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Biomedical subjects

A Sawada

Publications and source records attributed to A Sawada.

At least 37 records · Page 2Linked to original sources
PubMed2001

A 13C-urea breath test in children with helicobacter pylori infection: assessment of eradication therapy and follow-up after treatment.

PURPOSE: Our aim was to evaluate the usefulness of the 13C-urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, for assessment of the efficacy of eradication therapy, and for post-treatment follow-up in children. METHODS: Seventy-two patients who underwent endoscopy for symptoms related to the upper gastrointestinal tract were examined by rapid urease test, histology, and culture. The patients were also studied with serology and UBT. RESULTS: Forty-seven of the 72 patients were diagnosed with H. pylori infection, based on the results of biopsy-based tests and serology. As an initial diagnostic test to detect H. pylori infection, the sensitivity of the UBT was 95%, which was comparable with that of histology (94%), rapid urease test (96%), and serology (91%) and was greater than that of culture (79%). The specificity of the UBT was 100%, which was comparable with that of the other four tests. The efficacy of eradication therapy was assessed by biopsy-based tests and the UBT in 24 H. pylori-positive patients. For this purpose, the sensitivities of UBT and histology were 100%, while the sensitivities of culture and the rapid urease test were 88%. The specificity was 100% for all of these tests. Eleven patients were assessed by biopsy-based tests and UBT after more than 6 months of post-treatment follow-up. There were no discordances between the results of the UBT and those of the biopsy-based tests in any of the patients. CONCLUSIONS: The UBT may be useful for detecting H. pylori infection in children with upper gastrointestinal tract symptoms, for assessment of the efficacy of eradication therapy, and for the follow-up evaluation of patients after the therapy.

Adolescent↗
PubMed2001

Lack of the Polycomb-group gene rae28 causes maturation arrest at the early B-cell developmental stage.

The rae28 gene (rae28) is a murine homologue of the Drosophila polyhomeotic gene, which is a member of the Polycomb-group genes. In this study, we examined the role of rae28 in lymphocyte development. Because homozygous rae28-deficient (rae28-/-) mice died in the perinatal period, we examined lymphocyte development by generating chimeric mice reconstituted with green fluorescence protein-labeled mutant fetal liver cells as well as in in vitro culture systems. We further examined RAE28 expression by reverse transcriptase polymerase chain reaction assay in human leukemic cells with B-lineage acute lymphoblastic leukemia (ALL). Severe B-cell maturation arrest was observed in rae28-/- between pro- and pre-B lymphocyte stages. B-cell development was also delayed in heterozygous neonates. Furthermore, interleukin-7-dependent colony-forming ability was impaired not only in homozygous lymphocytes but also in heterozygotes. Its human homologue, RAE28, is located on chromosome 12p13, which frequently is associated with chromosomal abnormalities and loss of heterozygosity in patients with hematologic malignancies. To determine whether a link exists between RAE28 and leukemia, we examined RAE28 expression in leukemic cells from pediatric patients with B-lineage ALL. RAE28 expression was not detected in four B-cell precursor ALL cases of a total of 43 examined, although RAE28 is normally expressed constitutively during the process of B-cell maturation as assessed in isolated cell populations. rae28 plays an important role in the early B-cell developmental stage in a gene dosage-dependent manner. Furthermore, the human RAE28 locus may provide a candidate gene causing the molecular pathogenesis of childhood B-cell precursor ALL.

Animals↗
PubMed2001

Foscarnet therapy for ganciclovir-resistant cytomegalovirus retinitis after stem cell transplantation: effective monitoring of CMV infection by quantitative analysis of CMV mRNA.

We report three pediatric patients with ganciclovir-resistant cytomegalovirus (CMV) retinitis who were successfully treated with foscarnet. The patients were recipients of hematopoietic stem cell transplantation (SCT) from HLA-mismatched donors. Because these patients had developed or experienced progressive CMV retinitis during ganciclovir therapy, they received foscarnet therapy at 60 mg/kg every 8 h. Their retinitis resolved promptly after initiating foscarnet therapy, suggesting foscarnet's effectiveness in treating ganciclovir-resistant CMV infection. The amount of CMV mRNA was quantitatively measured using an NASBA technique, which amplified the beta2.7 transcripts specific for CMV replication. This technique was useful for monitoring disease activity in a more rapid and sensitive manner than the PCR assay for CMV DNA.

Adolescent↗
PubMed2001

Three cases with TT virus infection and idiopathic neonatal hepatitis.

We present three cases of infants with idiopathic neonatal hepatitis showing diffuse intrahepatic fatty degeneration. Prolonged cholestasis has improved immediately upon intravenous administration of a high-dose gammaglobulin treatment in all three patients. The TT virus (TTV) genome was detectable in the serum of two patients, in the duodenal fluid of one and in the liver of all three. By analyzing sequence homology, we observed that the respective TTV isolated from serum, duodenal fluid and liver tissue were completely identical in cases 2 and 3. These findings suggest that TTV infection was one of the contributing factors for neonatal cholestasis in these patients. TTV was isolated from the serum of two out of the three mothers. The viruses were either completely or almost identical in sequence to those isolated from their respective infants, suggesting that they had been transmitted from mother to infant in these 2 cases. The patients presented here, whose livers were infected with the TTV and showed a favorable response to gammaglobulin therapy, may represent a subset of idiopathic neonatal hepatitis patients.

Cholestasis↗
PubMed2001

Fgf signalling through MAPK cascade is required for development of the subpallial telencephalon in zebrafish embryos.

The telencephalon is formed in the most anterior part of the central nervous system (CNS) and is organised into ventral subpallial and dorsal pallial domains. In mice, it has been demonstrated that Fgf signalling has an important role in induction and patterning of the telencephalon. However, the precise role of Fgf signalling is still unclear, owing to overlapping functions of Fgf family genes. To address this, we have examined, in zebrafish embryos, the activation of Ras/mitogen-activated protein kinase (MAPK), one of the major downstream targets of Fgf signalling. Immunohistochemical analysis reveals that an extracellular signal-regulated kinase (ERK), a vertebrate MAPK is activated in the anterior neural boundary (ANB) of the developing CNS at early segmentation stages. Experiments with Fgf inhibitors reveal that ERK activation at this stage is totally dependent on Fgf signalling. Interestingly, a substantial amount of ERK activation is observed in ace mutants in which fgf8 gene is mutated. We then examine the function of Fgf signalling in telencephalic development by use of several inhibitors to Fgf signalling cascade, including dominant-negative forms of Ras (Ras(N17)) and the Fgf receptor (Fgfr), and a chemical inhibitor of Fgfr, SU5402. In treated embryos, the induction of telencephalic territory normally proceeded but the development of the subpallial telencephalon was suppressed, indicating that Fgf signalling is required for the regionalisation within the telencephalon. Finally, antisense experiments with morpholino-modified oligonucleotides suggest that zebrafish fgf3, which is also expressed in the ANB, co-operates with fgf8 in subpallial development.

Animals↗
PubMed2001

Fgf/MAPK signalling is a crucial positional cue in somite boundary formation.

The temporal and spatial regulation of somitogenesis requires a molecular oscillator, the segmentation clock. Through Notch signalling, the oscillation in cells is coordinated and translated into a cyclic wave of expression of hairy-related and other genes. The wave sweeps caudorostrally through the presomitic mesoderm (PSM) and finally arrests at the future segmentation point in the anterior PSM. By experimental manipulation and analyses in zebrafish somitogenesis mutants, we have found a novel component involved in this process. We report that the level of Fgf/MAPK activation (highest in the posterior PSM) serves as a positional cue within the PSM that regulates progression of the cyclic wave and thereby governs the positions of somite boundary formation.

Animals↗
PubMed2000

Changes of cytokines during the course of graft-versus-host disease following bone marrow transplantation: a case report.

Allogeneic bone marrow transplantation was performed in a 24-year-old woman with acute myelogenous leukemia in the first remission (FAB classification: M4). Graft-versus-host disease occurred from around day 150 after bone marrow transplantation. The levels of tumour necrosis factor-alpha, interleukin 12, and intercellular adhesion molecule-1 were elevated in the early stage of graft-versus-host disease, followed by elevation of interleukin 10 and interleukin 8. Her symptoms subsequently improved and all of these parameters became normal. The levels of thrombomodulin and plasminogen activator inhibitor type 1 showed changes that were in parallel with the clinical course. Interleukin 1beta, interleukin 6, interleukin 2, and interferon-gamma showed no changes throughout the course of her graft-versus-host disease. These findings suggested the possibility that release of inflammatory molecules occurred at the onset of graft-versus-host disease and caused vascular endothelial damage, which led to the exacerbation of her disease.

Adult↗
PubMed2000

Retrobulbar hemodynamics in normal-tension glaucoma with asymmetric visual field change and asymmetric ocular perfusion pressure.

PURPOSE: To investigate retrobulbar hemodynamics by means of color Doppler imaging in normal-tension glaucoma with asymmetric visual field change and asymmetric ocular perfusion pressure. METHODS: Forty-nine consecutive patients who met the enrollment criteria were enrolled in a prospective study. We measured intraocular pressure at 2-hour intervals for 24 hours and performed color Doppler imaging of the orbital arteries, 48-hour ambulatory blood pressure monitoring, and visual field testing. Color Doppler parameters were compared between subjects with higher ocular perfusion pressure in the eye that had a better mean deviation (concordant group) and worse mean deviation (discordant group). RESULTS: In the eyes with the better mean deviation, the end-diastolic velocity of the ophthalmic artery was significantly slower in the discordant group (P=.0145), while in the eyes with the worse mean deviation, the peak systolic and end-diastolic velocities of the ophthalmic artery were significantly slower and the resistance index of the ophthalmic artery was significantly higher in the discordant group (P=.0395, P=.0088, and P=.0324, respectively). In the concordant group, the end-diastolic velocity of the central retinal artery was slower in eyes with a worse mean deviation. CONCLUSION: Retrobulbar hemodynamics are significantly altered in patients with normal-tension glaucoma who have better ocular perfusion pressure in the eye that has a worse mean deviation.

Adult↗
PubMed2000

A microfilament formation inhibitor, cytochalasin strongly enhances the low-affinity Fc epsilon receptor II (CD23) expression on the human monocyte-like cell line, U937.

Enhancement of the low-affinity Fc epsilon receptor (CD23) expression by cytochalasin was analyzed on the human monocytelike cell line, U937. The CD23 expression on the U937 cells was enhanced at 24 hr after culture with cytochalasin B, D, or E, especially cytochalasin E having the most remarkable effect on it at the low concentration. This enhanced expression was found to be associated with a concomitant increase of a CD23 (about 45-kDa) protein on the U937 cells as assessed by Western blotting analysis. On the other hand, CD11a, CD18, CD31, CD49d, or CD54 was not markedly enhanced on the U937 cells by culture with cytochalasin E, although the mean fluorescence intensities (MFIs) of CD11a, CD18, and CD54 on U937 was partially up-regulated. Cell growth of U937 cultured with cytochalasin E was completely suppressed for 72 hr, but cell viability was sufficiently maintained (more than 95%). Soluble-formed CD23 (sCD23) also was released from the U937 cells at 24 to 72 hr after culture with cytochalasin E. In addition, the protein tyrosine kinase activity was detected in the U937 cells cultured with cytochalasin E for 24 hr using the enzyme immunoassay. Enhancement of the CD23 expression on the U937 cells at 24 to 72 hr cultured with cytochalasin E was sufficiently blocked by protein tyrosine kinase inhibitors herbimycin A and genistein, and a protein synthesis inhibitor, cychloheximide. On the other hand, protein kinase C inhibitors such as H-7 and H-8 had no effect on this CD23 expression. These results suggest that a mechanism underlying enhancement of the CD23 expression on the U937 cells cultured with cytochalasin E is mediated through tyrosine phosphorylation and protein synthesis.

Actin Cytoskeleton↗
PubMed2000

Juvenile myelomonocytic leukemia relapsing after allogeneic bone marrow transplantation successfully treated with interferon-alpha.

We report a 5-year-old boy with juvenile myelomonocytic leukemia (JMML) which relapsed after an allogeneic bone marrow transplant who was successfully treated with interferon-alpha (IFN-alpha). One year after starting the therapy, he remains clinically well and in complete remission while continuing treatment with IFN-alpha and bestatin. Although the precise mechanism by which remission was induced is uncertain, a GVL effect combined with a direct antileukemia effect of IFN-alpha may be responsible. Further assessment of the role of IFN-alpha in relapsed JMLL patients is warranted.

Antineoplastic Agents↗
PubMed2000

Analysis of intron 13 microsatellite repeat polymorphism of the factor VIII gene by capillary electrophoresis.

To establish a rapid and automatic gene analysis method, we used capillary electrophoresis (CE) for the analysis of the intron 13 microsatellite repeat polymorphism (MRP) of the coagulation factor VIII gene for the diagnosis of hemophilia A. In the analysis of a 20-bp DNA ladder marker, the reproducibility evaluated using the relative standard deviation (RSD) of the relative migration time for one fragment of each fragment were less than 0.01%, whereas the RSDs of the actual migration time of each fragment were 0.1-0.3%. Thus, the appropriate internal standard should be mixed with the sample when CE resolves polymerase chain reaction (PCR) products. We next analyzed the intron 13 MRP evaluated with (CA)n repeats of the factor VIII gene using a 200-bp DNA fragment as the internal standard. The results showed that the PCR products from the intron 13 MRP could be resolved using CE, even with the repeat numbers of 20 and 21, which differ by only 2 bp. These results suggest that CE is a suitable method for analyzing PCR products for gene diagnosis.

Adult↗
PubMed2000

Zebrafish Mesp family genes, mesp-a and mesp-b are segmentally expressed in the presomitic mesoderm, and Mesp-b confers the anterior identity to the developing somites.

Segmentation of a vertebrate embryo begins with the subdivision of the paraxial mesoderm into somites through a not-well-understood process. Recent studies provided evidence that the Notch-Delta and the FGFR (fibroblast growth factor receptor) signalling pathways are required for segmentation. In addition, the Mesp family of bHLH transcription factors have been implicated in establishing a segmental prepattern in the presomitic mesoderm. In this study, we have characterized zebrafish mesp-a and mesp-b genes that are closely related to Mesp family genes in other vertebrates. During gastrulation, only mesp-a is expressed in the paraxial mesoderm at the blastoderm margin. During the segmentation period, both genes are segmentally expressed in one to three stripes in the anterior parts of somite primordia. In fused somites (fss) embryos, in which all early somite boundary formation is blocked, initial mesp-a expression at the gastrula stage remains intact, but the expression of mesp-a and mesp-b is not detected during the segmentation period. This suggests that these genes are downstream targets of fss at the segmentation stage. Comparison with her1 expression (Müller, M., von Weizsäcker, E. and Campos-Ortega, J. A. (1996) Development 122, 2071-2078) suggests that, like her1, mesp genes are not expressed in primordia of the first several somites. Furthermore, we found that zebrafish her1 expression oscillates in the presomitic mesoderm. The her1 stripe, which first appears in the tailbud region, moves in a caudal to rostral direction, and it finally overlaps the most rostral mesp stripe. Thus, in the trunk region, both her1 and mesp transcripts are detected in every somite primordium posterior to the forming somites. Ectopic expression of Mesp-b in embryos causes a loss of the posterior identity within the somite primordium, leading to a segmentation defect. These embryos show a reduction in expression of the posterior genes, myoD and notch5, with uniform expression of the anterior genes, FGFR1, papc and notch6. These observations suggest that zebrafish mesp genes are involved in anteroposterior specification within the presumptive somites, by regulating the essential signalling pathways mediated by Notch-Delta and FGFR.

Amino Acid Sequence↗
PubMed2000

[Neuroprotective effect of N-methyl-D-aspartate receptor antagonists in an experimental glaucoma model in the rat].

PURPOSE: To evaluate the neuroprotective effect of memantine and dizocilpine, which are noncompetitive open-channel blockers of the N-methyl-D-aspartate (NMDA) receptor, on glaucomatous optic neuropathy in an experimental glaucoma model in the rat. METHODS: Experimental glaucoma was induced in the right eyes of 30 Wistar albino rats by intracameral injection of India ink followed by laser trabecular photocoagulation 4 days later. The left eye served as a control. Either memantine, dizocilpine, or phosphate-buffered saline (PBS) was injected intraperitoneally just before trabecular photocoagulation. Five days later, 3% fast blue was injected into both superior colliculi. The eyes were enucleated another 3 days later and flat mounts of the retinas were prepared. Labeled ganglion cells were counted in the area 1 mm away from the optic disc. RESULTS: Five days after laser application, no significant intraocular pressure (IOP) change in the right eye was found among the 3 groups. In eyes treated with memantine or dizocilpine, significantly more ganglion cells were labeled. CONCLUSION: Systemically applied memantine and dizocilpine had a neuroprotective effect against experimental glaucomatous optic neuropathy in the rat.

Animals↗
PubMed2000

Chronic graft-versus-host disease in children and adolescents after bone marrow transplantation from HLA-matched donors.

We analyzed 98 pediatric patients who underwent bone marrow transplantation (BMT) from serologically HLA-matched related donors (RD) or unrelated donors (UD) at our institute to clarify the actual status of chronic graft-versus-host disease (cGVHD). There were 36 evaluable cases of RD-BMT and 35 of UD-BMT. cGVHD was observed in 8 RD-BMT cases (22.2%) and in 23 UD-BMT cases (65.7%). In the RD-BMT cases, the limited and extensive types of cGVHD were observed in 4 cases each, whereas in the UD-BMT cases, the limited type was seen in 11 cases and the extensive type in 12. Prior acute GVHD was observed in 6 RD-BMT cases and in 18 UD-BMT cases. Two RD-BMT patients with extensive type cGVHD died of relapse and cytomegalovirus infection, and 4 UD-BMT patients died because of bronchiolitis obliterans, fungal infection, liver failure, and multiple organ failure, respectively. The incidence of cGVHD in these pediatric patients was as high as that in adult patients when UD-BMT was performed. Some UD-BMT patients required long-term immunosuppressive therapy after BMT. These findings suggest that cGVHD is a serious problem in pediatric UD-BMT. Therefore, intensive prophylaxis and treatment of GVHD must always be performed after UD-BMT.

Adolescent↗
PubMed2000

Enhanced video image guidance for biopsy using the safety map.

We present the system design and the methods of video-based guidance to assist with brain tumor biopsy procedures. The system comprises of a three-dimensional (3-D) position sensor, a CCD camera, a liquid crystal display (LCD) and a graphics computer equipped with a video capture board. The markers for positional measurement are attached to the CCD camera, a surgical tool, and the patient head. In order to be integrated into the camera-viewing capacity, 3-D images of the head and guidance indicators are visualized to form a life like video image. For reliable guidance, we also use the surgical plan, called the "safety map", which is a sphere surface highlighting the covering area of anatomically significant tissues and obstacles around the target for the indication of the biopsy needle's insertion starting-point. The safety map can be visualized in exactly the same way as it would be in a real life situation. The preliminary experiments were performed at the National Cancer Center. A high degree of flexibility in terms of views was created by using general apparatuses which are a CCD camera and a LCD. The display of the safety map enabled a successful completion of both craniotomy and biopsy needle insertion procedures.

Biopsy, Needle↗
PubMed2000

The effect of L-arginine on intraocular pressure in the human eye.

PURPOSE: L-Arginine, a non-toxic amino acid, is converted to nitric oxide (NO) by NO synthase. Recent findings have demonstrated that NO serves as an ocular hypotensive agent. The objectives of the present study were to clarify the effect of L-arginine on intraocular pressure (IOP), pupil size, refraction and accommodative amplitude in human eyes, and to examine whether L-arginine is converted to NO in vivo. METHODS: Fourteen volunteers received an intravenous drip-infusion of 100 ml of L-arginine (10.0 g) solution. IOP levels were measured before, during and after infusion using Goldmann applanation tonometry. Pupillary diameter, refraction and accommodative amplitude were also measured in human subjects. In rabbits, the nitrite levels in the aqueous humor were measured during L- or D-arginine infusion. RESULTS: The mean IOP of the L-arginine group was significantly decreased during infusion, but recovered rapidly after infusion. The mean IOP of the control group increased during infusion. The changes in pupillary diameter, refraction, and accommodative amplitude before and after infusion of L-arginine were not significant. L-Arginine significantly elevated the level of nitrite in the aqueous humor compared with the controls. CONCLUSIONS: These findings demonstrated that L-arginine lowers IOP mainly through the formation of NO.

Accommodation, Ocular↗
PubMed1999

Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma.

Glaucoma is an optic neuropathy with cupping of the optic disk, degeneration of retinal ganglion cells, and characteristic visual field loss. Because elevated intraocular pressure (IOP) is a major risk factor for progression of glaucoma, treatment has been based on lowering IOP. We previously demonstrated inducible nitric-oxide synthase (NOS-2) in the optic nerve heads from human glaucomatous eyes and from rat eyes with chronic, moderately elevated IOP. Using this rat model of unilateral glaucoma, we treated a group of animals for 6 months with aminoguanidine, a relatively specific inhibitor of NOS-2, and compared them with an untreated group. At 6 months, untreated animals had pallor and cupping of the optic disks in the eyes with elevated IOP. Eyes of aminoguanidine-treated animals with similar elevations of IOP appeared normal. We quantitated retinal ganglion cell loss by retrograde labeling with Fluoro-Gold. When compared with their contralateral control eyes with normal IOP, eyes with elevated IOP in the untreated group lost 36% of their retinal ganglion cells; the eyes with similarly elevated IOP in the aminoguanidine-treated group lost less than 10% of their retinal ganglion cells. Pharmacological neuroprotection by inhibition of NOS-2 may prove useful for the treatment of patients with glaucoma.

Animals↗