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Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 739 records · Page 41Linked to original sources

Discriminative and aversive properties of beta-carboline-3-carboxylic acid ethyl ester, a benzodiazepine receptor inverse agonist, in rhesus monkeys.

Rhesus monkeys were trained to discriminate injections of saline from those of beta-carboline-3-carboxylic acid ethyl ester (beta-CCE), a compound that binds to the benzodiazepine receptor, but often has actions opposite to those of the benzodiazepines. A benzodiazepine agonist midazolam and low doses of a specific benzodiazepine antagonist, Ro 15-1788, reversed the discriminative effects of beta-CCE. Higher doses of Ro 15-1788 produced stimulus effects similar to beta-CCE. In a separate experiment, monkeys responded to terminate intravenous infusions of beta-CCE, but not midazolam. This aversive effect of beta-CCE was reversed by Ro 15-1788. The behavioral effects of beta-CCE in these non-human primates are consistent with other data that have shown it to act on benzodiazepine receptors, and support the hypothesis that beta-CCE can be considered an inverse agonist at this receptor.

Animals↗

Long survival in Fukuyama congenital muscular dystrophy: occurrence of neurofibrillary tangles in the nucleus basalis of Meynert and locus ceruleus.

Three patients with Fukuyama congenital muscular dystrophy (FCMD), who died aged 23, 29 and 34 years, are reported. There was extensive brain malformation, but the most severe pattern of cortical dysplasia was absent in one case and in the other two localized bilaterally to small areas near the occipital poles. In two cases, numerous neurofibrillary tangles were observed in the locus ceruleus and nucleus basalis of Meynert. Electron microscopy revealed paired helical filaments, with a maximal width of about 25 nm and regular constrictions at approximately 80 nm intervals. The occurrence of neurofibrillary tangles, which is unknown in younger patients, suggests the presence of degenerative processes in the brains of the older patients with FCMD.

Adult↗

Sterol composition and biosynthesis in mouse salivary glands.

Sterol components of mouse submandibular, sublingual and parotid glands were studied by thin-layer and gas-liquid chromatography. The major sterol was cholesterol (5-cholesten-3 beta-ol; 26.7, 28.0, 18.8 micrograms/mg protein respectively), with minor amounts of squalene, lathosterol (5 alpha-cholest-7-en-3 beta-ol), desmosterol (cholesta-5,24-dien-3 beta-ol), lanosterol (4,4',14-trimethyl-5 alpha-cholesta-8,24-dien-3 beta-ol), dihydrolanosterol (4,4',14-trimethyl-5 alpha-cholest-8-en-3 beta-ol) and methylstenol. Chromatograms of salivary sterols were similar to those of liver, and different from those of skin in which the amount of lathosterol was much higher. Administration of the anticholesterolaemic agent, 20,25-diazacholesterol, resulted in accumulation of desmosterol in all tissues tested, and additional sterols also accumulated in skin. The gas-liquid chromatographic profiles of salivary sterols from the treated animals were similar to those of liver, but different from those of skin. Thus sterols were synthesized in salivary glands and the biosynthetic pathway was via C24-unsaturated side-chain intermediates, as in liver. This was verified by showing that [2-14C]-mevalonate was incorporated into sterols in vitro when it was incubated with homogenates of these glands.

Animals↗

The electromyographic activity of the inferior part of the human lateral pterygoid muscle during clenching and chewing.

The nature of activity in the two parts of the muscle is controversial. A reliable technique was developed for recording activity in its inferior part by means of an indwelling needle electrode. This part was most active during anteriorly- or contralaterally-directed intercuspal clenching, vertically-directed clenching with the jaw positioned to the contralateral side or anteriorly, and during jaw opening and least active during vertically-, ipsilaterally- or posteriorly-directed intercuspal clenching, and during vertically-directed clenches with the jaw positioned to the ipsilateral side. During chewing, activity appeared in the late intercuspal phase irrespective of the side used. It commenced earlier when chewing strokes were ipsilateral to the muscle. Activity during both ipsilateral and contralateral chewing strokes continued until maximum opening, when it ceased for the duration of the closing and crushing phases of the cycle. Thus the inferior part, with other muscles, may participate in bracing the condylar head against the articular eminence during vertical-clenching efforts involving condylar displacement, but not in the compressive or crushing phases of the cycle.

Adult↗

Specific gonadotrophin binding sites in the bullfrog testis.

We demonstrated the presence of specific binding sites for bullfrog luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in a testicular crude plasma membrane fraction of the bullfrog, Rana catesbeiana. The equilibrium analysis of the binding showed that a straight line was fitted to the Scatchard plot of LH and a curvilinear line to that of FSH, suggesting the presence of single-type binding sites for LH and the presence of multiple-type binding sites or negative cooperactivity of the binding for FSH. Competition experiments showed that bullfrog LH could replace the specific binding of bullfrog FSH and vice versa. Binding affinity of bullfrog LH to radioiodinated bullfrog FSH binding sites was as high as that of intact bullfrog FSH to the same sites. In contrast, binding properties of bullfrog FSH to radioiodinated bullfrog LH binding sites were not simple: the competition curve obtained with FSH against the binding of bullfrog LH had an extremely low slope value and was not parallel to that obtained with LH. These results suggest that differentiation of LH and FSH receptors is not complete in this species, although it has been reported that these hormones have separate actions on the testis. Competition experiments further showed that bullfrog testicular LH and FSH receptors possessed higher affinities for gonadotrophins of homologous or closely related animal species compared with phylogenically distant groups. Species specificity of the hormone-receptor interaction may cause species specificity of the gonadotrophin action.

Animals↗

Inconsistent reactivity of an anti-sperm monoclonal antibody and its relationship to sperm capacitation.

An anti-sperm monoclonal antibody was developed from female C57BL/6 mice immunized with epididymal sperm from a syngeneic male mouse. Immunofluorescence staining revealed that the antibody did not react to fresh epididymal sperm but attached to the capacitated sperm found in the peri-vitelline spaces of the ova. When the antibody was applied to sperm incubated in vitro, variously stained sperm were observed. It was presumed that the antigenic site detected by the antibody was hidden in the fresh epididymal sperm and was spread from the acrosomal cap region to the entire head during the capacitation process.

Animals↗

trans activation of the latent Epstein-Barr virus (EBV) genome after transfection of the EBV DNA fragment.

Transfection of Epstein-Barr virus (EBV)-nonproducer Raji cells with the BamHI Z fragment of EBV DNA induced antigens that were detected with human antiserum against EBV-specific early antigens. Northern blot analysis of transfected cells revealed that one intense RNA band hybridized with the BamHI H and F fragments but not with the BamHI Z fragment. Cooperation between the BamHI H, F, and BamHI Z regions was also confirmed in baby hamster kidney cells that were cotransfected with both fragments. These results indicate that the transfected BamHI Z fragment of EBV DNA induces a trans-acting factor which activates the gene expression of the BamHI H and F region and that the BamHI Z region possibly plays an important role in the latency of EBV.

Animals↗

Identification of coding regions for various Epstein-Barr virus-specific antigens by gene transfer and serology.

Baby hamster kidney cells were transfected with BamHI fragments of Epstein-Barr virus (EBV) DNA (B95-8 strain) cloned into the pLTR vector containing retroviral enhancer and promoter sequences. Seventeen fragments (BamHI-A, -B, -C, -D, -E, -G, -K, -L, -M, -O, -P, -Q, -R, -U, -V, -X, and -Z) expressed antigenically distinct EBV-specific products recognized by EBV-immune human sera.

Antigens, Viral↗

Effects of certain salts on glucosyltransferase synthesis by Streptococcus mutans strain PS-14.

We investigated the effects of various salts on the synthesis of extracellular glucosyltransferase in a partially defined medium (M4) by Streptococcus mutans strain PS-14 and by certain other selected strains. The levels of glucosyltransferase produced by S. mutans strain PS-14 were found to increase to a maximum of seven-fold with increasing (NH4)2SO4 concentrations. However, at a 2% concentration of the salt, the level was stimulated 2.5-fold, and the growth was inhibited by 75%. A 1% concentration of MgSO4 or NaCl also caused an increase of glucosyltransferase of six-fold or 2.4-fold, respectively. However, for S. mutans strain B-13N, the enzyme production was not stimulated by (NH4)2SO4, MgSO4, or NaCl. Moreover, the enzyme production by serotypes c, e, and f was found to be stimulated by 1% (NH4)2SO4, whereas the enzyme production by serotypes d and g was not affected.

Ammonium Sulfate↗

Effect of administration route on the selective lymphatic delivery of cyclosporin A by lipid-surfactant mixed micelles.

The absorption and lymphatic delivery of a new immunosuppressive drug, cyclosporin A (CsA), with the aid of lipid surfactant mixed micelles (MM) system using different administration routes were studied in the thoracic duct cannulated rat model at a dose level of 7 mg/kg. The rectal or intraperitoneal (i.p.) administration of CsA indicated a small amount of CsA in the plasma and in the lymph for 6 h. As oral routes, intrastomach (i.s.) and intraduodenal (i.d.) administration of CsA were performed and high lymph CsA levels were obtained. The i.s. administration of CsA resulted in the highest CsA levels in the lymph, 16 micrograms/ml, about twenty times higher than the rectal or i.p. administration. These results strongly support the usefulness of an oral CsA dosage form for the selective lymphatic delivery of CsA in clinical immunosuppressive therapy by means of a new mixed micelles system.

Administration, Oral↗

Enhancing effect of absorption promoters on percutaneous absorption of a model dye (6-carboxyfluorescein) as a poorly absorbable drug. III. Histological study after addition of various absorption promoters in rats.

We have studied the effect of various absorption promoters on the percutaneous absorption dynamics of 6-carboxyfluorescein (CF) which is a poorly absorbable drug. The absorption of CF was determined by fluorescence photographic image since CF emits a strong light yellow fluorescence. The co-administration of sodium dodecylsulfate (SDS) and 2-mercaptoethanol (MER), the pretreatment with calcium thioglycolate and the co-administration of Azone (AZ) and surfactant (HCO-60) were used to promote the absorption of CF. We have also studied the injury of skin tissue by the absorption promoters. The fluorescence photographic image of rat skin, after the co-administration of SDS and MER and after the co-administration of AZ and HCO-60 were similar to the image with the stratum corneum removed from the skin. These absorption promoters did not affect the histological nature of the rat skin tissue and the recovery experiment showed no injurious effect by these absorption promoters to the skin tissue.

Animals↗

Studies on sperm capacitation using monoclonal anti-body--disappearance of an antigen from the anterior part of mouse sperm head.

C57BL/6 mice were immunized with cauda epididymal sperm from syngenic mice. A monoclonal antibody (TSC4) was obtained using a hybridization method with myeloma (P3U1) cells. The antibody was examined for its reactivity to sperm from different regions of the reproductive tract of male mice. The antigen was recognized only when the sperm reached the corpus epididymis. The area of antigen present on the sperm membrane was topographically restricted to the anterior part of sperm head. The antigen remained on the sperm after washing with phosphate buffered saline, disappearing, however, when sperm was capacitated.

Animals↗

The mode of enhanced enteral absorption of macromolecules by lipid-surfactant mixed micelles. I.

The enhancement of absorption of water soluble macromolecules by lipid-surfactant mixed micelles (MM) was performed in two in vitro experimental systems using rat large intestine, which were isolated epithelial cells containing transcellular route alone and everted sac involving trans- and paracellular routes. Four kinds of fluorescein isothiocyanate-labelled dextrans (FDs) having different average molecular weights (9K-70K) were used as models of water soluble macromolecules. In the absence of MM, very poor transport of FDs was observed in both isolated epithelial cells and everted sac experiments. Linoleic acid-polyoxyethylated (60 mol) hydrogenated castor oil (HCO60) MM enhanced the transport of FDs in both systems, especially for smaller size FDs. This promotive effect by MM decreased with an increase in molecular weight of FDs in both systems. Although enhanced transport of the largest FD (molecular weight, 70K) by MM was clearly demonstrated in the everted sac, the enhanced transport of the same FD in the isolated cells was negligible. These results suggest the possibility of participation of paracellular route as well as transcellular route in the enhancing effect of MM on the large intestinal absorption of water soluble macromolecules.

Animals↗