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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 523 records · Page 29Linked to original sources
PubMed1990

Role of N-acetylneuraminic acid in rat renal brush-border membrane vesicle aggregation by aminoglycosides.

Interaction between aminoglycosides (AGs) and rat renal brush-border membrane (BBM) vesicles was investigated by the aggregation technique. The order of aggregation was gentamicin greater than dibekacin not equal to netilmicin greater than amikacin, and this order corresponds to the strength of the nephrotoxicity of the aminoglycosides in vivo rather than the number of amino groups in the aminoglycosides. BBM vesicles were aggregated through ionic interaction, as evident from the finding that aggregation ceased to occur at alkaline pH. By addition of N-acetylneuraminic acid (NANA) to the incubation medium, the vesicle aggregation induced by gentamicin was significantly inhibited. To affect the liberation of the NANA residue from BBM vesicles, the vesicles were treated with neuraminidase, resulting in an about 60% release with a significant decrease in the uptake of gentamicin into the vesicles. The decrease in the degree of vesicle aggregation was in proportion to the amount of NANA liberated. It follows from the findings that the NANA residue may in some way be responsible for the accumulation of aminoglycosides in renal proximal tubular cells.

Aminoglycosides↗
PubMed1990

Atrophy of the ipsilateral substantia nigra following middle cerebral artery occlusion in the rat.

Following occlusion of the left middle cerebral artery in the rat, marked atrophy was observed in the ipsilateral substantia nigra in and after the second week. The mechanism of this neuropathological change in the substantia nigra, which is remote from the site of infarction, may be explained by transsynaptic, neurotransmitter-mediated disinhibition as a result of infarction of the striatum.

Animals↗
PubMed1990

New antitumor promoters: (-)-epigallocatechin gallate and sarcophytols A and B.

EGCG, the main constituent of green tea, and sarcophytols A and B, isolated from a soft coral, inhibited tumor promotion by teleocidin in a two-stage carcinogenesis experiment on mouse skin. EGCG and sarcophytols showed inhibition of tumor development by chemical carcinogenesis. A possibility of developing these compounds as cancer chemopreventives for human beings is discussed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Effect of mequitazine on the pharmacokinetics of theophylline in asthmatic patients.

The effect of an oral anti-allergic drug, mequitazine, on the pharmacokinetics of theophylline has been investigated in seven asthmatic patients. They received chronic theophylline therapy (a sustained-release theophylline tablet 200-400 mg b.d. at 12 h intervals) and coadministered mequitazine 6 mg for 3 weeks. Plasma theophylline concentration-time curves and the urinary excretion of theophylline and its major metabolites before and after coadministration of mequitazine were compared. No significant change in the pharmacokinetic parameters of theophylline or in the urinary recovery of unchanged drug and its metabolites was observed. Thus, mequitazine did not influence the pharmacokinetics of theophylline and it should be safe for coadministration to asthmatic patients on chronic theophylline therapy.

Aged↗
PubMed1990

Ontogenetic development of synovial A cells in fetal and neonatal rat knee joints.

Ontogenetic development of the synovial A cells in fetal rat knee joints was investigated by immunohistochemistry, immuno-electron microscopy, cultivation, and autoradiography. At day 17 of gestation, immature macrophages were first seen in the articular interzone, and thereafter they differentiated into macrophages (synovial A cells), which were found in the synovial intima. The degree of reactivity of macrophages with five monoclonal antibodies increased in the developing synovial membranes of fetal rats as shown by immunohistochemistry. Similar findings were obtained in organ cultures of fetal knee joints. A marked difference of proliferative potential was found between A and B cells during ontogeny. A cells after birth did not incorporate 3H-thymidine in contrast to B cells. Before birth, B cells had a labelling index which was at least five times larger than that of A cells. The results of this study indicate that the synovial A cells are derived from both monocytes and fetal macrophages circulating in peripheral blood and that they differ from the synovial B cells in morphology, differentiation, and proliferative potential.

Animals↗
PubMed1990

Enzyme-linked immunosorbent assay employing monoclonal antibodies for direct identification of enteric adenoviruses (Ad40,41) in feces.

For detection and identification of enteric adenovirus (Ad) types 40 and 41 in stool specimens, enzyme-linked immunosorbent assay (ELISA) was developed with the use of three monoclonal antibodies: Ad group-specific, Ad40 type-specific, and Ad41 type-specific antibodies. Of 860 fecal samples from patients with acute gastroenteritis, 44 strains of Ad were isolated using Graham 293 cell cultures. Of these isolates, 20 were typed as Ad40, 18 were Ad41, and 6 were other Ads by neutralization tests with cell cultures. Results of the ELISA tests on these 860 fecal samples resulted in good agreement to those with the cell culture method. The ELISA tests using Ad type-specific monoclonal antibodies proved to be a specific and rapid technique for laboratory diagnosis of acute gastroenteritis caused by enteric Ads.

Acute Disease↗
PubMed1990

Comparison of theophylline and enprofylline effects on human neutrophil superoxide production.

1. We investigated effects of theophylline (widely used for the treatment of asthma) and enprofylline (a new xanthine derivative with negligible adenosine antagonism) on O2- production by human neutrophils with n-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulation. 2. Therapeutic concentrations of theophylline (1-100 mumol/L) enhanced O2- production, maximally by 43.1 +/- 24.4% at 30 mumol/L; the same concentrations of enprofylline inhibited O2- production. 3. When each agent was administered after pre-incubation with adenosine deaminase (ADA) (0.1 U/mL), O2- production was inhibited in a concentration-dependent manner in comparison with that under administration of ADA alone. 4. These results suggest that the difference of effects in the two xanthine derivatives at therapeutic concentrations might be due to the presence or absence of adenosine antagonism.

Adenosine↗
PubMed1990

Time course of recovery of beta- and alpha 1-adrenoceptors in experimental asthma.

1. The time course of recovery of reduced beta-adrenoceptors caused by ovalbumin (OA) challenge was investigated using guinea-pigs. 2. The effects of prednisolone on the recovery time course were also evaluated. 3. beta- and alpha 1-receptor assays were performed using lung membranes. Adenylate cyclase activity was also measured. 4. OA challenge reduced the number of beta-adrenoceptors by 35%, and a significant decrease (13%) persisted for 7 days. The number of beta-adrenoceptor recovered after 14 days. 5. OA challenge elevated the number of alpha 1-adrenoceptors. A significant increase (24%) was observed after 7 days, and it took a further 7 days for the recovery. 6. After OA challenge there was a significant decrease in adenylate cyclase activity after 7 days, which recovered after a further 7 days. 7. Inhalation of prednisolone accelerated the recovery of beta-adrenergic responsiveness, though it did not affect the recovery of the number of alpha 1-adrenoceptors. Prednisolone inhalation also elevated beta-adrenergic responsiveness in non-asthmatic subjects. 8. It is concluded that reduced beta-adrenergic responsiveness caused by OA challenge persisted for 7 days and recovered after a further 7 days. Steroid hormone increased beta-adrenoceptors.

Adenylyl Cyclases↗
PubMed1990

The possible mechanism of interaction between xanthines and quinolone.

To clarify the mechanism of interaction between theophylline and enoxacin, the effects of enoxacin and its metabolite, 4-oxo-enoxacin, on the disposition of new xanthine derivatives, 1-methyl-3-propylxanthine (MPX) and 3-propylxanthine (enprofylline), as models of theophylline have been investigated in rats. Pretreatment with enoxacin significantly delayed the elimination of MPX from plasma. No significant change in the volume of distribution of MPX was observed in the presence of enoxacin, but the total body clearance of MPX was significantly decreased by approximately 60 and 80% after pretreatment with 25 and 100 mg kg-1 of enoxacin, respectively. The amount of the decrease in total body clearance depended on the dose of enoxacin. 4-Oxo-enoxacin had little or no effect on MPX disposition. A newly developed quinolone, NY-198, which does not affect the disposition of theophylline, also did not affect the disposition of MPX. Enoxacin also had no effect on the disposition of enprofylline. These results indicate that the mechanism for decrease in theophylline clearance induced by enoxacin may not be due to its metabolite, 4-oxo-enoxacin, but to enoxacin itself, and that enoxacin does not inhibit solely the elimination process depending on cytochrome P450 isoenzyme for N-demethylation. It is likely that enoxacin has no influence on the renal excretion of xanthines.

Animals↗
PubMed1990

Effects of intracellular pH on calcium-activated potassium channels in rabbit tracheal smooth muscle.

1. The effects of intracellular pH (pHi) on calcium-activated potassium channels (Ca2(+)-activated K+ channels) were studied in membrane patches of smooth muscle freshly dispersed from the rabbit trachea. Single-channel currents were recorded with an 'inside-out' patch clamp technique, mainly at 0 mV, with the external (electrode) medium containing 130 mM-K+ and the internal (bath) medium 6 mM-K+. 2. With an internal Ca2+ concentration ([Ca2+]i) of 1 microM, the fraction of time during which the channel was in an open state (the open probability, Po) was more than 0.8 at pHi 7.4. The channel activity nearly disappeared at pHi 7.0. The [Ca2+]i-Po relationship was shifted to higher [Ca2+]i by acidosis, the shift being approximately an 8-fold increase for a fall in pHi of 0.5 units. 3. The membrane potential and current intensity (V-I) relationship of single channels between +30 and -50 mV was shifted in a hyperpolarizing direction by intracellular acidosis. The shift was roughly 10 mV for 1 pH unit at 1 microM [Ca2+]i. At pHi 7.4 [Ca2+]i 1 microM, the V-Po relationship was shifted in a depolarizing direction by acidification. When [Ca2+]i was increased to 10 microM, V-Po relationship became less sensitive to V as well as pHi changes. 4. When Po was high, the probability density function of open and closed time distributions could be fitted by two exponentials. When Po was decreased to less than 0.3, either by reducing [Ca2+]i or by lowering pHi, another component having long closed times appeared. At similar Po values, the time constant of open time distribution was smaller with lower pHi. 5. It is concluded that the main effect of an increase in intracellular hydrogen ions is to decrease the open probability of the Ca2(+)-activated K+ channel, by reducing the sensitivity to Ca2+ and also shortening the open state.

Action Potentials↗
PubMed1990

[Microtiter enzyme-linked immunosorbent assay for diphtheria antitoxin in human sera--application of parallel line assay method].

The antibodies against Diphtheria toxin in human sera were measured by the ELISA method and the antitoxin titer was calculated using the parallel line assay method which is a quantitative bioassay method. The reproducibility of this method and the comparison of the titer between this method and cell culture method were proven. The dose response curve of standard antiserum and test serum calculated by the parallel line assay method showed linearity, and the regression line of the test serum was parallel to the standard serum. The coefficients of variance (CV) of the antitoxin titers obtained from triplicate measurements of 3 serum samples ranged from 9.1 to 36.0%. The serum at low titer gave a higher CV level. A good correlation was observed between the Diphtheria antitoxin titer by the neutralizing test in cultured cells and that measured by ELISA by the parallel line assay method. The coefficient of regression was 0.996 and the coefficient of the correlation was 0.899.

Adolescent↗
PubMed1990

Ultrasonic spectroscopy in bovine serum albumin solutions.

Ultrasonic absorption and velocity spectra in bovine serum albumin (BSA) aqueous solutions have been measured at 20 degrees C over the broad frequency range 0.1-1600 MHz in the pH range 1.5-13.2. Five different techniques were used: the plano-concave resonator, plano-plano resonator, pulse-echo overlap, Bragg reflection, and high-resolution Bragg reflection methods. The absorption spectrum at neutral pH was well fitted to the relaxation curve assuming a distribution of relaxation frequency with a high-frequency cutoff and long low-frequency tail. The relaxation behavior was interpreted in terms of various degrees of hydration of BSA molecules. At acid pH's, excess absorption over that at pH 7 was explained by double relaxation. The pH dependences of the relaxation frequency and maximum absorption per wavelength showed that the relaxation at about 200 kHz was related to the expansion of molecules and that at 2 MHz resulted from the proton transfer reaction of carboxyl group. At alkaline pH's, the excess absorption was explained by triple relaxation. The relaxation at about 200 kHz was associated with a helix-coil transition, and the two relaxations at 2 and 15 MHz were attributed to the proton transfer reactions of phenolic and amino groups, respectively. The rate constants and volume changes associated with these processes were estimated.

Animals↗
PubMed1990

Effects of enoxacin on renal and metabolic clearance of theophylline in rats.

The effects of enoxacin and its metabolite 4-oxoenoxacin on the disposition of theophylline were investigated in rats. Systemic clearance of theophylline was significantly decreased by approximately 40, 46, and 50% after oral coadministration of 25, 100, and 200 mg of enoxacin per kg, respectively. No significant changes in the volume of distribution of theophylline were observed. 4-Oxoenoxacin had no direct effect on theophylline disposition. Significant changes in urinary excretion of theophylline and its metabolites were observed. (i) Urinary excretion of unchanged theophylline was significantly increased in proportion to increases in enoxacin dosage. (ii) Decreases in renal clearance of theophylline and metabolic clearance of 1-methyluric acid and 1,3-dimethyluric acid were observed. (iii) The percent decreases in the metabolic clearance of 1-methyluric acid were dependent on enoxacin dosage. It is likely that enoxacin inhibits the elimination process, which depends on cytochrome P-450-mediated isozymes for N demethylation and oxidation, and that the capacity of the inhibitory effect of enoxacin is greater in the N-demethylation pathway than it is in oxidation.

Animals↗
PubMed1990

[Effects of IT-066, a new histamine H2-receptor antagonist, on gastric acid secretion and experimental gastric ulcers in rats and dogs].

We examined the effects of a new histamine H2-receptor antagonist, 3-amino-4-(4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2- butenylamino)-3- cyclobutene-1,2-dione hydrochloride (IT-066), on gastric acid secretion and the healing process of experimental ulcers in rats and dogs. Famotidine, a well-established H2-receptor antagonist, was used as the reference drug. Male Donryu rats (240-260 g) and Beagle dogs of both sexes (8-10 kg), having Heidenhain pouches, were used. IT-066 dose-dependently inhibited the basal gastric acid secretion of rats, and this inhibition significantly persisted for 12 hr. In addition, the agent significantly inhibited histamine-stimulated acid secretion in both normal rats and rats with acetic acid ulcers. IT-066, given p.o. twice daily for 2 and 3 weeks after ulceration, significantly accelerated both spontaneous and delayed healing (with indomethacin) of acetic acid-induced gastric ulcers in rats. The effects of IT-066 on acid secretion and ulcer healing were almost the same or slightly more potent than those observed with famotidine. IT-066, when given i.v. or p.o., dose-dependently inhibited the gastric acid secretion stimulated by histamine, pentagastrin, or carbachol in dogs. The antisecretory effects of the agent on histamine-stimulated acid secretion significantly persisted for more than 6 hr. These results indicate that IT-066 appears to be a promising antisecretory and anti-ulcer agent.

Acetates↗
PubMed1990

[A neurochemical study on brain cholinergic neuron; a newly improved pyrolysis gas chromatography/mass spectrometry (PY/GC/MS) method and its application].

A new method for measuring the endogenous acetylcholine (ACh) and choline (Ch) levels using a PY/GC/MS was established, and then the alteration of cholinergic neurons in the iminodipropionitrile (IDPN) induced dyskinesia model rat brain was studied. In performing the determinations of small amounts of brain ACh and Ch levels using a curie point PY/GC/MS, the following points were improved upon in the present study: 1) We shortened the distance between the sample tube and injection port allowing the rapid transformation to an analytical system without sub-reaction and re-synthesis of demethylated products. 2) The suitable pyrolytic temperature (curie point) was adjusted to 333 degrees C. 3) Then the aqueous sample (2 microliters) was wrapped in a pyrofoil with a curie point of 333 degrees C followed by drying at 80 degrees C. Subsequently, the pyrofoil was formed by a 200 kgf/cm2 press. 4) A fused silica capillary column (DB-5) was used instead of a pre-packed column (Jenden Phase). By these improvements, both calibration curves of ACh and Ch have high linearities (r = 0.988) between 1 pmol and 2 pmol, and the apparent peak of quasi-molecular ion and less fragment ion of each Ch analog was obtained. In the globus pallidus, caudate nucleus, hippocampus and cerebellum of IDPN induced dyskinesia model rats, remarkable reductions of ACh levels were observed using our newly improved PY/GC/MS method. Thus, our improved method can be utilized for measuring ACh levels in small discrete brain regions.

Acetylcholine↗
PubMed1990

Emphysematous change in chronic asthma in relation to cigarette smoking. Assessment by computed tomography.

To evaluate the occurrence and the degree of emphysema in chronic asthma in relation to the effect of cigarette smoking, we examined 35 subjects with irreversible airway obstruction (17 nonsmokers and 18 smokers). We performed pulmonary function testing and CT scans on all subjects. The ES was assessed by a visual scoring system on CT scans. Between nonsmokers and smokers, there was a significant difference in the ES (p less than 0.05), but not in the FEV1, TLC, and Dsb/VA (expressed as percent predicted values). The ES was 2.3 +/- 4.7 percent (mean +/- SD) in nonsmoking subjects and 13.7 +/- 16.7 percent in smoking subjects. In all subjects the ES showed significant correlations with Dsb/VA (p less than 0.001) and pack-years of cigarette consumption (p less than 0.001) but did not show correlations with FEV1 and with TLC. We concluded that emphysema can occur in smoking asthmatic subjects because of the effect of cigarette smoking, and CT scans are useful for detecting this emphysematous change.

Asthma↗
PubMed1990

An electron microscopic study of ectomesenchymal contacts in rat incisors.

In order to clarify connections between epithelium and mesenchymal tissue in the early stage of odontogenesis, the formation of ectomesenchymal contacts and the presence of coarse-textured material at the interface between ameloblasts (AMs) and odontoblasts (ODs) on growing rat incisors were studied by electron microscopy. The presecretory zone was classified into five regions according to the ultrastructure of each preameloblast (PA). The region where collagen fibrils could be observed was designated PZ-2, the region where predentin existed PZ-3, the region where the basal lamina began to disappear PZ-4, and the region where the basal lamina had disappeared PZ-5. In PZ-2, the cytoplasmic processes of PAs penetrated the basal lamina and reached the dental papilla cells. In some locations, ectomesenchymal contacts were also observed, in which the cytoplasmic processes of the PAs were in contact with those of the preodontoblasts (POs). In PZ-3, the distal cytoplasm contained large amounts of type-1 vesicles, and secretory granules. In the distal membrane of the PA, membrane invaginations containing fibrillar structures were visible. Also in some areas, the cytoplasmic processes at the distal ends of the PAs invaded the predentin. In the predentin, a large amount of coarse-textured material, considered to be the precursor of the enamel matrix, was observed. In PZ-3, a large number of cytoplasmic processes extended into the predentin, while in PZ-4, microvillus-like processes extended from the distal ends of the PAs, showing a high frequency of ectomesenchymal contact. It was suggested that secretory activity of the PAs was induced after ectomesenchymal contact had been accomplished, but that the PAs did not undergo morphological change into secretory ameloblasts.

Ameloblasts↗