Search PubMed⌕ Search

Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 109 records · Page 6Linked to original sources
PubMed2000

Resectability of Spetzler-Martin grade IV and V cerebral arteriovenous malformations.

This study retrospectively analysed treatment modalities and outcomes in 63 cases of high grade cerebral arteriovenous malformations (Spetzler-Martin's classification grade IV 51, V 12) who were admitted to this institute between January 1986 and April 1998. Twenty-seven of 37 cases with haemorrhagic onset received surgical resection with or without pre-operative embolisation. Total extirpation was achieved in 23 cases, and small residual nidus was treated by postoperative radiosurgery in two of four subtotally resected cases. Another 6 of 37 haemorrhagic cases received radiosurgery with or without preradiosurgical embolisation. Four cases with haemorrhagic onset received partial embolisation. Finally, 29 of 37 haemorrhagic cases obtained complete disappearance of nidus. On the other hand, 4 of 26 non-haemorrhagic cases received surgical total resection, 5 radiosurgery, 9 partial embolisation and 8 observation without treatment. Microsurgical morbidity was 9% and mortality was 0%. Post-treatment haemorrhage was seen in 11 cases (1 after subtotal resection, 4 after radiosurgery, 6 after partial embolisation) and was fatal in 3 cases. Surgical resection can be achieved with acceptable morbidity, and complete obliteration of nidus should be accomplished in any treatment modality to avoid post-treatment haemorrhage.

Adolescent↗
PubMed2000

Prevalence of Japanese dialysis patients with an A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene.

BACKGROUND: A high prevalence of an A-to-G mutation at nucleotide 3243 of the mitochondrial genome in patients with diabetes mellitus (DM) and/or deafness has been reported previously. We investigated the prevalence of this mutation in Japanese dialysis patients with associated DM and/or deafness. METHODS: We studied 106 dialysis patients with DM, 26 with DM and deafness, and 26 with deafness alone, using peripheral leucocytes to detect an A-to-G transition at nucleotide 3243 of the mitochondrial gene. RESULTS: We identified this transition in 1 of 26 patients with DM and deafness. None of the 106 DM or 26 dialysis patients with deafness but no DM was positive for this mutation. A 42-year-old male patient on continuous ambulatory peritoneal dialysis (CAPD) who carried this mutation had a 20-year history of sensory hearing loss as well as hypertrophic cardiomyopathy. CONCLUSION: We found that a mitochondrial gene mutation at nucleotide 3243 was present in one dialysis patient with NIDDM and deafness. The prevalence of this mutation was found to be below 1% in diabetic end-stage renal disease patients in Japan.

Adult↗
PubMed2000

Severe proteinuria, sustained for 6 months, induces tubular epithelial cell injury and cell infiltration in rats but not progressive interstitial fibrosis.

BACKGROUND: Sustained proteinuria is reported to be very harmful to the tubulointerstitium, leading to severe interstitial injury. However, it remains unclear whether sustained proteinuria itself is responsible for severe interstitial injury because, in the previously reported models, the development of factors other than proteinuria in tubulointerstitial lesions could not be excluded completely. METHODS: After treatment to induce immune tolerance to mouse immunoglobulin, 20 rats were injected with anti-rat slit diaphragm monoclonal antibody (mAb) 5-1-6 twice a week for 6 months and were then sacrificed. RESULTS: mAb 5-1-6 induced massive proteinuria in 11 rats. In nine rats with mild proteinuria, no histological alteration could be detected with light microscopy and immunofluorescence. In nephrotic rats, light microscopy showed minor glomerular abnormalities, with interstitial oedema, tubular epithelial cell degeneration and interstitial cell infiltration. Immunofluorescence revealed increased expression of vimentin and an increased number of OX1-, OX19- and ED1-positive cells. However, we could not detect any accumulation of type I and IV collagen or laminin in the tubulointerstitium. RT-PCR showed that the expression of mRNA for type I collagen was not increased, compared with that in control rats. CONCLUSIONS: We succeeded in developing a model of persistent nephrosis without severe glomerular abnormalities, nephrectomy or other manoeuvres known to induce disturbed haemodynamics, using an agent without tubulointerstitial toxicity, and considered it to be suitable for investigating the direct toxicity of proteinuria. In this model, isolated massive proteinuria induced interstitial injury. However, the degree of injury was suggested to be much less than that observed in other previously developed models.

Animals↗
PubMed2000

Caspases cleave the amino-terminal calpain inhibitory unit of calpastatin during apoptosis in human Jurkat T cells.

We have previously reported the activation of procalpain mu (precursor for low-calcium-requiring calpain) in apoptotic cells using a cleavage-site-directed antibody specific to active calpain [Kikuchi, H. and Imajoh-Ohmi, S. (1995) Cell Death Differ. 2, 195-199]. In this study, calpastatin, the endogenous inhibitor protein for calpain, was cleaved to a 90-kDa polypeptide during apoptosis in human Jurkat T cells. The limited proteolysis of calpastatin preceded the autolytic activation of procalpain. Inhibitors for caspases rescued the cells from apoptosis and simultaneously inhibited the cleavage of calpastatin. The full-length recombinant calpastatin was also cleaved by caspase-3 or caspase-7 at Asp-233 into the same size fragment. Cys-241 was also targeted by these caspases in vitro but not in apoptotic cells. Caspase-digested calpastatin lost its amino-terminal inhibitory unit, and inhibited three moles of calpain per mole. Our findings suggest that caspases trigger the decontrol of calpain activity suppression by degrading calpastatin.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Phorbol ester-potentiated liposomal transfection to monocytic PLB-985 cells.

In order to improve transient gene transfer into PLB-985 cells, we treated cells with 12-tetradecanoylphorbol 13-acetate (TPA) 4 h before transfection, and increased by 540-fold the reporter activity of the firefly luciferase gene transfected by TFL-01, a cationic liposome. Dioctanolyglycerol added before TPA addition inhibited the TPA-dependent increase in activity, suggesting it to be a TPA competitor for PKC binding. H7, staurosporine, GO 6976, and H8, but not GF 109203X and forskolin, inhibited the TPA-dependent increase in reporter activity when added 8 h after TFL-01/gene addition. Forskolin and GF 109203X also inhibited the increase when added before TPA. Therefore, for the potentiation of transfection by the TPA/TFL-01 method, conventional PKC activity with significant but low protein kinase A (PKA) activity are first required, and then a novel PKC activity with significant PKA activity. TPA enhanced the uptake of FITC-labeled phosphorothioated oligonucleotides and their prolonged maintenance by cells, suggesting increased TFL-01-assisted plasmid uptake and its stabilization in TPA-treated PLB-985 cells. This method was used successfully for the sensitive analysis of the promoter function of the gp91(phox) gene, implying the method to be generally useful for promoter analyses of various genes expressed in differentiated human monocytic cells.

Amino Acid Sequence↗
PubMed2000

Serine-threonine protein kinase Akt does not mediate ischemic tolerance after global ischemia in the gerbil.

The protein kinase Akt/PKB has been implicated in antiapoptosis and neuronal survival. The authors now show that Akt is phosphorylated in the hippocampus during the early reperfusion period after 3.5 minutes bilateral carotid artery occlusion (BCAO) in the gerbil. Repeated sublethal ischemia induces ischemic tolerance, which is known as ischemic preconditioning. Ischemic preconditioning does not affect the amount of Akt protein, but rather decreases the phosphorylation of Akt at Ser-473 after 10 minutes reperfusion after 3.5 minutes BCAO. These results suggest that although Akt may play a role in neuronal survival after ischemia, it may not play a role in ischemic tolerance by preconditioning.

Animals↗
PubMed2000

Posttreatment sequelae of palliatively treated cerebral arteriovenous malformations.

OBJECTIVE: Posttreatment sequelae of palliatively treated cerebral arteriovenous malformations (AVMs) were studied to evaluate the significance of these nonradical treatments. METHODS: Between 1987 and 1997, 46 patients with cerebral AVMs were managed with treatments such as partial embolization, radiosurgery, subtotal resection, or feeder ligation alone. Their AVMs were not radically resected because of difficulties in radical treatment, hesitance to treat eloquent area lesions, or residual nidi after subtotal obliteration. The patients' posttreatment sequelae were evaluated. The duration of follow-up ranged from 0.5 to 169 months (mean, 49.4+/-39.8 mo). RESULTS: Twenty-six bleeding episodes from AVMs were documented in 18 patients. The annual risk of bleeding in this palliatively treated group was 14.6%. Persistent progressive neurological deficit was observed in one patient. Major neurological deficits occurred in 10 patients (23.3%), and the mortality rate was 9.3%. CONCLUSION: Palliative treatments cannot prevent bleeding and may even worsen the posttreatment course compared with the natural history of cerebral AVMs. A more conservative indication is required in recommending palliative treatment alone.

Carotid Arteries↗
PubMed2000

Oral supplementation with gamma-linolenic acid extracted from Mucor circinelloides improves the deformability of red blood cells in hemodialysis patients.

BACKGROUND: The development of abnormalities in red blood cell (RBC) deformability in patients undergoing hemodialysis remains a major problem, because it is related to peripheral microcirculation, oxygen supply, and various complications in such patients. gamma-Linolenic acid (GLA; 18:3n-6), one of the polyunsaturated fatty acids and a precursor of prostaglandin E(1), is reported to have a favorable effect on the deformability of circulating blood cells in diabetic patients. METHODS: In order to clarify the efficacy of GLA on RBC deformability in 7 patients undergoing maintenance hemodialysis, we examined in a pilot study the changes in the deformability of RBC and the changes in the phospholipid fatty acid composition in both plasma and RBC membrane before and after high-dose oral supplementation with GLA derived from Mucor circinelloides for 12 weeks. RESULTS: Before supplementation, the micropore passage time of RBC suspension, which is an indicator of RBC deformability, in these patients was markedly longer than that in healthy control subjects. After administering GLA, the prolonged passage time of the patients both rapidly and steadily decreased and nearly reached control levels. Light microscopic observations of RBCs using Giemsa stain revealed a decreased number of poikilocytes after supplementation. An analysis of the fatty acid composition before treatment and 8 weeks after starting the treatment showed the dihomo-gamma-linolenic acid (DGLA; 20:3n-6) level in the plasma to have increased (p < 0.05), while the arachidonic acid (AA; 20:4n-6) concentration in the RBC membrane decreased (p < 0.05). The level of DGLA in the RBC membrane, the level of GLA, and the ratio of GLA + DGLA/AA in plasma and RBC membrane did not change significantly; however, these all tended to increase. CONCLUSION: The results of this pilot study indicate that the oral supplementation of GLA extracted from M. circinelloides improves the poor RBC deformability in hemodialysis patients, partly by inducing changes in the composition of fatty acids in plasma and RBC membrane.

Adult↗
PubMed2000

Selenium and glutathione peroxidase mRNA in rat glioma.

The purpose of current study was to determine the step at which dietary selenium (Se) regulates the transcriptional expression of the gene for Se-glutathione peroxidase (Se-GPx) in rat brain and transplanted glioma tissue. Wistar rats were fed a Se-free diet or the same diet supplemented with 0.5, 2.0, and 4.0 mg Se/kg as sodium selenite for at least 3 wk. Then, the rats were transplanted with C6 rat glioma cells into the right frontal lobe parenchyma. All rats were observed for 30 d, then tumor and contralateral brain tissue were excised and divided into three portions for purification of selenium content, for the assay of Se concentration, Se-GPx activity, and for Se-GPx mRNA. Se concentration and Se-GPx activity are increased with Se supplementation both in tumor tissue and contralateral brain tissue, and Se concentration in tumor is higher than that in contralateral brain tissue at each dietary Se content. Se-GPx mRNA of brain and tumor were probed with fragments from a rat Se-GPx cDNA in Northern blot analysis. There was significant differences of Se-GPx mRNA transcription in brain tumor tissue among each dietary group of the Se content, and the steady-state level of Se-GPx mRNA was markedly reduced by Se deficiency. These results suggest that dietary Se exerts its augmenting effect on Se-GPx gene transcription.

Animals↗
PubMed2000

Osteomalacia that became symptomatic 13 years after a total gastrectomy.

A 66-year-old man who underwent a total gastrectomy 13 years ago was admitted to our hospital complaining of severe low back pain and muscle weakness. Biochemical examinations revealed hypocalcemia, hypophosphathemia, low serum 25 (OH) vitamin D and hyperparathyroidism. A chest CT scan revealed pseudofractured ribs, whereas plain X-photography did not show any significant findings. We diagnosed the illness as osteomalacia due to malabsorption. The patient has been receiving oral active vitamin D and calcium, and the pain and serum calcium and phosphate values have improved to the point that he can receive out-patient treatment.

Aged↗
PubMed2000

[Differential influences of bFGF and VEGF on the expression of vascular cell adhesion molecule-1 on human umbilical vein endothelial cells].

A fundamental feature of inflammation includes angiogenesis, adhesion of leukocytes to vascular endothelium, and entry of leukocytes into inflamed tissues. Recent studies have suggested that angiogenesis and cellular adhesion may be mutually linked processes. Both basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been shown to facilitate angiogenesis. However, their roles in the expression of adhesion molecules on the endothelial cells have not been clarified. The current studies therefore examined the effect of bFGF and VEGF on the expression of vascular cell adhesion molecule-1 (VCAM-1) on human umbilical vein endothelial cells (HUVEC) stimulated with tumor necrosis factor alpha (TNF-alpha). HUVEC (1 x 10(4)/well) were incubated in a 96 well microtiter plate with culture medium containing endothelial cell growth supplement (ECGS) for 24 h. After the incubation, culture medium was replaced by ECGS free culture medium with or without TNF-alpha (10 ng/ml), bFGF (10 ng/ml) and VEGF (10 ng/ml), and the culture was further carried out for additional 24 h. The expression of VCAM-1, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) was measured by cell ELISA and the proliferation of HUVEC was measured by MTT colorimetric assay. Soluble VCAM-1 (sVCAM-1) in the supernatants were assessed by ELISA. Although, both bFGF and VEGF supported the proliferation of HUVEC, bFGF, but not VEGF, selectively suppressed the expression of VCAM-1 on HUVEC stimulated with TNF-alpha. The expression of ICAM-1 and E-selectin induced by TNF-alpha was not inhibited by either bFGF or VEGF. In addition, bFGF also decreased the levels of sVCAM-1 in the supernatants of TNF-alpha stimulated HUVEC. The data indicate that bFGF, but not VEGF, suppresses the production of VCAM-1 by HUVEC under stimulation with TNF-alpha. These results therefore suggest that angiogenic cytokines bFGF and VEGF play different roles in the regulation of the expression of adhesion molecules on endothelial cells under inflammation.

Cells, Cultured↗
PubMed2000

Hyaluronic acid inhibits the expression of u-PA, PAI-1, and u-PAR in human synovial fibroblasts of osteoarthritis and rheumatoid arthritis.

OBJECTIVE: Intraarticular administration of hyaluronic acid (HA) has been widely used for the treatment of osteoarthritis (OA). Fibrinolysis is closely related to the pericellular proteolysis involved in inflammation. However, the role of HA in the regulation of fibrinolytic factors is not yet known. We investigated the effect of HA on the pericellular fibrinolytic system of human synovial fibroblasts derived from OA and rheumatoid arthritis (RA). METHODS: Human synovial fibroblasts obtained from OA and RA were cultured in the presence and absence of HA. The antigen of urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured by ELISA, and u-PA activity was evaluated by electrophoretic enzymography. The binding assay of u-PA and the immunohistochemical analysis of u-PA were employed to detect u-PA receptor (u-PAR). RESULTS: HA suppressed the secretion of both u-PA and PAI-1 antigens from the synovial fibroblasts of OA to their conditioned medium. Suppression of u-PA activity in OA synovial fibroblasts was more marked than in those of RA. The u-PA binding assay of OA and RA synovial fibroblasts revealed a single class of binding site: dissociation constant (Kd) 23.7 nM, maximal number of binding sites (Bmax) 3.11x10(4) binding sites/cell; Kd 16.5 nM, Bmax of 9.88x10(4) binding sites/cell, respectively. HA decreased Bmax in fibroblasts of both OA and RA. Immunohistochemical analysis showed that u-PAR was constitutively expressed in both synovial fibroblasts, but if these cells were treated with HA, the decrease of the staining of u-PAR was more pronounced in the cells of RA than in OA. CONCLUSION: Pericellular fibrinolytic activity mediated by the u-PA/u-PAR system and PAI-1 was attenuated by HA in synovial fibroblasts derived from OA and RA. Thus, HA may be a useful agent to inhibit the inflammation of arthritis.

Adjuvants, Immunologic↗
PubMed2000

[Preliminary report: first identification of known mutation in the ryanodine receptor gene in a Japanese malignant hyperthermia pedigree].

In Japan, the rate of Ca-induced Ca release (CICR) using skinned fibers of skeletal muscle has been employed as a diagnostic test for malignant hyperthermia (MH) susceptibility, since most of the typical fulminant MH patients showed an enhancement of CICR rate. Recently the Ca releasing channel responsible for the CICR was reported to be mainly the ryanodine binding Ca protein which was identified as the causative site of MH muscle according to recent genetic studies. Among patients with enhanced CICR rate, one point mutation for Arg 2434 His was recognized in a family. Although this site is related to the central core disease (CCD), this pathological change could not be observed in this patient. This is the first report describing a gene mutation in a MH family identified in Japan.

Asian People↗