Biomedical subjects

N Sakai

Publications and source records attributed to N Sakai.

At least 127 records · Page 7Linked to original sources

PubMed2000

Genistein attenuates peritoneal metastasis of azoxymethane-induced intestinal adenocarcinomas in Wistar rats.

The effects of the soybean isoflavonoid genistein on the development of bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas induced by azoxymethane (AOM) were investigated in male inbred Wistar rats. From the beginning of the experiment, rats were given 10 weekly s.c. injections of AOM (7.4 mg/kg body weight) and s.c. injections of bombesin (40 microg/kg body weight) every other day, and from week 16, s.c. injections of genistein (5 or 10 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and of cancer metastasis to the peritoneum. Although genistein administered at either dose had little or no effect on the enhancement of intestinal carcinogenesis by bombesin or on the location, histologic type, depth of involvement, labeling index, or growth pattern of intestinal cancers, it significantly decreased the incidence of cancer metastasis. Genistein also significantly decreased the incidence of lymphatic vessel invasion of adenocarcinomas, which was enhanced by bombesin. Our findings indicate that genistein attenuates cancer metastasis by inhibiting cancer cell invasion into lymphatic vessels through activities that do not affect the growth of intestinal cancers.

Animals↗

PubMed2000

Suppression by Chai-hu-gui-zhi-tang of the development of liver lesions induced by N-nitrosomorpholine in Sprague-Dawley rats.

The effects of Chai-hu-gui-zhi-tang (TJ-10) on the development of liver lesions induced by N-nitrosomorpholine and on labeling and apoptotic indices were investigated in male Sprague-Dawley rats. Rats were given chow pellets containing 0.5 or 1.0% TJ-10 and, from the beginning of the experiment, were given drinking water containing N-nitrosomorpholine for 8 weeks. Visible white liver nodules, cellular alteration foci, and hepatic foci staining positively for glutathione-S-transferase, placental type, were examined macroscopically or histochemically. In week 16, TJ-10 at both dosages significantly reduced the incidence, and/or number of visible white nodules and hepatic lesions. Quantitative histologic analysis also showed that prolonged feeding of TJ-10 at both dosages significantly reduced the number of hepatic foci positive for glutathione-S-transferase, placental type. Administration of TJ-10 at both dosages also significantly decreased the labeling index of adjacent liver and significantly increased the apoptotic index of adjacent liver but had no significant effect on those of neoplastic lesions. These findings indicate that TJ-10 suppresses the development of liver lesions and suggest that this effect might be related to TJ-10's inhibition of cell proliferation and induction of apoptosis in adjacent hepatocytes.

Animals↗

PubMed2000

Regional cerebral blood flow in male schizophrenic patients performing an auditory discrimination task.

Regional cerebral blood flow (rCBF) was measured in 11 schizophrenic patients amid 10 normal controls, both at rest and while performing an auditory discrimination task. Single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime was used for quantitative evaluation of rCBF. The schizophrenic patients showed greater rCBF in the temporal and parietal regions at rest than the controls, but no abnormalities were found in frontal perfusion. During task performance. on the other hand, the patients showed a reduced frontal rCBF. whereas there was no group difference in rCBF in the temporal and parietal regions. In addition, the left> right hemisphere asymmetries of rCBF observed in the controls during task performance were not present in the patients. although there was no group difference in hemisphere laterality in rCBF at rest. These findings suggest that the employment of a cognitive task for neuroimaging studies is useful for detecting abnormalities of brain activation. such as hypofrontality and altered hemisphere laterality. in patients with schizophrenia.

Adult↗

PubMed2000

Performance of bent-crystal monochromators for high-energy synchrotron radiation.

Two monochromators for high-energy synchrotron radiation have been studied at the elliptical multipole wiggler beamline BL08W of SPring-8. Both monochromator crystals are bent and indirectly water-cooled. In the 100 keV monochromator an efficient cooling scheme is employed. A monochromatic beam is successfully focused using new benders for the 100 keV and 300 keV monochromators. Measured radii of curvature of the bent crystal agree qualitatively with calculation.

Journal Article↗

PubMed2000

DNA fragmentation in the CA2 sector of gerbil hippocampus following transient forebrain ischemia.

It has been reported that following transient forebrain ischemia in the gerbil, "delayed neuronal death" and "reactive change" occur in hippocampal CA1 and CA2 sectors, respectively. In the present study, using the gerbil transient forebrain ischemia model, we examined brain sections after various recirculation periods and demonstrated, employing the in situ nick-end labeling (TUNEL) method, a nuclear DNA fragmentation in the damaged CA2 neurons.

Animals↗

PubMed2000

Effect of cyclic adenosine 3',5'-monophosphate and protein kinase A on ligand-dependent transactivation via the vitamin D receptor.

We examined the effects of cyclic adenosine 3',5'-monophosphate (cAMP) and protein kinase A (PKA) on the ligand-dependent transactivation mediated via the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) receptor (VDR). A human VDR expression plasmid was transfected into HeLa, Saos-2 and MG63 cells with a luciferase reporter gene construct containing the vitamin D responsive element. With the addition of 0.5 mM 8 bromo-cAMP, the response to 1,25(OH)2D3 was suppressed to 61 and 78% in the HeLa and Saos-2 cells, respectively. The suppressive effect of 8 bromo-cAMP was observed without the introduction of the VDR expression plasmid in the MG63 cells. In the HeLa cells the co-expression of PKA reduced the ligand-inducible transactivation to 61% and the fold induction by 1,25(OH)2D3 to 89% of that without PKA. The CREB binding protein (CBP) was recently reported to integrate the intracellular signals via the cAMP/PKA cascade and nuclear hormone receptors. However, the suppressive effect of cAMP was not influenced by the co-expression of CBP. Lastly, we introduced point mutations at possible PKA phosphorylation sites into the VDR expression vector at serine-172 and threonine-175, but both mutant receptors still exhibited reduced transactivation with the co-expression of PKA. These results indicate that the phosphorylation of proteins other than the VDR may also be involved in the inhibitory effect mediated by the cAMP/PKA cascade.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

Global experience in cervical carotid artery stent placement.

The purpose of this article is to review and update the current status of carotid artery stent placement in the world. Surveys to major interventional centers in Europe, North and South America, and Asia were initially completed in June 1997. Subsequent information from these 24 centers in addition to 12 new centers has been obtained to update the information. The survey asked the various questions regarding the patients enrolled, procedure techniques, and results of carotid stenting, including complications and restenosis. The total number of endovascular carotid stent procedures that have been performed worldwide to date included 5,210 procedures involving 4,757 patients. There was a technical success of 98.4% with 5,129 carotid arteries treated. Complications that occurred during the carotid stent placement or within a 30-day period following placement were recorded. Overall, there were 134 transient ischemic attacks (TIAs) for a rate of 2.82%. Based on the total patient population, there were 129 minor strokes with a rate of occurrence of 2.72%. The total number of major strokes was 71 for a rate of 1.49%. There were 41 deaths within a 30-day postprocedure period resulting in a mortality rate of 0.86%. The combined minor and major strokes and procedure-related death rate was 5.07%. Restenosis rates of carotid stenting have been 1.99% and 3.46% at 6 and 12 months, respectively. The rate of neurologic events after stent placement has been 1.42% at 6-12-month follow-up. Endovascular stent treatment of carotid artery atherosclerotic disease is growing as an alternative for vascular surgery, especially for patients that are high risk for standard carotid endarterectomy. The periprocedure risks for major and minor strokes and death are generally acceptable at this early stage of development and have not changed significantly since the first survey results. Cathet. Cardiovasc. Intervent. 50:160-167, 2000.

Carotid Stenosis↗

PubMed2000

ras p21 Isoprenylation inhibition induces flat colon tumors in Wistar rats.

PURPOSE: The effect of pravastatin, an inhibitor of ras p21 isoprenylation, on the gross type of colon tumors induced by azoxymethane was investigated in Wistar rats. METHODS: Rats received ten weekly subcutaneous injections of 7.4 mg/kg body weight of azoxymethane and intraperitoneal injections of 10 or 20 mg/kg body weight of pravastatin every other day until the end of the experiment at Week 45. RESULTS: Administration of pravastatin at both dosages had no significant effect on the incidence of colon tumors but significantly increased the incidence of rats with adenomas only. In contrast to the elevated adenomas in control rats, flat adenomas were significantly more prevalent in rats given pravastatin. Pravastatin at both doses significantly decreased the labeling index, but not the apoptotic index, of elevated adenomas, whereas it significantly decreased the labeling index but increased the apoptotic index of flat adenomas. Administration of pravastatin at both dosages also significantly decreased the amounts of membrane-associated ras p21 in colon tumors. CONCLUSIONS: These findings suggest that the ras oncogene may be closely related to the development of adenocarcinomas from adenomas and the development of elevated or polypoid tumors of the colon.

Adenocarcinoma↗

PubMed2000

Chordoid meningioma.

Chordoid meningioma is a relatively rare variant that is often associated with peritumoral lymphoplasmacellular infiltration causing Castleman syndrome (CS). We present a 44-year-old woman with chordoid meningioma not associated with CS. The patient presented with epilepsy and right hemiparesis (Todd's palsy) on admission. The radiological findings revealed an extraaxial mass lesion in the premotor cortex. They were compatible with a preoperative diagnosis of meningioma. No physical abnormalities related to CS were detected. A left frontal craniotomy was performed. The tumor surface was gelatinous, and it was totally resected with the attached dura mater (Simpson grade I). The patient had an uneventful recovery, and her seizures subsided. The pathological findings of the specimens revealed nests and cords of spindle and epithelioid cells with abundant myxoid matrix, mimicking the features of chordoma. On the basis of radiological, immunohistochemical, and electron microscopic findings, chordoid meningioma was verified, and a review of the literature was performed.

Adult↗

PubMed2000

High production of SPARC/osteonectin/BM-40 in mouse metastatic B16 melanoma cell lines.

Production of SPARC/osteonectin/BM-40 was determined in mouse B16 melanoma clones BL6 and F10 (high metastatic) and F1 (low metastatic). SPARC was produced greater amount in BL6 and F10 than in F1 cells, showing a good agreement with their metastatic potentials. Moreover, SPARC production was not influenced by culture pH, even in the acidic conditions (= pH 5.9). Although tumor tissues show often low pH due to excessive amount of acidic metabolites such as lactate, most studies have been done in neutral pH. High SPARC production in the acidic medium, therefore, is thought to be an important potential for tumor invasive behaviour.

Animals↗

PubMed2000

Secondary tethered cord syndrome in spinal dysraphism.

Secondary tethered cord syndrome following initial repair for spinal dysraphism is an important area of interest. In this study, 32 cases with spinal dysraphism in the lumbosacral region were enrolled, in whom radical repair with autologous material had been carried out in the early stage soon after birth. During the follow-up period of up to 19 years 10 months, surgery was considered to be indicated in 2 of the 8 lipomeningocele cases and in 6 of the 24 meningocele and meningomyelocele cases, because of the presence of tethered cord syndrome 4-19 years after the primary operation. In all 8 of these cases, MR imaging demonstrated tethered spinal cord in the form of low conus medullaris. In 6 of the 8 operated cases surgery was followed by improvement of the spinal neurological deterioration. According to our experience, early untethering for secondary tethered cord syndrome is essential. In addition, since the complications of Silastic duraplasty at untethering were all minor and the operative outcome was satisfactory, the use of silicone rubber sheeting as a dural substitute might be recommended to prevent adhesion of the spinal cord.

Adolescent↗

PubMed2000

Expression of CD44, vascular endothelial growth factor, and proliferating cell nuclear antigen in severe venous invasional colorectal cancer and its relationship to liver metastasis.

The first step in liver metastasis is venous invasion by cancer cells from the primary tumor. However, even among cases where the histology shows extensive venous invasion by the primary tumor, we sometimes find cases without synchronous liver metastases. As a result, there is a strong possibility that, besides the established causes of colorectal cancer and that of cancer cells invading the veins, some other important causes for liver metastasis must exist. We investigated the expression rates of CD44, proliferating cell nuclear antigen (PCNA), and vascular endothelial growth factor (VEGF) in 28 primary colorectal tumors using immunohistological techniques, and examined an association with liver metastasis. Cases that are strongly positive for CD44 or PCNA have a higher rate of synchronous liver metastases than cases with either no expression or a low expression. We could find no correlation between the VEGF expression and synchronous liver metastasis. In cases with severe venous invasion, VEGF is not correlated with liver metastasis whereas CD44 and PCNA are correlated with liver metastasis. In cases where severe venous invasion is histologically observed, an immunohistochemical analysis for CD44 and PCNA should be done to assess the likelihood of liver metastases.

Adult↗

PubMed2000

Mutation analysis of two Japanese patients with Fanconi-Bickel syndrome.

Fanconi-Bickel syndrome (FBS), or glycogen storage disease type XI, is a rare autosomal recessive disorder characterized by hepatorenal glycogen accumulation, Fanconi nephropathy, and impaired utilization of glucose and galactose. Recently, this disease was elucidated to link mutations in the glucose transporter 2 (GLUT2) gene. Only three mutations in three FBS families have been reported. Therefore, it is important to elucidate mutations in the GLUT2 gene in FBS by answering the question of whether the syndrome is a single gene disease. In this report, we describe two patients in two unrelated families clinically diagnosed with FBS. No mutation in the entire protein coding region of the GLUT2 gene was detected in patient 1, which suggested that no mutation existed in the GLUT2 gene, or that some mutations had affected the expression of the GLUT2 gene. In patient 2, a novel homozygous nonsense mutation (W420X, Trp at codon 420 to stop codon) was detected. These results support the correlation between GLUT2 gene mutation and FBS syndrome. However, many patients must be analyzed to determine whether other genes are involved in FBS.

Adult↗

PubMed2000

Diagnosis of the extent of gastric cancers by a new endoscopic ultrasonic tactile sensor.

BACKGROUND: Because gastrointestinal cancers are generally firm, the presence and extent of a tumor can be assessed by touch during surgery. However, an objective scale for evaluating tissue hardness does not exist. We developed a new instrument, the endoscopic ultrasonic tactile sensor, that allows objective evaluation of hardness. In this study the usefulness of this device for diagnosis of the extent of gastric cancers was evaluated. METHODS: Twenty-three patients with depressed or ulcerated early gastric cancers and 7 patients with active or healed gastric ulcers underwent endoscopic examination with the ultrasonic tactile sensor before gastrectomy. RESULTS: Gastric cancers were significantly harder than normal mucosa or gastric ulcers. The histologic type of gastric cancer and the presence of ulceration did not affect tumor hardness and mucosal cancers could not be differentiated from submucosal or deeper cancers. CONCLUSIONS: This new ultrasonic tactile sensor was useful for endoscopic diagnosis of the extent of gastric cancers.

Endosonography↗

PubMed2000

Molecular mechanisms, lipoprotein abnormalities and atherogenicity of hyperalphalipoproteinemia.

Hyperalphalipoproteinemia (HALP) is caused by a variety of genetic and environmental factors. Among these, plasma cholesteryl ester transfer protein (CETP) deficiency is the most important and frequent cause of HALP in the Asian populations. CETP facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein (apo) B-containing lipoproteins, and is a key protein in the reverse cholesterol transport system. The deficiency of CETP causes various abnormalities in the concentration, composition, and function of both HDL and low density lipoprotein (LDL). The significance of CETP in terms of atherosclerosis had been controversial. However, the in vitro evidence showed large CE-rich HDL particles in CETP deficiency are defective in cholesterol efflux. Similarly, scavenger receptor BI (SR-BI) knockout mice show a marked increase in HDL-cholesterol but accelerated atherosclerosis in atherosclerosis-susceptible mice. Recent epidemiological studies in Japanese-Americans and in Omagari area where HALP subjects with the intron 14 splicing defect of CETP gene are markedly frequent, have demonstrated an increased incidence of coronary atherosclerosis in CETP-deficient patients. Thus, CETP deficiency is a state of impaired reverse cholesterol transport which may possibly lead to the development of atherosclerosis. The current review will focus on the molecular mechanisms and atherogenicity of HALP, especially CETP deficiency.

Animals↗

PubMed2000

Non-adhesive cyanoacrylate as an embolic material for endovascular neurosurgery.

Endovascular neurosurgery is now becoming available as one of strategies for the treatment of cerebro-spinal arterio-venous malformations and aneurysms. For this treatment, a microcatheter is advanced into or close to a lesion and then an embolic material is administered through it to obliterate the lesion. N-butyl-2-cyanoacrylate (NBCA) has preferentially been used as an embolic material in Europe and America. However, its exceptionally strong adhesive force sometimes causes adhesion between the tip of the microcatheter and the artery. In this study, a new non-adhesive cyanoacrylate, isostearyl-2-cyanoacrylate (ISCA), was developed. It carries a long hydrophobic side isostearyl group with lower reactivity and adhesion than other cyanoacrylates. Its polymerization rate is, however, too low to obliterate a vascular lesion with a rapid blood flow. To increase the polymerization rate. ISCA was mixed with NBCA. As a result, the adhesive force of the mixture became extremely low, compared with that of NBCA. The viscosity of the mixture was low enough to allow its' use as an embolic material. Tissue reactions against the mixture was milder than those against NBCA. Radio-angiography became possible by mixing further with Lipiodol. The evaluation of this new embolic material with a rabbit renal artery showed that the obliteration effect of the mixture of ISCA and NBCA was excellent to use as an embolic material for clinical applications.

Animals↗

PubMed2000

Involvement of the actin cytoskeleton in the regulation of serotonin transporter (SET) activity: possible mechanism underlying SET regulation by protein kinase C.

Our previous report has revealed that PKC activation by 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited the uptake activity of serotonin transporter (SET), via an indirect mechanism unknown, but not likely via direct phosphorylation of SET by PKC (Sakai et al., 1997. J. Neurochem. 68, 2618-2624). To elucidate whether PKC can directly phosphorylate SET in vivo, FLAG-tagged SET (FLAG-SET) was expressed in COS-7 cells and the TPA-induced incorporation of (32)P into immunoprecipitated FLAG-SET was examined. PKC activation with TPA caused no phosphorylation of FLAG-SET expressed in COS-7 cells. On the other hand, morphological change associated with the disruption of filamentous actin (F-actin) was seen in TPA-treated COS-7 cells. Therefore, we studied the effects of cytochalasin D, an inhibitor of actin polymerization, on the uptake activity of the serotonin transporter (SET) to elucidate whether the actin cytoskeleton modulates the SET uptake activity. The treatment with cytochalasin D inhibited the uptake activity of both native and recombinant SET in a concentration-dependent manner. Eadie-Hofstee analysis revealed that cytochalasin D down-regulated the recombinant SET uptake activity by reducing the V(max), but not the K(m), mimicking the result observed in TPA-induced inhibition of SET activity (Sakai et al., 1997. J. Neurochem. 68, 2618-2624). The cytochalasin D-induced inhibition of SET activity was partially, but significantly, reversed by jasplakinolide, a cell permeable stabilizer of F-actin, whereas TPA-induced inhibition of SET activity was not reversed by jasplakinolide. To elucidate whether the subcellular localization of SET was changed in response to cytochalasin D or TPA, we expressed the SET fused with the green fluorescent protein (SET-GFP) in COS-7 cells and observed the subcellular distribution of SET-GFP under a confocal laser scanning fluorescent microscope. Neither cytochalasin D nor TPA markedly changed the SET-GFP cellular localization, although these drugs caused morphological change in the GFP-transfected COS-7 cells. In addition, SET activity was not altered by the treatment with either colchicine, an inhibitor of microtubule polymerization, or taxol, a stabilizer of microtubule polymerization. These results suggest that the SET uptake activity was regulated by the state of the actin cytoskeleton and that TPA exerts its inhibitory action on SET activity, in part, via disruption of F-actin and subsequent morphological change in cells.

Actins↗

PubMed2000

The influence of weakness in the vastus medialis oblique muscle on the patellofemoral joint: an in vitro biomechanical study.

OBJECTIVE: Investigation of the influence of weakness in the vastus medialis oblique muscle on patellar tracking. DESIGN: In vitro biomechanical study. BACKGROUND: Currently, the influence of weakness in the vastus medialis oblique muscle on patellar tracking has not been well understood. METHODS: Seven human cadaveric knees were used. The direction of loading forces in the rectus femoris/vastus intermedius, vastus medialis oblique, and the vastus lateralis muscles was decided by the muscle alignment of each cadaver knee measured at the time of dissection. The loads used were 60 N in the rectus femoris, 50 N in the vastus lateralis, and 40 N in the vastus medialis oblique, according to the ratio calculated from the cross-sectional study. The weakness of vastus medialis oblique was simulated at 30 N (75%), 20 N (50%), 10 N (25%), and 0 N (0%), and the patellar position was measured for each condition using a magnetic 3 Space Tracker System. The influence of weakness in the vastus medialis oblique muscle on patellar position was investigated with seven cadaver knees using a magnetic 3 Space Tracker System. RESULTS: At 0 degrees and 15 degrees of knee flexion, 75%, 50%, 25% and 0% of the normal vastus medialis oblique muscle led to a significant difference in lateral patellar shift compared to the normal (P<0.05). CONCLUSIONS: Weakness of the vastus medialis caused the patellar lateral shift at 0 degrees and 15 degrees of knee flexion. RELEVANCE: Weakness of the vastus medialis is thought to be an important factor causing patellar subluxation and dislocation. Understanding the relationship between the vastus medialis weakness and patellar tracking will be useful in diagnosis, treatment and prevention of patellar subluxation and dislocation.

Analysis of Variance↗