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Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary l-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+l-lysine·HCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. l-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary l-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of l-lysine. Dietary l-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/phosphate solution. In conclusion, dietary supplementation of l-lysine ameliorated VC by modifying key pathways that exacerbate VC.Medial vascular calcification is common in aging, diabetes, and CKD.14 Because the presence of vascular calcification is strongly associated with increased cardiovascular morbidity and mortality, several studies in both animals and humans have sought ways to reduce the extent of vascular calcification.510 However, satisfactory therapies have not yet been established.11Adenine-induced renal failure is one of the commonly used animal models for studying the development of vascular calcification, but the prevalence of vascular calcification in this model is not very high. Indeed, Price et al. reported that vascular calcification was detected in only 30% of rats with adenine-induced chronic renal failure (adenine rats) fed a normal-protein diet.5 These authors speculated that consistent vascular calcification might require a longer period of adenine feeding. On the basis of this idea, they designed a low-protein (LP) diet in an attempt to reduce the nitrogen load and thus enable the rats to thrive on the adenine diet for longer periods. As a result of this attempt, Price et al. unexpectedly found that adenine rats fed a LP diet had extensive vascular calcification without a longer feeding period.5 All 13 adenine rats fed the LP diet had uniform alizarin red staining of the aorta, whereas only 3 of the 11 adenine rats fed a normal-protein diet had partial calcification.5 These findings indicated that dietary protein deficiency correlates with the extent of vascular calcification.Proteins are usually made from 20 kinds of amino acids. On the basis of nutritional requirements, these amino acids can be divided into two groups: essential amino acids (EAAs) and non-EAAs. Because restriction of dietary protein results in a shortage of EAAs, the level of dietary EAAs may be relevant to the extent of vascular calcification. Among nine EAAs, this study focused on l-lysine (l-Lys) based on the following three reasons. First, l-Lys is the first-limiting amino acid in most cereal grains.12 Second, the safety of l-Lys supplementation has been verified in the area of animal husbandry. l-Lys has long been added to feed grains in order to improve the utility of feed proteins.13 Third, several studies have demonstrated that dietary supplementation with l-Lys protects bones from osteoporosis, a pathologic condition that often coexists with vascular calcification.14,15 These points prompted us to hypothesize that supplementation with l-Lys would ameliorate vascular calcification. Therefore, in this study, we tested this hypothesis using adenine rats.  相似文献   
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We present a unique case of IgD multiple myeloma (MM) preceding the development of extensive extramedullary disease without medullary involvement. A 63-year-old man was diagnosed with IgD-lambda MM when he developed anemia. After 3 months of chemotherapy, he was in complete remission as evidenced by the disappearance of bone marrow (BM) plasmacytosis, monoclonal IgD protein in his serum, and Bence Jones proteinuria. Six months after diagnosis, his disease took an unusual course with the development of plasmacytomas in the skin, without medullary involvement. He then received chemotherapy, resulting in the complete disappearance of the subcutaneous plasmacytomas. Two years after the initial diagnosis, his disease took an aggressive clinical course with retroperitoneal relapse, leading to the patient's death within 1 month. The two separate episodes of extramedullary disease were associated with elevated serum lactic dehydrogenase levels and the absence of plasma cells in the BM. This case provides evidence of two separate transformations of the original malignant MM clone.  相似文献   
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Acute immune thrombocytopenia (ITP) is a common benign bleeding disorder of variable etiology characterized by isolated thrombocytopenia. Intravenous immunoglobulin (IVIG) treatment is generally given as an initial treatment to pediatric patients with ITP, but markers predictive of the response to IVIG remain poorly defined. We retrospectively evaluated whether clinical and laboratory findings before treatment could predict response to IVIG and progression to chronic ITP in Japanese children with ITP. Between April 1997 and December 2011, a total of 49 children with newly diagnosed ITP were initially treated with IVIG. Their medical records were retrospectively reviewed. In multivariate analyses, lower white blood cell (WBC) count was the only unfavorable factor for response to IVIG and progression to chronic ITP. Patients with WBC count <7.0 × 109/L had a lower probability of thrombocytopenia-free survival (41 vs. 77 %, P = 0.003) and a higher rate of progression to chronic ITP (29 vs. 6 %, P = 0.040) than those with WBC count ≥7.0 × 109/L. These results suggest that ITP with lower WBC count may represent a distinct subgroup requiring initial treatment other than IVIG.  相似文献   
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An IL‐2 receptor antagonist, basiliximab, decreases the frequency of ACR in liver transplant (LT) recipients as induction therapy. The aim of this study was to evaluate the effectiveness of basiliximab against SRR as rescue therapy in pediatric LT patients with ALF. Forty pediatric ALF patients underwent LT between November 2005 and July 2013. Among them, seven patients suffering from SRR were enrolled in this study. The median age at LT was 10 months (6–12 months). SRR was defined as the occurrence of refractory rejection after more than two courses of steroid pulse therapy. Basiliximab was administered to all patients. The withdrawal of steroids without deterioration of the liver function was achieved in six patients treated with basiliximab therapy without patient mortality, although one patient developed graft loss and required retransplantation for veno‐occlusive disease. The pathological examinations of liver biopsies in the patients suffering from SRR revealed severe centrilobular injuries, particularly fibrosis within one month after LT. We demonstrated the effectiveness and safety of rescue therapy consisting of basiliximab for SRR in pediatric LT recipients with ALF.  相似文献   
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CPM is one of the most serious neurological complications that can occur after OLT and is characterized by symmetrical demyelinization in the basis pontis. The etiology of CPM remains unclear, although the rapid correction of the serum sodium and CNI concentrations may be associated with the development of CPM. With recent advances in MRI technology, early diagnosis of CPM has become possible. Here, we present the case of a five‐yr‐old female who developed CNI‐associated CPM after undergoing LDLT. A decreased level of consciousness and dysphasia was noted one wk after LDLT, and MRI revealed findings compatible with a diagnosis of CPM. The patient fully recovered from the neurological deficits related to CPM following the switch from the CNI to sirolimus. We propose MRI to be promptly considered for patients with abnormal neurological findings, together with the substitution of CNI with an mTOR inhibitor as a management regimen for CNI‐related CPM.  相似文献   
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