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Previous studies using citrin/mitochondrial glycerol-3-phosphate (G3P) dehydrogenase (mGPD) double-knockout mice have demonstrated that increased dietary protein reduces the extent of carbohydrate-induced hyperammonemia observed in these mice. This study aimed to further elucidate the mechanisms of this effect. Specific amino acids were initially found to decrease hepatic G3P, or increase aspartate or citrulline levels, in mGPD-knockout mice administered ethanol. Unexpectedly, oral glycine increased ammonia in addition to lowering G3P and increasing citrulline. Subsequently, simultaneous glycine-plus-sucrose (Gly + Suc) administration led to a more severe hyperammonemic state in double-KO mice compared to sucrose alone. Oral arginine, ornithine, aspartate, alanine, glutamate and medium-chain triglycerides all lowered blood ammonia following Gly + Suc administration, with combinations of ornithine-plus-aspartate (Orn + Asp) or ornithine-plus-alanine (Orn + Ala) suppressing levels similar to wild-type. Liver perfusion and portal vein-arterial amino acid differences suggest that oral aspartate, similar to alanine, likely activated ureagenesis from ammonia and lowered the cytosolic NADH/NAD+ ratio through conversion to alanine in the small intestine. In conclusion, Gly + Suc administration induces a more severe hyperammonemic state in double-KO mice that Orn + Asp or Orn + Ala both effectively suppress. Aspartate-to-alanine conversion in the small intestine allows for effective oral administration of either, demonstrating a pivotal role of inter-organ aspartate metabolism for the treatment of citrin deficiency.

In this study, we enrolled early rheumatoid arthritis (RA) patients at multiple institutes who fulfilled the American Rheumatism Association 1987 revised criteria for the classification of RA, and followed the clinical results of disease-modifying anti-rheumatic drug (DMARD) treatment prospectively. With the aim of developing therapeutic guidelines using the disease activity score 28 (DAS28) as disease indices, we investigated the usefulness of bucillamine (BUC), one of the most widely used DMARDs in Japan. Eighty-one patients with early RA who had not previously been treated with DMARDs were suitable for BUC therapy as first-choice treatment. After 24 months of treatment, at least moderate improvement was seen in 87.5% of patients using the DAS28 erythrocyte sedimentation rate (ESR). After 24 months of BUC therapy, 7 patients (43.8%) met the remission criterion of DAS28 (ESR)

We report a Japanese boy who died at Day 28 of life because of severe carbamoyl phosphate synthetase I (CPS1) deficiency that was proven by enzyme assay. By analysis of cDNA and genomic DNA, he was shown to be a compound heterozygote with two point mutations of the CPS1 gene, 840G>C leading to an aberrant splicing and 1123C>T (predicting Q375X). The 840G>C was a mutation described in another Japanese family. Since his parents carried each mutation heterozygously, we performed prenatal diagnosis at 16 weeks of his mother's next gestation by multiplex PCR and melting curve analysis in a single capillary containing two-color fluorescent (LC-Red 640 and LC-Red 705) probes on LightCycler. We analyzed genomic DNA extracted from amniotic cells and found that the fetus was homozygous for the wild-type alleles. At term a healthy girl was born without hyperammonemia.

The expression of carbamoyl phosphate synthetase I (CPS) gene is suppressed in the liver of carnitine-deficient juvenile visceral steatosis (JVS) mice at weaning and under starvation at adult age. To clarify the suppression mechanism, we produced CPSL transgenic JVS mice carrying a transgene composed of the chloramphenicol acetyltransferase (CAT) gene with the upstream region (−12 kb to +138) of the rat CPS gene and CPSE transgenic JVS mice carrying a transgene composed of the luciferase gene with minimal promoter (299 bp from −161 to +138) and enhancer (469 bp around −6.3 kb) fragments of the rat gene. The expression of the CAT gene as well as the endogenous CPS was suppressed in CPSL transgenic JVS mice, but luciferase gene expression was not suppressed in CPSE transgenic JVS mice. We isolated the 5′-upstream region of the mouse CPS gene and identified an activator protein-1 (AP-1) site downstream of the minimum enhancer region of both rat and mouse CPS genes. In conjunction with the 313-bp mouse promoter region, the 714-bp mouse enhancer fragment conferred a cell-type-dependent hormone responsiveness. In rat primary cultured hepatocytes, the addition of oleic acid suppressed reporter gene expression induced by dexamethasone in the construct containing the enhancer fragment of 714 bp with the AP-1 site, but not in its AP-1 site mutants or in 519 bp without the AP-1 site. These results strongly suggest that direct protein–protein interaction between AP-1 and glucocorticoid receptor is not involved in the suppression of the CPS gene in JVS mice and that the AP-1 element is the cis-element which is responsible for the suppression.

We documented a case of systemic lupus erythematosus with clinical features of multiple sclerosis who developed transverse myelopathy. Magnetic resonance imaging showed the presence of an abnormal high signal intensity in the gray matter of a swollen spinal cord corresponding to the patient's neurological deficits. After two previous episodes of exacerbation and remission consistent with the clinical diagnosis of multiple sclerosis, right hemiparesis and hemisensory disturbances ensued, then lupus nephritis was confirmed by a renal biopsy.

In patients with SjOgren's syndrome (SS), the salivary and lacrimal glands are often affected, although other epithelial tissues can become inflamed. Here, we report the first case of abacterial prostatitis in a patient with SS complicated by primary biliary cirrhosis. Histologically, the distribution and subpopulation of infiltrating lymphocytes were similar in the salivary gland, liver, and prostate. Treatment with steroid was successful. We speculate that the prostate may be one of the target organs in SS.

(2011). Erratum to: A multicentre trial of bucillamine in the treatment of early rheumatoid arthritis (SNOW study) Modern Rheumatology: Vol. 21, No. 3, pp. 258-259.

症例32才,男性.昭和62年2月頃より左前腕の腫脹および疼痛, 7月頃より左手指の屈曲拘縮が出現し, 10月当院整形外科入院,血沈促進, CRP強陽性,高免疫グロブリン血症を認め,また骨シンチを契機として左水腎症および尿管狭窄を指摘され精査目的に同年12月当科に転科.後腹膜生検より後腹膜線維症と診断し,薬物使用・悪性腫瘍等はなく,特発性と診断した.さらに,左前腕の生検で筋・筋膜・血管壁への細胞浸潤およびfibrosis,肝生検でもfibrosisを認め,多発性にfibrosisをきたすまれな病態と考えた.過去に同様の特発性後腹膜線維症の記載はなく, multifocal fibrosclersisの1群に新たに加えられるべきと考えられた.

当科126例のSLE群と, 70例の非SLEリウマチ疾患群においてARA新旧両基準について検討した. SLE群の臨床症状では関節炎90%,蝶形紅斑62%が多く, Tanらの報告と比較すると新基準では漿膜炎が低頻度である以外に有意差はなかつた. ARA新基準に加えられた項目では,抗核抗体99%,抗DNA抗体83%と高かつた. Sm抗体は陽性率26%であるがLE細胞やBFPと同様に特異度はきわめて高かつた. ARA基準の平均陽性項目数はSLE群では旧基準5.40項目,新基準5.61項目であり, 4項目以上陽性症例の割合はそれぞれ88.1%, 96.8%と有意に増加が認められた.対照群の特異度は98.6%から95.7%と減少したが有意差はなく,新基準は感度に勝ることが示された.

症例は35才女性.昭和57年3月顔面,三叉,嗅神経麻痺にて発症,約1カ月後にレイノー現象,関節痛が出現した.検査所見では白血球減少,抗核抗体640×陽性(斑紋型),抗RNP抗体16×陽性を認め,唾液腺造影所見および小唾液腺生検所見より,乾燥症状を欠くsubclinical Sjogren症候群(SJS)と診断した. SJSの末梢性脳神経障害の報告は少なく,多発性脳神経障害を初発症状とするSJS例は極めてまれと考えられたので報告する.