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Biomedical subjects

Y Ohkubo

Publications and source records attributed to Y Ohkubo.

At least 91 records · Page 5Linked to original sources

Structural study of cell wall mannan of a Candida albicans (serotype A) strain.

The structure of the mannan of Candida albicans NIH A-207 strain (serotype A) was investigated by adopting mild acetolysis followed by enzymolysis with an Arthrobacter GJM-1 exo-alpha-mannosidase. The resultant oligosaccharides, from pentaose to octaose (where manp = D-mannopyranose), were identified as manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp, manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)- manp alpha (1----2)manp, manp beta (1----2)manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp and manp beta (1----2)manp beta (1----2)manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp, respectively. Analyses of alpha-linked oligosaccharides obtained by acetolysis under conventional conditions gave the same oligosaccharides, from biose to heptaose, as those obtained from the mannans of C. albicans NIH B-792 (serotype B) and J-1012 (serotype A, formerly serotype C).

Candida albicans↗

Presence and properties of acyl coenzyme A synthetase for medium-chain fatty acids in rat intestinal mucosa.

A system was developed for assay of acyl coenzyme A (acyl CoA) activity on medium-chain fatty acids in rat intestinal mucosa. Using this system, we compared the characteristics of octanoyl (C8:0) CoA synthetase activity and palmitoyl (C16:0) CoA synthetase activity. Palmitoyl CoA synthetase activity as a function of palmitate concentration followed Michaelis-Menten kinetics, but octanoyl CoA synthetase activity as a function of octanoate concentration showed a biphasic reaction curve. The distributions of octanoyl CoA synthetase activity and palmitoyl CoA synthetase activity along the gastrointestinal tract were similar, both activities being present mainly in the middle portion of the small intestine. Incubation of octanoate with a homogenate of intestinal mucosa revealed that octnoate, like palmitate, is incorporated into phospholipids and triglycerides after its CoA activation. Oral administration of medium chain triglycerides induced a nearly 2-fold increase in octanoyl CoA synthetase activity in rat intestinal mucosa, whereas oral administration of long chain triglycerides did not affect the palmitoyl CoA synthetase activity. These results indicate that acyl CoA synthetase for medium-chain fatty acids in rat intestinal mucosa plays a key role in the utilization of medium-chain fatty acids for lipid synthesis, and that it is regulated in a different manner from acyl CoA synthetase for long-chain fatty acids.

Adenosine Triphosphate↗

Concomitant increase in putrescine incorporation with transferrin uptake into rat reticulocytes.

Concomitant increase in putrescine incorporation with transferrin uptake into rat reticulocytes was found. [14C]Putrescine incorporation occurred in the presence of transferrin at 37 degrees C. The subcellular distribution of incorporated [14C]putrescine showed that the incorporation in the plasma membrane time dependently increased. Both 125I-labeled transferrin uptake and [14C]putrescine incorporation decreased when ethylene glycol bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid was added, while it increased with the addition of A23187.

Animals↗

The relationship of putrescine incorporation to transferrin uptake by reticulocytes.

We previously reported that putrescine incorporation occurred during transferrin uptake by rat reticulocytes (1). Both the putrescine incorporation and transferrin uptake were enhanced by the presence of Ca2+ and A23187. Furthermore, putrescine dose-dependently increased the transferrin uptake. Additionally, transglutaminase inhibitors partially blocked not only the putrescine incorporation but also the transferrin uptake.

Animals↗

Effect of FR121196, a novel cognitive enhancer, on the memory impairment of rats in passive avoidance and radial arm maze tasks.

Passive avoidance performance was impaired in young rats by scopolamine (1.0 mg/kg) or by nucleus basalis magnocellularis lesions and in aged rats (24-26 months old). FR121196[N-(4-acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide+ ++], a newly introduced cognitive enhancer, ameliorated the failure in memory retention with bell-shaped dose-response curves in doses ranging from 0.1 to 10 mg/kg. Similar dose-response curves also were obtained with methamphetamine (0.1-10 mg/kg), whereas physostigmine (0.01-1.0 mg/kg) attenuated the amnesia in scopolamine-treated rats, but hardly affected that in nucleus basalis magnocellularis-lesioned or aged rats. In radial arm maze tasks, behavioral indices of spatial memory, such as first correct choices and number of errors, were impaired by an injection of scopolamine (0.5 mg/kg) or by lesions of the medial septum or fimbria-fornix. FR121196 ameliorated the scopolamine-induced memory deficit with a bell-shaped dose-response curve, whereas methamphetamine had the opposite effect. These two drugs had little effect on memory deficits brought about by medial septum or fimbria-fornix lesioning, whereas physostigmine ameliorated these deficits in scopolamine-treated and medial septum-lesioned rats, but not in fimbria-fornix-lesioned rats. Behavioral studies using Animex demonstrated that FR121196, in contrast with methamphetamine, does not increase locomotor activities in rats up to a dose of 10 mg/kg. These results are discussed in relation to the cholinergic and dopaminergic mechanisms of memory.

Aging↗

Involvement of dopamine in the mechanism of action of FR64822, a novel non-opioid antinociceptive compound.

A novel compound, FR64822(N-(4-pyridylcarbamoyl)amino 1,2,3,6,-tetrahydropyridine), displays antinociceptive activities in a variety of assays with mice and rats. It has a strong antinociceptive activity in the acetic acid writhing test (ED50 = 1.8 mg/kg p.o.), whereas it has little antinociceptive activity in the tail flick test. The antinociceptive profile is similar to that of nefopam but different from that of anti-inflammatory agents. The involvement of monoamines in the mechanism of action of FR64822 was investigated. Pretreatment with reserpine (2 mg/kg) significantly reduced the antinociceptive activity of FR64822, when tested against acetic acid writhing. A similar reduction of activity was found in mice pretreated with sulpiride (10 mg/kg), a dopamine D2 receptor antagonist, but not with Sch23390 (0.25 mg/kg), a dopamine D1 receptor antagonist. Pretreatment with p-chlorophenylalanine, yohimbine and naloxone hardly affected the antinociceptive activity of FR64822. These results were compared with those for nefopam and clonidine. It is suggested that FR64822 induces antinociceptive activity through a novel mechanism of action, indirect stimulation of dopamine D2 receptors, which differs from that of nefopam in that no specific neurotransmission could be determined in nefopam analgesia.

Acetates↗

Differential effects of physostigmine and pilocarpine on the spatial memory deficits produced by two septo-hippocampal deafferentations in rats.

Rats that had received two kinds of septo-hippocampal deafferentations, medial septum (MS) lesion and fimbria-fornix (FF) transection, were assayed for brain cholineacetyltransferase (ChAT) activity and spatial memory in an 8-arm radial maze task. Both lesions produced profound and long-lasting spatial memory impairments, which were characterized by a reduction in the numbers of correct arm choices and first correct choices, a reduction in the percent of correct choices and an increase in the number of errors. The degree of memory impairment was severer in FF- than in MS-lesioned rats, and paralleled that of decreases in ChAT activity in the hippocampus. MS lesion reduced ChAT activity in the hippocampus by approximately 45%, while FF lesion almost completely depleted the activity. An intraperitoneal injection of physostigmine (0.0032-0.32 mg/kg), an acetylcholinesterase (AChE) inhibitor, significantly ameliorated the spatial memory deficit induced by MS lesion, but hardly affected that by FF lesion. In contrast, intraperitoneal doses (0.032-3.2 mg/kg) of pilocarpine, a muscarinic agonist, showed a significant improvement of both types of memory deficit with bell shaped dose-response curves. The drug was more potent in the FF- than in the MS-lesioned rats. These results suggest that the septo-hippocampal cholinergic system plays a crucial role in the maintenance of spatial memory, and that the degree of septo-hippocampal deafferentation affects the efficacy of cholinergic drugs.

Animals↗

Changes in transglutaminase activity in carbon tetrachloride-damaged rat liver.

A significant decrease in transglutaminase (TGase) activity was observed in the cytosol and nuclear fractions of carbon tetrachloride-damaged rat liver. The degree of decrease in TGase activity in the cytosol fraction was closely related to the serum transaminase level. Gel filtration studies revealed that TGase activity in 80 kDa fractions significantly decreased, but that in 160 kDa fractions slightly increased after carbon tetrachloride treatment.

Alanine Transaminase↗

An investigation on rheumatoid factor of different immunoglobulin classes in hepatitis B virus carriers.

Rheumatoid factor (RF) is known to be present very frequently in HB virus carriers. When RF was assayed in 140 asymptomatic carriers by agglutination method, 20.0% were found to be positive, whereas 2.7% in the controls (p less than 0.01). ELISA for detection of RF isotypes showed RF in carriers to be almost IgMRF only. IgMRF showed a tendency to react more readily to human IgG rather than to rabbit IgG. The incidence of IgMRF positivity was higher among anti-HBe antibody-positive carriers than among anti-HBe antibody negative ones, but the difference between the two populations was not significant. However, the incidence of IgMRF positivity in the group showing hepatic dysfunctions was found to be significantly higher than in the group with normal hepatic functions.

Agglutination Tests↗

Characterization of a novel aldose reductase inhibitor, FR74366, and its effects on diabetic cataract and neuropathy in the rat.

FR74366 (FK366) ([3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4- tetrahydroquinazolin-1-yl] acetic acid) is a chemically novel aldose reductase (AR) inhibitor. It exhibited a highly potent, reversible, and mixed type inhibition of partially purified AR from the rat sciatic nerve (IC50 = 3.6 nmol/L) and rat lens (IC50 = 4.4 nmol/L). FR74366 inhibited sorbitol accumulation in the isolated human erythrocyte (IC50 = 1.6 mumol/L), rat lens (IC50 = 39 mumol/L), and rat sciatic nerve (IC50 = 17 mumol/L) incubated with high glucose concentrations. The oral administration of FR74366 to streptozotocin (STZ)-induced diabetic rats for 2 weeks decreased sorbitol levels (ED50 = 3.7 mg/kg for sciatic nerve, 23 mg/kg for lens, 52 mg/kg for retina, and 62 mg/kg for renal cortex). Administration of FR74366 to diabetic rats for 17 weeks delayed cataract formation and admixture of 0.028% FR74366 in the diet completely inhibited the cataract formation. Moreover, the recovery of reduced motor nerve conduction velocity by FR74366 in diabetic rats was demonstrated in prevention and reversal experiments. This recovery effect correlated well with reduction of accumulated sorbitol and fructose levels and normalization of decreased myoinositol levels. The duration and tissue specificity of inhibitory effects of FR74366 on sorbitol accumulation also correlated well with the levels of FR74366 in various tissues of diabetic rats. These data indicate that both decreases in tissue sorbitol levels and improvement of functional defects reflect FR74366 levels in tissue rather than plasma in diabetic rats. These results, taken together, suggest that FR74366, which is currently undergoing clinical trials in Japan and the United States, will be a useful therapeutic agent for diabetic complications.

Aldehyde Reductase↗

Studies on 67Ga uptake by mouse granuloma tissues.

In connection with the uptake of 67Ga into the inflammatory tissues, such as granuloma tissues produced with turpentine oil, the influence of Fe3+ on the uptake of 67Ga into mouse granuloma and normal tissues and on the uptake of 125I-labeled transferrin and 59Fe were investigated. Fe3+ decreased the uptake of 67Ga into the liver and spleen, but had no influence on the uptake of 67Ga into the granuloma tissues. The uptake patterns of 125I-labeled transferrin and 59Fe in the granuloma tissues were not consistent with that of 67Ga at all. These results show that the uptake of 67Ga into the granuloma tissues occurs in a free, transferrin-unbound form, but into the liver and spleen in a transferrin-bound form.

Animals↗

Internalization model using rat liver plasma membrane for receptor-mediated endocytosis of epidermal growth factor.

We have demonstrated the internalization of epidermal growth factor (EGF) using membrane isolated from rat liver. The isolated membrane exhibited a saturation curve of the binding of 125I-EGF. Furthermore, competition between the binding of 125I-EGF and unlabeled EGF to the isolated membrane was observed. These results were similar to those obtained from whole hepatocytes. In order to confirm whether or not the present experimental system using the isolated membrane can be used for the study of receptor-mediated endocytosis, the internalization of pre-bound EGF in the isolated membrane was assessed by two different methods. First, acid-insensitive 125I-EGF time-dependently increased following incubation at 37 degrees C. Secondly, EGF became inaccessible to the exogenous 125I-anti-EGF antibody when under the same condition. These processes were dependent on adenosine triphosphate, but independent of Ca2+ and stimulated by guanosine triphosphate. These results demonstrate that receptor-mediated endocytosis occurred in the isolated membrane.

Animals↗

Modulation of epidermal growth factor binding to receptor by isoproterenol and cholera toxin in primary cultured hepatocytes.

The treatment of rat hepatocytes with isoproterenol induced the increase in the affinity of high affinity binding sites and the decrease in the number of low affinity binding sites of epidermal growth factor (EGF). Similar results were obtained from the pretreatment of hepatocytes with cholera toxin. These results suggest that adenylate cyclase affects the affinity and number of EGF-receptor in hepatocytes.

Adenylyl Cyclases↗

T-zone lymphoma in association with systemic lupus erythematosus.

Two patients with systemic lupus erythematosus (SLE) and T-zone lymphoma are described. On admission, both showed arthralgia, generalized lymphadenopathy, hypergammaglobulinemia and positive antinuclear antibody. Lymph node biopsies revealed diffuse infiltration of atypical T-lymphocytes in the expanded interfollicular area (T-zone), a finding characteristic for the T-zone lymphoma. Renal biopsy showed lupus nephritis and neoplastic lymphoid cell infiltration in the glomeruli of one patient, but only diffuse infiltration of neoplastic lymphoid cells and mature plasma cells were observed in the interstitium of the other patient. Both patients responded remarkably well to prednisolone (1 mg/kg/day).

Humans↗

[Hairy cell leukemia expressing SIgM+, SIgG-, CD11b+ and CD21+ and accompanying lymphadenopathy without splenomegaly].

Hairy cell leukemia (HCL) expressing both surface monocytoid antigen and IgM (kappa) was reported. A 62-year-old male was admitted to our hospital in September 21, 1989 because of leukocytosis. Physical examinations showed axillary and inguinal lymphadenopathy but no hepato-splenomegaly. The leukocyte count was 12,600/microliters with 73% of abnormal cells like large lymphocytes which had abundant cytoplasm and hairy appearance under phase microscopy. They had ruffles with microvilli under electron microscope. Bone marrow puncture showed normocellular marrow with 71.2% of abnormal cells similar to the peripheral blood. Surface markers were CD11b+, CD21+, HLA-DR+, Tac- and IgM (kappa). They were positive for ++acid phosphatase staining, but negative for peroxidase and tartrate-resistant acid phosphatase staining. He was diagnosed as Japanese type HCL. HCL expressing both surface monocytoid antigen and IgM is rare and the clinical features of our case are compared with those reported in Japan.

Antigens, Differentiation, B-Lymphocyte↗

[A case report of anomalous left brachiocephalic vein].

An anomalous case of a left brachiocephalic vein passing behind the ascending aorta was observed in a 49-year Japanese man. This is known as anomalous left brachiocephalic vein. The anomalous left brachiocephalic vein descended along the left mediastinum in a position identical to that of a persistent left superior vena cava, so the diagnosis of this venous abnormally require carefully considered. Many cases of anomalous left brachiocephalic vein have been reported based on autopsy findings, but this venous anomaly was recently demonstrated by ultrasonography, CT, and MRI.

Brachiocephalic Veins↗

Tissue reaction to collagen-coated porous hydroxyapatite.

To give tenacity to high porosity (80%-90%) hydroxyapatite (HA) and to make a stronger bone substitute, a collagen-coated porous HA (C-HA) was prepared, and its compressive strength was examined. By implanting C-HA into the femoral condyle of adult rabbits, the capacity for new bone formation and foreign-body reactivity were quantitatively compared with those of HA alone. The compressive strength of C-HA was 4.3 times greater than HA. At four weeks after implantation, the mean areal ratio of the newly formed bone in the C-HA block in each rabbit was 9.9%, which was somewhat less than the 13.7% in the HA block; the mean number of multinucleated giant cells (MGC) per visual field at x25 in the C-HA-implanted specimens in each rabbit was 14.4, significantly larger than the 6.1 in the HA specimens. However, 12 weeks after C-HA implantation, the areal ratio of new bone increased to 32.7%, the number of MGC decreased to 9.4, and the differences compared to the values in HA cases, 31.5% and 6.8, disappeared. These results showed that C-HA is mechanically stronger than HA and that there is no difference between HA and C-HA in capacity for new bone formation or foreign-body reaction.

Animals↗