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Biomedical subjects

Y Hirashima

Publications and source records attributed to Y Hirashima.

At least 55 records · Page 3Linked to original sources

Clinical features in patients requiring reoperation after failed endoscopic procedures for hydrocephalus.

The aim of this study was to clarify the clinical features of patients at risk of secondary obstruction following endoscopic fenestration. Clinical notes and endoscopic findings for 15 patients treated with endoscopic procedures were retrospectively reviewed. Endoscopic third ventriculostomy (ETV) was performed as initial treatment in 4 patients with non-communicating hydrocephalus, including a neonate with myelomeningocele, and as an alternative to shunt revision in 4 patients. Two patients with non-communicating hydrocephalus caused by tumor or arachnoid cyst were also managed with third ventriculostomy. Four patients with loculated hydrocephalus underwent endoscopic septostomy. A child with an isolated fourth ventricle was treated with endoscopic aqueductoplasty. Of the 15 patients undergoing endoscopic procedure, 4 required reoperation. Of the 10 patients treated with ETV, only the neonate with myelomeningocele required a ventriculoperitoneal shunt because of failure of the initial procedure. Of the 4 patients treated with endoscopic septostomy, 2 children with loculated hydrocephalus following intraventricular hemorrhage (IVH) underwent a second septostomy. In a patient with an isolated fourth ventricle following posthemorrhagic hydrocephalus, recurrence was noted 8 months after the initial procedure. He underwent a second procedure using a stent implanted into the aqueduct to maintain CSF circulation. Sufficient stomal size or implantation of a stent may be required in the under-2-year age group with hydrocephalus accompanied by IVH and associated with myelomeningocele, in whom the risk of secondary obstruction may be high.

Adolescent↗

Human myometrial cells in culture express specific binding sites for urinary trypsin inhibitor.

Urinary trypsin inhibitor (UTI), which is present in amniotic fluid, prevents uterine contractility during pregnancy possibly via specific binding protein mechanisms. To test for the presence of UTI binding sites on the cell surface, we prepared cultured myometrial cells obtained at biopsy from 12 pregnant women and performed binding, competition, and cross-linking experiments using a specific radiolabelled UTI as a ligand. We report for the first time two classes of binding sites of differing affinities. Scatchard analysis at 4 degrees C, using radioiodinated UTI, revealed that UTI binds to 35 000 high affinity binding sites/cell (K(d) = 9.1x10(-9) mol/l) and 450 000 lower affinity binding sites/cell (K(d) = 3.5x10(-7) mol/l) in cultured myometrial cells. It appears to be the low affinity site that is internalized, and this has been identified as a protein of approximately 45 kDa by cross-linking and immunoaffinity labelling studies. Monoclonal antibodies against the NH(2)-terminal fragment of UTI abrogated specific binding of this protein to the cells. Treatment of the cells with hyaluronidase resulted in >80% inhibition of the [(125)I]-labelled UTI binding to the cells. These data show that the UTI binding site, which is hyaluronidase sensitive, is expressed on the surface of human uterine myometrial cells to accumulate the UTI molecule during pregnancy.

Antibodies, Monoclonal↗

Endovascular treatment of unusual multiple aneurysms of the internal carotid artery-posterior communicating artery complex--case report.

A 79-year-old female presented with subarachnoid hemorrhage due to rupture of a rare true posterior communicating artery (PCoA) aneurysm and with poor general condition. Endovascular therapy was performed in the chronic stage. Right carotid angiography just before embolization demonstrated unusual multiple aneurysms of the internal carotid artery (ICA)-PCoA complex. Superselective angiography and aneurysmography using microcatheter revealed two separate aneurysms arising from the PCoA and the ICA-PCoA junction. Endovacular embolization using Guglielmi detachable coils (GDCs) was successfully performed for both aneurysms and complete occlusions were achieved with the PCoA fully patent. Embolization with GDCs is a good alternative to surgical clipping for PCoA aneurysm after careful evaluation of superselective angiography.

Aged↗

Correlation of glutamate-induced apoptosis with caspase activities in cultured rat cerebral cortical neurons.

In cultured rat cortical neurons lactate dehydrogenase (LDH) activity in the medium, a cell-death marker, increased gradually after exposure to glutamate (100 microM to 1 mM) for 60 min and reached a plateau at 24 to 30 h. Neuronal death was mainly apoptotic as suggested by typical electron microscopic findings, fluorescent double staining with membrane-permeating and nonpermeating chromatin dyes, nick end labeling, and assessment of DNA fragmentation by agarose gel electrophoresis. After 1 mM glutamate exposure, a rise of interleukin-1beta converting enzyme (ICE)-like protease activity in neurons was parallel to cysteine protease p32 (CPP32)-like protease activity and declined before CPP32-like protease activity reached the peak (at 6 h). LDH activity in the medium of glutamate-exposed neurons was decreased by specific ICE and/or CPP32 inhibitors, acetyl-L-tyrosyl-L-valyl-L-alanyl-L-aspart-1-al (Ac-YVAD-CHO) and acetyl-L-aspartyl-L-glutamyl-L-valyl-L-aspart-1-al (Ac-DEVD-CHO), respectively, in a dose-dependent manner. Fluorescent double staining of nuclei also demonstrated that at 100 microM each inhibitor prevented neuronal apoptosis and that this effect was additive. Among agonists corresponding to various glutamate receptor subtypes, N-methyl-D-aspartate (NMDA) and kainate induced apoptosis in cortical neuronal cultures while alpha-amino-3-hydroxy-5-methylisoxazole-4-propinate (AMPA) did not. The metabotropic glutamate receptor agonist, 1-aminocyclopentane-1S, 3R-dicarboxylate (ACPD) prevented apoptosis. Interestingly, apoptosis at 24 h after agonist or antagonist exposure correlated closely with caspase activity 6 h after exposure.

Animals↗

Deficient platelet-activating factor and related enzymes in hemimegalencephaly.

Platelet-activating factor (PAF) may influence neuronal migration, and gyral anomaly in hemimegalencephaly is believed to result from a neuronal disorder. A 7-month-old girl with hemimegalencephaly presented with intractable seizures, for which graded hemispherectomy was performed. In the resected specimen, we could not detect PAF, and related enzyme activities were low. These results suggest a role of PAF in neuronal migration.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Growth inhibition and radiosensitization of cultured glioma cells by nitric oxide generating agents.

The authors examined the effect of nitric oxide (NO) generating agents on the growth and radiosensitivity of cultured glioma cells. Three glioma, rat C6, and human T98G and U87 cell lines were treated with the NO generating agents, S-nitroso-N-acetyl-penicillamine (SNAP) or sodium nitroprusside (SNP). These agents released NO in the cell culture media and inhibited the growth of the glioma cells. Growth-inhibition was attenuated by hemoglobin, a known inhibitor of NO, suggesting it is mediated by NO. When C6 and T98G cells were irradiated in the presence of SNAP or SNP at 100 microM, radiosensitization was observed. SNAP at 100 microM exhibited a sensitizer enhancement ratio (SER) of 1.4 for C6 cells and 1.8 for T98G cells. SNP at 100 microM only radiosensitized T98G cells with a SER of 1.9. The effect of SNP on radiosensitization of C6 cells was unclear. We conclude that NO generating agents are potential growth inhibitors and radiosensitizers for malignant glioma cells. NO mediated radiosensitization of glioma cells by NO generating agents may offer a new therapeutic approach for malignant glioma.

Animals↗

An experimental model for side-to-side microvascular anastomosis.

Side-to-side microvascular anastomosis may be required in certain clinical situations, although the technique is difficult and the incidence of usage remains low. A new experimental model using rat femoral vessels for side-to-side microvascular anastomosis is presented, in which 100 percent patency was accomplished immediately and was maintained for 7 days after anastomosis. This model can provide a training tool for acquisition of advanced microsurgical technique for side-to-side anastomosis of small vessels.

Anastomosis, Surgical↗

Extrinsic pathway of blood coagulation and thrombin in the cerebrospinal fluid after subarachnoid hemorrhage.

OBJECTIVE: The involvement of thrombin in the pathophysiology of subarachnoid hemorrhage (SAH) was investigated by comparing thrombin expression and extrinsic pathway activation in the cerebrospinal fluid (CSF) and blood of patients with SAH with the neurological grades, outcome, and presence of delayed cerebral vasospasm. METHODS: Blood and CSF samples were obtained from 38 patients with SAH on Days 3 through 5, 7 through 9, and 12 through 14 after the onset of SAH. CSF samples were also obtained from control patients. Thrombin-antithrombin III complex, prothrombin fragment F1 +2, tissue factor, and tissue factor pathway inhibitor were analyzed using enzyme-linked immunosorbent assay. RESULTS: No markers in the blood or CSF were correlated with neurological grades and outcome. Thrombin-antithrombin III complex and prothrombin fragment F1 +2 levels were significantly higher in the CSF of patients with SAH than in the blood or the CSF of control patients and were significantly higher in patients with vasospasm than in patients without vasospasm on Days 7 through 9. Tissue factor levels were significantly higher in the CSF of patients with SAH than in the blood, but the levels were close to those in the CSF of control patients. Tissue factor pathway inhibitor levels in the CSF of patients with SAH and control patients were under the detection limit. CONCLUSION: Thrombin in the blood may not reflect the pathophysiology of SAH. Imbalance between tissue factor and tissue factor pathway inhibitor in the CSF may tend to thrombin generation under normal physiological conditions and also after SAH. Thrombin in the CSF may be involved in the pathophysiology of vasospasm.

Adult↗

Identification of link protein during follicle development and cumulus cell cultures in rats.

Cumulus oocyte complex (COC) expansion is induced through hyaluronic acid production and accumulation of proteins of the inter-alpha-trypsin inhibitor family in the gonadotropin-stimulated cumulus cells. Link protein, a glycoprotein found in cartilage, interacts specifically with hyaluronic acid and stabilizes the binding of proteoglycan monomers to hyaluronic acid to form aggregates. The aim of this study was to investigate the expression of immunoreactive link protein during follicle development in rats and in cumulus cells in culture by immunohistochemistry and Western blot as well as by specific enzyme-linked immunosorbent assay. Immunohistochemical analysis revealed that the extracellular matrix of cumulus cells that were morphologically at a stage of COC expansion were markedly stained for link protein, whereas granulosa cells from immature follicles were not stained. Cumulus cells deposited link protein into the extracellular matrix in an in vitro culture system. The staining intensity was negated by the treatment with hyaluronidase, suggesting that the link protein is bound to hyaluronic acid. We have identified a 42-kDa immunoreactive link protein in rat ovary during the preovulatory period and in COC extracts. Addition of FSH to the medium of cumulus cells in culture supplemented with 10% FBS and oocyte-conditioned medium resulted in an increased rate of link protein synthesis. This work suggests that the cumulus cells synthesize the link protein that may stabilize the binding of inter-alpha-trypsin inhibitor or dermatan sulfate proteoglycan to hyaluronic acid to make up hyaluronic acid-rich matrix aggregate.

Animals↗

Endoscopic aqueductal plasty via the fourth ventricle through the cerebellar hemisphere under navigating system guidance--technical note.

A 1-year 8-month-old boy presented with isolated fourth ventricle after ventriculoperitoneal shunting for hydrocephalus associated with ventricular and subarachnoid hemorrhage. The therapeutic endoscope was inserted through the thin left cerebellar hemisphere. Endoscopic aqueductal plasty was performed via the enlarged fourth ventricle under guidance from a navigating system. Endoscopic aqueductal plasty via the fourth ventricle under navigating system guidance is a useful procedure enabling less invasive surgery for isolated fourth ventricle associated with slit-like ventricle after shunt placement.

Cerebellum↗

Suboccipital meningocele presenting as a huge retropharyngeal mass in a patient with neurofibromatosis Type 1. Case report.

The authors report an extremely rare case of neurofibromatosis Type 1 (NF1) with a suboccipital meningocele presenting as a huge retropharyngeal mass. A 73-year-old woman with typical cutaneous manifestations of NF1 presented with nasal obstruction and dysphagia due to a retropharyngeal mass. Magnetic resonance imaging revealed a huge mass lesion extending from the right occipital bone defect to the retropharynx through the right paravertebral region. Computerized tomography scanning after intrathecal administration of contrast material confirmed that the mass was a meningocele protruding through a right occipital bone defect. The authors attempted to ligate this meningocele, most of which was excised via a suboccipital approach, but a second transcervical operation was required. Finally, the meningocele resolved and the patient was discharged without symptoms.

Aged↗

A bifunctional hybrid molecule of the amino-terminal fragment of urokinase and domain II of bikunin efficiently inhibits tumor cell invasion and metastasis.

Urinary trypsin inhibitor (UTI) inhibits efficiently tumor cell invasion and the formation of metastasis. The anti-metastatic effect is dependent on the COOH-terminal domain II of UTI [UTI-(78-136)-peptide]. To develop a molecule that binds with high affinity to the urokinase (uPA) receptor (uPAR) on tumor cell surfaces, a bifunctional hybrid molecule [uPA-(1-134)-UTI-(78-136)] consisting of the uPAR-binding NH2-terminal fragment [UTI-(78-136)-peptide] of uPA at the NH2-terminus of UTI-(78-136)-peptide was produced in Escherichia coli by genetic engineering. The purified hybrid protein inhibited trypsin and plasmin 2-3-fold less effectively than UTI-(78-136)-peptide and was found to bind to human tumor cells via uPAR, which was confirmed by cell binding and competition experiments. Using a modified Boyden chamber and an artificial basement membrane, Matrigel, it was found that the hybrid protein is very effective at inhibiting invasion by uPAR-expressing human tumor cells. Sensitivities of tumor cells towards the anti-invasive effect of uPA-(1-134)-UTI-(78-136) correlated with the density of uPAR on human tumor cells. Furthermore, in the spontaneous metastasis model, the hybrid protein inhibited the formation of lung and/or lymphatic metastasis by human ovarian carcinoma and choriocarcinoma cells. The hybrid protein was much more effective than uPA-(1-134)-peptide, UTI-(78-136)-peptide, or UTI. We conclude that this approach extends the possibility of applying recombinant protein for therapeutic use in inhibition of human tumor cell metastasis.

Amino Acid Sequence↗

Identification and characterization of the cell-associated binding protein for urinary trypsin inhibitor.

Urinary trypsin inhibitor (UTI) inhibits not only tumor cell invasion but also production of experimental and spontaneous metastasis. Cell-binding experiments indicated that human choriocarcinoma SMT-cc1 cells have specific binding sites for UTI on their cell surface. [Kobayashi et al., J. Biol. Chem. 269, 1994, 20,642-20,647]. UTI binding protein (UTIBP) was purified to homogeneity by a combination of UTI-coupled affinity beads, preparative polyacrylamide gel electrophoresis and reverse phase HPLC. This protein is very similar to a truncated form of human cartilage link protein (LP). LP was identified structurally by its apparent molecular mass with and without deglycosylation treatment: Immunologically by the reactivity with anti-UTIBP antibody, and functionally by its ability to bind the NH2-terminal domain of UTI. UTI and UTIBP are distributed uniformly in the cytoplasm and/or over the cell surface of tumor cells and fibroblasts. The level of staining for hyaluronic acid, UTIBP and UTI is much lower in sections digested with hyaluronidase. These results suggest that the cell membrane-derived UTI-associated binding protein is the LP of proteoglycan-hyaluronic acid aggregates, which interacts with hyaluronic acid. Cell-associated LP may play a role in modulating protease activity to the environment close to tumor and fibroblast cell surface.

Chromatography, High Pressure Liquid↗

Administration of methylprednisolone acetate into the subdural cavity in an infant with subdural fluid collection. PAF is a good indicator of the efficacy of the treatment.

We report on the successful treatment of a case of infantile subdural fluid collection after cardiac surgery by administration of methylprednisolone acetate into the subdural cavity. The protein content in subdural fluid did not change even after administration of this steroid and was not a good indicator of the efficacy of treatment; however, the content of platelet-activating factor (PAF), an inflammatory mediator, in the fluid removed from the subdural cavity decreased rapidly after administration of the steroid. Subdural fluid collection subsequently decreased and mental retardation was improved. Our findings suggest that PAF content is a good indicator of the severity of infantile subdural fluid collection.

Anti-Inflammatory Agents↗

Internalization of urinary trypsin inhibitor in human uterine fibroblasts.

We have characterized the molecular species and internalization of urinary trypsin inhibitor (UTI) in human uterine fibroblasts. Link protein (LP) has previously been identified as one of the cell-associated UTI binding proteins. The truncated forms of UTI were readily detectable in the cells after incubating the cells with purified UTI. Immunoblotting analysis with a panel of domain-specific antibodies revealed that the UTI species lacked the amino-terminal domain of UTI, but contained the carboxyl-terminal domain. We have examined whether LP is involved in the UTI internalization in the cells. Internalization of 125I-labelled UTI was blocked by the intact UTI, but not by the carboxyl-terminal domain of UTI. Treatment with a polyclonal antibody to the UTI binding domain of LP partially inhibited UTI binding to the cells, but did not significantly prevent UTI internalization. In addition, preincubation of the cells with hyaluronidase reduced the UTI binding to the cells, but had no effect on the rate with which UTI was internalized. These data allow us to conclude that there are at least two different mechanisms for internalization of UTI. The major one is via unknown UTI receptors in a Ca2+, Mg2+-sensitive manner and another is via LP.

Calcium↗

Serological and immunohistochemical diagnosis of amniotic fluid embolism.

The purpose of this study was to evaluate whether serological assays and immunohistochemical staining, employing antibody TKH-2, are sensitive methods for the serological and histologic diagnosis of amniotic fluid embolism (AFE). TKH-2 is a sensitive antibody directed to sialyl Tn (STN), NeuAcalpha2-6GalNAc. Nineteen samples of maternal sera with clinical AFE and 120 control sera and 15 specimen of formalin-fixed, paraffin-embedded lung tissue sections were examined in this study. Tissue sections were stained using the streptavidin-biotin-immunoperoxidase method. The concentration of STN in serum was measured by an immunoradiometric competitive inhibition assay using the monoclonal antibody TKH-2 in a one-step procedure. Remarkable positive TKH-2 stainings were easily seen within the pulmonary vasculature in 14 of the 15 (93%) patients with AFE. The serum STN levels (mean+/-SD) in patients with AFE (110.8+/-48.1 U/ml) showed significantly higher concentrations compared with those of patients with non-AFE (17.3+/-2.6 U/ml) (p <0.01). Seventeen of 19 sera (89%) were diagnosed as AFE by serum TRH-2 level. We conclude that both TKH-2 immunostaining and serum STN assay are sensitive methods to diagnose patients with AFE.

Antigens, Tumor-Associated, Carbohydrate↗