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Biomedical subjects

Akira Saito

Publications and source records attributed to Akira Saito.

At least 19 recordsLinked to original sources
PubMed2004

Comparison between various strategies for the disease-gene mapping using linkage disequilibrium analyses: studies on adenine phosphoribosyltransferase deficiency used as an example.

Recently, linkage disequilibrium analyses have been used to detect disease-causing loci based on the common disease-common variant hypothesis. To see what methods can effectively identify the genes, we have to apply them to the practical data obtained from the human population. We extensively performed linkage disequilibrium and haplotype analyses on adenine phosphoribosyltransferase ( APRT) genes in both control and deficient subjects. To examine the power to detect disease-causing loci, we analyzed SNPs, STRPs, and VNTR within and around the APRT gene. When only SNPs were used, P values did not necessarily show significant difference, even at loci close to the mutation site for APRT*J that is exclusively observed among Japanese. However, the examination of the same samples with haplotypes based on the haplotype block data gave sufficient significance. In the case of STRP and VNTR, some single-marker loci showed significant difference. Our study suggested that the use of haplotype analysis based on the haplotype-block structure is more powerful than single-marker locus analysis for the detection of disease-related loci.

Adenine Phosphoribosyltransferase↗
PubMed2004

Evaluation of long-term transport ability of a bioartificial renal tubule device using LLC-PK1 cells.

BACKGROUND: Haemodialysis therapy does not provide renal tubule function, such as active fluid and solute transport, nor metabolic or endocrine action. Moreover, this treatment is usually associated with serious complications and high mortality. We constructed a bioartificial renal tubule device by using renal tubule epithelial cells in an artificial membrane, and evaluated transport properties of the device for 2 weeks. METHODS: A renal epithelial cell line, LLC-PK(1) (Lewis-lung cancer porcine kidney), was seeded on polysulfone hollow fibres in small and large modules. We studied perfusion and leakage of urea nitrogen (UN) and creatinine (Cr), as well as reabsorption of water, glucose and sodium for a period of 2 weeks. RESULTS: Cell-lined hollow fibre membranes significantly reduced the leakage of UN and Cr throughout the 2 week period. Reabsorption of water, glucose and sodium were adequate from days 3 to 10 and gradually decreased thereafter. LLC-PK(1) cells actively transported these substances. Scanning electron microscopy revealed that cells in the hollow fibres on day 8 became completely confluent. However, they became multi-layered and almost obstructed the hollow fibres on day 13. CONCLUSIONS: This bioartificial renal tubule device functioned to reabsorb water, glucose and sodium for approximately 10 days. This is the first report of successful long-term evaluation of a bioartificial renal tubule device. This device, in combination with continuous haemofiltration, may provide treatment to prevent complications of dialysis and raise the quality of life in chronic renal failure patients.

Animals↗
PubMed2004

Timing of first cannulation and vascular access failure in haemodialysis: an analysis of practice patterns at dialysis facilities in the DOPPS.

BACKGROUND: Optimal waiting time before first use of vascular access is not known. METHODS: Two practices-first cannulation time for fistulae and grafts, and blood flow rate-were examined as potential predictors of vascular access failure in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Access failure (defined as time to first failure or first salvage intervention) was modelled using Cox regression. RESULTS: Among 309 haemodialysis facilities, 2730 grafts and 2154 fistulae were studied. For grafts, first cannulation typically occurred within 2-4 weeks at 62% of US, 61% of European and 42% of Japanese facilities. For fistulae, first cannulation occurred <2 months after placement in 36% of US, 79% of European and 98% of Japanese facilities. Overall, the relative risk (RR) of graft failure in Europe was lower compared with the USA (RR = 0.69, P = 0.04). The RR of graft failure (reference group = first cannulation at 2-3 weeks) was 0.84 with first cannulation at <2 weeks (P = 0.11), 0.94 with first cannulation at 3-4 weeks (P = 0.48) and 0.93 with first cannulation at >4 weeks (P = 0.48). The RR of fistula failure was 0.72 with first cannulation at <4 weeks (P = 0.08), 0.91 at 2-3 months (P = 0.43) and 0.87 at >3 months (P = 0.31) (reference group = first cannulation at 1-2 months). Facility median blood flow rate was not a significant predictor of access failure. CONCLUSIONS: Earlier cannulation of a newly placed vascular access at the haemodialysis facility level was not associated with increased risk of vascular access failure. Potential for confounding due to selection bias cannot be excluded, implying the importance of clinical judgement in determining time to first use of vascular access.

Arteriovenous Shunt, Surgical↗
PubMed2004

A new mouse model for renal lesions produced by intravenous injection of diphtheria toxin A-chain expression plasmid.

BACKGROUND: Various animal models of renal failure have been produced and used to investigate mechanisms underlying renal disease and develop therapeutic drugs. Most methods available to produce such models appear to involve subtotal nephrectomy or intravenous administration of antibodies raised against basement membrane of glomeruli. In this study, we developed a novel method to produce mouse models of renal failure by intravenous injection of a plasmid carrying a toxic gene such as diphtheria toxin A-chain (DT-A) gene. DT-A is known to kill cells by inhibiting protein synthesis. METHODS: An expression plasmid carrying the cytomegalovirus enhancer/chicken beta-actin promoter linked to a DT-A gene was mixed with lipid (FuGENE trade mark 6) and the resulting complexes were intravenously injected into adult male B6C3F1 mice every day for up to 6 days. After final injection, the kidneys of these mice were sampled on day 4 and weeks 3 and 5. RESULTS: H-E staining of the kidney specimens sampled on day 4 revealed remarkable alterations in glomerular compartments, as exemplified by mesangial cell proliferation and formation of extensive deposits in glomerular basement membrane. At weeks 3 and 5, gradual recovery of these tissues was observed. These mice exhibited proteinuria and disease resembling sub-acute glomerulonephritis. CONCLUSIONS: Repeated intravenous injections of DT-A expression plasmid DNA/lipid complex caused temporary abnormalities mainly in glomeruli of mouse kidney. The disease in these mice resembles sub-acute glomerulonephritis. These DT-A gene-incorporated mice will be useful as animal models in the fields of nephrology and regenerative medicine.

Actins↗
PubMed2004

Effective reduction of antigenicity of hen egg lysozyme by site-specific glycosylation.

Various mutant lysozymes were constructed by genetic modification and secreted in yeast expression system to evaluate the changes in the antigenicity of hen egg lysozyme (HEL). Although Arg68, the most critical residue to antigenicity of HEL, was substituted with Gln, the binding of monoclonal antibodies (mAbs) with the mutant lysozyme did not critically reduce, remaining 60% of the binding with mAb. In contrast, glycosylated mutant lysozyme G49N whose glycine was substituted with asparagine dramatically reduced the binding with mAb. The oligomannosyl type of G49N lysozyme reduced binding with mAb to one-fifth, while the polymannosyl type of G49N lysozyme completely diminished the binding with mAb. This suggests that the site-specific glycosylation of lysozyme in the interfacial region of lysozyme-antibody complex is more effective to reduce the antigenicity than the mutation of single amino acid substitution in the interfacial region.

Amino Acid Substitution↗
PubMed2004

Ultrapure dialysate decreases plasma pentosidine, a marker of "carbonyl stress".

BACKGROUND: Advanced glycation end products (AGEs) and their reactive carbonyl precursors accumulate in renal failure ("carbonyl stress"). Carbonyl stress derives from a broad derangement in the nonenzymatic biochemistry of both carbohydrates and lipids. We tested the influence of dialysate quality on plasma level of pentosidine, an AGE moiety taken as a surrogate marker of carbonyl stress, in hemodialysis patients. METHODS: Plasma pentosidine is measured by means of high-performance liquid chromatography in patients hemodialyzed successively with a conventional and an ultrapure endotoxin-free dialysate. RESULTS: Dialysate endotoxin level decreased from 0.040 +/- 0.017 EU/mL before the switch to the new water supply system to less than the detection limit (<0.001 EU/mL) after the switch. Plasma pentosidine levels decreased from 1.55 +/- 0.61 nmol/mL before the switch to 1.38 +/- 0.52 nmol/mL (P < 0.0001) and 1.31 +/- 0.50 nmol/mL (P < 0.0001) 3 and 6 months after the switch to an ultrapure dialysate, respectively. Decreases in plasma pentosidine levels were similar regardless of dialyzer membrane type; ie, high-flux polysulfone, high-flux polymethylmethacrylate, and low-flux cellulose acetate membranes. Unexpectedly, plasma triglyceride levels decreased from 150 +/- 116 mg/dL (1.69 +/- 1.31 mmol/L) before the switch to 124 +/- 79 mg/dL (1.40 +/- 0.89 mmol/L; P < 0.01) and 119 +/- 75 mg/dL (1.34 +/- 0.85 mmol/L; P < 0.01) 3 and 6 months after the switch despite unchanged total cholesterol levels, respectively. Changes in pentosidine levels were unrelated to those in triglycerides, and both were unrelated to C-reactive protein levels, which remained stable throughout the study. CONCLUSION: Ultrapure dialysate reduces plasma pentosidine levels and improves plasma triglyceride levels in hemodialysis patients through still undefined mechanisms.

Arginine↗
PubMed2004

International variation in vitamin prescription and association with mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: The prevalence of water-soluble vitamin use among hemodialysis (HD) patients and whether mortality and hospitalization are associated with water-soluble vitamin use by HD patients have not previously been reported. The present study investigates patterns of water-soluble vitamin use among HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) I and evaluates outcomes associated with vitamin use. METHODS: The study sample came from the DOPPS I, a prospective observational study of adult HD patients (N = 16,345) randomly selected from 308 representative dialysis facilities in France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States. Time-dependent Cox regression models were used to assess relative risk (RR) for mortality and hospitalization for patients administered water-soluble vitamins versus those not administered water-soluble vitamins. RESULTS: There was large variation by region in the percentage of patients administered water-soluble vitamins: Europe ranged from a low of 3.7% in the United Kingdom to a high of 37.9% in Spain; 5.6% in Japan; and 71.9% in the United States. Patient use of water-soluble vitamins was associated with a substantially and significantly lower risk for mortality (RR, 0.84; P = 0.001). Lower RR for facility-level mortality also was associated with greater water-soluble vitamin use (RR, 0.98; P = 0.05 per 10% more patients administered water-soluble vitamins at the facility). CONCLUSION: Although only a randomized trial could prove that water-soluble vitamins improve outcomes, use of water-soluble vitamins is a minimal-risk practice pattern associated with improved outcomes in this prospective observational study.

Adult↗
PubMed2004

Research into the development of a wearable bioartificial kidney with a continuous hemofilter and a bioartificial tubule device using tubular epithelial cells.

Current hemodialysis treatment is insufficient because of intermittent treatment and loss of tubular function. In order to overcome the loss of tubular function, a bioartificial kidney has been developed consisting of continuous hemofiltration (CHF) with 10 L/day of filtrate and a bioartificial tubule device using proximal tubular epithelial cells and hollow fiber membranes. Ten L/day of CHF enabled plasma levels of urea, creatinine, uric acid and, beta2-microglobulin in eight renal failure patients to be maintained at remarkably low levels. The concept was tested with 6 L (4 mL/min) of 10 L/day (7 mL/min) filtrate regenerated by a bioartificial tubule device and 4 L/day (3 mL/min) replaced by food and drinks. Lewis lung cancer-porcine kidney 1 (LLC-PK1) cells with a cell density of 107 cells/mL were seeded inside polysulfone hollow fiber modules four times at 1 h intervals while rotating the module 90 degrees each time, and were cultured for 48 h to form confluent monolayers. The leak rates of urea and creatinine across LLC-PK1 cell-attached polysulfone membrane modules (membrane areas: 56 cm2 and 4000 cm2) were investigated. Via conversion from 56 m2 to 1 m2 hollow fiber modules with LLC-PK1 cells for 24 h, the transport rates of H2O, glucose and Na+ were, respectively, 40, 65 and 35% of the target transported amounts from 6 L/day of filtrate. The rates are expected to approach 100% when 4-5 g/dL of albumin is added to the basal portion of the medium since the results were obtained without the addition of albumin for colloidal osmotic pressure.

Animals↗
PubMed2004

Structural and functional properties of chicken lysozyme fused serine-rich heptapeptides at the C-terminus.

Two serine-rich heptapeptides, Ser-Ser-Ser-Lys-Ser-Ser-Ser (S6K) and Ser-Ser-Ser-Ser-Ser-Ser-Ser (S7), were fused to the C-terminus of chicken lysozyme (Lz) by genetic modification to improve the functional properties of lysozyme. The cDNAs of S6K-lysozyme (S6K-Lz) and S7-lysozyme (S7-Lz) were inserted into the expression vector of Pichia pastoris and secreted in yeast cultivation medium. The secretion amounts of S6K-Lz and S7-Lz were about 60% of that of wild-type lysozyme (Wt-Lz). The CD spectra showed that the conformation of S6K-Lz and S7-Lz was conserved regardless of the attachment of serine-rich peptides. The denaturation curves of S6K-Lz and S7-Lz also showed that the conformational changes were very small. The lytic activity of S6K-Lz and S7-Lz was almost the same as that of Wt-Lz, while the bactericidal activity against Escherichia coli of S6K-Lz and S7-Lz was greatly increased. The acetic acid-urea PAGE of phosphatase-treated S6K-Lz and S7-Lz indicated the possibility of phosphorylation of the fused serine-rich heptapeptides.

Amino Acid Sequence↗
PubMed2004

Alpha-1 antitrypsin deficiency with severe pulmonary emphysema.

Alpha-1 antitrypsin (AAT) deficiency is a hereditary disorder characterized by an early onset of emphysema. While this disease is common in the Caucasian population, it is quite rare in Japan. To date, only 15 traits have been reported and it can be speculated that many cases of this genetic deficiency may have been overlooked. We report an additional case of AAT deficiency with severe emphysema that is genetically determined as S(iiyama) variant by allele-specific polymerase chain reaction (PCR) analysis.

Alleles↗
PubMed2004

Efficacy of continuous cleansing with teicoplanin on post-CABG methicillin-resistant staphylococcus aureus (MRSA) mediastinitis: report of a case.

The patient was a 48-year-old male who was diagnosed with unstable angina. He had worsening cardiogenic shock during coronary angiography. Emergency coronary artery bypass grafting (CABG) was performed. He had a methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis on day 22 after CABG. Drains were placed in the anterior mediastinum, left thoracic cavity, and abscess cavity, and another drain was placed in the mediastinal space for continuous cleansing with povidone iodine, oxydol. For antibiotics, teicoplanin (TEIC) was administered intravenously and to the local site via the cleansing drain for about one month. No MRSA was detected by culture in discharges from the mediastinal drain. Inflammatory findings were improved, and the patient was discharged and resumed everyday life without recurrence of inflammation as of eight months. Although the number of cases of MRSA mediastinitis is small and accumulation of cases is necessary to investigate therapeutic methods and selection of antibiotics, our department will select closed continuous cleansing and TEIC for antibiotics as the first choice for MRSA mediastinitis, and accumulate cases to investigate its efficacy.

Anti-Bacterial Agents↗
PubMed2004

Association of predialysis serum bicarbonate levels with risk of mortality and hospitalization in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Experimental and some clinical data suggest that metabolic acidosis contributes to poor nutritional status, a strong predictor for mortality in hemodialysis patients. However, recent cross-sectional studies indicate that severe predialysis metabolic acidosis is associated with a greater normalized protein catabolic rate (nPCR) and greater serum albumin levels. Given this controversy, we analyzed data from the Dialysis Outcomes and Practice Pattern Study (DOPPS) for associations between predialysis serum bicarbonate and albumin concentrations, nPCR, and patient risk for mortality and hospitalization. METHODS: Data from more than 7,000 representative and randomly selected hemodialysis DOPPS patients from France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States were analyzed. Serum bicarbonate (total CO2 ) levels predialysis were corrected to the midweek interdialytic interval. RESULTS: The midweek predialysis serum bicarbonate level averaged 21.9 mEq/L (mmol/L) and correlated inversely with nPCR, serum albumin, and serum phosphorus values. Before and after adjusting for 15 comorbidities, nutrition, and equilibrated Kt/V, a U-curve best represented the association between predialysis serum bicarbonate level and risk for mortality or hospitalization. Patients with midweek predialysis serum bicarbonate levels of 20.1 to 21.0 mEq/L (mmol/L) faced the lowest risk for mortality, whereas those with bicarbonate levels of 21.1 to 22.0 mEq/L faced the lowest risk for hospitalization. Both high (>27 mEq/L) and low (< or =17 mEq/L) serum bicarbonate levels were associated with increased risk for mortality and hospitalization. CONCLUSION: Moderate predialysis acidosis seems to be associated with better nutritional status and lower relative risk for mortality or hospitalization than is observed in patients with normal ranges of midweek predialysis serum bicarbonate concentration (approximately 24 mEq/L) or severe acidosis (<16 mEq/L).

Acidosis↗
PubMed2003

Asymmetric skeletal rearrangement of symmetrically alpha,alpha-disubstituted alpha-amino aldehydes: a new entry to optically active alpha-hydroxy ketones.

A unique asymmetric skeletal rearrangement of symmetrically alpha,alpha-disubstituted alpha-amino aldehydes has been accomplished for the first time using a chiral organoaluminum Lewis acid 1. For instance, treatment of (S)-2,2'-bis(trifluoromethanesulfonylamino)-1,1'-binaphthyl with Me3Al (1.0 equiv) in toluene at room temperature for 15 min and at 110 degrees C for an additional 15 min produced (S)-1, and a subsequent reaction with alpha -amino aldehyde 2a (R = CH2Ph) at -78 degrees C for 4 h and at -40 degrees C for 12 h resulted in the smooth rearrangement to the zwitterionic iminium intermediate A, which furnished the alpha-hydroxy ketone 3a (R = CH2Ph) in 93% isolated yield with 95% ee (S) after acidic hydrolysis. This result, together with other representative examples, clearly demonstrates the effectiveness of the present method for the hitherto difficult asymmetric synthesis of acyloins. Furthermore, we found that the treatment of the in situ generated A with DIBAH afforded the corresponding anti amino alcohol exclusively without loss of enantiomeric excess. Our approach casts light on the previously unexplored yet potential utility of alpha-amino aldehydes as synthetic building blocks and also provides a new entry to optically active alpha-hydroxy ketones and 1,2-amino alcohols.

Alcohols↗
PubMed2003

Gliding movement in Peranema trichophorum is powered by flagellar surface motility.

A colorless euglenoid flagellate Peranema trichophorum shows unique unidirectional gliding cell locomotion on the substratum at velocities up to 30 micro m/s by an as yet unexplained mechanism. In this study, we found that (1) treatment with NiCl(2) inhibited flagellar beating without any effect on gliding movement; (2) water currents applied to a gliding cell from opposite sides caused detachment of the cell body from the substratum. With only the anterior flagellum adhering to the substratum, gliding movement continued along the direction of the anterior flagellum; (3) gentle pipetting induced flagellar severance into various lengths. In these cells, gliding velocity was proportional to the flagellar length; and (4) Polystyrene beads were translocated along the surface of the anterior flagellum. All of these results indicate that a cell surface motility system is present on the anterior flagellum, which is responsible for cell gliding in P. trichophorum.

Animals↗