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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 559 records · Page 31Linked to original sources

Erythrocytes suppress calcitonin gene-related peptide- and vasoactive intestinal polypeptide-like immunoreactivities in cerebrovascular nerve fibers after subarachnoid hemorrhage.

Changes of calcitonin gene related-peptide (CGRP)- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities (LI) in cerebrovascular nerve fibers on the dog basilar artery were immunohistochemically examined by using whole-mount preparations after single percutaneous injection of blood components into the cisterna magna. Blood components were prepared from autologous arterial blood. CGRP- and VIP-LI in cerebrovascular nerve fibers were highly suppressed after the injection of washed erythrocytes, but only moderately after the injection of platelet-rich or platelet-poor plasma. The results suggest that erythrocytes may suppress CGRP- and VIP-LI in cerebrovascular nerve fibers after subarachnoid hemorrhage.

Animals↗

Efficient tumor suppression by glioma-specific murine cytotoxic T lymphocytes transfected with interferon-gamma gene.

We have recently shown that exogenous expression of the mouse interferon-gamma (IFN-gamma) gene augmented the cell-killing potential of a line of cytotoxic T lymphocytes (CTLs) specific against a murine glioma line (203-glioma). In the present work, we further investigated the in vivo antitumor effects of the E gamma-6 and E gamma-9 sublines of this CTL line transfected with the IFN-gamma gene. Using the Winn assay to test the neutralization of subcutaneous gliomas, we determined that these CTL sublines were more effective than the E-4 parent CTL line and that suppression of the tumor growth was dependent on the number of effector cells (CTLs). Moreover, intravenous injection of E gamma-9 cells was more effective in suppressing the tumor growth than intravenous injection of E-4 cells. These results suggest that transfection of antitumor effector cells with the IFN-gamma gene could improve the efficacy of adoptive immunotherapy against cancer.

Animals↗

Decreased susceptibility of lined human gliosarcoma cells to lymphokine-activated killer cell cytolysis by gamma-interferon treatment.

The susceptibility of the established cultured gliosarcoma line GI-1 to lymphokine-activated killer (LAK) cells was analyzed with and without interferon (IFN)-gamma treatment of target GI-1 cells. IFN-gamma treatment decreased the susceptibility of GI-1 cells to LAK cell cytolysis in a dose-dependent manner. Acid treatment of GI-1 cells increased their susceptibility to cytolysis compared with untreated cells. IFN-gamma treatment and acid treatment of GI-1 cells respectively increased and decreased the expression of class I HLA antigens on GI-1 cells. The susceptibility of GI-1 cells to LAK cell cytolysis and their expression of HLA class I molecules were inversely correlated. Subpopulation depletion experiments on the LAK cells with monoclonal antibodies and complement revealed that phenotypically natural killer type (CD16+) cells had a high cytotoxic activity against untreated GI-1 cells but a relatively low activity against IFN-gamma-treated GI-1 cells in both the precursor and effector phases. On the other hand, phenotypically T-type (CD3+) cells did not show these tendencies at all in both the precursor and the effector phases.

Antigens, Differentiation↗

Evaluation of glucose transport in malignant glioma by PET.

Using dynamic PET mode and 18FDG, glucose transport in patients with gliomas were investigated. The values for transfer rate constants k1*, k2*, k3*, and glucose consumption were found to be low in the low-grade glioma as compared to those of the high-grade glioma and the contralateral cerebral cortex. The differences were statistically significant with the exception of k2*. There were no statistically significant differences between the high-grade glioma and the contralateral cerebral cortex. In contrast, the distribution volumes k1*/k2* and k1*/(k2* + k3*) were low in high-grade glioma and the difference between the high-grade glioma and the contralateral cerebral cortex was statistically significant. A difference in k1*/(k2* + k3*) was noted between the low-grade and the high-grade gliomas. Thus, the distribution volumes are most sensitive for differentiation between high-grade glioma and cerebral cortex.

Biological Transport↗

Ischaemic brain oedema and xanthine-xanthine oxidase system.

The formation of oxygen-derived free radicals in cerebral ischaemia has been implicated in altering the BBB permeability, cause oedema and tissue damage. However little attention has been paid regarding the involvement of xanthine oxidase in the cerebral ischaemic events. Recently we demonstrated that cerebral ischaemia promotes the conversion of xanthine oxidase type D (nicotinamide adenine dinucleotide-dependent dehydrogenase) to type 0 (oxygen-dependent superoxide-producing oxidase). This investigation was concerned with elucidating the relationship between the conversion of xanthide oxidase and the duration of brain ischaemia. Four vessel-occlusion served as a model for the induction of cerebral ischaemia in rats. Xanthine oxidase was assayed by high pressure liquid chromatography using ultraviolet and electrochemical detection. The enzymatic conversion of xanthine oxidase from type D to type O increased with time from 7.6-15% during 5 min ischaemia to 27% and 36% at 15 min and 30 min after ischaemia, respectively. These results support the contention that xanthine oxidase may participate in free radical-induced ischaemic brain oedema.

Animals↗

Dose escalation trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage.

The initial dose-escalating clinical trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage is reported. AT877 is characterized by its strong spasmolytic activity, its inhibition of intracellular calcium ion activity, and the inhibition of several protein kinases. A total of 113 patients (Hunt and Hess grades I to IV) who had undergone surgery within 3 days of aneurysmal rupture entered the study. Patients were divided into 5 groups according to the total daily dose of AT877: I: 20 mg; II: 40 mg; III: 60 mg; IV: 90 mg; and V: 120-180 mg. AT877 was given by intravenous infusion over 30 min two or three times a day for 14 days after surgery. Although AT877 did not completely abolish angiographic vasospasm, severe vasospasm was seen less frequently in patients given higher doses. Vasospasm was the cause of a poor clinical outcome (Glasgow outcome scale rating 3 or greater) in 19%, 7%, 9%, 8%, and 6% of the patients in groups I to V, respectively. The results indicated a favourable clinical effect of AT877 at doses above 40 mg per day. Only mild hypotension was seen, even when 60 mg of AT877 was infused over 30 min. AT877 appears to be effective in patients with subarachnoid haemorrhage. Part of its effect may be attributable to protection of the brain from ischaemic insults due to chronic cerebral vasospasm. However, the drug still needs to be evaluated in a placebo-controlled double-blind trial (which is currently being carried out).

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Changes of glycogen and ATP contents of the major cerebral arteries after experimentally produced subarachnoid haemorrhage in the dog.

The contents of glycogen and ATP in the major cerebral arteries were examined in dogs undergoing subarachnoid haemorrhage (SAH). SAH was produced by a single injection of autologous arterial blood (1 ml/kg body weight) into the cisterna magna. Vertebral angiograms showed biphasic basilar arterial narrowings after the injection of blood: Early arterial narrowing occurred immediately after the injection and continued for a few hours. Late arterial narrowing occurred from Day 1 to Day 14 of post-SAH period, and recovered to the normal level on Day 21 of post-SAH period. The content of glycogen in the large pial arteries significantly decreased from Day 1 to Day 14 and returned to the control level on Day 21. The content of ATP in the large pial arteries also decreased from Day 1 to Day 7 and returned to the control level on Day 14. These results show that energy stores in the major cerebral arteries might be diminished during late arterial narrowing.

Adenosine Triphosphate↗

Clonal analysis in the ultrastructure of cell-to-cell interaction between a human glioma cell line and autologous tumor-specific cytotoxic T lymphocytes.

The clonal analysis in the ultrastructure of tumor-lymphocyte interaction was carried out in order to investigate the precise mechanism responsible for CTL-mediated cytolysis of tumor cells. A glioma-derived cell line (GI-1) and autologous tumor-specific cytotoxic T lymphocyte (CTL) clones were established. The CTL lines were composed of the morphologically homogeneous lymphocytes with intracytoplasmic electron-dense secretory granules. After the stimulation by GI-1, the size of the CTLs increased, and the intracytoplasmic organellas were developed. It was noted that the intracytoplasmic secretory granules markedly increased in number and size, and many of them exhibited an "immature" appearance. On the other hand, the tumor cells underwent a progressive degeneration. In contrast, the stimulation by other antigens caused only small morphological changes in the CTLs. It is suggested, therefore, that the secretory function of tumor-specific CTLs is activated by the stimulation of the specific antigen, and that soluble factors in the secretory granules in the CTLs may be closely associated with the mechanism of target cell lysis.

Cell Communication↗

Intracerebral malignant lymphoma with fluctuating regression and spatial evolution.

Seven patients with histologically proven primary intracerebral malignant lymphoma, characterized by a fluctuating nature with both transient regression and spatial evolution of the tumors without contiguity to the initial lesion, are presented. Although the overall outcome was unfavorable, two cases had a long-term survival of 3 years or more and one of them showed a good quality of life. Correlation among characteristic clinical presentations, computed tomography scans, and prognostic factors after management with surgery, radiation, and chemotherapy, including steroids, is discussed.

Aged↗

Two surgically cured cases of subependymoma with emphasis on magnetic resonance imaging.

The authors describe two surgically cured cases of symptomatic subependymomas located in the lateral ventricle and septum pellucidum with emphasis on magnetic resonance imaging study. Both computed tomography and MRI revealed a calcified mass with repeated intratumoral hemorrhages. Cerebral angiograms disclosed rather hypovascular lesions. The histologic diagnosis was proven to be of subependymoma. The pertinent literature of surgically treated subependymomas is reviewed, and the characteristic biologic features are also discussed.

Adult↗

Supratentorial malignant glioma: an analysis of radiation therapy in 178 cases.

To analyze treatment results of supratentorial malignant gliomas in the megavoltage era, all the histologic specimens were reviewed and glioblastoma multiforme (GBM) was distinguished from anaplastic astrocytoma (AA) by the presence of necrosis. Among those who had completed radiotherapy and who had been followed for at least one year, 135 GBM and 43 AA patients were found. The median survival time (MST) after operation was 12 months for GBM and 18 months for AA. The 5-year survival rate was 0.9% for GBM and 18% for AA. The size of radiation field had little influence on survival time; MST was 12 months for GBM patients treated with a local field covering tumor plus less than 2 cm margin, 12 months for those treated with a generous field (2 cm or more margin), and 13 months for those treated to whole brain. Also for AA, whole brain radiation did not prolong survival. Initial relapse of GBM and AA developed within the irradiated volume in 86% of the cases treated with a generous field. Whole brain radiation seemed useless for the treatment of malignant gliomas. Survival time appeared to be dose-dependent; MST was 10, 13, and 16 months for GBM patients who received 45-57, 57-63, and 63-72 Gy, respectively. Extensive surgical resection was associated with a better prognosis in GBM. AA patients 60 years old or older had a poorer prognosis than younger patients, but age was not a significant prognostic factor for GBM. Chemotherapy appeared to prolong survival slightly without improving long-term survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Gene expression of fibroblast growth factors in human gliomas and meningiomas: demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues.

The growth autonomy of human tumor cells is considered due to the endogenous production of growth factors. Transcriptional expression of candidates for autocrine stimulatory factors such as basic fibroblast growth factor (FGF), acidic FGF, and transforming growth factor type beta were determined in human brain tumors. Basic FGF was expressed abundantly in 17 of 18 gliomas, 20 of 22 meninglomas, and 0 of 5 metastatic brain tumors. The level of mRNA expression of acidic FGF in gliomas was significant. In contrast, transforming growth factor type beta 1 was expressed in all the samples investigated. The mRNA for basic FGF and its peptide were localized in tumor cells in vivo by in situ hybridization and immunohistochemistry, showing that basic FGF is actually produced in tumor cells. Our results suggest that tumor-derived basic FGF is involved in the progression of gliomas and meningiomas in vivo, whereas acidic FGF is expressed in a tumor origin-specific manner, suggesting that acidic FGF works in tandem with basic FGF in glioma tumorigenesis.

Blotting, Northern↗

Treatment of a giant aneurysm of the cavernous internal carotid artery associated with a persistent primitive trigeminal artery: case report.

A case of an unruptured giant aneurysm of the cavernous portion of the left internal carotid artery associated with a persistent primitive trigeminal artery (PTA) is presented. The usual surgical approach to giant aneurysms at this site, including ligation of the ipsilateral internal carotid artery (ICA) and an extracranial-intracranial (EC-IC) bypass, was inadequate because of continued blood supply to the aneurysm via the PTA from the vertebrobasilar system. The patient was successfully treated with a combination of EC-IC bypass surgery, ICA ligation, and simultaneous intravascular balloon obliteration of the ICA just distal to the junction of the PTA and immediately proximal to the aneurysmal neck. Follow-up radiological investigations showed thrombosis of the aneurysm.

Carotid Artery, Internal↗

Angiographic study of induced cerebral aneurysms in primates.

Five cynomolgus monkeys treated with unilateral carotid ligation, renal hypertension, and beta-aminopropionitrile feeding were studied repeatedly by cerebral angiography to clarify the growth process of saccular cerebral aneurysms. Repeated angiography demonstrated saccular cerebral aneurysms in three of five monkeys; two aneurysms were found 15 months and a third 12 months after the operation. At autopsy, one saccular aneurysm was found to be bilocular in shape, and the others were unilocular. Fusiform aneurysms were also observed in four monkeys. Microscopic studies revealed the walls of the saccular aneurysms were very thin and consisted of fibrous tissue. In one aneurysm, the aneurysmal sac was almost obstructed by a well-organized thrombus. No evidence of intramural hemorrhage was found in any of the saccular cerebral aneurysms. The conversion of early aneurysmal changes into saccular aneurysms was found to occur abruptly, and no consistent growth rate was noted. The multiloculation of saccular aneurysms was closely related to the size of an aneurysm. The present study indicates that a saccular cerebral aneurysm may grow abruptly from one of several different kinds of early aneurysmal changes.

Aminopropionitrile↗

Evaluation of mizoribine as an immunosuppressant in subrenal capsule assay using immunocompetent mice.

We studied the application of mizoribine (MZR) to normal immunocompetent mice in subrenal capsule assay (SRCA) by means of tumor growth curve determination, histological analysis and autoradiography. At 400 mg/kg, MZR prolonged the actual tumor growth and moderately reduced the host reaction. Doses below 200 mg/kg did not effectively suppress the host reaction. The maximal weight loss of mice in the 400 mg/kg group reached 29%, but did not exceed 10% within 8 days. Hence, we applied 400 mg/kg of MZR to SRCA for up to eight days for cancer chemotherapy testing. This dose of MZR did not affect the labeling index of tumor cells compared with the control.

Animals↗

[HTLV-I associated interstitial pneumonia--a case report and bronchoalveolar lavage study].

A 70-year-old male was admitted to our hospital because of fever and dyspnea. The patient was seropositive for HTLV-I and ATL cells were seen in the peripheral blood in the percentage of 2-5. The proviral DNA was positive and the diagnosis of smoldering ATL was made. His chest X-ray film showed diffuse reticulo-nodular infiltrates in both lung fields. The lung tissue obtained by transbronchial lung biopsy showed the lymphocytic infiltrations in the alveolar septa and the submucosa of the bronchioles. Bronchoalveolar lavage (BAL) fluid showed an increased proportion of lymphocytes that consisted mainly of CD3+ DR+ cells and the CD4+/CD8+ ratio was 2.1 during exacerbation and 0.8 after steroid therapy. Anti-HTLV-I IgG and IgA antibodies were positive in both serum and BAL fluid by Western blotting method. It is suggested that T-lymphocyte alveolitis may occur in patients who are seropositive for HTLV-I and the immunological mechanism seems to be responsible.

Aged↗

Elastic skeleton of intracranial cerebral aneurysms in rats.

In an attempt to clarify the developmental mechanism of cerebral aneurysms, we studied the elastic skeleton of experimentally induced cerebral aneurysms in rats under scanning electron microscopy after hot formic acid extraction followed by freeze-drying. We produced cerebral aneurysms in 19 rats by unilaterally ligating the common carotid artery, inducing renal hypertension, and feeding beta-aminopropionitrile fumarate. The first noted change was the loss of folds protruding from the internal elastic lamina. Morphologic changes of the internal elastic lamina, considered to be primarily responsible for aneurysmal formation, occurred after the loss or disintegration of the elastic skeleton of first the intima, then the media. In large aneurysms with thick domes, we found proliferation of elastic lamellae that may reduce the risk of rupture. It seems probable that the complex elastic skeleton of the arterial wall may account for the mechanical properties of the artery and that growth of an aneurysm occurs due to disintegration of the elastic skeleton and not simply to rupture of the internal elastic lamina. We believe that such changes in the elastic skeleton are a property of the functional state of the cells that produce elastin.

Animals↗