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Biomedical subjects

M Hirata

Publications and source records attributed to M Hirata.

At least 613 records · Page 34Linked to original sources
PubMed1984

Changes of intracellular free Ca2+ in macrophages following N-formyl chemotactic peptide stimulation. Direct measurement by the loading of quin 2.

The changes in the intracellular free Ca2+ in guinea pig peritoneal macrophages induced by N-formyl chemotactic peptides were examined using a fluorescent Ca2+-indicator, quin 2. The ATP contents of quin 2-loaded macrophages were also examined. The intracellular free Ca2+ was immediately raised about 4-fold by the addition of chemotactic peptides both in the presence and absence of extracellular Ca2+, and returned to the basal level within 6 min. A mitochondrial uncoupler had no effect on basal free Ca2+ concentration and the increase in intracellular free Ca2+ induced by chemotactic peptides. A23187 increased the intracellular free Ca2+ concentration and minimized the increase by chemotactic peptides. Chlorpromazine also gradually increased the basal level, in agreement with our previous report that this drug induced Ca2+ release from the store sites. The results indicate that the increase in the intracellular free Ca2+ induced by chemotactic peptides is due to Ca2+ release from the membraneous store site(s), other than mitochondria. Extracellular Ca2+ was raised by the addition of a chemotactic peptide, when assayed in free Ca2+-free saline using quin 2. The second addition of the chemotactic peptide, after the intracellular free Ca2+ concentration had returned to the basal level, was ineffective. Recovery of the free Ca2+ change induced by chemotactic peptide was observed only when the macrophages were freshly incubated in Ca2+-containing saline for more than 20 min at 37 degrees C. These results suggest that the Ca2+ released from the store site(s) may be effluxed through the plasma membrane. Quin 2 loaded in macrophages may interfere with mitochondrial ATP synthesis.

Adenosine Triphosphate↗
PubMed1984

[An experimental study on neurotoxicity of 2,5-hexanedione. Visual and somatosensory cortical evoked potentials in rats].

In order to clarify the effects of 2,5-hexanedione (2,5-HD) on the central nervous system, the somatosensory evoked potentials (SEP) and the visual evoked potentials (VEP) were experimentally studied. Eight male rats (Jcl-Wistar) were given subcutaneously 300 mg/kg/day of 2,5-HD five days a week for three weeks. Another eight male rats group served as the control. One week after ending the administration, the SEP and VEP of rats were measured under artificial respiration using bipolar and monopolar recording methods. The caudal nerve conduction velocities (C-NCVs) were also measured before the administration was begun, and weekly during the experiment, using Ono's method. Significant findings observed in the 2,5-HD administered group in comparison with the control group were as follows: delayed latencies in P1 and N1 components of VEP, reduced amplitude between N1 and P2 components of VEP and decreased caudal nerve conduction velocities. It was also observed that latencies of SEP components of the 2,5-HD administered group tended to prolong in spite of shorter conducting length. Alterations of VEP and a tendency of prolongation in latencies of SEP components were considered to be dysfunctions of the visual and somatosensory afferent pathway attributable of 2,5-HD. The present experiments suggest that for further understanding of the effects of 2,5-HD, on the central nervous system, it is necessary to utilize more sophisticated techniques which can quantitatively detect neurophysiological changes in the ascending tract from the periphery to the cortex.

Animals↗
PubMed1984

[Therapeutic effectiveness of ceftizoxime on severe infections associated with hematologic disorders].

One hundred patients with severe infections associated with hematologic disorders, including leukemia and lymphoma, were treated with ceftizoxime (CZX) in daily doses of 4 approximately 9 g for an average of 8.9 days. In the 84 patients who completed the trial, response was excellent in 27 (32.1%) and moderate in 25 (29.8%). The rate of effectiveness was 61.9%. The only side effect seen during the treatment was skin rash in 3 patients. Hepatic disorders were observed in 5 patients. The relation between CZX and these abnormal findings was not established. These results indicate that CZX is a therapeutically effective and safe antibiotic for the treatment of severe infections in patients with underlying hematologic disorders.

Adolescent↗
PubMed1984

Cerebral circulatory and cardiac effects of vinpocetine and its metabolite, apovincaminic acid, in anesthetized dogs.

Cerebral circulatory and cardiac actions of vinpocetine and its metabolite, apovincaminic acid (AVA), were studied in anesthetized dogs. Injections of vinpocetine (0.03 to 1.0 mg/dog) into the vertebral or coronary artery produced dose-dependent increases in the blood flow of each artery. The action was more prominent in the vertebral than in the coronary artery. Intravenous bolus injections of vinpocetine (0.3 and 1.0 mg/kg) transiently increased vertebral flow and superior sagittal sinus flow velocity in a dose-dependent manner. Femoral flow was slightly increased with a fall in diastolic pressure. AVA (1.0 to 5.0 mg/kg) did not significantly increase vertebral, but increased femoral flow, which was accompanied by systemic hypotension. A similar trend of actions was noted after i.v. infusion of both agents (0.15 and 0.5 mg/kg/min for 30 min). An i.d. administration of vinpocetine (10 mg/kg) increased vertebral and regional cerebral cortical flows, accompanying with a fall in diastolic blood pressure. Femoral flow was not affected. An i.v. bolus injection of vinpocetine (1, 3 and 10 mg/kg) transiently decreased systemic blood pressure, left ventricular maximum dp/dt and heart rate in a dose-dependent manner. Cardiac output tended to be increased, and total peripheral resistance decreased. Coronary flow was transiently increased at 1 and 3 mg/kg, but tended to be decreased at 10 mg/kg. AVA, in the same dose range, decreased systemic blood pressure and total peripheral resistance, and increased cardiac output and coronary flow in a dose-dependent manner. An i.v. infusion of vinpocetine (0.5 mg/kg/min for 30 min) decreased systemic blood pressure, left ventricular maximum dp/dt, total peripheral resistance and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1983

Stimulation of Ca2+ efflux by N-formyl chemotactic peptides in guinea-pig peritoneal macrophages.

Effects of N-formyl chemotactic peptides on the Ca2+ influx and efflux were investigated in guinea-pig peritoneal macrophages using an isotope tracer. fMet-Leu-Phe did not enhance the influx of 45Ca2+ into macrophages, whereas it stimulated the efflux of 45Ca2+ from macrophages at concentrations ranging from 10(-10) M to 10(-7) M. fMet-Met-Met and fMet-Leu also stimulated the 45Ca2+ efflux, albeit at much higher concentrations, while there was no stimulation with fMet. The mitochondrial inhibitors, oligomycin and NaN3, did not modify the 45Ca2+ efflux induced by the chemoattractants, yet they did induce the release of 45Ca2+ from the mitochondria. On the other hand, higher concentrations of the calmodulin antagonists, chlorpromazine and trifluoperazine, induced the release of 45Ca2+ from the NaN3-insensitive Ca2+ store site and mimicked the enhancement of the 45Ca2+ efflux by N-formyl chemotactic peptides. Thus, N-formyl chemotactic peptides appear to increase the levels of intracellular free Ca2+ in guinea-pig peritoneal macrophages, probably by inducing the release of Ca2+ from the NaN3-insensitive Ca2+ store site.

Animals↗
PubMed1983

Intramolecular cross-linkage of lysozyme. Imidazole catalysis of the formation of the cross-link between lysine-13 (epsilon-amino) and leucine-129 (alpha-carboxyl) by carbodiimide reaction.

The salt bridge between Lys-13 (epsilon-NH3+) and Leu-129 (alpha-COO-) in lysozyme was converted to an amide bond by 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (EDC) reaction in the presence of imidazole (0.3-1 M) at pH 5 and room temperature, followed by dialysis at pH 10. Absence of imidazole under a similar condition did not give this intramolecularly cross-linked lysozyme derivative (CL-lysozyme) but resulted in the formation of intermolecularly cross-linked lysozyme oligomers. From the mechanistic studies on the formation of CL-lysozyme, imidazole was suggested to play the following three roles. (1) Some carboxyl groups activated by EDC in lysozyme were converted to acylimidazole groups which protected them from the reaction with amino groups in other lysozyme molecules at pH 5. These could be hydrolyzed at pH 10 to regenerate free carboxyls. (2) High concentrations of imidazole (pH 5) increased the ionic strength of the solution which weakened the salt bridge in lysozyme and facilitated the activation of the alpha-carboxyl group by EDC. (3) The alpha-carboxyl group activated by EDC was converted to an acylimidazole group which could react with the epsilon-amino group of Lys-13 in the same molecule to form an amide bond. The last step may involve some conformational change of the backbone of lysozyme and be slower than the hydrolysis reaction of the alpha-carboxyl group activated by EDC itself. However, acylimidazole groups are stable against hydrolysis at pH 5. This may afford enough time to allow the epsilon-amino group of Lys-13 to attack the acylimidazole group of Leu-129.

Animals↗
PubMed1983

Enzyme-induced aziridine formation by isolated hepatocytes.

The metabolism of 2-bromoethylaminonaphthoquinone in hepatocytes isolated from rats was studied. This compound was chemically inert in the reaction system used. However, in buffer solution containing isolated hepatocytes, it was gradually converted into aziridinylnaphthoquinone. Under the same reaction conditions, 4-chlorobutylaminonaphthoquinone also gave the cyclization products, pyrrolidinylnaphthoquinone. Cellular GSH decreased in both reactions.

Animals↗
PubMed1983

Glucuronidation and sulfation of p-nitrophenol in isolated rat hepatocyte subpopulations. Effects of phenobarbital and 3-methylcholanthrene pretreatment.

Parenchymal cells, isolated from untreated (control), phenobarbital(PB)-or 3-methylcholanthrene(3-MC)-treated rats, were separated into four subpopulations according to cell density, and glucuronidation and sulfation of p-nitrophenol (PNP) in the hepatocyte subpopulations were investigated. PB enhanced the glucuronidation almost 2-fold but not the sulfation, while 3-MC enhanced both glucuronidation (3-fold) and sulfation (2-fold) in the original cell suspensions. Some gradation trends were found in the conjugation activities among the hepatocyte subpopulations: In the control experiment, the extent of glucuronidation in four subpopulations was virtually the same but sulfation in high-density hepatocytes was slightly higher than in low-density ones. Both glucuronidation and sulfation were higher in low-density hepatocytes from PB-treated rats, though the gradation was very modest. Glucuronidation and sulfation tended to be slightly higher in middle-density hepatocytes in the 3-MC experiment. However, no definite correlation in conjugation activities vs. cell density, like those seen in cytochrome P-450s vs. cell density in the hepatocytes isolated from PB-treated rats, were found in the subpopulations from control or inducer-treated rats. Simultaneous studies on acetylation of p-aminobenzoic acid (PABA) revealed that the activities in the subpopulations were virtually the same and the inducers had little influence on the activity.

4-Aminobenzoic Acid↗
PubMed1983

Preventive effect of a quinonyl derivative of N-acetylmuramyl dipeptide, QMDP-66, against adriamycin-induced ECG abnormalities in rats.

The effects on adriamycin cardiotoxicity of an immunoadjuvant, 2-[2-acetamido-2-deoxy-6-0-[10-(2,3-dimethoxy-5-methyl-1, 4-benzo-quinon-6-yl) decanoyl]-D-glucopyranos-3-0-yl]-D-propionyl-L-valyl D-isoglutamine methyl ester (QMDP-66), and a reference compound, ubiquinone-10, were studied in Wistar Kyoto (WKY) rats. Adriamycin, 1 mg/kg/day intra-peritoneally (i.p.) for 23 days, elicited cardiotoxicity, as judged by widening of the QRS complexes in ECGs. Electron microscopic examination of myocytes from the treated rats revealed many cytoplasmic vacuoles possibly originating from deranged endoplasmic reticula or mitochondria. In addition, the treatment significantly inhibited body weight gain, and decreased ventricular weight. QMDP-66 alone, 1 mg/kg/day i.p. for 23 days, had no effect on the parameters described above. When QMDP-66 (1 mg/kg/day, i.p.) or ubiquinone-10 (3 mg/kg/day, i.p.) was administered together with adriamycin, the widening of the QRS complexes was significantly depressed, and cytoplasmic vacuoles in myocytes were rarely observed. The QMDP-66 or ubiquinone-10 treatment, however, did not alleviate the decrease in body weight gain or ventricular weight due to adriamycin. Heart rate was not significantly changed by any of the treatments. These findings suggest that QMDP-66 is an effective antidote against adriamycin cardiotoxicity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Ca2+ release in the endoplasmic reticulum of guinea pig peritoneal macrophages.

Passive permeability of the endoplasmic reticulum of saponin-treated macrophages to Ca2+ was studied by the filtration method using 45Ca. The Ca2+ release from the endoplasmic reticulum of macrophages was enhanced by the presence of submicromolar concentrations of Ca2+ in the medium. The Ca2+ release was enhanced by caffeine, and suppressed by MgCl2. These phenomena are similar to the Ca2+-induced Ca2+ release reported for the sarcoplasmic reticulum of skeletal muscle. On the other hand, adenine suppressed the Ca2+ release from the endoplasmic reticulum, while it reportedly enhanced the Ca2+-induced Ca2+ release of the skeletal muscle. The threshold concentration of Ca2+ for the Ca2+-induced Ca2+ release was approximately 10(-8) M in the presence of 0.95 mM MgCl2 in macrophages. The spontaneous spreading of macrophages and spontaneous migration of macrophages were inhibited by adenine, and also by caffeine in spite of the enhancement of the Ca2+-induced Ca2+ release.

Animals↗
PubMed1983

Primary malignant fibrous histiocytoma of the endometrium.

Malignant fibrous histiocytoma (MFH) has become one of the most common malignancies occurring in soft tissue. To our knowledge, the present case is the first of MFH occurring in the endometrium. The uterus removed from a 47-year-old woman demonstrated a large multinodular endometrial lesion with gross invasive foci in the myometrium and the left oviduct. Microscopically, the endometrial tumor and the invasive lesions were composed of dense sheets of markedly pleomorphic cells consisting of fibroblast-like cells, histiocyte-like cells, foamy histiocytes, benign appearing multinucleated giant cells resembling either osteoclasts or Touton giant cells, and bizarre tumor giant cells. Some of the tumor cells showed phagocytic activities. The tumor cells were oriented in a random or haphazard fashion and classical storiform and fascicular patterns were not observed. The tumor was diagnosed as MFH consisting exclusively of so-called pleomorphic pattern. The patient is alive without evidence of disease, months following total hysterectomy and bilateral salpingo-oophorectomy.

Female↗