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Biomedical subjects

M Takiguchi

Publications and source records attributed to M Takiguchi.

At least 163 records · Page 9Linked to original sources
PubMed1996

[A case report of papillary fibroelastoma of the aortic valve].

A 69-year-old woman was referred to our hospital with an aortic valve tumor. She had shown signs of chronic heart failure due to atrial fibrillation and hypertension for 4 years. There was no history of thromboembolism such as stroke and myocardial infarction, unaccountable fever, weight loss, and systemic symptoms. With two-dimensional echocardiography, a cardiac valve tumor was detected during a routine examination for heart failure. Echocardiographic findings showed a homogeneous mass with a diameter of approximately 1.5 cm, fixed directly to the noncoronary aortic valve cusp. During the operation, a papillary neoplasm, 1.5 by 1 cm, was observed at the midportion of the left ventricular side of noncoronary cusp without a peduncle. The tumor was excised together with all cusps. A 21-mm SJM aortic valve was implanted in position, and thereafter she remained free from symptoms. Histopathological examination of the tumor revealed benign papillary fibroelastoma. Two-dimensional echocardiography was utilized for a diagnosis of the aortic papillary fibroelastoma.

Aged↗
PubMed1996

[Identification of T cell epitopes by reverse immunogenetics].

Novel Strategy to identify CTL epitopes called "reverse immunogenetics" was introduced. CTL epitopes were identified as follows; (i) Identification of the motif of HLA class I binding peptides (ii) Selection of sequences matched to the motif of HLA class I binding peptides from HIV proteins and synthesis of peptides (iii) Identification of HLA class I binding peptides by the peptide binding assay (iv) Induction of CTL from PBL of HIV 1 infected individuals by HLA class I binding peptides. Multiple HIV-I epitopes presented by HLA-B35 were identified using this strategy.

Epitopes↗
PubMed1996

[Evaluation of the bite block wedged between the maxillary and mandibular molars].

The purpose of this study was to compare our original bite block (T-X Block) wedged between the maxillary and mandibular molars, with the standard gum bite block, in 200 patients whose tracheas were intubated. During emergence from isoflurane anesthesia, no trouble occurred in T-X Block group (n = 100). On the other hand, lip damage and ejection of the bite block were found in 11 and 10 cases, respectively, in gum bite block group (n = 100). As another study, an opening between the maxillary and mandibular incisor edges was measured with T-X Block placed in twenty patients under general anesthesia. The inter-incisal distances in one way of using it as a smaller wedge and in the other way as a bigger one were 21.6 +/- 2.4 and 25.2 +/- 2.6 mm, respectively. Those values were significantly larger than thickness of the gum bite block. T-X Block is very useful because its use causes no complications and makes it easier to insert a naso-gastric tube as well as to clean the oral cavity with suction by giving a larger opening of the mouth.

Adolescent↗
PubMed1996

Use of epidural anesthesia in non-cardiac surgery in two cases complicated by hypertrophic cardiomyopathy.

Two patients with hypertrophic cardiomyopathy (HCM) who underwent non-cardiac surgery were managed successfully using epidural anesthesia as the principal intraoperative anesthesia. Epidural block was induced by inserting an epidural catheter from the lumbar vertebrae toward the caudal side. Epidural anesthesia is usually avoided in HCM patients because of the risk of a decreased preload or afterload causing stenosis in the left ventricular outflow tract. However, in surgery that requires an anesthesia level at L1 or below, which has little effect on sympathetic nerves, epidural anesthesia that maintains a stabilized hemodynamic state appears to be an excellent option.

Adult↗
PubMed1996

Respiratory impedance estimated from airway and intrapleural pressure curves.

At the cessation point of inspiratory flow on an airway pressure curve of constant-flow CMV (controlled mechanical ventilation), the pressure falls rapidly at first and then gradually tapers down to an endinspiratory plateau. By fitting these two pressure changes to the voltage changes in the respiratory circuit model, the resistance and compliances in the lung periphery and the resistance in the large airway can be estimated. We designed an algorithm estimating the values of circuit elements using a circuit simulator MicroCap III. The validity of this method was examined on the mechanical lung model. The sensitivity came to within +/- 15%. Further validation was carried out on five Beagles treated with methacholine. The large airway resistance, the small airway resistance and compliance, and alveolar compliance demonstrated a two- to three-fold increase in resistances and a two thirds to one-half decrease in compliances, when compared with the base-line values before administration of methacholine. This method can be applied not only to patients during CMV, but also during surgery.

Airway Resistance↗
PubMed1995

Inhibition of gamma delta T cell recognition by receptors for MHC class I molecules.

NK cells have receptors for MHC class I molecules that inhibit cytotoxicity against target cells. We show that recognition of gamma delta CTL is negatively regulated by receptors for MHC class I molecules. Cytolysis of C1R cells by gamma delta CTL clones was inhibited by the expression of polymorphic HLA class I molecules on target cells and was restored by blocking with anti-HLA class I mAb, suggesting the presence of inhibitory receptors for HLA class I molecules. The receptors for HLA class I molecules on gamma delta T cells were heterogenous. The immune responses to various Ags may be regulated via these inhibitory receptors on T cells and NK cells.

Clone Cells↗
PubMed1995

A single nine-amino acid peptide induces virus-specific, CD8+ human cytotoxic T lymphocyte clones of heterogeneous serotype specificities.

It is generally accepted that virus-specific CD8+ cytotoxic T lymphocytes (CTLs) recognize nine-amino acid peptides in conjunction with HLA class I molecules. We recently reported that dengue virus-specific CD8+ CTLs of two different serotype specificities, which were established by stimulation with dengue virus, recognize a single nine-amino acid peptide of the nonstructural protein NS3 of dengue virus type 4 (D4V) in an HLA-B35-restricted fashion. To further analyze the relationships between the serotype specificities of T cells and the amino acid sequence of the recognized peptides, we examined the ability of this viral peptide D4.NS3.500-508 (TPEGIIPTL) to stimulate T lymphocytes of an HLA-B35-positive, dengue virus type 4-immune donor. Peptide stimulation of the PBMC generated dengue virus-specific, HLA-B-35-restricted CD8+ CTL clones. These clones lysed dengue virus-infected autologous cells, as well as autologous target cells pulsed with this peptide. Four patterns of dengue virus serotype specificities were demonstrated on target cells infected with dengue-vaccinia recombinant viruses or pulsed with synthetic peptides corresponding to amino acid sequences of four dengue virus serotypes. Two serotype-specific clones recognized only D4V. Three dengue virus subcomplex-specific clones recognized D1V, D3V, and D4V, and one subcomplex-specific clone recognized D2V and D4V. Three dengue virus serotype-cross-reactive clones recognized D1V-D4V. Thus, a single nine-amino acid peptide induces proliferation of a heterogeneous panel of dengue virus-specific CD8+ CTL clones that are all restricted by HLA-B35 but have a variety of serotype specificities. Peptides that contain a single amino acid substitution at each position of D4.NS3.500-508 were recognized differently by the T cell clones. These results indicate that a single epitope can be recognized by multiple CD8+ CTLs that have a variety of serotype specificities, but the manner of recognition by these multiple CTLs is heterogeneous.

Amino Acid Sequence↗
PubMed1995

An epitope-selective, transporter associated with antigen presentation (TAP)-1/2-independent pathway and a more general TAP-1/2-dependent antigen-processing pathway allow recognition of the HIV-1 envelope glycoprotein by CD8+ CTL.

The lysis of virally infected cells by CTLs requires the recognition of processed fragments of viral proteins presented in association with class I MHC molecules on the surfaces of infected cells. Processing begins in the cytosol with the degradation of viral proteins into peptides that are then transported into the endoplasmic reticulum (ER) for association with newly synthesized class I molecules. Transport is mediated by a heterodimer of the MHC-encoded proteins, transporter associated with Ag presentation (TAP)-1 and TAP-2. Uncertainty exists over the site of processing of viral envelope (env) proteins. The extracellular domains of env proteins are not present in the cytosol, the site in which the class I-restricted Ag-processing pathway begins. Rather, the ecto-domains of env proteins are cotranslationally translocated into the ER during biosynthesis. We have analyzed the processing of the HIV-1 env protein by using a large series of env-specific human CD8+ CTL clones. These studies have led to the delineation of two distinct processing pathways. The first pathway permits a subset of class I-restricted epitopes in the ecto-domain of the env protein to be generated efficiently by a TAP-1/2-independent mechanism localized to the ER or a premedial Golgi compartment. A second, more general pathway that is capable of generating all env epitopes uses as a substrate env protein mislocalized to the cytosol and produces peptides that are transported from the cytoplasm to the ER in a TAP-1/2-dependent fashion.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Fine tuning of peptide binding to HLA-B*3501 molecules by nonanchor residues.

The prerequisites of peptide HLA-B*3501 interactions have been revisited by quantitative peptide binding assays with 190 chemically synthesized peptide possessing two anchor residues corresponding to the HLA-B*3501 peptide motif and a statistical residue-position analysis of binding and nonbinding peptides. According to the peptide motif of HLA-B*3501, aliphatic hydrophobic (Leu, Ile, and Met) or aromatic residues (Tyr and Phe) specify the main anchor at the C terminus, and position 2 renders an auxiliary anchor for proline. The importance of these residues was confirmed as a minimum requirement for peptide binding. Moreover, we demonstrated that high affinity peptide binding requires more than one favorable position of positions 3, 4, and 7. Aliphatic hydrophobic residues and residues that contain -OH or -SH side chains in position 3, 7, and 4 significantly enhance binding. Positions 1 and 5, or 7 may deteriorate peptide binding if these positions are held by proline and small residues (Ala and Gly) or basic residues carrying positively charged side chains (Arg and Lys), respectively. Positions 6 and 8 were statistically free of constrains. Yet, bulky aromatic residues and basic residues with a positively charged side chain at position 8 decreased the binding affinity. These findings were used to assess the predictability of binding and nonbinding peptides. Our binding predictions of 28 nonamers were verified by experimental data. Taking into account the importance of anchor and nonanchor positions in peptide binding and their practical value in peptide binding prediction, the search for peptide epitopes becomes more efficient.

Amino Acid Sequence↗
PubMed1995

Dengue virus-specific, HLA-B35-restricted, human CD8+ cytotoxic T lymphocyte (CTL) clones. Recognition of NS3 amino acids 500 to 508 by CTL clones of two different serotype specificities.

Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas of the world. We analyzed dengue virus-specific CD8+ CD4- CTL at the clonal level to further understand the role of CD8+ CTL in dengue virus infections. Dengue virus-specific CD8+ CTL clones were established from lymphocytes of a dengue 4-immune adult. Three patterns of dengue serotype specificities were identified: 1) specific for dengue 4, 2) cross-reactive for dengue 2 and dengue 4 (subcomplex-specific); and 3) cross-reactive for all four dengue virus serotypes. Three dengue 4-specific clones and one dengue 2/dengue 4 cross-reactive clone were further analyzed. All four of the clones were HLA-B35 restricted and recognized NS3. The epitopes were mapped to amino acids (aa) 483 to 618 of NS3. The epitope was then defined by using synthetic peptides. Three dengue 4-specific clones and one dengue 2/dengue 4 cross-reactive clone recognized the same peptide (TPEGIIPTL) encompassing aa 500 to 508 of dengue 4 NS3. The peptide encompassing aa 500-508 of dengue 2 NS3 was recognized by a dengue 2/dengue 4 cross-reactive clone but was not recognized by the dengue 4-specific clones. Dengue 4-specific and dengue 2/dengue 4 cross-reactive clones used different TCR. These results indicate that CD8+ CTL clones that use different TCR and demonstrate two distinct serotype specificities recognize the same 9-mer peptide in the context of HLA-B35.

Adult↗
PubMed1995

Several HLA alleles share overlapping peptide specificities.

Herein we describe the establishment of assays to measure peptide binding to purified HLA-B*0701, -B*0801, -B*2705, -B*3501-03, -B*5401, -Cw*0401, -Cw*0602, and -Cw*0702 molecules. The binding of known peptide epitopes or naturally processed peptides correlates well with HLA restriction or origin, underscoring the immunologic relevance of these assays. Analysis of the sequences of various HLA class I alleles suggested that alleles with peptide motifs characterized by proline in position 2 and aromatic or hydrophobic residues at their C-terminus shared key consensus residues at positions 9, 63, 66, 67, and 70 (B pocket) and residue 116 (F pocket). Prediction of the peptide-binding specificity of HLA-B*5401, on the basis of this consensus B and F pocket structure, verified this hypothesis and suggested that a relatively large family of HLA-B alleles (which we have defined as the HLA-B7-like supertype) may significantly overlap in peptide binding specificity. Availability of quantitative binding assays allowed verification that, indeed, many (25%) of the peptide ligands carrying proline in position 2 and hydrophobic/aromatic residues at the C-terminus (the B7-like supermotif) were capable of binding at least three of five HLA-B7-like supertype alleles. Identification of epitopes carrying the B7-like supermotif and binding to a family of alleles represented in over 40% of individuals from all major ethnic groups may be of considerable use in the design of peptide vaccines.

Alleles↗
PubMed1995

Excessive function of peripheral blood neutrophils from patients with Behçet's disease and from HLA-B51 transgenic mice.

OBJECTIVE: To elucidate the role played by HLA-B51 in the neutrophil hyperfunction of Behçet's disease, we determined the superoxide production by purified peripheral blood neutrophils from Behçet's disease patients, from HLA-B51 positive healthy individuals, and from HLA-B51 transgenic mice. METHODS: Neutrophil function was evaluated by flow cytometric analysis, detecting the conversion of 2',7'-dichlorofluorescin diacetate into dichloroflurescein, induced by superoxide in the neutrophils. RESULTS: A significant correlation between the neutrophil hyperfunction and the possession of HLA-B51 phenotype, regardless of the presence of the disease, was observed in humans. FMLP-stimulated neutrophils (without in vitro priming) from HLA-B51 transgenic mice, but not those from HLA-B35 transgenic mice or from nontransgenic mice, produced substantial amounts of superoxide. CONCLUSION: The HLA-B51 molecule itself may be responsible, at least in part, for neutrophil hyperfunction in Behçet's disease.

Animals↗
PubMed1995

Peptide motifs of HLA-B51, -B52 and -B78 molecules, and implications for Behćet's disease.

Here we report peptide motifs of five HLA-B molecules, B*5101, B*5102, B*5103 B*5201 and B*7801. Motifs were obtained by pool sequencing of natural ligands eluted from the respective molecules expressed in C1R cells upon transfection. A number of individual ligands that could be sequenced confirmed the motifs. All five HLA-B molecules belong to the HLA-B5, B35-cross-reactive group and are closely related as indicated by similar sequences. B51 and B52 are associated with Bw4, whereas B78 is associated with Bw6. One of the HLA-B molecules investigated here, HLA-B*5101, is associated with Behçet's disease, a multisystemic inflammatory disease affecting various organs. This disease is especially frequent among the Japanese population. The subtle differences between the peptide motifs of B*5101 as compared with the motifs of the four other closely related but not disease-associated molecules could shed light on the nature of the HLA-association of Behçet's disease.

Amino Acid Sequence↗
PubMed1995

Isolation of a human allo-peptide presented by HLA-B51 molecules.

Recent studies have demonstrated directly that alloreactive mouse CTL recognize peptides presented by MHC class I molecules. However, there is no direct evidence that human alloreactive CTL recognize peptides presented by HLA class I molecules. We have isolated an HLA-B51 alloreactive CTL clone, 2B3, that did not kill the TAP defective cell lines T2 and .174, whereas it killed the TAP-positive cell line T1 and .174 cells transfected with TAP genes. These findings suggested that this clone recognizes a TAP-dependent allo-peptide. We attempted to isolate the human allo-peptide recognized by the 2B3 clone from HLA-B51 molecules. A naturally occurring HLA-B*5101 binding peptide isolated from T1 cells was recognized by the 2B3 clone. The peptide was also isolated from HLA-B*5101 molecules purified from C1R-B*5101 cells. In the present study, we directly demonstrated that a human alloreactive CTL clone recognizes peptide presented by HLA class I molecules.

Antigen Presentation↗
PubMed1995

Preparation of recombinant argininosuccinate synthetase and argininosuccinate lyase: expression of the enzymes in rat tissues.

Nitric oxide (NO) is synthesized from arginine by nitric oxide synthase, generating citrulline as another product, which can be recycled to arginine by argininosuccinate synthetase and argininosuccinate lyase. Rat argininosuccinate synthetase was expressed in Escherichia coli as a fusion protein with maltose binding protein, cleaved from binding protein, and purified. The purified synthetase had no enzyme activity. Rat argininosuccinate lyase was expressed in E. coli using pET-3a as a vector, and purified. The purified enzyme had a specific enzyme activity of arginine formation of 2.6 mumol/min/mg protein at 37 degrees C, the value being somewhat lower than those of the enzyme purified from various tissues. Antibodies against these enzymes were produced in rabbits. Immunoblot analyses showed that the two enzymes are most abundant in the liver, followed by kidney and testis. Smaller amounts of the enzyme proteins were present in other tissues. RNA blot analysis showed that the argininosuccinate synthetase mRNA was most abundant in the liver and kidney, followed by testis and other tissues. On the other hand, argininosuccinate lyase mRNA was most abundant in the testis, followed by kidney and liver, and by other tissues. These results show that argininosuccinate synthetase and argininosuccinate lyase are expressed both tissue-specifically and ubiquitously, and that practically all tissues have activities to convert citrulline to arginine.

Animals↗