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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 415 records · Page 23Linked to original sources

Recent advances in the microinsemination of laboratory animals.

Microinsemination techniques were applied to laboratory animals, including mice, Mongolian gerbils, mastomys, guinea pigs and cynomolgus monkeys. After micro-insemination with spermatozoa or round spermatids, their oocytes were successfully fertilized and subsequently developed into 4-cells to blastocysts, depending on species. The efficiencies of microinsemination techniques for producing fertilized oocytes were comparable with, or superior to those of IVF in these species.

Animals↗

Inhibitory effect of intestinal anti-Gb3 IgA antibody on verotoxin-induced cytotoxicity.

The effect of intestinal IgA antibody against the receptor for verotoxin (VT), globotriaosylceramide (Gb3), on VT-mediated cytotoxicity was examined. Intestinal IgA antibodies against Gb3 were prepared by oral immunization of mice with Gb3 and adjuvant monophosphoryl lipid A (MPL)-containing liposomes composed of dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylserine and cholesterol (1 : 1 : 2, molar ratio) (PS-liposome). Oral administration with Gb3 and MPL-containing PS-liposome induced significant IgA responses to Gb3 in the intestinal lavage fluid in all mice tested. Furthermore, anti-Gb3 IgA antibodies in the lavage fluid effectively inhibited the cytotoxicity of VT2 to Vero cells in a dose-dependent manner. These results suggest that anti-Gb3 IgA antibodies produced in the intestinal tract, upon oral immunization with Gb3-containing liposome, function as inhibitors against VT and also indicate the potential usefulness of oral PS-liposome vaccines containing MPL for the induction of a protective mucosal immune response against intestinal diseases.

Animals↗

Viscoelastic properties of denture base resins obtained by underwater test.

The viscoelastic properties of denture base polymers, such as poly(methylmethacrylate) (PMMA), polycarbonate (PC), polysulfone (PSF) and polyethersulfone (PES) which have been used in current clinical dentistry were investigated. In addition, water absorption, diffusion coefficient of water into material, cubical expansion, specific volume and residual monomer were also determined. From the results of this study, the viscoelastic behaviours of the denture base polymers in water have been discussed. The relaxation modulus (Er(5)) which was calculated using a stress at 5 s from the start of measurement for the specimen which reached an equilibrium moisture content (wet specimen), decreased from 23.1 to 25.5% compared with that of PMMA stored in a desiccator (37 degrees C) for 1 week (dry specimen). In contrast, this decreasing ratio was 7.0 to 10.0% for PC, PSF and PES. It is suggested that this phenomenon is caused by the increase of specific volume (cm3/g) with water absorption in each material. The water absorption of the PMMA group was relatively large in comparison with other material and was 1.81-1.85%. This value was within the range from 0.38 to 1.74% for PC, PSF and PES. The diffusion coefficients of water for PC, PSF and PES increased by approximately 1.5-2.7 times that of PMMA. Furthermore, the coefficient of cubical expansion of the wet specimen was larger than that of the dry specimen. The increasing ratio was 1.03-1.10 times for the PMMA group and 1. 18-2.38 times for PC, PSF and PES. The variation of Er(5) of the PMMA group with temperature in water was larger than those of PC, PSF and PES.

Absorption↗

Dynamic viscoelastic properties of photo-activated composite resins containing short glass fibres.

The dynamic shear modulus in torsion (G'), water absorption, thermal expansion and residual monomer of the reinforced materials produced by adding four short glass fibres (19 microm in mean diameter and 86.1--763 microm in mean length) and one spherical E glass (11.1 microm in mean diameter) were examined and discussed in comparison with those of the materials without filler. G' of short fibre reinforced composites increased with fibre length and reached a maximum value near 382 microm for a dry specimen and near 156 microm for a wet one. In addition, the coefficient of thermal expansion of the fibre reinforced composites and the amount of residual monomer decreased considerably compared with those of composites containing spherical glass. There was no significant difference in water absorption between the fibre reinforced composites and the composites containing spherical glass. Therefore, it was concluded that the reinforcement method of adding short glass fibres is favourable for improving the viscoelastic properties of the materials.

Absorption↗

Extracellular ATP triggers tumor necrosis factor-alpha release from rat microglia.

Brain microglia are a major source of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), which have been implicated in the progression of neurodegenerative diseases. Recently, microglia were revealed to be highly responsive to ATP, which is released from nerve terminals, activated immune cells, or damaged cells. It is not clear, however, whether released ATP can regulate TNF-alpha secretion from microglia. Here we demonstrate that ATP potently stimulates TNF-alpha release, resulting from TNF-alpha mRNA expression in rat cultured brain microglia. The TNF-alpha release was maximally elicited by 1 mM ATP and also induced by a P2X(7) receptor-selective agonist, 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate, suggesting the involvement of P2X(7) receptor. ATP-induced TNF-alpha release was Ca(2+)-dependent, and a sustained Ca(2+) influx correlated with the TNF-alpha release in ATP-stimulated microglia. ATP-induced TNF-alpha release was inhibited by PD 098059, an inhibitor of extracellular signal-regulated protein kinase (ERK) kinase 1 (MEK1), which activates ERK, and also by SB 203580, an inhibitor of p38 mitogen-activated protein kinase. ATP rapidly activated both ERK and p38 even in the absence of extracellular Ca(2+). These results indicate that extracellular ATP triggers TNF-alpha release in rat microglia via a P2 receptor, likely to be the P2X(7) subtype, by a mechanism that is dependent on both the sustained Ca(2+) influx and ERK/p38 cascade, regulated independently of Ca(2+) influx.

Adenosine Triphosphate↗

Identification of novel genes expressed during metanephric induction through single-cell library screening.

BACKGROUND: Development of the mature kidney is dependent on a series of inductive events between a portion of the epithelial bud at the distal end of the nephric duct and a neighboring domain of committed metanephric mesenchyme. Several genes have been identified to date that are critical in the inductive process. For example, the deletion of Bmp7 from the mouse genome results in dysgenesis or agenesis of the kidney. These findings suggest that Bmp7 controls the expression of genes important for nephrogenesis, but the identity of these genes has remained largely undetermined. METHODS: Single cells were isolated from mouse metanephric mesenchyme during the time of induction (between E11.0 and E11.5) and cDNA libraries constructed from induced and uninduced tissue. Subtractive hybridization was performed to isolate genes that were expressed during E11.5 but not E11.0. RESULTS: Using this approach, we identified eight previously known genes, three of which were known to be involved in metanephric induction, thus validating our approach, and nine novel genes. Eight of these genes were completely novel, whereas one was similar to a member of the yeast Anaphase Promoting Complex. CONCLUSIONS: Through subtractive hybridization of mouse E11.0 and E11.5 metanephric mesenchyme single-cell cDNA libraries, we have identified novel genes that are candidates for involvement in nephrogenesis through their up-regulation during the inductive process.

Amino Acid Sequence↗

Involvement of keratinocyte activation phase in cutaneous graft healing: comparison of full-thickness and split-thickness skin grafts.

BACKGROUND: Little is known about keratinocytic activation in the graft take and healing process. OBJECTIVE: To investigate the clinical and molecular differences between pure epidermal sheet graft (PESG), split-thickness skin graft (STSG), and full-thickness skin graft (FTSG). METHODS: Three different thickness skin grafts (PESG, STSG, and FTSG) were performed onto three kinds of porcine wounds: shallow, deep, and full. Graft take, contraction, and Ki-67 and beta1 integrin expression in epidermis were studied. RESULTS: All grafts took well. As expected, full wounds covered by PESG and STSG contracted more than those covered by FTSG, whereas shallow wounds covered by FTSG contracted more than those covered by STSG. No difference in contracture was observed among deep wounds covered by PESG, STSG, and FTSG. Up-regulation of Ki-67 and beta1 integrin expression was greater in PESG and STSG, compared with little expression in FTSG. CONCLUSION: The keratinocytic activation phase may occur both in the STSG and PESG healing process, as well as serum imbibition, inosculatory, and revascularization phases.

Animals↗

Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan.

Hepatic resection (HX), percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TCAE) have all been used in the treatment of patients with small-sized hepatocellular carcinomas (HCCs). However, the indications for these therapeutic modalities remain unclear. Therefore, the first step to minimize the debate on these indications is to review the standard results from each treatment based on an extensive survey. The participants in this study were patients with HCCs less than 5 cm in diameter who were enrolled in The Liver Cancer Study Group of Japan. The survival rates in the HX (n = 8,010), PEI (n = 4,037), and TCAE (n = 841) groups were calculated in relation to the number of tumors and the clinical stage. In the clinical stage I cases with a solitary tumor less than 2 cm in diameter and in all clinical stages with a solitary tumor greater than 2 cm and in the clinical stage II cases with 2 tumors greater than 2 cm, the HX group showed higher survival rates than the nonsurgical groups. The HX group had a higher male/female ratio and a younger mean age than the PEI or TCAE group. The ratio of HBs antigen-positive cases/hepatitis C virus antibody-positive cases in the PEI group was lower than that in the corresponding HX group. In contrast, the PIVKA-II values in the HX group tended to be higher than in the PEI group. In conclusion, these findings will provide useful information for selection of a therapeutic modality for small-sized HCCs.

Age Distribution↗

Regulatory mechanisms for transforming growth factor beta as an autocrine inhibitor in human hepatocellular carcinoma: implications for roles of smads in its growth.

Transforming growth factor beta (TGF-beta) initiates signaling through heteromeric complexes of transmembrane type I and type II serine/threonine kinase receptors. Activated TGF-beta type I receptor phosphorylates receptor-regulated Smads (2 and 3). Antagonistic Smad 7 forms stable association with the activated TGF-beta type I receptor, blocking phosphorylation of receptor-regulated Smads. On the other hand, elevated serum concentration of TGF-beta along with resistance to its growth-inhibitory effect is commonly observed in human hepatocellular carcinoma (HCC) patients. In this study, we investigated the mechanisms of resistance to tumor-derived TGF-beta in human HCC and hepatoblastoma-derived cell lines, focusing on the roles of receptor-regulated Smads and antagonistic Smad 7. HuH-7 and HepG2 cells showed poor response to TGF-beta-mediated growth inhibition. Because neutralization of TGF-beta in the medium or blockage of signal transduction pathway by inductions of dominant negative Smad 2/3 resulted in a stimulation of cell growth, tumor-derived TGF-beta signal acts on cell growth negatively. However, Smad 7 induced by TGF-beta negatively regulated Smad 2 action and rendered most Smad 2 proteins in the cytoplasm. Taken together, these results indicate that endogenous TGF-beta-mediated induction of Smad 7 results in a higher "threshold" for the antiproliferative signals mediated by receptor-regulated Smads, and can be involved in reduced responsiveness to the cytokine in some human HCC cells.

Carcinoma, Hepatocellular↗

The relationship between photosensitive temporal lobe epilepsy and eye closure activity.

We describe a 16-year-old female patient affected by photo-induced temporal lobe epilepsy. During intermittent photic stimulation she showed a photoparoxysmal response in the EEG. This case was diagnosed from clinical symptoms, single photon emission computer tomography, and EEG data. The clinical symptoms were relieved by the administration of carbamazepine. As these photoparoxysmal responses were observed not only during photic stimulation, but also when patient was closing her eyes during an eye-opening test in complete darkness, we propose the existence of an alternative pathway such as from the extraocular muscles or orbicularis oculi, or activation of cortical activity due to the change of consciousness by closing eyes in inducing photosensitive epilepsy. We describe an additional case and discuss a novel aspect of photo-induced temporal lobe epilepsy.

Adolescent↗

Effect of activated human protein C on experimental venous thrombosis induced by stasis with operative invasion in mice.

Protein C (PC) is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C: APC) by thrombin in the presence of thrombomodulin. APC plays an important role in regulating blood coagulation and fibrinolysis by inhibiting not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). In this study, it was reported that the antithrombotic effect of a human APC product (designated as CTC-111) compared with that of heparin and human PC on the deep venous thrombosis (DVT) model induced in mice by stasis caused by inferior vena cava ligation and operative invasion. Drugs were injected into a tail vein at -2, 30, 60, and 120 min after the inferior vena cava ligation. One-fifth amount of the total dosage of a given drug was injected at each time point. The wet weight of thrombus formed was reduced by APC or heparin administration, however, PC, which was equal to APC in protein amount, did not show any antithrombotic effect. To confirm whether human PC could be activated by mouse thrombin, PC was treated with mouse or human thrombin to measure the amount of APC formed. Mouse thrombin could activate human PC at a similar activation rate as human thrombin. These results suggest that externally administrated PC cannot exhibit antithrombotic effect in this DVT model due to slow activation rate to APC and that APC is a better antithrombic agent than PC for treating thrombotic diseases.

Animals↗

Long-term survival and prognostic factors in the surgical treatment of mass-forming type cholangiocarcinoma.

BACKGROUND: Mass-forming type cholangiocarcinoma is a distinct from of cholangiocellular carcinoma, with pathologic and biologic behavior different from those of other types. The clinical consequences of these differences have never been clarified. METHODS: Fifty-two consecutive patients (32 men and 20 women, mean age 62 years) with mass-forming type cholangiocarcinoma that had been treated with curative surgical resection between 1980 and 1998 were retrospectively evaluated. Long-term survival and disease-free survival were calculated, and univariate and multivariate analysis of various prognostic factors was conducted. RESULTS: The 30-day postoperative mortality rate was 2%, and the overall and disease-free 5-year survival rates were 36% and 34%, respectively. Univariate analysis identified 5 significant risk factors for overall survival: surgical margin, lymph node metastasis, lymph node dissection, vascular invasion, and left-side location of the main tumor. Two risk factors were identified for disease-free survival: surgical margin and lymph node metastasis. Multivariate analysis confirmed that surgical margin, lymph node metastasis, and vascular invasion were independently significant variables for overall survival. CONCLUSIONS: This is the first reported study on the effectiveness of liver resection for the treatment of mass-forming type cholangiocarcinoma, showing that surgical therapy can prolong survival if local radicality can be achieved and lymph-node metastases are absent.

Adult↗

Intrahepatic inflow areas of the drainage vein of the gallbladder: analysis by angio-CT.

BACKGROUND: The drainage veins of the gallbladder (cystic veins) are important hepatic metastatic routes of gallbladder cancer. We studied the cystic vein inflow portions of the intrahepatic vessels by computed tomography during angiography (angio-CT). METHODS: The subjects were 27 unoperated pancreatic-biliary patients. After superselective catheterization of the cystic artery, angio-CT was performed, and cystic veins and sinusoidal filling were visualized. We identified the cystic vein inflow routes and the vessels they fed. RESULTS: We found 72 cystic veins in 26 patients. All cystic veins flowed into the intrahepatic portal branches or sinusoids. The cystic veins took either of two routes: one into the liver through the hepatic hilum (17 patients, 21 veins), taken mainly by the portal branch for subsegment 4a (P4a), the anterior portal branch, and the umbilical portion of the portal branch; and the other through the hepatic bed (23 patients, 51 veins), taken mainly by S4a sinusoid, S5 sinusoid, P4a, and P5. CONCLUSIONS: Angio-CT is useful for detecting the cystic vein inflow portions of the intrahepatic vessels. It makes possible identification of areas where there is a possibility for micrometastasis of the gallbladder cancer.

Adult↗

Expression of nuclear factor-kappaB in Helicobacter pylori-infected gastric mucosa detected with southwestern histochemistry.

BACKGROUND: The transcription factor nuclear factor-kappaB (NF-kappaB) plays a pivotal role in inflammatory responses by upregulating mRNA expression of, for example, proinflammatory cytokines and chemokines. Although in vitro studies have shown that Helicobacter pylori can induce NF-kappaB activation in gastric cancer cell lines, there is little information on cellular localization of NF-kappaB in H. pylori-infected gastric mucosa. METHODS: H. pylori-infected and -negative patients with various endoscopic findings were examined. NF-kappaB expression was studied by means of Southwestern histochemistry, a new method of localizing transcription factors. Labeled double-stranded oligo-DNA with specific consensus sequence for the NF-kappaB binding site was reacted with frozen sections from gastric biopsy specimens. We compared mucosal interleukin-8 (IL-8) and IL-1beta levels as measured with enzyme-linked immunosorbent assay with the degree of NF-kappaB expression. RESULTS: NF-kappaB expression was often evident in nuclei of epithelial cells in H. pylori-infected gastric mucosa. The degree of NF-kappaB expression on the epithelium was significantly more severe in H. pylori-infected than in -negative mucosa. The degree of NF-kappaB expression also correlated with mucosal IL-8 levels but not with IL-8. CONCLUSIONS: H. pylori infection increases the expression of NF-kappaB in gastric mucosa, suggesting that NF-kappaB is involved in inflammatory responses to H. pylori.

Enzyme-Linked Immunosorbent Assay↗

Focal ductal branch dilatation on magnetic resonance cholangiopancreatography: a hint for early diagnosis of pancreatic carcinoma.

A 63-year-old man with a combination of early pancreatic carcinoma and an intraductal papillary adenoma was reported. A pancreatic cyst was detected by chance at the head of the pancreas by computed tomography for a follow-up study of early rectal carcinoma previously operated. Detailed studies by endoscopic retrograde pancreatography (ERP) showed irregular narrowing of the main pancreatic duct at the pancreatic body and magnetic resonance cholangiopancreatography (MRCP) revealed dilatation of ductal branches draining there. Brushing cytology of the pancreatic duct demonstrated cancer cells and total pancreatectomy was performed. Stepwise histo-pathological examinations of the specimen showed two foci of invasive carcinoma in the neck and body and multiple foci of severe dysplasia, some of which contained carcinoma in situ, in the body of the pancreas. The cystic tumor in the head of the pancreas was an intraductal papillary adenoma. In this case, the scrutiny of a pancreatic cyst including MRCP and ERP led to an early diagnosis of pancreatic cancer. Dilatation of ductal branches depicted by MRCP might be a new hint for early diagnosis of pancreatic carcinoma.

Adenoma↗

Ethnic-related differences in the frequency distribution of genetic polymorphisms in the CYP1A1 and CYP1B1 genes in Japanese and Caucasian populations.

1. Race-related differences in the frequency distribution of genetic polymorphisms in the CYP1A1 and CYP1B1 genes were studied in 39 Japanese and 45 Caucasians. 2. Four types of CYP1A1 polymorphism, namely m1 (a nucleotide change at T6235C in the 3'-flanking region), m2 (A4889G at exon 7), m3 (T5639C in the 3'-flanking region) and m4 (C4887A at exon 7), and three types of CYP1B1 genetic polymorphism, namely m1 (C488G and G701T leading to Arg48Gly and Ala119Ser exchanges respectively), m2 (C1294G leading to a Leu432Val exchange) and m3 (A1358G leading to an Asn453Ser exchange) were studied. 3. The distribution of the m1-, m2-, m3-, and m4-types of CYP1A1 polymorphism in the Japanese population was 30.8, 17.9, 0 and 0% respectively; those in Caucasians were 3.3, 6.7, 0 and 2.2% respectively. Two types (m1, and m2) of CYP1B1 polymorphism were expressed at 14.1 and 21.8% respectively in the Japanese, and by 28.9 and 37.5% respectively in the Caucasian. Ethnic differences were also noted in the m3-type CYP1B1 polymorphism in which the incidence in Caucasians was 23.9%, whereas no cases in the 39 Japanese subjects were observed. 4. No apparent association was found in the incidence in each of the genetic polymorphisms of CYP1A1 and CYP1B1 genes, nor in methylenetetrahydrofolate reductase gene, except that the occurrence of the m2-type of CYP1A1 genetic polymorphism was related to that of the m1-type CYP1A1 polymorphism in the Japanese population. 5. These results suggest that there are race-related differences in the occurrence of genetic polymorphisms in both CYP1A1 and CYP1B1 genes in Japanese and Caucasian populations and that these differences in P450 genetic polymorphisms may, in part, cause differences in the occurrence of lung and breast cancers in these ethnic groups.

Alleles↗

Long-term prospective study on the natural history of Wolff-Parkinson-White syndrome detected during a heart screening program at school.

UNLABELLED: In the period 1985 to 1993, a total of 802 school-aged children (284 first-graders and 518 seventh-graders) were referred to our hospital for further evaluation of electrocardiographic abnormalities. Among them, 57 (male 24 and female 33) children were confirmed as having Wolff-Parkinson-White (WPW) syndrome based on the findings of 12-lead surface electrocardiograms (ECG). According to Lindsay's criteria, the locations of the accessory pathways were as follows: Left-lateral in 10 (18%), left-posterior in 2 (4%), right-free-wall in 28 (49%), anterior-septum in 13 (23%) and posterior-septum in 3 (5%). One 12-y-old girl had multiple accessory pathways. Six patients had associated diseases: Ebstein's anomaly in 4, epilepsy in 1 and mental retardation with scoliosis in 1. Follow-up periods ranged from 2.0 to 13.0 y (mean +/- SD: 8.0 +/- 3.3 y) for 23 first-graders with WPW syndrome, and from 2.0 to 13.0y (mean +/- SD: 7.3 +/- 4.2y) for 34 seventh-graders, respectively. Initially, 5 children had at least one episode of supraventricular tachycardia (SVT) by history and 6 children developed SVT during the follow-up. One girl with multiple accessory pathways and recurrent SVT required long-term drug therapy. CONCLUSIONS: The outcome of children with WPW syndrome detected by a heart screening program at school was favorable. Our 8 y follow-up of 57 children with WPW syndrome will serve as additional information concerning the indication of radio-frequency catheter ablation therapy for WPW syndrome in children.

Adolescent↗

Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis.

Concentrations of interleukin (IL)-6 and IL-8 in serum and synovial fluid obtained from patients with osteoarthritis (OA) of the knee were determined by the chemiluminescence-ELISA (CL-ELISA) method, the sensitivity of which is 100-1,000 times greater than that of the conventional ELISA method. The results were compared with those obtained from patients with rheumatoid arthritis (RA) and from healthy subjects. The mean IL-6 and IL-8 levels in synovial fluid indicated higher concentrations in RA than in OA. The IL-6 and IL-8 levels in serum were significantly higher in RA and OA relative to controls. Among OA patients in whom remarkable improvement was noted in hydrarthrosis, the synovial fluid IL-6 and IL-8 levels at the initial examination were relatively higher, and were markedly decreased after treatment with sodium hyaluronate (NaHA). Among those in whom no improvement was noted in hydrarthrosis, the synovial fluid IL-6 and IL-8 levels at the time of initial examination were relatively lower, and hydrarthrosis was not significantly improved even after treatment with NaHA. In addition, there was a tendency for the synovial fluid IL-6 and IL-8 levels to decrease as HA levels increased. Evaluation of X-ray findings revealed that the IL-6 levels in synovial fluid at the initial examination in low-grade cases tended to be significantly higher than in high-grade cases. In low-grade cases, as determined by X-ray findings, there was a significant decrease in IL-6 levels in synovial fluid after treatment with NaHA.

Adjuvants, Immunologic↗