Stimulation-induced release of arachidonic acid from membrane phospholipid in mast cells.
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Animals↗
Biomedical subjects
S Nakashima
Publications and source records attributed to S Nakashima.
[The clinical evaluation of ceftizoxime suppositories in the pediatric field].
Clinical evaluation of ceftizoxime suppository (CZX-S), a new antibiotic rectal suppository, was performed in 5 cases with bacterial infections in pediatric field (2 with acute bronchitis, 1 with acute tonsillitis, UTI and pertussis, respectively) and the following results were obtained; Blood levels of CZX at 10-20 minutes after administration of CZX-S at a dose of 10.0-26.3 mg/kg in 5 cases were 3.26-23.3 micrograms/ml and the urinary excretion rates within 6 hours were 15.2, 60.1, 60.2% in 3 of 5 cases measured respectively. Clinical effects were excellent in 3 and good in 2 cases. Slight elevation of GOT and GPT was observed in 1 case. No other side effects were observed. The patients' tolerability against rectal suppository was good. From the above results, we concluded that CZX-S is useful for treating the pediatric patients with various infections.
Bacteria↗
Phospholipid (diacyl, alkylacyl, alkenylacyl) and fatty acyl chain composition in murine mastocytoma cells.
The phospholipids from murine mastocytoma FMA3 and P-815 clone cells were quantitatively analyzed, and the major glycerophospholipids were examined for their fatty acyl chain distribution. In these cells, the content of histamine was less than 1/100 of normal mouse mast cells, and FMA3 cells had 1.5-fold as much histamine content as P-815 cells. The predominant phospholipid species of both mastocytoma FMA3 and P-815 were choline-containing glycerophospholipids (48%) and ethanolamine-containing glycerophospholipids (29%). The remaining minor constituents were sphingomyelin (6%, 7%), phosphatidylinositol (7%, 5%), phosphatidylserine (2%, 5%), cardiolipin (4%, 3%), and phosphatidic acid (2%, 1% for FMA3 and P-815, respectively). The choline-containing glycerophospholipids consisted of high amounts of 1-O-alkyl-2-acyl type (31%, 25%) and 1,2-diacyl type (63%, 66%) and a smaller amount of 1-O-alk-1'-enyl-2-acyl type (7%, 8%). In contrast, ethanolamine-containing glycerophospholipids were characterized by high contents of 1-O-alk-1'-enyl-2-acyl type (36%, 31%) and 1,2-diacyl type (55%, 58%), and a lower level of 1-O-alkyl-2-acyl type (12% and 11% for FMA3 and P-815, respectively). Unlike choline-containing glycerophospholipids and sphingomyelin that were rich in palmitic acid, ethanolamine-containing glycerophospholipids, phosphatidylserine and phosphatidylinositol showed a high proportion of stearic acid in the overall fatty acid composition. The content of arachidonic acid was highest in phosphatidylinositol. Sphingomyelin had a large amount of long chain and polyunsaturated fatty acids. In both choline- and ethanolamine-containing glycerophospholipids, the predominant fatty acids in the sn-1-position were palmitic, stearic, and oleic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylglucosaminidase↗
Compositional changes in brain lipids, especially cerebroside and gangliosides, of rats treated with methylmercury chloride.
Rats were orally given 4 mg of methylmercury chloride per kg per day up to 14 days, and killed at 4-day or arbitrary intervals. Parietal gray matter and cerebellum were taken for lipid analyses. The ganglioside content increased during the early stage before the manifestation of clinical symptoms. After the onset of clinical signs, the total lipid concentration was elevated, and especially the levels of phosphatidylethanolamine and cerebroside were increased. The ganglioside distribution patterns were also altered in the late stage, showing decreased proportion of GD1a and increased percentages of GD1b and GQ1b.
Animals↗
[Fundamental and clinical studies of aztreonam in pediatric infections].
Fundamental and clinical studies were carried out with aztreonam (AZT), a new monocyclic beta-lactam antibiotic, in pediatric infections. Results were as follows. The mean half-lives in the vein blood were 1.09 hours, 1.18 hours, 1.22 hours after injection, when the doses were 10, 20 and 40 mg/kg, respectively. Dose response was observed. The average recovery rates in the urine between 0 and 6 hours were 40.2%, 42.3%, 50.8% when the doses were 10, 20 and 40 mg/kg, respectively. The antibacterial activity of AZT against 16 clinical isolates were determined in comparison with those of ABPC, CPZ, LMOX and CTX. Against 8 clinical isolates of E. coli and 3 of H. influenzae, the activity of AZT was equal or superior to that of CPZ, LMOX and CTX, and way by far superior to that of ABPC. Twenty-three pediatric patients received AZT in doses ranging from 48 to 79 mg/kg divided 3 times a day; 12 cases of urinary tract infection, 9 cases of respiratory tract infection and 2 cases of bacterial enterocolitis. The rate of clinical effectiveness was 100%. No side effect was observed. Slight elevation of GOT and GPT were observed in 2 cases, increase of platelet count in 2. All were considered to be transient and mild.
Age Factors↗
Effects of dibutyryl cyclic AMP and forskolin on phospholipid biosynthesis in thrombin-stimulated human platelets.
The influence of forskolin, an adenylate cyclase activator, and of dibutyryl cyclic AMP (Bt2cAMP) on [3H]glycerol incorporation into glycerolipids was investigated in human platelets. It was found that preincubation with 2.5 mM Bt2cAMP produced a 2-4-fold increase in thrombin-induced incorporation into phospholipids compared to platelets activated by thrombin alone. Pretreatment with forskolin, which increased cellular cAMP content, also resulted in an increase in thrombin-stimulated [3H]glycerol incorporation into phospholipids. These findings demonstrate that a rise in platelet cAMP can accentuate thrombin-induced de novo synthesis of phospholipids from [3H]glycerol. Since the content of cellular cAMP was correlated with its ability to inhibit platelet activation monitored by serotonin release, it seems likely that glycerolipid, in particular phospholipid biosynthesis, is involved in controlling platelet activation by thrombin.
Adult↗
Self-adaptive modification of red-cell membrane lipids in lecithin: cholesterol acyltransferase deficiency. Lipid analysis and spin labeling.
In a patient with lecithin: cholesterol acyltransferase deficiency, free cholesterol was markedly increased, and esterified cholesterol was diminished. In the patient's plasma, an increase in phosphatidylcholine (PC) and a decrease in sphingomyelin were observed. Concomitantly, an increase in a shorter acyl chain 16:0 was noted in PC, sphingomyelin and phosphatidylethanolamine (PE). In contrast to these results, longer chains such as 22:0 and 24:0 were decreased, especially in sphingomyelin. Unsaturated double bonds such as 18:1 was also increased in PC and PE. In the red-cell membrane lipids, the increase in free cholesterol was counteracted by an increase in PC and by a decrease in sphingomyelin and PE, reflecting changes in the patient's plasma lipids. Increased 16:0 (in PC) and decreased 18:0 and 24:0 were observed. The increased plasma free cholesterol due to metabolic defect (lecithin: cholesterol acyltransferase deficiency) led to decreased red-cell membrane fluidity. This effect appeared to be counteracted by changing phospholipid composition (increased PC and decreased sphingomyelin and PE), by increasing shorter chains (16:0), by decreasing longer chains (18:0 and 24:0) and by increasing unsaturated double bonds (18:2). These results can be interpreted as a self-adaptive modification of lecithin: cholesterol acyltransferase deficiency-induced red-cell membrane abnormalities, to maintain normal membrane fluidity. This speculation was supported by the ESR spin-label studies on the patient's membrane lipids. The normal order parameters in intact red cells and in total lipid liposomes were decreased if cholesterol-depleted membrane liposomes were prepared. Thus, the hardening effect of cholesterol appeared to be counteracted by the softening effects described above. Overall membrane fluidity in intact red cells of the lecithin: cholesterol acyltransferase-deficient patient was maintained normally, judged by order parameters in ESR spin-label studies.
Cholesterol↗
Differential activation of membrane phospholipid turnover by compound 48/80 and ionophore A23187 in rat mast cells.
Membrane phospholipid turnover was investigated during histamine release from rat mast cells. Addition of calcium ionophore A23187 (0.5 microgram/ml) to mast cells prelabeled with [3H]glycerol induced the rapid and progressive increase in phosphatidic acid (PA) and 1,2-diacylglycerol (DG), which was concomitant with the small rise in phosphatidylinositol (PI). Loss of the level in triacylglycerol (TG) was very marked. Polyamine compound 48/80 (5 micrograms/ml) was shown to cause rises in PA, 1,2-DG, and PI without any significant changes in TG. Both stimuli increased incorporation of exogenous [3H]glycerol into phospholipids, indicating the involvement of de novo synthesis in phospholipid metabolism. Studies with [3H]arachidonic acid-labeled mast cells showed an enhanced liberation of radioactive arachidonate and metabolites upon histamine release. There were associated decreases of radioactivity in phosphatidylcholine (PC) and TG when exposed to A23187, while phosphatidylethanolamine (PE) was degraded as a result of 48/80 activation. The transient increases of [3H]arachidonoyl-1,2-DG and PA were caused by 48/80, while A23187 showed a gradual rise in the radioactivity in these two lipid fractions. These findings reflect activation of phospholipase C. When mast cells were activated by low concentrations of A23187 (0.1 microgram/ml) and 48/80 (0.5 microgram/ml), different behaviors of PI metabolism were observed. An early degradation of PI and a subsequent formation of 1,2-DG and PA suggest that the lower concentrations of these agents stimulate the PI cycle initiated by PI breakdown rather than de novo synthesis. These results demonstrate that marked and selective changes in membrane phospholipid metabolism occur during histamine release from mast cells, and that these reactions seem to be controlled by the coordination of degradation and biosynthesis, depending on the type and the concentration of stimulants. A23187 stimulates arachidonate release perhaps via the cleavages of PC and TG, whereas 48/80 liberates arachidonate from PE.
Animals↗
Tyrosine hydroxylase protein in Lewy bodies of parkinsonian and senile brains.
Immunohistochemistry with the antisera against tyrosine hydroxylase (TH) was performed on the neurons with Lewy bodies (LBs) in the sections at the level of the basal ganglia, midbrain, pons, medulla oblongata and spinal cord. These were obtained from 3 autopsy cases with Parkinson's disease and 2 senile brains without parkinsonism. In catecholamine neurons, stained positively with the antisera to TH, specific immunoreactions were found in the LBs. These specific stainings were accentuated and/or restricted to the peripheral, less dense, zone of the LBs in the neurons of catecholaminergic regions. LBs in the neurons of the innominate substance, raphe nuclei of the brain stem and spinal cord did not stain positively with TH antisera. This suggests that the production of LBs is complicated, but that it is also closely correlated to the biochemical properties of each neuron in the various regions. In catecholamine neurons in which LBs frequently occurred, TH enzyme protein might play an important part in the productions of LBs.
Aged↗
Phospholipid and fatty acid composition of erythrocyte membrane from wild Japanese serow (Capricornis crispus).
The phospholipid composition and fatty acid composition of the individual phospholipids were determined in erythrocyte membrane of wild Japanese serow, Capricornis crispus, and compared with those of Japanese cattle. Sphingomyelin (SM) contributed more than 50% to the total phospholipids, with only 3% phosphatidylcholine, 30% phosphatidylethanolamine and 11% phosphatidylserine. This phospholipid composition and ratio of phospholipid to protein in erythrocyte membrane of wild serow were quite similar to those of Japanese cattle. However, marked differences in fatty acid composition were found, especially in lignoceric acid 24:0 and nervonic acid 24:1 of sphingomyelin which were major constituents (approximately 60%) of that phospholipid.
Animals↗
Sequential expansion of antibody heterogeneity during the response to bacterial alpha-amylase.
By analyzing antibody heterogeneity during the primary immune response to bacterial a-amylase (B alpha A) in high-responder F1 hybrid mice between C57BL/6 (B6) and C3H/He (C3) mice with the use of isoelectric focusing (IEF), it was shown that the maturation of the primary IgG antibody response consisted of at least two stages. The response of every mouse tested was initiated with the production of specific antibody focused as a limited set of bands in a narrow pH range, and the subsequent rise in antibody titer was associated with the sequential expansion of the spectra involving the appearance of new bands in the pH gradient adjacent to the initial bands. A further rise was accompanied only by intensified staining of the pre-existing bands. These two stages were distinguishable regardless of the antigen dose, although increasing the dose led to widely distributed spectra of focused antibodies and an early shift from the first stage to the second. The sequential expansion of spectra following the appearance of initial antibodies with limited isoelectric point (pI) values was not unique to the anti-BaA antibody response, because similar results were obtained with the antibody response to an immunologically unrelated antigen, Taka-amylase A (TAA). Thus, the appearance of initial antibodies in a limited pH range, overlapping among all F1 hybrids tested, is not a direct reflection of similarity in the determinant specificities of these antibodies among different mice.
Animals↗
Abnormal phosphatidylinositol-cycle of platelet membrane in schizophrenia--a preliminary study.
Phosphatidylinositol (PI)-cycle in the platelet membrane was examined in eight untreated patients with psychotic symptoms. A defect of PI-cycle in the transformation from 1,2-diacylglycerol into phosphatidic acid was found in three patients, who were diagnosed as having Schizophrenic Disorders or Schizophreniform Disorder according to the DSM-III criteria. Two out of the three patients were reexamined while undergoing neuroleptic medication, and they showed the same abnormality in PI-cycle. Further studies were required to determine the nature of the abnormality in PI-cycle in the platelets of schizophrenics.
Adolescent↗
Lipid analyses and fluidity studies by electron spin resonance of red cell membranes in hereditary high red cell membrane phosphatidylcholine hemolytic anemia.
Membrane lipid analyses and electron spin resonance (ESR) studies of membrane fluidity were carried out on the red cells of a Japanese patient with hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA). Increased amounts of phosphatidylcholine (PC) and cholesterol were found in the membrane lipids of the affected patient, despite normal plasma lipids. The order parameter of cholesterol-free pure phospholipid liposomes prepared from this patient's red cells was decreased, apparently because of the increased PC. In contrast, the order parameter of the total red cell lipid liposomes (containing free cholesterol) was essentially normal. The overall fluidity of the intact red cells was determined by ESR with a spin probe, 5-SAL. Again, the order parameters were normal in the intact red cells of the patient with HPCHA. This suggests that the concomitant increase of membrane cholesterol and phosphatidylcholine serves to maintain normal membrane fluidity in the HPCHA red cells.
Aged↗
[Tyrosine hydroxylase in the catecholamine neurons of the autopsy brains with degenerative neurological disorder].
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Adolescent↗
In vitro boost of human NK activity by a triethylphosphine gold derivative.
Human PBL incubated in vitro with the new anti-rheumatic drug triethylphosphine gold (Auranofin) show a rapid concentration-dependent increase in NK reactivity to a variety of targets (Raji, K-562, HAE 70). The process is not affected by major changes in the proportion of monocytes present and is only slightly affected by actinomycin D or cycloheximide. In contrast to TPG, the effect of interferon is to boost the activity of K cells as well as NK cells, and this boost appears to be more sensitive to inhibition of protein or RNA synthesis. These factors suggest that TPG may be working through a different mechanism.
Anti-Inflammatory Agents↗
Accelerated expansion of antibody heterogeneity by complete Freund's adjuvant during the response to bacterial alpha-amylase.
Changes in the isoelectric focusing (IEF) spectra of specific antibodies were followed during the response of individual mice to bacterial alpha-amylase (B alpha A) in either incomplete or complete Freund's adjuvant (IFA or CFA). The response to a suboptimal dose of B alpha A was maximally enhanced by employing CFA at an optimal dose of Mycobacterium tuberculosis. Regardless of the strain difference in responsiveness to B alpha A between C3H/He (C3) and C57B1/6 (B6) mice, the enhancing effect of CFA was characterized by an accelerated expansion of IEF spectra and by the intensified stain of focused antibody, compared with the response of mice immunized with the same antigen dose in IFA. The manner and the rate of heterogeneity expansion during the enhanced antibody response to a low dose in CFA were quite similar to the strictly restricted expansion of spectra during a response of a high dose of B alpha A in IFA, although each mouse showed an individual banding pattern with a different degree of heterogeneity, depending on the antibody titre. Thus, CFA accelerated the expansion of IEF spectra during the response to B alpha A without affecting the general manner of sequential expansion of anti-B alpha A antibody heterogeneity.
Animals↗
[Topography of the serotonin neurons in the brain stem of human fetus: an immunohistochemical study].
The distribution of serotonin neurons in the central nervous system (CNS) has been intensively examined in mammals, such as rats, cats and monkeys. However, the details of serotonin neuron system have been remained uncertain in human CNS, although two fluorescence histochemical studies were reported in human fetus. In this study, we performed immunohistochemical examination on the distribution of serotonin neurons in the brain stem of human fetuses. The brain stems from five human fetuses (CRL: 120-275 mm, GA: 15-27 wks) were fixed with 4% paraformaldehyde, dehydrated with graded ethanol, and embedded in paraffin. Serial sections, 6 micron in thickness, were cut from seven different levels of the brain stem of each fetus. The initial several sections were used for usual histological observations. The following serial ones were stained by peroxidase-antiperoxidase (PAP) technique using anti-serotonin sera. The anti-serotonin sera used were raised in rabbits by the methods of Ranadive and Sehon (1967), Grota and Brown (1974), and Steinbusch et al (1978). Before the use, the specificity of the antisera was confirmed by the immunohistochemical examination of the CNS of rat embryos and adults. Positively stained serotonin neurons were clearly demonstrated in the brain stems of all cases examined (Figs. 1A-1H). They were small to medium in size, 10 X 20 micron to 20 X 40 micron, and varied in shape, showing round to oval cell somata with unipolar, bipolar and multipolar processes. The distribution of serotonin neurons in the brain stems was almost the same among five human fetuses (Figs. 2A-2K). A large number of serotonin neurons were located in the midline raphe nuclei. In addition, numerous serotonin neurons were observed widely in the other tegmental area. The nuclei containing serotonin neurons were listed in Table 2 according to the terminology by Olszewski and Baxter (1982). The distribution of the serotonin neurons in the raphe nuclei of human fetuses was fundamentally similar to those of many mammals reported previously. However, the lateral extension of serotonin neurons to the other tegmental area beyond the midline raphe nuclei in human fetuses was much greater than in any other mammals. This distribution pattern of serotonin neurons was considered to be peculiar to human fetus. Since the histological architecture of the brain stems of five fetuses examined was very similar to that of human adults, the distribution of serotonin neurons demonstrated here may also represent that of human adults.
Brain Mapping↗
A mouse model for Niemann-Pick disease: phospholipid class and fatty acid composition of various tissues.
Recently, a strain of mice bearing an autosomal recessive gene, spm, has been described. On the basis of clinical and pathological findings these mice have been suggested as a useful model of human Niemann-Pick disease. Phospholipids and their fatty acid compositions were analyzed for liver, spleen, whole brain, erythrocytes, and blood plasma from "Niemann-Pick"animals (spm/spm) and heterozygous controls (spm/+). Sphingomyelin and bis(monoacylglycero)phosphate accumulated in the liver and spleen of the affected mice, whereas no significant proportional change of phospholipids was observed in the whole brain. The phospholipid composition in erythrocytes and blood plasma of the homozygous mice was not different from that of the heterozygous controls. The fatty acyl chain profile of accumulated bis(monoacylglycero)phosphate was characterized by the high content (more than 80%) of unsaturated fatty acids; the main components were oleic acid, linoleic acid, and docosahexaenoic acid. A high unsaturation index of the fatty acyl chain was found in sphingomyelin accumulated in organs and in almost all phospholipids of brain, erythrocytes, and blood plasma of "Niemann-Pick" mice. It is conceivable that desaturation of fatty acids is enhanced in the "Niemann-Pick" mice.
Animals↗