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Biomedical subjects

Y Terai

Publications and source records attributed to Y Terai.

At least 19 recordsLinked to original sources

Gene expression of adhesion molecules and matrix metalloproteinases in endometriosis.

Various types of cell adhesion molecules and matrix metalloproteinases (MMPs) seem to play an important role in the invasion process of endometriosis; however, limited investigation has focused on their gene expression in human peritoneal endometriotic lesions. A total of 63 endometriotic tissues were surgically obtained from 35 women with endometriosis, which included 43 pigmented and 20 non-pigmented lesions. Gene expression levels of E-cadherin, alpha- and beta-catenin, MMP-2, MMP-9 and membrane-type 1 (MT1)-MMP in these endometriotic lesions were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis. MMP-2, MMP-9 and MT1-MMP mRNA expression in pigmented lesions was significantly higher than that in normal endometrium (p < 0.05), whereas E-cadherin, alpha- and beta-catenin mRNA expression was not suppressed in endometriotic lesions. There was a close correlation between MMP-2 or MT1-MMP and E-cadherin, alpha- or beta-catenin gene expression in 63 endometriotic tissues examined (p < 0.01). Immunohistochemical expression of E-cadherin, alpha- and beta-catenin in glandular epithelial cells was positive not only for all of seven cases with normal eutopic endometrium but also for 9 of 11 with ovarian endometriosis. MMP expression in ectopic endometrium was much greater than that in eutopic endometrium. These results suggest that endometriotic tissues expressing MMPs might be invasive and simultaneously possess cell-to-cell adhesion property in pelvic peritoneal foci.

Cadherins↗

Magnetic-field-induced superconductivity in a two-dimensional organic conductor.

The application of a sufficiently strong magnetic field to a superconductor will, in general, destroy the superconducting state. Two mechanisms are responsible for this. The first is the Zeeman effect, which breaks apart the paired electrons if they are in a spin-singlet (but not a spin-triplet) state. The second is the so-called 'orbital' effect, whereby the vortices penetrate into the superconductors and the energy gain due to the formation of the paired electrons is lost. For the case of layered, two-dimensional superconductors, such as the high-Tc copper oxides, the orbital effect is reduced when the applied magnetic field is parallel to the conducting layers. Here we report resistance and magnetic-torque experiments on single crystals of the quasi-two-dimensional organic conductor lambda-(BETS)2FeCl4, where BETS is bis(ethylenedithio)tetraselenafulvalene. We find that for magnetic fields applied exactly parallel to the conducting layers of the crystals, superconductivity is induced for fields above 17 T at a temperature of 0.1 K. The resulting phase diagram indicates that the transition temperature increases with magnetic field, that is, the superconducting state is further stabilized with magnetic field.

Journal Article↗

Correlation between thymidine phosphorylase expression and invasion phenotype in cervical carcinoma cells.

The correlation between thymidine phosphorylase (dThdPase) expression and invasion phenotype in human uterine cervical carcinoma cells was investigated using 10 cervical carcinoma cell lines. Semi-quantitative reverse transcription-polymerase chain reaction analysis was performed to investigate the mRNA levels of dThdPase and matrix metalloproteinase (MMP)-2 with beta-actin coamplified as an internal standard. dThdPase protein expression levels were detected by highly sensitive enzyme-linked immunosorbent assay. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were evaluated by haptotactic migration and invasion assay. Although dThdPase mRNA and protein expression levels differed remarkably among the cell lines, there was a statistical correlation between them (r = 0.743, p = 0.0139). dThdPase gene and protein expression levels were well correlated with the number of cells that migrated and invaded (p < 0.05). Moreover, there was a close correlation between MMP-2 gene and dThdPase gene and protein expression levels (p < 0.05). Tumor cells that produce dThdPase may have a higher invasive and metastatic potential because of their capacity to pass through tissue barriers.

Carcinoma, Squamous Cell↗

Vascular smooth muscle cell growth-promoting factor/F-spondin inhibits angiogenesis via the blockade of integrin alphavbeta3 on vascular endothelial cells.

Vascular smooth muscle cell growth-promoting factor (VSGP) was originally isolated from bovine ovarian follicular fluid as a stimulator of vascular smooth muscle cell proliferation. Homology searches indicate that bovine and human VSGPs are orthologs of rat F-spondin. Here, we examined whether recombinant human VSGP/F-spondin affected the biological activities of endothelial cells. VSGP/F-spondin did not affect the proliferation of human umbilical vein endothelial cells (HUVECs); however, it did inhibit VEGF- or bFGF-stimulated HUVEC migration. To clarify the mechanism of this inhibitory effect, we examined the adhesion of HUVECs to extracellular matrix proteins. VSGP/F-spondin specifically inhibited the spreading of HUVECs on vitronectin via the functional blockade of integrin alphavbeta3. As a result, VSGP/F-spondin inhibited the tyrosine phosphorylation of focal adhesion kinase (FAK) when HUVECs were plated on vitronectin. Moreover, VSGP/F-spondin inhibited the activation of Akt when HUVECs on vitronectin were stimulated with VEGF. VSGP/F-spondin inhibited tube formation by HUVECs in vitro and neovascularization in the rat cornea in vivo. These results indicate that VSGP/F-spondin inhibits angiogenesis at least in part by the blockade of endothelial integrin alphavbeta3.

Animals↗

Vascular endothelial growth factor C gene expression is closely related to invasion phenotype in gynecological tumor cells.

OBJECTIVE: The correlation between the gene expression of various angiogenic factors and in vitro invasive activity in 16 human gynecological cancer cell lines was investigated. METHODS: Semiquantitative reverse transcription polymerase chain reaction analysis was performed to investigate the mRNA expression levels of vascular endothelial growth factors (VEGF-A, -B, -C, and -D), basic fibroblast growth factor (bFGF), and matrix metalloproteinase (MMP)-2 with beta-actin coamplified as an internal standard. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were evaluated by haptotactic migration and invasion assay. RESULTS: Expression of VEGF-A mRNA was detected in all 16 cell lines, whereas the relative expression levels of other VEGF family members and bFGF, differed markedly among the cell lines. There was a statistical correlation between VEGF-C gene expression and the number of cells that migrated and invaded (P < 0.01). However, expression of mRNAs of other angiogenic factors did not correlate with motility and invasive activity of the cells. Moreover, there was a close correlation between VEGF-C and MMP-2 gene expression levels (P < 0.05). CONCLUSION: Tumor cells that produce VEGF-C may have a higher invasive and metastatic potential because of their capacity to pass through tissue barriers.

DNA, Neoplasm↗

Selective measurement of digital nerve conduction velocity.

We developed a new method to measure the nerve conduction velocity of a single digital nerve. In 27 volunteers (27 hands), we separately stimulated each digital nerve on the radial and ulnar sides of the middle and ring fingers. A double-peaked potential was recorded above the median nerve at the wrist joint when either the radial-side nerve or the ulnar-side nerve of the middle finger was stimulated. The first peak of this potential had disappeared after the digital nerve was blocked under the stimulating electrodes, and the peak appeared again coinciding with the decrease of anesthesia. Shifting the stimulating electrodes on the digital nerve resulted in no significant difference in the peak conduction velocity. It is possible that each peak of the potential was attributable to conduction of an action potential along one of the two digital nerves. This new method allows the assessment of a single digital nerve, and may be clinically useful for assessing the rupture of a digital nerve and the sensory nerve action potentials in carpal tunnel syndrome.

Action Potentials↗

Phylogenetic relationships and ancient incomplete lineage sorting among cichlid fishes in Lake Tanganyika as revealed by analysis of the insertion of retroposons.

Lake Tanganyika harbors numerous endemic species of extremely diverse cichlid fish that have been classified into 12 major taxonomic groups known as tribes. Analysis of short interspersed element (SINE) insertion data has been acknowledged to be a powerful tool for the elucidation of phylogenetic relationships, and we applied this method in an attempt to clarify such relationships among these cichlids. We studied insertion patterns of 38 SINEs in total, 24 of which supported the monophyly of three clades. The other 14 loci revealed extensive incongruence in terms of the patterns of SINE insertions. These incongruencies most likely stem from a period of adaptive radiation. One possible explanation for this phenomenon is the extensive incomplete lineage sorting of alleles for the presence or absence of a SINE during successive speciation events which took place about 5-10 MYA. The present study is the first to report the successful application of the SINE method in demonstrating the existence of such possible "ancient" incomplete lineage sorting. We discuss the possibility that it might potentially be very difficult to resolve the species phylogeny of a group that radiated explosively, even by resolving the genealogies of more than 10 nuclear loci, as a consequence of incomplete lineage sorting during speciation.

Alleles↗

[Brain abscess and ventriculitis associated with entrapment of the lateral ventricle appearing more like remarkable brain edema than ventricular dilatation--a case report].

We present a case with brain abscess associated with entrapment of the lateral ventricle appearing more like remarkable brain edema in the temporo-occipital lobe than ventricular dilatation. A 72-year-old man suffering from headache and vomiting visited our clinic. CT and MRI showed brain abscess in the right parieto-occipital lobe, associated with ventriculitis. Lumbar puncture also revealed purulent meningitis. Both symptoms and CSF findings improved after administration of antibiotics. The improved condition continued for two months after admission, but disturbed consciousness and left hemiparesis than appeared. MRI and CT showed entrapment of the lateral ventricle and brain edema of the right temporo-occipital region without ventricular dilatation. Because brain edema was thought to be caused by transudate of the CSF through the ventricular wall, lobectomy of the right temporal lobe and opening of the temporal horn were carried out. Although left hemiparesis and disturbed consciousness and brain edema disappeared after the operation, subdural effusion appeared. Using a subdural-peritoneal shunt, the subdural effusion was prevented and disappeared. In this case, we thought Hounsfield Unit (HU) of the brain edema caused by transudate of CSF through the ventricular wall (12.6) was markedly lower than that of so-called vasogenic edema (25.1) due to active inflammation. Measurement of the HU seemed to be a useful means to differentiate the types of brain edema in this situation from that of vasogenic edema caused by brain abscess, and thus a means for selection of the appropriate treatment.

Aged↗

Roles of two VEGF receptors, Flt-1 and KDR, in the signal transduction of VEGF effects in human vascular endothelial cells.

Vascular endothelial growth factor (VEGF) is a principal regulator of vasculogenesis and angiogenesis. VEGF expresses its effects by binding to two VEGF receptors, Flt-1 and KDR. However, properties of Flt-1 and KDR in the signal transduction of VEGF-mediated effects in endothelial cells (ECs) were not entirely clarified. We investigated this issue by using two newly developed blocking monoclonal antibodies (mAbs) against Flt-1 and KDR. VEGF elicits DNA synthesis and cell migration of human umbilical vein endothelial cells (HUVECs). The pattern of inhibition of these effects by two mAbs indicates that DNA synthesis is preferentially mediated by KDR. In contrast, the regulation of cell migration by VEGF appears to be more complicated. Flt-1 regulates cell migration through modulating actin reorganization, which is essential for cell motility. A distinct signal is generated by KDR, which influences cell migration by regulating cell adhesion via the assembly of vinculin in focal adhesion plaque and tyrosine-phosphorylation of focal adhesion kinase (FAK) and paxillin.

3T3 Cells↗

Tumor angiogenesis and thymidine phosphorylase expression in ovarian carcinomas including serous surface papillary adenocarcinoma of the peritoneum.

To clarify biological and clinical significance of tumor angiogenesis in the development of ovarian carcinoma, we investigated the relationship between tumor vascularity, the expression of thymidine phosphorylase (dThdPase), which is an angiogenic factor identical to platelet-derived endothelial cell growth factor (PD-ECGF), and patient outcome in ovarian carcinoma, including serous surface papillary carcinoma (SSPC). Primary tumor specimens (stages I-IV) from 54 patients were examined. Intratumoral microvessel density (IMVD) and dThdPase expression were evaluated immunohistochemically using anti-CD34 and anti-dThdPase antibodies, and results were correlated with clinicopathologic parameters and prognosis. IMVD for the 54 tumors ranged from 22.5 to 120.7 (number/0.73686 mm2/field). Twenty-three tumors were positive, and 31 tumors were negative for dThdPase expression. IMVD positively correlated with the expression of dThdPase (p < 0.01), tumor size, and peritoneal metastases (p < 0.05). However, there was no statistical correlation between IMVD, dThdPase expression, and clinical outcome. Of the 54 patients examined, 30 were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV primary ovarian carcinoma, and 9 were diagnosed with SSPC. There were no significant differences between the two groups with respect to clinicopathologic features, IMVD, dThdPase expression, or patient outcome. In conclusion, angiogenic activity may be necessary for the growth of metastatic implants in ovarian carcinoma and SSPC.

Cystadenocarcinoma, Papillary↗

Regulation of dihydropyrimidine dehydrogenase and pyrimidine nucleoside phosphorylase activities by growth factors and subsequent effects on 5-fluorouracil sensitivity in tumor cells.

Dihydropyrimidine dehydrogenase (DPD) and pyrimidine nucleoside phosphorylase (PyNPase) are the first and rate-limiting enzymes that regulate 5-fluorouracil (5-FU) metabolism, and tumoral DPD activity appears to be a promising predictor of 5-FU sensitivity. However, the regulatory mechanisms determining these enzyme activities have not been fully understood. We investigated the biological effects of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha on cell growth and tumoral DPD and PyNPase activities, and the subsequent effects on 5-FU sensitivity in uterine cervical carcinoma SKG-IIIb cells. The treatment of tumor cells with EGF or TGF-alpha resulted in a concentration-dependent increase in tumor cell growth and PyNPase activity, whereas tumoral DPD activity was inhibited. Their stimulatory effects on tumor cell growth correlated well with PyNPase activity, but were inversely related to DPD activity (P < 0.01). 5-FU sensitivity of tumor cells increased in the presence of EGF or TGF-alpha. These growth factors were shown to stimulate the first, rate-limiting enzyme activity in 5-FU anabolism and to inhibit that in 5-FU catabolism, leading to enhancement of the antiproliferative action of 5-FU at achievable therapeutic levels. The tumor environmental factors, EGF and TGF-alpha, may act as intrinsic regulators of DPD and PyNPase activities that affect the 5-FU sensitivity of individual tumors.

Antimetabolites, Antineoplastic↗

[Transvenous embolization for cavernous dural arteriovenous shunts: about the intracranial venous approach to the cavernous sinus].

Recently, the first choice of therapy for cavernous dural arteriovenous shunts (CdAVS) is transvenous embolization. Usually the approach routes for cavernous sinus are the inferior petrosal sinus (IPS), the superior ophthalmic vein (SOV) in most cases and the superior petrosal sinus (SPS) in rare case. But, it is difficult for us to treat patients in whom there are no extracranial veins through which to approach the cavernous sinus, with transvenous embolization. We presented the case in which intracranial transvenous approach to the cavernous sinus and transvenous embolization were performed and in which we achieve good results. In this article, we presented a case with Barrow's type D CdAVS and cortical venous drainage. At first, transarterial embolization was performed to decrease the amount of venous drainage for the purpose of eliminate convulsions and consciousness disturbance. However, cortical venous drainage continued. Moreover bilateral dilated SOVs normalized and bilateral IPSs were not visible, so we decided that it was impossible to carry out the transvenous embolization via extracranial veins. Transvenous embolization to the left cavernous sinus via the intracranial ophthalmic vein between the superior ophthalmic fissure and the inferior ophthalmic fissure after craniotomy was performed. Then, the transvenous embolization to the right cavernous sinus was carried out through the right superficial middle cerebral vein after craniotomy. The results were good and chemosis and bilateral abducens palsy diminished immediately. Trans-intracranial venous embolization for CdVAS is a very useful therapy when no extracranial veins exist for transvenous embolization.

Aged↗

A novel phosphodiesterase type 4 inhibitor, YM976 (4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one), with little emetogenic activity.

We synthesized a novel phosphodiesterase type 4 (PDE4) inhibitor, YM976, that is structurally different from the other PDE4 inhibitors like rolipram. In the present study, the pharmacological profile of YM976 was investigated. YM976 exhibited a strong and competitive inhibition against PDE4 purified from human peripheral leukocytes with an IC(50) of 2.2 nM. IC(50) values of rolipram and RP73401 were 820 and 0.43 nM, respectively. Test compounds had no effects on the other PDE isozymes, PDE1, -2, -3, and -5. YM976 potentiated prostaglandin E(2)-induced cAMP accumulation in a human mononuclear cell line, U937, and inhibited tumor necrosis factor-alpha production from human peripheral blood mononuclear cells stimulated by lipopolysaccharide. Anti-inflammatory activities of PDE4 inhibitors were compared in rat carrageenan-induced pleurisy models. YM976, rolipram, and RP73401 inhibited the cell infiltration into the pleural cavity with oral ED(30) values of 9.1, 10, and 7.4 mg/kg, respectively. YM976 produced no emesis up to 10 mg/kg, whereas rolipram and RP73401 induced emesis at oral doses of 3 mg/kg. To evidence the dissociation of anti-inflammatory activity from emesis, the anti-inflammatory effect of YM976 was examined in ferrets. YM976 dose dependently reduced carrageenan-induced leukocyte infiltration at the doses of 1, 3, and 10 mg/kg, p.o. On the other hand, rolipram failed to show obvious inhibition at doses that do not induce emesis. In conclusion, YM976 is a novel and orally active PDE4 inhibitor and possesses a good separation of emetogenicity from anti-inflammatory activity.

Animals↗

Electromyographic evaluation after endoscopic carpal tunnel release in idiopathic carpal tunnel syndrome.

The purpose of this study was to electromyographically evaluate results in patients with carpal tunnel syndrome (CTS) who underwent endoscopic carpal tunnel release (ECTR). The subjects were 26 patients with idiopathic CTS (37 hands) who were followed for at least 6 months after ECTR. To compare results informatively, hands were classified into four groups: those with normal distal motor latency (DML) and sensory conduction velocity (SCV) were classified as group A, those with normal DML and abnormal SCV as group B, those with an abnormal DML and normal SCV as group C, and those with abnormal DML and SCV as group D. All but one of the hands were classified as group D on the basis of preoperative electromyographic evaluation, while one was classified as group C. The mean preoperative obtainable DML and SCV values were 7.2 m and 27.3 m/s, respectively. Postoperatively, 12 hands were in group A, 8 hands in group B, 2 hands in group C, and 15 hands in group D. The mean DML and SCV values at final follow-up were 4.3 ms and 40.8 m/s, respectively. Of the 25 hands with muscle atrophy before surgery, 6 hands were in group A, 5 hands were in group B, 1 hand was in group C, and 13 hands were in group D at final follow-up. Thenar muscle atrophy and denervation potentials were present before surgery in 13 of the 15 hands classified as group D at the final follow-up.

Adult↗

Correlation between tumor angiogenesis and expression of thymidine phosphorylase, and patient outcome in uterine cervical carcinoma.

The relationship between tumor angiogenesis and the expression of thymidine phosphorylase (dThdPase) in uterine cervical carcinoma tissues, as well as patient outcome, were investigated. Primary tumor specimens surgically obtained from 54 patients (stages Ib to IIIb) receiving neither chemotherapy nor radiation therapy before surgery were examined. Intratumoral microvessel density (IMVD) and dThdPase expression were evaluated immunohistochemically using anti-CD34 and anti-dThdPase antibodies and were correlated with clinicopathologic parameters and prognosis. IMVD for the 54 tumors ranged from 24.8 to 118.6, with a median value of 57.7 (number/0.7386 mm2/field). For immunoreactivity of dThdPase, 16 tumors were graded as -, 20 as 1+, and 18 as 2+. IMVD was significantly associated with the expression of dThdPase (P<.01). Both IMVD and dThdPase expression were well correlated with depth of myometrial invasion, endometrial invasion, and pelvic lymphnode metastasis (P<.05). Overall survival rates for 18 patients with strong dThdPase-staining tumors, assessed as 2+, were lower than those for 36 with weak dThdPase staining tumors (P = .0108). However, there was no statistical correlation between IMVD and patient outcome. The expression of dThdPase plays a role in the promotion of angiogenesis and affects the patient's survival in uterine cervical carcinomas.

Antigens, CD34↗

Biological implications of growth factors on the mechanism of invasion in gynecological tumor cells.

We investigated the effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on migration, invasion and proteinase expression of gynecological cultured cancer cells (SKG-IIIb cervical squamous cell carcinoma, OMC-4 cervical adenocarcinoma, SNG-M endometrial adenocarcinoma and OMC-3 ovarian adenocarcinoma), and whether these growth factors affect thymidine phosphorylase/platelet-derived endothelial cell growth factor expression of tumor cells. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. The zymography of tumor-conditioned medium showed that the treatment of tumor cells with EGF and TGF-alpha resulted in the increase of type IV collagenases, stromelysin and urokinase-type plasminogen activator which was partly confirmed by immunoblot analysis. The expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor which has angiogenic activity, was also upregulated by these growth factors. These results suggest that EGF and TGF-alpha act as positive regulators on the invasion process of gynecological tumor cells which may be associated with their stimulatory action on the motility of tumor cells, the expression of proteinases secreted by tumor cells and the angiogenic phenotype.

Adenocarcinoma↗

Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex.

Based on the X-ray structure of the complex of Ac-Tyr-Val-Ala-Asp-H (L-709049) and interleukin-1 beta converting enzyme (ICE), we synthesized compounds which were derived from 2-NapCO-Val-Pro-Asp-CH2OPh (1) to obtain a potent inhibitor in the cell assay. Among these compounds, (3S)-N-methanesulfonyl-3-[[1-[N-(2-naphthoyl)-L-valyl]-L-prolyl]amino]- 4-oxobutanamide (27c) showed high potency not only in the enzyme assay but also cell assay with IC50 values of 38 nM and 0.23 microM, respectively. Compound 27c, with a c log P value of 1.76, had a more hydrophilic character compared with 1. Compound 27c also dose dependently inhibited LPS-primed ATP-induced IL-1 beta release in mice. The crystal structure of the complex of compound 27c and ICE revealed that compound 27c had further interactions with ICE in the naphthoyl group at the P4 position and in the methyl group of the methanesulfonamidecarbonyl group at the P1 position, compared with L-709049. To our knowledge, compound 27c is the first example that shows a strong inhibitory activity without the carboxyl group at the P1 position.

Animals↗

[Partial liver resection with small skin incision for multidisciplinary treatment of hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is likely to be detected as multiple intrahepatic metastases, and trans-arterial embolization (TAE) is the treatment of choice. However, other therapy is needed when TAE is not effective for a tumor. We performed partial liver resection with small skin incision in two such patients. One patient had two HCCs of segment 6 (S6) and S7, and TAE was performed twice. However, HCC of S7 was viable, and we partially resected the tumor of S7. In the other patient, HCC was multiple in segment 6 and 7. TAE was performed three times, and in segment 6 we detected a tumor which grew into the extrahepatic space and seemed uneffected by TAE. We performed a partial resection of liver segment 6. After 3 months, TAE was repeated in the latter. The operation time was about three hours, and no blood transfusion was performed. Two of the patients were discharged on the 13th postoperative day. We concluded that partial liver resection with small skin incision was useful for one case of multidisciplinary treatment for hepatocellular carcinoma.

Aged↗