PubMed Health⌕ Search

Biomedical subjects

M Takiguchi

Publications and source records attributed to M Takiguchi.

At least 199 records · Page 11Linked to original sources

[Structure of MHC molecules and binding peptides].

MHC class I associates with beta 2-microglobulin and one of a range of short peptides which bind to the groove formed by two alpha helix and beta sheet on the alpha 1 and alpha 2 domains of the class I molecules. The class I molecules present the peptides with allele-specific motif to T cells. Recent studies showed that melanoma specific CTL and minor histocompatibility specific CTL recognize peptides presented by the class I molecules. Further studies of peptides bound to the class I and class II molecules are expected to identify peptides which induce autoimmune disease.

Animals↗

[Effect of preoperative liver function on serum lidocaine level during continuous epidural block].

To determine whether the blood lidocaine level during the continuous epidural block correlates with the preoperative liver function, i.e. serum albumin level, serum cholinesterase (ChE) activity, glutamic pyruvic transaminase (GPT) and indocyanine green retention rate (ICG R15), we measured the arterial serum lidocaine level in 45 abdominal surgical patients. The epidural catheter was advanced cephalad from Th10-L2 interspace, for a distance of 4 to 5 cm. Anesthesia was induced with thiopental, and maintained with continuous epidural block plus N2O, O2 and low concentration of isoflurane inhalation. We started epidural block with 0.3 ml.kg-1 body weight of 1.5% lidocaine and added half of the initial dose every 30 minutes for 2 hours. Serum lidocaine concentration was measured every 15 minutes after the lidocaine injection into epidural space. The result revealed that the lower the serum albumin level and ChE activity were, the higher the serum lidocaine level was and, that it had no significant correlation with GPT and ICG R15. We conclude that any patient with hypoalbuminemia and low serum ChE activity might have higher blood lidocaine levels during the continuous epidural block.

Adult↗

Cloning and sequence analysis of a full length cDNA encoding human mitochondrial 3-oxoacyl-CoA thiolase.

The cDNA sequence of human mitochondrial 3-oxoacyl-CoA thiolase was determined. The nucleotide sequence contains an open reading frame of 1191 base pairs and encodes an amino acid sequence of 397 residues which exhibits 86.6% homology with that of the rat enzyme. Northern blot analysis gave a single mRNA species of 1.6 kb in the human liver, fibroblasts and intercostal muscle.

Acetyl-CoA C-Acyltransferase↗

Behçet's disease associated with one of the HLA-B51 subantigens, HLA-B* 5101.

The strong association of Behçet's disease with HLA-B51 in several ethnic groups is well known. Because the HLA-B51 antigen has been recently identified to comprise three alleles, HLA-B* 5101, HLA-B* 5102, and HLA-B* 5103, we sought to investigate whether there is any correlation of one particular allele among them with B51-positive patients with Behçet's disease. Forty-six Japanese patients with Behçet's disease and HLA-B51 were typed by using the alloantisera, which allowed the subdivision of B51 antigen by the microlymphocyte toxicity assay. All the patients were found to carry HLA-B* 5101. This result suggests that amino acid substitutions at residue 167 or 171 prevent the development of Behçet's disease, because HLA-B* 5101 differs from HLA-B* 5102 and HLA-B* 5103 by single amino acid substitution at residues 171 and 167, respectively, or that another non-HLA gene tightly linked to the HLA-B* 5101-associated haplotype around the HLA class I gene region is responsible for the susceptibility to Bechçet's disease. This study provides insight into the molecular mechanism underlying an HLA association with Behçet's disease.

Alleles↗

Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses transcription from the promoter of the gene for ornithine transcarbamylase in a manner antagonistic to hepatocyte nuclear factor-4 (HNF-4).

Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) and hepatocyte nuclear factor-4 (HNF-4) are orphan members of the steroid/thyroid receptor superfamily and exhibit ubiquitous and liver-enriched tissue distribution, respectively. The gene for rat ornithine transcarbamylase (OTC), an ornithine cycle enzyme, is mainly expressed in the liver and is under the control of the promoter and the 11-kilobase upstream enhancer, both of which are liver-selective. Two sites of the promoter region and two sites of the enhancer region of the OTC gene, as well as the ovalbumin promoter site, were recognized by both HNF-4 and COUP-TF, showing that these two factors have closely related binding specificities. Since HNF-4 activated expression from the OTC promoter in cotransfection analysis, this factor appears to participate in liver-selective activation of the OTC gene. On the other hand, COUP-TF repressed the expression from the OTC promoter, whereas it activated expression from several other promoters. Therefore, COUP-TF plays a dual regulatory role depending on the promoter context. Repression of a tissue-specific promoter by a ubiquitous transactivator and derepression by a related tissue-enriched transactivator is potentially an important mechanism for tissue-specific activation of a gene.

Animals↗

Different effects of substitutions at residues 224 and 228 of MHC class I on the recognition of CD8.

Previous studies indicated that weak xenoresponse to HLA class I by mouse T cells is due to the inefficient interaction of mouse CD8 with the alpha 3 domain of HLA class I. The present study using chimeric H-2Kb molecules with recombinant alpha 3 domain between H-2Kb and HLA-B7 as well as single amino acid mutants of H-2Kb demonstrated that each substitution at residues 224 and 228 affects recognition of CD8-dependent mouse CTL clones. On the other hand, reactivity of IL-2-producing H-2Kb-specific T cell hybridoma transfected with mouse CD8 alpha was abrogated by substitution at residue 224 but not by that at residue 228. This indicates that the substitution at residue 228 affects recognition of CD8-dependent CTL but does not critically affect binding of CD8 to MHC class I molecules, although residue 224 abrogates binding of CD8. The model structure of the alpha 3 domain of H-2Kb suggests that the substitution at residue 224 induces conformational change of CD8 binding loop, whereas minimum structure change by the substitution at residue 228 is expected. It is therefore speculated that minimum structure change of CD8 binding loop by substitution at residue 228 may influence binding affinity of CD8, which abrogates recognition of CD8-dependent CTL but not IL-2 production of the CD8-dependent T cell hybridoma.

Amino Acid Sequence↗

Molecular analysis of HLA-B39 subtypes.

Serological studies have suggested the presence of a new HLA-B39 subtype (B39.2) in the Japanese population. To identify the new HLA-B39 subtype and compare it with an other HLA-B39 subtype (B39.1), the genes encoding HLA-B39.1 (B*39013) and B39.2 (B*3902) have been cloned from Japanese. We have sequenced these genes and completed the sequence of HLA-B39.1 (B*39011) gene from a Caucasian that was partially sequenced. Comparison of the sequence data revealed that B*3902 and B*39013 differ by three nucleotide substitutions which result in a two amino acids change at residues 63 and 67, while one silent substitution at codon 312 is found between B*39011 and B*39013. These results suggest that B*3902 has evolved from B*39013 rather than B*39011.

Amino Acid Sequence↗

Different rates of HLA class I molecule assembly which are determined by amino acid sequence in the alpha 2 domain.

Assembly of HLA class I molecules was studied using pulse-chase labeling of B-lymphoblastoid cell lines with 35S-methionine, immunoprecipitation with antibodies detecting free or beta 2-microglobulin-associated heavy chain and isoelectric focusing. Marked differences between the products of different class I alleles were noted. HLA-B51 assembled very inefficiently, with considerable free heavy chain still detected in an unsialated form after a four hour chase. The closely related molecule HLA-B35 was in contrast rapidly assembled, all newly synthesized heavy chain being detected in a beta 2m-associated sialated form within 30 minutes. Analysis of naturally occurring variants related to HLA-B35 and HLA-B51 localized the region determining assembly efficiency to the alpha 2 domain, in which these molecules differ at eight amino acid residues. The effect was not due to a linked dominant gene, as both patterns of assembly were observed in a single cell line.

Amino Acid Sequence↗

Recognition of the Qa-2k tumor antigen by T cell receptor gamma/delta of an immunopotentiator-induced tumoricidal T cell of mice.

Tumor-specific expression of Qa-2k antigen coded by the Q5k gene on various mouse tumor cells and immunological response of the host mice to the antigen have been demonstrated [Seo et al. (1992) J Exp Med 175: 547; Tanino et al. (1992) Cancer Immunol Immunother 35: 230]. The possibility was examined that Qa-2 antigen is one of the recognition target molecules of immunopotentiator-induced, H-2-nonrestricted tumoricidal lymphocytes of Qa-2-mice. Lymphocytes stimulated in vivo with P. acnes or culture-induced anomalous killers of B6.K1 mice did not exhibit significant in vitro cytotoxicity against B6.K1 lymphoblasts but lysed their Qa-2,3-congenic counterpart B6 lymphoblasts. To demonstrate the Qa-2 specificity of such cytotoxic cells more precisely, an L cell transformant clone (LQ7b/Kb), which expressed the alpha 1 and alpha 2 domains of the Qa-2 antigen (Q7b gene product), was generated by transfecting a cloned plasmid DNA containing a hybrid gene constructed from the 5' half of the Q7b gene and the 3' half of the H-2Kb gene (pQ7b/Kb). Using LQ7b/Kb cells as the target cells and the nylon-wool-nonadherent fraction of lymphocytes from P. acnes-stimulated (C3H/He x B6.K1)F1 mice (H-2k, Qa-2-) as the effector cells of the in vitro cytotoxicity reaction, the presence of cytotoxic cells that recognize the alpha 1/alpha 2 region of the Q7b gene product was demonstrated. The cytotoxic activity was dependent on T cells bearing T cell receptors of the gamma/delta type (TCR gamma/delta). The (C3H/He x B6.K1)F1 effector cells, as well as the B6.K1 effector cells also lysed BW5147 lymphoma cells (Qa-2k+) derived from AKR mice (Qa-2-, H-2k). By target-competition experiments it was shown that some of the effector cells lytic to BW5147 were identical to those that lysed LQ7b/Kb. Therefore some of the tumoricidal cells induced by the immunopotentiator interact with the target tumor cells through recognition of the alpha 1/alpha 2 region of the Qa-2k tumor antigen by TCR gamma/delta.

Adjuvants, Immunologic↗

Natural frequency/damping coefficient relationship of the catheter-manometer system required for high-fidelity measurement of the pulmonary arterial pressure.

Using a digital simulation method, we analyzed the relationship between natural frequency (fn) and damping coefficient (Zeta) of the catheter-manometer system required for high-fidelity measurement of the pulmonary arterial pressure. The pulmonary artery pressure waveform was obtained with a catheter-tip transducer and it was fed into a dynamic simulator programmed on a computer. The original waveform and the output of the simulator were compared and judged visually for the fidelity. From this analysis, the combination of fn and Zeta was obtained and was plotted on a fn-Zeta diagram. It showed as an area, which was convex on the left side and open on the right side. The left-convex endpoint was located at a damping coefficient of about 0.7. At a lower heart rate, this area was extended to the lower frequency side, while, at a higher heart rate, this area was limited to the higher frequency side. The fn-Zeta diagram was also constructed theoretically by calculating the relations between natural frequencies and damping coefficients of a second order system with the amplitude and phase error tolerance set at +/-5% respectively.

Journal Article↗

Structural analysis of HLA-B40 epitopes.

Two genes encoding HLA-B60 or HLA-B61 were cloned from Japanese and the exons of their genes were sequenced. One silent mutation was observed at the exon 1 between HLA-B60 (B*40012) and B*40011. Seven nucleotide substitutions were seen at the exon 3 between HLA-B61 (B*4006) and B*4002. Three substitutions at codon 95, CTC in B*4002 to TGG in B*4006, changed Leu in B*4002 to Trp in B*4006, while two substitutions at codon 97, AGC in B*4002 and ACG in B*4006, changed Ser in B*4002 to Thr in B*4006. Since B*4002 shares the epitope of alloantibodies specific for HLA-B61, two HLA-B61 subtypes are discriminated by two amino acid substitutions at residues 95 and 97. B*40012 and B*4006 differ by four amino acid substitutions on the beta sheet and five amino acid substitutions on the alpha 2 helix. Since the residues at the beta sheet seem hardly to affect the binding of alloantibody, it is suspected that the residues on the alpha 2 helix provide epitopes for alloantibodies that discriminate allospecificity between HLA-B60 and HLA-B61.

Amino Acid Sequence↗

Isolation and characterization of two new functional subtypes of HLA-B35.

Human minor histocompatibility antigen-specific, HLA-B*3501-restricted cytotoxic T-cell clones were assayed on a panel of 25 different target cells previously typed by serology as HLA-B35. Cells from 6 donors were not killed and cells from 2 of these were further studied by molecular cloning to characterize their HLA class I alleles. Two new HLA-B35 subtypes were identified. The sequence of one of them differs from B*3501 by one nucleotide change at codon 156, replacing a Leu for an Arg. The sequence of the other new subtype also shows a single nucleotide change compared to B*3501, with Gly-->Val substitution at residue 16. With these new variants, the allelic complexity of HLA-B35 extends now to eight subtypes.

Alleles↗

A novel ornithine transcarbamylase present in mycoplasma-infected myeloma cells.

A myeloma cell line (KHM-4) from a patient with multiple myeloma and idiopathic hyperammonemia, and another myeloma cell line (RPMI8226) were seen to have activity to form ammonia from arginine. High activity of ornithine transcarbamylase (OTC), a hepatic urea cycle enzyme, was detected in these cell lines. OTC of these cells was much more heat-stable than the liver enzyme, and did not cross-react with an antibody against the liver enzyme. As the OTC activity was also detected in the culture medium of the myeloma cells and because the activity was markedly decreased by the antimycoplasma drug MC-210, the OTC activity was assumed to be associated with mycoplasma infection. Polymerase chain reaction, using degenerate oligonucleotide mixtures corresponding to the two highly conserved sequences of OTC, amplified a DNA sequence that apparently encodes a portion (about 67% in length) of mycoplasma OTC. The predicted amino acid sequence of the mycoplasma enzyme was 33-47% identical with those of the enzymes of bacteria, yeast and mammals.

Amino Acid Sequence↗

Nature of heme metabolizing enzymes in a mutant rat with hyperbilirubinuria.

Eisai hyperbilirubinuria rat (EHBR) is a mutant strain which is originated from Sprague Dawley rats. The activities of heme metabolizing enzymes in EHBR were compared with those of Sprague Dawley rats as the control. The activity of delta-aminolevulinic acid (delta-ALA) synthetase, the initial and rate-limiting enzyme in heme biosynthesis, was significantly higher in the liver of EHBR. However, no significant difference in the activity of heme oxygenase, the first and rate-limiting enzyme in heme degradation, was observed in EHBR as compared to control rats. DDC, a porphyrinogenic agent, caused marked and prolonged increase in the activity of delta-ALA synthetase in EHBR. However, the contents of microsomal total heme and cytochrome P-450 were significantly decreased in EHBR 24 hrs after DDC injection. The activity of heme oxygenase by CdCl2, a inducer of heme oxygenase, was considerably higher in EHBR than in control rats. These results indicate some specific hypersensitivity for heme metabolizing enzymes in EHBR.

Animals↗

[A better method to attach an endotracheal tube to the stylet of the Bullard laryngoscope].

The Bullard laryngoscope with its introducing stylet is useful in a variety of patients with airway problems, but it poses difficulties in some cases where an endotracheal tube (ETT) catches on the ary-epiglottic fold and cannot be advanced into the trachea. This difficult may be avoided by slightly angulating the tip of the ETT so that it is directed in a better alignment toward the rima glottis. The efficacy of the two methods of angulation was studied. One hundred and eight patients were randomly assigned to one of three groups. In group 1 (control, 36 patients), the ETT was attached naturally to the stylet with the bevel facing left. In group 2 (36 patients), the ETT was hooked on the distal end of the stylet at the Murphy eye, as recommended by the manufacturer. In group 3 (36 patients), the ETT was set over the stylet after being rotated 180 degrees so that the bevel was directed to the right. Intubation on the first attempt was successful in 56% of group 1, 83% in group 2 and 100% in group 3. The patients in groups 1 & 2 in whom first attempt failed were all successfully intubated on the second trial with the method used in group 3. This method (180 degrees rotation of the ETT on the stylet), is applicable to any ETT with or without the Murphy eye.

Adolescent↗