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T Yamazaki

Publications and source records attributed to T Yamazaki.

At least 541 records · Page 30Linked to original sources
PubMed1993

Competition for electron transfer between cytochromes P450scc and P45011 beta in rat adrenal mitochondria.

Rat adrenal mitochondria contain approximately equal levels of P450scc and P45011 beta, each reduced by NADPH through adrenodoxin reductase (ADX-reductase) and adrenodoxin (ADX). Constitutive cholesterol side-chain cleavage (SCC) can be increased over 20-fold through a combination of hormonal activation and inhibition of cholesterol metabolism in vivo prior to isolation of the mitochondria. This stimulation, which results from accumulated reactive cholesterol, does not significantly affect either the dependence of activities on the concentration of isocitrate (IC) and succinate (SU) or the ratio of maximum activities [3:1] supported by these reductants. Thus, the rate of cholesterol SCC is determined independently by electron transfer and the amount of reactive cholesterol. Hydroxylation of deoxycorticosterone (11 beta and 18 positions) required much higher levels of each reductant, indicating less effective reductant transfer to P45011 beta. Reactions at P450scc and P45011 beta, mediated by IC, are enhanced by low concentrations of various dicarboxylates anions (fumarate, SU). The actions of SU dehydrogenase inhibitors and the activity of fumarate, a poor direct reductant, suggest that higher production of NADPH results from malate-enhanced uptake of isocitrate. Only synergistic combinations of reductants are sufficient to sustain maximum rates of 11-deoxycorticosterone (DOC) metabolism, whereas IC is fully effective for P450scc. Increased reaction at P450scc (cholesterol loading or addition of 20 alpha-hydroxycholesterol) decreased simultaneous DOC metabolism at P45011 beta in inverse proportion to the estimated intramitochondrial generation of NADPH (1 mM or 10 mM SU > 1 mM IC > 10 mM IC). These decreases were reversed by inhibition of P450scc. Crossover inhibition caused by maximum DOC metabolism was less pronounced. EGTA/albumin treatment, which enhanced activities at both P450scc and P45011 beta, presumably via increased NADPH, diminished this cross-competition. The differential dependence on reductants and the characteristics of crossover competition are consistent with a roughly three-fold more favorable partitioning of electron transfer to P450scc, possibly caused by preferential interaction of reduced adrenodoxin with P450scc.

Adrenal Cortex↗
PubMed1993

A feasible method for expansion of peripheral blood lymphocytes by culture with immobilized anti-CD3 monoclonal antibody and interleukin-2 for use in adoptive immunotherapy of cancer patients.

Cultivation of T lymphocytes with immobilized anti-CD3 monoclonal antibody and human recombinant interleukin-2 induced a rapid proliferative response. This procedure was applied to expansion culture of peripheral blood lymphocytes obtained from cancer patients for use in adoptive immunotherapy. Peripheral blood mononuclear cells were separated from 20 ml of blood and cultured in anti-CD3 coated flasks with rIL-2 for 6 days, then transferred to a gas-permeable culture bag and culture continued for an additional 8 days with an increasing volume of medium. Cell numbers increased about 2000-fold during this 2-week culture. The final population contained about 30% CD4+ and 60% CD8+ cells, and all were CD3+ & HLA-DR+. NK cells comprised less than 5%. In clinical trials involving 12 cases receiving 35 infusions, the mean number of harvested T cells after 14 days culture was 3.5 x 10(10) (R = 1.6-6.8 x 10(10)), and the mean expansion index was 1560-fold (R = 409-4091). This method could be of benefit not only in immunotherapy but also for obtaining somatic cells from a small volume of blood for use in molecular or genetic analysis instead of having to perform EB virus transformation of B cells.

Antibodies, Monoclonal↗
PubMed1993

Differential regional responses of myocardial interstitial noradrenaline levels to coronary occlusion.

OBJECTIVE: The aim was to investigate the influence of coronary occlusion on myocardial interstitial noradrenaline levels in the ischaemic and non-ischaemic regions, using the dialysis technique. METHODS: In nine anaesthetised cats, regional ischaemia was produced by occlusion of the left anterior descending coronary artery for 90 min. Using the dialysis technique, dialysates were sampled from both the ischaemic region and the nonischaemic left circumflex coronary artery region. Dialysate noradrenaline concentrations, as an index of myocardial interstitial noradrenaline content, were measured by high performance liquid chromatography. Myocardial blood flows in the ischaemic and non-ischaemic regions were measured by the hydrogen clearance method. RESULTS: In the non-ischaemic region, neither myocardial blood flow nor dialysate noradrenaline concentration showed significant change. In the ischaemic region, myocardial blood flow decreased significantly, from 117(SEM 12) at control to 23(3) ml.min-1 x 100 g-1, and dialysate noradrenaline concentration increased significantly, from 56.8(4.5) pg.ml-1 at control to 528.8(155.4) pg.ml-1 at 0-30 min of occlusion, 4212.0(1447.7) pg.ml-1 at 30-60 min, and 4179.8(1668.5) pg.ml-1 at 60-90 min. At 0-30 min of the reperfusion period, dialysate noradrenaline concentration in the postischaemic region decreased significantly to 420.2(152.1) pg.ml-1. CONCLUSIONS: Coronary occlusion increased myocardial interstitial noradrenaline levels in the ischaemic region, but not in the non-ischaemic region.

Animals↗
PubMed1993

Cyclic hexapeptide analogs of somatostatin containing bridge modifications. Syntheses and conformational analyses.

The cyclic hexapeptide c[Pro6-Phe7-D-Trp8-Lys9-Thr10-Phe11] displays higher bioactivity than native somatostatin in inhibiting the release of growth hormone. The superscript numbers refer to the location of the residues in native somatostatin. To investigate the structural role played by the Phe11-Pro6 bridging region, we have synthesized a series of cyclic hexapeptide analogs of somatostatin incorporating peptidomimetics and retro-inverso modifications at the bridging region. Among them, two analogs contain the retro-inverso modification mAla6-gPhe11 at the bridging region, and five analogs contain 2-aminocyclopentane carboxylic acid (2-Ac5c) and 1-aminocyclopentane carboxylic acid (1-Ac5c) as proline mimetics. The conformational preferences of these analogs have been studied using 1H-NMR and computer simulations. All of these analogs maintain conformations similar to those of the parent cyclic hexapeptide around the Phe7-D-Trp8-Lys9-Thr10 tetrapeptide region consisting of a beta II' turn. However, they display different conformational features around the bridging region. The R-mAla analog and the five Ac5c analogs show only a trans amide bond for Phe11-Pro6 in the bridging region, while the S-mAla analog displays a cis/trans isomerization for the same amide linkage in the bridging region. The R-mAla and the five Ac5c analogs do not bind to the somatostatin receptor, while the S-mAla analog displays a high binding activity. Applying our recently proposed model for bioactivity of somatostatin analogs, we examined the structure-bioactivity relationships for these somatostatin analogs. This investigation provides valuable insight into the structural role played by the bridging region.

Amino Acid Sequence↗
PubMed1993

Embryonic development and postnatal changes in free D-aspartate and D-serine in the human prefrontal cortex.

We have analyzed free chiral amino acids (aspartate and serine) in the human frontal cortex at different ontogenic stages (from 14 weeks of gestation to 101 years of age) by HPLC with fluorometric detection after derivatization with N-tert-butyl-oxycarbonyl-L-cysteine and o-phthaldialdehyde. Exceptionally high levels of free D-aspartate and D-serine were demonstrated in the fetal cortex at gestational week 14. The ratios of D-aspartate and of D-serine to the total corresponding amino acids were also high, at 0.63 and 0.27, respectively. The concentration of D-aspartate dramatically decreased to a trace level by gestational week 41 and then remained very low during all postnatal stages. In contrast, the frontal tip contained persistently high levels of D-serine throughout embryonic and postnatal life, whereas the D-amino acid content in adolescents and aged individuals was about half of that in the fetuses. Because D-aspartate and D-serine are known to have selective actions at the NMDA-type excitatory amino acid receptor, the present data suggest that these D-amino acids might play a pivotal role in cerebral development and functions that are related to the NMDA receptor.

Adolescent↗
PubMed1993

Noradrenaline contributes to modulation of the carotid sinus baroreflex in the nucleus tractus solitarii area in the rabbit.

The authors examined the contribution of the noradrenergic system to central cardiovascular regulation in the dorso-medial region of the medulla oblongata, including the nucleus tractus solitarii (NTS) area, in anaesthetized rabbits. First, to determine the modulation of the carotid sinus baroreflex system by alpha-blocker, which blocks the action of noradrenaline, the open loop relationship between isolated carotid sinus pressure (CSP) and renal nerve activity (RNA) was examined before and after injection of alpha-blocker (phentolamine, 10 micrograms, bilateral). alpha-Blocker injected to the NTS area caused a decrease in RNA at low CSP level (40-50 mmHg), and RNA response remained higher at high CSP levels (130 mmHg), in comparison with control. Baroreflex sensitivity was attenuated significantly from 10.9 +/- 2.2 to 5.0 +/- 0.5% (mmHg-1). The data show that the NTS area is one of the important sites in central modulation of the carotid sinus baroreflex function. It is suggested that the noradrenergic system in the NTS area contributed to facilitating carotid sinus baroreflex function. Second, using the dialysis technique, a dialysis probe was implanted in the dorso-medial region of the medulla oblongata, including the NTS area, and perfused with Ringer's solution. Dialysates were collected from this region and noradrenaline (NA) output was determined by high-performance liquid chromatography/electrochemical methods. Drug-induced hypotension caused a 30% decrease in arterial pressure and an increase in dialysate NA levels from 6.8 +/- 0.2 to 9.0 +/- 0.4 pg sample-1. The results show that noradrenaline in the NTS area is involved in the regulation of arterial pressure through the central modulation of arterial baroreflex function.

Animals↗
PubMed1993

[Polypeptide profiles of Chlamydia pneumoniae strains isolated from Japan and western blot analysis using patients' sera].

Polypeptide profiles were compared among Chlamydia pneumoniae strain of AC-43, which was isolated from a Japanese child, and other strains of C. pneumoniae. There was no distinctive differences among these strains. All strains showed marked band on 39.5 KDa area, which is equivalent with the major outer membrane protein (MOMP). Patients infected with C. pneumoniae were analyzed by Western blot using AC-43. Reaction for 98, 68, 60 KDa proteins were recognized among sera which showed positive results for anti-C. pneumoniae IgG antibody. There were two family members from whom C. pneumoniae was not isolated and anti-C. pneumoniae IgG antibody was negative. Sera obtained from them also showed weak reaction on 98 KDa protein area. Strong reaction on MOMP area was demonstrated in one patient from whom C. pneumoniae was isolated. Monoclonal antibody produced from AC-43 strain showed no reaction against homologous antigen. Reaction to 98 KDa protein was detected in all of the patients infected with C. pneumoniae. However, recognition to MOMP of C. pneumoniae seems to be different among patients. This result might suggest the presence of subtype among C. pneumoniae strains.

Blotting, Western↗
PubMed1993

[A report of 4 cases from whom Chlamydia pneumoniae was isolated].

Chlamydia pneumoniae (C. pneumoniae) was isolated from respiratory tract of 4 girls. Case 1 is 5-year-old, diagnosed as pneumonia, had had a prolonged productive cough. She was treated with RKM with improvement of symptoms, however, C. pneumoniae was isolated repeatedly and was not deleted. Neither anti-mycoplasmal nor viral antibodies were positive and no significant pathogens were cultured from nasophrayngeal swabs. Case 2, the sister of case 1, is a 3-year-old girl with acute bronchitis treated with EM. C. pneumoniae was negative on the tenth day after treatment. Case 3, a 5-year-old girl, had a fever and was diagnosed as bronchopneumonia with a mild attack of bronchial asthma. She was initially treated with CFIX followed by therapy including EM. Her symptoms had disappeared after treatment and anti-mycoplasmal antibody was 1:320. Case 4 was an asymptomatic carrier of C. pneumoniae. Specimen was obtained at regular health examinations of junior high school. C. pneumoniae was isolated from a 14-year-old girl without respiratory symptoms. Clinical figures of C. pneumoniae infections varies from asymptomatic carrier to pneumonia. Pathogens other than C. pneumoniae could modify symptoms of infections. Precise examinations of these cases would establish a proper management of a C. pneumoniae infection.

Adolescent↗
PubMed1993

Therapeutic effect of cefozopran (SCE-2787), a new parenteral cephalosporin, against experimental infections in mice.

The therapeutic effect of cefozopran (SCE-2787), a new semisynthetic parenteral cephalosporin, against experimental infections in mice was examined. Cefozopran was more effective than cefpiramide and was as effective as ceftazidime and cefpirome against acute respiratory tract infections caused by Klebsiella pneumoniae DT-S. In the model of chronic respiratory tract infection caused by K. pneumoniae 27, cefozopran was as effective as ceftazidime. The therapeutic effect of cefozopran against urinary tract infections caused by Pseudomonas aeruginosa P9 was superior to that of cefpirome and was equal to those of ceftazidime and cefclidin. In addition, cefozopran was more effective than ceftazidime and was as effective as flomoxef in a thigh muscle infection caused by methicillin-sensitive Staphylococcus aureus 308A-1. Against thigh muscle infections caused by methicillin-resistant S. aureus N133, cefozopran was the most effective agent. The potent therapeutic effect of cefozopran in those experimental infections in mice suggests that it would be effective against respiratory tract, urinary tract, and soft tissue infections caused by a variety of gram-positive and gram-negative bacteria in humans.

Animals↗
PubMed1993

Dopamine D1 receptors in Parkinson's disease and striatonigral degeneration: a positron emission tomography study.

Striatal dopamine D1 receptors were investigated in 11 patients with Parkinson's disease (PD), five patients with striatonigral degeneration (SND) and six age-matched controls by positron emission tomography and carbon-11 labelled SCH23390. The SND patients showed mean 12%, 21%, and 31% declines in the ratios of radioactivity in the caudate, anterior putamen, and posterior putamen compared with that in the occipital cortex. These ratios were not significantly altered in the PD patients. The results may explain the different therapeutic responses to levadopa between SND and PD patients, and this technique might prove useful for their differentiation.

Adult↗
PubMed1993

[Pharmacological studies on small peptide fraction derived from soybean. The effects of small peptide fraction derived from soybean on fatigue, obesity and glycemia in mice].

The present research was an attempt to determine the pharmacological actions as for anti-fatigue, anti-obesity and hypoglycemia of small peptide isolated from soybean in mice. Small peptide administration prevented the decrease in sporting movement induced by concussion stress for 3 h in mice. In addition, it should be noted that the recovery rate of fatigue in 60 min after small peptide administration was over one hundred percentage in comparison with that after pretreatment, while the equivalent dose administration of amino acid mixture with the same small peptide amino acid composition did not prevent the decrease in sporting movement. In gold-thioglucose (500 mg/kg (i.p.))-induced obese mouse body weight gain, liver weight and body lipid level around uterine were significantly reduced by the chronic oral administration of small peptide (200, 1000 mg/kg). Administration in 1000 mg per kg of small peptide significantly lowered hyperglycemia in 30 and 120 min after glucose (3 g/kg (p.o.)) administration, whereas the equivalent amino acid mixture showed no effect. In conclusion, it suggested that small peptide isolated from soybean might have some pharmacological effects of anti-fatigue, anti-obesity, and hypoglycemia.

Animals↗
PubMed1993

Spontaneous mutation rates in null and band-morph mutations of enzyme loci in Drosophila melanogaster.

Spontaneous mutations were accumulated for a total of 1,678,388 allele-generations in several hundred replicate second chromosome lines. These lines were compared of a Cy chromosome and one of three different lethal bearing chromosomes from natural populations. Electrophoretic mobility and/or activity change was screened for seven enzyme loci. Forty-four null mutations were detected, but no band-morph mutations were observed. There is significant variation in null mutation rate among enzyme loci and among lethal chromosomes. This may be attributable to differences in the distribution of transposable elements among the lines. The band-morph mutation rate is pooled with previous results and becomes 7.48 x 10(-7) with a 95% confidence limit of 2.04 x 10(-7) to 1.91 x 10(-6) per locus per generation. Similarly, the pooled null mutation rate becomes 1.30 x 10(-5) with 95% confidence limit of 1.15 x 10(-5) to 1.52 x 10(-5) per locus per generation.

Animals↗
PubMed1993

Benastatins C and D, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. Production, isolation, structure determination and biological activities.

Benastatin C, a new member of the benastatins, has been isolated from the culture broth of Streptomyces sp. MI384-DF12. The structure of benastatin C was elucidated as 2-decarboxy-benastatin A by NMR studies. Benastatin D, 2-decarboxybenastatin B, was derived from benastatin B. Benastatins C and D showed inhibitory activities against human pi class glutathione S-transferase (GST pi) and excellent stimulatory activities on the murine lymphocyte blastogenesis in vitro.

Animals↗