Citrulline is generally a non-proteineous amino acid and an intermediate for arginine and urea syntheses. Citrullinemia is caused by a deficiency of argininosuccinate synthetase (ASS) and a deficiency of mitochondrial aspartate glutamate carrier (AGC). We discovered SLC25A13 as the causative gene of adult-onset type II citrullinemia (CTLN2), which encodes citrin, and established a disease entity of citrin deficiency. Citrin deficiency results in not only CTLN2 but also neonatal cholestatic hepatitis (NICCD). NICCD patients suffer from a variety of symptoms such as citrullinemia, prolonged jaundice, hypoglycemia, galactosemia and hypoproteinemia. Citrin, as the liver-type AGC, playsa role not only in urea, protein and nucleotide biosynthetic pathways by transporting aspartate from mitochondria to cytosol, but also in aerobic glycolysis by transporting NADH reducing equivalent from cytosol to mitochondria as a member of malate aspartate shuttle, which is probably the reason why citrin deficiency patients suffer from a variety of symptoms. The most critical point so far we have known concerning the therapy is that carbohydrate intake or administration may deteriorate the symptoms.

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The increase in circulating peroxide lipids is considered as a promoting factor of atherosclerotic disease, because peroxide lipids in the subendothelial space directly induce formation of atherosclerotic plaques. Recently, lysophosphatidylcholine (LPC) and oxidative low-density lipoprotein (oxLDL) have been measured as biological markers of atherosclerosis. To clarify the clinical implication of the measurement of LPC, plasma concentrations of LPC and also oxLDL and high-sensitivity C-reactive proteins (hs-CRP) were measured in 147 patients with type 2 diabetes, and these measurements were compared in relationship to clinical characteristics and diabetic vascular complications. LPC concentration was also investigated in 24 healthy subjects (12 males and 12 females) as a reference of circulation LPC values.
Plasm a LPC concentration in male type 2 diabetics (mean ± standard deviation, 0.221 ± 0.059 mmo1/1) was lower than that in female diabetics (0.202 ± 0.055). This gender difference in plasma LPC concentration was also confirmed in healthy subjects (males 0.256 ± 0.048, and females 0.220 ± 0.031). Plasma oxLDL had a good correlation with plasma LDL cholesterol (LDL-C) in diabetics, and oxLDL concentration in female diabetics (55.3 ± 17.3 U/1) was significantly higher than that in male diabetics (48.9 ± 14.8). There was no significant correlation between LPC and oxLDL concentrations. LPC and oxLDL did not correlate with hs-CRP in diabetics. As for diabetic complications, plasma LPC in diabetics with ischemic heart disease (IHD) was lower (0.179 ± 0.057) than that without IHD (0220 ± 0.049). Plasma LPC in diabetics with macroangiopathy (cerebral infarction, IHD and arteriosclerosis obliterans 0.195 ± 0.054) was also lower than that without macroangiopathy (0.222 ± 0.059). In males and females plasma LPC in diabetics with macroangiopathy or IHD was lower than those without macroangiopathy or IHDrespectively. hs-CRP was significantly higher in diabetics with IHD (4.77 ± 7.27 mg/l) than those without IHD (1.99 ± 4.86). However, there was no significant difference in oxLDL between those with and without complications.
hs-CRP and oxLDL have been considered to be useful markers to detect vascular complications. However,
our results suggest that LPC was equal or superior hs-CRP and oxLDL in detecting vascular complications in type 2 diabetics.

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Although the immunoseparation method is exclusively used to estimate remnant lipoprotein cholesterol as remnant-like particle cholesterol (RLP-C), a new detergent-based method has recently been developed and applied to a reagent for automated analyzer (RemL-C, Kyowa Medex Co.). Therefore, we conducted a comparative study of these two methods.
Fifty-three serum samples and 41 other serum samples were used for the studies on correlation and precision, respectively. Apolipoprotein E (apoE)-deficient VLDL fraction isolated from VLDL fraction (d<1.006) by immunoseparation was used to study the effect of apoE elimination on determination.
A strong linear correlation was found between RemL-C and RLP-C levels, and modeled with the following regression equation: RemL-C (mg/dL) = 0.853×RLP-C+3.18 (r=0.743). The average of differences between RemL-C and RLP-C indicated that RemL-C levels were generally higher. There were five discrepant cases in which the serum RemL-C level was 10mg/dL or more higher than the serum RLP-C level, all five were women, and all but one were pregnant. In contrast, there were two reversed discrepant cases that were both men, and both were elderly and had malignant tumors. Precision was inferior in RLP-C especially in the range of lower values. In apoE-deficient VLDL, the percentage of RemL-C/total cholesterol was similar to that in control VLDL, whereas the percentage of RLP-C/total cholesterol was lower than that in control VLDL.
From these fi ndings, it is suggested that RemL-C and RLP-C have a similar clinical significance but show a different reactivity to some species of lipoprotein.

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Committee on JSCC and JDS has been promoting standardization activities of HbA1c measurement. Commutabilityo f measuredv alues of HbA1icn clinical laboratoryi s maintainedb y using the referencem aterial of JDS in Japan.T o standardizeH bA1mc easurement, IFCC WG established reference measurement procedure (RMP) using HPLC-CE or HPLC-ESI/-MS after protease hydration against specified? A-N-fructosyl-hemoglobin as measurand. Furthermore, international harmonization must be needed for HbA1c measurements. Committee on Diabetes Mellitus Indices of JSCC project cooperated with JDS has established JSCC reference measurement system for HbA1c measurement traceable to IFCC RMP and IFCC primary calibrator. JSCC RMP as reference method uses a HPLC method based on KO500 procedure presented by Hoshino and his colleagues. The KO500 procedure defines? A-N-mono-fructosyl-hemoglobin as measurand. To maintain reliability and commutability of HbA_1c measurement in national and international standardization, a guideline of reference laboratory (RL) network system is constituted. The RL is responsible to perform assigned values of matrix reference materials, performance evaluation of routine measurement procedures, and target values of external quality assessment in proficiency testing. And also the RLs are committed to IFCC reference network for global harmonization activity. In RLs, the specification and standard for requirement of RL are specified as the Glycohemoglobin Standardization System in Japan.

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[in Japanese]

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