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1. 高IgM症候群 hyperimmunoglobulin m syndromes
2. ガラクトース血症：臨床的特徴および診断 galactosemia clinical features and diagnosis
3. 血小板生物学 platelet biology
4. 心不全における骨格筋機能低下および運動耐容能低下 skeletal muscle dysfunction and exercise intolerance in heart failure
5. シドフォビル：概要 cidofovir an overview

English Journal

2-Chloroadenosine reverses hyperglycemia-induced inhibition of phosphoinositide synthesis in cultured human retinal pigment epithelial cells and prevents reduced nerve conduction velocity in diabetic rats.

Kato K, Thomas TP, Stevens MJ, Greene DA, Nakamura J.Author information Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0354, USA.AbstractThe effect of the adenosine (AD) analog 2-chloroadenosine (C-AD) on glucose-induced inhibition of phosphoinositide synthesis was studied in human retinal pigment epithelial (RPE) cells by monitoring the level of the phosphatidylinositol (PI) synthase substrate, cytidine diphosphate diglyceride (CDP-DG). In high-aldose reductase (AR)-expressing RPE 91 cells, C-AD decreased CDP-DG at 5 mmol/L glucose and reversed the increase by 20 mmol/L glucose. AD deaminase (ADA), which inactivates endogenously released AD, potentiated the hyperglycemia-induced increase in CDP-DG. Theophylline, an AD-A1 and AD-A2 receptor antagonist, caused an increase in CDP-DG at 20 mmol/L glucose. C-AD did not alter CDP-DG in low-AR-expressing RPE 45 cells, but did decrease CDP-DG after cells were conditioned in 300 mmol/L glucose for 1 week (which induces AR). The mechanism by which AD regulates PI synthase in cells with high AR activity is unknown, but it is independent of Gi or Gs proteins, adenylate cyclase and phospholipase C (PLC) activation, myo-inositol (MI) uptake, or MI efflux. Administration of C-AD to streptozotocin-induced diabetic rats prevented the slowing of motor nerve conduction velocity (MNCV). Thus, AD derivatives, which reverse a glucose-induced deficit in phosphoinositide metabolism, might serve as a useful pharmacological tool to intervene in hyperglycemia-induced diabetic complications.
Metabolism: clinical and experimental.Metabolism.1999 Jul;48(7):827-33.
The effect of the adenosine (AD) analog 2-chloroadenosine (C-AD) on glucose-induced inhibition of phosphoinositide synthesis was studied in human retinal pigment epithelial (RPE) cells by monitoring the level of the phosphatidylinositol (PI) synthase substrate, cytidine diphosphate diglyceride (CDP-
PMID 10421220

Plasmenylcholine (1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphocholine) biosynthesis in guinea-pig heart and liver: cholinephosphotransferase is a bifunctional enzyme for the synthesis of phosphatidylcholine and plasmenylcholine.

Xu YF, O K, Choy PC.Author information Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.AbstractPlasmenylcholine is present in significant proportion (32% of choline phosphoglycerides) in the guinea-pig heart but exists as a minor component (3% of choline phosphoglycerides) in the guinea-pig liver. In this study, the biosynthesis of plasmenylcholine in these two organs was examined. The organs were perfused with labelled choline for 15 min and chased with unlabelled choline for up to 7 h. The labelling of phosphatidylcholine was 6-fold higher than that of plasmenylcholine in the heart and about 60-fold higher in the liver. However, the same labelling ratio was maintained throughout the chase period in both organs. Alterations in the specific radioactivity of CDP-choline caused corresponding changes in the labelling of phosphatidylcholine and plasmenylcholine. Our results suggest that in guinea-pig heart and liver, CDP-choline is the immediate precursor of biosynthesis of phosphatidylcholine and plasmenylcholine. The biochemical cause for the difference in their rates of formation between the two organs was explored. The enzyme activities for the formation of both choline phosphoglycerides were determined. The two reactions share the same characteristics, and 1,2-diacylglycerol and 1-alk-1'-enyl-2-acylglcerol were found to be mutually inhibitory in a competitive fashion. The pool sizes of 1,2-diacylglycerol and 1-alk-1'-enyl-2-acylglycerol were determined, and their ratios were found to be 42 in the heart and 422 in the liver. We conclude that cholinephosphotransferase catalyses the formation of both phosphatidylcholine and plasmenylcholine in the guinea-pig tissues and the rate of plasmenylcholine biosynthesis is dependent on the availability of 1-alk-1'-enyl-2-acylglycerol. Plasmenylcholine biosynthesis is also subjected to modulation by the 1,2-diacylglycerol content of the tissue.
The Biochemical journal.Biochem J.1994 Jul 1;301 ( Pt 1):131-7.
Plasmenylcholine is present in significant proportion (32% of choline phosphoglycerides) in the guinea-pig heart but exists as a minor component (3% of choline phosphoglycerides) in the guinea-pig liver. In this study, the biosynthesis of plasmenylcholine in these two organs was examined. The organs
PMID 8037660

Immunotargeting of liposomes containing lipophilic antitumor prodrugs.

Mori A, Kennel SJ, Huang L.Author information Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261.AbstractPotential therapeutic applications of recently developed liposomes with a reduced affinity to the reticuloendothelial systems and a prolonged circulation time as targeting systems for lipophilic prodrugs were examined. In these studies, liposomes composed of phosphatidylcholine and cholesterol, additionally containing monosialoganglioside (GM1) or polyethylene glycol conjugated to phosphatidylethanolamine (PEG-PE), were used. Three antitumor lipophilic prodrugs, N-trifluoroacetyl-adriamycin-14-valerate (AD32), araC-diphosphate-diglyceride (araCdPdG), and 3',5'-o-dipalmitoyl-5-fluoro-2'-deoxyuridine (dpFUdR), were used to examine the effect of lipophilic prodrug incorporation into long-circulating liposomes and immunoliposomes on their biodistribution in mouse. Biodistribution studies with antibody-free liposomes containing lipophilic prodrugs showed that the activities of GM1 or PEG2000-PE in prolonging the circulation time of liposomes appeared to be preserved in the presence of each of the three lipophilic prodrugs at a drug/lipid molar ratio of 3:97. The effect of lipophilic prodrug incorporation on target binding of immunoliposomes was then examined using a mouse model. Incorporation of AD232 or dpFUdR into immunoliposomes, directed to the normal endothelium, did not affect the targetability of immunoliposomes, suggesting a potential effectiveness of these lipophilic prodrug-containing immunoliposomes in therapy for lung tumors. On the contrary, incorporation of araCdPdG resulted in significantly reduced target binding of immunoliposomes by yet unknown mechanism(s).
Pharmaceutical research.Pharm Res.1993 Apr;10(4):507-14.
Potential therapeutic applications of recently developed liposomes with a reduced affinity to the reticuloendothelial systems and a prolonged circulation time as targeting systems for lipophilic prodrugs were examined. In these studies, liposomes composed of phosphatidylcholine and cholesterol, addi
PMID 8483832