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Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 127 records · Page 7Linked to original sources
PubMed2000

Application of a biomagnetic measurement system (BMS) to the evaluation of gastrointestinal transit of intestinal pressure-controlled colon delivery capsules (PCDCs) in human subjects.

PURPOSE: For determination of the transit time through various parts of the gastrointestinal (GI) tract, we developed a method that provides the location of disintegration and drug release. This method involves GI magnetomarkergraphy (GIMG) using a 129-channel Shimadzu vector biomagnetic measurement system (BMS). METHODS: To magnetically label the pressure-controlled colon delivery capsule (PCDC) containing 75.0 +/- 0.5 mg of caffeine as a tracer drug, small capsule caps containing 90 mg of ferric oxide powdered magnetite (Fe2O3) were attached to PCDCs. After orally administration to fasted human volunteers, saliva samples were collected hourly and salivary caffeine concentration was measured. At the same time, locations of the magnetic PCDC were detected by BMS just after the PCDCs were magnetized with the coils of a magnetic resonance imaging (MRI) system. The magnetic field distributions were analyzed and the estimated positions were shown on the MRI picture of the same subject's abdominal structure. RESULTS: We magnetized PCDC with permanent magnets or an electromagnet before ingestion and the estimated locations of PCDC in the GI tract exhibited high estimation error. In order to increase the precision of estimated localization of PCDCs, PCDCs were magnetized within the coils of the MRI. As a result, these PCDCs had strong magnetic dipoles that were parallel to the sensor unit of BMS in every measurement, and therefore the spatial resolution of the PCDC's two-dimensional positions in the organs of the GI tract was within a range of several millimeters. CONCLUSIONS: GIMG is a powerful tool for the study of colon delivery efficiencies of PCDCs. The main advantage of GIMG is the capability to obtain even more detailed knowledge of the behavior and fate of solid pharmaceutical formulations during GI passage.

Abdomen↗
PubMed2000

Palatally displaced upper lateral incisors: relapse after orthodontic treatment and its correlation with dentoskeletal morphology.

The purpose of the present study was to determine whether the relapse tendency of the palatally positioned upper lateral incisor differs in patients treated with or without premolar extraction, and if there is any correlation between the amount of upper lateral incisor relapse and pretreatment dentoskeletal morphology or post-treatment changes. Forty-six patients with bilateral palatally displaced upper laterals who also exhibit maxillary dental constriction were separated into two groups: a premolar extraction (30 cases) group and a non-extraction (16 cases) group. All subjects had undergone orthodontic treatment with quad helix and edgewise appliances, followed by a 2-year retention period. Differences in the amount of the upper lateral incisor relapse and their correlations with the dentoskeletal morphology before and after treatment were determined on the lateral and postero-anterior cephalograms and dental casts. Results revealed that the upper lateral incisor relapse in the extraction group was significantly greater (p=0.0002) than the relapse in the non-extraction group. There was a positive correlation between incisor relapse and the distance of lateral incisor movement in both groups (r=0.539; p=0.030). Relapse in the non-extraction group was correlated with the widths of the upper dental arch (r</=-0.507, p</=0.044), with the naso-maxillary variables before treatment (r=-0.514, p=0.041), and also with changes in the upper inter-premolar and inter-molar widths during retention (r=0.514, p=0.040).

Journal Article↗
PubMed2000

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↗
PubMed2000

A study of carboplatin-coated tube for the unresectable cholangiocarcinoma.

Most cases of cholangiocarcinoma have reached an unresectable stage by the time they are discovered despite significant progress of diagnostic modalities. Many of these patients with obstructive jaundice are often treated by biliary drainage using stents to relieve the jaundice. However, the stent patency period is as short as 3 to 9 months because of tumor ingrowth or overgrowth, and mean survival is at most 12 months. Therefore, both continuous relief of obstructive jaundice and local control of the tumor are required in the treatment for advanced cholangiocarcinoma. In this investigation, we developed a new percutaneous transhepatic biliary drainage tube coated with carboplatin (carboplatin-coated tube; CCT). CCT continuously released a fixed amount of carboplatin for 4 weeks and showed an antitumor effect on human cholangiocarcinoma cell line HuCC-T1 in vitro. When CCT was embedded in subcutaneous tumor inoculated in nude mice, a significant reduction of tumor size with no apparent damage to normal adjacent tissue was observed. On the basis of these studies, 5 patients with inoperable cholangiocarcinoma were treated with CCT for 4 weeks. Overall efficacy rate of 5 patients with cholangiocarcinoma was 60% (partial response in 3 and no change in 2). No apparent side effect was observed in these patients. Thus, CCT may provide a new treatment modality for this disease. Randomized controlled trials comparing CCT therapy with palliative stenting are required to confirm these results.

Aged↗
PubMed2000

Isolated heterotopic pancreas causing intussusception.

Pediatric intussusception is usually idiopathic in origin, and a pathological lesion at the leadpoint is identified in only a small proportion of cases. Meckel's diverticulum is the most common location when such a lesion is found. Heterotopic pancreas has been seen most frequently in the stomach or duodenum; however, ileal lesions are rare. In the ileum, heterotopic pancreas is usually associated with Meckel's diverticulum and may cause intestinal obstruction by intussusception. However, isolated heterotopic pancreas in the ileum is distinctly rare and usually discovered incidentally during surgery for other conditions. In a review of English language literature, there were only a few pediatric cases of isolated ileal heterotopic pancreas causing intussusception. We report three additional pediatric cases and discuss the clinical significance of this unexpected rare entity.

Choristoma↗
PubMed2000

Detection of Epstein-Barr virus DNA in hepatocellular carcinoma tissues from hepatitis C-positive patients.

BACKGROUND: We have previously shown that hepatitis C virus (HCV) replication is promoted by the Epstein-Barr virus (EBV) in vitro. The aim of this study was to examine the EBV load in hepatocellular carcinoma (HCC) tissues from HCV antibody-positive patients. METHODS: DNA was extracted from paraffin sections from 168 HCC patients. After amplification of a region in the EBV BamHI W sequence by means of the polymerase chain reaction (PCR), it was detected by Southern hybridization and semi-quantified. Ten hyperplastic lesions from HCV-positive patients and 35 non-tumorous samples from hepatitis-negative patients served as controls. The PCR results were analyzed on the basis of the patient's hepatitis status. Univariate and multivariate analyses were performed to identify clinicopathologic factors for predicting EBV infection in HCC tissues. RESULTS: More than one copy of EBV DNA per 100 cells was detected in 56 (33%) of the HCC sections. The detection ratio in HCC tissues from HCV antibody-positive patients was 40% (45 of 113), which was significantly higher than that in tissues from HBV surface antigen-positive patients (14%, 5 of 37; P = 0.0018). The patient's serum HBV surface antigen and HCV antibody independently predicted the EBV positivity of HCC tissues. CONCLUSIONS: These results support our hypothesis that EBV could play an important role in the development of HCV-related HCC.

Blotting, Southern↗
PubMed2000

Characterization of monoclonal antibodies against mouse and rat platelet glycoprotein V (CD42d).

The mouse- and rat-platelet-specific hamster monoclonal antibody (MAb) 1C2, previously found to react with a thrombin-sensitive 74-kD glycoprotein, was now shown to recognize platelet glycoprotein V (GPV, CD42d). 1C2 reacted with NIH-3T3 cells in which recombinant mouse or rat GPV was expressed. Both 1C2 and 4A5, another mouse-platelet-specific rat MAb, immunoprecipitated GVP, although they recognized different epitopes. Side-by-side comparison confirmed that 1C2 as well as RPM.9, a MAb against rat GPV, recognized the same rat platelet molecule. In a mouse bone marrow culture, 1C2+ megakaryocytes emerged from CD41 (GPIIb)+1C2- megakaryocytes. Because 1C2+ megakaryocytes exhibited higher DNA ploidy distribution than CD41+ cells, GPV likely appears in the late stage of megakaryocyte maturation. This study established 1C2 as a MAb against mouse and rat GPV, namely CD42d, and as useful tool to study rodent megakaryopoiesis.

Animals↗
PubMed2000

Dental follicle cell-conditioned medium enhances the formation of osteoclast-like multinucleated cells.

An influx of mononuclear cells and the subsequent increase of osteoclasts around tooth germs suggests that the dental follicle (DF) regulates or influences bone resorption required for tooth eruption. In order to study the effects of DF cell products on osteoclast formation during tooth eruption, a conditioned medium (CM) was created in which DF cells were added to mouse bone marrow cultures. Tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleated cells were formed in the presence of 10 nM 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The CM, dose-dependently, stimulated the formation of TRAP-positive cells in the presence of 1,25(OH)2D3 for 14 days culture. The number of these cells decreased due to degradation in the control culture. A semi-solid methylcellulose assay in the presence of CM showed little expression of colony-stimulating activity. These results suggest that the DF cells of a developing tooth produce factor(s) that enhance osteoclast formation and bone resorption necessary for tooth eruption.

Acid Phosphatase↗
PubMed2000

Supraspinal, not spinal, alpha(2) adrenoceptors are involved in the anesthetic-sparing and hemodynamic-stabilizing effects of systemic clonidine in rats.

UNLABELLED: Clonidine, an alpha(2) agonist, reduces the anesthetic requirement and attenuates harmful hemodynamic responses to noxious stimuli. We examined the responsible sites of action in the central nervous system for the minimum alveolar anesthetic concentration (MAC) and MAC blocking adrenergic response (MAC-BAR) reducing effects of systemically administered clonidine in halothane-anesthetized rats. The MAC for halothane was determined by the tail clamp method, and MAC-BAR was defined as the MAC which attenuated hemodynamic responses within 10% after the tail clamp. We examined the effect of IV clonidine in the presence of rauwolscine, an alpha(2) antagonist given through IV, intrathecal (IT), intracisternal (IC), or intracerebroventrical (ICV) routes. IV clonidine reduced MAC and MAC-BAR dose-dependently. IV and ICV rauwolscine antagonized the MAC-reducing effect of clonidine, whereas IC and IT rauwolscine did not. In comparison, IV, ICV, and IC rauwolscine antagonized the MAC-BAR-reducing effect of clonidine; IT rauwolscine had no effect. Our data demonstrate that the alpha(2) adrenoceptors in the regions above mesencephalon and both the regions above mesencephalon and the lower brainstem are responsible for the MAC and MAC-BAR-reducing effect of systemic clonidine in rats, respectively. However, the spinal alpha(2) adrenoceptors were not involved in these effects of clonidine. IMPLICATIONS: In the regions above mesencephalon, alpha(2) adrenoceptors were the most responsible for the minimum alveolar concentration-reducing effect and both the lower brainstem and regions above mesencephalon were involved in the minimum alveolar concentration blocking adrenergic response-reducing effect of clonidine. The spinal alpha(2) adrenoceptors did not significantly contribute to these effects of clonidine.

Adrenergic alpha-Agonists↗
PubMed2000

Production, characterization, and application of monoclonal antibodies which distinguish four glucosyltransferases from Streptococcus sobrinus.

A 1,3-alpha-glucan synthase (GTF-I), a highly branched 1, 6-alpha-glucan synthase (GTF-U) and a 1,6-alpha-glucan synthase (GTF-T) were purified to near homogeneity from the culture fluid of Streptococcus sobrinus strain B13N (serotype d) and characterized. In addition, a crude preparation of a recombinant oligo-isomaltosaccharide synthase (rGTF-S) was prepared from a cell-free extract of Escherichia coli MD124 transformant. Using four homogeneous GTF preparations including previously purified rGTF-S as antigens for immunization, 11 murine hybridomas producing a monoclonal antibody (MAb) were established through the fusion of myeloma cells (P3X63-Ag8-U1) and spleen cells of immunized BALB/c mice. When the immunoreactivities of the resultant MAbs were tested, all five MAbs raised against GTF-I, all three MAbs raised against GTF-T, and two of three MAbs raised against GTF-U reacted specifically with the homologous enzyme alone, while one MAb (B86) raised against GTF-U cross-reacted strongly with all GTFs. Although no MAb monospecific for rGTF-S was obtained, precise recognition of GTF-S was possible using the nonspecific B86 antibody together with the MAbs monospecific for the three glucan synthases. Thus, a set of four typical MAbs (B17, B76, B19 and B86) were successfully used for the identification of gene products expressed in 24 previously constructed E. coli phage clones, and the findings suggested that six phage clones might express a gtfU gene encoding GTF-U which has not been hitherto isolated.

Animals↗
PubMed2000

Regulation of transcription of the mph(A) gene for macrolide 2'-phosphotransferase I in Escherichia coli: characterization of the regulatory gene mphR(A).

The synthesis of macrolide 2'-phosphotransferase I [Mph(A)], which inactivates erythromycin, is inducible by erythromycin. The expression of high-level resistance to erythromycin requires the mph(A) and mrx genes, which encode Mph(A) and an unidentified protein, respectively. We have studied the mphR(A) gene, which regulates the inducible expression of mph(A). An analysis of the synthesis of Mph(A) in minicells and results of a complementation test indicated that mphR(A) is located downstream from mrx and that its product, MphR(A), represses the production of Mph(A). DNA sequencing indicated that the mph(A), mrx, and mphR(A) genes exist as a cluster that begins with mph(A) and that the deduced amino acid sequence of MphR(A) can adopt an alpha-helix-turn-alpha-helix structure. To study the regulation of gene expression by MphR(A), we performed Northern blotting and primer extension. A transcript of 2. 9 kb that corresponded to the transcript of mph(A) through mphR(A) was detected, and its level was elevated upon exposure of cells to erythromycin. Gel mobility shift assays and DNase I footprinting indicated that MphR(A) binds specifically to the promoter region of mph(A), and the amount of DNA shifted as a results of the binding of MphR(A) decreased as the concentration of erythromycin was increased. These results indicate that transcription of the mph(A)-mrx-mphR(A) operon is negatively regulated by the binding of a repressor protein, MphR(A), to the promoter of the mph(A) gene and is activated upon inhibition of binding of MphR(A) to the promoter in the presence of erythromycin.

Amino Acid Sequence↗
PubMed2000

CD21-mediated entry and stable infection by Epstein-Barr virus in canine and rat cells.

We developed an adenovirus vector for transduction of the human CD21 gene (Adv-CD21), the Epstein-Barr virus (EBV)-specific receptor on human B lymphocytes, to overcome the initial barrier of EBV infection in nonprimate mammalian cells. Inoculation of Adv-CD21 followed by exposure to recombinant EBV carrying a selectable marker resulted in the successful entry of EBV into three of seven nonprimate mammalian cell lines as evidenced by expression of EBV-determined nuclear antigen (EBNA). The EBV-susceptible cell lines included rat glioma-derived 9L, rat mammary carcinoma-derived c-SST-2, and canine kidney-derived MDCK. Subsequent selection culture with G418 yielded drug-resistant cell clones. In these cell clones, EBV existed as an episomal form, as evidenced through the Gardella gel technique. Among the known EBV latency-associated gene products, EBV-encoded small RNAs, EBNA1 and transcripts from the BamHI-A rightward reading frame (BARF0), and latent membrane protein 2A were expressed in all EBV-infected cell clones. The viral lytic events could be induced in these cell clones by simultaneous treatment with 12-O-tetradecanoylphorbol-13-acetate and n-butyric acid, but they were abortive, and infectious virus was not produced. These results indicate that once the initial barrier for attachment is overcome artificially, EBV can establish a stable infection in some nonprimate mammalian cells, and they raise the possibility that transgenic animals with the human CD21 gene could provide an animal model for EBV infection.

Adenoviridae↗
PubMed2000

Epstein-Barr virus and gastric carcinoma.

The Epstein-Barr virus (EBV) is detected in the tissue of about 10% of gastric carcinoma cases throughout the world. In each case, 100% of carcinoma cells are infected with EBV. Analysis of EBV in carcinoma biopsies indicates that carcinoma is formed by the proliferation of a single EBV infected cell. These findings suggest that EBV plays an important role in the development of EBV positive gastric carcinomas. The EBV genes expressed are EBV determined nuclear antigen 1 (EBNA1), two small non-polyadenylated RNAs known as EBER1 and EBER2, and the transcripts from the BamHI-A region (BARF0); in addition, some cases also express a small amount of latent membrane protein 2A (LMP2A). Epithelial cells are refractory to EBV infection in vitro. This has hampered the study of the role of EBV in epithelial malignancies. The use of recombinant EBV carrying a selectable marker has enabled this difficulty to be overcome. EBV infected cell clones can be obtained from most carcinoma cell lines examined, and it was found that cell to cell contact was an efficient mode of EBV infection. Furthermore, it was possible to immortalize primary gastric epithelial cells by EBV infection. The cells expressed identical EBV genes to those typically seen in EBV positive gastric carcinoma, and showed accelerated malignant properties, including growth in soft agarose and tumorigenicity in severe combined immunodeficient (SCID) mice. These results suggest that EBV contributes to the maintenance of the malignant phenotype of EBV positive gastric carcinoma.

Animals↗
PubMed2000

Colon delivery efficiencies of intestinal pressure-controlled colon delivery capsules prepared by a coating machine in human subjects.

Large quantities of pressure-controlled colon delivery capsules (PCDCs) were prepared by a Hicoater-mini pharmaceutical coating machine and colon delivery efficiencies were evaluated in man. Caffeine powder as a model drug was suspended with a polyethylene glycol (PEG) 1000 suppository base at 50 degrees C, and was hardened in no. 0- and no. 2-sized capsular shapes. The capsule-shaped suppositories were coated with 5% w/v ethanolic ethylcellulose (7G grade) solution using the coating machine. By increasing the coating weight of ethylcellulose from 28.6 +/- 1.1 mg to 45.3 +/- 0.2 mg, the mean coating thickness of no. 0 PCDCs increased from 56 +/- 1 microm to 64 +/- 1 microm. With no. 2 PCDCs, the mean coating thickness increased from 50 micro +/- 1 microm to 57 +/- 1 microm by increasing the coating weight of ethylcellulose from 8.1 +/- 0.5 mg to 11.2 +/- 0.3 mg. The no. 0 PCDCs, having a mean ethylcellulose coating membrane thicknesses of 56 +/- 1 microm (type 1) and 64 +/- 1 microm (type 2), as well as no. 2 PCDCs, having thicknesses of 50 +/- 1 microm (type 3) and 57 +/- 1 microm (type 4), were used for in-vivo evaluation in man. After oral administration of test preparations containing 75 mg of caffeine, saliva samples were obtained and salivary caffeine levels were measured by an HPLC method. The first appearance time, Ti, of caffeine in the saliva was used as a parameter for the estimation of the release time of caffeine from PCDCs in the gastrointestinal tract. The mean Ti values of no. 0 PCDCs were 3.3 +/- 0.3 h for type- 1 and 5.3 +/- 0.3 h for type-2 preparations while the mean Ti values of no. 2 PCDCs were 4.3 +/- 0.5 h for type 3 and 5.3 +/- 0.3 h for type 4. There were good correlations between ethylcellulose coating membrane thicknesses and in-vivo Ti values. A colon arrival time of 5 h was reported in our subjects by gastrointestinal magnetomarkergraphy. PCDCs having a mean coating thickness of 64 +/- 1 microm for no. 0 capsules and of 57 +/- 1 microm for no. 2 capsules were thought to deliver caffeine to the human colon efficiently.

Adult↗