basis of the present observations.

CDPdiacylglycerol-Serine O-Phosphatidyltransferase↗
PubMed1986

Collagenase production by human mononuclear cells in culture: inhibition by gold containing compounds and other antirheumatic agents.

Human peripheral blood mononuclear cells in adherent cultures have been shown to synthesise and secrete collagenase. In the present study we have examined the modulation of collagenase production in these cultures by several antirheumatic agents. Incubation of monocytes in serum free medium with sodium aurothiomalate in concentrations varying from 7.7 X 10(-7) to 7.7 X 10(-3) mol/l resulted in marked dose dependent inhibition of the collagenase production. This inhibition was apparently selective in that total protein synthesis or the viability of the cells were not affected. Similar inhibition of the collagenase production was also noted with auranofin, aurothioglucose, and chloroauric acid. The inhibition with auranofin was achieved with a concentration as low as 7.4 X 10(-8) mol/l. To examine the mechanisms of the inhibition of the collagenase activity induced by sodium aurothiomalate the production of prostaglandin E2 was also measured in the same cell cultures. Sodium aurothiomalate in concentrations greater than 7.7 X 10(-4) mol/l significantly inhibited the prostaglandin E2 production; the prostaglandin E2 production was not inhibited, however, in 7.7 X 10(-5) mol/l concentration, while the collagenase production was reduced by 51.0%. Also, exogenous prostaglandin E2 added to the cultures only slightly reversed the inhibition of the collagenase production by sodium aurothiomalate. Thus the inhibition of collagenase production by sodium aurothiomalate in human adherent mononuclear cell cultures appears to be independent of the inhibition of prostaglandin E2 production. The inhibition of collagenase produced by monocyte-macrophages, as shown here in vitro, may contribute to the clinical efficacy of the compounds tested in the treatment of rheumatoid arthritis.

Anti-Inflammatory Agents↗
PubMed1986

Stimulatory effect of veratridine on lysophosphatidylethanolamine formation in rat brain synaptosomes.

[3H]-Arachidonic acid incorporation into phospholipids of synaptosomal lysates prepared from veratridine-treated synaptosomes was examined. Synaptosomal lysates were shown to acylate exogenously added lysophosphatidylcholine, lysophosphatidylinositol, and lysophosphatidylethanolamine, when incubated with [3H]-arachidonic acid, ATP, CoA and MgCl2, yielding the respective phospholipids. Preincubation of synaptosomes with veratridine for 30 sec gave rise to an increase in [3H]-arachidonic acid incorporation into phosphatidylethanolamine, but not phosphatidylcholine nor phosphatidylinositol, indicating that lysophosphatidylethanolamine might be produced by veratridine. This increase of radioactivity in phosphatidylethanolamine caused by veratridine was completely inhibited by 1 microM tetrodotoxin or in calcium-free condition. These observations show that lysophosphatidylethanolamine was formed in a calcium-dependent manner and accumulated in synaptosomes treated with veratridine, which may relate to its action on the sodium channel and enhanced calcium influx.

Animals↗
PubMed1986

[Pancreatic acinar cell carcinoma curatively resected by pancreaticoduodenectomy].

The incidence of acinar cell carcinoma among malignant pancreatic tumors is about 1%, and the prognosis is reported to be poor. We resected an acinar cell carcinoma that had arisen on the pancreatic head by pancreaticoduodenectomy in December 1983. This tumor occupied the pancreatic head, and it measured 10 X 9.5 X 9.5 cm. The microscopic findings showed that the tumor cell was well-differentiated and acinar formation was uniform. The growth of the tumor was expansive, and the lesion was clearly capsulated by fibrous tissue. There was no lymph node metastasis, so the curative operation was performed by the enbloc resection of the tumor. Zymogen granules in the tumor cells were confirmed by electron microscopy. Consequently, we concluded that the origin of the tumor was acinar cells.

Carcinoma↗
PubMed1985

The effect of ionic strength on the lipid peroxidation of porcine intestinal brush-border membrane vesicles.

The effects of salt concentration gradient (inside to outside) on the lipid peroxidation of porcine intestinal brush-border membrane vesicles have been studied and several interesting features of the peroxidation have been elucidated. The addition of dithiothreitol and Fe2+ is far more effective in induction of the lipid peroxidation than any of the other metal ion species tested (Fe3+, Cu2+, Ni2+, Zn2+ and Cr3+). The peroxidation rate of the membrane vesicles induced by dithiothreitol plus Fe2+ was sensitive for the incubation temperature and was increased with increase of the temperature. Imposition of an inward salt concentration gradient on the membrane vesicles preloaded with 300 mM mannitol by addition of 100 mM chloride of K+, Na+, Li+, Rb+, NH4+ or choline to medium produces a very large reduction of the lipid peroxidation induced by dithiothreitol plus Fe2+. The membrane peroxidation is depressed more with the mannitol (300 mM)-preloaded vesicles than with the K2SO4 (100 mM)-preloaded vesicles when they are incubated in medium containing 20-100 mM of K2SO4. Addition of membrane-permeant anions such as SCN- and I-, but not addition of NO3-, to incubation medium has been found to decrease markedly the lipid peroxidation of the mannitol-preloaded vesicles. From these results it is suggested that the lipid peroxidation of the brush-border membranes by addition of dithiothreitol plus Fe2+ is sensitively changed with change in ionic strength.

Animals↗
PubMed1985

Genetic manipulation of membrane phospholipid composition in Escherichia coli: pgsA mutants defective in phosphatidylglycerol synthesis.

Unique mutants of Escherichia coli K-12, defective in phosphatidylglycerol synthesis, have been isolated from a temperature-sensitive strain incubated at its nonpermissive temperature. The parent strain had excess phosphatidylglycerol by harboring both the pss-1 allele [coding for a temperature-sensitive phosphatidylserine synthase (EC 2.7.8.8)] and the cls- allele (responsible for a defective cardiolipin synthase). The newly acquired mutations caused better growth at higher temperatures. One of the mutations (pgsA3) has been identified in the structural gene for phosphatidylglycerophosphate synthase [glycerophosphate phosphatidyltransferase (EC 2.7.8.5)]. Phospholipid compositions of these mutants were remarkable; phosphatidylethanolamine was the sole major lipid. In media with low osmotic pressures, these cells grew more slowly than the wild-type cells. They grew normally without recovering from the phospholipid abnormality in media appropriately supplemented with sucrose and MgCl2. Formation of cardiolipin and phosphoglycerol derivatives of membrane-derived oligosaccharides was reduced in a pgsA3 mutant. E. coli strains having the pgsA3, pss-1, and cls- mutations, either individually or in combination, constitute an empirical system in which the molar ratio of three major membrane phospholipids can be variously altered.

Cardiolipins↗
PubMed1985

Dynamic behavior of the imino protons of the gamma OR3 17mer in H2O solution studied by high-resolution NMR.

The imino proton resonances of gamma OR3 17mer in water were observed at 500 MHz with the time-shared Redfield pulse train. All of the 17 imino proton resonances could be assigned specifically to individual base pairs by utilizing the trace of NOE connectivities between the imino and adenine C2H protons and between imino protons themselves. AT1 and 17 showed abnormally high chemical shifts in comparison with the other AT pairs. On raising the temperature, broadening of the signal occurred in a sequential manner from the terminals except for AT10 and AT11, which were broadened at a lower temperature than GC12. The relaxation rates of the imino protons were measured by the inversion recovery method. The rates at higher temperatures represent the exchange rates of the imino protons. From the temperature dependences, activation energies of about 15 kcal/mol for the AT imino protons and 23-26 kcal/mol for the GC imino protons were obtained.

Bacteriophage lambda↗
PubMed1985

Irreversible inhibition of calcium uptake in synaptosomes by quinacrine mustard: relationship to labeling sites of quinacrine mustard.

The sites of interaction of quinacrine with synaptic membranes were labeled with quinacrine mustard. Quinacrine mustard had an inhibitory effect on depolarization-induced calcium uptake by synaptosomes similar to that of quinacrine. The inhibition of depolarization-induced calcium uptake by quinacrine was reduced by 70% after washing, whereas that by quinacrine mustard was not affected. Fluorescence electrophoretograms of the quinacrine mustard-treated synaptic membranes showed that quinacrine mustard specifically labeled two proteins, with corresponding molecular weights of about 37,000 and 32,000.

Animals↗