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Biomedical subjects

Y Hirashima

Publications and source records attributed to Y Hirashima.

At least 91 records · Page 5Linked to original sources

Plasma platelet-derived growth factor-B chain is elevated in patients with extensively large brain tumour.

The plasma concentration of the platelet-derived growth factor (PDGF)-B chain and the plasma platelet factor 4 (PF4) levels were measured in 17 healthy controls and 55 brain tumour patients. In the 17 normal controls, the plasma PDGF-B and PF4 levels were 523 +/- 157 pg/ml (mean +/- SD) and 84 +/- 37 ng/ml, respectively. In the brain tumour patients, these values were 881 +/- 854 pg/ml and 93 +/- 64 ng/ml, respectively. The plasma PDGF-B concentration was elevated above the upper limit of normal individuals in 12 (22%) of the 55 patients. However, since the corresponding PF4 levels suggested the platelet activation, the increased plasma PDGF-B may have originated from platelets. To address this, platelet releasing experiments were performed on citrated blood samples from 5 normal individuals. The plasma PDGF-B and PF4 levels from the 17 normal controls and those observed in the platelet releasing experiments correlated with a regression line of Y = 240 + 4.86X (Y:PDGF, X:PF4). There were only 6 (11%) patients whose plasma PDGF-B level was elevated above the 95% confidence limit estimated from the corresponding PF4 value. In these patients, the tumour volumes were extensively large, and those elevated PDGF-B values decreased after treatment and became elevated again in three patients with recurrent glioblastoma. Although the plasma tumour-derived PDGF-B was detected only in an extensively large brain tumour, it might be a useful plasma marker evaluating the effects of therapy and prognosis in such patients.

Adolescent↗

Anti-phospholipid antibodies and cerebral vasospasm following subarachnoid haemorrhage.

Delayed ischaemic deficits due to cerebral vasospasm contribute to the high morbidity and mortality rates associated with subarachnoid haemorrhage. We evaluated the usefulness of measuring anti-phospholipid antibodies (aPLs) for prediction of the occurrence of symptomatic vasospasm and the outcome after subarachnoid haemorrhage. 32 consecutive patients with subarachnoid haemorrhage due to ruptured cerebral aneurysms were studied. They were admitted and operated on within 72 hours after the onset of subarachnoid haemorrhage. aPLs such as lupus anticoagulants, anti-cardiolipin IgG and anti-cardiolipin IgM were measured repeatedly after admission. Furthermore, platelet count, platelet aggregability and plasma platelet factor 4 were also measured. Eleven among the 32 patients (34.4%) showed positive in the examination for aPLs. Although aPLs could not predict symptomatic vasospasm, once symptomatic vasospasm occurred, patients with aPLs frequently demonstrated cerebral infarction and therefore their outcome was worse. aPLs were associated with a severe initial clinical grade and SAH grade on CT scan. Therefore it may explain the association of aPLs with worse outcome. aPLs were detected between 1 and 7 days. Four of 6 patients (67%) with aPLs became negative between 7 and 13 days after subarachnoid haemorrhage. The mechanism of transient aPLs is unclear but it is more likely to occur in the severer grade patients. The reduction in platelet count, the increased platelet aggregability, and the increased plasma platelet factor 4 concentration were also observed in aPLs-positive patients with symptomatic vasospasm.

Adult↗

Platelet-activating factor (PAF) and the formation of chronic subdural haematoma. Measurement of plasma PAF levels and anti-PAF immunoglobulin titers.

In order to estimate the contribution of platelet-activating factor (PAF) to the formation of chronic subdural haematomas (CSH), we measured plasma PAF and anti-PAF antibody levels in head-injured patients with and without CSH and normal volunteers. Plasma PAF and anti-PAF IgG levels were higher in patients with CSH than in patients without CSH or in normal volunteers. Furthermore, plasma PAF and anti-PAF IgG levels increased in a time-dependent manner over the first 35 days following head injury. These data suggest that PAF may be involved in the generation of CSH.

Adult↗

Clinical study of enlarged infundibular dilation of the origin of the posterior communicating artery.

Although some aneurysmal dilations of the origin of the posterior communicating artery (PCoA) that are revealed on carotid angiogram are true aneurysms or preaneurysmal lesions, the authors warn that diagnosis should not be based only on the size and shape of the dilation, especially when the PCoA does not fill. In the present retrospective study, the authors analyzed intraoperative and angiographic findings in 32 patients with 34 lesions of the PCoA that were preoperatively diagnosed as aneurysms. Only 10 of the lesions were true aneurysms (six cases) or enlarged infundibular dilations with reddish bulges (that is, preaneurysmal bulge; four cases) at the origin of the PCoA. All of the other 24 lesions, including one lesion with PCoA occlusion, were merely enlarged infundibular dilations without any wall abnormality. A well-developed PCoA was observed only in cases of true aneurysm and dilation with reddish bulge. No other clinical or angiographic characteristics proved useful in identifying the type of lesions. These findings may be helpful to the physician in evaluating the clinical features of such lesions and in determining the diagnosis of enlarged infundibular dilation of the PCoA.

Aged↗

Platelet-activating factor and antiphospholipid antibodies in subarachnoid haemorrhage.

The purpose of this study was to measure plasma platelet-activating factor (PAF) concentration, PAF-acetylhydrolase activities, anti-phospholipid antibody (aPLs) titers, and platelet function in patients with subarachnoid haemorrhage (SAH) and to assess the association of these variables with the development of cerebral vasospasm. Thirty-two patients with SAH due to ruptured cerebral aneurysm were studied. Plasma PAF concentration, PAF-acetylhydrolase activity, platelet count and aggregability, and plasma factor 4 (PF4) concentrations were measured regularly until approximately 2 weeks after SAH. aPLs, including lupus anticoagulant and anti-cardiolipin IgG and IgM were measured within 3 days after SAH. Plasma PAF concentration in patients with SAH showed the highest value on the occasion during 5 to 9 days after SAH. The concentrations were higher in patients with infarction due to vasospasm than in patients without cerebral infarction on any occasions after SAH. Plasma PAF-acetylhydrolase activities did not change in patients, regardless of the presence of cerebral infarction after SAH. Increased platelet consumption and aggregability and higher concentrations of PF 4 were detected in patients with cerebral infarction and not in patients without cerebral infarction. The patients with cerebral infarction due to cerebral vasospasm had aPLs more frequently than the control volunteers. Our findings indicate that increased plasma PAF and aPLs may contribute to the pathogenesis of cerebral vasospasm after SAH.

Adult↗

An experimental model of symptomatic vasospasm induced by oxyhemoglobin in rabbits.

BACKGROUND AND PURPOSE: There are many experimental models for studies of cerebral vasospasm. However, no ideal model has been established thus far to comparatively reproduce the ischemic state of the brain that may occur in patients after subarachnoid hemorrhage. METHODS: In the present study, we attempted to induce severe vasospasm in rabbits by using an oxyhemoglobin-rich blood product prepared from hemolyzed arterial blood and evaluate neurological symptoms, cerebral angiogram, cerebral blood flow, and histology. RESULTS: Clinically significant neurological symptoms were observed in about half of the rabbits. There was no significant correlation between angiographic results of the vasospastic state of the main artery and the severity of neurological symptoms observed. However, the cerebral blood flow was significantly lower than in the control group and significantly correlated with the severity of neurological symptoms. On histological examination, lesions were found in about half of the rabbits. Development of obvious infarction was found more frequently than in other reported models. CONCLUSIONS: These results suggest that this model is appropriate as an experimental model of vasospasm occurring after subarachnoid hemorrhage and is especially useful in that it induces vasospasm intense enough to cause obvious infarction.

Animals↗

Analysis of plasma and hematoma lipids related to choline glycerophospholipid in patients with chronic subdural hematoma.

The levels of platelet-activating factor (PAF) and lipid metabolites related to choline glycerophospholipid were measured in the plasma and hematoma samples obtained from patients with chronic subdural hematoma. The ratio of lyso-choline glycerophospholipids (lysoPC) to choline glycerophospholipids (PC) in hematoma correlated with the interval between the onset of symptoms and surgery. PC and lysoPC fatty acyl moieties in plasma and hematoma were essentially similar. These results suggest that the lysoPC to PC ratio in hematoma can determine the age of the chronic subdural hematoma, and that the origin of hematoma may be circulating blood. The levels of PAF in the plasma of chronic subdural hematoma patients were significantly greater than in healthy volunteers. PAF may be involved in the enlargement of chronic subdural hematoma.

Aged↗

Platelet-activating factor (PAF) concentration and PAF acetylhydrolase activity in cerebrospinal fluid of patients with subarachnoid hemorrhage.

The authors studied the sequential changes in platelet-activating factor (PAF) and PAF acetylhydrolase in the cerebrospinal fluid (CSF) of patients with subarachnoid hemorrhage (SAH). Levels of PAF in CSF showed a gradual increase after the onset of SAH, with a subsequent decrease. The PAF concentration between 5 and 9 days after SAH was greater in patients with cerebral infarction due to vasospasm than in patients without infarction. Conversely, PAF acetylhydrolase activity decreased gradually after SAH, then increased. The enzyme activity for the same period was smaller in patients with cerebral infarction than in patients without infarction. The distribution of the days of maximum PAF concentration and minimum PAF acetylhydrolase activity did not differ significantly between the two groups. The CSF as a source of PAF acetylhydrolase activity gave an apparent Michaelis constant value of 90.8 microM and a maximum velocity of 0.2 nmol/min/mg. The optimum pH level for the PAF acetylhydrolase activity obtained from CSF was 6.5. The enzyme activity of CSF increased, depending on the incubation temperature, ranging from 25 degrees to 45 degrees C. Ethylene-glycol tetra-acetic acid (1 mM) was found to inhibit PAF acetylhydrolase activity in CSF obtained from patients with SAH. Unaltered PAF acetylhydrolase activity was inhibited by adding an aliquot of CSF and minimum PAF acetylhydrolase activity decreased following SAH. Two peaks of inhibitory activity were detected on Sephacryl S-200 HR gel filtration: one was eluted in void volume and the other with an apparent molecular mass of 13 kD. The inhibitory activity was very labile and was lost completely within 3 days of incubation at 4 degrees C. The regulation of the PAF concentration in the CSF of SAH patients is discussed.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Sequential changes in the platelet count in patients with symptomatic vasospasm after subarachnoid hemorrhage.

The platelet count in 110 patients with subarachnoid hemorrhage (SAH) was analyzed retrospectively. Changes in the platelet count in 102 patients undergoing intracranial aneurysm surgery showed that the minimum platelet count was similar in patients with and without symptomatic vasospasm, but the minimum occurred later in symptomatic vasospasm patients, regardless of Hunt and Hess grade or operation timing. Sixty-five of 67 non-symptomatic vasospasm patients (97%) showed the minimum platelet count within 4 days of SAH and two (3%) on the 5th day. In contrast, only 10 of 35 symptomatic vasospasm patients (29%) showed a minimum platelet count within 4 days after SAH and 25 (71%) between the 5th and 11th days. Analysis of the eight patients not receiving surgery showed that the minimum platelet count occurred 2 days after SAH in two non-symptomatic vasospasm patients, but after the 5th day in five of six symptomatic vasospasm patients. Therefore, monitoring of the platelet count can provide an indicator of the occurrence of symptomatic vasospasm.

Adult↗

Platelet-activating factor and cerebral vasospasm following subarachnoid hemorrhage.

This study examines whether platelet-activating factor (PAF) is involved in the occurrence of vasospasm after subarachnoid hemorrhage (SAH). A vasospasm model was produced in rabbits, with animals in six experimental groups receiving two subarachnoid injections of autologous arterial blood with the addition of one of the following; saline (Control Group 1), 25% dimethyl sulfoxide (Control Group 2), PAF (1, 2.5, 5, or 10 micrograms), CV6209 (10 or 100 micrograms), BN52021 (10 or 100 micrograms), or anti-PAF immunoglobulin G (IgG, 50 or 500 micrograms). No significant differences were detected between Control Groups 1 and 2 with regard to neurological deterioration and basilar artery constriction after SAH was induced. Administration of PAF together with autologous blood aggravated neurological deficits in a dose-dependent manner (r = 0.724, p < 0.001) and produced basilar artery constriction at two doses each of 2.5 micrograms (p < 0.05), 5 micrograms (p < 0.01), and 10 micrograms (p < 0.01). Neurological deterioration was prevented in rabbits receiving an intracisternal administration of either PAF antagonist CV6209 or BN52021 or anti-PAF IgG (p < 0.01 at a total dose of 20 micrograms and p < 0.05 at a total dose of 200 micrograms CV6209, p < 0.01 at total doses of 20 and 200 micrograms BN52021, and p < 0.01 at total doses of 100 and 1000 micrograms anti-PAF IgG). A reduction in basilar artery constriction was achieved by the injection of anti-PAF IgG (p < 0.05 at total doses of 100 and 1000 micrograms). Histological examination at autopsy on Days 14 to 21 showed mainly ischemic changes in the brain, including selective neuronal necrosis and cerebral infarction. The control and PAF groups showed marked ischemic changes. On the other hand, no ischemic changes were noted in the anti-PAF IgG group, and only 9% of animals in the CV6209 group and 25% in the BN52021 group demonstrated selective neuronal necrosis or infarction. This study thus provides evidence to support the role of PAF in the pathogenesis of vasospasm after SAH.

Animals↗

Immunofluorescent localization of platelet-activating factor (PAF) in the rat.

An immunofluorescent staining method for detecting platelet-activating factor (PAF) is described. This method employs a polyclonal anti-PAF rabbit antibody. When rat brain, heart, lung, liver or kidney tissue was stained using this method, the heart, lung and kidney exhibited PAF-specific staining. Analysis of the amount of PAF in different organs, either by immunofluorescence or by bioassay, showed that kidney tissue contains the greatest amount of PAF.

Animals↗

[Intraperitoneal chemotherapy of CDDP and etoposide in patients with advanced ovarian cancer].

Intraperitoneal disseminated ovarian cancer has a poor prognosis and its treatment is difficult. Recently, we undertook intraperitoneal chemotherapy (IP) of CDDP (Pt) and etoposide (Et) using an implantable reservoir. The subjects were 14 patients with advanced ovarian cancer. One hundred mg of Pt and 200 mg of Et were administered intraperitoneally through the reservoir, and the therapeutic results were evaluated. In 6 patients, levels of total platinum (t-Pt), free platinum (f-Pt) and Et were determined in the blood and intraperitoneal fluid by flameless atomic absorption spectrophotometry. 1. The 14 patients received 82 courses of IP. In 10 cases of IIIrd stage, no recurrence was detected in 5 radical operable cases, and 4 of 5 inoperable cases were able to undergo radical operation after IP. One case was inoperable even after IP. Recurrences were detected in 2 of 4 cases which subsequently became operable. In a case of IVth stage, remission was achieved, but the tumor markers began rising again 18 months after operation. No further recurrence was detected in a treated recurrence case. In 2 cases of metastatic cancer, recurrences were detected 3 and 7 months after operation, respectively. As a side effect, the incidence of gastrointestinal toxicities, anemia, leukocytopenia and alopecia was high, but the grade was almost 1 or 2. Intraperitoneal mean maximum concentrations were t-Pt: 21.98 +/- 5.78; f-Pt: 17.72 +/- 4.97; Et: 62.98 +/- 23.94 micrograms/ml. Blood mean maximum concentrations were t-Pt: 2.84 +/- 0.41; f-Pt: 0.84 +/- 0.22; Et: 11.38 +/- 2.12 micrograms/ml. Mean AUC of the blood were t-Pt: 57.76 +/- 6.62; f-Pt: 2.96 +/- 0.47; Et: 108.76 +/- 18.94 micrograms.h/ml. 2. IP is considered to be effective for advanced ovarian cancer not only as a local therapy but as a general therapy, and is feasible as maintenance therapy with the implantable reservoir and tolerable side effects.

Adult↗

Identification and purification of calcium-independent phospholipase A2 from bovine brain cytosol.

Substantial amounts of phospholipase A2 activity were detected in bovine brain cytosol. The major phospholipase A2 activity was present in the precipitate at 40% saturation with solid ammonium sulfate. After the desaltate of the precipitate was loaded onto an Ultrogel AcA 54 gel filtration column, almost all the activity eluted in the void volume when chromatographed without 1 M KCl. However, when buffer with 1 M KCl was used as the eluent, two active peaks were obtained. One peak (peak I) eluted in the void volume, and the other (peak II) eluted with an apparent molecular mass of 39 kDa as compared with standards. The former was active with diacylglycero-3-phosphoethanolamine, whereas the latter was active with both diacylglycero-3-phosphoethanolamine and 1-alk-1'-enyl-2-acylglycero-3-phosphoethanolamine (plasmenylethanolamine). The apparent molecular mass of peak I was estimated to be 110 kDa as compared with standards on an Ultrogel AcA 34 gel filtration column. Both peaks were purified further with a hydrophobic chromatography column (AffiGel 10 coupled with plasmenylethanolamine) and then by high-resolution liquid chromatography on an MA7Q column. The phospholipase A2 obtained from peak II migrated as one main band with a 40-kDa molecular mass and two minor bands with 14- and 25-kDa molecular masses. Phospholipase A2 obtained from peak I eluted as a single peak on high-resolution liquid chromatography but contained two bands with apparent molecular masses of 100 and 110 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in lipid metabolites and enzymes in rat brain due to ischemia and recirculation.

Thirty and 60-min ischemic insults resulted in an increase in free fatty acid and 1,2- diacylglycerol contents of rat forebrain. No significant changes were detected in phospholipids except phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate during ischemic insult. Phosphatidylinositol 4-monohosphate and phosphatidylinositol 4,5-bisphosphate contents decreased during ischemia. Although the increase in free fatty acid contents continued, 1,2-diacylglycerol did not show further increase after 30-min ischemia. These results suggest that there may be another pathway for the accumulation of free fatty acids in addition to phospholipase C coupled to di- and monoacylglycerol lipase. Free fatty acid and 1,2-diacylglycerol contents increased transiently and thereafter decreased to control levels within 90 min after postischemic recirculation. The decrease in arachidonic acid content preceded those of other FFA. Phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate contents gradually increased after the initiation of recirculation in ischemic brains. Lysophosphatidylcholine decreased gradually after temporary increase during 15 and 5-min recirculations in 30 and 60-min ischemic groups. Phospholipase A, phospholipase C, and di- and monoacylglycerol lipase activities did not show significant changes during entire course of recirculation. Total activities of lysophospholipase and acylation enzymes of lysophospholipid demonstrated 1.5-and 2.2-fold increase during 30-min recirculation.

Animals↗

Phospholipase A2 activities with a plasmalogen substrate in brain and in neural tumor cells: a sensitive and specific assay using pyrenesulfonyl-labeled plasmenylethanolamine.

We have developed a new assay method for phospholipase A2 (EC 3.1.1.4.), towards ethanolamine plasmalogen using pyrenesulfonyl-labeled plasmenylethanolamine as the substrate. This procedure is sensitive to about 3 pmol/ml per min and is absolutely specific for plasmalogen. In this method, the product of phospholipase A2, pyrenesulfonyl-labeled lysoplasmalogen, is hydrolyzed to aldehyde and labeled glycerophosphoethanolamine with hydrochloric acid exposure, and after TLC separation, the pyrenesulfonyl-glycerophosphoethanolamine is quantitated spectrofluorometrically. The excitation and emission wave lengths were 340 and 376 nm, respectively. The activity of bovine brain homogenate was 44.1 +/- 6.47 pmol/min per mg protein (n = 3). Among bovine brain subcellular fractions, the distribution and specific activity of the enzymes were highest in cytosol (38.7 +/- 1.58% and 102.6 +/- 16.2 pmol/min per mg protein, n = 3). The activities of neural tumor cells, PC12 pheochromocytoma, Neuro2A and SKNSH neuroblastoma and U1242MG glioblastoma, were 34.4 +/- 6.83 (n = 5), 7.05 +/- 0.97 (n = 4), 5.25 +/- 1.69 (n = 5), and 9.68 +/- 1.35 (n = 4), pmol/min per mg protein (M +/- S.E.M.), respectively.

Adrenal Gland Neoplasms↗

Purification of plasmalogens using Rhizopus delemar lipase and Naja naja naja phospholipase A2.

Bovine heart ChoGpl (choline glycerophospholipid) and bovine brain EtnGpl (ethanolamine glycerophospholipid) contain diacyl, alkenylacyl and alkylacyl analogs. Purification of plasmalogens was achieved using R. delemar lipase and N. naja naja phospholipase A2 digestion. The R. delemar lipase hydrolyzes the acyl bond at the 1-position of 1,2-diacyl glycerophospholipids. The N. naja naja phospholipase A2 has greater activity with diacyl and alkylacyl than with alkenylacyl glycerophospholipids. These enzymes were mainly used to remove diacyl and alkylacyl analogs respectively. When the diacyl types were removed by double incubation with R. delemar lipase, the plasmalogen content was 94.2% +/- 0.21% (mean +/- S.E.M., n = 4) for PlsCho (plasmenylcholine) and 94.9% +/- 0.19% (mean +/- S.E.M., n = 3) for PlsEtn (plasmenylethanolamine). Recoveries were 74% and 88% respectively. These partially purified plasmalogens were treated with N. naja naja phospholipase A2. Finally, 97.7% +/- 0.24% (mean +/- S.E.M., n = 4) and 98.8% +/- 0.27% (mean +/- S.E.M., n = 3) pure plasmalogens were obtained for PlsCho and PlsEtn respectively. Plasmalogens were recovered in an overall yield of 7.7% +/- 0.7% (mean +/- S.E.M., n = 4) and 10.2% +/- 1.2% (mean +/- S.E.M., n = 3) for PlsCho and PlsEtn.

Animals↗