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Biomedical subjects

A Fujita

Publications and source records attributed to A Fujita.

At least 19 recordsLinked to original sources
PubMed1992

Production of a unique multi-lamella structure in the nuclei of yeast expressing Drosophila copia gag precursor.

Drosophila retrotransposon copia produces virus-like particles (VLPs) in the nuclei of cultured Drosophila cells. The VLPs contain copia RNA and reverse transcriptase activity, and thus, play a major role in copia replication. Here we have expressed the copia gag polyprotein precursor in yeast. The precursor, which includes copia protease itself, showed correct autoprocessing to produce a unique multi-lamella structure in the nuclei of the yeast cells. This expression system should be useful for the analysis of nuclear localization of the major copia VLP protein, and furthermore, would provide important information concerning the mechanism of copia VLPs formation.

Animals↗
PubMed1992

The yeast SFL2 gene may be necessary for mating-type control.

We previously reported the isolation of the yeast suppressor gene for flocculation, SFL2 (TUP1). SFL2 gene disruption results in pleiotropic phenotypes; the sfl2 null mutation also causes a morphological change similar to shmoo in both the MAT alpha and MATa/alpha cells. The MAT alpha and MATa/alpha sfl2 null mutant cells incorporate chitin into the new growth zone in the same way as the alpha-factor-treated MATa cells. In order to clarify the molecular basis of this morphological change, we examined the effect of the sfl2 null mutation on the mRNA production of various genes involved in mating-type control. The transcripts of both the STE2 (an a-specific gene) and STE3 (an alpha specific gene) genes are detected in the MAT alpha and MATa/alpha cells carrying the sfl2 null mutation. In addition, mRNA of the GPA1 gene (haploid-cell-specific gene) is also detected in the MATa/alpha sfl2 cells. However, there is no significant difference in the levels of the MAT alpha 2 and MATa1 transcripts. These results suggest that the SFL2 gene product may be necessary for alpha 2 and a1-alpha 2 repression.

Chitin↗
PubMed1992

Cardiovascular and adenylate cyclase stimulant properties of NKH477, a novel water-soluble forskolin derivative.

The cardiovascular effects of NKH477 (6-(3-dimethylaminopropionyl)forskolin hydrochloride), a novel water-soluble forskolin derivative, were investigated in dogs. Intravenous (i.v.) injections of NKH477 (1-30 micrograms/kg) caused dose-related increases in left ventricular dP/dtmax (LVdP/dtmax), coronary and femoral artery blood flow (CBF, FBF), heart rate (HR), and myocardial oxygen consumption (MVO2) and a dose-related decrease in blood pressure (BP) in anesthetized dogs. The regression analysis between CBF and MVO2 showed that NKH477 did not influence substantially the balance of oxygen supply and demand. Infusions of NKH477 (0.15-0.6 microgram/kg/min i.v.) also increased LVdP/dtmax, cardiac output (CO), and HR and decreased BP, pulmonary arterial diastolic pressure, and total peripheral resistance (TPR) in a dose-dependent manner. In contrast to forskolin, NKH477 administered intraduodenally (0.05-0.2 mg/kg) and orally (0.15 and 0.3 mg/kg) clearly exhibited cardiovascular actions, as it did in i.v. administration, indicating that NKH477 is orally active. No arrhythmias were induced by NKH477 in any study. NKH477, like forskolin, showed adenylate cyclase stimulant activity in guinea pig ventricular membrane but did not inhibit Na+, K(+)-ATPase or phosphodiesterase (PDE) activity. Thus, NKH477 can be characterized as a potent, orally active, water-soluble forskolin derivative, which suggests that NKH477 is a useful inodilator for treatment of heart failure, especially in the severe stage with beta-adrenoceptor downregulation.

Adenylyl Cyclases↗
PubMed1992

Clearance function of eustachian tube and negative middle ear pressure.

Two experimental studies were performed using 18 cats in order to elucidate the mechanism of the long-lasting course of otitis media with effusion. First, the middle ear (ME) pressure was monitored for 2.5 to 7 hours after filling the whole ME space with saline. On average, -150 mm H2O of negative ME pressure was induced in 3.1 hours. Second, the residual volume of saline with antibiotics, which was put into the ME space 2 to 7 days before, was compared between the side on which tubal ventilatory function was abolished (resection of tensor veli palatini muscle and hamulus pterygoideus) and the opposite, control side. The percentage of the residual volume to the original volume put into the ME was significantly higher on the experimental side (Wilcoxon's ranking test, t = 27.0, p less than .05), and in one ear on the experimental side, the ME pressure showed-150 mm H2O just before the bulla was opened 2 to 7 days later. These results seem to indicate that tubal ciliary clearance function can induce negative ME pressure when there is fluid in the ME, and that the negative ME pressure induced by clearance of the ME fluid may disturb further clearance of the ME fluid. This condition may cause the long-lasting course of otitis media with effusion.

Animals↗
PubMed1992

Pathogenesis of experimental otitis media with effusion caused by a combination of eustachian tube dysfunction and immunosuppression.

Inflammatory factors appear to play an important role in the development of otitis media with effusion (OME). However, otitis media experimentally induced by endotoxin injection or secondary immunoresponse was not persistent. In order to produce refractory OME, two pathologic conditions were necessarily combined: tubal ventilatory dysfunction and suppression of the immunologic defense mechanism by immunosuppressive drugs. In the presence of these two pathologic conditions, all cases that evidenced negative middle ear pressure due to tubal dysfunction developed OME. In the control group with either tubal dysfunction or immunosuppression alone, only 1 of 20 ears developed OME. Transtubal infection due to negative middle ear pressure caused by tubal ventilatory dysfunction may be one of the most important etiologic factors in OME.

Animals↗
PubMed1992

Improvement of drug-induced cardiac failure by NKH477, a novel forskolin derivative, in the dog heart-lung preparation.

The efficacy of NKH477, a novel water-soluble forskolin derivative, in improving cardiac failure was assessed in dog heart-lung preparations. Cardiac functions depressed by pentobarbital, propranolol or verapamil so that cardiac output had been reduced by about 40-50% of the respective control were all improved by NKH477 (10-100 micrograms) in a dose-dependent manner. With 100 micrograms NKH477, almost complete restoration of cardiac performance was attained in the respective cardiac failures. In the combination of NKH477 with ouabain (30 micrograms), 30 micrograms of NKH477 completely restored the cardiac function depressed by pentobarbital, associated with a slight but not significant increase in heart rate. No arrhythmias were induced by any of the NKH477 doses used in the experiments. These results suggest that NKH477 should be subjected to clinical trials in the treatment of cardiac failure.

Animals↗
PubMed1992

Role of PGE2 in neurotransmission from pre- to post-ganglionic hypogastric nerves of guinea pigs.

The hypogastric nerve to guinea pig vas deferens was stimulated pre- or post-ganglionically by adjusting the position of the suction electrode. Both stimulations induced a biphasic contraction consisting of a rapid transient phase and a delayed tonic phase. Indomethacin partially inhibited the contraction induced by pre-ganglionic stimulation, but did not inhibit that induced by post-ganglionic stimulation. Prostaglandin (PG) E2 counteracted the inhibitory effect of indomethacin. Mepacrine also inhibited the contraction induced by pre-ganglionic stimulation. Arachidonic acid and PGE2 both reversed the inhibition. The PGE2-receptor antagonist SC-19220 inhibited the contraction induced by pre-ganglionic, but not post-ganglionic nerve stimulation. These results suggested that endogenous PGE2 is important in neurotransmission in the pelvic ganglion of guinea pigs.

Animals↗
PubMed1992

Selective inhibitory effects of calcium channel antagonists on the two components of the neurogenic response of guinea pig vas deferens.

The effects of L-type calcium channel antagonists and omega-conotoxin on the contractile responses of guinea pig vas deferens were examined in vitro. Electrical stimulation of the postganglionic hypogastric nerve induced biphasic contraction consisting of rapid phasic and delayed tonic components. L-type calcium channel antagonists, such as diltiazem, verapamil and nicardipine, mainly inhibited the delayed tonic component, whereas omega-conotoxin mainly inhibited the rapid phasic component. Stimulations in the presence of prazosin and alpha, beta-methylene ATP induced rapid transient and delayed contraction, respectively, which were inhibited by omega-conotoxin and L-type calcium channel antagonists, respectively. Short-term stimulation with five pulses induced a small fast phasic contraction. This contraction, which could be desensitized by alpha, beta-methylene ATP, was inhibited by omega-conotoxin, but not by L-type calcium channel antagonists. At the concentrations used in the present study, none of the calcium channel antagonists inhibited the contractions induced by exogenously added ATP or norepinephrine. These findings suggest that L-type calcium channel antagonists and omega-conotoxin inhibit the neurotransmissions mediated by norepinephrine and ATP, respectively, from the postganglionic nerve to the vas deferens of the guinea pig. Inhibition of the voltage-dependent calcium channel is discussed in relation to the mechanism of cotransmission in this preparation.

Adenosine Triphosphate↗
PubMed1992

[Diffuse large cell lymphoma with spontaneous regression in the lung and lymph nodes. Case report].

An 84-year-old woman was admitted to our hospital because of swelling of the cervical lymph nodes and multiple tumorous lesions observed on radiographic studies. Transcutaneous lung biopsy was performed, but necrosis of the tissue was too marked to make a diagnosis. The diagnosis of diffuse large-cell lymphoma was made based on a biopsy of the pretracheal lymph node. During the first two months after admission, the left cervical lymph nodes and most of the pulmonary lesions regressed not withstanding of special treatment for lymphoma. The patient eventually died of generalized peritonitis. At autopsy, metastasis of systemic organs by malignant lymphoma was observed. Most of the lung regions were cicatrized, but clusters of atypical lymphocytes were observed in the necrotic tissue. The tumor in the mucosa of the small intestine showed necrosis, which accounted for the intestinal perforation. The total clinical course after admission was about six months. Spontaneous regression of diffuse large cell lymphoma is rare, and this is the second reported case in Japan.

Aged↗
PubMed1992

Lipoprotein lipase enzyme expression in 3T3-L1 adipocytes is posttranscriptionally down-regulated by retinoic acid.

The effects of all-trans retinoic acid (RA) on the lipoprotein lipase (LPL) activity, synthesis and mRNA content in 3T3-L1 adipocytes were studied. When fully differentiated 3T3-L1 adipocytes were exposed to RA, dose-dependent suppression of LPL activity was observed. The loss of activity reached a maximum of 60% of the control level and appeared to be due to an effect on synthesis of the enzyme, as judged from the decreased incorporation of [35S] methionine and [35S] cysteine into immunoprecipitable LPL. The LPL mRNA level remained unchanged under the same conditions. In contrast, no significant reduction in glycerol-3-phosphate dehydrogenase activity or change in the morphological signature occurred on 24 hr exposure of 3T3-L1 adipocytes to RA. These results suggest that RA can specifically down-regulate LPL enzyme expression in adipocytes at the posttranscriptional level.

Adipose Tissue↗
PubMed1992

[A case of primary antiphospholipid syndrome with fever, pulmonary thromboembolism and endocardial lesion].

A previously healthy 16-year-old girl complaining of fever, hemosputum, chest pain and dyspnea was hospitalized. On admission, physical examination revealed mental confusion, holosystolic heart murmur, and swelling of the left foot. Laboratory investigations showed anemia, leukocytosis, thrombocytopenia, activation of inflammatory reactions, prolongation of PT and APTT, and hypoxia. Antinuclear antibody test was negative. There were no other findings suggestive of collagen diseases such as SLE. Chest X-ray showed consolidation in the left lower lung field and pleural effusion. Echocardiography disclosed a mass lesion in the left atrium in contact with the mitral valve, and mitral regurgitation. No findings indicative of an infectious etiology were present. The patient rapidly improved with high dose corticosteroid and anticoagulant therapy. A venogram of the lower extremity disclosed deep venous thrombosis. A lung ventilation-perfusion scan revealed multiple pulmonary thromboemboli. Elevation of anticardiolipin antibody was noted. Based on these findings, the diagnosis of primary antiphospholipid syndrome was made. Further administration of steroid and anticoagulant resulted in decrease of the titer of anticardiolipin antibody. This is the second report of primary antiphospholipid syndrome in Japan. The clinical significance of this disease is also discussed.

Adolescent↗
PubMed1992

[Alpha 1-antitrypsin deficiency with bronchiectasis in two sisters].

Two sisters with alpha 1-antitrypsin deficiency and bronchiectasis are reported. The 53-year-old older sister (propositus) had pneumonia 3 times during her forties. She developed dyspnea on exertion in February, 1988, and a few months later she was seen at our hospital. Her serum alpha 1-antitrypsin level was 11 mg/dl. Vascular markings on chest X-ray were mildly decreased. Bronchography showed generalized cystic bronchiectasis. The younger sister was seen at our hospital at the age of 50. She had been in good health until one year previously when she had developed pneumonia, and thereafter she had suffered from productive cough and dyspnea on exertion. Her alpha 1-antitrypsin level was 22 mg/dl. Chest X-ray showed ring-like shadows and tram lines. Chest CT scans of both sisters revealed cystic changes, dilatation of bronchi, and the connection of these lesions diffusely. The alpha 1-antitrypsin phenotype of these sisters was found to be PiSiiyama (homozygote). Family study revealed that alpha 1-antitrypsin levels of 7 members were intermediate and no members had symptoms. We consider that bronchiectasis may have been related to alpha 1-antitrypsin deficiency in these sisters.

Bronchiectasis↗
PubMed1991

Inhibition of HIV-reverse transcriptase activity by some phloroglucinol derivatives.

Four phloroglucinol derivatives, named mallotophenone (5-methylene-bis-2,6-dihydroxy-3-methyl-4-methoxyacetophenone), mallotochromene (8-acetyl-5,7-dihydroxy-6-(3-acetyl-2,4- dihydroxy-5-methyl-6-methoxybenzyl)-2,2-dimethylchromene), mallotojaponin (3-(3,3(dimethylallyl)5-(3(acetyl-2,4- dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) and mallotolerin (3-(3-methyl-2-hydroxybut-3-enyl)-5(3-acetyl-2,4- dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone), have been tested for their ability to inhibit the activity of human immunodeficiency virus (HIV)-reverse transcriptase. Under the reaction conditions with (rA)n.(dT)12-18 as the template.primer, the enzyme activity was inhibited by approximately 70% in the presence of 10 micrograms/ml mallotochromene or mallotojaponin, whereas mallotophenone and mallotolerin were much less inhibitory to the enzyme. The enzyme activity was also inhibited, though to lesser extent, by these compounds under similar conditions with initiated MS-2 phage RNA as the template.primer. The mode of inhibition was, as analyzed with mallotojaponin, competivite with respect to the template.primer, (rA)n.(dT)12-18, and non-competitive with respect to the triphosphate substrate, dTTP. The Ki value of mallotojaponin for HIV-reverse transcriptase was determined to be 6.1 microM.

Base Sequence↗
PubMed1991

Purification and characterization of Streptomyces griseus metalloendopeptidases I and II.

Two metalloendopeptidases, designated as Streptomyces griseus metalloendopeptidases I and II (SGMPI and SGMPII), were isolated from a commercial Pronase P by a method including affinity chromatography on carbobenzoxy-L-alaninyl-triethylenetetraminyl-Sepharose (Z-Ala-T-Sepharose). The two enzymes differed from each other in behavior on ion-exchange chromatography but showed the same amino-terminal sequence at least up to the 20th residue. Their molecular weights were both estimated to be 37,000 by SDS-polyacrylamide gel electrophoresis. Elemental and amino acid composition analyses indicated that both of them contained about 1 g atom of zinc and one cystine residue per mol of protein. Cleavage specificities of the two enzymes toward synthetic peptide-substrates were very similar to those observed with thermolysin. EDTA, o-phenanthroline, and phosphoramidon strongly inhibited these enzymes, while typical serine-protease inhibitors and cysteine-protease inhibitors had no effect. The findings clearly indicate that SGMPI and SGMPII can be classified into the family of zinc-endopeptidases. It was unexpectedly found, however, that these metalloendopeptidases were strongly inhibited by protein serine-protease inhibitors produced by Streptomycetes, such as Streptomyces subtilisin inhibitor (SSI), alkaline protease inhibitor-2c' (API-2c'), and plasminostreptin (PS).

Amino Acids↗
PubMed1991

Interactions of Streptomyces serine-protease inhibitors with Streptomyces griseus metalloendopeptidase II.

Streptomyces griseus metalloendopeptidase II (SGMPII) was shown to form tight complexes with several Streptomyces protein inhibitors which had been believed to be specific to serine proteases, such as Streptomyces subtilisin inhibitor (SSI), plasminostreptin (PS), and alkaline protease inhibitor-2c' (API-2c'), as well as with Streptomyces metalloprotease inhibitor (SMPI). The dissociation constants of complexes between SGMPII and these inhibitors were successfully determined by using a novel fluorogenic bimane-peptide substrate. The values ranged from nM to pM. The results of studies by gel chromatographic and enzymatic analyses indicated that SGMPII is liberated from the complex with SSI by the addition of subtilisin BPN'. SGMPII and subtilisin BPN' proved, therefore, to interact with SSI in a competitive manner, despite the difference in the chemical nature of their active sites.

Base Sequence↗
PubMed1991

Middle ear pressures of children with otitis media with effusion.

Middle ear (ME) pressures were measured in 30 children with chronic otitis media with effusion (OME) transtubally with the use of a catheter pressure transducer (Mikro-tip, PC-330F). They were found to range from 40 to -185 mm H2O, the average being mildly negative (-54.33 +/- 59.04 mm H2O). About two thirds of these children had pulsating changes of ME pressure; the range of the pressure change was between 10 and 50 mm H2O. The ME pressure tended to be lower in ears with serous effusion than in those with mucoid effusion, but there was no significant difference between them.

Child↗
PubMed1991

ABR latency in infants: properties and applications of various measures.

ABR latency ratios have been proposed as useful clinical tools in the assessment of infants at risk for auditory or neurologic deficits. These parameters, together with classical absolute and interwave latency measures, were examined in 131 infants with normal ABR thresholds at 48-64 weeks post-conceptional age, and with no conventional risk factor for hearing impairment or neurological abnormality. Latency of wave I is unaffected by age or gender, but that of waves III and V decreases linearly with age and is smaller in females. These effects must be accounted for in clinical evaluation. However, latency ratios V/I, V/III and III/I show no significant age or gender effects. Wave I latency and the V/I latency ratio both permitted very good discrimination between normal infants and those with presumed conductive hearing losses, but the effects of sensorineural impairment have yet to be determined. On a priori grounds it seems improbable that latency ratios will outperform classical ABR parameters, at least for the goals and age range considered in this study.

Acoustic Stimulation↗