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Biomedical subjects

S Nishio

Publications and source records attributed to S Nishio.

At least 19 recordsLinked to original sources

Cerebral neurocytoma. A new subset of benign neuronal tumors of the cerebrum.

Three cases of patients with unusual neuronal tumors in the cerebral hemisphere are reported. All were associated with long-standing epileptic seizures. Computed tomography disclosed low-density lesions without contrast enhancement, which were interpreted as either arachnoid cysts or a cerebral infarction at initial diagnosis. Magnetic resonance imaging scans, however, revealed the lesions to be solid tumors. At surgery, the tumors were found to be relatively well demarcated, soft, and gelatinous. Histologically, all tumors were composed of small uniform stellate cells, which proliferated in a loose myxoid fibrillary matrix and resembled either oligodendroglial or astrocytic tumors. Ultrastructurally, however, all tumors showed neuronal differentiation, including numerous clear and occasional dense-core vesicles, microtubules, and a number of synapses. A review of the literature uncovered no other such cases, and therefore it was decided to classify these tumors as a distinct group of benign neuronal tumors, designated as "cerebral" neurocytoma compared with "intraventricular" neurocytoma. Related nosologic problems of neuronal tumors of the central nervous system and their possible histogenesis are also discussed.

Adult

Glycoprotein Ia/IIa-mediated activation-dependent platelet adhesion to collagen.

In the presence of anti-glycoprotein (GP) IIb/IIIa antibody at the concentration which completely inhibit platelet aggregation, ADP (0.5-3 microM) increased platelet adhesion to collagen in a concentration-dependent manner under static conditions when platelet-rich plasma (PRP) was used for the assay instead of washed platelets. This was also supported by the results of scanning electron microscopic analyses. The ADP-induced platelet adhesion to collagen was inhibited by PGI2 or beraprost, a stable analogue of PGI2, in a concentration-dependent manner (1-10 ng/ml). These findings suggested the presence of activation-dependent platelet adhesion to collagen. ADP-induced platelet adhesion to collagen was almost completely inhibited by anti-GPIa/IIa and anti-GPIIa antibodies. In the present study, we provide the first direct evidence that the activation-dependent platelet adhesion to collagen is induced by ADP and that GPIa/IIa also plays an important role in the mechanisms of this adhesion.

Adenosine Diphosphate

Hypophyseal metastatic hypernephroma mimicking a pituitary adenoma. Case report.

A patient with a remote history of nephrectomy for hypernephroma presented a visual field defect with hypopituitarism. Neuro-imaging studies showed a highly vascularized sellar mass with suprasellar extension. Surgery, which was performed via the subfrontal approach, disclosed the pituitary tumor to be a hypernephroma. Although anterior pituitary involvement is rare, chiasmal compression is much rarer in metastatic pituitary carcinomas, a review of previously reported cases of metastatic pituitary hypernephroma and our own case indicated that pituitary metastasis from this carcinoma, in contrast to other metastatic pituitary tumors, often mimics pituitary adenoma.

Adenoma

The effects of beraprost Na, a stable prostacyclin analog, on animal models of stroke.

We evaluated the effects of beraprost Na (Sodium (+-)-(1R*,2R*, 3aS*,8bS*)-2,3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3- hyd roxy-4-methyl-1- octen-6-ynyl]-1H-cyclopenta[b]benzofuran-5-butylate, beraprost), a stable and orally active prostacyclin (PGI2) analog with potent antiplatelet and vasodilating properties, on two stroke models, namely sudden death induced by arachidonate (AA) in rabbits and spontaneous stroke in stroke-prone spontaneously hypertensive rats (SHRSP). In the AA-induced sudden death model, 30 min after beraprost administration (1 or 3 mg/kg, po), AA was injected into the rabbit internal carotid artery, and incidence of convulsion and sudden death were assessed. Beraprost decreased both incidence of convulsion and mortality of rabbits. In SHRSP, orally administered beraprost (100 micrograms/kg, twice a day from 56-385 d of age) improved survival rate and decreased incidence of stroke. Preventive effects of beraprost on the two stroke models may have been caused mainly by the improvement of cerebral circulation. These results indicate that beraprost may have potential in the treatment and/or prevention of the cerebral circulatory disorders.

Animals

Combined effect of interleukin 2 and cyclophosphamide in therapy of mice with transitional cell carcinoma.

We investigated the effect of combination therapy with interleukin 2 (IL-2) and cyclophosphamide (CPM) in C3H/HeN mice implanted with mouse bladder tumor cells (MBT2). MBT2-bearing mice were treated with a single intraperitoneal injection of 120 mg/kg CPM on day 10 and/or subcutaneous administration of 5 x 10(4) units IL-2/day from day 11 to day 20. As a result, the growth of tumor in mice treated with IL-2 alone was slightly suppressed. On the other hand, regression was observed in all mice treated with CPM alone, although regrowth of tumor was seen in all of them. However, when IL-2 was administered with CPM, regrowth of tumor was completely suppressed. An immunologic study was done that showed cytotoxicity against YAC-1 and P815 in the spleen cells was suppressed in mice treated with CPM alone, but that both recovered to control levels when IL-2 was administered with CPM. Cytotoxicity against MBT2 in the spleen cells was most elevated in mice treated with both IL-2 and CPM. These findings suggested that clinical evaluation of combination therapy with IL-2 and CPM may be worthwhile.

Animals

Identification of the external branch of the superior laryngeal nerve during thyroidectomy.

Seventy-six patients underwent preoperative vocal evaluation and were randomized into 3 groups: (1) those with the superior thyroid pole dissected by the first author, with the external branch of the superior laryngeal nerve (EBSLN) identified by means of a nerve stimulator; (2) those patients whose dissection was executed by a resident, with no nerve search; and (3) those whose dissection was undertaken by the first author, without any nerve search. Postoperative analysis consisted of voice evaluation and electromyography of the cricothyroid muscle. No lesion occurred in patients in group 1. Twenty-eight percent of patients in group 2 and 12% in group 3 experienced a complete lesion of the EBSLN (p = 0.0123). When the patients in group 1 were compared with the patients with 62 nerves corresponding to nonoperated thyroid lobes, patients in group 1 exhibited no increased risk, whereas a significantly increased hazard was evident in both groups 2 (p = 0.0002776) and 3 (p = 0.0346393). In this study, effective prevention of iatrogenic EBSLN lesions during thyroidectomies was achieved only by the intraoperative identification of the nerve with the nerve stimulator.

Adult

Cytoprotective action of beraprost sodium against peroxide-induced damage in vascular endothelial cells.

Using a peroxide-injured endothelial cell model, beraprost sodium (beraprost) was tested in relation to the action to protect against the damage of vascular endothelial cells employing the viability of the cells and change in lipid peroxides as the indicators. At a concentration of 1-3 mumol/l or higher, beraprost significantly inhibited the decrease in viability of the cells and the increase in lipid peroxides level caused by t-butyl hydroperoxide or 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid. When similar tests were conducted with prostaglandin I2, its inhibiting action was equal to or slightly weaker than that of beraprost unlike PGE1 and PGD2. This action of beraprost in inhibiting cell damage caused by peroxides suggests that beraprost may be useful for protecting cells from damage due to ischemic diseases.

Animals

Peritumoral brain edema in meningiomas--influence of vascular supply on its development.

In a series of 35 patients with intracranial meningiomas, factors influencing the development of peritumoral brain edema (PTBE) were analyzed. We used numbers of the Edema Index as the extent of PTBE, which was obtained from the size of the meningioma and associated PTBE on a T2-weighted image of magnetic resonance imaging. We evaluated a relationship between the Edema Index and some factors that may play a role in the development of PTBE. Tumors in the frontal region and at the sphenoid ridge tended to be associated with larger PTBE than those in other locations (P less than 0.05). Histologically, meningotheliomatous and transitional meningiomas tended to be associated with larger PTBE than fibroblastic meningiomas (P less than 0.05). The meningiomas that had a vascular supply from the intrinsic cerebral arteries on angiography significantly correlated with severe PTBE compared with those supplied only from the meningeal side (P less than 0.01). We concluded that location, histology, and vascular supply from intrinsic cerebral arteries were the factors influencing PTBE. It is stressed that the vascular supply from the intrinsic cerebral arteries may have an influence on the extensive PTBE of meningioma.

Blood-Brain Barrier

Relationship of cytochrome P-450 activity to Clara cell cytotoxicity. I. Histopathologic comparison of the respiratory tract of mice, rats and hamsters after parenteral administration of naphthalene.

The purpose of this study was to define the sites of cytotoxicity within the respiratory tract (nasal cavity and tracheobronchial airway tree) resulting from administration of naphthalene, an organic chemical whose cytotoxic properties require metabolic activation via the cytochrome P-450 monooxygenase system. Three species were compared: mouse, hamster and rat. Naphthalene was administered in corn oil at these doses: mouse (0-400 mg/kg), hamster (0-800 mg/kg) and rat (0-1600 mg/kg), and the animals were sacrificed 24 hr later. In mice, naphthalene produced Clara cell cytotoxicity at 50 mg/kg. The primary alteration was swelling and vacuolation of Clara cells in terminal bronchioles. At 100 mg/kg, the number of terminal bronchioles with vacuolated Clara cells and the number of Clara cells within terminal bronchioles which showed vacuolation increased. At 200 and 300 mg/kg, almost all of the nonciliated cells lining terminal bronchioles in mice were exfoliated and necrotic. In contrast, there was no apparent effect on Clara cells or ciliated cells of terminal bronchioles in rats treated with up to 1600 mg/kg. At 800 mg/kg, minor alterations in Clara cells in some terminal bronchioles were observed in hamsters. At 300 mg/kg, lobar bronchus and trachea showed swelling 'and vacuolation of nonciliated cells in mice, but no detectable change at 200 mg/kg or below. The trachea and lobar bronchus were unaffected in rats, but showed cytotoxic changes in hamsters. In the nasal cavity of mice, cytotoxicity was observed only in the olfactory epithelium and only in animals treated with 400 mg/kg. There were minimal alterations in the respiratory epithelium. The only epithelial population showing cytotoxicity in the rat was the olfactory epithelium. Complete necrosis was observed at 200 mg/kg and higher. In the hamster there was no discernible alteration in the olfactory epithelium at 100 and 200 mg/kg. At 400 mg/kg, the olfactory epithelium was necrotic. Naphthalene injury to the tracheobronchial epithelium of the mouse is: 1) Clara cell specific; 2) dose-related in the terminal bronchiole; and 3) involves more proximal airways in a dose-dependent fashion. The tracheobronchial epithelium of the rat is refractory to Clara cell injury even at the LD50, but proximal airways are more susceptible than distal airways in the hamster. The nasal cavity shows specific injury in one zone (olfactory epithelium) in a dose and species specific manner. The susceptibility to naphthalene-induced injury in the olfactory epithelium does not correlate with the susceptibility of Clara cells in more distal portions of the respiratory tract.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Distribution of cytochrome P450 1A1 and NADPH-cytochrome P450 reductase in lungs of rabbits treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin: ultrastructural immunolocalization and in situ hybridization.

Induction of cytochrome P450 1A1 (P450 1A1) in a variety of tissues is a well established consequence of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Although localization of the induced protein within the lung has been described, the precise intracellular distribution of the enzyme is not clear. Analysis of tissue sections, microsomal proteins, and mRNA from lungs of treated and untreated rabbits established that P450 1A1 had been induced by treatment with TCDD. Rabbit lungs from animals treated with TCDD were examined with immunocytochemistry and in situ hybridization, to identify the cell types that contain P450 1A1 and those that contain mRNA encoding P450 1A1. Endothelial cells of the entire vascular bed of rabbit lung reacted markedly with anti-P450 1A1. Likewise, cells lining both arteries and veins, as well as capillary endothelial cells, reacted strongly with the cDNA probe for mRNA encoding P450 1A1. Clara cells at all levels of airway labeled prominently for both P-450 1A1 and P450 1A1 mRNA. In addition, type 2 cells, alveolar macrophages, and to a lesser degree, ciliated cells reacted with the cDNA probe. P450 reductase, which is required for P450 activity, has previously been identified in Clara cells, type 2 cells, and alveolar macrophages, but not in endothelium of rabbit lung. We have now obtained similar results for the localization of mRNA encoding P-450 reductase. This finding brings into question the function of P450 1A1 in endothelium.

Animals

Architecture of mixed calcium oxalate dihydrate and monohydrate stones.

Calcium oxalate dihydrate (COD) and monohydrate (COM) are the most frequent constituents of urinary stones, and there still exist some questions about the interrelation between the two hydrates. Architecture of mixed COD and COM stones was observed by electron microscopy to solve the questions. The fractured surface of a stone is composed of the fractured face of the crystals. In this situation a morphological criterion of typical dipyramid shape is useless to identify COD. But we could identify COD using the partial dissolution method, which etched square pits on COD crystals. COD and COM formed distinctly separate layers. COD was always found in the stone surface and COM in the center. The stone surface was covered by a thick layer of organic matrix, and the intercrystalline space was filled with matrix. The crystals were grown thrusting the matrix aside to minimize the space. Although COD is more soluble than COM, the urine contains specific substances that favor the formation of COD. Supposing the stone matrix excludes these substances selectively, the gel-state matrix provides a preferable condition for COM formation. This hypothesis is suitable to explain the high incidence of COM stones. An abrupt change of the crystalline constituent can be explained by COD crystal deposition on COM stones. Frequent COD crystalluria can explain why COD is always found in the stone surface. Once the stone surface is covered with COD crystals, they continue to grow in the gel-state matrix or deposit further to form the bulk of the stone.

Calcium Oxalate

Enhancement by beraprost sodium, a stable analogue of prostacyclin, in thrombomodulin expression on membrane surface of cultured vascular endothelial cells via increase in cyclic AMP level.

Prostacyclin and beraprost sodium (beraprost), a stable analogue of prostacyclin, increased cyclic AMP (cAMP) levels of cultured human umbilical vein endothelial cells (HUVEC) in a concentration-dependent manner. The elevation of cAMP by beraprost was sustained longer than that by prostacyclin. The expression of thrombomodulin (TM) on membrane surface of HUVEC was enhanced by beraprost and prostacyclin, and the persistence of the increase in TM expression by beraprost was greater than prostacyclin. Dibutyryl cAMP (db-cAMP) mimicked the effects of beraprost and 3-isobutyl-1-methylxanthine enhanced the effects. Beraprost, prostacyclin and db-cAMP also effectively blocked the interleukin-1- and tumor necrosis factor-induced depression of TM expression substantially. These results suggest that TM expression is positively regulated by cAMP in HUVEC, and that beraprost may be potentially effective for reducing thrombotic events through the mechanism which initiates the stimulation of cAMP/TM system in vascular endothelial cells.

1-Methyl-3-isobutylxanthine

Pineal and third ventricle tumours in the CT and MR eras.

We have experienced 29 cases of tumour in the pineal region and posterior third ventricle in the CT and MR eras (from 1976 to 1989). An aggressive surgical removal was performed except for germinomas and suspected germinomas. The aggressive surgical cases were 5 teratomas including one inclusion foetus, one yolk sac tumour, 3 astrocytomas, one neurocytoma, one cavernous haemangioma and one telangiectasia. The surgery was performed by either the infratentorial supracerebellar approach or the occipital transtentorial approach. There was no surgical death and the quality of postoperative survival was good in patients with benign tumours. The cases of a typical teratoma, teratoma with an arterio-venous shunt, inclusion foetus, haemorrhagic nodule of telangiectasia etc. are briefly presented. A remarkable progress in the diagnosis and surgical treatment of tumours in the pineal region in the CT and MR eras is noted in our results.

Adolescent

Tetrodonic acid-like substance; a possible precursor of tetrodotoxin.

A tetrodonic acid-like substance which was hardly distinguishable from authentic tetrodonic acid in thin-layer chromatography, high performance liquid chromatography, etc., was successfully purified from the ribbon worm and flatworm by a method consisting mainly of Bio-Gel P-2 column chromatography. The tetrodonic acid-like substance showed a specific toxicity of approximately 700 mouse units/mg as tetrodotoxin, unlike tetrodonic acid which is a completely non-toxic substance. Instrumental analyses including gas chromatography-mass spectrometry, secondary ion mass spectrometry and thin-layer chromatography/fast atom bombardment mass spectrometry disclosed that the tetrodonic acid-like substance had a structure similar to, but not the same as, that of tetrodotoxin. This, along with its high convertibility into tetrodotoxin during storage and other experimental operations, suggested that the tetrodonic acid-like substance is a precursor of tetrodotoxin.

Animals

Combined effect of interleukin 2 and bacillus Calmette-Guérin in the therapy of mice with transitional cell carcinoma.

We investigated the effect of combination therapy with interleukin 2 (IL-2) and Bacillus Calmette-Guérin (BCG) on C3H/HeN mice implanted with mouse bladder tumor cells (MBT2). MBT2-bearing mice were treated with a local injection of BCG into the tumor at a dose of 1 mg/day for a total of 3 times and/or a 10-day continuous subcutaneous infusion of 5 x 10(4) units IL-2/day from day 11 to day 20. As a result, the growth of the tumor in mice treated with IL-2 alone was slightly suppressed, while tumor growth was hardly suppressed in mice treated with BCG alone. However, when IL-2 was administered with BCG, tumor growth was strongly suppressed and mean survival time was prolonged. Natural killer cell activity in the spleen cells was most elevated in mice treated with IL-2 and BCG, while lymphokine-activated killer cell activity was not observed in all groups. Lymphocyte subset analysis showed that there was little change in the ratio of Lyt2-positive lymphocytes or that of L3T4-positive lymphocytes. These findings suggested that clinical evaluation of combination therapy with IL-2 and BCG may be worthwhile.

Animals

Combined effect of tumor necrosis factor alpha and anticancer chemotherapeutic agents against human renal carcinoma cell lines.

Antitumor effect of recombinant human tumor necrosis factor alpha (TNF) alone or in combination with various anticancer chemotherapeutic agents was tested using an in vitro antiproliferative assay on four human renal carcinoma cell lines (VMRC-RCW, VMRC-RCZ, Caki-1 and A-498). When the dose-dependent effect of TNF was studied, none of the four cell lines showed a 50% or more inhibition even at a concentration of 10,000 U/ml of TNF, so that the susceptibility to TNF was low. An enhancing effect of TNF on the cytotoxic effect of almost all the chemotherapeutic agents tested was observed against VMRC-RCZ and A-498. Against VMRC-RCW and Caki-1, the combination of TNF with the chemotherapeutic agents did not result in an enhancing effect. Mitomycin C showed an enhancing effect of TNF against all four cell lines. These results suggested that the combined treatment of TNF with chemotherapeutic agents may have favorable results in clinical trials.

Antineoplastic Agents

Ultrastructural immunohistochemical localization of Clara cell secretory protein in pulmonary epithelium of rabbits.

Highly purified Clara cells (93 +/- 3%) isolated from the lungs of rabbits were used to produce an antiserum against Clara cell secretory proteins. This antiserum was used to identify and study the biosynthesis and secretion of [35S]methionine-labeled proteins from isolated Clara cells. The antiserum recognized one major secretory protein with apparent molecular weight of 6 kDa and reacted weakly with a higher molecular weight protein of about 180 kDa. Biosynthesis and secretion of these proteins was not detected in preparations of isolated alveolar type II cells or alveolar macrophages. Immunocytochemical localization of the antigen with colloidal gold indicated a dual localization in bronchiolar Clara cells. Gold labeling was found over the osmiophilic secretory granules of Clara cells and smooth endoplasmic reticulum. In tracheal Clara cells, labeling was found mostly in association with secretory granules and relatively little in association with the smooth endoplasmic reticulum. Labeling was also found over the lamellar bodies of type II cells, although the reaction was weak. Labeling of ciliated cells, alveolar type I cells, capillary endothelial cells, and alveolar macrophages was not distinguishable from background. These data indicate that Clara cells of both the bronchioles and trachea of rabbits synthesize and secrete the low molecular weight protein previously called Clara cell secretory protein (CCSP). This antigen does not belong to that group of surfactant proteins whose molecular weights range from 26 to 40 kDa.

Animals

Brain stem glioma: the role of a biopsy.

A retrospective review of the clinical and histopathological features of 31 patients with brain stem gliomas treated between 1965 and 1990 at Kyushu University Hospital was performed to determine the role of biopsy on these lesions. These 16 male and 15 female patients ranged in age from 3 to 50 years at diagnosis (average: 18.1 years). The primary site of the tumour was the pons in 20 patients, followed by the medulla oblongata and midbrain, and the final histological diagnoses of the lesions based on either the biopsy or autopsy materials were grade I astrocytomas in five patients, grade II in nine, grade III in 10, grade IV in five, and ependymoma in two patients. No consistent correlation could be obtained between the CT findings and histological diagnoses. Open surgical posterior fossa exploration was performed on 17 patients (diagnostic biopsy: 10; volume reduction by tumour removal with or without cyst evacuation: 7) and stereotaxic biopsy on three patients, without any mortality related to these procedures. In our biopsy series, half of the patients with grade II astrocytoma died within 12 months after diagnosis, whereas three out of four patients with grade I astrocytoma survived more than 10 years after diagnosis. Because of the relative safety of the tissue sampling technique, and the importance of an accurate diagnosis in order to select appropriate treatment modalities, histological verification of the lesion should be considered for all patients harbouring a brain stem mass lesion.

Adolescent