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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 343 records · Page 19Linked to original sources

[A case of arteriovenous malformation successfully treated with functional mapping of the language area by PET activation study].

The authors report a case of temporal AVM safely treated by mapping the language area with PET activation study. The patient was a 50-year-old woman with temporal epilepsy as her chief complaint. MRI and angiography revealed a right temporal AVM. Before surgical treatment, we assessed the dominant hemisphere with PET activation study. We performed PET scanning while the patient was playing "capping" (called "Shiritori" in Japanese), from which we subtracted PET images performed when she was in a resting state, and then we superimposed those images upon MRIs. The blood flow increased in the left frontal operculum (Broca's area), the left caudal head, the left putamen and the right cerebellar hemisphere. We were thus able to determine that her left hemisphere was dominant, and that it was safe to undertake embolization and operation for the AVM. Postoperative course was uneventful and higher cortical functions were preserved perfectly. In cases of cerebral AVMs, unusual dominancy of cerebral hemispheres is often encountered, and so, preoperative evaluation of the relation of AVM to the eloquent cortex is essential. In our study, blood flow increased in some areas other than the language area, but they were considered to be areas related to phonation, and we think that we were able to map the language area. Though this method is still in its preliminary stage, we think it gives us useful information for surgical treatment of cerebral AVMs.

Brain↗

Increased in vitro and in vivo tumoricidal activity of a macrophage cell line genetically engineered to express IFN-gamma, IL-4, IL-6, or TNF-alpha.

Genetically engineered monocytes and macrophages may have potential as effector cells for the adoptive immunotherapy of cancer. As a first step, we have transfected the genes encoding either mouse interferon (IFN)-gamma, human interleukin (IL)-6, mouse IL-4, or mouse tumor necrosis factor (TNF)-alpha into the mouse macrophage cell line, J774A.1 cells using retroviral vectors. In vitro activation of J774A.1 cells by gene modification was assessed by morphological changes, proliferative activity was determined by [3H]-TdR uptake, and cytolytic activity was assessed using an 18-hour chromium-51 (51Cr) release assay. In vivo tumoricidal activity was studied by means of local adoptive immunotherapy using intratumoral injection of transfected effector cells. IFN-gamma gene-transfected J774A.1 [J7(IFN-gamma)] cells developed filamentous processes, increased doubling times, and enhanced tumoricidal activity against three tumor cell lines: the TNF-sensitive fibrosarcoma line WEHI 164 and the TNF-alpha-resistant cell lines B16 melanoma and C1300 neuroblastoma. IL-6-, TNF-alpha-, and IL-4-gene-transfected J774A.1 cells also had augmented tumoricidal activity but did not display any changes in morphology or growth. Cytolytic activity was markedly reduced after the addition of anti-TNF-alpha antibodies. Cytolytic J7(IFN-gamma) cells showed upregulated expression of TNF-alpha messenger RNA. After intratumoral injection of J7(IL-4) and J7(IFN-gamma) cell mixtures, 50% of established B16 melanomas were rejected by C57BL/6 mice, thereby demonstrating synergistic killing. Further studies on gene-transfected macrophages should better define their potential usefulness in tumor immunotherapy.

3T3 Cells↗

[A case of renal vein thrombosis and pulmonary embolism associated with diffuse membranous glomerulonephritis: the usefulness of low-molecular-weight heparin and urokinase therapy].

We report a case of renal vein thrombosis (RVT) and pulmonary embolism associated with diffuse membranous glomerulonephritis. A 44-year-old Japanese male was referred to the Nephrology Department with heavy proteinuria. Renal biopsy revealed diffuse membranous glomerulonephritis and we administered PSL 30mg/day and dipyridamole 300mg/day. Three weeks later, he was admitted with severe chest pain, dyspnea and massive proteinuria. RVT and pulmonary embolism were detected on CT scan and perfusion lung scan. After a few days of continuous intravenous unfractionated heparin (UFH) therapy, we used 72 U (anti-FXa)/kg of intravenous low-molecular-weight heparin (LMWH) every 12 hours for 10 days. He also received urokinase at the dose of 120,000 U/day for 4 weeks and long-term therapy with warfarin potassium at the dose of 3 mg/day. One month later, the thrombi in the pulmonary arteries and inferior vena cava disappeared on CT scan and perfusion lung scan. LMWHs have a longer biological half-life and a lower bleeding tendency than UFH for an equivalent antithrombotic effect. This case indicates that intermittent intravenous LMWH administration combined with urokinase is effective against RVT and pulmonary embolism without any side effect.

Adult↗

[Essential thrombocythemia transformed to minimally differentiated acute myeloid leukemia].

A 64-year-old female diagnosed for essential thrombocythemia was treated with MCNU 50 mg four times in the course of the disease. Six months after the last administration, in May 1991, she was admitted because of decreasing thrombocyte count and appearance of blasts in the peripheral blood. On admission, laboratory findings were as follows: WBC 700/microliters with 5% of blasts, RBC 331 x 10(4)/microliters, and PLT 17.9 x 10(4)/microliters. Bone marrow aspiration revealed hypocellular marrow with 39% blasts. About 5% of the blasts were positive for myeloperoxidase by electron microscopy analysis. Leukemic cells were positive for CD 7, 13, 33 and 34, negative for other lymphoid lineage markers, and demonstrated no rearrangement of TCR-beta, gamma and IgH genes. Although she was treated with low-dose cytosine arabinoside, no response was observed. Subdural hematoma and sequential pneumonia developed and the patient died eight months after leukemic transformation. In conclusion, we think that the leukemic transformation might have been developed in the natural course of essential thrombocythemia in the present case. However, we cannot exclude the influence of MCNU.

Cell Transformation, Neoplastic↗

[MRI of the pituitary adenomas with reference to the hormonal activity].

Many studies in Magnetic Resonance Imaging (MRI) of pituitary adenomas are already performed. However, few reports exist about MRI findings of pituitary adenomas with reference to the hormonal activity, therefore, we evaluated this problem on the viewpoint of the signal intensity in MRI and pathological features. Fifteen patients with growth hormone producing adenoma (GH-group), 6 patients with prolactin producing adenoma (PRL-group), 15 patients with endocrinologically non-functioning adenoma (Null-group) and 9 cases with normal pituitary gland (normal control group) were examined. Signal intensity values in adenoma (or anterior lobe in normal control group) and in pons as standard value were measured in each cases, then their rates were calculated as signal intensity ratio (SIR). In 24 cases (14 in GH-group, 3 in PRL-group, 7 in Null-group), cellular density were examined with surgically resected specimens. In the T1-weighted images (T1 WIs), PRL-group and Null-group presented more hypointense tendency than normal control group. In the T2-weighted images (T2 WIs), only Null-group presented more hyperintense tendency than other groups. But significant correlation was not observed between SIR and cellular density.

Adenoma↗

[A case of multiple cranial neuropathy due to varicella-zoster virus infection: detection of involvement of cranial ganglia with MRI].

We describe here a 50-year-old patient who had multiple cranial nerve palsies (lt.VIII,IX,X,XI and rt.VII, IX,X) with varicella-zoster virus (VZV). He developed hoarseness, dysphagia on 30th, November, 1994. On the 8th day after the onset, he suffered from left tinnitus and left facial nerve palsy. Neurological examination on the 10th day revealed left peripheral facial nerve palsy, lt. vocal cord palsy, mild dysphagia and loss of bilateral taste. He did not show signs of meningeal irritation. On the 11th day, he felt vertigo and had horizontal nystagmus on the right lateral gaze. The cerebrospinal fluid findings revealed increased protein content but not pleocytosis. The antibody titer for varicella zoster virus elevated both in cerebrospinal fluid and in serum. Cranial magnetic resonance imaging (MRI) revealed gadlinium enhancement on the left geniculate ganglion and left superior or inferior ganglion of IX and X nerves, indicating that multiple cranial nerve palsies associated with VZV infection originate in the cranial ganglia. Focal brainstem encephalitis does not seem to be the main cause of multiple cranial neuropathy in this case.

Cranial Nerve Diseases↗

Transcriptional regulation of basic fibroblast growth factor gene by p53 in human glioblastoma and hepatocellular carcinoma cells.

Mutations of the p53 gene are found in various human cancers. The frequency of its mutation is reported to increase during tumor progression in most tumors. In human gliomas, mutations of the p53 gene are found in about one-third of the malignant forms and in few of the benign ones, indicating their possible involvement in tumor progression. On the other hand, we have recently shown that basic fibroblast growth factor (basic FGF) plays a crucial role in tumor progression as an autocrine growth factor in tissues of human gliomas. Therefore, we hypothesized that p53 might regulate the promoter activity of the basic FGF gene, which has several GC boxes and no typical TATA box. In this study, cotransfection assays using human glioblastoma and hepatocellular carcinoma cells and establishment of stable cell lines expressing mutant-type p53 were performed. The basic FGF gene promoter was demonstrated to be regulated by p53 at the transcriptional level and its basal core promoter was found to be responsive to p53. Expression of endogenous basic FGF was also demonstrated to be activated by mutant type p53. Wild-type p53 repressed gene expression of the basic FGF and its mutant activated it in vitro, implying one of the possible pathways in tumor progression.

Carcinoma, Hepatocellular↗

Interleukin-4 acts as a potent stimulator for expression of monocyte chemoattractant JE/MCP-1 in mouse peritoneal macrophages.

The recruitment of monocyte/macrophages to inflammatory sites is one of the important events in inflammatory reactions. We show herein that interleukin-4 (IL-4) acts as a potent stimulator for expression of monocyte chemoattractant JE/MCP-1 in mouse peritoneal macrophages. IL-4 induced the JE/MCP-1 gene expression in dose and time dependent fashion. Run-on assay suggests that IL-4 stimulates the JE/MCP-1 gene expression at transcriptional level. Monocyte chemotactic activity was detected in culture medium of the cytokine-treated cells. The chemotactic activity in the culture supernatant was completely neutralized by anti-JE/MCP-1 antiserum.

Animals↗

The role of cerebrospinal fluid cytology in radiotherapy planning for intracranial germinoma.

PURPOSE: The association between the cerebrospinal fluid cytology findings and the clinical features of patients with intracranial germinoma was investigated to determine whether cerebrospinal fluid cytology could be helpful in determining the optimal radiation treatment volume. METHODS AND MATERIALS: Between 1976 and 1992, cerebrospinal fluid cytology was performed in 42 germinoma patients using a cytocentrifugation method. Forty patients received irradiation and 2 received chemotherapy with cisplatin and etoposide. RESULTS: Cerebrospinal fluid cytology was positive in 22 of the 42 patients (52%). Dissemination via cerebrospinal fluid (intraventricular or spinal) was present at the initial diagnosis in eight (36%) of the 22 cytology-positive patients and none of the 20 negative patients. After treatment, cerebrospinal fluid dissemination developed in four (18%) of the cytology-positive patients and one (5%) of the negative patients. Two of the former four patients had received chemotherapy alone as initial treatment. Five patients with positive cytology received irradiation to a smaller volume than the cerebrospinal axis (primary tumor site plus spinal axis in three and whole brain in two), but they have not developed recurrence in the 4 to 14 years since therapy. The 5-year survival rate was 93% for the cytology-positive patients and 94% for the negative patients. CONCLUSION: Cerebrospinal fluid cytology-positive patients have a higher risk of cerebrospinal fluid dissemination and it seems reasonable to give them low-dose (20-24 Gy) prophylactic craniospinal irradiation. When properly irradiated, the prognosis of cytology-positive patients is as good as that of negative patients.

Adolescent↗

Differential induction of mRNA species encoding several classes of stress proteins following focal cerebral ischemia in rats.

We report here the time-dependent expression of several classes of HSP mRNAs following focal cerebral ischemia in rats. HSP70, GRP78, HSP27, HSP90 and HSP47 have been reported to possess distinct functions under normal and/or stress conditions. These different classes of HSP mRNAs were differentially induced by ischemia, as determined by Northern blot analysis. Messenger RNAs of the HSP70 family proteins were induced within 4 h after ischemia and then rapidly decreased, whereas HSP27 and HSP47 mRNAs reached a maximum level of expression at 24 h and 48 h after ischemic treatment, respectively. In situ hybridization showed that the expression of inducible HSP70 mRNA was observed predominantly in regions adjacent to the ischemic core except during the early periods of ischemia. HSP27 mRNA was expressed over a broad area of the ipsilateral cerebral neocortex except for the ischemic center 24 h after ischemia. The unique induction kinetics for each HSP mRNA species may reflect their distinct roles in the brain during various physiological stresses. We will also discuss that stress proteins may be involved in the central nervous system after ischemia in two important aspects: early protection against stress and restoration of damaged lesions in the brain at later stages after ischemia.

Animals↗

Transfection with a bcl-2 expression vector protects transplanted bone marrow from chemotherapy-induced myelosuppression.

The use of cytokines such as granulocyte-colony-stimulating factor (G-CSF) to ameliorate chemotherapy-induced myelosuppression may not only stimulate the recovery of normal hematopoietic cells but may also enhance the proliferation of the tumor cells with functional receptors for these cytokines. In this study, we show that administration of recombinant human (rh) G-CSF decreased the in vitro and in vivo cytotoxic effects of Adriamycin or etoposide on L1210 murine leukemic cells with receptors for rhG-CSF. Transplantation of bone marrow cells expressing high levels of bcl-2 from a retroviral construct [MPZenNeo(bcl-2)] (bcl-2-BMT) did not decrease the in vivo cytotoxic effect of etoposide on L1210 cells, but enabled recovery of myelopoiesis following etoposide-induced myelosuppression to almost the same extent as did the administration of rhG-CSF. These findings suggest the possibility that bcl-2 transfection could be used to protect transplanted bone marrow from chemotherapy-induced myelosuppression on behalf of administration of rhG-CSF, in case of treatment of tumors with functional receptors for rhG-CSF.

Animals↗

[Perioperative management of coagulation and fibrinolytic activity in endosaccular embolization of cerebral aneurysms].

Endosaccular embolization is an innovative and effective treatment for surgically formidable cerebral aneurysms. Platinum microcoils are soft, easily fit to complex configuration of aneurysms, highly thrombogenic, so that suitable for this purpose. Recently developed Guglielmi detachable coils have more advantages in terms of retrievability and electrothrombotic effect. However, distal migration of intraaneurysmal thrombus produces thromboembolism in normal cerebral arteries, leading to neurological deficits. Three cases are presented in which thromboembolic complications occurred during or after embolization of cerebral aneurysms with platinum microcoils. Emergent fibrinolytic treatment resolved neurological deficits in each case without any other complications. From these lessons, a protocol of intra- and postoperative anticoagulation and antiplatelet therapy is presented. In conclusion, perioperative management of fibrinolytic and coagulation activity is extremely important in preventing thromboembolic complication and obtaining successful result.

Adult↗

Immunohistochemical study for basic fibroblast growth factor and fibroblast growth factor receptor I in pituitary adenomas.

Immunohistochemistry and RT-PCR of basic fibroblast growth factor (bFGF) and one of its receptors (FGFR-I) were performed in pituitary adenomas. Sixty percent of pituitary adenomas showed strong or moderate immunoreactivity to bFGF. The immunoreactivity for FGFR-I in tumor tissues showed positive correlation to that for bFGF (X2 = 6.176, P = 0.0456). Basic FGF-positive cells consisted of pituitary adenoma cells as well as folliculostellate cells and, their distribution was heterogeneous. Expressions of bFGF and FGFR-I were not related to cell proliferation of pituitary adenomas or hormones produced, suggesting that bFGF plays some role other than progression of pituitary adenomas.

Adenoma↗

Ischemia-induced changes in catecholamine release and their mechanisms: a study using cultured bovine adrenal chromaffin cells.

Ischemia-induced changes in neurotransmitter release and their mechanisms were examined using cultured bovine adrenal chromaffin cells. When the cells were incubated in glucose-free media equilibrated with 0% O2/100% N2 (ischemia), ATP content decreased and reached the minimum level within 40 min. Control incubation was done in media equilibrated with 21% O2 in N2. After 10-min incubation under ischemic conditions, basal catecholamine (CA) release was elevated and the elevation persisted up to 90 min. High K(+)-evoked CA release was transiently enhanced at 10 min, but after that, it decreased to reach the minimum level at 60 min. At 10 min, cytosolic free Ca2+ concentration ([Ca2+]i) and 45Ca2+ uptake of the resting cells (basal values) and high K(+)-evoked increases in these two parameters were unchanged, but CA release from permeabilized cells in response to Ca2+ in media was augmented. After 60-min incubation under ischemic conditions, basal [Ca2+]i was elevated: the elevation was observed even in the absence of extracellular Ca2+. In contrast, high K(+)-evoked increases in [Ca2+]i and in 45Ca2+ uptake were suppressed, but basal 45Ca2+ uptake into intact cells and CA release from permeabilized cells were unchanged. These results suggest that in an early phase (10 min) of ischemia, both basal and stimulation-evoked CA release are augmented because of increased sensitivity of exocytotic machinery to Ca2+. In the late phase (60 min), basal CA release is augmented because of an increase in basal [Ca2+]i, which is due to accumulation of Ca2+ derived from intracellular Ca2+ pools: stimulation-evoked CA release is suppressed because of inhibition of stimulation-evoked increase in [Ca2+]i, which is due to functional disturbance of voltage-dependent Ca2+ channels.

Adenosine Triphosphate↗