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Biomedical subjects

N Nakayama

Publications and source records attributed to N Nakayama.

At least 19 recordsLinked to original sources
PubMed1992

Use of mammalian cell expression cloning systems to identify genes for cytokines, receptors, and regulatory proteins.

Mammalian cell expression cloning has become a standard technique for the isolation of mammalian genes or cDNAs. Its advantage is that the biological functions of the gene of interest are used for cloning. Therefore, the identified cDNAs or genes should be functional in vivo, and there is no need for physical or chemical information about the gene products, so that protein purification in sufficient quantity to raise antibodies or to obtain amino acid sequences is not necessary. Here, we summarize recent progress in mammalian cell cloning systems, and discuss the possible directions in which this technique will lead.

Animals↗
PubMed1992

A new series of natural antifungals that inhibit P450 lanosterol C-14 demethylase. I. Taxonomy, fermentation, isolation and structural elucidation.

A new series of antifungal antibiotics, Ro 09-1470 and its 6 congeners were isolated from the fermentation broth of Penicillium sp. NR6564. Their structures were determined as tetrahydropyran derivatives with an alkenyl side chain on the basis of their spectroscopic and physico-chemical properties. Among these compounds, Ro 09-1470 and Ro 09-1545 possessing a glycyl N-substituted glycyl ester residue had high antifungal activity. Ro 09-1469, one of the congeners, was found in the fermentation broth of several strains of Aspergillus sclerotiorum Huber.

Antifungal Agents↗
PubMed1992

A new series of natural antifungals that inhibit P450 lanosterol C-14 demethylase. II. Mode of action.

From a Penicillium sp. we identified a new series of antifungals having a tetrahydropyran skeleton with an alkenyl side chain. We elucidated the mode of action of Ro 09-1470, the most active compound of the series. Treatment of Candida albicans with the compound caused an accumulation of C-14 methyl intermediates of ergosterol at concentrations of which no significant interference with the biosyntheses of other macromolecules and respiration was observed. P450 lanosterol C-14 demethylase (P450(14DM)) activity was inhibited and furthermore, the binding of Ro 09-1470 to the heme of the enzyme was demonstrated by a difference spectrum. We conclude that Ro 09-1470 is the first natural antifungal that inhibits the P450(14DM) of fungi.

Candida albicans↗
PubMed1992

[Pharmacokinetic and clinical studies of cefprozil fine granules in children].

Cefprozil (CFPZ, BMY-28100) is a new oral cephem antibiotic without an ester linkage. Pharmacokinetic and clinical studies using CFPZ 10% fine granules were performed in pediatric patients. 1. Pharmacokinetic investigation Peak serum concentrations of CFPZ after dose of 7.5 mg/kg and 10 mg/kg were, respectively, 3.65 +/- 0.24 micrograms/ml and 6.38 +/- 3.23 micrograms/ml at 1-2 hours. The average half-life with 7.5 mg/kg administration was 0.90 +/- 0.16 hours and that with 10 mg/kg was 1.29 +/- 0.50 hours. The urinary excretion of CFPZ was about 45% (35.3-50.0%) in 6 hours. 2. Clinical investigation Enrolled in the study were 22 patients including 4 with pharyngitis, 3 with tonsillitis, 3 with bronchitis, 5 with pneumonia, 4 with urinary tract infection, and 1 each with pertussis, purulent lymphadenitis and otitis media. Responses were excellent in 14 patients, good in 5 patients and fair in 1 patient. In the assessment of the bacteriological efficacy, 8 out of 17 strains of organism identified previous to the treatment were eradicated, 5 strains were found replaced by other bacteria and 4 strains persisted, hence the eradication rate was 76.5%. 3. No adverse reactions attributable to the drug were observed. From the above results, it has been concluded that CFPZ is a highly effective and safe agent for moderate respiratory and urinary tract infections in children.

Administration, Oral↗
PubMed1991

Isolation of two toxic heptapeptide microcystins from an axenic strain of Microcystis aeruginosa, K-139.

Two toxic heptapeptides were isolated from an axenic Microcystis aeruginosa strain, K-139. Using mainly a non-destructive NMR method, we determined the structure of the major toxin to be 7-desmethylmicrocystin LR which lacks an N-methyl group of the dehydroalanine moiety of microcystin LR. The minor toxin was deduced to be 3,7-didesmethylmicrocystin LR. The chromatographic and NMR analyses of 7-desmethylmicrocystin LR were compared with those of 3-desmethylmicrocystin LR.

Amino Acid Sequence↗
PubMed1991

Colony-stimulating factors and cytokine receptor network.

Cytokines play a vital role in coordinating immune and inflammatory responses. As many cytokine gene hunters have begun to focus their efforts on receptors, novel aspects of hemopoietic growth factor receptors have emerged. Two types of growth factor receptors have been classified--the cytokine receptor family and growth factor receptor family with tyrosine kinase activity. The two types of receptors may have unique roles in 'inducible' and 'constitutive' hemopoiesis which are controlled by immunological stimuli and by interaction with stromal cells, respectively.

Animals↗
PubMed1991

Structural studies on avidinorubicin, a novel anthracycline with platelet aggregation inhibitory activity.

Avidinorubicin (MW 1,214, C60H86N4O22) was isolated from the cultured broth of strain NR0576 (which was identified as Streptomyces avidinii Stapley et al.) by butyl alcohol extraction, Sephadex LH-20 column chromatography and preparative HPLC. Avidinorubicin inhibited thrombin-induced platelet aggregation with an IC50 being 7.9 microM and was determined to be a novel anthracycline possessing two units of a new aminosugar, avidinosamine, in place of two decilonitrose groups in decilorubicin.

Anthracyclines↗
PubMed1991

[Laboratory and clinical studies on cefpirome in pediatrics].

Laboratory and clinical studies on cefpirome (CPR, HR 810), a newly developed cephem antibiotic, were performed. The results obtained are summarized as follows: 1. Absorption and elimination of the drug were examined in a total of 7 children including 3 cases of administered with 20 mg/kg intravenous bolus injection (i.v.), 2 cases with 20 mg/kg drip infusion (d.i.v.) for 60 minutes and 2 cases with 40 mg/kg (d.i.v.) for 60 minutes. Maximum serum levels were attained immediately after i.v. or d.i.v. Cmax's were 233 +/- 7.6, 88.5 +/- 14.5, and 116 +/- 15 micrograms/ml, respectively for the above 3 modes of administration. These values were determined using a bioassay method with Bacillus subtilis ATCC 6633. T 1/2 (beta)'s were 1.18 +/- 0.17, 1.61 +/- 0.28 and 2.68 +/- 0.83 hours, respectively. Cumulative urinary recovery rates were 40.2-69.8% in a period of 0-6 hours after admissions. 2. Clinical efficacies were evaluated in a total of 20 patients with ages ranging from 9 months to 11 years. The treated cases were 6 cases of acute pneumonia, 4 cases of acute bronchitis, 4 cases of acute purulent tonsillitis, 2 cases of acute urinary tract infections, 2 cases of cellulitis, 1 case of purulent lympadenitis and 1 case of acute otitis media. The clinical efficacy rate was 94.7%. Adverse reactions occurred in no patients. Abnormal changes in laboratory test values involved only 1 case with elevated GOT and GPT. CPR was considered to be a safe and useful drug in treating various infectious diseases in children.

Bacterial Infections↗
PubMed1990

Regulation of the yeast pheromone response pathway by G protein subunits.

The yeast GPA1, STE4, and STE18 genes encode proteins homologous to the respective alpha, beta and gamma subunits of the mammalian G protein complex which appears to mediate the response to mating pheromones. Overexpression of the STE4 protein by the galactose-inducible GAL1 promoter caused activation of the pheromone response pathway which resulted in cell-cycle arrest in late G1 phase and induction of the FUS1 gene expression, thereby suppressing the sterility of the receptor-less mutant delta ste2. Disruption of STE18, in turn, suppressed activation of the pheromone response induced by overexpression of STE4, suggesting that the STE18 product is required for the STE4 action. However, overexpression of both the STE4 and STE18 proteins did not generate a stronger pheromone response than overexpression of STE4 in the presence of wild-type levels of STE18. These results suggest that the beta subunit is the limiting component for the pheromone response and support the idea that beta and gamma subunits act as a positive regulator. Furthermore, overexpression of GPA1 prevented cell-cycle arrest but not FUS1 induction mediated by overexpression of STE4. This implies that the alpha subunit acts as a negative regulator presumably through interacting with beta and gamma subunits in the mating pheromone signaling pathway.

Amino Acid Sequence↗
PubMed1990

Antihypertensive activity of OPC-13340, a new potent and long-acting dihydropyridine calcium antagonist, in rats.

The antihypertensive action of OPC-13340, a new dihydropyridine, was studied in rats and compared with the action of nicardipine and other dihydropyridines. OPC-13340 showed more potent and longer hypotensive action than nicardipine when administered either intravenously (i.v.) or orally in normotensive and hypertensive rats. Among 6 compounds tested, (OPC-13340, nifedipine, nitrendipine, nisoldipine, nicardipine and diltiazem), OPC-13340 was the most potent and long-acting when administered orally to spontaneously hypertensive rats (SHR). Tachycardia after administration of OPC-13340 was less or diminished earlier than that of nicardipine. Oral administration of OPC-13340 (3 mg/kg) once daily for 13 days did not cause any rebound phenomena in SHR. The compound inhibited Ca- or K-induced contractions in isolated rat aorta and shortened action potential duration in guinea pig papillary muscle, suggesting Ca channel blocking action. OPC-13340 might be useful as a drug for once-daily therapy of essential hypertension.

Action Potentials↗
PubMed1976

[A new valve controlled system for ventricular drainage. (Technical description and clinical results)].

A new valve controlled system for continuous ventricular drainage has been described. The clinical experiences (114 patients) are very satisfactory, even after a drainage duration of 15 days. The main advantages of the method are the resistance of all connexions against traction, the fixed position of the ventricular catheter, the variable opening pressure of the valve and the insensitivity to air or gas bubbles, at last the protection of the valve against blood and protein clots by use of filters. We have used the system for the continuous monitoring of the ICP and for diagnostic purposes (ventriculography, examination of cerebrospinal fluid) with good results.

Autoantibodies↗
PubMed1976

Serial magnification angiography under hypocapnia and hypertension.

Serial magnification angiography under hypocapnia and hypertension was performed in 200 cases of cerebral tumours and cerebrovascular lesions. The advantages over conventional angiography are evident; the extent of a tumour is easier to determine as well as in most cases the nature of the mass lesion.

Blood Pressure↗