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Biomedical subjects

M Takiguchi

Publications and source records attributed to M Takiguchi.

At least 73 records · Page 4Linked to original sources
PubMed1999

Hyperammonemia: regulation of argininosuccinate synthetase and argininosuccinate lyase genes in aggregating cell cultures of fetal rat brain.

Hyperammonemia in the brain leads to poorly understood alterations of nitric oxide (NO) synthesis. Arginine, the substrate of nitric oxide synthases, might be recycled from the citrulline produced with NO by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL). The regulation of AS and AL genes during hyperammonemia is unknown in the brain. We used brain cell aggregates cultured from dissociated telencephalic cortex of rat embryos to analyze the regulation of AS and AL genes in hyperammonemia. Using RNase protection assay and non-radioactive in situ hybridization on aggregate cryosections, we show that both AS and AL genes are induced in astrocytes but not in neurons of aggregates exposed to 5 mM NH4Cl. Our work suggests that the hyperammonemic brain might increase its recycling of citrulline to arginine.

Ammonia↗
PubMed1999

A newly identified MAGE-3-derived epitope recognized by HLA-A24-restricted cytotoxic T lymphocytes.

Five MAGE-3-derived peptides carrying an HLA-A24-binding motif were synthesized. Binding capacity of these peptides was analyzed by an HLA-class-I stabilization assay. Two of the 5 peptides bound to HLA-A*2402 molecule with high affinity, and 3 peptides with low affinity. Peripheral-blood mononuclear cells (PBMC) depleted of CD4+T cells were stimulated with the peptides to determine whether these peptides would induce cytotoxic T lymphocytes (CTL) from PBMCs obtained from 7 healthy HLA-A*2402+ donors. Peptide M3-p97 (TFPDLESEF; corresponding to amino-acid residues 97-105 of MAGE-3), with high binding capacity to the HLA-A*2402 molecule, elicited the peptide-specific and HLA-A24-restricted CD8+CTL lines in 2 of the 7 donors, while none of the 4 other peptides induced CTL specific for the corresponding peptide in any of the donors. CTL lines induced by stimulation with peptide M3-p97 exhibited cytolytic activities against HLA-A*2402 transfectant cell lines (C1R-A*2402) in the presence of peptide M3-p97, but not in unloaded or irrelevant peptide-pulsed C1R-A*2402 cells. The CTL lines and a cloned CD8+CTL isolated from one of the bulk populations by limiting dilution could lyse MAGE-3+/HLA-A*2402+ squamous-cell-carcinoma(SCC) lines but neither MAGE-3-/HLA-A*2402+ nor MAGE-3+/HLA-A*2402- SCC lines, indicating that M3-p97 can be naturally processed and presented on the tumor-cell surface in association with HLA-A*2402 molecules. Combined with the 4 currently reported CTL epitopes derived from MAGE-3 and presented by HLA-A1, HLA-A2, HLA-A24 or HLA-B44, identification of this CTL epitope presented by the HLA-A*2402 molecule will extend the application of MAGE-3-derived peptides for immunotherapy for cancer patients.

Antigens, Neoplasm↗
PubMed1999

Overlapping peptide-binding specificities of HLA-B27 and B39: evidence for a role of peptide supermotif in the pathogenesis of spondylarthropathies.

OBJECTIVE: Previous studies indicated the increase of HLA-B39 among HLA-B27 negative patients with spondylarthropathies (SpA). This study was performed to examine whether the natural ligands of HLA-B27 are capable of binding to HLA-B39. METHODS: Peptides were synthesized according to the sequences of known natural ligands of HLA-B27 or B39 and were tested for their binding to HLA-B*3901 and B*2705 by quantitative peptide binding assay, using a TAP-deficient RMA-S cell line transfected with human beta2-microglobulin and HLA class I heavy chain genes. RESULTS: Four of the 10 HLA-B27 binding peptides significantly bound to HLA-B*3901. All 4 peptides had hydrophobic/aromatic amino acids (Leu or Phe) at the C-terminus. In contrast, peptides with basic residues (Lys, Arg) or Tyr at the C-terminus did not bind to B*3901. In parallel experiments, 1 of the 2 natural ligands of HLA-B*3901 was found to bind to B*2705. CONCLUSION: A subset of natural HLA-B27 ligands was capable of binding to B*3901. In addition to Arg at position 2 (Arg2), hydrophobic/aromatic C-terminal residues, such as Leu or Phe, seemed to be crucial for the cross-specificity. These results suggested that HLA-B27 and B39 recognize overlapping peptide repertoires, supporting the hypothesis that the peptides presented by both of these class I antigens play a role in the pathogenesis of SpA.

Amino Acid Sequence↗
PubMed1999

Differential expression of CCAAT enhancer binding protein family in rat alveolar epithelial cell proliferation and in acute lung injury.

Although alveolar reorganization after acute lung injury depends on regeneration of alveolar epithelial cells, there is little knowledge of regulation of pulmonary healing process. Transcription factors may play key roles in this regulation. To investigate whether the CCAAT enhancer binding protein (C/EBP) family, alpha, beta, and delta, were involved in alveolar reorganization after injury, we examined expression of C/EBP proteins and mRNAs in lung injuries induced by lipopolysaccharide (LPS) or bleomycin (Bleo) and in cell proliferation by keratinocyte growth factor (KGF). By immunohistochemistry, we demonstrated that C/EBP alpha and C/EBP beta were expressed in alveolar type II cells and alveolar macrophages, but C/EBP delta was expressed restrictedly in some of alveolar type II cells in a spatial pattern in the control lungs. Further, these three C/EBP family members were differentially expressed in alveolar cell proliferation and in acute lung injury, in which, interestingly, C/EBP alpha and C/EBP delta were reciprocally expressed in alveolar type II cell proliferation and in pulmonary fibrosis. However, expressions of their mRNAs by in situ hybridization were dramatically increased in the affected lesions of the lungs by LPS and Bleo, and Northern blot analysis showed an increased abundance of the mRNA for C/EBP beta in LPS-treated lungs and for C/EBP delta in Bleo-treated lungs, compared with those in the control lungs. Thus, differential expression of the C/EBP family may be required to maintain and reorganize the basic integrity of alveolar structure during pathological states, which suggests an important role for the C/EBP family in maintaining normal alveolar architecture and function and in repairing the damaged epithelium after injury.

Animals↗
PubMed1999

Structure of the immediate early gene of canine herpesvirus.

The nucleotide sequence of the immediate early (IE) gene of canine herpesvirus was determined. This gene was located in the inverted repeat regions, encoding a polypeptide of 1,383 amino acids. The predicted amino acid sequence was most closely related to that of the feline herpesvirus 1 IE protein among those of other alphaherpesviruses. DNA binding and transcriptional activation domains were found in the IE protein. A spliced region of the IE gene transcript was determined in its 5' non-coding region.

Amino Acid Sequence↗
PubMed1999

Identification of multiple HIV-1 CTL epitopes presented by HLA-B*5101 molecules.

We attempted to identify and characterize HIV-1 CTL epitopes presented by HLA-B51 which is associated with a slow progression to AIDS. HLA-B*5101 stabilization assay showed that 33 out of 172 HIV-1 peptides carrying HLA-B*5101 anchor residues bound to HLA-B*5101. Seven peptides were suggested as HIV-1 CTL epitopes presented by HLA-B*5101 because the specific CTL was induced for these peptides in PBMC from three HIV-1 seropositive individuals carrying HLA-B51 by stimulation with HLA-B*5101 binding peptides. Analysis of these epitopes using the specific CTL clones confirmed that six of seven HIV-1 peptides are epitopes presented by HLA-B*5101. Three epitopes presented by HLA-B*5101 are highly conserved among the clade B strain, suggesting that the specific CTL for these epitopes might play an important role in recognition of HIV-1 infected cells. These epitopes will be useful to analyze CTL responses in HIV-1 infected individuals.

Antigen Presentation↗
PubMed1999

Role of anchor residues in peptide binding to three HLA-A26 molecules.

To investigate the role of anchor residues in HLA-A26 binding peptides, we analyzed the binding of various peptides to three HLA-A26 molecules using the HLA class I stabilization assay. Of twenty nonamer peptides carrying anchors at P2 and P9, 3, 6 and 3 peptides bound to HLA-A*2601, HLA-A*2602 and HLA-A*2603, respectively The peptide EV-IPMFSAL bound most strongly to these three HLA-A26 molecules. Analysis using mutants of this peptide at P1, P2 or P9 showed that acidic amino acids at P1 and five hydrophobic residues (Val, Thr, Ile, Leu and Phe) at P2 are anchor residues for the three HLA-A26 molecules while with exception of positively charged amino acids, a broad range of amino acids function as P9 anchor residues. These anchors were further evaluated using 38 nonamer peptides carrying anchor residues at P1, P2 and P9. Nineteen of these peptides bound to at least one HLA-A26 molecule. The frequency of HLA-A26 binding peptides was higher for peptides carrying all three anchor residues than for peptides carrying only P2 and P9 anchor residues. These results indicate that in addition to P2 and P9 anchors, the P1 anchor plays an important role in peptide binding to three HLA-A26 molecules.

Amino Acid Sequence↗
PubMed1999

Detection of canine herpesvirus DNA in the ganglionic neurons and the lymph node lymphocytes of latently infected dogs.

To determine the site of latent infection of canine herpesvirus (CHV), tissues from dogs convalescent from acute infection with CHV were examined for the presence of viral genome DNA by the nested polymerase chain reaction. CHV DNA was detected in the trigeminal ganglia and the retropharyngeal lymph nodes. In situ hybridization study of the tissues revealed that CHV genome persisted in the nuclei of ganglionic neurons and lymphocytes.

Animals↗
PubMed1999

[The blood sugar levels after hypothermic cardiopulmonary bypass in diabetic patients: their relation to preoperative values of hemoglobin-A1c and medication].

We studied the blood sugar levels after hypothermic cardiopulmonary bypass (CPB) in diabetics and non-diabetics. Twenty eight patients were divided to the following four groups by the preoperative value of hemoglobin-A1c (HbA1c) and medication; (1) HbA1c < 6.0 and given oral anti-diabetic medication, (2) HbA1c > 6.0 and given oral anti-diabetic medication, (3) HbA1c > 6.0 and given insulin injection, and (4) non-diabetics. Both in diabetics and non-diabetics, the blood sugar levels were higher than 300 mg.dl-1 during cardiopulmonary bypass. In group (1) and (4), the blood sugar levels went down lower than 250 mg.dl-1 at 60 minutes after CPB, without any treatment. In group (2) and (3), the blood sugar levels after 60 minutes of CPB were higher than 250 mg.dl-1, and insulin 8 units were given. After 30 minutes of insulin injection, the blood sugar levels of group (2) were lower than 250 mg.dl-1, but those in group (3), the blood sugar levels were still higher than 250 mg.dl-1, and another 8 units of insulin were given. The diabetic patients whose HbA1c levels were higher than 6.0 and given anti-diabetic medication before operation, need insulin after CPB.

Adult↗
PubMed1999

Blockade of CD28/CTLA4-B7 pathway prevented autoantibody-related diseases but not lung disease in MRL/lpr mice.

We studied the role of CD28/CTLA4 costimulatory T-cell activation pathway on the pathogenesis of MRL/lpr mice. Administration of CTLA4IgG from day 0 significantly inhibited autoantibody production such as anti-double-stranded DNA antibody and rheumatoid factor. In addition, end-organ diseases in kidney, salivary gland, and liver were significantly improved. Improvement of pathologic findings coincided with a significant improvement in survival. At 350 days of age, 90% of mice treated with CTLA4IgG from day 0 were still alive, compared with none of mice treated with hIgG. As expected, activation of conventional T cells was significantly inhibited after CTLA4IgG treatment. However, lung disease that was characterized by perivascular accumulation and interstitial infiltration of lymphocytes and macrophages was not inhibited. Even after CTLA4IgG treatment from day 0, pathologic findings of lung disease were not improved. Additionally, the expression of activation markers such as B7-1, B7-2, CD71, ICAM1, and LFA1 on Mac1+ fraction in both spleen and lung and the concentration of TNFalpha in bronchoalveolar lavage fluid were not significantly suppressed. These results demonstrated that lung disease was independent of the CD28/CTLA4-B7 pathway. Thus, this study emphasizes the differential dependence of the CD28/CTLA4-B7 pathway in development of diseases in MRL/lpr mice.

Abatacept↗
PubMed1999

[Optimal length of nasopharyngeal airway and its correlation with height and body weight].

We studied 26 patients (11 males and 15 females) undergoing elective surgery under general anesthesia. The purpose of this study was to decide how long the length of nasopharyngeal airway should be by measuring distance A (permitting airway obstruction to be released), distance B (giving the most effective ventilation), and distance C (between nostril and arytenoid). The values of distance A in male group and female group were 12.73 +/- 0.85 cm and 11.70 +/- 0.75 cm, respectively. The values of distance B were 14.55 +/- 0.96 cm in male group and 13.93 +/- 1.12 cm in female group. The values of distance C were 18.84 +/- 0.90 cm in male group and 17.40 +/- 0.97 cm in female group. This showed that it is necessary to advance the nasopharyngeal airway about 2 cm from the distance A to give the most effective ventilation to the patients with airway obstruction. Therefore, most of standard nasopharyngeal airways commercially available are too short. In addition, the distance B has no correlation with height and body weight and it is difficult to predict the optimal length of the airway.

Anesthesia, General↗
PubMed1999

[A case of simple coarctation].

We report a successful surgical repair of the simple coarctation of a 80-day-old girl by extended end-to-end aortic arch reconstruction. She was admitted to our hospital at the age of 4 days because of poor pulsation of femoral arteries. The systolic blood pressure gradient between the arm and the leg was 30 mmHg. Echocardiography on admission revealed a simple coarctation and patent foramen ovale, with the mildly impaired left ventricular contraction (left ventricular fractional shortening was 23%). Although aortography demonstrated an isolated interrupted segment at the aortic isthmus with collaterals (type A classification of Celoria-Patton), the tubular connection between the distal arch and the descending aorta, of which intralumen was obstructed with abundant ductal tissues, was found at operation. The obstruction of the lumen of aortic isthmus in our case, which was originally patent, might be caused by ductal closure and present as a simple coarctation.

Aortic Coarctation↗
PubMed1999

[PGE1 and dopamine administration in a pediatric patient during hepatectomy].

A 2-year-old male underwent medial inferior hepatectomy for the treatment of metastatic tumors. Due to congenital hepatoblastoma, at 6-months of age, right lobectomy of his liver had been performed. To protect liver functions, PGE1 and dopamine were administered during the surgery. Although half of his circulating blood volume was lost, his perioperative hemodynamics was stable, with no development of postoperative liver dysfunction. PGE1 and dopamine may thus be beneficial in pediatric hepatectomy.

Alprostadil↗
PubMed1999

The use of sevoflurane anesthesia during early pregnancy.

Sevoflurane has favorable pharmacodynamic properties such as a rapid, smooth induction and emergence from anesthesia. However, there is only one report of sevoflurane anesthesia during early pregnancy. We report the use of sevoflurane for maintenance of general anesthesia in a pregnant patient undergoing non-obstetric surgery. A 25-year-old, female patient, at 13 weeks gestation, was diagnosed as having a strangulated ileus. General anesthesia was performed and maintained with oxygen, nitrous oxide, and sevoflurane. Six months later a healthy infant without abnormalities was delivered.

Adult↗