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Biomedical subjects

Y Hirashima

Publications and source records attributed to Y Hirashima.

At least 73 records · Page 4Linked to original sources
PubMed1998

Intracerebral temperature in patients with hydrocephalus of varying aetiology.

Brain temperature was measured at various depths beneath the pial surface in patients with hydrocephalus of varying aetiology. Temperature increased gradually with depth in all patients, with the highest temperature found in the ventricle. The difference between intraventricular and rectal temperatures (delta v-r) was greater in patients who underwent continuous ventricular drainage than in patients who underwent ventriculoperitoneal shunt (continuous ventricular drainage; 1.2 (SD 0.40) degrees C, mean (SD), n=5 v ventriculoperitoneal shunt; 0.4 (SD 0.45) degrees C, n=16; p< 0.05). The difference between intracerebral and rectal temperatures (delta b2-r) was also greater in patients with continuous ventricular drainage than in patients with ventriculoperitoneal shunt (continuous ventricular drainage; 0.1 (SD 0.86) degrees C, n=5 v ventriculoperitoneal shunt; -0.7 (0.86) degrees C, n=16; p< 0.05). Among patients with normal pressure hydrocephalus, these differences were greater in the patients with better outcomes after shunt surgery than in the less improved group (delta v-r; 0.7 (SD 0.27) degrees C, n=7 v 0.1 (SD 0.40) degrees C, n=5, p< 0.01, delta b2-r; -0.2 (SD 0.61) degrees C, n=7 v -1.4 (0.90) degrees C, n=5, p< 0.01).

Adult↗
PubMed1998

Anticardiolipin antibody aggravates cerebral vasospasm after subarachnoid hemorrhage in rabbits.

BACKGROUND AND PURPOSE: We previously reported that patients with antiphospholipid antibodies (aPLs) frequently demonstrate cerebral infarction due to cerebral vasospasm after subarachnoid hemorrhage (SAH). To examine the participation of aPLs in the pathogenesis of vasospasm after SAH, we studied the relationships of aPLs and SAH in an animal model. METHODS: SAH was produced in 34 rabbits that received two subarachnoid injections of autologous arterial blood. The animals were divided into four experimental groups: SAH was induced in group A (n=9), intracutaneous injection of cardiolipin (CL) was performed before the induction of SAH in group B (n=5), intravenous injection of CL was performed before SAH in group C (n=12), and cyclosporin A was infused intravenously after the intravenous injection of CL and induction of SAH in group D (n=8). Enzyme-linked immunosorbent assay identifying the titer of IgG CL antibodies, neurological evaluation, cerebral angiography, and histological examination were performed in all four groups. RESULTS: A significant elevation of anti-CL antibodies, aggravation of neurological deficit, and reduction of caliber of the basilar artery were observed in rabbits that received the intravenous immunization of CL (group C). The administration of cyclosporin A reduced the titer of anti-CL antibody, aggravation of neurological deficit, constriction of basilar artery, and the incidence of cerebral infarction (group D). CONCLUSIONS: Anti-CL antibodies may therefore be involved in the deterioration of cerebral vasospasm after SAH.

Animals↗
PubMed1998

Platelet-activating factor and edema surrounding meningiomas.

OBJECT: The purpose of this study was to evaluate the involvement of platelet-activating factor (PAF) in the formation of edema surrounding meningiomas. METHODS: Volumes of tumor and peritumoral edema were calculated based on three-dimensional reconstructed magnetic resonance images in 31 patients with intracranial meningiomas. The authors measured tumor concentrations of PAF and localized PAF and leukocytes in the tumors by using immunohistochemical studies. A significant positive correlation was found between peritumoral edema and PAF concentration. Both PAF and leukocyte common antigen were localized to the interstitial tissue of the tumor. Edema production was related to the degree of leukocyte infiltration in meningiomas. CONCLUSIONS: It appears that PAF, which may arise from infiltrating leukocytes, is important to the development of peritumoral edema in patients with meningioma.

Adult↗
PubMed1997

Involvement of platelet-activating factor (PAF) in glutamate neurotoxicity in rat neuronal cultures.

To clarify the role of platelet-activating factor (PAF) in glutamate neurotoxicity, in vitro experiments using primary neuronal cultures were performed. The anti-PAF immunoglobulin-G (aPAF-IgG) and the three PAF receptor antagonists (BN52021, CV6209, and E5880) were tested for their neuroprotective activity in primary neuronal cultures isolated from embryonic rat cerebral cortex. The cultured neurons were exposed to glutamate (1 mM) for 60 min. Twenty-four hours after this exposure, aPAF-IgG demonstrated evidence of protective effects against neuronal damage in a dose-dependent manner. Protective effects also were observed in cultures treated with the three PAF antagonists (P < 0.05 at 1 microg/ml aPAF-IgG, P < 0.01 at 100 microM BN52021, P < 0.05 at 10 nM CV6209 and P < 0.01 at 10 nM E5880). The Fura-2 assay was used to estimate whether low dosages of exogenous PAF affect cultured neurons. The cultured neurons were loaded with Fura-2/AM. After preincubation for 120 min, the Fura-2-loaded neurons were exposed to various concentrations of PAF for 60 min. By measuring the fluorescent intensity of the medium as representing the amount of Fura-2 released from damaged neurons, we detected an increased release of Fura-2, even at low doses of PAF (P < 0.01 at 10 nM PAF). We further studied PAF production by neurons in response to glutamate. The level of PAF measured in the medium exposed to glutamate was significantly higher than the level in the medium unexposed to glutamate (P < 0.05). Our results suggest an important role of PAF in glutamate neurotoxicity.

Animals↗
PubMed1997

Inter-alpha-trypsin inhibitor is concentrated in the pericellular environment of mouse granulosa cells through hyaluronan-binding.

OBJECTIVE: The binary complex involving hyaluronan and inter-alpha-trypsin inhibitor (ITI) is an important component of the cumulus oocyte complex. The aim of this study is to investigate the physiological association between ITI and its derivatives and hyaluronan or its binding protein (HABP). STUDY DESIGN: ITI and its derivatives (heavy chains of ITI and urinary trypsin inhibitor, UTI) were tested for their ability to interact with hyaluronan or HABP. HABP was used to locate the distribution of hyaluronan in mice ovaries. RESULT: ITI and heavy chains of ITI, but not UTI, could specifically bind to immobilized hyaluronan. Furthermore HABP could specifically bind immobilized hyaluronan with high affinity, and also to immobilized ITI and its derivatives. 6 h after the injection of human chorionic gonadotropin, the hyaluronan staining in the preovulatory ovaries displayed a heterogenous appearance in which the most intense stainings were observed in cumulus oocyte complex. The distribution of ITI was found to be similar to that of hyaluronan. CONCLUSION: The hyaluronan binding sites of ITI are located in the heavy chains of this molecule. ITI is concentrated in the pericellular environment of granulosa cells through hyaluronan-binding. The altered amount of hyaluronan and ITI in the preovulatory ovaries may contribute to their important clinical characteristics including cumulus oocyte complex expansion.

Alpha-Globulins↗
PubMed1997

Elevation of platelet activating factor, inflammatory cytokines, and coagulation factors in the internal jugular vein of patients with subarachnoid hemorrhage.

The aim of the present study was to examine the changes of inflammatory and coagulation factors in blood of the internal jugular vein, not of peripheral vein, in patients with subarachnoid hemorrhage (SAH). The results show that while interleukin-6 (IL-6) and platelet activating factor (PAF) concentrations increased within first 4 days after SAH and remained elevated up to 14 days, interleukin-1 beta (IL-1 beta) showed a transient increase between 5-9 days after SAH and tumor necrosis factor-alpha (TNF-alpha) remained unchanged. Also different coagulation factors were increased between 5-9 days after SAH. Moreover, patients with delayed ischemic neurological deficits (DIND) displayed the highest levels of PAF and the coagulation factors, von Willebrand factor (vWF) and thrombin-antithrombin III complex (TAT). These results suggest that elevation of PAF and other inflammatory cytokines following SAH may cause the hypercoagulation state that is associated with cerebral vasospasm and internal jugular vein may be more adequate vessel for sampling blood to examine these factors.

Adult↗
PubMed1997

Cerebrospinal fluid tissue factor and thrombin-antithrombin III complex as indicators of tissue injury after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: No marker that reflects and predicts brain injury due to subarachnoid hemorrhage (SAH) and cerebral vasospasm has been reported. We hypothesized that membrane-bound tissue factor (mTF) and thrombin-antithrombin III complex (TAT) in the cerebrospinal fluid (CSF) of patients with SAH become markers indicating brain injury. To evaluate the hypothesis, we correlated levels of mTF and TAT in the CSF of patients with SAH with clinical severity, the degree of SAH, and outcome. METHODS: We assayed CSF mTF, TAT and myelin basic protein (MBP) in patients with SAH at intervals that included days 0 to 4 and days 5 to 9 after ictus. Classification of clinical severity of disease on admission was based on Hunt and Hess grade, degree of SAH on CT on Fisher's grading, and outcome 3 months after SAH on the Glasgow Outcome Scale. RESULTS: In the interval from days 0 to 4, mTF and TAT correlated with Hunt and Hess and Fisher grades, and occurrence of cerebral infarction due to vasospasm. Only mTF correlated significantly in this period with outcome. TAT, mTF, and MBP all correlated significantly with each other. From days 5 to 9, only mTF correlated with cerebral infarction, infarction volume, MBP levels, and outcome. CONCLUSIONS: Both mTF and TAT reflected brain injury from SAH and predicted vasospasm, though mTF was more sensitive and a better predictor of outcome. Unlike mTF, TAT did not correlate with vasospasm during the interval when it most commonly occurs, which raised doubt about thrombin activation as a cause.

Adult↗
PubMed1996

In vitro hypoxia of cortical and hippocampal CA1 neurons: glutamate, nitric oxide, and platelet activating factor participate in the mechanism of selective neural death in CA1 neurons.

We prepared neuron-rich cultures from cortical and hippocampal CA1 regions of postnatal day 1 (P1) rats. Using these cultures, we investigated the sensitivity of neurons to hypoxic insults. The effects of MK-801, cycloheximide, NG-nitro-L-arginine (L-NNA), and anti-platelet-activating factor (anti-PAF) IgG on neuronal injury under hypoxic conditions also were examined. The percentage of astroglial cells was higher in CA1 than cortical cultures despite use of the same culture procedure. Despite this finding, the percentage of lactate dehydrogenase (LDH) released into the medium was greater in CA1 than cortical cultures under the conditions of 24-h hypoxia and 24-h incubation (P < 0.05). We then added MK-801 (500 nM), cycloheximide (3 microM), L-NNA (100 microM) and anti-PAF IgG (50 micrograms/ml) prior to inducing the hypoxia and measured LDH in the medium after 24-h hypoxia and 48-h incubation. Under the hypoxic condition, MK-801, L-NNA, and anti-PAF IgG significantly protected the CA1 neurons from hypoxic injury compared with cortical neurons, while cycloheximide protected both cultures equally. These results suggest that CA1 neurons are more sensitive to hypoxia than cerebral cortical neurons, and glutamate, nitric oxide, and PAF may participate in the mechanism of selective neural death in neurons of the CA1 region due to hypoxia.

Animals↗
PubMed1996

Inter-alpha-trypsin inhibitor bound to tumor cells is cleaved into the heavy chains and the light chain on the cell surface.

Inter-alpha-trypsin inhibitor (ITI), a human serum protease inhibitor of molecular mass 240 kDa which may release physiological derivatives, has been shown to interact with hyaluronic acid (HA), resulting in pericellular matrix stabilization (Chen, L., Mao, S.J.T., McLean, L. R., Powers, R. W., and Larsen, W. J. (1994) J. Biol. Chem. 269, 28282-28287). The purpose of this study is to determine whether ITI binding to tumor cell surface is mediated by urinary trypsin inhibitor (UTI)-receptor or cell-associated hyaluronic acid (HA). We demonstrated specific complex formation of the heavy (H) chains of ITI with HA. Binding of the H-chains of ITI to immobilized HA was detected and quantified using colorimetric immunoassays. Binding was time-, temperature-, and concentration-dependent. However, UTI and HI-8 (the carboxyl terminus of UTI) failed to bind to immobilized HA. ITI bound to HA remained functional protease inhibiting activity. After incubation of SMT-cc1 cells with purified biotinylated ITI, biotinylated ITI is bound to the cells, dissociated, and gives rise to the H-chains and UTI on the cell surface. The cell surface receptor-bound UTI derived from ITI may be the result of the limited proteolysis on the cell surface. In the cells treated with hyaluronidase, bound H-chains disappeared from the surface of the cells, while most of the cell surface ITI derivatives was present in deglycosylated UTI (28 kDa). It is suggested that the binding of ITI to the cell surface is mediated by HA on the cells. This was confirmed by the fact that the hyaluronidase-treated cells can abolish the ITI binding. The cell surface UTI formation was inhibited by diisopropyl fluorophosphate, phenylmethylsulfonyl fluoride, and eglin C, suggesting that elastase-like enzyme(s) may be responsible for the UTI formation. Preincubation of the cells with UTI did not decrease in exogenously added ITI on the cell surface. A model for cell surface UTI formation is proposed in which ITI binding to cells from serum used for the culture is followed by the limited proteolysis by trace amounts of active serine proteases, to form cell-surface receptor-bound UTI and the H-chains intercalated into cell surface HA. This process is subject to regulation of cell-associated UTI and of stabilization of pericellular matrix.

Alpha-Globulins↗
PubMed1996

Acute pathologic features with angiographic correlates of the nearly or completely occluded lesions of the cervical internal carotid artery.

BACKGROUND: The true pathologic process of nearly or completely occluded lesions of the cervical internal carotid artery (ICA) has not been studied sufficiently. This information is important in determining the critical indications for endarterectomy. METHODS: Acute pathologic features of these advanced occlusive lesions of the ICA were studied in 40 patients who underwent emergency carotid endarterectomy. Gross morphologic and histopathologic features of these occlusive lesions were examined, and the relationship between the clinical information and the pathologic characteristics was investigated. RESULTS: Thirty-seven lesions had histologic features of advanced atherosclerosis complicated by fresh intraplaque hemorrhages with or without transintimal extension. Thinwalled neovessels were thought to be an important etiologic factor in producing intraplaque hemorrhage. The remaining three lesions without these changes had strangulated embolic material at the occluded portion. A good correlation between these pathologic features and angiographic findings was found. CONCLUSION: The presented results clearly indicate that intraplaque hemorrhage is the most important factor in producing and determining the acute pathologic features of symptomatic and advanced atheromatous occlusive ICA lesions.

Acute Disease↗
PubMed1996

Indications for cisternal irrigation with urokinase in postoperative patients with aneurysmal subarachnoid haemorrhage.

The use of cisternal drainage can lead to complications such as shunt-dependent hydrocephalus and meningitis. We assessed the indications for cisternal irrigation with urokinase in postoperative patients with aneurysmal subarachnoid haemorrhage (SAH). The SAH scores by CT on admission and on the day after surgery were used to evaluate two parameters: the total amount of subarachnoid blood on admission and the clearance rate of subarachnoid blood by surgery. In patients whose parameters values belonged to the range where the total SAH score on admission exceeded 10 points and the surgical clearance rate was less than 50%, the possibility of cerebral infarction was significantly higher in patients without than in those with irrigation (p < 0.05). However, there was no difference between patients with and without irrigation for parameter values outside of the range. Therefore, this range may be useful in providing stricter indications for irrigation therapy with urokinase and thus avoiding the complications of cisternal drainage.

Adult↗
PubMed1996

No effect of high-protein food on the stereoselective bioavailability and pharmacokinetics of verapamil.

The effects of high-protein food on the bioavailability of both the racemate and individual enantiomers of verapamil were investigated in 12 healthy volunteers using a randomized crossover design. Food had no effect on any parameter of bioavailability for both the racemate and the individual enantiomers of verapamil except time to maximum concentration (tmax), which was significantly prolonged after food intake. The pharmacokinetics of the enantiomers of norverapamil were not significantly changed by food intake. These results suggest that high-protein food does not alter the pharmacokinetics and bioavailability of either the racemate or the individual enantiomers of verapamil. Therefore, the clinical efficacy of verapamil is not related to food intake, except for a slight prolongation in the time to onset of the pharmacologic effects. The present data can be applied to the high-protein content meal intake.

Administration, Oral↗
PubMed1996

Elevated plasma basic fibroblast growth factor in brain tumor patients.

We attempted to determine whether the plasma concentration of basic fibroblast growth factor (bFGF) was elevated in brain tumor patients. The plasma concentration of bFGF was measured in 55 brain tumor patients and 17 normal subjects by enzyme immunoassay. Upper limit of plasma bFGF in the normal subjects was 1.6 pg/ml. Elevated plasma bFGF levels were observed in 28 patients including 13 of 17 glioma patients, eight of 19 benign tumor patients, and seven of 19 malignant tumor patients. Twelve of 14 malignant glioma patients had elevated plasma bFGF levels. There was a good correlation (r = 0.42, p < 0.05) between the elevated plasma bFGF level and the tumor volume. Further studies are needed to determine whether the plasma bFGF level is a clinically useful diagnostic and prognostic marker for patients with brain tumors.

Adult↗
PubMed1996

Prevention of cerebrovasospasm following subarachnoid hemorrhage in rabbits by the platelet-activating factor antagonist, E5880.

Recently, an important role of platelet-activating factor (PAF), an inflammation mediator, has been demonstrated in the genesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). In the current study, the authors examined whether intravenous administration of the novel PAF antagonist, E5880, can prevent vasospasm following SAH in rabbits. A vasospasm model was produced in three groups of rabbits using two subarachnoid injections of autologous arterial blood, followed by intravenous administration of distilled water (control), a low dose of E5880 (0.1 mg/kg in distilled water), or a high dose of E5880 (0.5 mg/kg in distilled water). Neurological deterioration was largely prevented in the rabbits that received E5880. Basilar artery constriction was also reduced by both doses of E5880. Histological examination at autopsy predominantly showed ischemic changes in the brain. Animals in each E5880-treated group exhibited ischemic changes less frequently than those in the control group. Plasma thromboxane B2 concentrations were reduced in rabbits treated with E5880. Platelet-activating factor was immunolocalized in the intima and media of the basilar artery in the control group. The PAF immunoreactivity demonstrated in the basilar artery was decreased in the E5880 groups in a dose-dependent manner. Thus, this study provides evidence that PAF may play a role in the pathogenesis of vasospasm after SAH and that intravenous administration of E5880 is a promising approach in preventing vasospasm.

Animals↗
PubMed1995

Inhibition of tumor cell invasion through matrigel by a peptide derived from the domain II region in urinary trypsin inhibition.

Urinary trypsin inhibitor (UTI) has a multipotent inhibitory effect on proteases such as trypsin, chymotrypsin, plasmin, human leukocyte elastase, or hyaluronidase. UTI can bind easily to its receptors on various types of tumor cells (human ovarian cancer HOC-I cells, human choriocarcinoma SMT-cc1 cells, and murine Lewis lung carcinoma 3LL cells). Our results show that the UTI receptors of some tumor cells have a possible role in modulating plasmin activity on the cell surface and prevention of tumor cell invasion and metastasis (H. Kobayashi et al., J. Biol. Chem., 269; 20642-20647, 1994). UTI interacts with tumor cells as a negative modulator of the invasive cells. We investigated whether this effect may be mediated by UTI binding to the cell surface receptors. In addition, the role of peptide sequences from each UTI domain and their interaction with tumor cells were investigated. UTI derivatized with biotin or FITC was taken up by tumor cells in a dose-dependent manner. This cell association was inhibited with a monoclonal antibody D1, which specifically recognizes NH2 terminus (domain I) of UTI. The binding was inhibited by fluid phase UTI, but not HI-8, COOH terminus (domain II) of UTI, suggesting that UTI binds to cells through a site in the UTI domain I. Furthermore, we found that UTI, HI-8 and a number of peptides containing Arg-Gly-Pro-Cys-Arg-Ala-Phe-Ile promoted the inhibition of tumor cell invasion. This site corresponds to the plasmin-inhibiting domain within HI-8. The possibility that UTI binding to tumor cells might be involved in the prevention of tumor cell invasion in vitro was excluded since HI-8, lacking domain I, promotes the inhibition of tumor cell invasion with essentially the same affinity as UTI. All these data allow us to conclude that inhibition of tumor cell invasion is mediated by domain II, which possesses anti-plasmin activity.

Amino Acid Sequence↗
PubMed1995

Inhibitory effect of a conjugate between human urokinase and urinary trypsin inhibitor on tumor cell invasion in vitro.

Proteolytic enzymes such as urokinase-type plasminogen activator (uPA), plasmin, and collagenase mediate proteolysis by a variety of tumor cells. uPA secreted by tumor cells can be bound to a cell surface receptor via a growth factor-like domain within the amino-terminal fragment (ATF) of the uPA molecule with high affinity. Urinary trypsin inhibitor (UTI) efficiently inhibits the soluble and the tumor cell-surface receptor-bound plasmin and subsequently reduces tumor cell invasion and the formation of metastasis. The anti-invasive effect is dependent on the anti-plasmin activity of the UTI molecule, domain II in particular. We synthesized a conjugate between ATF of human uPA and a native UTI molecule or domain II of UTI (HI-8). The effect of the conjugates (ATF.UTI or ATF.HI-8) on tumor cell invasion in vitro was investigated. ATF.UTI and ATF.HI-8 bound to U937 cells in a rapid, saturable, dose-dependent, and reversible manner. A large part of receptor-bound ATF-UTI and ATF.HI-8 remains on the cell surface for at least 5 h at 37 degrees C. Inhibition of tumor cell-surface receptor-bound plasmin by ATF.UTI and ATF.HI-8 was markedly enhanced when compared with tumor cells treated either with ATF, UTI, or HI-8. Results of a cell invasion assay showed that ATF.UTI and ATF.HI-8 is very effective at targeting HI-8 specifically to uPA receptor-expressing tumor cells, whereas tumor cells devoid of uPA receptor may be less affected by the conjugates. Our results indicate that cell surface uPA and plasmin activity is essential to the invasive process and that the conjugates exhibit plasmin inhibition to the close environment of the cell surface and subsequently inhibit the tumor cell invasion through Matrigel in an in vitro invasion assay.

Amino Acid Sequence↗
PubMed1995

The use of computed tomography in the prediction of delayed cerebral infarction following acute aneurysm surgery for subarachnoid haemorrhage.

In order to predict the occurrence of cerebral infarction after aneurysmal surgery in patients with subarachnoid haemorrhage, we measured the amount of subarachnoid blood on initial and on postoperative computed tomograms. We used a reliable grading method to estimate the amount of blood on computed tomograms in 24 patients with infarction due to vasospasm and 45 patients without cerebral infarction, all of whom underwent aneurysmal surgery within 48 hours after the ictus. The total amount of subarachnoid blood on admission and on the day after operation was more in the cerebral infarction group than in the non-infarction group. The clearance rate of subarachnoid blood by surgery was lower in patients with cerebral infarction than in patients without infarction and the predominant site of subarachnoid blood corresponded with the site of the infarct. Of 24 patients with cerebral infarction, 22 (92%) belonged to the group whose initial total blood score was more than 10 on admission and whose clearance rate by surgery was less than 50%. Therefore, we propose this range to be an indication for the occurrence of cerebral infarction in postoperative patients due to cerebral vasospasm. The presence of intracerebral haematoma and the amount of ventricular blood and their clearance by surgery were also estimated for the prediction of delayed cerebral infarction after aneurysmal surgery. However, they had no relation to the occurrence of cerebral infarction due to vasospasm.

Adult↗