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Biomedical subjects

M Shinkai

Publications and source records attributed to M Shinkai.

At least 37 records · Page 2Linked to original sources
PubMed2000

Bystander-killing effect and cyclic induction of TNF-alpha gene under heat-inducible promoter gadd 153.

The bystander-killing effect and cyclic induction of tumor necrosis factor (TNF)-alpha gene expression under the heat-inducible promoter gadd 153 (growth arrest and DNA damage) were investigated. The plasmid harboring the TNF-alpha gene under the control of the gadd 153 promoter (pGadTNF) was introduced into cells of the human glioma cell line U251-SP. When the transfected cells were exposed to heat treatment, TNF-alpha gene expression was induced. The heated pGadTNF-transfected cells were co-cultured the nonheated pGadTNF-transfected cells as bystander cells. As a result, TNF-alpha gene expression in the bystander cells was observed. The level of TNF-alpha gene expression was further enhanced in the co-cultured cells. Due to this cyclic induction, a strong cytotoxic effect on the bystander cells was observed. Based on this bystander-killing effect, it was concluded that the transfection of the TNF-alpha gene under the control of the gadd 153 promoter into tumor cells combined with hyperthermia would be a potent tool for cancer therapy.

Journal Article↗
PubMed1999

Synergism between mild hyperthermia and interferon-beta gene expression.

In the present study, the synergistic effect of mild hyperthermia in combination with gene expression of interferon-beta (IFN-beta) was examined in vitro in the human glioma cell line U87MG. The cells transiently expressed the IFN-beta gene under the control of the mouse mammary tumor virus promoter and were then subjected to temperature elevation (41 degrees C for 1 h). In terms of the cell killing effect, the optimum scheme was obtained by transfection for 4 days before hyperthermia, i.e. rate in the time course of IFN-beta gene expression. The relative specific growth rate decreased to 32% compared with the control while it was only 40% under the hyperthermic conditions. These observations suggest that IFNbeta expression was able to enhance the sensitivity of transfected glioma cells to mild hyperthermia.

Animals↗
PubMed1999

Synthesis of an artificial glycoconjugate polymer carrying Pk-antigenic trisaccharide and its potent neutralization activity against Shiga-like toxin.

Fluorescence-labeled glycoconjugate polymers carrying carbohydrate segments of a globotriaosyl ceramide (Gb3) were synthesized and subjected to biological assays using Escherichia coli O-157 strains and Shiga-like toxins (Stx-I and Stx-II). For the fluorescence labeling, a new polymerizable fluorescent monomer with a TBMB carbonyl chromophore (Ex. 325 nm, Em. 410 nm) was designed. A glycosyl monomer of the trisaccharide segment of Gb3 was prepared from p-nitrophenyl beta-lactoside and copolymerized with acrylamide and the fluorescent monomer to prepare a fluorescence-labeled glycoconjugate copolymer carrying [alpha-D-galactopyranosyl-(1-->4)-beta-D-galactopyranosyl]-(1-->4)-beta- D-glucopyranoside. The polymer showed potent neutralization activity against Stx-I and also binding activity onto E. coli O-157 strains.

Antigens↗
PubMed1999

Effect of functional magnetic particles on radiofrequency capacitive heating.

Magnetic particles (magnetite) were used to make radiofrequency (RF) capacitive hyperthermia effective to a specific site. In an agar phantom experiment, a magnetite-containing agar piece was buried in a large agar phantom and heated by an 8 MHz-RF capacitive heating device. The magnetite-containing agar piece was heated more than the magnetite-free agar phantom, and the specific adsorption rate in the phantom was increased 1.5 times by the magnetite particles. The temperature distribution in the large agar phantom showed that the highest temperature was obtained at the center of the magnetite-containing piece. The rate of temperature increase was approximately proportional to the magnetite concentration to the power 0.8. This method was applied to an in vivo experiment using a pig. Magnetite was prepared as a colloidal material dispersed in a carboxymethylcellulose solution (CMC-Mag) and intramuscularly injected in the pig femur. As a result of 8 MHz-RF heating, the temperature at the CMC-Mag-injected point increased to over 43 degrees C after 7 min, while the temperature at a point without magnetite was under 40 degrees C at the same time. The specific adsorption rate in the magnetite-containing tissue was twice that of the magnetite-free tissue. In addition, the time required to reach a temperature of over 43 degrees C was only 7 min, while it was over 15 min in the case without the CMC-Mag.

Animals↗
PubMed1998

The first cooperative living-related donor liver transplantation performed by two separate institution teams: The Kanagawa Liver Transplantation Program.

With the cooperation of surgeons in two separate institutes, living-related donor liver transplantation was safely performed at the Kanagawa Children's Medical Center. The donor operations were carried out at Kanagawa Cancer Center by surgeons of the hepatobiliary division and the liver grafts were immediately transported to Kanagawa Children's Medical Center by ambulance, and transplanted orthotopically. Since January 1995, five children with biliary atresia have been given partial liver grafts obtained from their mothers. The liver grafts were transported within 20 min, and functioned immediately after transplantation. The development of a pediatric liver transplantation program requires a multidisciplinary approach that can be provided only in a large tertiary referral children's medical center. Preparation for the clinical program involves training of surgical and nursing team members, both in an animal laboratory and at an established liver transplantation center. Special support for the program by the institute is essential and involves medical, nursing, and administrative divisions as well as social services, operating room personnel, and intensive care unit facilities. After careful planning, and with the invaluable help of the donor operating team, the Kanagawa Liver Transplantation Program has been realized, and its first transplantations conducted safely and successfully.

Adolescent↗
PubMed1998

Intracellular hyperthermia for cancer using magnetite cationic liposomes: an in vivo study.

The effect of hyperthermia on solid glioma tissue formed subcutaneously in the left femoral region of female F344 rats was investigated. Magnetite cationic liposomes (MCLs), which have a positive surface charge, were used as heating mediators for intracellular hyperthermia. MCLs were injected into the solid tumors, which were then subjected to irradiation by an alternating magnetic field (118 kHz, 384 Oe). The rats were divided into four groups, which received no irradiation (control: group I), or irradiation for 30 min given once (group II), twice (group III) or three times (group IV), and the hyperthermic effect on tumor growth was evaluated. Complete tumor regression was observed in 87.5% of the rats in group IV. In the other groups, tumors completely regressed in 20 and 60% of the rats in groups II and III, respectively. Histological observations showed that in group I tumors, MCLs were localized only around the point where they were injected, while in group II tumors they were a little more dispersed. In the cases of group III and IV tumors, however, the distribution of the MCLs was found to be widespread, and necrotic cells were observed throughout almost the entire tumor tissue. The high percentage of complete regression of group IV is considered to be due to this wide distribution of the MCLs. Furthermore, the treated rats showed no severe side-effects. These results suggest that our magnetic particles are potentially effective tools for the treatment of solid tumors.

Animals↗
PubMed1998

Antitumor immunity induction by intracellular hyperthermia using magnetite cationic liposomes.

Induction of antitumor immunity to T-9 rat glioma by intracellular hyperthermia using functional magnetic particles was investigated. Magnetite cationic liposomes (MCLs), which have a positive surface charge, were used as heating mediators for intracellular hyperthermia. Solid T-9 glioma tissues were formed subcutaneously on both femurs of female F344 rats, and MCLs were injected via a needle only into the left solid tumors (treatment side). The rats were then divided into two groups, which received no irradiation, or irradiation for 30 min given three times at 24-h intervals with an alternating magnetic field (118 kHz, 384 Oe). On the treatment side, the tumor tissue disappeared completely in many rats exposed to the magnetic field. The tumor tissue on the opposite side also disappeared completely, even though MCLs were not injected into the right solid tumors. To examine whether a long-lasting and tumor-specific immunity could be generated, the rats that had been cured by the hyperthermia treatment were rechallenged with T-9 cells 3 months later. After a period of transient growth, all tumors disappeared. Furthermore, immunocytochemical assay revealed that the immune response induced by the hyperthermia treatment was mediated by both CD8+ and CD4+ T cells and accompanied by a marked augmentation of tumor-selective cytotoxic T lymphocyte activity. These results suggest that our magnetic particles are potentially effective tools for hyperthermic treatment of solid tumors, because in addition to killing of the tumor cells by heat, a host immune response is induced.

Animals↗
PubMed1998

[Determinants of long-term outcome for operative survivors of acute aortic dissection].

Predictability of aorta-related complications and survival was examined in 79 operative survivors of acute aortic dissection. Follow-up was 94.9% complete and totaled 458 patient-years. Actuarial survival was 93 +/- 3% (+/- S.E.) (n = 43) at 5 years, and 74 +/- 8% (n = 13) at 10 years. Survival was significantly lower in patients having neurological complication. Freedom from aorta-related complications was 82 +/- 5% (n = 37) at 5 years, and 67 +/- 8% (n = 11) at 10 years. Multivariate Cox regression analysis identified residual entry and leak on anastomotic site as independent predictors of aorta-related complications. We conclude that in the treatment of acute aortic dissections, reducing the incidence of residual entry and leak on anastomotic site improves long-term outcome.

Acute Disease↗
PubMed1998

[Transrectal ultrasound guided transperineal systematic prostate biopsy].

We retrospectively reviewed the files of patients who had transperineally undergone a systematic six sextant prostate biopsy under guidance of transrectal ultrasound in longitudinal transsection by using Biopsy needle with the spring-roaded Biopsy gun. Of the 442 patients with suspicious glands visiting our clinic between May in 1992 and February in 1998, 486 biopsies were taken and pathological diagnosis was made to be prostate cancer in 153 (34.6%) patients, benign prostate hyperplasia in 270 and prostatitis in 19. Positive predictive values obtained in this series were calculated to be 49.4% in digital rectal examination (DRE), 55.0% in transrectal ultrasonogram (TRUS), 47.8% in prostate-specific antigen (PSA) level 4 ng/mL or greater and 83.5% if a patient had positive DRE and TRUS and PSA level 4 ng/mL or more. Relationship between number of positive cores and clinical stage of the patients was found (p < 0.0001). No complications relating to the biopsy were observed. This transrectal ultrasound guided transperineal systematic six sextant prostate biopsy was thought to be one of useful tools of the biopsy for detecting prostate cancer.

Aged↗
PubMed1997

Inhibitory action of sphingosine or ceramide on amylase secretion from isolated rat pancreatic acini.

Sphingosine and ceramide, products of sphingomyelin hydrosis by sphingomyelinase, have recently been regarded as second messengers for cell biological actions. On the other hand, exocrine pancreas is a typical organ to perform regulatory secretion of digestive enzymes, depending upon extracellular signals. We investigated the effects of sphingosine or ceramide on amylase secretion from isolated rat pancreatic acini. Either sphingosine or cell-permeable ceramide inhibits CCK8- or carbachol-induced enzyme secretion from isolated rat pancreatic acini in a dose-dependent manner. Sphingosine or ceramide itself does not affect basal amylase secretion from the acini. Ceramide also inhibits NaF-induced amylase secretion, indicating that it acts post the activation of receptor-linked GTP-binding protein. In our experiments, ceramide inhibited Ca2+ ionophore-induced amylase secretion, but not phorbol ester-induced secretion. These results indicate that ceramide affects secretory processes post intracellular Ca2+ mobilization in the exocrine pancreas.

Amylases↗
PubMed1997

Association of elongation factor 1 alpha and ribosomal protein L3 with the proline-rich region of yeast adenylyl cyclase-associated protein CAP.

CAP is a multifunctional protein; the N-terminal region binds adenylyl cyclase and controls its response to Ras while the C-terminal region is involved in cytoskeletal regulation. In between the two regions, CAP possesses two proline-rich segments, P1 and P2, resembling a consensus sequence for binding SH3 domains. We have identified two yeast proteins with molecular sizes of 48 and 46 kDa associated specifically with P2. Determination of partial protein sequences demonstrated that the 48-kDa and 46-kDa proteins correspond to EF1 alpha and rL3, respectively, neither of which contains any SH3-domain-like sequence. Deletion of P2 from CAP resulted in loss of the activity to bind the two proteins either in vivo or in vitro. Yeast cells whose chromosomal CAP was replaced by the P2-deletion mutant displayed an abnormal phenotype represented by dissociated localizations of CAP and F-actin, which were colocalized in wild-type cells. These results suggest that these associations may have functional significance.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Utility of urine and leukocyte cultures and plasma DNA polymerase chain reaction for identification of AIDS patients at risk for developing human cytomegalovirus disease.

Urine and blood leukocyte cultures and qualitative plasma polymerase chain reaction (PCR) and quantitative competitive (QC) PCR were evaluated for their ability to identify AIDS patients at risk for human cytomegalovirus (HCMV) disease. AIDS patients were followed with urine and blood specimens every 3 months. During a mean follow-up of 12 months, 26 (28%) developed HCMV disease. The sensitivity, specificity, positive predictive value, and negative predictive value for urine culture were 85%, 29%, 31%, and 83%; for leukocyte culture were 38%, 74%, 69%, and 81%; for qualitative plasma PCR were 89%, 75%, 58%, and 94%; for QC-PCR (>1000 copies/microL) were 35%, 100%, 100%, and 80%; and for QC-PCR (>100 copies/microL) were 73%, 90%, 73%, and 90%, respectively. Of 41 patients identified by qualitative PCR to have HCMV DNA in plasma, the 24 who developed HCMV disease had 1510 +/- 448 (mean +/- SE) peak copies of HCMV DNA/microL by QC-PCR, versus 161 +/- 52 for the 17 patients who did not develop disease (P = .0007). Thus, plasma PCR is superior to culture for identification of AIDS patients at risk for HCMV disease, and quantitation of plasma DNA further identifies high-risk persons.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Xenon provides faster emergence from anesthesia than does nitrous oxide-sevoflurane or nitrous oxide-isoflurane.

BACKGROUND: Xenon, an inert gas with anesthetic properties (minimum alveolar concentration [MAC] = 71%), has an extremely low blood:gas partition coefficient (0.14). Therefore, we predicted that xenon would provide more rapid emergence from anesthesia than does N2O+isoflurane or N2O+sevoflurane of equivalent MAC. METHODS: Thirty American Society of Anesthsiologists class I or II patients undergoing total abdominal hysterectomy were randomly assigned to receive 60% xenon, 60% N2O + 0.5% isoflurane, or 60% N2O + 0.70% sevoflurane (all concentrations are end-tidal: n = 10 per group). After placement of an epidural catheter, anesthesia was induced with standardized doses of midazolam, thiopental, and fentanyl. Thirty minutes later, xenon, N2O+isoflurane, or N2O+sevoflurane was started as previously assigned. These regimens were supplemented with epidural anesthesia with mepivacaine so that the mean arterial pressure and heart rate were controlled within 20% of the preoperative values. At the end of operation lasting approximately 2 h, all inhalational anesthetics were discontinued, and the patients were allowed to awaken while breathing spontaneously on an 8 l/min inflow of oxygen. A blinded investigator recorded the time until the patient opened her eyes on command (T1), was judged ready for extubation (T2), could correctly state her name, her date of birth, and the name of the hospital (T3), and could count backward from 10 to 1 in less than 15 s (T4). RESULTS: Emergence times from xenon anesthesia were: T1, 3.4 +/- 0.9 min; T2, 3.6 +/- 1 min; T3, 5.2 +/- 1.4 min; and T4, 6.0 +/- 1.6 min (mean +/- SD). These were one half to one third of those from N2O+sevoflurane (T1, 6.0 +/- 1.7 min; T4, 10.5 +/- 2.5 min) or N2O+isoflurane (T1, 7.0 +/- 1.9 min; T4, 14.3 +/- 2.8 min) anesthesia. The three groups did not differ in terms of patient demographics, the duration of anesthesia, the amount of epidural mepivacaine administered, or the postoperative pain rating. No patient could recalls intraoperative events. CONCLUSIONS: Emergence from xenon anesthesia is two or three times faster than that from equal-MAC N2O+isoflurane or N2O+sevoflurane anesthesia.

Adult↗
PubMed1997

Intracellular hyperthermia for cancer using magnetite cationic liposomes: ex vivo study.

Heating properties of magnetite cationic liposomes (MCL) were investigated in ex vivo experiments using implanted cell pellets. The cell pellets, which consisted of rat glioma T9 cells into which MCL had been incorporated in a petri dish, were implanted subcutaneously in the left femoral region of female F344 rats. The rats were placed in a magnetic field generating coil and irradiated with an alternating magnetic field (384 Oe, 118 kHz) for 60 min. The cell pellets were heated to over 43 degrees C by MCL in the magnetic field, but other body parts of the rats were not heated. After 3 cycles of magnetic heating, all glioma cells were killed and no tumor take was observed.

Animals↗