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Biomedical subjects

T Oka

Publications and source records attributed to T Oka.

At least 127 records · Page 7Linked to original sources

Effects of peptidase inhibitors on anti-nociceptive action of dynorphin-(1-8) in rats.

Previous in vitro studies showed that the degradation of dynorphin-(1-8) [dyn-(1-8)] by cerebral membrane preparations is almost completely prevented by a mixture of three peptidase inhibitors (PIs), amastatin, captopril and phosphoramidon. In the present investigations, effects of the three PIs on the anti-nociception induced by the intra-third-ventricular (i.t.v.) administration of dyn-(1-8) were examined. The inhibitory effect of dyn-(1-8) on the tail-flick response was increased more than 100-fold by the i.t.v. pretreatment of rats with the three PIs. The inhibition produced by dyn-(1-8) in rats pretreated with any combination of two PIs was significantly smaller than that in rats pretreated with three PIs, indicating that any residual single peptidase could inactivate significant amounts of dyn-(1-8). The antagonistic effectiveness of naloxone, a relatively selective mu-opioid antagonist, indicates that dyn-(1-8)-induced inhibition of tail-flick response in rats pretreated with three PIs is mediated by mu-opioid receptors. Furthermore, mu-receptor-mediated inhibition induced by dyn-(1-8) was significantly greater than that produced by [Met5]-enkephalin in rats pretreated with three PIs. The data obtained in the present investigations together with those obtained in previous studies strongly indicate that dyn-(1-8) not only has well-known kappa-agonist activity but also has high mu-agonist activity.

Analgesics, Opioid↗

Differentiation of rat thymic myoid progenitor cell line established by coculture with human T-lymphotropic virus type-I producing human T cells.

A thymus-derived myoid precursor cell line (ST1), which differentiates to myoid cells in the growth arrest condition, was established by the cocultivation of F344 rat thymic cells with human T-lymphotropic virus type-I (HTLV-I)-producing human lymphoid cells. No integration of HTLV-I was detected in ST1 cells by Southern blot hybridization. In a differentiation culture condition such as confluent culture or serum starvation, ST1 cells began to fuse, creating multinuclear giant cells, with the induced expression of MyoD1 and various muscle-specific antigens, including alpha-sarcomeric actin, skeletal muscle myosin, myoglobin, desmin, and acetylcholine receptor. Ultrastructural investigation revealed that differentiated ST1B cells created aggregates of thick and thin filaments with Z-band-like composition, then formed sarcomeric structures and tubular honeycomb arrays. Finally, these cells spontaneously contracted with a frequency of 0.5-2.0 Hz and synchronized with adjoining cells. Transplantation of ST1B cells into nude mice produced a small tumor nodule, showing clear differentiation to skeletal muscle cells. ST1B cells did not indicate any colony-forming activities in soft agar, demonstrating that ST1B cells retain some of the physiologically normal phenotypes. This rare cell line is promising for use in various physiological and pathological investigations including functional research of thymic myoid cells and the pathological role in autoimmune diseases, as well as animal model experiments of cell therapy related to muscular degenerative disorders or regeneration of injured muscles.

Animals↗

Ultrasonic coagulator for video-assisted internal mammary artery harvest.

BACKGROUND: The Harmonic Scalpel (HS; Ethicon Endo-Surgery, Cincinnati, OH, USA) is an ultrasonic coagulator that generates less heat than electrocautery. We compared canine internal mammary arteries (IMAs) harvested using the HS or electrocautery and reviewed the early clinical outcome after thoracoscopic IMA takedown with the HS. METHODS: Using HS and bipolar electrocautery (BE), 51 and 49 IMA branches, respectively, in six mongrel dogs were divided. The divided branches were subjected to a pressure tolerance test. The impact of coagulation on the main trunk was investigated microscopically. Thoracoscopic IMA harvesting with the HS was performed in 41 patients. Seven human IMA segments including 10 branches were examined microscopically. Postoperative angiography of 40 IMA grafts (97.6%) was performed. RESULTS: All the IMA branches withstood intraluminal pressures up to 250 mmHg. With BE, coagulation reached the adventitia of the main trunk in six segments (12.2%), but the HS caused no injury. Thoracoscopic IMA harvesting with excellent hemostasis was achieved using only the HS in all 41 patients. The main trunks of the human IMA segments were microscopically intact, and postoperative angiography demonstrated that the IMA grafts were intact. CONCLUSION: The HS appears to be a reliable coagulator for thoracoscopic IMA harvesting with minimal damage.

Animals↗

Details of hyperplastic polyps of the stomach shrinking after anti-Helicobacter pylori therapy.

The precise etiology of hyperplastic polyps of the stomach is unknown, but recent studies suggest that they arise as a consequence of inflammation occurring in intimate association with Helicobacter pylori infection. The process of polyp regression after anti-H. pylori therapy, however, is unclear. Here we report a patient with large hyperplastic polyps of the stomach that regressed markedly after anti-H. pylori therapy. Histological examination of the regressed polyps revealed a decrease in the height of the hyperplastic foveolar epithelium and a decrease in the amount of inflammatory cell infiltration in the stroma. In addition, the percentage of Ki-67-positive hyperplastic epithelial cells markedly decreased after anti-H. pylori therapy, indicating that the epithelial cell proliferation rate had markedly decreased after treatment. At the same time, the degree of cyclooxygenase-2 expression in epithelial cells in the polyps decreased after treatment. Because cyclooxygenase-2 is expressed at sites of inflammation or neoplasm, these findings are consistent with a decrease in inflammatory cell infiltration, and represent resolving inflammation.

Anti-Bacterial Agents↗

Video-assisted thoracoscopic treatment for spontaneous pneumothorax as two-day surgery.

BACKGROUND: To see whether video-assisted thoracoscopic surgery (VATS) for spontaneous pneumothorax (SP) as 2-day surgery is a safe and cost-effective procedure, we retrospectively compared VATS as 2-day surgery with standard VATS. METHODS: From April 1994 to March 2000, 139 SP patients were operated on: 115 patients were operated on by means of standard VATS and 24 were treated by 2-day surgery. The parameters we compared were the postoperative complications, hospitalization cost, and relapses. RESULTS: Excepting that 2 of those selected for 2-day surgery required another hospitalization, short-term complications were considered to be similar for the two groups. The median economic cost of 2-day surgery was about $5,822 US dollars and was lower than that of standard VATS. The difference in the recurrence rate between the two groups was not significant. CONCLUSIONS: We conclude that VATS as 2-day surgery is a safe and cost-effective procedure.

Adolescent↗

Intraoperative balloon angioplasty for aortic coarctation after Norwood operation.

We report intraoperative balloon angioplasty for recurrent aortic coarctation in hypoplastic left heart syndrome. After bidirectional Glenn anastomosis, balloon angioplasty was performed via ascending aorta. Pressure gradient across the coarctation decreased from 45 to 8 mm Hg. Intravascular ultrasound revealed successful splits of thickened intima without any extensive dissection. Intraoperative balloon angioplasty is a safe and favorable procedure for hypoplastic left heart syndrome because balloon inflation before bidirectional Glenn anastomosis could induce serious ventricular collapse or arrhythmias.

Angioplasty, Balloon↗

Evidence of [Ca(2+)]i elevation by anti-calreticulin immunoreactive protein in neurons.

Calreticulin is a multifunctional Ca(2+)-binding protein. The effect of anti-calreticulin antibody on intracellular free calcium concentration [Ca(2+)]i was studied in cultured neurons using fura-2 based microfluorometry. Anti-calreticulin increased [Ca(2+)]i in a dose dependent manner. The anti-calreticulin antibody produced a rapid transient [Ca(2+)]i peak followed by a long slowly decaying plateau. Anti-calreticulin induced extracellular Ca(2+) influx in cultured neuron cells was blocked partially by N-methyl-D-aspartate receptor (NMDAR) antagonist 2-amino-5-phosphonovaleric acid (AP5) and spider polyamine toxin JSTX-3, which is recognized as a blocker of glutamatergic nervous system. Furthermore, anti-calreticulin induced intracellular Ca(2+) desensitized NMDAR. Dual immunofluorescent staining studies revealed that NMDAR co-localized with calreticulin in the cultured neurons. Thus, the signal transduction system of NMDA might be closely concerned with the extracellular calreticulin like protein.

Amphibians↗

Effects of N-methyl-D-aspartate, kainate or veratridine on extracellular concentrations of free D-serine and L-glutamate in rat striatum: an in vivo microdialysis study.

Using an in vivo microdialysis technique, we have investigated the effect of N-methyl-D-aspartate (NMDA) or kainate on the extracellular concentrations of free D-serine and L-glutamate in the striatum. A intrastriatal perfusion of NMDA or kainate caused a significant increase in the extracellular release of L-glutamate, but a significant decrease in that of D-serine. Co-perfusion of an NMDA receptor antagonist, MK-801, or an alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid/kainate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), with NMDA or kainate significantly reversed the NMDA- or kainate-induced decrease in the extracellular level of D-serine, respectively. The NMDA- or kainate-evoked increase in the extracellular L-glutamate level was also reversed by co-perfusion of MK-801 or CNQX, respectively. Because D-serine acts as a potent and selective agonist for the glycine site of the NMDA receptor and because intracerebroventricularly injected D-serine is accumulated in the astrocytes, D-serine could be taken up by the astrocytes following synaptic activation. Furthermore, because cortical ablation to remove corticostriatal glutamatergic inputs attenuates the excitotoxic effects of kainate in the striatum, L-glutamate may enhance its own release through a presynaptic NMDA and/or non-NMDA receptor-mediated mechanism.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Molecular cloning and characterization of three novel cytochrome P450 2D isoforms, CYP2D20, CYP2D27, and CYP2D28 in the Syrian hamster (Mesocricetus auratus).

We cloned three novel cytochrome P450 (CYP) 2D cDNAs in the Syrian hamster (Mesocricetus auratus). Each clone contained an open reading frame of 1500 nucleotides encoding a protein of 500 amino acids. The deduced amino acid sequences of these had high identities with those of the other CYP2D members, therefore, the clones were assigned as CYP2D20, CYP2D27, and CYP2D28. Northern blot analysis showed that the CYP2D27 mRNA was expressed in liver, but not in kidney, small intestine, and brain, while the CYP2D20 and CYP2D28 mRNAs were not detected in these tissues examined. The expression of CYP2D27 mRNA in liver did not show sex difference and was not induced by either 3-methylcholanthrene or phenobarbital treatment. We characterized the enzyme activities of recombinant CYP2D27 expressed in COS-7 cells. The CYP2D27 protein had the bufuralol 1'-hydroxylase and debrisoquine 4-hydroxylase activities that are specific to the CYP2D subfamily.

Amino Acid Sequence↗

Flow cytometric analysis of lymphoid cells in thymic epithelial neoplasms.

OBJECTIVE: There have been conflicts concerning the criteria for diagnosing malignant epithelial neoplasms of thymic origin. To differentiate thymic carcinomas from thymomas, the maturation stage of T-lineage lymphoid cells infiltrating thymomas and thymic carcinomas was examined by flow cytometry to associate it with the degree of tumor malignancy. METHODS: Multidimensional flow cytometric analysis was performed on the lymphoid cells extracted from 27 thymic epithelial neoplasms (14 encapsulated thymomas, ten invasive thymomas, and three thymic carcinomas) by using anti-CD3, -CD4, -CD8, -CD10, -CD20, -CD38, -CD45RA, and -CD45RO monoclonal antibodies. RESULTS: CD4 and CD8 were co-expressed on 76.8% of the lymphoid cells in encapsulated thymoma (N=14), 59.2% in invasive thymoma (N=10), and 6.7% in thymic cancer (N=3). The percentage of CD4- or CD8- single positive cells was 11.4% in encapsulated thymoma, 23.9% in invasive thymoma, and 77.7% in thymic cancer. The percentage of CD10-positive cells was 20.8% in encapsulated thymoma, 13.2% in invasive thymoma, and 6.0% in thymic cancer. The percentage of CD20-positive cell was 2.6% in encapsulated thymoma, 3.3% in invasive thymoma, and 31.6% in thymic cancer. There were significant statistical differences in the percentages of CD4/CD8 double positive cells, CD4- or CD8-single positive cells, CD10-positive cells and CD20-positive cells among the three groups. Two cases classified as invasive thymoma by pathohistological examination, however, showed the infiltration of mature lymphocytes like as thymic cancers. CONCLUSIONS: CD4+CD8+ or CD10+ T-lineage cells were the most reliable markers of the benignancy of thymic epithelial tumors. CD4- or CD8-single positive cells or CD20-positive cells were characteristic in thymic carcinoma. Flow cytometry on the maturity of lymphoid cells infiltrating thymic epithelial tumors was feasible for determining their degree of malignancy. Some invasive thymomas showed the intermediate characteristics with thymomatous epithelia and mature lymphoid cells.

Adult↗

Epstein-Barr virus infection to Epstein-Barr virus-negative nasopharyngeal carcinoma cell line TW03 enhances its tumorigenicity.

Almost all nasopharyngeal carcinomas (NPCs) are infected by Epstein-Barr virus (EBV), but most ex vivo NPC cells lose EBV genomes during passages. In this study, an EBV-negative NPC cell line, TW03, established from EBV-carrying NPC was reinfected with EBV by cocultivation with irradiated Akata cells carrying recombinant EBV containing a neomycin-resistant gene. The reinfected EBV (+) TW03 cells expressed EBERs and EBNA1, but not EBNA2, lytic proteins (ZEBRA and EA-D), or LMP1. They had an epithelial appearance similar to that of EBV (-) TW03 cells. The doubling times of EBV (+) and EBV (-) TW03 cells were almost identical. However, the EBV (+) TW03 cells formed larger colonies with ragged contours in anchorage-independent cultures. An in vitro invasion assay showed that EBV (+) TW03 cells had a higher invasive activity than EBV (-) TW03 cells (p < 0.01). Both EBV (-) and EBV (+) TW03 cells formed poorly differentiated squamous cell carcinomas in SCID and nude mice. EBV (+) TW03 cells showed a higher tumorigenicity to nude mice (12 of 13) than EBV (-) TW03 cells (1 of 9) (p < 0.001). In the severe combined immunodeficiency (SCID) tumors of EBV (+) TW03 cells, not all of the tumor cells were EBER-1 positive. EBER-1 was more frequently detected in the peripheral regions and daughter nodules of the tumors than in the central areas. The microdissection polymerase chain reaction showed that the EBER-1-negative TW03 cells in the EBV (+) TW03 SCID tumors lost EBV genomes. EBER-1-negative cells showed as high a rate of Ki-67 positivity as EBER-1-positive cells, indicating that the former were proliferating rather than dead or dying. In horny pearls, keratinizing cells were ZEBRA-positive and EBER-negative. Loss of EBV genomes was not associated with squamous differentiation. These data indicated that reinfection of EBV promotes the tumorigenicity of EBV (-) TW03 cells by enhancing the invading activity.

Animals↗

New polymorphisms of human CD80 and CD86: lack of association with rheumatoid arthritis and systemic lupus erythematosus.

The crucial role of costimulatory molecules, CD28, CTLA-4, CD80 and CD86, for T cell activation and inhibition has been established. In the previous study, we reported the results of a polymorphism screening of human CTLA-4 gene. In this study, we screened for polymorphisms of human CD28, CD80 and CD86 genes, and detected that polymorphisms were tested for the association with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Variations were identified in the coding regions of CD80 (452G/A, 614C/G and 864A/G) and CD86 (1057A/G), while no variation was observed in the coding region of CD28. The variations at CD80 position 452 and CD86 position 1057 were present in a substantial proportion of the Japanese population, and were considered to be single nucleotide polymorphisms within the coding sequence (cSNPs). CD80 864 (G-->A) leads to the amino acid substitution N186D, and CD86 1057 (A-->G) results in A304T substitution. Furthermore, in the analysis of CD80 5'-flanking region, six SNPs, -454C/A, -387T/C, -232G/A, -79G/C, -7T/C and /A, and one insertion, -558ins (CATGA), were identified. The combination of these variations was found to constitute four promoter alleles of CD80. None of the observed variations was significantly associated with RA or SLE. Further studies will be of particular interest to examine the functional difference of the promoter alleles for the transcriptional activity of CD80, as well as the evolutionary pathway of the four alleles.

Alleles↗

Rotavirus infection among infants with diarrhea in Pakistan.

Rotavirus was examined in 818 diarrheal stool samples collected in Karachi, Pakistan, from 1990 to 1997. Rotavirus was detected in 112 samples (13.7%). The predominant serotypes were G1 and G4 and G3 was not detected. The predominant type changed between years. Rotavirus was found in all seasons and most infections were found in children aged less than 2 years.

Diarrhea↗

Feasibility study of autologous peripheral blood stem cell transplantation for the treatment of childhood acute myelogenous leukemia.

BACKGROUND: The primary object of this study was to identify treatment-related variables that may predict relapse of acute myelogenous leukemia (AML) after autologous peripheral blood stem cell transplantation (PBSCT), which will be critical for the development of a suitable protocol for wider application. METHODS: A total of 28 children (age 0-18 years) with AML underwent PBSCT and have had a minimum follow-up of 25 months; including 24 patients in their first complete remission (CR) and four in their second CR. The patients were divided into two cohorts according to the study phase: 16 patients were treated in an early phase pilot study and 12 patients in their first CR were treated in a prospective trial. Fifteen of the first-CR patients had any of the cited high-risk features of high WBC count (>100x10(9)/l; n = 5), FAB M0/M4/M5/M7 subtypes (n = 11) or delayed achievement of CR (n = 9). Except in one patient, cytoreductive regimens did not include total body irradiation (TBI). RESULTS: After PBSCT, one patient died of veno-occulsive disease (VOD) and another patient relapsed early on day 43, but the remaining patients showed engraftment. Leukemic relapse was observed 1-29 months after PBSCT (median, 8 months); in all of the 4 children treated in their second CR and in 11 of the 24 patients (46%) treated in their first CR. The remaining patients have been disease-free for 24 to 97 months (median, 53 months). Using a multivariate analysis, the timing of apheresis was the most significant prognostic factor for those treated in their first CR (p = 0.03); 12 of the 16 patients whose PBSC were collected beyond 2.5 months of CR continue to remain in CR, while seven of the eight patients whose PBSC were harvested within 2.5 months of CR relapsed. CONCLUSION: Although the small number of patients studied does not allow firm conclusions to be drawn regarding the relative effectiveness of this therapy, the results do suggest the feasibility of further studies of PBSCT for the treatment of childhood AML with high-risk features including the assessment of minimum residual disease.

Adolescent↗