Cynomolgus monkey did not hyperacutely reject skin xenograft of N-acetylglucosaminyltransferase III gene transgenic pig.
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Animals↗
Biomedical subjects
H Murakami
Publications and source records attributed to H Murakami.
Influence of apolipoprotein E genotype on the response to caloric restriction in type 2 diabetic patients with hyperlipidaemia.
AIMS: Hyperlipidaemia is a major predisposing factor to atherosclerosis in patients with type 2 diabetes. Apolipoprotein (apo) E polymorphism influences lipoprotein metabolism, and the present study was undertaken to explore the relation, in type 2 diabetics, between apo E genotype and the plasma lipid response to dietary therapy. METHODS: The subjects were 104 patients with type 2 diabetes and hyperlipidaemia, and the difference, due to apo E genotype, in dietary response was followed for 4-6 weeks. The caloric intake was maintained in the range 20-25 kcal/kg, and the medications for diabetes were not changed during the follow-up period. RESULTS: Plasma total cholesterol (TC) and triglyceride (TG) levels were significantly lowered by the dietary treatment in patients with apo E genotypes of epsilon3/3, epsilon2/3 and epsilon3/4; however, the lipid levels in patients with epsilon2/4 did not respond to the diet. CONCLUSIONS: apo E genotype should be taken into consideration in the treatment of hyperlipidaemia in diabetic patients.
Adult↗
Effects of 12 months of exercise training on salivary secretory IgA levels in elderly subjects.
BACKGROUND: The immune system declines in efficiency with advancing age, making the elderly less resistant to pathogenic microorganisms. Upper respiratory tract infection (URTI) is a common illness. Recent studies have shown that suppression of secretory immunoglobulin A (SIgA) is associated with increased incidence of URTI. OBJECTIVE: To assess the effect of exercise on salivary SIgA in elderly subjects. METHODS: Forty five elderly subjects (18 men, 27 women; mean (SD) age 64.9 (8.4) years) performed both 60 minute resistance and 60 minute moderate endurance training a week for 12 months. Saliva samples were obtained before training, and at four and 12 months during the training period. Salivary SIgA concentrations were measured by enzyme linked immunosorbent assay, and the SIgA secretion rate was calculated. RESULTS: SIgA concentrations before training, and at four and 12 months during training were 24.7 (14.4), 27.2 (14.2), and 33.8 (18.5) micro g/ml respectively. SIgA secretion rates were 29.5 (26.0), 33.8 (27.2) and 46.5 (35.1) micro g/min respectively. The results indicate that both the concentration and secretion rate of SIgA significantly (p<0.01) increased during 12 months of exercise in these elderly subjects. CONCLUSION: Regular moderate exercise seems to enhance mucosal immune function in elderly subjects.
Aged↗
[Long-term results after the total cavopulmonary connection].
Between July, 1988 and November, 2002, 108 patients underwent total cavopulmonary connection (TCPC) at Kobe Children's Hospital. The primary malformation was univentricular heart in 40 tricuspid atresia in 21, mitral atresia in 16, and other complex cardiac defects in the remaining 31. Fenestrated TCPC, staged TCPC, and off-pump TCPC were performed in 39, 26, and 15 high risk patients, respectively. Nitric oxide inhalation was administered in 46 patients. The mean follow-up period was 4.3 years (range, 1 month to 14 years). There were 10 early deaths due to low cardiac output syndrome in 4, thrombosis in 3, tracheal bleeding in 2, and disseminated intravascular coagulation in 1. There were 5 late deaths due to congestive heart failure in 2 patients, arrhythmia in 1, cerebral infarction in 1, and subarachnoid hemorrhage in 1. Late complications included arrhythmia in 17 patients, systemic desaturation caused by abnormal systemic venous channels in 10, pleural or pericardial effusion in 3, chylothorax in 1, and aortic valve incompetence in 1.
Adolescent↗
Influence of porosity and composition of porous carriers on the uptake of nutrients.
The current paper assesses the potential of industrial solid wastes utilization such as blast furnace slag (BFS) and zeolite synthesized from fly ash (ZFA), which are effective as well as economically attractive for the uptake of phosphate and ammonium from polluted seawater. The solidification of BFS and ZFA has been developed in different proportions of BFS/ZFA (30/70, 50/50 and 70/30 (w/w)) with different porosities (25%, 40% and 52%, respectively) to cylindrical porous carriers using a Hydrothermal Hot-Pressing (HHP) method. The concentrations of heavy metals in ZFA and BFS were too low to affect the aquatic environment. The main finding is that the high rate of BFS (70%) in porous carriers enhanced phosphate uptake explained by the higher percentage of calcium (35.7%) in porous carriers and high pH conditions. The efficient ammonium uptake was observed with high rate of ZFA (70%) in porous carriers. Results found through this experimental work imply that porous carriers with BFS/ZFA proportion of 70/30 are suitable for potential practical application in the aquatic environment due to their efficient uptake of phosphate and ammonium. The choice was made upon their porosity (40%) and their compressive strength (56 kgf/cm2) which are relatively higher than those with BFS/ZFA proportion of 30/70 and 50/50.
Ammonia↗
ZD0473 pharmacokinetics in Japanese patients: a Phase I dose-escalation study.
ZD0473 is new platinum agent that was rationally designed to circumvent platinum resistance and reduce the potential for nephro-and neurotoxicity. This Phase I dose-escalating study investigated the pharmacokinetics, tolerability and efficacy of ZD0473 in Japanese patients with solid, refractory tumours. ZD0473 was administered as a 1-h intravenous infusion every 3 weeks. Nine patients received a total of 16 cycles of ZD0473 (median 1 cycle/patient), with 3 patients treated at each of 3 doses (60, 90, 120 mg/m2). The maximum plasma concentration (C(max)) and the area under the concentration-time curve to infinity (AUC(0-infinity)) increased with dose in a linear fashion for both total platinum and ZD0473 in plasma ultrafiltrate, suggesting that the pharmacokinetics of ZD0473 are linear. Haematological and non-haematological toxicities such as nausea and vomiting were mild (grade 1 or 2) and transient. No clinically significant nephro-, oto- or neurotoxicity was observed. Dose-limiting toxicity (DLT) was not observed and the maximum tolerated dose (MTD) was not identified. ZD0473 treatment showed evidence of disease stabilisation in 3 patients (33%). In conclusion, ZD0473 appears to have linear pharmacokinetics, and an acceptable tolerability profile at doses up to 120 mg/m2 in Japanese patients with refractory solid malignancies. Following evaluation of the data from all the Western trials, the ZD0473 development programme changed and this Japanese trial was stopped.
Adult↗
Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study.
In order to improve the disappointing prognosis of adult patients with acute lymphoblastic leukemia (ALL), we applied similar induction therapy as that used for acute myeloid leukemia (AML), ie frequent administration of doxorubicin (DOX). DOX 30 mg/m(2) was administered from days 1 to 3 and from days 8 to 10 together with vincristine, prednisolone, cyclophosphamide and L-asparaginase, followed by three courses of consolidation and four courses of intensification. From December 1993 to February 1997, 285 untreated adult patients with de novo ALL were entered. Of 263 evaluable patients (age 15 to 59; median 31), 205 (78%) obtained complete remission (CR). At a median follow-up period of 63 months, the predicted 6-year overall survival (OS) rate of all patients was 33%, and disease-free survival (DFS) rate of CR patients was 30%, respectively. By multivariate analysis, favorable prognostic factors for the achievement of CR were age <40 and WBC <50 000/microl; for longer OS were age <30 and WBC <30 000/microl; and for longer DFS of CR patients were FAB L1 and ALT <50 IU/l. Among 229 patients who had adequate cytogenetic data, 51 (22%) had Philadelphia (Ph) chromosome. Ph-negative chromosome was a common favorable prognostic factor for CR, longer OS and DFS. DFS was not different between early sequential intensification (n = 48) and intermittent intensification (n = 43) during the maintenance phase. Among CR patients under 40 years old, the 6-year survival was not different between the allocated related allo-BMT group (34 patients) and the allocated chemotherapy group (108 patients). However, among patients with Ph-positive ALL, the survival of patients who actually received allo-BMT was superior to that of patients who received chemotherapy (P = 0.046).
Antibiotics, Antineoplastic↗
Macrophage migration inhibitory factor activates antigen-presenting dendritic cells and induces inflammatory cytokines in ulcerative colitis.
The level of macrophage migration inhibitory factor (MIF) and the functions of dendritic cells (DC) are up-regulated in the peripheral blood, and the numbers of MIF-expressing cells and mature DC are increased at the colonic mucosa from patients with ulcerative colitis (UC). However, a functional relationship between MIF and DC, and the role of MIF in the pathogenesis of UC, are not clear. In this study, we showed that a pure population of peripheral blood DC is a new and still unknown source of MIF. DC from UC patients produced significantly higher levels of MIF (17 x 5 +/- 9 x 8 ng/ml, n = 10) compared with patients with Crohns disease (CD) (4 x 6 +/- 2 x 5 ng/ml, n = 5, P< 0 x 01) and control subjects (5 x 0 +/- 2 x 6 ng/ml, n = 10, P< 0 x 01). A double immunofluorescence study revealed the expression of MIF by CD83-positive mature DC at the colonic mucosa from UC patients. Blood DC treated with high amounts of MIF (500 ng/ml) showed a significantly higher stimulatory capacity (43287 +/- 5998 CPM, n = 5) in an allogenic mixed leucocyte reaction compared with untreated DC (27528 +/- 8823 CPM, n = 5, P< 0 x 05). Study of intracellular cytokine expression showed that MIF induced significant levels of interleukin (IL)-1 and IL-8 in monocytes and DC from UC and CD patients. These results showing the capacity of MIF to induce increased functional capacity of DC, and to produce IL-1 and IL-8 from monocytes and DC, indicate a role of MIF in the induction and/or perpetuation of the inflammatory environment in UC.
Cells, Cultured↗
A case of POEMS syndrome associated with reactive amyloidosis and Waldenström's macroglobulinaemia.
A72-year-old Japanese man presented with a 5-year history of fatigue, night sweats, oedema of dorsum of foot, muscle weakness, and paresthesia of the lower extremities. On examination, the patient fulfilled the diagnostic criteria for POEMS syndrome, but was unusual in that he also had underling Waldenström's macroglobulinaemia with IgM kappa. The M protein of POEMS syndrome is usually IgG and IgA with lambda light chains. To our knowledge, there are only three cases of POEMS syndrome with IgM kappa including our case. Autopsy findings revealed that small lymphocytes were more prominent than plasma cells in the bone marrow. These plasma cells were stained with IgM kappa. Amyloid deposits identified by Congo red stain were detected predominantly in the vascular walls of the gastrointestinal tract, pancreas and kidney. This amyloid protein was classified as amyloid associated protein. This is the first case of POEMS syndrome associated with reactive amyloidosis and Waldenström's macroglobulinaemiae.
Aged↗
An unusual reduction technique prior to surgical treatment for traumatic spondylolisthesis in the lower cervical spine.
Traumatic spondylolisthesis in the lower cervical spine is rare and only a few cases have been reported. We present a 56-year-old man who had severe C6-C7 spondylolisthesis without major neurological complications, caused by a traffic accident. Plain CT images showed a pedicular fracture on the right side and a laminar fracture on the left side at C6, but magnetic resonance images revealed no spinal cord compression. Application of a halo brace and maintaining the neck in slight flexion without traction resulted in reduction of the spondylolisthesis to nearly normal alignment. Anterior fusion using an autogeneous bone graft and a plate was easily performed without loss of correction. We suggest that preoperative reduction using a halo brace in slight flexion without longitudinal skull traction is useful and effective for severe traumatic spondylolisthesis in the lower cervical spine.
Cervical Vertebrae↗
Fenofibrate improves insulin sensitivity in connection with intramuscular lipid content, muscle fatty acid-binding protein, and beta-oxidation in skeletal muscle.
We investigated the effect of fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, on insulin sensitivity including lipid metabolism in skeletal muscle. Six-week-old male Sprague-Dawley rats were divided into two groups: those fed a standard chow (control) or a fructose-rich chow (fructose-fed rats (FFRs)) for 6 weeks. FFRs were treated either with a vehicle or with 30 mg/kg per day of fenofibrate for the last 2 weeks. Insulin sensitivity (M-value) was estimated by the euglycemic hyperinsulinemic glucose clamp method. Fatty acid-binding protein (FABP) in skeletal muscle was measured by ELISA, and the expression of FABP mRNA was analyzed by semi-quantitative RT-PCR. The serum and muscle triglyceride (sTG and mTG) levels and the activity of 3-hydroxyacyl-CoA dehydrogenase (HADH), a beta-oxidation enzyme, in muscle were also determined. FFRs showed a lower M-value and higher blood pressure, sTG and mTG than did the control group. The mTG was correlated positively with sTG and negatively with the M-value. Fenofibrate treatment for 2 weeks did not change blood pressure but significantly improved the M-value, sTG and mTG. FABP content and mRNA in the soleus muscle were significantly elevated in FFRs compared with those in the control group. Fenofibrate treatment further increased FABP. The HADH activity was comparable between the control group and FFRs, but significantly increased by fenofibrate treatment. These results suggest that fenofibrate improves insulin sensitivity not only by lowering serum lipids and subsequent influx of fatty acids into muscles but also by reducing intramuscular lipid content via further induction of FABP and stimulation of beta-oxidation in muscles.
3-Hydroxyacyl CoA Dehydrogenases↗
A non-natural amino acid for efficient incorporation into proteins as a sensitive fluorescent probe.
A small and highly fluorescent non-natural amino acid that contains an anthraniloyl group (atnDap) was incorporated into various positions of streptavidin. The positions were directed by a CGGG/CCCG four-base codon/anticodon pair. The non-natural mutants were obtained in excellent yields and some of them retained strong biotin-binding activity. The fluorescence wavelength as well as the intensity of the anthraniloyl group at position 120 were sensitive to biotin binding. These unique properties indicate that the atnDap is the most suitable non-natural amino acid for a position-specific fluorescent labeling of proteins that is highly sensitive to microenvironmental changes.
Amino Acids↗
Macrophage migration inhibitory factor in hepatocellular carcinoma and liver cirrhosis; relevance to pathogenesis.
The levels of macrophage migration inhibitory factor (MIF), a proinflammatory and carcinogenic cytokine, were significantly higher in the sera from patients with hepatocellular carcinoma (HCC; 25.6+/-15.3 ng/ml, n=55) and liver cirrhosis (LC; 18.9+/-10.7 ng/ml, n=26) compared with sera from patients with gastrointestinal cancer (6.8+/-7.5 ng/ml, n=29) and normal controls (5.6+/-1.2 ng/ml, n=45; P<0.01). Hepatocytes from patients with LC and HCC, but not from chronic hepatitis, expressed very high levels of MIF. A possible association between overexpression of MIF and hepatocarcinogenesis is suggested.
Adult↗
Incorporation of nonnatural amino acids into proteins by using various four-base codons in an Escherichia coli in vitro translation system.
Incorporation of nonnatural amino acids into proteins is a powerful technique in protein research. Amber suppression has been used to this end, but this strategy does not allow multiple incorporation of nonnatural amino acids into single proteins. In this article, we developed an alternative strategy for nonnatural mutagenesis by using four-base codons. The four-base codons AGGU, CGGU, CCCU, CUCU, CUAU, and GGGU were successfully decoded by the nitrophenylalanyl-tRNA containing the complementary four-base anticodons in an Escherichia coli in vitro translation system. The most efficient four-base decoding was observed for the GGGU codon, which yielded 86% of the full-length protein containing nitrophenylalanine relative to the wild-type protein. Moreover, highly efficient incorporation of two different nonnatural amino acids was achieved by using a set of two four-base codons, CGGG and GGGU. This work shows that the four-base codon strategy is more advantageous than the amber suppression strategy in efficiency and versatility.
Amino Acids↗
Five-base codons for incorporation of nonnatural amino acids into proteins.
Extension of the genetic code for the introduction of nonnatural amino acids into proteins was examined by using five-base codon-anticodon pairs. A streptavidin mRNA containing a CGGUA codon at the Tyr54 position and a tRNA(UACCG) chemically aminoacylated with a nonnatural amino acid were added to an Escherichia coli in vitro translation system. Western blot analysis indicated that the CGGUA codon is decoded by the aminoacyl-tRNA containing the UACCG anticodon. HPLC analysis of the tryptic fragment of the translation product revealed that the nonnatural amino acid was incorporated corresponding to the CGGUA codon without affecting the reading frame adjacent to the CGGUA codon. Another 15 five-base codons CGGN(1)N(2), where N(1) and N(2) indicate one of four nucleotides, were also successfully decoded by aminoacyl-tRNAs containing the complementary five-base anticodons. These results provide a novel strategy for nonnatural mutagenesis as well as a novel insight into the mechanism of frameshift suppression.
Amino Acid Sequence↗
Mouse Atp6f, the gene encoding the 23-kDa proteolipid of vacuolar proton translocating ATPase.
The 23-kDa proteolipid subunit of mouse vacuolar-type proton-translocating ATPase (V-ATPase) was predicted to be a hydrophobic polypeptide of 205 amino acid residues with five putative transmembrane segments. It exhibits sequence similarity to Vma16p of Saccharomyces cerevisiae and vha-4 of Caenorhabdittis elegans (83 and 84%, respectively). Southern blot analysis indicated that the proteolipid is encoded by a single gene, Atp6f, in the mouse genome. Atp6f was mapped to approximately 55 cM on chromosome 4, and its genomic organization is similar to that of the human gene: 8 exons separated by 7 introns, with boundaries matching the GT-AG rule. RNA blotting demonstrated that Atp6f is transcribed as 1.0- and 1.8-kb mRNAs in multiple tissues to varying degrees. The major transcription initiation sites are at -13 and -58 bp upstream of the translation initiation codon. The epitope-tagged 23-kDa protoelipid was localized in endomembrane organelles in CHO cells, as expected for a component of a vacuolar-type proton pump.
Alternative Splicing↗
Remodeling of the major pig xenoantigen by N-acetylglucosaminyltransferase III in transgenic pig.
We have been successful in generating several lines of transgenic mice and pigs that contain the human beta-d-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) gene. The overexpression of the GnT-III gene in mice and pigs reduced their antigenicity to human natural antibodies, especially the Galalpha1-3Galbeta1-4GlcNAc-R, as evidenced by immunohistochemical analysis. Endothelial cell studies from the GnT-III transgenic pigs also revealed a significant down-regulation in antigenicity, including Hanganutziu-Deicher antigen, and dramatic reductions in both the complement- and natural killer cell-mediated pig cell lyses. Changes in the enzymatic activities of other glycosyltransferases, such as alpha1,3-galactosyltransferase, GnT-IV, and GnT-V, did not support cross-talk between GnT-III and these enzymes in the transgenic animals. In addition, we demonstrated the effect of GnT-III in down-regulating the xenoantigen of pig heart grafts, using a pig to cynomolgus monkey transplantation model, suggesting that this approach may be useful in clinical xenotransplantation in the future.
Animals↗
Carbohydrate recognition of gramicidin S analogues in aqueous medium.
We have designed and synthesized of carbohydrate-binding peptides, gramicidin S analogues. Asn/Asp/Gln and Trp residues in the peptides were employed as the binding sites for carbohydrates by hydrogen-bonding interaction and the creation units for hydrophobic pocket to promote the interaction, respectively. The data of fluorescence spectroscopy and affinity column chromatography indicated that the peptides possessed the binding ability for some carbohydrates in aqueous medium. As a result of 1H NMR study, nuclear Overhauser effects between aromatic side chains of a peptide, [Gln(1,1'),Trp(3,3')]-gramisidin S and mannose were observed, indicating that the interaction of the peptide with the sugar occurred in the hydrophobic environment formed by Trp and Phe residues.
Bacillus↗