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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 451 records · Page 25Linked to original sources

[Delayed cerebral dysautoregulation after recirculation of cerebral ischemia].

Sequential changes of cerebral autoregulation were studied in 20 cats after recirculation of cerebral ischemia. The cerebral autoregulation was evaluated by autoregulation index (A.I.), calculating % delta cerebral blood flow (CBF)/delta cerebral perfusion pressure (CPP), with changing the mean arterial blood pressure (MABP) within 80-130 mmHg. Duration of ischemic insult was 15 min after disappearance of direct cortical response (DCR). Following recovery of cerebral circulation, MABP, CBF and intracranial pressure (ICP) were observed sequentially for at least 48 hours. In 6 of 20 cats the autoregulation was disturbed early after recirculation, and the ICP was increased, resulting in no cerebral blood flow (early deteriorated group). In the other 14 cats the autoregulation was restored immediately, but in 7 of the 14 cats it was disturbed again after 24 hours following recirculation (delayed deteriorated group), finally the ICP was elevated and the CBF became 0 as same as early deteriorated group. In another 7 cats it was not disturbed until 5 days. The changes in CBF following insult were five patterns. These were classified into type A (Gradual decrease), type B (Transient increase), type C (Constant maintenance), type D (Relatively rapid decrease) and type E (Rapid decrease). The delayed cerebral dysautoregulation occurred in the types except for type A and type E. These results suggested there was close relation between delayed dysautoregulation and delayed neuronal dysfunction that we reported previously. Moreover, we considered the delayed dysautoregulation could be speculated from the value of ICP/CBF immediately after recirculation and the pattern of the changes in CBF during ischemic insult.

Animals↗

[A large vertebrobasilar junction aneurysm grown at the proximal end of basilar artery fenestration--usefulness of balloon occlusion test with 99mTc-HMPAO SPECT under induced hypotension and consideration in therapeutic strategies].

A 48-year-old lady suffered a transient loss of consciousness. CT and MRI revealed a large vascular lesion compressing the left lower pons. Angiography revealed a large aneurysm at vertebro-basilar junction, dome of which projected anteriorly and left to midline. Her previous vertebral angiogram taken 10 years ago when she suffered a subarachnoid hemorrhage from the left MCA aneurysm, had showed a fenestration of lower basilar artery without apparent aneurysm. Bilateral super-selective vertebral angiograms revealed that the aneurysm arose at the proximal end of the fenestration, and vertebrobasilar junction was incorporated into the aneurysm indicating broad neck aneurysm. The left posterior communicating artery was well developed. Balloon test occlusion (BTO) of bilateral vertebral artery was performed under normotension and induced hypotension. 99mHM-PAO SPECT was used to examine cerebral blood flow (CBF) during hypotensive BTO. The patient tolerated the test and CBF imaging showed insignificant sight decrease in bilateral cerebellar hemispheres. Exploration of the aneurysm was carried out by the right far lateral suboccipital approach. Bilateral vertebral arteries and the right segment of the basilar artery fenestration were identified. Neck clipping of the aneurysm with reconstruction of the parent vessels were tried with fenestrate clip. However, narrow operative field and large dome of the aneurysm made it hard to identify the left segment of the fenestration. Neck clipping was given up and clipping of bilateral vertebral arteries were performed distal to posterior inferior cerebellar artery with three body clippings. The patient showed moderate postoperative left lower nerve palsy, which was gradually improved in several weeks. Follow-up angiography revealed no opacification of the aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

Basilar Artery↗

[Effects of interferon-gamma on cytotoxicity of murine activated macrophages against murine glioma cells].

We studied the effects of mouse IFN-gamma on the cytotoxic activity of murine activated macrophages (M phi) against mouse VM-Glioma cells (H-2b). Activated M phi were obtained from peritoneal exudate cells of mice from four strains, C57BL/6 (H-2b), C3H/He(H-2k), DBA/2 (H-2d), and BALB/c (H-2d), following intraperitoneal injection of (1) LPS 200 micrograms, (2) BCG 200 micrograms, (3) C. parvum 200 micrograms, or (4) MDP 350 micrograms 7 days prior to 20-hr 51Cr release-assay. Of the various combination of mouse strains and activating agents tested, that of activated M phi of the C3H/He mouse with induction by LPS had the most tumoricidal effect against the glioma cells, which was not MHC restricted. Although LPS-activated M phi underwent marked loss of cytotoxicity following initiation of in vitro culture, this 24 hr pretreatment with IFN-gamma inhibited this reduction in tumoricidal effects in a dose-dependent fashion. On the other hand, 24 hr pretreatment of target cells with IFN-gamma did not increase their susceptibility to lysis by activated M phi. These findings suggest that IFN-gamma augments the in vitro tumoricidal activation of M phi; This effect appears to be unrelated to any influence of IFN-gamma on target sensitivity to lysis by macrophages.

Animals↗

[Vertebral artery occlusion therapy for a VA-PICA giant aneurysm: hemodynamic analysis by hydraulic vascular model].

Although therapeutic occlusion of the vertebral artery has been an accepted treatment for an inaccessible VA giant aneurysm, several problems have been reported such as incomplete thrombosis, growth or rupture of the aneurysms, and cerebral embolism originating from the aneurysmal cavity. Hemodynamic changes after occlusion therapy are suspected to be responsible for these phenomena. It is usually difficult to solve these problems or to predict them before operation because multiple factors are related in a complex fashion in a living body. One of the effective means is to simulate these hemodynamic conditions by a hydraulic vascular model. To evaluate hemodynamics after gradual therapeutic occlusion of the vertebral artery, a glass sphere of 2.5 cm in diameter was placed in a hydraulic model and regarded as a VA-PICA aneurysm. 40% glycerol solution at 25 degrees C, having similar viscosity and specific gravity to human whole blood at 37 degrees C, was used as a perfusate in this study. The dye was injected into the aneurysm and intensity change of the transmitted light was measured. Half-life of the dye was calculated from the thus-obtained clearance curve and was regarded as an index of intra-aneurysm stagnation. The flow volumes of each arterial site have been estimated in our previous study: 60 ml/min to the territory of one posterior cerebral artery, and 80 ml/min to the cerebellum and the brain stem. Clearance curves were recorded in the following various conditions. The flow value of the PICA was set to be 5, 10, 15, 20, 25, and 30 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrovascular Circulation↗

[Identification of Mycobacterium avium-intracellulare complex in Tohoku district of Japan by using DNA probes].

Attempts were made to identify Mycobacterium avium and Mycobacterium intracellulare in the M. avium-intracellulare complex (MAC) isolated in the Tohoku district of Japan by using DNA probes (Gen-Probe; Rapid Diagnostic System) which are specific for M. avium, M. intracellulare and M. tuberculosis complex, respectively. In the Tohoku district, the ratio of M. avium isolates (80%) exceeded that of M. intracellulare isolates. It was thus shown that, in the Tohoku district where no data concerning the ratio of M. avium to M. intracellulare isolates had been available, the ratio of M. avium by far exceeded that of M. intracellulare.

DNA Probes↗

Bone morphogenetic proteins (BMP-2 and BMP-3) induce the late phase expression of the proto-oncogene c-fos in murine osteoblastic MC3T3-E1 cells.

Here we report that bone morphogenetic proteins 2 and 3 (BMP-2 and BMP-3) induced marked expression of c-fos mRNA in a biphasic manner, i.e. the late phase (48 to 60 h) as well as the immediate-early phase (0.5 h), in murine osteoblastic MC3T3-E1 cells in vitro. The BMP-induced late phase c-fos gene expression was temporally associated with the onset of marked expression of the genes for osteocalcin and alkaline phosphatase, differentiation markers of mature osteoblasts. In contrast, none of TGF-beta 1, 10% FBS, IGF-I and IGF-II, which induced only the immediate-early c-fos mRNA expression, stimulated the expression of osteocalcin and alkaline phosphatase genes. These data suggest that in osteoblasts BMP-2 and BMP-3 induce the late phase expression of c-fos, which may play a role in transcriptional activation of the genes involved in differentiation of osteoblasts.

Animals↗

The effect of active vitamin D3 analogs and dexamethasone on the expression of osteocalcin gene in rat tibiae in vivo.

We tested the effects of 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3), 2 beta-(3-hydroxypropoxy)-1 alpha,25-dihydroxyvitamin D3 (ED-71) and dexamethasone on osteocalcin mRNA levels in rat tibiae in vivo. Northern blot analysis showed that both 1,25-(OH)2D3 and ED-71 caused an increase in osteocalcin mRNA levels in bone: 1,25-(OH)2D3 induced a transient increase in the mRNA levels followed by a decrease in the control level by 12 h post administration. In contrast, ED-71 caused a persistent increase in osteocalcin mRNA level for seven days post administration. Serum osteocalcin levels paralleled the osteocalcin mRNA level in bone in both groups. Dexamethasone caused a marked reduction in both osteocalcin mRNA and serum osteocalcin levels. Suppressive effect of dexamethasone on osteocalcin expression was persistent for seven days at higher dose. Our results represent the first demonstration of the effect of active vitamin D and corticosteroid on the expression of osteocalcin mRNA in bone in vivo.

Amino Acid Isomerases↗

Possible activity of acidic fibroblast growth factor as a progression factor rather than a transforming factor.

Acidic and basic fibroblast growth factors (aFGF and bFGF) are mitogens for mesoderm- and neuroectoderm-derived cells. The facts that FGF-related proteins are oncogenic and that FGFs are expressed in a variety of tumor cell lines or tumor tissues suggest the transforming activities of FGFs. To examine such an activity of aFGF, we introduced a human aFGF expression vector into two populations of Rat-1 cells; one was non-transformed (nRat-1), the other was partially-transformed (tRat-1). tRat-1 cells transfected with aFGF cDNA formed larger colonies in soft agar and produced larger and more malignant tumors in nude mice than those of parental cells. In contrast, nRat-1 cells transfected with aFGF cDNA neither formed colonies in soft agar nor produced tumors in nude mice. Our results suggest that high expression of aFGF may enhance a tumorigenic potential of Rat-1 cells rather than confer such a potential de novo.

Animals↗

Identification of the binding site of 55kDa tumor necrosis factor receptor by synthetic peptides.

We have synthesized a series of peptides, which cover almost the whole range of the N-terminal extracellular domain of human 55kDa TNF receptor (55kDa TNF-R). The peptides were examined for the binding activity to TNF by solid phase binding assay and for the inhibition of TNF cytotoxicity to mouse L-M cells. The peptide 159-178 exhibited remarkably higher binding activity to TNF than other peptides did. The specificity of the TNF binding to the peptides was confirmed by their inability to bind other cytokines. The peptide 159-178 also inhibited TNF cytotoxicity. These results indicate that the specific binding site of 55kDa TNF-R to TNF might reside within the peptide segment of amino acid numbers 159 to 178 in the N-terminal extracellular domain.

Amino Acid Sequence↗

Direct evidence for interaction between COOH-terminal regions of cytochrome b558 subunits and cytosolic 47-kDa protein during activation of an O(2-)-generating system in neutrophils.

Cytochrome b558 in phagocytes is a transmembrane protein composed of large and small subunits and considered to play a key role in O2- generation during the respiratory burst. The COOH-terminal regions of the cytochrome subunits protrude to the cytoplasmic side and are assumed to be the sites for association with cytosolic components to form an active O(2-)-generating complex (Imajoh-Ohmi, S., Tokita, K., Ochiai, H., Nakamura, M., and Kanegasaki, S. (1992) J. Biol. Chem. 267, 180-184). We show here that two synthetic peptides corresponding to the COOH-terminal region of each subunit inhibit NADPH-dependent oxygen uptake induced by sodium dodecyl sulfate (SDS) in a cell-free system consisting of plasma membrane and cytosol. The inhibition was observed when either peptide was added to the system before, but not after, the activation with SDS suggesting that interaction between the COOH-terminal regions of the cytochrome subunits and cytosolic components is important for the assembly and the activity of the O(2-)-generating system. Using the cross-linking reagent dimethyl 3,3'-dithiobis-propionimidate, we found that the cytosolic 47-kDa protein, an essential component of the O(2-)-generating system, interacted with the synthetic peptides in the presence of SDS. In addition to the 47-kDa protein, a 17-kDa protein was found to be associated with the peptide corresponding to the COOH-terminal region of the small subunit. These results indicate that the cytosolic COOH-terminal regions of cytochrome b558 subunits are the binding sites for both the cytosolic 47-kDa protein and the 17-kDa protein and that the binding takes place during activation of the system.

Amino Acid Sequence↗

Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer.

BACKGROUND: The efficiency of anti-CD3 antibody (OKT3) for adoptive immunotherapy using lymphokine-activated killer (LAK) cells generated from tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) was investigated. METHODS: TIL, RLNL, and PBL derived from 39 patients with gastrointestinal cancers (16 gastric cancers, 17 colorectal cancers, and 6 esophageal cancers) were cultured for 4 weeks with 200 U/ml of recombinant interleukin-2. To one group, solid-phase 10 micrograms/ml OKT3 was added during the initial culture period (day 2 or 4). Cytotoxicity against K562 cells (NK-like activity) and Daudi cells (LAK activity) and the phenotypes of effector cells generated after culturing for 2-3 weeks were studied. RESULTS: Proliferative responses were significantly increased by OKT3 in each type of effector cell (P less than 0.01); in particular, TIL expanded more by OKT3 than PBL and RLNL (P less than 0.01). The population of CD8+ CD11b- cytotoxic T-cells in OKT3-stimulated groups was significantly larger than that in unstimulated groups (P less than 0.01), whereas no differences were observed with CD4+ cells (helper/inducer T-cells) and CD8+ CD11b+ cells (suppressor T-cells). OKT3 enhanced the NK-like activity of TIL and PBL but did not affect their LAK activity. OKT3 suppressed the NK and LAK activity of RLNL. CONCLUSIONS: OKT3 stimulation did not significantly enhance the LAK activity, but the authors propose that OKT3 could be an effective addition to adoptive immunotherapy using TIL due to an increased proliferation and generation of a large cytotoxic T-cell population.

Aged↗

Distribution of the glucose transporters in human brain tumors.

In the present study, we have investigated the expression of both the erythrocyte-type (GLUT1) and the brain-type (GLUT3) glucose transporter isoforms in primary human brain tumors. In situ hybridization made it possible to localize and semiquantify both GLUT1 and GLUT3 mRNAs of individual cells in all 18 samples examined. More signals for GLUT3 mRNA than for GLUT1 mRNA were found over astrocytoma cells, while the reverse was the case in all 6 meningiomas. In astrocytomas, for both mRNAs, the density of silver grains over tumor cells was well correlated with the malignancy of the cells. This correlation was, as was also confirmed by Northern blot analysis, more marked with GLUT3 mRNA than with GLUT1 mRNA. In 2 of 5 anaplastic astrocytomas and in all 3 glioblastomas, numerous tumor cells with large amounts of both mRNAs tended to surround the perivascular regions. "Tumor vessels" with endothelial proliferation, an almost pathognomonic feature of glioblastomas, expressed much GLUT3 mRNA but no significant GLUT1 mRNA, while a single- or a few-layered capillary endothelium expressed much GLUT1 mRNA. The distribution of both mRNAs was in good accordance with that of both proteins. Our results suggest that the expression of both glucose transporter isoforms may contribute to the maintenance of human brain tumors and that the expression of the GLUT3 isoform may be closely related to the malignant change of astrocytomas and particularly related to the aberrant neovascularization which accompanies glioblastomas.

Astrocytoma↗

Expression of murine interleukin 7 in a murine glioma cell line results in reduced tumorigenicity in vivo.

We have examined the immunoregulatory effect of local and continuous secretion of interleukin 7 (IL-7) from murine glioma cells (203-glioma) engineered by murine IL-7 gene transfection. Secretion of IL-7 from glioma cells did not result in morphology or growth rate changes but did reduce tumorigenicity in vivo in proportion to the amount of IL-7 produced. This reduction in tumorigenicity could be reversed in a dose-dependent fashion by injection of anti-IL-7 neutralizing monoclonal antibody at the tumor site. Mice immunized with IL-7-producing glioma cells showed a specific immune response to 203-glioma but not to two other syngeneic cell lines (B-16, a melanoma, and YM-12, a fibrosarcoma). IL-7-producing glioma cells were not rejected in mice depleted of CD8+ cells but were rejected in mice depleted of CD4+ or NK1.1+ cells. These results suggest that CD8+ T cells may play an important role in tumor rejection.

Animals↗

Changes in cerebral energy metabolism and calcium levels in relation to delayed neuronal death after ischemia.

Using a brief transient ischemic model, we examined changes in regional tissue calcium content and energy metabolism in the hippocampus. In the CA1 region, tissue calcium ions began to increase 24 h after reperfusion, accompanied by changes in tissue pH and ATP. In the CA3 region, energy metabolism remained unchanged for 72 h after reperfusion, and the calcium pool was first noted 24 h after reperfusion, while tissue calcium ions began to increase 48 h after reperfusion. These results suggest that the neurons in the CA3 region seem to survive because of the well-preserved metabolic function to cope with excessive calcium ions.

Adenosine Triphosphate↗