Effects of Reducing L-Carnitine Supplementation on Carnitine Kinetics and Cardiac Function in Hemodialysis Patients: A Multicenter, Single-Blind, Placebo-Controlled, Randomized Clinical Trial.

L-carnitine (LC) supplementation improves cardiac function in hemodialysis (HD) patients. However, whether reducing LC supplementation affects carnitine kinetics and cardiac function in HD patients treated with LC remains unclear. Fifty-nine HD patients previously treated with intravenous LC 1000 mg per HD session (three times weekly) were allocated to three groups: LC injection three times weekly, once weekly, and placebo, and prospectively followed up for six months.

Kinetics of Serum Carnitine Fractions in Patients with Chronic Kidney Disease Not on Dialysis.

Background: Carnitine plays a pivotal role in energy synthesis through β-oxidation in mitochondria. Serum and tissue levels of free carnitine are significantly decreased in dialysis patients, whereas acylcarnitine levels are increased. However, the precise kinetics and fate of carnitine fractions in chronic kidney disease (CKD) patients who are not on dialysis have not been clarified.

l-carnitine supplementation vs cycle ergometer exercise for physical activity and muscle status in hemodialysis patients: A randomized clinical trial.

Serum carnitine is decreased in hemodialysis patients, which induces muscle atrophy. Thus, we examined the different effects of l-carnitine and exercise on exercise activity and muscle status in hemodialysis patients. Twenty patients were divided into l-carnitine and cycle ergometer groups and were followed for 3 months.

Dihydropyrimidinase deficiency in four East Asian patients due to novel and rare DPYS mutations affecting protein structural integrity and catalytic activity.

Dihydropyrimidinase (DHP) is the second enzyme of the pyrimidine degradation pathway and catalyzes the ring opening of 5,6-dihydrouracil and 5,6-dihydrothymine. To date, only 31 genetically confirmed patients with a DHP deficiency have been reported and the clinical, biochemical and genetic spectrum of DHP deficient patients is, therefore, still largely unknown. Here, we show that 4 newly identified DHP deficient patients presented with strongly elevated levels of 5,6-dihydrouracil and 5,6-dihydrothymine in urine and a highly variable clinical presentation, ranging from asymptomatic to infantile spasm and reduced white matter and brain atrophy.

L-Carnitine Supplementation Improves Self-Rating Depression Scale Scores in Uremic Male Patients Undergoing Hemodialysis.

Background: Depression is highly prevalent in uremic patients undergoing hemodialysis (HD). We previously found that low free-carnitine levels are associated with depression severity in male patients undergoing HD. However, whether L-carnitine supplementation improves the depression state in male patients undergoing HD remains unclear.

Translation and Initial Validation of the Japanese Version of the Self-Beliefs Related to Social Anxiety Scale.

Cognitive models of social anxiety posit that there are several types of maladaptive beliefs responsible for persistent social anxiety. Although these beliefs are theoretically important, currently there is no validated measure of these beliefs in Japan. In the present study, we translated into Japanese a well-validated measure of these beliefs, the Self-Beliefs Related to Social Anxiety (SBSA) Scale.

Isovaleric acidemia: Therapeutic response to supplementation with glycine, l-carnitine, or both in combination and a 10-year follow-up case study.

Unlabelled: Isovaleric acidemia (IVA) is an organic acid disease caused by a deficiency of isovaleryl-CoA dehydrogenase. Deficiency of this enzyme leads to accumulation of organic acids, such as isovalerylcarnitine and isovalerylglycine. The proposed IVA treatments include leucine restriction and l-carnitine and/or glycine supplementation, which convert isovaleric acid into non-toxic isovalerylcarnitine and isovalerylglycine, respectively.

Clinical, biochemical and molecular analysis of 13 Japanese patients with β-ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation [corrected].

β-ureidopropionase (βUP) deficiency is an autosomal recessive disease characterized by N-carbamyl-β-amino aciduria. To date, only 16 genetically confirmed patients with βUP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese βUP deficient patients.

Effect of the edible mushroom Mycoleptodonoides aitchisonii on transient global ischemia-induced monoamine metabolism changes in rat cerebral cortex.

We performed a transient bilateral common carotid artery occlusion on rats and investigated whether feeding an aqueous extract of Mycoleptodonoides aitchisonii, an edible mushroom, affected metabolism of monoamines in the cerebral cortex, possibly protecting against ischemic damage. Seventeen days after the surgery, concentrations of the dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and of homovanillic acid (HVA) in the cerebral cortex of the M. aitchisonii-fed group (MV) were higher than in the control ischemia (CV) group.

[New functional proteins identified by proteomic analysis in the epidermal growth factor receptor-mediated signaling pathway and application for practical use].

To clarify the whole picture of epidermal growth factor (EGF) signaling pathway, we identified proteins from the EGF-stimulated A431 cells by anti-phospho-tyrosine antibody column chromatography. Over 150 proteins were detected including previously unidentified proteins as well as well-studied proteins. Among these proteins, we picked up four proteins that had not been known in EGF signaling pathway and analyzed their functions.

GAREM, a novel adaptor protein for growth factor receptor-bound protein 2, contributes to cellular transformation through the activation of extracellular signal-regulated kinase signaling.

Adaptor proteins for the various growth factor receptors play a crucial role in signal transduction through tyrosine phosphorylation. Several candidates for adaptor proteins with potential effects on the epidermal growth factor (EGF) receptor-mediated signaling pathway have been identified by recent phosphoproteomic studies. Here, we focus on a novel protein, GAREM (Grb2-associated and regulator of Erk/MAPK) as a downstream molecule of the EGF receptor.

Novel tyrosine phosphorylated and cardiolipin-binding protein CLPABP functions as mitochondrial RNA granule.

We identified a new protein containing the pleckstrin homology (PH) domain through tyrosine phosphoproteomics using epidermal growth factor-stimulated cells. The tandem PH domains of this protein can bind to mitochondria-specific phospholipid, cardiolipin or its dehydro product, phosphatidic acid; therefore, we have designated this protein as cardiolipin and phosphatidic acid-binding protein (CLPABP). In this study, we show that CLPABP is localized on the tubulin network and the mitochondrial surface in the granular form along with other proteins and RNA.

CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP.

To decipher the global network of the epidermal growth factor (EGF) receptor-mediated signaling pathway, a large scale proteomic analysis of tyrosine-phosphorylated proteins was conducted. Here, we focus on characterizing a novel protein, CFBP (CIN85/CD2AP family binding protein), identified in the study. CFBP was found to be phosphorylated at tyrosine 204 upon EGF stimulation, and the CIN85/CD2AP family was identified as a binding partner.

Suppression of the ligand-mediated down-regulation of epidermal growth factor receptor by Ymer, a novel tyrosine-phosphorylated and ubiquitinated protein.

The ligand-mediated down-regulation of the growth factor receptors is preceded by the involvement of various other factors. In particular, a ubiquitin ligase, Cbl, plays a central role in this event. Several candidates that have potential effects on the negative control of the epidermal growth factor (EGF) receptor have now been identified by our recent studies in phospho-proteomics.