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Biomedical subjects

K Iwamoto

Publications and source records attributed to K Iwamoto.

At least 127 records · Page 7Linked to original sources

Factors affecting acetohexamide reductase activities in microsomes and cytosol from the kidney of male rats: age and castration.

Acetohexamide reductase activity in microsomes from the kidney of male rats increased markedly at puberty to approach the maximum level at 8 weeks of age; it was not detected until 4 weeks of age. Furthermore, castration suppressed effectively the activity in kidney microsomes at 8 weeks of age. These findings clearly indicate that the activity in kidney microsomes can be regulated by androgens. On the other hand, in cytosol from the kidney of male rats, a higher acetohexamide reductase activity was observed at all weeks of age tested. Castration had no significant effect on the activity in kidney cytosol.

Aging↗

[A case of optic neuritis associated with anticardiolipin antibodies].

We reported a case of optic neuritis with the persistence of severe visual loss and central scotoma in a 26-year-old woman who was proven to have biologic false positive test for syphilis, and the elevated serum titres of IgG and IgM anticardiolipin antibodies. C.S.F. findings showed the absence of oligoclonal bands and the presence of IgM anticardiolipin antibody. She was treated twice at intervals of two weeks with methylprednisolone 1000 mg intravenously daily for three days (pulse therapy), and was started on oral prednisolone 60 mg daily which tapered gradually. After the second treatment of the pulse therapy, her visual acuity was improved remarkably and the titre of anticardiolipin antibodies became normal. Her clinical course seemed to be different from that of the optic neuritis of multiple sclerosis, in which many of patients recover near normal visual acuity after a first attack. We suggested that antiphospholipid antibodies might play a role in the etiology of her optic neuritis.

Adult↗

Polysaccharide-coated oil droplets in oil-in-water emulsions as targetable carriers for lipophilic drugs.

Surface of oil droplets in an oil-in-water (o/w) emulsion were coated with naturally occurring polysaccharides (such as mannan, amylopectin, and pullulan) which were, in part, bearing a cholesterol moiety. The mean size of the colloidal droplets was not altered much, even by coating with the polysaccharide derivatives, while the surface charge of the droplet decreased upon coating. Mannan and amylopectin derivative-coated droplets aggregated upon addition of Concanavalin A. These observations suggest that the terminal sugar moiety of the specific polysaccharides on the surface of colloidal droplets can be recognized by lectin. After intravenous injection of the emulsions into guinea pigs, kinetics of the blood clearance and the tissue distribution of the polysaccharide-coated oil droplets, which contain [14C]coenzyme Q10 as the marker, were investigated. In the initial rapid phase of blood clearance of the radioactivity, the polysaccharide-coated droplets were cleared from the blood stream slower than the uncoated ones. The lung uptake of the mannan derivative-coated droplet emulsion at 30 min after intravenous injection was approximately 15 times higher than that of the conventional emulsion without the polysaccharide coat.

Animals↗

Improvement in the proliferative activity of human-human hybridomas at low cell density by transfection with bFGF gene.

Highly purified recombinant basic fibroblast growth factor (rbFGF) and acidic FGF (aFGF) stimulated the proliferation of human-human (h-h) hybridomas to the extent of over four-fold from a low cell density such as 1 x 10(3) cells per ml in a serum-free medium in 24-well plates. The stimulatory effect of rbFGF was also observed in various lymphoid cell lines. Expecting that FGF could be an autocrine growth factor, we introduced bFGF gene into a h-h hybridoma using an expression plasmid induced by dexamethasone. The transformed cells thus obtained, HPO-75.11 bFGF-7, were able to grow well from a low inoculum density in a serum-free medium and antibody production was also increased when bFGF gene expression was induced. The transformed cells could grow at clonal density in a serum-free medium in 96-well plates, though the original cells could not. We also obtained a more practical transfectant, HPO-75.29-H74, using a high-shear stress adapted clone as the recipient and an expression plasmid having bFGF gene under the control of metallothionein-I promoter. The HPO-75.29-H74 cells were capable of growing and producing human monoclonal antibody against hepatitis B virus surface antigen from an inoculum density of 1 x 10(3) cells per ml in an agitation vessel without addition of an inducer.

Animals↗

Salivary excretion of mexiletine in normal healthy volunteers.

To investigate the kinetics and correlation between serum and saliva levels of mexiletine, serum (total and unbound) and saliva drug concentration-time courses have been analysed in five normal healthy volunteers after administration of a single oral dose (200 mg) of the drug. Mexiletine levels in saliva were always higher than those in serum. The drug concentration-time curve in each sample was analysed according to the non-linear least squares regression program MULTI, for a two-compartment model with first-order absorption. The saliva drug concentration in the post-absorption phase was found to be well correlated with either corresponding serum total or serum unbound drug level in four of the subjects. Although there was a large inter-individual variation in the ratio of saliva to serum drug concentrations as well as in the pharmacokinetic parameters, an almost consistent ratio was obtained in each individual.

Administration, Oral↗

Pharmacokinetics of [6]-gingerol after intravenous administration in rats.

A high-performance liquid chromatographic method to determine [6]-gingerol, a pungent constituent of ginger, in rat plasma was developed and a pharmacokinetic study was performed in rats. Quantitative analysis with high reproducibility was achieved for [6]-gingerol over the concentration range of 0.2-40 micrograms/ml. After bolus intravenous administration at a dose of 3 mg/kg, the plasma concentration-time curve was described by a two-compartment open model. [6]-Gingerol was rapidly cleared from plasma with a terminal half-life of 7.23 min and a total body clearance of 16.8 ml/min/kg. Serum protein binding of [6]-gingerol was 92.4%.

Animals↗

Enhanced entry of ciprofloxacin into the rat central nervous system induced by fenbufen.

The effects of fenbufen on the transport of ciprofloxacin (CPFX) into the brain and cerebrospinal fluid (CSF) were investigated in rats. Periodically after a bolus i.v. dose of CPFX (10 mg/kg), alone or with fenbufen (20 mg/kg), to rats, aliquots of CSF and blood were collected and then the whole brain was readily excised from the animal after sacrifice by microwave irradiation. Serum levels of CPFX in the terminal phase were significantly elevated by the coadministration with fenbufen. However, the extent of CPFX binding to serum protein was not affected by fenbufen. Immediately after the coadministration with fenbufen, brain and CSF levels of CPFX were raised by about 15 to 70% and 70 to 100%, respectively. Both brain/serum unbound and CSF/serum unbound level ratios were increased by fenbufen at relatively early periods after drug injection. Analysis based on physiological models indicated that fenbufen significantly increased the apparent diffusion clearances of CPFX across blood-brain and blood-CSF barriers. These findings suggest that coadministered fenbufen may facilitate the entry of CPFX into the central nervous system not only by elevation of serum level but also by enhancement of permeability across the blood-brain or blood-CSF barrier.

Animals↗

[A case of Günther vena caval filter insertion for recurrent pulmonary embolism].

We report that the Günther vena caval filter was successfully inserted in a case of recurrent pulmonary embolism resulting from ilio-femoral venous thrombosis. A 42-year-old woman was admitted to Osaka City University Medical School Hospital for dyspnea and chest pain on April 19, 1988. Pulmonary perfusion scintigraphy and pulmonary arterial angiography proved pulmonary emboli. The combination therapy of heparin and urokinase was performed, and her condition markedly improved. Then an ilio-femoral venography revealed only iliac vein compression but no thrombi. Therefore she was followed as an out patient with anticoagulant therapy. Nevertheless on April 10, 1989 she was admitted again complaining dyspnea and cyanosis. By venography at this time, some filling defects due to thrombi in right iliac vein were found. Therefore, we decided the insertion of the Günther vena caval filter for recurrent pulmonary embolism using Seldinger method via right internal jugular vein. We expect that the Günther vena caval filter will be useful for preventing pulmonary embolism resulting from ilio-femoral venous thrombosis because its procedure is easy, non-invasive and without significant complications.

Adult↗

Synthesis and characterization of 1,2-dimyristoylamido-1, 2-deoxyphosphatidylcholine as an artificial boundary lipid.

The synthesis and characterization of an artificial boundary lipid, 1,2-dimyristoylamido-1,2-deoxyphosphatidylcholine (DDPC), are described. DDPC has two amide bonds instead of ester bonds of regular lecithins such as 1,2-dimyristoylphosphatidylcholine (DMPC). In differential scanning calorimetry (DSC) measurements, DDPC gave two endothermic peaks: one was at 18.0 degrees C (delta H = 10.74 kJ.mol-1) and the other at 23.0 degrees C (delta H = 12.91 kJ.mol-1). The former peak was sharp and considered to be the phase transition of the hydrocarbon region, while the latter was assigned to the melt of the hydrogen-belt formed by the amide groups of DDPC. Addition of DDPC to DMPC made the DMPC membrane less fluid in the region close to the surface, and significantly increased the reconstitution efficiency of glycophorin into the membrane. This effect of DDPC was much larger than that of naturally occurring lipid, sphingomyelin.

Animals↗

Mechanism in 1,25(OH)2D3-induced suppression of helper/suppressor function of CD4/CD8 cells to immunoglobulin production in B cells.

On the basis of previous data that 1,25(OH)2D3 suppressed both helper and suppressor activities of CD4 and CD8 cells in the pokeweek mitogen-stimulated culture, we examined the further effect of 1,25(OH)2D3 on both cells to define how 1,25(OH)2D3 is involved in the deterioration of their functions. 1,25(OH)2D3 suppressed the pokeweed mitogen and phytohemagglutinin-induced DNA synthesis of CD4 and CD8 cells. The suppression by 1,25(OH)2D3 of DNA synthesis was caused by a time lag in reaching maximal response. 1,25(OH)2D3 also suppressed interleukin-2 production of CD4 and CD8 cells. 1,25(OH)2D3 did not, however, affect their interleukin-2 receptor expression detected within 24 hr after phytohemagglutinin stimulation. In addition, 1,25(OH)2D3 failed to suppress DNA synthesis of CD4 and CD8 cells when cultured with a large amount of interleukin-2. Suppression by 1,25(OH)2D3 of proliferation and interleukin-2 production in CD4 and CD8 cells would bring about the decrease of their helper or suppressor functions by inhibiting their expansion or maturation.

Antibody-Producing Cells↗

Improvement in the antibody productivity of human-human hybridomas by transfection with Tac gene.

The presence of a highly purified recombinant interleukin-2 (rIL-2) increased the production of immunoglobulin (IgM or IgG) by human-human hybridomas to 1.5-2.0 times the production by untreated cells. However, these cells did not react with anti-Tac (IL-2 receptor alpha) antibody. To enhance the response of the hybridoma cells to rIL-2, Tac gene was introduced by co-transfection with Tac gene expression plasmid pTB459 and G418 resistant gene expression plasmid pRSVneo. Tac cDNA transfected hybridoma (HBW-4.16.459-6-126) was induced to produce 6 times as much IgG by rIL-2 as was the control. This antibody production promoting phenomenon mediated by rIL-2 was depressed by anti-Tac antibody.

Antibodies, Monoclonal↗

A possible reduction in the renal clearance of ciprofloxacin by fenbufen in rats.

The change in plasma concentration-time profile, serum protein binding and renal and biliary clearances of ciprofloxacin caused by coadministration of fenbufen has been studied in rats administered an intravenous dose of ciprofloxacin (5 mg kg-1) alone or with fenbufen (10 mg kg-1). Coadministered fenbufen significantly prolonged the plasma elimination half-life of ciprofloxacin from 40.5 to 57.6 min and tended to reduce the total body clearance of this quinolone by about 20%. The extent of ciprofloxacin binding to rat serum protein was not affected by fenbufen, nor did it affect the biliary clearance of the quinolone. However, fenbufen tended to reduce renal clearance and significantly decreased the cumulative renal excretion of the quinolone during at least the first 3 h after drug administration. These results suggest a possible reduction of ciprofloxacin clearance owing to inhibition of renal excretion by fenbufen.

Animals↗

Restrictive cardiomyopathy following acute myocarditis--a case report.

A fifty-five-year-old man developed intractable heart failure four weeks after upper respiratory infection. His central venous pressure was as high as 300 mmH2O. Two-dimensional echocardiogram revealed no muscular hypertrophy of the ventricles, no pericardial thickness, and no pericardial effusion. On catheterization, hemodynamic data were compatible with restrictive cardiomyopathy. Transvenous endomyocardial biopsy of the left ventricle was performed. Histologic examination strongly suggested that cardiomyopathy developed after acute myocarditis.

Biopsy↗

A minor possibility of pharmacokinetic interaction between enoxacin and fenbufen in rats.

In order to clarify the possibility of pharmacokinetic interaction between quinolone and fenbufen, the plasma concentration-time profiles and serum protein binding of enoxacin, fenbufen and its active metabolite, felbinac, were investigated in rats. The rats were administered an intravenous dose of enoxacin (5 mg/kg) and fenbufen (10 mg/kg) alone or concomitantly. Coadministration with fenbufen tended to prolong the plasma elimination half-life of enoxacin by about 20%, whereas it showed no effect on the area under plasma concentration-time curve, total body clearance or distribution volume of enoxacin. The extent of enoxacin binding to rat serum tended to be slightly reduced by fenbufen in vivo and in vitro. Plasma concentration-time curves, pharmacokinetic parameters and serum protein binding of fenbufen and felbinac were not affected at all by the coadministration with enoxacin. These aspects suggest that there may be only a minor possibility of the pharmacokinetic interaction between enoxacin and fenbufen.

Animals↗

Transcellular permeation of nitrophenols through newborn rat skin epidermal cells in monolayer culture.

The permeation of nitrophenols through epidermal cells from newborn rat skin cultured on type IV collagen-coated Millipore filters was studied under various conditions. The order of permeation through the cultured skin cells was found to be p- greater than m- greater than o-nitrophenol at both 10 and 37 degrees C. This order was the same as that of their affinities to isolated skin cells. The permeation of nitrophenols was not inhibited by the inhibitors of energy transduction 2-deoxyglucose and NaN3. These results suggest that the permeation of nitrophenols across a cultured cell layer occurs by simple diffusion. The order of permeation of nitrophenols across newborn abdominal epidermis was exactly the opposite of that of their permeation across a cultured cell layer.

Animals↗