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Biomedical subjects

T Nishizaki

Publications and source records attributed to T Nishizaki.

At least 19 recordsLinked to original sources

A key role for a 145-kDa cytosolic protein in the stimulation of Ca(2+)-dependent secretion by protein kinase C.

Cytoplasmic Ca2+ is a major regulator of exocytosis in secretory cells; however, the Ca(2+)-dependent mechanisms that trigger secretion have not been elucidated. Protein kinase C (PKC) has been proposed to be an important Ca(2+)-dependent component of this regulation; however, the effects of this enzyme on the exocytotic apparatus have not been identified. We developed a PKC-deficient, semi-intact PC12 cell system in which direct stimulatory effects of purified PKC on Ca(2+)-dependent norepinephrine secretion were studied. The reconstitution of optimal Ca(2+)-activated norepinephrine secretion by semi-intact PC12 cells required the addition of MgATP and cytosolic proteins. PKC-deficient cytosol exhibited reduced reconstituting activity that was fully restored by the addition of purified PKC. The restoration of Ca(2+)-dependent norepinephrine secretion by PKC required the presence of other proteins in the cytosol, in particular, a high molecular weight protein. The high molecular weight protein was identified as p145, a recently characterized 145-kDa brain protein. The addition of PKC enhanced phosphorylation of p145 under conditions of fully reconstituted Ca(2+)-activated norepinephrine secretion. The results indicate that 1) PKC is neither necessary nor sufficient for Ca(2+)-activated secretion, whereas other cytosolic proteins are required; and 2) the stimulation of Ca(2+)-activated secretion by PKC is dependent upon cytosolic proteins such as p145 and may be largely mediated through the phosphorylation of p145.

Adenosine Triphosphate

Glial fibrillary acidic protein (GFAP) expression and nucleolar organizer regions (NORs) in human gliomas.

The frequency of nucleolar organizer regions (NORs) in each glioma tissue and the relation between the expression of glial fibrillary acidic protein (GFAP) and the frequency of NORs was investigated. The number of Ag-NORs per cell for glioblastoma multiforme was significantly higher than that for anaplastic astrocytoma (P less than 0.05) and that for astrocytoma (P less than 0.01). The number of Ag-NORs per cell for GFAP-positive cells was significantly lower than that for GFAP-negative cells in each histopathological grade (P less than 0.01). Moreover, the linear relationship was demonstrated between the Ag-NORs numbers of GFAP-negative cells and bromodeoxyuridine (BUdR) labeling indices. From these results, it is concluded that many GFAP-positive glioma cells may have low growth potential in glioma tissue and GFAP-negative cells may have a close relation to cell proliferation. The combination of immunohistochemical and silver colloid staining is a useful method for investigating the biological characteristics of brain tumors.

Astrocytoma

Protective effect of adenosine on the anoxic damage of hippocampal slice.

To investigate the effect of adenosine on anoxic damage of brain tissue, energy metabolism in relation to neural activity was studied using hippocampal slices from the guinea-pig. For the index of energy metabolism, adenosine triphosphate and creatine phosphate in each slice were measured and also postsynaptic potentials (population spike potentials) were recorded in the granule cell layer of the slices. After preparation of the slices, one group of slices was incubated for 120 min in standard medium and another in the medium containing adenosine (5 mM). The adenosine triphosphate content of the former group was 8.8 mmol/kg protein whereas that of the latter was 15.8 mmol/kg protein. During deprivation of oxygen and glucose, adenosine triphosphate and creatine phosphate in the control slices and the slices treated with adenosine decreased rapidly. Adenosine did not alter the rate of consumption of high energy phosphates in both slices. The pretreatment of slices with adenosine (5 mM), however, considerably enhanced the recovery of the adenosine triphosphate level during reoxygenation with glucose after deprivation of oxygen and glucose for 15 and 30 min. Postsynaptic potentials in the granule cell layer of the slice were recorded before and after 10, 15, 20 or 25 min deprivation of oxygen and glucose in the control slice and the slices pretreated with adenosine (5 mM) for 60 min. In the control slices, postsynaptic potentials in one of 10 slices could be recorded after 60 min reoxygenation following 15 min anoxia/aglycemia, while postsynaptic potentials in 10 of 15 slices treated with adenosine could be detected even after 15 min of anoxia/aglycemia. Thus the functional recovery of postsynaptic potentials agreed well with the results of the recovery of adenosine triphosphate level in the slices treated with adenosine. These results indicate that adenosine has a protective effect against anoxic/aglycemic damage of brain tissue by facilitating the resynthesis of tissue adenosine triphosphate during the recovery period.

Action Potentials

Malignant meningioma metastasizing through the cerebrospinal pathway.

A case of malignant meningioma metastasizing through the cerebrospinal pathway is presented. The primary tumor was a parasagittal malignant meningioma invading into the brain. The tumor seeded to the cerebellopontine angle cistern and thoracic spine after multiple operations. Although this type of tumor borders the CSF, metastasis through the cerebrospinal pathway is rare, and only 18 such cases have been reported (2, 3, 10, 12).

Brain Neoplasms

Tunicamycin increases desensitization of junctional and extrajunctional acetylcholine receptors expressed in Xenopus oocytes by a mechanism independent of N-glycosylation blocking.

Extrajunctional and junctional mouse muscle acetylcholine receptors (AChRs) expressed in Xenopus oocytes in the presence of tunicamycin desensitized more rapidly than the corresponding AChRs synthesized in the absence of tunicamycin. The two types of AChR expressed in non-tunicamycin-treated oocytes could be distinguished by their different rates of desensitization, but tunicamycin diminished this difference. The effect of tunicamycin on the AChR desensitization appeared to be reversible, and coapplication of tunicamycin with acetylcholine (ACh) also caused a similar effect on desensitization of these AChRs suggesting that the effect of tunicamycin was mediated by a mechanism independent of N-glycosylation blocking. In addition, tunicamycin increased the amplitude of membrane current elicited by application of lower doses of ACh and accelerated the rate of desensitization, which suggests that tunicamycin favors an open channel state and, therefore, accelerates transition towards a desensitized state. Tunicamycin also increased the membrane current decay elicited by ACh in oocytes expressing incomplete AChRs, missing the beta, gamma, epsilon, or delta subunits.

Animals

Combined hepatic and vena caval resection with autogenous caval graft replacement.

Right-sided and caudate hepatic lobectomy with resection of the retrohepatic vena cava were performed in a 34-year-old woman with recurrent adrenal carcinoma. The vena cava was replaced with a graft constructed from autogenous superficial femoral vein. Included herein is a review of the literature detailing the three previously reported cases of combined hepatic and caval resection; to our knowledge, there are no prior reports of the use of an autogenous vein graft in this setting. With surgical and anesthetic techniques, including total vascular exclusion of the liver and venovenous bypass, methods that were developed in large part through experience in liver transplantation, this type of surgery can be performed with a high rate of success.

Adrenal Gland Neoplasms

Primitive neuroectodermal tumor of the leptomeninges.

Primitive neuroectodermal tumor (PNET) without an obvious intraparenchymal mass lesion and with diffuse spread in the subarachnoid space is rare. We report such a rare case and discuss the computed tomography (CT) and magnetic resonance (MR) features.

Adolescent

Major histocompatibility complex expression in brain of rats with graft-versus-host disease.

In a healthy state, the central nervous system (CNS) is believed to be an immunologically privileged site, which does not participate in the immune reactions of the rest of the body, and in which identifiable components of the immune system are rare or non-existent. In this study, an immunohistochemical examination of the CNS of F1 hybrid rats following induction of graft-versus-host disease (GVHD) was carried out to determine whether specific immune reactions in the normal CNS could occur during a systemic immune reaction. The results revealed extensive parenchymal and vascular expression of class I and II major histocompatibility complex (MHC) encoded cell surface molecules. The strongest expressors of class I and II molecules were endothelial cells and parenchymal cells, respectively, the latter being apparently activated microglia, in the cerebrum and cerebellum of rats with GVHD. In addition, occasional scattered lymphocytes were detected in the CNS of GVHD rats without blood-brain barrier disruption. Thus, evidence was obtained for the presence of immune responses such as MHC antigen expression and lymphocyte infiltration in the CNS during a strong systemic immune response such as GVHD, microglia and endothelial cells apparently playing an important role.

Animals

Brain metastasis of testicular tumor with massive hemorrhage--report of two cases.

The authors report two cases of brain metastasis from testicular tumor with massive, sudden intratumoral hemorrhage. In both cases, the hemorrhage occurred during the 1st admission day and carried a high risk of fatality. Early, aggressive surgical removal is advisable before general deterioration. Postoperative chemotherapy with an agent different from the one applied to primary lesion is also recommended because of drug tolerance.

Adult

[Immunohistochemical expression of alpha-1-antitrypsin in human gliomas].

The present paper describes the analysis of immunostaining patterns of four antibodies, alpha-1-antitrypsin (alpha-AT), glial fibrillary acid protein (GFAP), S-100 protein (S-100), and vimentin in 31 human gliomas. The gliomas were 10 astrocytomas, 10 anaplastic astrocytomas, and 11 glioblastoma multiforme tumors. The immunoreactivity for vimentin and alpha-AT that is one of the main proteinase inhibitors changed in proportion to the degree of histological malignancy. As alpha-AT was localized mainly in the cytoplasm of tumor cells and partially in extracellular spaces, it was thought to have been derived from tumor cells. Preparations immunolabelled with anti-GFAP and anti-S-100 showed no increasing loss of immunoreactivity parallel with increasing malignancy.

Adolescent

[One pedigree of "moyamoya" disease].

One familial case of "moyamoya" disease affecting three patients is reported. The patient in Case 1 was a 28-year-old female. She had suffered from motor weakness of the right limbs in her infantile period. She visited our hospital because of sudden headache and left motor weakness associated with nausea and vomiting. On admission, CT scan revealed cerebral hemorrhage in the right caudate nucleus with intraventricular clots and infarction in the left parietal lobe. Angiography showed stenosis of the left ICA terminal portion and occlusion of the right side, with moyamoya vessels in the basal area. The patient in Case 2 was a 54-year-old female, who was the mother of Case 1. After an operation for acute upper intestinal bleeding, she suffered from cerebral infarction. CT scan revealed large low density areas in the territory of the bilateral MCA. Angiography showed stenosis of the bilateral ICA terminal portions, occlusion of the right MCA, stenosis of the left MCA, and moyamoya vessels in the basal area. The patient in Case 3 was a 40-year-old female, who was a younger sister of Case 2. She had a convulsive attack in her infantile period. She visited our hospital because of gradually worsening headache. CT scan revealed multiple infarctions in the left paraventricle, the right parieto-occipital and occipital lobe. Angiography showed occlusion of the bilateral ICA terminals with moyamoya vessels in the basal and the ethmoidal areas. The patient in Case 2 died immediately. Surgery for reconstruction of hemodynamics was performed in Case 1 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Development of the rat meninx: experimental study using bromodeoxyuridine.

The development of the rat meninx from the viewpoint of cell proliferation was studied microscopically and immunohistochemically using bromodeoxyuridine (BUdR). A compact cell layer around the neural tube, the meninx primitiva, was observed in 12- and 13-day fetuses. A reticular structure resembling the subarachnoid space appeared in the 14-day fetus. The ectomeninx, consisting of a collagen fiber layer, part of which became the dura mater, appeared in 15-day fetuses, allowing discrimination of the endomeninx, the arachnoid cell layer. The primordium of the choroid plexus also appeared in the lateral ventricle on the same day. Bone appeared in the primitive dura mater, and stratification of the meninx was almost complete in 21-day fetuses. BUdR-positive cells were confirmed in the meninx from day 12 of gestation to day 15 postpartum. The number of BUdR-positive cells was greatest in fetuses aged about 12 or 13 days, reaching nearly 50%, but decreased gradually toward the neonatal period. The findings of this study suggest that, after the migration of neural crest cells, marked cell proliferation in the meninx begins. Differentiation into various layers then follows and is almost complete before birth, whereas the proliferation of arachnoid cells continues even in the early neonatal period.

Animals

Transferrin receptors in injured brain.

Recent studies have demonstrated the presence of transferrin receptors (Tf-R) in the central nervous system. The present study of Wistar rats with experimentally induced brain injuries, using immunohistochemistry at the light microscopy level, demonstrated the presence of Tf-R in regenerated endothelial cells, reactive astrocytes and in other cells, probably macrophages. Although Tf-R were seen in proliferating cells, Tf-R were also observed in non-proliferating cells, many of them macrophages. The receptors perhaps bind transferrin in edema fluid and play an important role in lesion repair.

Animals

Surgical manipulation of VX2 carcinoma in the rabbit liver evokes enhancement of metastasis.

To search for possible untoward effects of surgical manipulation of a malignant tumor, a series of experiments was carried out using VX2 carcinoma of rabbits. Fourteen days after inoculation of VX2 carcinoma into the liver, the rabbits were separated into two groups: Group I, manual manipulation during relaparotomy; and Group II, relaparotomy alone without manual manipulation of the tumor. After these procedures, the tumor was surgically removed and histologic examinations were made. The incidence of vascular permeation of liver tumor cells into the hepatic vein was significantly higher in Group I (P less than 0.01). On the 14th day after resection of the tumor, the number of metastatic nodules in the lungs was significantly increased in Group I (P less than 0.01). Survival time of rabbits after resection of tumor was significantly shorter in Group I (P less than 0.01). These results are taken to mean that manual manipulation of a tumor may well enhance metastasis.

Animals

Nucleolar organizer regions in meningioma.

Seventy-eight cases of meningioma and related tumors were examined independently using a simple and reproducible argyrophilic method for the demonstration of nucleolar organizer regions (AgNORs) and staining with bromodeoxyuridine monoclonal antibody. The mean number of AgNORs per cell and the bromodeoxyuridine labeling index were shown to be linearly related (r = 0.84, P less than 0.001). The mean AgNOR number was 2.99 for meningeal sarcoma, 2.29 for anaplastic meningioma, 2.08 for hemangiopericytic meningioma. 1.72 for recurrent meningioma without atypical histological findings, and 1.52 for nonrecurrent meningioma. We noted that the mean number of AgNORs reflected the cellular kinetics of a tumor and was related to histological grade and clinical behavior.

Bromodeoxyuridine

Subependymal giant cell astrocytoma associated with tuberous sclerosis: with special reference to cell kinetic studies--case report.

The authors report a case of subependymal giant cell astrocytoma associated with tuberous sclerosis in a 15-year-old boy. Computed tomographic scans showed a large intraventricular mass with peritumoral calcification and a cyst in the left lateral ventricle. Left dominant unilateral hydrocephalus was also revealed. Magnetic resonance images clearly demonstrated the lesion. The tumor was subtotally removed and a ventriculoperitoneal shunt was performed because of the hydrocephalus. The proliferation potential was assessed by measuring the bromodeoxyuridine (BUdR) labeling index employing the in vitro labeling method, and determining the deoxyribonucleic acid (DNA) content by flowcytometry. BUdR-positive cells were found to be rare, and the DNA histogram demonstrated no evidence of high proliferative activity or aneuploidy.

Adolescent