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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 271 records · Page 15Linked to original sources
PubMed1999

Comparison of p53, Ki-67, and CD44v6 expression between primary and matched metastatic lesions in ovarian cancer.

OBJECTIVE: Many studies have demonstrated that clinically evident tumor cells already carry multiple genetic alterations and further accumulation of genetic alteration causes tumor progression which plays a role in metastasis. Therefore, it could be expected that malignant potential in the metastatic site is more aggressive than that in the primary site. Using several immunohistochemical markers (p53, Ki-67, and CD44v6), we investigated an alteration of malignant potential. METHODS: We immunohistochemically examined expression of p53, Ki-67, and CD44 in primary and metastatic lesions of ovarian cancer. Fifty-six samples of primary lesions and matched metastatic sites from 56 patients with primary epithelial ovarian cancers were included in this study. RESULTS: In 16 cases (28%), the histological grade of the metastatic lesion increased. This difference was statistically significant (P = 0.0232). In 16 cases (28%), the expression of p53 increased in the metastatic lesions, in 5 pairs from negative to positive, whereas the case decrease in the metastatic lesions was only 1. This difference was statistically significant (P = 0.0046). There was no significant difference in Ki-67 labeling indices and expression of CD44v6 between the primary and matched metastatic lesions. The degree of p53 expression in the metastatic lesions significantly correlated with disease-free survival (P = 0.0482), whereas that in the primary lesions did not. Moreover, high p53 expression in the metastatic lesions significantly correlated with disease-free survival in multivariate analysis. CONCLUSIONS: The p53 expression in metastatic lesions may reflect an aggressive biologic behavior in ovarian cancer.

Adenocarcinoma↗
PubMed1999

Overexpression of salt-tolerant glutaminase from Micrococcus luteus K-3 in Escherichia coli and its purification.

A high-expression plasmid, pKSGHE3-1, containing the salt-tolerant glutaminase (EC 3.5.1.2) from marine bacterium Micrococcus luteus K-3 was constructed. pKSGHE3-1 was made by inserting the DNA fragment (1.43 kb) containing the structural gene synthesized by polymerase chain reaction into the downstream region of the tac promoter of expression vector pKK223-3. The translational start codon was located 10 bases downstream of the Shine-Dalgarno sequence (AGGA) of pKK223-3. Escherichia coli JM109 transformed with pKSGHE3-1 exhibited more than 190-fold higher glutaminase activity than M. luteus K-3 under optimal culture conditions. The enzyme was purified to homogeneity through three column chromatography steps with a final yield of 17.1%. The recombinant enzyme showed the same enzymatic properties, including salt tolerance, as those of M. luteus K-3. This glutaminase expression system allows the production of sufficient quantities of glutaminase for basic structure-function studies including chemical modification and future X-ray crystallization analysis.

Bacterial Proteins↗
PubMed1999

Correlation of the therapeutic effect of activated tumor-draining lymph node cells with specific interferon-gamma production in vitro.

It has been established that lymphocytes obtained from tumor-draining lymph nodes (DLN) are sensitized to the tumor antigen in vivo. Moreover, after being activated in vitro, these cells can be utilized for adoptive immunotherapy. In the present study, DLN cells, obtained from C57BL/6 mice with fibrosarcoma (MC-1), were activated and expanded with anti-CD3 monoclonal antibody followed by culture with recombinant interleukin-2 (rIL-2). These CD4- CD8+ CD25+ CD44+ T-cells showed specific antitumor efficacy to the pulmonary micrometastases of an autologous tumor, against which lymphokine-activated killer cells were ineffective; however, they did not show cytolytic activity in vitro. The supernatant, obtained by coculturing the activated DLN cells with MC-1 cells, exhibited the specific production of interferon-gamma (IFN-gamma) which was enhanced by rIL-2. The therapeutic effect of the activated DLN cells correlated with the specific IFN-gamma production better than with the cytolytic activity.

Animals↗
PubMed1999

Pharmacological profile of MS-377, a novel antipsychotic agent with selective affinity for sigma receptors.

RATIONALE: MS-377 ((R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]me thyl-2- pyrrolidinone L-tartrate) was discovered as a new chemical entity with affinity for sigma receptors and without affinities for dopamine receptors. OBJECTIVE: In the present study, we examined the antipsychotic profile of MS-377 in several in vitro and in vivo experiments. METHODS: As in vitro assays, radioligand binding assays for sigma 1, sigma 2, D2 and 5-HT2 receptors were performed. As in vivo animal models, the effects of MS-377 on several behavioral models induced by phencyclidine (PCP), (+)-N-allylnormetazocine (NANM), apomorphine (Apo) and 5-hydroxytryptamine (5-HTP) were evaluated. All assay systems were conducted using the clinically active antipsychotic agents as reference standards. RESULTS: MS-377 displaced ligand bound to sigma 1 receptors in vitro. However, no such displacement was observed at sigma 2 or 5-HT2 receptors in vitro, or at D2 receptors either in vitro or in vivo. In behavioral studies, MS-377 inhibited both NANM- and PCP-induced head-weaving at low doses in mice and rats, whereas antipsychotic agents used in the present study were only effective against NANM-induced head-weaving behavior in mice. In addition, MS-377 antagonized Apo-induced climbing behavior and 5-HTP-induced head-twitching behavior in mice. MS-377 was inactive in models of extrapyramidal side effect (EPS) liability such as prevention of Apo-induced stereotypy and induction of catalepsy in rats. CONCLUSION: The present study demonstrated that MS-377 had not only anti-PCP activity but also anti-dopaminergic and anti-serotonergic activities in vivo, without acting directly through D2 or 5-HT2 receptors. Therefore, MS-377 could be a novel antipsychotic agent with clinical efficacy for overall symptoms of schizophrenia including its negative symptoms and without EPS liability.

Amisulpride↗
PubMed1999

Imaging of calvarial eosinophil granuloma.

We reviewed the imaging of four pathologically proven calvarial eosinophil granulomas. The diameter of the lesions ranged from 13 to 40 mm; three were biconvex, but the other had a collar-stud appearance. Two lesions were in the frontal and two in the parietal bone. On bone-window CT, a bevelled edge was seen in three cases and button sequestration in one, but no sclerotic rim was shown. Although one lesion had a low-density area, the lesions were slightly denser than grey matter. They were isointense with grey or white matter on T1-weighted MRI and gave heterogeneous high signal on proton-density and T2-weighted images. All enhanced markedly, with a less strongly enhancing portion within them. A tail of dural enhancement and reactive change in the overlying galea or temporal muscle were seen in all cases.

Bone Diseases↗
PubMed1999

Bilateral optic neuritis in a child diagnosed with Gd-enhanced MR imaging using fat-suppression technique.

A 4-year-old boy developed bilateral optic neuritis. Although precise neuro-ophthalmological evaluation was difficult, the diagnosis was made with gadolinium-enhanced MR imaging using fat-suppression technique in the initial stage of the disease. Enhancement and enlargement of the intraorbital and intracanalicular optic nerve were demonstrated bilaterally as well as protrusion of the optic nerve head. The disease responded dramatically to intravenous steroid therapy. The etiologies in children usually differ from those in adolescent and adult patients.

Adipose Tissue↗
PubMed1999

Upright posture blunts postprandial splanchnic hyperemia in patients with cirrhosis and portal hypertension.

The aim of this study was to compare postprandial hemodynamic changes observed during assumption of the recumbent posture and upright posture in patients with cirrhosis and portal hypertension. Eleven patients with cirrhosis and portal hypertension were studied. Echo-Doppler examinations were performed to measure flow volume in the portal vein (PV), superior mesenteric artery (SMA), and splenic artery (SA) in the fasting condition. Collateral blood flow was indirectly calculated by determining the difference between the sum of SMA, SA, and PV blood flows. After these measurements were done, each patient received a standardized liquid meal and was then randomly assigned to either maintain supine or upright posture, in a crossover design, on 2 different days (recumbent day and upright day). On each study day, the above-mentioned measurements were repeated 30 min and 60 min after the meal. PV blood flow increased significantly after the meal on the recumbent day (P < 0.01) but not on the upright day (P = 0.78). Although there were significant postprandial increases in SMA blood flow on both study days (P < 0.01, P < 0.01), the effect was less pronounced on the upright day than on the recumbent day (P < 0.01). Postprandial SA blood flow showed no change on the recumbent day (P = 0.64), but decreased significantly on the upright day (P < 0.01). The calculated postprandial collateral blood flow increased significantly on the recumbent day (P < 0.05), but showed no change on the upright day (P = 0.53). These results suggest that the upright posture blunts postprandial splanchnic hyperemia in patients with cirrhosis and portal hypertension.

Aged↗
PubMed1999

Impact of tranilast on restenosis after coronary angioplasty: tranilast restenosis following angioplasty trial (TREAT).

BACKGROUND: Tranilast is an antiallergic drug that suppresses the release of cytokines such as platelet-derived growth factor, transforming growth factor-beta1, and interleukin-1beta and prevents keloid formation after skin injury. Treatment with this drug reduced the restenosis rate after percutaneous transluminal coronary angioplasty in a preliminary study. METHODS AND RESULTS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial. A total of 255 patients with 289 lesions were randomly assigned to treatment with the oral administration of 600 mg/d tranilast, 300 mg/d tranilast, or a placebo for 3 months after successful angioplasty. Angiographic follow-up was done at 3 months, and a clinical follow-up examination was performed at 12 months. Two hundred ten (72.7%) lesions of 188 (73.7%) of the patients met the criteria and were eligible for the assessment of restenosis. The restenosis rates defined as >/=50% loss of the initial gain were 14.7% in the 600 mg/d tranilast group, 35.2% in the 300 mg/d tranilast group, and 46.5% in the placebo group (P <. 0001 for 600 mg/d tranilast vs placebo). The restenosis rates defined as percent diameter stenosis of >/=50% at follow-up were 17. 6% in the 600 mg/d tranilast group, 38.6% in the 300 mg/d tranilast group, and 39.4% in the placebo group (P =.005 for 600 mg/d tranilast vs placebo). CONCLUSIONS: The oral administration of 600 mg/d of tranilast for 3 months markedly reduced the restenosis rate after percutaneous transluminal coronary angioplasty.

Administration, Oral↗
PubMed1999

Expression of platelet-derived endothelial cell growth factor and its potential role in up-regulation of angiogenesis in scarred kidneys secondary to urinary tract diseases.

The mechanism of neovascularization secondary to renal interstitial fibrosis is not well understood. Platelet-derived endothelial cell growth factor (PD-ECGF) is known to promote angiogenesis. We examined the expression of PD-ECGF immunohistochemically in 9 normal kidneys and 26 scarred kidneys secondary to urinary tract diseases. To estimate up-regulation of angiogenesis, microvessels were counted by immunostaining endothelial cells for CD34. Immunostaining of PD-ECGF was observed in most Bowman's capsules, occasional tubules, and some interstitial mononuclear cells in normal kidneys. A remarkable increase of immunostained PD-ECGF was found in the tubules and interstitial mononuclear infiltrates in the scarred kidneys. The predominant cell type in the infiltrate was T cells (CD3(+)). The microvessel count and mean numbers of PD-ECGF(+) tubular and interstitial mononuclear cells increased with increasing interstitial fibrosis. A significant correlation was noted between microvessel count and the number of PD-ECGF(+) tubular cells (P = 0.0002) or PD-ECGF(+) interstitial mononuclear cells (P < 0.0001). Immunostaining of endogrin, a marker of endothelial proliferation, increased in the microvessels located in the fibrotic interstitial spaces. These results suggest that angiogenesis may play a critical role in the progression of tubulointerstitial injuries and that up-regulation of PD-ECGF may contribute to neovascularization.

Adolescent↗
PubMed1999

Hepatic arterial infusion chemotherapy using percutaneous catheter placement with an implantable port: assessment of factors affecting patency of the hepatic artery.

OBJECTIVE: To assess the factors affecting patency of the hepatic artery during hepatic arterial infusion chemotherapy (HAIC) with an implantable port system inserted percutaneously. PATIENTS AND METHODS: Ninety patients with malignant hepatic tumours were given HAIC using percutaneous catheter placement. An end-hole catheter was inserted into the hepatic artery (conventional method) in 41 patients. An end-closed and side-hole catheter was used in 49 patients, in which the catheter tip was fixed in the gastroduodenal artery and the side hole was placed in the common hepatic artery (fixed catheter-tip method). The patency of the hepatic artery was evaluated with computed tomography (CT) arteriography using the implantable port system and angiography. Then, the factors affecting hepatic arterial patency were analysed. RESULTS: Hepatic arterial occlusion was observed in 15 patients (17%). The overall patency of the hepatic artery was 86.9%, 78.4% and 51.5% at 6 months, 1 year and 2 years, respectively. The patency rate of the hepatic artery was significantly higher in patients with catheter placement using fixed catheter-tip method than those using conventional method (P = 0.01), and in patients without transcatheter arterial chemoembolization (TACE) prior to catheter placement than those with prior TACE (P = 0.01). When the variables affecting patency of the hepatic artery were studied together by multivariate analyses, the important factors were the method of catheter placement and the presence or absence of prior TACE. CONCLUSION: We consider that it is important for long-term patency of the hepatic artery during HAIC to use fixed catheter-tip method for percutaneous catheter placement instead of conventional method, and to select patients without prior TACE.

Adult↗
PubMed1999

Human parathyroid hormone (1-34) increases urinary excretion of lysosomal enzymes in rats.

The kidney is the major target of parathyroid hormone (PTH), and PTH influences the urinary excretion of calcium, phosphate and hydrogen ions. It was previously reported that the urinary, excretion of N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme, transiently increases after human PTH (hPTH) (1-34) infusion in normal subjects and idiopathic hypoparathyroidism patients, but not in pseudohypoparathyroidism type I patients. Here we report that intravenous infusion of hPTH(1-34) to rats transiently increased the urinary excretion of various lysosomal enzymes, such as beta-glucuronidase and acid phosphatase as well as NAG. However, it did not affect the urinary excretion of tubular brush border membrane enzymes, i.e. alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl transpeptidase. Human PTH(1-34) dose-dependently increased the urinary excretion of NAG in rats with a peak at 30 min, which returned to a baseline within 60 min. The increase in the urinary NAG excretion caused by hPTH(1-34) positively correlated with the increase in the urinary cAMP excretion (r = 0.844, p < 0.01), and infusion of dibutyryl cAMP at a dose of 20 mg/kg similarly increased the urinary excretion of NAG. These results suggested that the increase in the urinary excretion of lysosomal enzymes caused by hPTH(1-34) may be a functional response to hPTH(1-34) occurring in the renal tubules via PTH signaling pathway.

Acetylglucosaminidase↗
PubMed1999

Parallel neural networks for learning sequential procedures.

Recent studies have shown that multiple brain areas contribute to different stages and aspects of procedural learning. On the basis of a series of studies using a sequence-learning task with trial-and-error, we propose a hypothetical scheme in which a sequential procedure is acquired independently by two cortical systems, one using spatial coordinates and the other using motor coordinates. They are active preferentially in the early and late stages of learning, respectively. Both of the two systems are supported by loop circuits formed with the basal ganglia and the cerebellum, the former for reward-based evaluation and the latter for processing of timing. The proposed neural architecture would operate in a flexible manner to acquire and execute multiple sequential procedures.

Animals↗
PubMed1999

Effect of transcatheter arterial chemoembolization on kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma.

BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) may have deleterious effect on the kidney in patients with cirrhosis and hepatocellular carcinoma. The aim of the study was to test this hypothesis. METHODS: Twenty-four patients with cirrhosis and hepatocellular carcinomas were included. They consisted of 16 patients undergoing a single TACE and eight patients undergoing diagnostic angiography. Doppler ultrasonography was used to measure hepatic artery pulsatility index (HA-PI) and renal artery pulsatility index (RA-PI) before and 1 day and 10 days after the procedure. Similarly, kidney function was assessed by measuring creatinine clearance. In addition, plasma renin activity, noradrenaline, and endothelin-1 were also measured. RESULTS: In patients receiving diagnostic angiography, no significant changes in HA-PI were observed after the procedure. In contrast, HA-PI increased significantly 1 day after the procedure (19%, p<0.01) in patients undergoing TACE, although it returned to baseline value 10 days after the procedure. In patients undergoing diagnostic angiography, no significant changes in RA-PI were observed after the procedure. Similarly, no detectable changes in RA-PI were noted in patients undergoing TACE. A transient small reduction in creatinine clearance was noted after the procedure in patients undergoing diagnostic angiography (-12%, p<0.05) and in those undergoing TACE (-11%, p<0.05). However, the effect was similar in the two groups (two-way ANOVA, p=0.72). No significant changes in plasma renin activity, noradrenaline, and endothelin-1 were observed after either diagnostic angiography or TACE. CONCLUSIONS: These results suggest that TACE per se has no deleterious effect on the kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma.

Aged↗
PubMed1999

Fatty acid composition of choline and ethanolamine glycerophospholipid subclasses in heart tissue of mammals and migratory and demersal fish.

The distribution and fatty acid composition of cardiac choline and ethanolamine glycerophospholipids in both migratory and demersal fish and bovine and pig were determined. Phospholipid contents (mg/g heart) were 4.7-9.4 in demersal fish, 14.0-16.5 in migratory fish, and 16.8-20.6 in mammals. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were the major components in the phospholipid fraction. Diacyl forms represented 50.2-88.1% of PC in all animals, while plasmalogens comprised 47.0% in bovine, 8.2% in pig and 6.2-7.2% in four species of fish. In PE, plasmalogens varied from 45.0% in bovine and 57.9% in pig to 26.1-29.7% in fish. This glycerophospholipid subclass was identified as containing higher proportions of polyunsaturated fatty acids (PUFAs; 20:4, 20:5, and 22:6) than found in alkylacyl- and diacyl-glycerophospholipids. Qualitative and quantitative differences were found in PE-plasmalogen between land mammals and fish, especially with regard to n-3 fatty acid composition, but no significant difference was noted between migratory and demersal fish.

Animals↗
PubMed1999

Effects of phospholipids on growth of Chinese hamster ovary cells in serum-free media.

The effects of phosphatidic acid (PA) and lysophosphatidic acid (LPA) dispersed in serum-free media on the growth of Chinese hamster ovary (CHO) cells were investigated. After cells were incubated in serum-free media supplemented with PA or LPA for 3 d, the cellular growth was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Supplementing PA from egg yolk lecithin to basal synthetic media such as alpha-MEM (minimum essential medium, alpha modification) markedly promoted the growth of CHO cells. PA from egg yolk lecithin also enhanced the cell growth in a serum-free medium containing insulin and transferring. When PA analogues with different acyl chains of C14-18 were compared, PA with unsaturated acyl chains, dioleoyl-PA (C18: 1), was most effective for stimulating the growth of CHO cells. Similar results were obtained when LPA was examined. These results suggest that PA and LPA, especially those with unsaturated acyl chains, are promising growth-promoting supplements for use as constituents in a low-protein serum-free medium.

Journal Article↗
PubMed1999

Mutational analysis of human immunodeficiency virus type 1 vif gene.

Mutations were introduced into scattered regions of the HIV-1 vif gene. The twelve in-frame mutants generated were evaluated for the replication potentials in cells by transfection and infection experiments. All the mutants produced a normal level of progeny virions upon transfection, indicating the absence of the late function of HIV-1 Vif protein. The infectivity of virions obtained was monitored in H9 cells, which are non-permissive for HIV-1 without the Vif function. Most of the mutations in various parts of the vif gene, including those in the three conserved regions among HIV/SIV, abrogated the infectivity of the virus. In contrast, the cysteine residue at position 133, which was reported to be critical for viral infectivity, was found not to be essential. In addition, the C-terminal eight amino acid residues (185-192) in the Vif protein could be deleted with no effects on viral growth potential.

Gene Products, vif↗
PubMed1999

Dietary heme iron does not prevent postgastrectomy anemia but fructooligosaccharides improve bioavailability of heme iron in rats.

Gastrectomized rats exhibit iron deficiency anemia. We observed the effects of dietary heme-iron and short chain frucooligosaccharides (Sc-FOS) in relation to prevention of postgastrectomy anemia in rats. Twelve laparotomized (sham-operated) rats were fed iron-citrate (control) as iron source diet without or with Sc-FOS (75 g/kg of diet) and twenty four totally gastrectomized (Bilroth II) rats, were fed a iron-citrate (control) or heme-iron (heme) as iron source diet without or with Sc-FOS (75 g/kg of diet) for 4 weeks. All rats received an intramuscular injection of vitamin B-12 every two weeks. Tail blood was collected every other week for determination of hematocrit and hemoglobin concentration. At the end of the experiment, the rats were killed and whole blood was collected. The total gastrectomy induced the postgastrectomy anemia. Dietary Sc-FOS increase iron absorption and thereby prevented completely this anemia in gastrectomized rats fed the control diet but this effect of Sc-FOS in rats fed heme diet was not complete. Dietary heme iron could not prevent postgastrectomy anemia itself, but fructooligosaccharides improve bioavailability of not only non-heme iron such as iron-citrate, but also heme-iron in rats.

Anemia↗