Predominant role of N-terminal residue of nonamer peptides in their binding to HLA-B* 5101 molecules.
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Amino Acid Sequence↗
Biomedical subjects
M Takiguchi
Publications and source records attributed to M Takiguchi.
Identification of an extended half-site motif required for the function of peroxisome proliferator-activated receptor alpha.
BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor superfamily and regulate many genes of the proteins involved in lipid metabolism, including peroxisomal acyl-CoA oxidase (AOX). Through heterodimerization with retinoid X receptors (RXRs), PPAR was believed to recognize the sequence elements consisting of two directly repeating 6-bp half-sites spaced by one nucleotide (DR-1), located in the regulatory regions of these genes. RESULTS: Employing the peroxisome proliferator-responsive enhancer of the rat AOX gene, we analysed the minimal sequence requirements for enhancer activity and PPARalpha/RXRalpha binding. We found that the sequence just downstream of the DR-1 motif is indispensable for both functions. By a direct selection procedure of high-affinity binding sites from a random sequence pool, we identified a consensus sequence at the four positions next to DR-1. We also suggest that PPARalpha binds to the downstream half-site, whereas RXRalpha binds to the upstream half-site of the AOX DR-1. CONCLUSIONS: An extended half-site of 10-bp, but not a simple 6-bp half-site, is required for the PPARalpha binding, upon heterodimer formation with RXRalpha. The binding polarity of PPARalpha/RXRalpha seems to be opposite to that of other RXR-involving heterodimers.
Acyl-CoA Oxidase↗
Suppressed expression of the urea cycle enzyme genes in the liver of carnitine-deficient juvenile visceral steatosis (JVS) mice in infancy and during starvation in adulthood.
Systemic carnitine-deficient juvenile visceral steatosis (JVS) mice exhibit decreased expression of some liver-selective genes including those for the urea cycle enzymes during the infantile period. At 25 days, carbamoylphosphate synthetase (CPS) mRNA level was remarkably low in the liver of JVS mice, and the HNF-4 and C/EBP-alpha mRNA contents were also reduced. HNF-3 alpha and C/EBP-beta mRNAs were slightly higher in the liver of JVS mice, and HNF-1 mRNA remained normal. These results, together with the developmental changes of these transcription factor mRNA levels, suggest that HNF-4 and C/EBP-alpha are involved in the suppression of CPS expression. If JVS mice survived the crisis at 4-5 weeks, their body weight caught up with that of control mice around 7 weeks. The steady-state levels of CPS and argininosuccinate synthetase (ASS) mRNAs in the liver of JVS mice were normalized by no later than 8 weeks. Starvation for 48 h caused an increase of about twofold in CPS and ASS mRNA levels in the liver of control mice, while the same treatment failed to increase their levels in the liver of JVS mice. The starvation similarly caused increases in HNF-4 and C/EBP-beta mRNA levels in the liver of both control and JVS mice, but the increases were significantly less in JVS mice than in control mice. Thus, the lack of induction of CPS and ASS mRNAs during development and under starvation in JVS mice correlated with the lower induction of HNF-4 and C/EBP-alpha mRNAs, and of HNF-4 and C/ EBP-beta mRNAs, respectively. Furthermore, all these changes seemed to correlate with the presence of fatty liver and the high serum free fatty acid levels, suggesting that disturbance of fatty acid metabolism affects nitrogen metabolism at least in part via altered gene expression of transcription factors such as HNF-4, C/EBP-alpha, and C/EBP-beta.
Age Factors↗
Separation and quantification of corticosteroid-induced, bone and liver alkaline phosphatase isoenzymes in canine serum.
Quantifying alkaline phosphatase (ALP) isoenzymes in canine serum would provide a useful index in a clinical laboratory. To achieve this goal, we tested a semi-automatic assay combining wheat germ lectin (WGL) precipitation and chemical inhibition of isoenzymes of the TNS gene with levamisole to quantify bone ALP (BALP) and corticosteroid-induced ALP (CALP), respectively. The liver ALP (LALP) isoenzyme was then calculated from the equation: TALP = BALP + LALP + CALP BALP, LALP and CALP standards from serum of puppies, bile-duct ligated dogs and dogs on 4.4 mg/kg/day prednisolone for 30 days, respectively, were used. The suitability of standard sera was tested by affinity electrophoresis. Levamisole (4.2 mM) inhibits 98% of BALP and LALP but only 42% CALP. Multiplying measured CALP by 1.8 gives the total CALP value in serum. WGL precipitated 92.3% BALP, 23.3% LALP and 26.8% heated CALP standards. These values were used to adjust precipitated ALP to obtain the exact levels of BALP. WGL was then tested on pooled serum standards in which the relative proportions of all the ALPs were known and controlled. BALP was adequately quantified except when LALP and CALP levels were extremely high. The assay was also applicable under conditions resulting in high ALP. Therefore, combining WGL and levamisole inhibition provides an adequate separation and quantification of canine ALP isoenzymes. The method has great potential for diagnostic use and should be tested further for routine implementation.
Adjuvants, Immunologic↗
Human immunodeficiency virus type 2 envelope glycoprotein binds to CD8 as well as to CD4 molecules on human T cells.
We report here that human immunodeficiency virus type 2 (HIV-2) envelope glycoprotein (gp105), but not HIV-1 gp120, can bind to CD8 molecules as well as to CD4 molecules on human T cells. This phenomenon may lead to differences in the life cycles of HIV-1 and HIV-2, and it may be related to the differences in disease manifestations of HIV-1 and HIV-2 infection, including longer survival of HIV-2-infected patients.
CD4 Antigens↗
The age dependent levels of serum ALP isoenzymes and the diagnostic significance of corticosteroid-induced ALP during long-term glucocorticoid treatment.
Three isoenzymes of total alkaline phosphatase (TALP) are known in canine serum: Bone alkaline phosphatase (BALP), liver alkaline phosphatase (LALP) and corticosteroid-induced alkaline phosphatase (CALP). Using an assay developed by combining selective precipitation of BALP by wheat germ lectin (WGA) and an automated levamisole inhibition method for quantifying CALP, age-related reference ranges of the isoenzymes in 75 canine serum samples were investigated. BALP comprised 96, 38 and 26% of TALP in young, middle aged and old dogs, respectively, and CALP was respectively 12, 11 and 27% of TALP. LALP was less than 10% in the young but represented more than 50% of TALP in middle aged and old dogs. Furthermore, the significance of monitoring LALP and CALP and their relationship to hepatopathy in dogs receiving long term prednisolone therapy was assessed. In this study, TALP increased in all dogs receiving prednisolone. But only LALP was responsible in dogs with minor vacuolization of the liver, while in severely degenerated cases both LALP and CALP increased. It is concluded that a high TALP due solely to LALP, rather than LALP and CALP represents lesser liver pathologic involvement. Monitoring the 2 isoenzymes has greater significancy in assessing in the level of liver damage than relying on an increased TALP value alone. Quantifying the individual isoenzymes may further be useful in assessing the clinical significance of these isoenzymes in various conditions that result in elevated TALP values.
Adrenal Cortex Hormones↗
[Peptide binding motif for HLA class I and autoimmune disease].
Some HLA class I alleles are strongly associated with autoimmune diseases, such as HLA-B27 for ankylosing spondylitis (AS), and HLA-B51 for Behçet's disease. But it is not clear how the class I molecules play a role in induction of the diseases. Recent studies have shown that HLA class I associates with beta 2-microglobulin and one of a range of naturally processed short peptides. The peptides bind into a groove formed by two alpha helices and a beta-pleated sheet of HLA class I molecules. HLA class I molecules present peptides with allele-specific motifs to T cells, and CTL recognize the peptides on HLA class I molecules. Further studies of peptides bound to HLA class I molecules are expected to identify peptides associated with autoimmune disease.
Amino Acid Sequence↗
[The leaflet fracture of a 19 mm SJM (HP) valve during valve insertion to the calcified small aortic annulus].
Aortic valve replacement was undergone in a 70-year-old woman with calcified aortic stenosis. Calcified and fused tricuspid aortic valve was excised and a 21 mm sizer passed with some difficulty through the annulus. A 19 mm SJM HP serious was selected and the horizontal mattress suturing technique was used. The valve was held at the cuff near the hinge guard and seated into the annulus by the usual amount of pressure, however, one leaflet fracture was retrieved and the valve was removed. A 19 mm standard SJM valve was then successfully implanted. The potential factors of leaflet fracture suggested that the leaflet thickness of smaller sized SJM valves showed smaller values than other bileaflet valves in the same sized-valves. In addition, the SJM valve does not have an orifice stiffening ring like other bileaflet valves. So, needless to say direct pressure to the leaflet, indirect pressure might cause valve destruction during insertion. The abnormal pressure applied to the direction from one hinge guard to the other can introduce deforming of the orifice ring resulting in leaflet fracture like this case. The pressure directed to the perpendicular direction may introduce leaflet escape due to the deforming of the valve orifice.
Aged↗
[Relationship between the dose of lidocaine administered endotracheally in small children and the serum lidocaine level--recommended dose prior to endotracheal intubation].
To determine the optimum dose of lidocaine administered in the trachea prior to endotracheal intubation, we divided 102 surgical patients 3-5 years of age into 3 groups, i.e., group 1; 1 mg.kg-1 was sprayed in the trachea, group 2; 2 mg.kg-1 was sprayed in the trachea, group 3; 1 mg.kg-1 was sprayed in the trachea, and 1 mg.kg-1 in the pharynx and the oral cavity simultaneously. The venous serum concentration of lidocaine was measured two times either 1.5, 3, 5, 10, 15, 20, 30 or 45 min after the spray in each case. In group 1, the mean concentration of lidocaine reached the maximum of 1.05 micrograms.ml-1 at 5 min and decreased gradually after that with a small inter-individual variation. In group 2, after reaching the mean maximum concentration of 3.51 micrograms.ml-1 at 3 min, the serum level dropped quickly and then gradually decreased. There were a few cases where serum level was over 7 micrograms.ml-1. In group 2, after reaching the mean maximum concentration of 1.38 micrograms.ml-1 at 5 min, the serum level decreased more slowly, suggesting a slow absorption from the pharynx and/or the oral cavity. We conclude that the recommended dose of lidocaine for endotracheal administration is less than 2 mg.kg-1.
Administration, Inhalation↗
[A case of anastomotic aneurysm-enteric fistula].
We successfully performed circulation reconstructive surgery and repair of a small intestine resection, primarily at an anatomical position, for perforation of a pseudoaneurysm in the small intestine, which occurred in an anastomosis site of the right leg of a Y graft of an artificial blood vessel and internal iliac artery graft on a patient, at the remote time of 18 years after she had received a Y-type artificial blood vessel. The patient's life was saved. The results suggest that it is important to make a definitive diagnosis quickly after the occurrence of symptoms and to select an appropriate surgical technique according to the findings of infection adjacent to the perforation site.
Aged↗
Short-term hemodialysis treatment in dogs and cats with total uretic obstruction.
This study evaluated the single-pass system for the short-term dialysis treatment of dogs and cats with experimental renal failure. The hemodialyzer was equipped with a thin and highly permeable Cuprophan membrane. Four animals (two dogs and two cats) with total uretic obstruction were dialyzed twice in a one-week period. The vascular access by venipuncture of external jugular vein delivered more than 5 ml/min/kg/body weight of blood repeatedly, even for the cats. The evaluation of the effects of the blood flow, dialysate flow and ultrafiltration pressure revealed that the blood flow was the most important factor for effective dialysis. A 300 ml/min dialysate flow provided enough clearance of blood urea nitrogen and creatinine. The ultrafiltration pressure played an important role in ensuring that the fluid removal was constant. Laboratory studies revealed a 50.0% (range 42.0 to 59.3%) reduction of blood urea nitrogen, a 48.7% (range 42.5 to 58.7%) reduction of creatinine, and a 49.8% (range 34.3 to 66.2%) reduction of inorganic phosphate during the dialysis treatment. No dialysis disequilibrium syndrome was shown by the clinical signs. We conclude that this short-term dialysis using a single-pass system for small animals was sufficiently applicable to dogs and cats, and that the optimal duration of the dialysis was 2 hours.
Animals↗
Application of genetic search in derivation of matrix models of peptide binding to MHC molecules.
T cells of the vertebrate immune system recognise peptides bound by major histocompatibility complex (MHC) molecules on the surface of host cells. Peptide binding to MHC molecules is necessary for immune recognition, but only a subset of peptides are capable of binding to a particular MHC molecule. Common amino acid patterns (binding motifs) have been observed in sets of peptides that bind to specific MHC molecules. Recently, matrix models for peptide/MHC interaction have been reported. These encode the rules of peptide/ MHC interactions for an individual MHC molecule as a 20 x 9 matrix where the contribution to binding of each amino acid at each position within a 9-mer peptide is quantified. The artificial intelligence techniques of genetic search and machine learning have proved to be very useful in the area of biological sequence analysis. The availability of peptide/MHC binding data can facilitate derivation of binding matrices using machine learning techniques. We performed a simulation study to determine the minimum number of peptide samples required to derive matrices, given the pre-defined accuracy of the matrix model. The matrices were derived using a genetic search. In addition, matrices for peptide binding to the human class I MHC molecules, HLA-B35 and -A24, were derived, validated by independent experimental data and compared to previously-reported matrices. The results indicate that at least 150 peptide samples are required to derive matrices of acceptable accuracy. This result is based on a maximum noise content of 5%, the availability of precise affinity measurements and that acceptable accuracy is determined by an area under the Relative Operating Characteristic curve (Aroc) of > 0.8. More than 600 peptide samples are required to derive matrices of excellent accuracy (Aroc > 0.9). Finally, we derived a human HLA-B27 binding matrix using a genetic search and 404 experimentally-tested peptides, and estimated its accuracy at Aroc > 0.88. The results of this study are expected to be of practical interest to immunologists for efficient identification of peptides as candidates for immunotherapy.
Amino Acid Sequence↗
[Thoracoscopic unilateral fold plication method in lung volume reduction surgery for diffuse pulmonary emphysema].
We have devised a 'Fold Plication Method', which helps ensure safe and simple lung volume reduction surgery (LVRS) for pulmonary emphysema and prevent air leakage from pulmonary stumps, which is most crucial problem, in addition to postoperative interstitial pneumonia that is occasionally caused by the use of the bovine pericardium. We performed LVRS on seven patients with the disease, using this method and the thoracoscopic surgery, which is based on the 'Two Windows Method' we had previously developed. The operation was performed without observable bleeding within approximately one hour for all patients, who then recovered favorably.
Aged↗
[One stage operation for sternal turnover with preserved rectus muscle pedicles and aortic root replacement associated with Marfan's syndrome].
A 40-year-old man with Marfan's syndrome had annulo aortic ectasia with Sellers grade 4 aortic valve regurgitation and Wada grade 3 pectus excavatum. Simultaneous operation was successfully performed by aortic valve composite graft insertion and sternal turnover with the rectus muscle pedicles. Following a midline skin incision, the cost-sterno complex (plastron) was dissected together with the bilateral rectus muscle pedicles, and the sternum was divided transversely through the second intercostal space. The plastron with muscle pedicles was retracted away from the anterior chest toward the abdomen and was covered by the moistened sternal bag made of polyethylene to prevent dryness and contamination during the composite graft insertion. The aortic root was replaced with a composite graft consisting of a 25 mm SJM valve and a 26 mm Hemashield graft. A short interposed 10 mm Hemashield graft was inserted between the ostia of the left coronary artery and the composite graft. The right coronary artery was reimplanted in the aortic conduit using the button technique with a doughnut pledget. This one stage method offered excellent operative exposure and enabled us to prevent possible necrosis of the sternum, infection of the mediastinal sinus, and postoperative cardiac failure resulting from chest wall compression. In this procedure, active usage of the rapid autologous transfusion system effectively reduced the total amount of blood transfusion.
Adult↗
[Surgical relief of airway obstruction from a double aortic arch associated with corrected transposition of the great arteries, pulmonary atresia and bilateral patent ductus arteriosus in a neonate].
A rare 20-day-old male with double aortic arch, corrected transposition of the great arteries (cTGA), pulmonary atresia and bilateral patent ductus arteriosus (PDA) was transported to our institute because of severe respiratory dysfunction and cyanosis. The patient had been already intubated and ventilated on respirator. A echocardiography and cine-angiography demonstrated that the both sides aortic arch had almost identical sizes, originating common carotid arteries and subclavian arteries and PDAs respectively, and the descending aorta located on the left side of the mid-line. At the first surgery, the distal of the right aortic arch was divided just proximal to the descending aorta after complete tissue dissection around the arch. The divided right sided aortic arch was mobilized from posterior to anterior aspect of the bronchus. Then the right subclavian artery was divided and an original Blalock-Taussig shunt was employed. The right sided PDA was ligated. After the first surgery, respiratory dysfunction lasted for weeks mainly because of the PGE1 dependent left sided PDA. At the second surgery, left sided modified Blalock-Taussig shunt was constructed and the left sided PDA was divided. These procedures resulted in stable respiratory status and oxygen saturation. The patient was extubated three days later and now in satisfactory clinical condition.
Abnormalities, Multiple↗
Identification of HTLV-1-specific CTL directed against synthetic and naturally processed peptides in HLA-B*3501 transgenic mice.
Previous studies of CTL responses to influenza peptides in HLA single transgenic mice resulted in the identification of at most one immunodominant epitope. Since HLA-B*3501 is known to present multiple HIV-1-specific T cell epitopes we tested the cellular immune response of HLA-B*3501 transgenic mice to synthetic HTLV-1 peptides mixed with the lipohexapeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteinyl-seryl-lysyl-l ysyl- lysyl-lysine, which is a biocompatible, Th-epitopeindependent adjuvant. Eleven of 37 tested HLA-B*3501 binding peptides mounted a CTL response after three in vitro stimulations. The HLA-B*3501 affinity of peptides correlated with their ability to induce CTL in HLA-B*3501 transgenic mice. Seven peptides derived from env-gp46 (VPSPSSTPLL, VPSSSSTPL, YPSLALAPH, and YPSLALAPA), pol (QAFPQCTIL), gagp19 (YPGRVNEIL), and tax (GAFLTNVPY) proteins induced peptide-specific CTL Bulk CTL generated by four peptides derived from env-gp46 (SPPSTPLLY, VPSPSSTPLLY, and VPSPSSTPLL) and pol (QAFPQCTILQY) killed peptide-pulsed and recombinant vaccinia-infected target cells. The latter peptides therefore present T-cell epitopes and are vaccine candidates for our transgenic mouse model.
Animals↗
Endoderm-specific gene expression in embryonic stem cells differentiated to embryoid bodies.
Mouse embryonic stem cells can differentiate into various cell types within cell aggregates called embryoid bodies (EBs). This structure consists of ectodermal, mesodermal, and endodermal tissues, which resemble the embryo of egg-cylinder stage. After 8-10 days in culture, about half of the EBs expand into large cystic structures homologous to visceral yolk sac of postimplantation embryos. To study endoderm differentiation at molecular level, we examined expression of endoderm marker genes during the processes of EB development. alpha-Fetoprotein (AFP) and transthyretin (TTR) transcripts increased at the stage when embryoid bodies began to form yolk-sac-like structures and were expressed strongly thereafter. Expression of hepatocyte nuclear factor (HNF) 4, a variant form of HNF1 (also called HNF1beta), and HNF3beta started before the onset of AFP and TTR expression. HNF1 (also called HNF1alpha) expression began a few days after the onset of the expression of the transcription factors described above. Serum albumin (ALB) transcript was only found in late large cystic EBs. Also, AFP gene expression preceded ALB gene expression. These results suggest that the patterns of endoderm gene expression during EB development reflect the order found during mouse development in vivo, and EB formation may serve as an in vitro system to study the differentiation process.
Animals↗
Molecular cloning of cDNA for nonhepatic mitochondrial arginase (arginase II) and comparison of its induction with nitric oxide synthase in a murine macrophage-like cell line.
Arginase exists in two isoforms. Liver-type arginase (arginase I) is expressed almost exclusively in the liver and catalyzes the last step of urea synthesis, whereas the nonhepatic type (arginase II) is expressed in extrahepatic tissues. Arginase II has been proposed to play a role in down-regulation of nitric oxide synthesis. A cDNA for human arginase II was isolated. A polypeptide of 354 amino acid residues including the putative NH2-terminal presequence for mitochondrial import was predicted. It was 59% identical with arginase I. The arginase II precursor synthesized in vitro was imported into isolated mitochondria and proteolytically processed. mRNA for human arginase II was present in the kidney and other tissues, but was not detected in the liver. Arginase II mRNA was coinduced with nitric oxide synthase mRNA in murine macrophage-like RAW 264.7 cells by lipopolysaccharide. This induction was enhanced by dexamethasone and dibutyryl cAMP, and was prevented by interferon-gamma. Possible roles of arginase II in NO synthesis are discussed.
Amino Acid Sequence↗