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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 361 records · Page 20Linked to original sources
PubMed1994

The effects of atrial natriuretic peptide on brain edema, intracranial pressure and cerebral energy metabolism in rat congenital hydrocephalus.

Atrial natriuretic peptide (ANP) regulates fluid and electrolyte homeostasis in the central nervous system. In this study, we evaluated the effects of ANP on brain edema, intracranial pressure (ICP) and cerebral energy metabolism in congenital hydrocephalus in rats. Brain edema, indicated by the longitudinal relaxation time (T1), was evaluated by 1H-magnetic resonance imaging (MRI). The ICP was monitored with a miniature pressure-transducer with telemetric system. Cerebral energy metabolism, indicated by PCr/Pi ratio, was measured by 31P-magnetic resonance spectroscopy (MRS). The rats were given 10 microliters of ANP in the left cerebral ventricle. Three different concentrations of ANP were given; 0.2 (group I), 2.0 (group II) and 20.0 (group III) micrograms/10 microliters, respectively. 10 microliters of saline was injected into the ventricle of the control group rats. There were no significant changes of ICP, T1 value and PCr/Pi ratio among the control group, group I and group II. In group III, in contrast, ICP decreased significantly at 20 minutes after ANP administration and stayed at this ICP level for 60 minutes. The T1 value decreased and PCr/Pi ratio increased 30 minutes after ANP administration. This study revealed that intraventricularly administered ANP could decrease ICP, reduce brain edema and improve the cerebral energy metabolism in rats with congenital hydrocephalus.

Animals↗
PubMed1994

Experimental study and clinical use of poly(vinyl acetate) emulsion as liquid embolisation material.

A new material, an emulsion of poly(vinyl acetate) was experimentally developed and clinically used to overcome several disadvantages in currently used liquid embolisation materials. The emulsion microparticles, 0.3-0.7 microns in size, possessed cationic charge on the surface and hence aggregated immediately on contact with fluids containing anions. This inert polymer has the advantage that it does not induce a deleterious reaction in living tissue. Moreover, its medium is water and it is not adhesive, like the cyanoacrylates. Several concentrations of emulsion were injected into the renal arteries of dogs. For the investigation of tissue reactions and the possibility of recanalisation, the emulsion was injected into rats both subcutaneously and into the renal arteries. The renal artery injections in dogs showed adequate radiopacity and consistent complete occlusion. The lower the concentration of the emulsion, the smaller the arteries which could be occluded. Even at very low concentrations, however, venous occlusion did not occur. Histological study of the embolised rat kidney revealed no detectable damage in the vessel wall and no recanalisation for up to 6 months. The subcutaneously injected PVAc emulsion elicited mononuclear cell infiltration and gradual centripetal fibrosis, without any deleterious effect on the surrounding tissue. A cerebral arteriovenous malformation (AVM) was embolised using the material. Histology of the resected nidus showed findings similar to those in the animal experiments.

Adult↗
PubMed1994

Primary central nervous system lymphoma in Japan--a retrospective, co-operative study by CNS-Lymphoma Study Group in Japan.

This manuscript reports the results of the first cooperative study on primary central nervous system lymphoma (PCNSL) in Japan. Of 196 patients registered, 170 were judged as having PCNSL. No patients were immunocompromised. Of the 170 patients with PCNSL, 93 were males and 77 were females. The mean was 56.7 years. One hundred and nineteen tumors were confirmed histopathologically, and 51 were diagnosed by neuroimaging alone. All the tumors were non-Hodgkin's lymphoma. According to the Working Formulation for Clinical Usage (WF), 96 out of 119 tumors were classifiable: 53 were diffuse large cell type (55.2%), 17 immunoblastic type (17.7%), 9 diffuse small cleaved type (9.4%), 6 diffuse mixed type (6.3%), 5 polymorphous type (5.2%), 5 small lymphocytic type (5.2%) and 1 small non-cleaved type (1.0%). Of 21 tumors studied immunohistochemically, 18 were B-cell type and 3 were T-cell type. Irradiated patients (144) survived significantly longer than non-irradiated patients, (median survival time, MST: 19.2 and 2.7 months, respectively; p < 0.001). There was a remarkable difference in survival among patients of the intermediate lymphomas; MST (18 months) of patients with large cell lymphoma was significantly shorter than MST (over 96 months) of patients with other intermediate grade lymphomas (small cleaved and mixed) (p < 0.001) and had no significant difference from MST (9 months) of patients with high grade lymphomas. If patients were irradiated with more than 40 Gy, higher doses and different modes of irradiation brought no further survival advantage. Chemotherapy was performed in 87 of 144 irradiated patients (60.4%). No regimens were effective in prolonging survival. Of 144 irradiated patients, a complete or partial response to initial treatment was demonstrated in 91 (63.2%) and 43 patients (29.9%), respectively. Improvement in performance status was confirmed in 82 patients (57.0%). Despite a good response to initial treatments, 88 out of 144 evaluatble patients have died of PCNSL (MST: 19 months). Multivariate analysis based on the Cox hazard model revealed that histology of tumor, age at onset, performance status, and radiotherapy were prognostic factors. Neither chemotherapy nor mode of surgery was a beneficial factor.

Adolescent↗
PubMed1994

Scintigraphic detection of neural-cell-derived small-cell lung cancer using glioma-specific antibody.

Radiolabeled GA-17, a murine monoclonal antibody that reacts specifically with glioma cells, bound to a small-cell lung cancer (SCLC) cell line NCI-H69 derived from neural cells, both in vitro and in vivo. The affinity constant of GA-17 F (ab')2 fragment binding to NCI-H69 was 1.02 x 10(8)/M while that to the glioma cell line U87MG was 1.22 x 10(8)/M. Iodine-125-labeled GA-17 F(ab')2 fragments injected i.v. localized well in NCI-H69 cells xenografted in nude mice. The percentage of the injected dose per gram accumulated in the xenografted tumor was 6.87 +/- 1.34% g-1 (mean +/- SD, n = 5) 24 h after injection. On the other hand, control monoclonal F(ab')2 fragments accumulated in the xenografted tumor at 0.75 +/- 0.30% g-1. The tumor-to-blood ratio was 1.8 for NCI-H69, while that of control F(ab')2 was 0.60. In conclusion, the radiolabeled GA-17 F(ab')2 fragment is expected to be useful clinically to visualize the small-cell lung cancer and in radioimmunotherapy.

Animals↗
PubMed1994

Pathogenetic and therapeutic considerations of carotid-cavernous sinus fistulas.

Carotid-cavernous sinus fistula (CCF) is a syndrome in which arteriovenous shunts exist between the carotid artery and the cavernous sinus. These shunts vary widely in pathogenesis, angiogram, haemodynamics and treatment. Several systems of classification in terms of either haemodynamics, aetiology and/or pathogenesis have been reported, but they are not comprehensive. A more comprehensive and simpler nomenclature of classification is now required. Fifty seven cases of CCFs were analyzed and were classified according to their pathogenesis, angiography and treatment modalities. There were 11 traumatic CCFs with direct shunts (T-D group), and 2 traumatic CCFs with indirect shunts (T-I group). Spontaneous CCFs were divided into three groups. There were 37 spontaneous CCFs caused by dural arteriovenous shunts that were naturally classified as being indirect shunts (SD-I group). There were 5 spontaneous CCFs caused by suspected connective tissue disorders, such as fibromuscular dysplasia, Ehlers-Danlos syndrome etc.; these had direct shunts. Care was needed to avoid dissection of the artery or complications due to the fragility of connective tissue (SC-D group). There were 2 spontaneous CCFs caused by the rupture of an inflaclinoid aneurysm without any background of connective tissue disorder; these had direct shunts (SA-D group). By this system of grouping and use of abbreviations, each case of CCF can be clearly delineated in terms of its pathogenesis and selection for appropriate treatment.

Adult↗
PubMed1994

Disseminated Trichosporon beigelii infection in patients with malignant diseases: immunohistochemical study and review.

Trichosporon beigelii is a causative agent of opportunistic infection and summer-type hypersensitivity pneumonitis in Japan. However, as the diagnosis of Trichosporon beigelii infection is sometimes difficult, the actual incidence of this disease may be underestimated. Of 203 autopsy patients with malignant disease, seven (7.7%) were diagnosed with disseminated Trichosporon beigelii infection by immunohistochemical investigation of formalin-fixed, paraffin-embedded tissue sections. Including these seven, a total of 43 patients with Trichosporon beigelii infection have been reported in Japan. The majority of them had underlying hematologic malignancies, for which they received cytotoxic chemotherapy resulting in neutropenia. This study indicates that the immunohistochemical method, which can be applied to biopsy specimens, is an excellent tool for specific diagnosis of Trichosporon beigelii infection, which is an emerging fatal mycosis in immunocompromised patients with profound neutropenia.

Aged↗
PubMed1994

Dietary analysis of Japanese patients with chronic pancreatitis in stable conditions.

In order to examine the malnutritional condition of outpatients with pancreatitis, a dietary investigation was conducted in Japanese patients with chronic pancreatitis (n = 38) and healthy subjects (n = 35) of the same age for 3-7 consecutive days, and the characteristics of their food intake were examined. The patients with pancreatitis took in less calories, fat, carbohydrate, and protein than the healthy subjects, by 900 kcal, 20 g, 150 g, and 20 g, respectively. On the other hand, the fat energy ratio in the patients was 20%, similar to that in the healthy subjects. Also, when the fat intake was classified according to origin, i.e., animal, marine, or plant, the proportions for animal (g) and plant (g) were low, while marine fat accounted for a significantly higher percentage than in the healthy subjects. The intake of cholesterol and Ca in the patients was significantly smaller than that in the healthy subjects, but no significant difference was observed in the intake per body weight of proteins and Ca. It seems, possible that the low calorie, low protein, low fat, and low carbohydrate intake may be factors in the malnutritional condition of the patients with chronic pancreatitis. Analysis of covariance and principal component analysis showed that the body weight of the patients was closely correlated with decreases of caloric intake and intake of carbohydrate. The above results revealed that low body weight in patients with chronic pancreatitis was closely related to the decrease of calorie and carbohydrate intake, in addition to maldigestion and malabsorption of nutrients.

Adult↗
PubMed1994

LTP of mossy fiber-stimulated potentials in CA3 during learning in rats.

The study was done to determine whether long-term potentiation (LTP) of the potentials occurs at mossy fiber (MF)-CA3 synapses with the advance of learning in unrestrained and unanesthetized rats. The rats were divided into two groups, the test and control groups. The test group was given daily learning tasks in the radial arm maze, whereas the control group was similarly handled without learning tasks. Complete acquisition of learning was observed in the test group on day 5, and the learning was maintained over 3 days. Under freely moving conditions, a significant increase in population spikes (PS) elicited by MF stimulation with the progress in learning was observed in the test group, and the PS potentiation remained stable after day 4. Furthermore, on day 7, when MF stimulation-induced PS in the test group were compared with that in the control group in pentobarbital-anesthetized rats, the responses were comparatively higher in the former. As the training-induced PS potentiation in CA3 occurred with the advance of learning, these findings suggest that LTP in CA3 induced by learning may be related to memory storage.

Animals↗
PubMed1994

Cerebral vasospasm caused by cisternal injection of polystyrene latex beads in rabbits is inhibited by a serine protease inhibitor.

During subarachnoid hemorrhage (SAH), coagulated blood in the subarachnoid space may be regarded as foreign by the immune system. To investigate how cerebral arteries are affected by activation of the host immune system, foreign body, polystyrene latex beads were injected into the cerebrospinal fluid (CSF) space of rabbits, and the caliber changes of the basilar arteries were studied for 7 days by angiography. Prolonged arterial narrowing peaking on day 2 was observed after cisternal injection of the beads. The increase in peak narrowing correlated with an increase in the number of beads injected. The course of the change in vessel caliber over 7 days was similar to that seen in cerebral vasospasm caused by SAH. Also investigated was the preventive effect of the synthetic serine protease inhibitor, FUT-175 on the arterial narrowing caused by the cisternal injection of the latex beads. The administration of FUT-175 significantly prevented latex beads-induced vasospasm (p < 0.01). The possible role of a non-specific immune response is discussed, and also the role of the serine protease cascades in the development of cerebral vasospasm.

Animals↗
PubMed1994

Effects of protease inhibitor and immunosuppressant on cerebral vasospasm after subarachnoid hemorrhage in rabbits.

The possible role of the immune-defense system in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated in rabbits. We used a synthetic serine protease inhibitor, gabexate mesilate (GM), a glucocorticoid, betamethasone sodium phosphate (B-P), and an immunosuppressant, ciclosporin (Cyclosporin A, CYA), to prevent cerebral vasospasm. These agents were administered intra-venously every 12 hours for three injections, starting 20 minutes after SAH. In the group treated with GM, B-P, or CYA, there were no statistically significant differences in arterial calibers between treated and untreated controls on day 2. The synthetic serine protease inhibitor, FUT-175 has been reported to prevent cerebral vasospasm when the treatment is started 20 minutes after SAH in rabbits [38]. In rabbits treated with FUT-175 at different starting times from 3 to 6 hours, reductions in arterial caliber on day 2 were significantly prevented in each group. The contrasting effects of the two serine protease inhibitors, GM and FUT-175, are discussed.

Animals↗
PubMed1994

Activation of systemic and mucosal immune response following nasal administration of liposomes.

Adjuvant effects of liposomes on systemic and mucosal immune response were investigated following nasal administration to Balb/c mice. Bovine serum albumin (BSA)-specific serum IgG and salivary IgA levels were significantly elevated when BSA-associated liposomes were administered intranasally twice at 4-week intervals. Systemic immune response was activated only by negatively charged liposomes, while activation of mucosal immune response was independent of liposomal charge. Antigen localization in liposomes affected immune adjuvant effect; the mucosal immune response could be activated only by liposomes to whose surface BSA was attached, but the systemic immune response was activated by both liposomes to which antigens were attached and in which the encapsulating antigens occurred. The results suggest that the contribution of antigen-presenting cells in activation of systemic and mucosal immunity following intranasal administration is different.

Adjuvants, Immunologic↗
PubMed1994

Topographical organization of subicular neurons projecting to subcortical regions.

Direct projections from the subiculum to the septum, thalamus, and hypothalamus were studied in the rat by the fluorescent retrograde double-labeling technique with Fast blue and Diamidino yellow. The results confirm and extend the previously reported findings. The dorsal subiculum projects primarily to the lateral septum, anterior and midline thalamus, and mammillary complex. The distribution areas of cell bodies of these projection neurons are substantially segregated, depending on their target region, and few single neurons project to two of the target regions by way of axon collaterals. The ventral subiculum projects mainly to the lateral septum, midline thalamus, and ventromedial hypothalamic area. The distribution areas of cell bodies of these projection neurons are considerably overlapped with one another, and a number of single neurons send axon collaterals to two of the lateral septum, midline thalamus, and ventromedial hypothalamic area. It is, thus, indicated that the populations of subicular neurons projecting to each of the subcortical structures examined are more distinctly segregated in the dorsal subiculum than in the ventral subiculum.

Amidines↗
PubMed1994

Tumour necrosis factor-alpha induces an increase in susceptibility of human glioblastoma U87-MG cells to natural killer cell-mediated lysis.

The mechanism by which tumour necrosis factor (TNF)-alpha increases the susceptibility of U87-MG human glioblastoma cells to lysis by natural killer (NK) cells was studied. Treatment with TNF-alpha (100 units ml-1) for 48 h enhanced the susceptibility of tumour cells to lysis by NK cells. Increased susceptibility to lysis was associated with enhanced expression of intercellular adhesion molecule 1 (ICAM-1) and HLA class I antigen. Antisense ICAM-1 oligonucleotide inhibited lysis by NK cells of TNF-alpha-treated tumour cells. In contrast, acid treatment following TNF-alpha treatment increased lysis by NK cells. These findings indicate that TNF-alpha treatment of glioblastoma cells increased their susceptibility to lysis by NK cells, since ICAM-1 up-regulation would have more profound effects on NK susceptibility than would HLA class I antigen up-regulation.

Antigens, Neoplasm↗
PubMed1994

bcl-2 gene enables rescue from in vitro myelosuppression (bone marrow cell death) induced by chemotherapy.

Recent studies have shown that the use of cytokines such as granulocyte colony-stimulating factor (G-CSF) to ameliorate chemotherapy-induced myelosuppression may enhance the viability of tumour cells with functional receptors for these cytokines. In this study, therefore, we used murine bone marrow (BM) cells in an in vitro model in an attempt to determine whether topoisomerase inhibitors (camptothecin, etoposide and doxorubicin) induce myelosuppression (BM cell death) and whether novel treatments other than the administration of G-CSF can be used for rescue from myelosuppression. DNA fragmentation assay, ultrastructural analysis and cell cycle analysis demonstrated that these chemotherapeutic agents induced apoptosis in BM cells. We demonstrated in addition that enforced expression of the bcl-2 gene in BM cells by MPZenNeo (bcl-2) retroviral gene transfer increased resistance to the apoptosis induced by these agents. These findings suggest the possibility that enforced expression of the bcl-2 gene in BM cells using gene transfer techniques may enable rescue from chemotherapy-induced myelosuppression.

Animals↗
PubMed1994

Ischemia induces the expression of the platelet-derived growth factor-B chain in neurons and brain macrophages in vivo.

To elucidate the role of the platelet-derived growth factor (PDGF)-B chain in the brain, we examined its expression in rat brains with focal ischemia. Focal ischemia was induced by permanent tandem occlusion of the middle cerebral and common carotid arteries in spontaneously hypertensive rats (SHRs). Northern analysis demonstrated that ischemia transiently increased mRNA expression of the PDGF-B chain, but not the PDGF-A chain, in the injured neocortex. The larger transcript (3.5 kb) of the B chain gradually increased to threefold by 16 h, whereas the smaller transcript (2.6 kb) of the B chain markedly increased sixfold by 4 h. Immunohistochemistry revealed enhanced immunoreactivity in the neurons in the infarct and in the periinfarct area from 16 h to days 4-7, with a peak at 24 h. Furthermore, the brain macrophages that accumulated in the infarct showed intense immunostaining in their perinuclear region from days 2 to 14, with a peak at days 5-6. The present study demonstrates that ischemia induces the expression of the PDGF-B chain, first in neurons and later in brain macrophages, and suggests an important role of the PDGF-B chain in the healing process of the injured brain.

Animals↗
PubMed1994

Induction of essential components of the superoxide generating system in human monoblastic leukemia U937 cells.

Cytochrome b558 composed of large and small subunits, and cytosolic 47- and 65-kDa proteins are important constituents of the superoxide (O2-) generating system in phagocytes and B lymphocytes. In this paper, we describe changes in O2(-)-generating activity and expression of O2(-)-generating components during differentiation of human monoblastic leukemia U937 cells to macrophage-like cells. Undifferentiated U937 cells generated no O2- in response to a stimulation, although they expressed the three components other than the cytochrome b558 large subunit. When U937 cells were cultured with agents that induced the cell differentiation, such as vitamin D3, retinoic acid, interferon-gamma, and tumor necrosis factor, O2(-)-generating activity increased 5- to 200-fold depending on the agent used. Immunoblotting analysis revealed that the amounts of the four protein components essential for O2- generation increased, although their induction levels were significantly different between inducers. Among the four protein components, the cytochrome subunits were induced in low levels by all agents tested, which may explain why the O2(-)-generating activity of differentiated U937 cells was much lower than that of neutrophils from peripheral blood.

Antibodies↗
PubMed1994

Characterization of hamster CYP1A1 gene: inducible expression and negative regulation.

A genomic clone encoding the hamster CYP1A1 gene was isolated from a hamster EMBL-3 genomic library and characterized. The CYP1A1 gene contained seven exons including the noncoding first exon as determined for CYP1A1 of other species. DNA sequence analysis up to -2307 bp of the CYP1A1 gene revealed the occurrence of five consensus xenobiotic responsive elements (XREs) and one basal transcription element (BTE) in addition to the canonical TATA box. For functional analysis, transfection experiments were performed in human hepatoma HepG2 cells with reporter gene constructs consisting of fragments with various lengths of the 5'-flanking region of the CYP1A1 gene and bacterial chloramphenicol acetyltransferase (CAT) gene. External deletion of the upstream region from the reporter gene resulted in a stepwise decrease of the CAT activity, suggesting that XREs were responsible for inducible expression of CYP1A1 gene by 3-methylcholanthrene (MC). A negative regulatory element (NRE) was also identified in the 5'-flanking region at -833 to -642. Removal of the NRE from the CYP1A1-CAT fusion gene resulted in about 3-fold increase of MC-inducible CAT activity. Using gel retardation assays with HepG2 nuclear extract, we demonstrated the presence of a specific protein which bound to the NRE fragment. Further competition analysis and methylation interference assays revealed that the nuclear protein bound to a 22-base fragment (from -688 to -709) of the NRE region, whose sequences were conserved among hamster, human, and rat CYP1A1 genes.

Animals↗