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T Sekine

Publications and source records attributed to T Sekine.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effect of inelastic deformation on crystallite size in post-shock 6H polytype SiC.

Shock-recovery experiments have been conducted on 6H polytype silicon carbide to 135 GPa and post-shock samples have been analyzed by Raman spectroscopy, x-ray diffraction, and electron microscopy. Results indicate that at up to 25-30 GPa, crystallite size is reduced faster than above this pressure, when reduction slows. Shock-induced inelastic deformation of 6H-SiC is known to develop fully for stress above 25 GPa, coinciding with the pressure range observed where crystallite size reduction decreases. Inelastic deformation appears to be responsible for this slowed crystallite size reduction.

Journal Article↗
PubMed2000

Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial.

BACKGROUND: Postsurgical recurrence of hepatocellular carcinoma (HCC) is frequent and fatal. Adoptive immunotherapy is active against HCC. We assessed whether postoperative immunotherapy could lower the frequency of recurrence. METHODS: Between 1992 and 1995, we did a randomised trial in which 150 patients who had undergone curative resection for HCC were assigned adoptive immunotherapy (n=76) or no adjuvant treatment (n=74). Autologous lymphocytes activated vitro with recombinant interleukin-2 and antibody to CD3 were infused five times during the first 6 months. Primary endpoints were time to first recurrence and recurrence-free survival and analyses were by intention to treat. FINDINGS: 76 patients received 370 (97%) of 380 scheduled lymphocyte infusions (mean cell number per patient 7.1x10(10) [SD 2.1]; CD3 and HLA-DR cells 78% [16]), and none had grade 3 or 4 adverse events. After a median follow-up of 4.4 years (range 0.2-6.7), adoptive immunotherapy decreased the frequency of recurrence by 18% compared with controls (45 [59%] vs 57 [77%]) [corrected] patients. Time to first recurrence in the immunotherapy group was significantly longer than that in the control group (48% [37-59] vs 33% [22-43] at 3 years, 38% [22-54] vs 22% [11-34] at 5 years; p=0.008). The immunotherapy group had significantly longer recurrence-free survival (p=0.01) and disease-specific survival (p=0.04) than the control group. Overall survival did not differ significantly between groups (p=0.09). INTERPRETATION: Adoptive immunotherapy is a safe, feasible treatment that can lower recurrence and improve recurrence-free outcomes after surgery for HCC.

Adult↗
PubMed2000

Detection of tumor cells in blood using CD45 magnetic cell separation followed by nested mutant allele-specific amplification of p53 and K-ras genes in patients with colorectal cancer.

A new method for detecting circulating tumor cells that is based on magnetic-activated cell separation (MACS) and nested mutant allele-specific amplification (nested MASA) was evaluated in patients with colorectal cancer using the p53 and K-ras genes as genetic markers. By negative selection with anti-CD45 monoclonal antibody-conjugated supermagnetic microbeads, the proportion of tumor cells was enriched 9-fold. By the combination of MACS and nested MASA, 10 tumor cells in 10(7) normal peripheral blood mononuclear cells could be detected without false-positives. Using this method, we examined blood taken from the tumor drainage veins of 23 patients with colorectal cancer. Eighty-seven percent (20/23) of primary tumor tissues showed p53 and/or K-ras gene mutations. Forty-five percent (9/20) of patients with p53 and/or K-ras mutations in the primary tumor showed the same mutated genes in the blood samples. There was a significant association between the presence of p53 and K-ras gene mutation in the blood and tumor size, depth of invasion, and venous invasion. Blood gene mutation was detected in 80% (4/5) of samples from patients with synchronous liver metastases. Sixty percent (3/5) of patients with mutant genes in the blood developed asynchronous liver metastases after surgery. The overall survival of patients with p53 and/or K-ras gene mutation-positive findings in blood was significantly shorter than that of patients testing negative on Kaplan-Meier analysis. Our results suggest that the method may be useful for reliable detection of tumor cells circulating in the blood and may help to identify patients at high risk for relapse.

Adenocarcinoma↗
PubMed2000

Peripheral nerve regeneration across an 80-mm gap bridged by a polyglycolic acid (PGA)-collagen tube filled with laminin-coated collagen fibers: a histological and electrophysiological evaluation of regenerated nerves.

We evaluated peripheral nerve regeneration across an 80-mm gap using a novel artificial nerve conduit. The conduit was made of a polyglycolic acid (PGA)-collagen tube filled with laminin-coated collagen fibers. Twelve beagle dogs underwent implantation of the nerve conduit across an 80-mm gap in the left peroneal nerve. In four other dogs used as negative controls, the nerve was resected and left unconnected. Histological observation showed that numerous unmyelinated and myelinated nerve fibers, all smaller in diameter and with a thinner myelin sheath than normal nerve fibers, regrew through and beyond the gap 12 months after implantation. The distribution of the regenerated axonal diameters was different from that of the normal axonal diameters. Compound muscle action potentials, motor evoked potentials, and somatosensory evoked potentials were recorded in most animals 3 months after implantation. Peak amplitudes and latencies recovered gradually, which indicating the functional establishment of the nerve connection with the target organs. In addition to the ordinary electrophysiological recoveries, potentials with distinct latencies originating from Aalpha, Adelta and C fibers became distinguishable at the 6th lumbar vertebra following stimulation of the peroneal nerve distal to the gap 12 months after implantation. The pattern of walking without load was restored to almost normal 10-12 months after implantation. Neither electrophysiological nor histological restoration was obtained in the controls. Our nerve conduit can guide peripheral nerve elongation and lead to favorable functional recovery across a wider nerve gap than previously reported artificial nerve conduits.

Animals↗
PubMed2000

Single-Microparticle Injection and Microabsorptiometry: Direct Analysis of Sorption Processes.

Sorption processes of methylene blue in a single silica gel microparticle in an aqueous solution was kinetically analyzed by a new technique combined with the microcapillary injection/manipulation and microabsorptiometry of the single particle. The observed sorption rates were analyzed in terms of the solute concentration in water and the particle size. The sorption processes were governed by diffusion of the solute in the particle. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta.

A cDNA encoding a novel multispecific organic anion transporter, OAT4, was isolated from a human kidney cDNA library. The OAT4 cDNA consisted of 2210 base pairs that encoded a 550-amino acid residue protein with 12 putative membrane-spanning domains. The amino acid sequence of OAT4 showed 38 to 44% identity to those of other members of the OAT family. Northern blot analysis revealed that OAT4 mRNA is abundantly expressed in the placenta as well as in the kidney. When expressed in Xenopus oocytes, OAT4 mediated the high affinity transport of estrone sulfate (K(m) = 1.01 microM) and dehydroepiandrosterone sulfate (K(m) = 0.63 microM) in a sodium-independent manner. OAT4 also mediated the transport of ochratoxin A. OAT4-mediated transport of estrone sulfate was inhibited by several sulfate conjugates, such as p-nitrophenyl sulfate, alpha-naphthyl sulfate, beta-estradiol sulfate, and 4-methylumbelliferyl sulfate. By contrast, glucuronide conjugates showed little or no inhibitory effect on the OAT4-mediated transport of estrone sulfate. OAT4 interacted with chemically heterogeneous anionic compounds, such as nonsteroidal anti-inflammatory drugs, diuretics, sulfobromophthalein, penicillin G, and bile salts, whereas tetraethylammonium, an organic cation, did not. OAT4 is the first member of the multispecific organic anion transporter family, which is expressed abundantly in the placenta. OAT4 might be responsible for the elimination and detoxification of harmful anionic substances from the fetus.

Amino Acid Sequence↗
PubMed2000

Analysis of accumulated T cell clonotypes in patients with systemic lupus erythematosus.

OBJECTIVE: To compare the accumulated T cell clonotypes in peripheral blood (PB) samples obtained at various times, and the accumulated T cell clonotypes in a PB sample and in an affected kidney, from patients with systemic lupus erythematosus (SLE). METHODS: Peripheral blood mononuclear cells (PBMC) were obtained at 2-4 different times from each of 5 SLE patients, with or without flare-up of the disease; in addition, a biopsied kidney tissue sample was obtained from 1 of the patients. RNA was extracted from each sample and complementary DNA was prepared. Genes that encode the variable region of T cell receptor (TCR) B chains (BV) of 3 BV families, 5S1, 8, and 14, were amplified by reverse transcription-polymerase chain reaction (PCR), and the PCR products were cloned for sequencing. RESULTS: A total of 877 cloned TCR genes was detected in the PBMC samples and the kidney sample. Oligoclonal T cell expansion was detected in 34 of the 36 PCR-amplified BV samples from PBMC (amplification of 3 BV families in 2-4 samples from 5 patients). The composition of clonally expanded T cell clonotypes was relatively stable in the patients with inactive SLE. In contrast, the composition of clonotypes in the PB changed drastically after the patient experienced the active phase of the disease. T cell clonotypes that had accumulated in the kidney appeared to be restricted and distinct from those that had accumulated in the PB of the same patient. CONCLUSION: Different T cell clonotypes expand at different times and at different sites in patients with active SLE. The sensitizing antigens may change over the course of the disease and may be different at each site.

Adult↗
PubMed2000

The multispecific organic anion transporter (OAT) family.

Organic anion transporters play important roles in the elimination of a variety of endogenous substances, xenobiotics and their metabolites from the body. During the last decade, molecular cloning has identified several families of multispecific organic anion transporters mediating the renal and hepatic elimination of organic anions and, most recently, the OAT (organic anion transporter) family, the founding member of which (OAT1) is the basolateral p-aminohippurate (PAH) transporter in the renal proximal tubule. So far, four isoforms have been identified. OATs are membrane proteins with 12 putative membrane-spanning domains and function as sodium-independent exchangers or facilitators. OATs show weak structural similarity to organic cation transporters (OCTs) and OCTN/carnitine transporters. OATs are multispecific organic anion transporters, the substrates of which include both endogenous (e.g. cyclic nucleotides, prostaglandins, urate, dicarboxylates) and exogenous anions (various anionic drugs and environmental substances). All members of the OAT family are expressed in the kidney, while some are also expressed in the liver, brain and placenta. The OAT family represents the renal secretory pathway for organic anions and is also involved in the distribution of organic anions in the body.

Animals↗
PubMed2000

Regulation by protein kinase C of organic anion transport driven by rat organic anion transporter 3 (rOAT3).

The organic anion transporter 3 (rOAT3) is a multispecific OAT localized at the basolateral membrane of the proximal tubule. The purpose of this study was to elucidate the role of protein kinase C (PKC) in the regulation of organic anion transport driven by rOAT3 and its mechanism of action. For this purpose, we established and utilized cells derived from the second segment of proximal tubule from mice stably expressing rOAT3 (S2 rOAT3). Phorbol 12-myristate 13-acetate (PMA), a PKC stimulator, attenuated the cellular uptake of estrone sulfate (ES), a prototype organic anion for rOAT3, in a dose- and time-dependent manner. PMA treatment resulted in a decrease in the Vmax, but not the Km of uptake of ES in S2 rOAT3. Treatment of S2 rOAT3 with other PKC stimulators or diacylglycerols also inhibited the uptake of ES, whereas that with an inactive phorbol ester did not. Chelerythrine chloride, a PKC inhibitor, reversed the PMA-induced decrease in uptake of ES in S2 rOAT3. These results suggest that PKC activation downregulates rOAT3-mediated organic anion transport. This down-regulation may be due to the inhibition of translocation or internalization of the rOAT3 protein, resulting in the decrease in the Vmax of rOAT3-mediated organic anion transport.

Animals↗
PubMed2000

Developmental changes in multispecific organic anion transporter 1 expression in the rat kidney.

BACKGROUND: The cDNA of the multispecific organic anion transporter 1 (OAT1) responsible for the tubular secretion of organic anions was recently isolated. In the current study, we investigated the developmental changes in OAT1 expression in the rat kidney. METHODS: Ontogenic expression of rat OAT1 was investigated by Northern blot, in situ hybridization, Western blot, and immunohistochemical analysis. In addition, para-aminohippurate (PAH) accumulation was measured using fetal, neonatal, and adult rat kidney slices. RESULTS: In Northern blot analysis, OAT1 was detected as early as on embryonic day 18 in the fetal kidney. The expression level of OAT1 mRNA increased remarkably just after birth (postnatal day 0). In situ hybridization revealed OAT1 expression on embryonic day 19. In both the fetal and neonatal kidneys, OAT1 mRNA was localized in a relatively deep region in the cortex. Western blot analysis detected OAT1 protein on embryonic day 20, and the expression level increased after birth. Immunohistochemical analysis did not reveal OAT1 staining in the fetal kidneys. A faint signal of OAT1 protein was detected on postnatal day 0; thereafter, the expression level increased. In the functional study using kidney slices, low but definite probenecid-sensitive PAH accumulation was noted in fetal rat kidney on embryonic day 20. After birth, probenecid-sensitive PAH uptake was increased. CONCLUSIONS: The present study consistently demonstrates the remarkable increase of OAT1 expression after birth, and the immature excretory capacity of the proximal tubules of the neonatal kidney can be attributed, at least in part, to the low expression level of OAT1.

Aging↗
PubMed2000

Experimental carinal replacement with an Y-shaped collagen-conjugated prosthesis.

BACKGROUND: A new prosthesis was designed for reconstruction of the bifurcation of the trachea and used for experimental carinal replacement in dogs. METHODS: The main Frame of the new prosthesis consists of Y-shaped Marlex mesh tube reinforced with polypropylene spirals. It is coated with collagen extracted from porcine skin to provide biocompatibility and airtightness. Carinal replacement with omentopexy was performed in 17 dogs. RESULTS: Seven dogs survived the postoperative period, and 10 dogs died within 11 days after the operation. The main causes of early postoperative death were fistula and air leakage from the prosthesis. Causes of late postoperative death were obstruction of the main bronchus (two) and lung abscess (one). The four long-term survivors had no stenosis or dehiscence until they were sacrificed 15 months after the operation. Histological examination of these dogs revealed that the luminal surface was covered either with ciliated columnar epithelium or non-ciliated squamous epithelium. CONCLUSIONS: The study results suggest the possibility of successful prosthetic carinal reconstruction with epithelial regrowth using this Y-shaped prosthesis.

Animals↗
PubMed2000

Carinal reconstruction with a Y-shaped collagen-conjugated prosthesis.

BACKGROUND: Carinal reconstruction by direct suturing is associated with a high mortality because high tension at the anastomosis can lead to tracheobronchial fistula. A new tracheal prosthesis was therefore designed for reconstruction of the tracheal bifurcation and applied for experimental carinal replacement in dogs. METHODS: The main frame of the new prosthesis consists of a Y-shaped Marlex mesh tube (C.R. Bard, Inc, Billerica, Mass) reinforced with polypropylene spirals, to which collagen extracted from porcine skin is chemically conjugated to provide biocompatibility and airtightness. This conjugated collagen is composed of amorphous and sponge collagen layers. The tracheobronchial bifurcation was replaced with the prosthesis in 10 beagle dogs. RESULTS: Eight dogs survived the postoperative period, and 2 dogs died within 4 days after the operation. Bronchoscopic examination revealed that the tracheal prosthesis was covered with smooth whitish tissue and that no stenosis or dehiscence was present in the 8 dogs even 6 months after the operation. Slight mesh exposure was recognized in 1 dog. Histologic examination revealed that approximately one half of the luminal surface was covered with ciliated columnar epithelium or nonciliated squamous epithelium. In the remaining lumen, especially in the middle portion of the prosthesis, connective tissue without epithelium was observed. CONCLUSIONS: These long-term results indicate that our bifurcated tracheal prosthesis can be used for reconstruction of the tracheobronchial bifurcation with long-term safety.

Animals↗
PubMed2000

Immunosuppressant-free allotransplantation of the trachea: the antigenicity of tracheal grafts can be reduced by removing the epithelium and mixed glands from the graft by detergent treatment.

OBJECTIVE: To develop a method for eliminating the epithelium and mixed glands from tracheal grafts by detergent treatment and evaluate these grafts for immunosuppressant-free allotransplantation in dogs. METHODS: Fresh canine tracheal grafts were treated with a detergent (1% Triton X-100 t-octylphenoxypolyethoxyethanol; T-9284; Sigma Chemical Co, St Louis, Mo) at 4 degrees C for 48 hours. The grafts were then used for intrathoracic 5-ring tracheal replacement in other dogs without immunosuppressant treatment (n = 6, detergent treatment group). In the control group (n = 6) fresh untreated canine tracheal segments were implanted as allografts. All the implanted grafts were covered with an omental pedicle. RESULTS: In the detergent treatment group the chondrocytes in the graft had a similar appearance to those in the fresh trachea, indicating that the chondrocytes remained viable after the detergent treatment. In 5 of the 6 grafts, the epithelium and mixed glands had been removed completely. After transplantation, these 5 grafts were incorporated by the host trachea without stenosis. In the remaining treated tracheal graft, in which removal of the epithelium was incomplete, moderate stenosis was observed at the fourth week after implantation, although this was not progressive. In the control group, granulation tissue of the graft and significant stenosis were observed after transplantation. CONCLUSION: The antigenicity of tracheal grafts can be greatly reduced by removing the epithelium and mixed glands by the use of detergent treatment. The epithelium and mixed glands of the graft appear to be the determining elements involved in rejection after tracheal allotransplantation.

Animals↗
PubMed2000

Six-year disease-free survival of a patient with metastatic eyelid squamous cell carcinoma and colon adenocarcinoma after repeated postoperative adoptive immunotherapy.

A 74-year-old male was affected concurrently with squamous cell carcinoma of the left eyelid and adenocarcinoma of the colon, both with lymph node metastasis. He underwent exenteration of the left orbit with left modified radical neck dissection and subsequently resection of the transverse colon with regional lymph node dissection. The patient has been treated by an adoptive immunotherapy as a sole postoperative modality without receiving any chemotherapeutic agents causing immunosuppression. For the adoptive immunotherapy, autologous peripheral blood lymphocytes were activated with an immobilized anti-CD3 antibody and IL-2 for 14 days (the CD3-AT cells). The infusion with 1.38 x 10(10) CD3-AT cells has been repeated 150 times in total at the time of writing. Neither recurrence nor additional metastasis has been detected for 6 years after surgery.

Adenocarcinoma↗
PubMed2000

Synthesis and pharmacological activity of O-(5-isoxazolyl)-L-serine.

A novel isoxazole derivative, O-(5-isoxazolyl)-L-serine (OIS, 1), was synthesized by a Mitsunobu reaction of isoxazolin-5-one (4) with N-Boc-L-serine tert-butyl ester (5) and subsequent deprotection of the coupling product. Its structure was elucidated by spectroscopic analyses. The pharmacological activity of 1 was also examined with cloned glutamate receptors and transporters using a Xenopus oocyte-expressing system showing substrate activity on an excitatory amino acid carrier 1 (EAAC 1) as a glutamate transporter.

ATP-Binding Cassette Transporters↗