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Biomedical subjects

H Takeuchi

Publications and source records attributed to H Takeuchi.

At least 685 records · Page 38Linked to original sources

Production and characterization of monoclonal antibodies against particulate guanylate cyclase in porcine kidney.

Three monoclonal antibodies (Ig G1 type) to particulate guanylate cyclase from porcine kidney cortex have been produced by fusing spleen cells from immunized BALB/c mouse with P3X63 myeloma cells. The antibodies were detected by their ability to bind immobilized antigen and by immunoprecipitation of enzyme activity. After subcloning by limiting dilution, hybridomas were injected intraperitoneally into mice to produce ascitic fluid. The antibodies recognized a 180,000 dalton protein in Lubrol-PX extract of porcine kidney cortex membrane, and when immobilized on Sepharose 4B, they co-precipitated both [125I]human atrial natriuretic peptide (ANP)-receptor complex and guanylate cyclase activity. The antibodies caused a greater increase in generation of cGMP than that of ANP.

Animals↗

Suppression of calcium current in a snail neurone by eperisone and its analogues.

The effects of eperisone, tolperisone and isoperisone on the calcium current (ICa) were studied in an identified neurone of Achatina fulica under voltage clamping. At a holding voltage of -50 mV, these drugs inhibited ICa dose dependently without affecting activation time. Eperisone (IC50 = 0.348 mM) and isoperisone (0.226 mM) were significantly more effective than tolperisone (1.089 mM). Eperisone binds competitively with Ca2+ to the Ca2+ channels, based on its effects seen with various extracellular Ca2+ concentrations. The three drugs shifted the steady state inactivation curves in the hyperpolarizing direction. The mean dissociation constants for inactivated Ca2+ channels were calculated to be 0.070 mM (eperisone), 0.162 mM (tolperisone) and 0.014 mM (isoperisone). These values were much lower than their IC50 at Vh of -50 mV, which are reflected as the dissociation constants for resting Ca2+ channels. High frequency stimulation did not potentiate ICa suppression, suggesting that the drugs hardly bind to activated Ca2+ channels. These findings indicate that the selectivities of the Ca2+ channels to the drugs are in the order of their inactivated, resting and open states.

Animals↗

Tongue-muscle-controlling motoneurons in the Japanese toad: neural inputs from the thalamus.

The anuran tongue is an effector organ specialized for snapping up prey during visually guided prey-catching behavior. As a step toward elucidating the control mechanisms of the tongue movement and overall organization of visually guided behavior, properties of neural inputs from the thalamus (of which electrical stimulation elicited a behavior very similar to the visually guided predator-avoidance behavior under freely behaving conditions) were investigated in paralyzed Japanese toads. Tongue-muscle-controlling motoneurons (tongue-protractor motoneurons (PMNs) and tongue-retractor motoneurons (RMNs)) were identified antidromically, and synaptic inputs in response to electrical stimuli applied to various points in the thalamus (mainly the posterocentral thalamic nucleus) were examined. Hyperpolarizing potentials were evoked in both PMNs and RMNs in response to single electrical stimuli applied to the thalamus contralateral or ipsilateral to the recording side. Since these potentials reversed to depolarizing ones after injecting Cl- ions into the cell interior, these hyperpolarizing potentials were concluded to be the usual fast type of inhibitory postsynaptic potentials (IPSPs). On the other hand, depolarizing potentials which were superimposed on the underlying IPSPs were evoked when repetitive electrical stimuli were applied to the thalamus. The amplitude of these depolarizing potentials was decreased when depolarizing currents were injected intracellularly, while it was increased when hyperpolarizing currents were injected, indicating that these depolarizing potentials are excitatory postsynaptic potentials (EPSPs).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Preparation of controlled-release microspheres of ibuprofen with acrylic polymers by a novel quasi-emulsion solvent diffusion method.

A novel quasi-emulsion solvent diffusion method to prepare the controlled-release microspheres of ibuprofen with acrylic polymers has been developed. An ethanol solution of ibuprofen and acrylic resin was poured into aqueous medium with stirring. The finely dispersed ethanolic droplet-like coacervates formed in aqueous medium were gradually solidified and transformed into microspheres during agitation. The size of microspheres was determined by the concentrations of drug and polymer and the agitation speed of the system. The flowability, the packability, and the compressibility of the resultant microspheres were much improved compared with the raw crystals of the drug. The drug release rate from the microspheres could be controlled by the type and the concentration of polymer formulated. A unique principle of the present method and the resultant microspheres, having a matrix- or sponge-like texture, can provide characteristic advantages compared with a conventional reservoir-type device drug, like a microcapsule.

Acrylates↗

Detection by light microscopy of Candida in thin sections of bladder stone.

We detected fungi morphologically resembling Candida albicans in an infected bladder stone by light microscopy of thin sections. The fungi were found in the layers precipitated with oxalate crystals and were invading the interstices surrounded with apatite or struvite crystals as in tissue infection. This presumably represents a superimposed infection due to changes in flora following treatment with antibiotics.

Aged↗

Change in small intestinal brush border membranes of rats following methotrexate administration.

Change in small intestinal brush border membranes of rats following methotrexate administration was monitored by the fluorescence spectra and polarization of the cationic fluorescent probe, safranin 0. Total protein content of brush border membranes of treated rats was less than that of control rats, whereas no significant difference in total sialic acid content of brush border membranes was observed between them. Thus, an apparent increase in the electronegative charge of brush border membrane vesicles per unit of membrane protein following methotrexate administration may possibly cause the change in fluorescence spectra and polarization of safranin 0.

Animals↗

Structural gene and complete amino acid sequence of Pseudomonas aeruginosa IFO 3455 elastase.

The DNA encoding the elastase of Pseudomonas aeruginosa IFO 3455 was cloned, and its complete nucleotide sequence was determined. When the cloned gene was ligated to pUC18, the Escherichia coli expression vector, bacteria carrying the gene exhibited high levels of both elastase activity and elastase antigens. The amino acid sequence, deduced from the nucleotide sequence, revealed that the mature elastase consisted of 301 amino acids with a relative molecular mass of 32,926 daltons. The amino acid composition predicted from the DNA sequence was quite similar to the chemically determined composition of purified elastase reported previously. We also observed nucleotide sequence encoding a signal peptide and "pro" sequence consisting of 197 amino acids upstream from the mature elastase protein gene. The amino acid sequence analysis revealed that both the N-terminal sequence of the purified elastase and the N-terminal side sequences of the C-terminal tryptic peptide as well as the internal lysyl peptide fragment were completely identical to the deduced amino acid sequences. The pattern of identity of amino acid sequences was quite evident in the regions that include structurally and functionally important residues of Bacillus subtilis thermolysin.

Amino Acid Sequence↗

Neurofibromatosis associated with renovascular hypertension due to stenosis and aneurysm of the left renal segmental artery: report of a case.

We report a case of renovascular hypertension due to renal segmental artery stenosis and aneurysm seen in a 16-year-old boy with neurofibromatosis. Hypertension was successfully treated with partial nephrectomy. Histopathologic examination disclosed proliferation of arterial intima not only in the stenotic portion and the aneurysm but also in intralobular arteries of the kidney. Review of the literature revealed that treatment for such patients has varied.

Adolescent↗

Preparation of prolonged-release spherical micro-matrix of ibuprofen with acrylic polymer by the emulsion-solvent diffusion method for improving bioavailability.

Prolonged-release spherical micro-matrices of ibuprofen with acrylic polymer (Eudragit RS) were prepared using a novel emulsion-solvent diffusion method. It was found by examining cross sections of the spherical matrix before and after dissolution tests with a scanning electron microscope and a porosimeter that the resultant micro-matrix had a sponge-like internal structure. The spherical matrices were successfully recovered with a relatively high concentration of the drug in ethanol (0.4-0.6 g/ml) and over a wide range of temperatures (5-35 degrees C). The size of the spherical matrix could be easily controlled by varying the agitation speed of the system and the concentration of emulsifier added to the aqueous medium. The drug release rate from the spherical matrix decreased with increasing concentration of polymer formulated due to the reduced diffusion path and increased tortuosity in the matrix. Spherical matrices with ibuprofen:Eudragit RS = 3:1 improved the bioavailability of the drug and prolonged the drug action in beagle dogs.

Acrylates↗

Effects of methyl-group acceptors on the regulation of plasma cholesterol level in rats fed high cholesterol diets.

The effects of methyl-group acceptors such as glycine, guanidinoacetic acid, and nicotinamide on cholesterol metabolism and phosphatidylcholine(PC) biosynthesis were investigated with rats fed a 25% casein diet containing cholesterol with or without methionine supplement. The effect of ethanolamine, an indirect methyl-group acceptor via phosphatidylethanolamine(PE) formation, was also compared with those of methyl-group acceptors. The methyl-group acceptors and ethanolamine decreased or tended to decrease plasma total cholesterol level when added to the 25% casein diet. These compounds also significantly depressed the methionine-induced enhancement of plasma cholesterol level. The activity of PE N-methyltransferase was decreased by the addition of glycine, guanidinoacetic acid, and nicotinamide, but not ethanolamine, to the reaction mixture when assayed using the postmitochondrial fraction of liver homogenate, suggesting that PE N-methyltransferase activity can be depressed by glycine N-methyltransferase, guanidinoacetic acid N-methyltransferase, and nicotinamide N-methyltransferase systems. The PE N-methyltransferase activity in liver microsomes, however, did not decrease in response to the dietary addition of methyl-group acceptors. The in vitro incorporation of [CH3-14C]methionine into PC of liver slices was also significantly inhibited by the addition of glycine and nicotinamide, but not guanidinoacetic acid and ethanolamine, to the incubation medium. It is suggested that methyl-group acceptors can decrease plasma cholesterol level at least in part through the depression of PC biosynthesis via PE N-methylation pathway, and that the mechanism for the plasma cholesterol-lowering effect of ethanolamine is different from that of methyl-group acceptors.

Animals↗

[Sequential combination chemotherapy consisting of vincristine, peplomycin, methotrexate, cis-diamminedichloroplatinum (II) and adriamycin in urothelial cancer].

The VPM-CisA (vincristine (VCR), peplomycin (PLM), methotrexate (MTX), cisplatin (CDDP) and doxorubicin (ADM), regimen was used to treat 33 patients with urothelial tract tumors. Twenty-two patients had bi-dimensionally measurable disease parameters and 11 patients with locally advanced tumors were given postoperative adjuvant chemotherapy. The protocol consisted of 0.6 mg/m2 VCR on days 1 and 3, 3 mg/m2 PLM on days 1 to 4, 3 mg/m2 MTX on days 2 and 4, 35 mg/m2 CDDP on day 4, and 20 mg/m2 ADM on day 5. These doses were adjusted for each case: the above mentioned dose x [(80/(40+Age]2 +[(Karnofsky's performance status/100)2]. Of these patients, 28 (86 percent) were treated adequately, including 8 (36 per cent) who achieved a complete (2) or partial (6) remission. The mean duration of survival was 65.2 weeks for complete and partial responders, and 48.8 weeks for non-responders, which was not a statistically significant difference. Of 11, who were given post-operative adjuvant chemotherapy (mean observation period: 83.5 weeks) 9 were alive without evidence of disease, 1 had a recurrence 8 months after first chemotherapy, 1 died due to pulmonary and liver metastasis 2 years after the chemotherapy. Toxicity included mild myelosupression, moderate anorexia, vomiting, and severe gastric ulcer, pulmonary fibrosis.

Adenocarcinoma↗

[Regulation of osteoclastic bone resorption. 1. Limitation of osteoclast motile activity by fibroblast-like cells].

The cell-to-cell interaction between osteoclasts and fibroblast-like cells, which were mechanically disaggregated from long bones of neonatal rabbits, was investigated to clarify the cellular mechanisms responsible for the regulation of osteoclastic bone resorption by using phase-contrast time lapse recording and fluorescent microscopy for visualization of F-actin cytoskeleton. Osteoclasts showed rapid extension and retraction of pseudopodia with intense ruffling activity and active translocation over a glass surface when there was enough open space around them, while fibroblast-like cells seemed much more stationary. Osteoclasts were not able to cross over cell bodies of fibroblast-like cells which interfered with migration of the osteoclasts. As fibroblast-like cells proliferated, they gradually took over the open glass surface and finally tightly surrounded the osteoclasts. Such osteoclasts usually became contracted and pseudopodial and migratory activities decreased. Fluorescent microscopy of well-spread osteoclaststs stained with rhodamine-labeled phalloidin revealed development of a band-like structure composed of a number of brightly fluorescent F-actin dots at the cell periphery and fine F-actin bundles which run through the cell bodies. On the other hand, contracted osteoclasts tightly surrounded by fibroblast-like cells showed conglomerates composed of accumulated F-actin dots instead of the band-like structure. An F-actin pattern of fibroblast-like cells, which was very different from that of osteoclasts, displayed thick and straight bright bundles with in the cell bodies. The present observation suggests that ongoing osteoclastic bone resorption may be regulated by fibroblast-like cells through limitation of osteoclastic motile activity, and alteration of cytoskeleton and cell-substratum interaction which occurred in osteoclasts may be involved in the mechanism.

Actins↗

Case report of chondroma of the tongue.

A 20-year-old Japanese woman was referred to the hospital for examination and treatment of an asymptomatic swelling of the left dorsum of the tongue. Intraoral examination revealed that the tumor was covered with normal mucosa and oval, firm on palpation and measured 1.5 cm in diameter. The lesion was movable suggesting benignity in nature. No cervical lymph node was palpated. The cut surface of the extirpated tumor after fixation showed a chalky white "core region" surrounded with a yellowish white adipose tissue. Histopathological examination revealed the lesion to be a benign cartilaginous tumor. We report this case of chondroma which arose from the tongue because of its rarity, and reviewed related literature.

Adolescent↗

[Dental findings in a case of idiopathic hypoparathyroidism].

Idiopathic hypoparathyroidism is characterized by a deficiency of the parathyroid hormone, origin unknown, and causes a low serum calcium and a high serum inorganic phosphorus. This report concerns a clinical observation of a case of idiopathic hypoparathyroidism. This case was examined from the dental point of view. The findings were as follows: 1. The roentgenographic findings revealed that there was no demonstrable abnormality concerning bone age indicated between the ages of 5 and 6 years. 2. Severe dental caries were noted in the deciduous teeth and the permanent teeth. 3. Hypoplasia and hypocalcemia were recognized in most of the permanent teeth. 4. Large pulp chambers were observed in the deciduous teeth and the permanent teeth, and thickening of the lamina dura was observed in the permanent teeth. 5. The histological findings of the extracted deciduous teeth and the upper right first molar were such that: (1) there was hypoplasia and hypocalcemia in the dentin of deciduous teeth, and there were multiple resorptions in the cementum. (2) there was hypoplasia in the enamel of the upper right first molar. 6. Electron probe microanalysis of the upper left second molar revealed that the degree of mineralization and concentration of Ca, P and Mg in the dentin of the root showed a lower intensity than in the dentin of the normal one. 7. It was assumed from the dental point of view that this hypoparathyroid condition first appeared at about 11'months approximately 18'months of age.

Child, Preschool↗

[Urease activity of bacteria in urine].

Urea splitting bacteria are related to the formation of struvite or apatite. We investigated the urease activity of bacteria by two methods; the direct measurement of urease activity of viable bacteria and sonicated bacteria from amounts of ammonia by the indophenol method, and the measurement of urease activity by alkalization of infected urine. Proteus mirabilis and Pseudomonas aeruginosa had moderate activity of urease, and Morganella morganii and Staphylococcus epidermidis had the most powerful activity. P. mirabilis caused the strongest alkalization in infected urine.

Humans↗

[Laboratory and clinical studies on clarithromycin in the field of pediatrics].

Laboratory and clinical studies on clarithromycin (TE-031, A-56268), a new macrolide antibiotic, were carried out in the field of pediatrics. The results obtained are summarized as follows: 1. Serum concentrations, urinary concentrations and urinary recovery rates were determined upon oral administration on fasting of TE-031 at doses of 5 mg/kg granules in 1 case and tablets in 2 cases, and 10 mg/kg granules in 1 and 15 mg/kg granules in 1. Peak serum levels were obtained at 30 minutes in 2 cases, at 1 hour in 2 cases and at 2 hours in 1 case after administration of the drug with a range of 2.29-7.10 micrograms/ml with half-lives of 2.2-7.5 hours. Urinary recovery rates in 6 hours after administration ranged from 7.1-34.5%. 2. MICs of TE-031 against 49 clinical isolates (Streptococcus pyogenes 5 strains, Streptococcus pneumoniae 9, Staphylococcus aureus 3, Branhamella catarrhalis 4, Haemophilus influenzae 14, Haemophilus parainfluenzae 7, and Campylobacter jejuni 7) were compared with those of josamycin (JM), erythromycin (EM), and ampicillin (ABPC). The antibacterial activity of TE-031 was superior to those of JM and equal to those of EM. 3. Fifty-five pediatric patients with acute infectious diseases (scarlet fever 3 cases, pharyngitis and tonsillitis 15, pertussis 2, pneumonia 10, bronchitis 14, Campylobacter enteritis 11) were treated with TE-031 at daily doses of 10-35 mg/kg t.i.d. as a rule. The efficacy rates were 96% clinically and 72% bacteriologically. 4. Side effects or abnormal laboratory test values were not observed. 5. None of children refused TE-031.

Adolescent↗

[Bacteriological, pharmacokinetic and clinical studies on cefpodoxime proxetil in the pediatric field].

Bacteriological, pharmacokinetic and clinical studies on cefpodoxime proxetil (CPDX-PR, CS-807), a new oral cephem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized as follows. 1. Antibacterial activities of R-3746 (Na-salt of cefpodoxime (CPDX] against clinically isolated strains of Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Enterococcus faecalis, Branhamella catarrhalis, Escherichia coli, Proteus mirabilis and Haemophilus influenzae were compared with those of cefaclor, cephalexin and cefadroxil. R-3746 is superior to other antibiotics against S. pneumoniae, S. pyogenes, B. catarrhalis and Gram-negative rods. 2. Serum concentrations of CPDX after administration of CPDX-PR at doses of 3 mg/kg (fasting), 6 mg/kg (non-fasting) and 6 mg/kg (fasting) were determined. Mean AUC (area under curve)'s of CPDX obtained were 9.60, 31.35 and 17.89 micrograms.hr/ml, respectively for the 3 dosages. The mean half-lives of CPDX were 3.35, 1.88 and 1.76 hours, respectively. The mean urinary recovery rate within 8 hours after administration of CPDX-PR at a dose of 3 mg/kg (fasting) was 39.2%. 3. CPDX-PR was administered to 37 pediatric patients with various bacterial infections (pyelonephritis 9, cystitis 4, pneumonia 7, acute bronchitis 3, otitis media 2, tonsillitis 10, subcutaneous abscess 1 and purulent lymphadenitis 1). The overall clinical efficacy rate was 91.9% and the overall bacteriological eradication rate was also 91.9%. 4. No adverse reactions were observed. Abnormal laboratory findings were moderate, eosinophilia in 2 and slight elevation of GOT and GPT in 1. The taste and the odor of the CPDX-PR preparation was sufficiently tolerable. From the above results we have concluded that CPDX-PR is a useful oral antibiotic in the treatment of bacterial infections in children.

Bacteria↗