Elevated urinary β2 microglobulin in the first identified Japanese family afflicted by X-linked myopathy with excessive autophagy

Here we report what is to our knowledge the first identified Japanese family afflicted by X-linked myopathy with excessive autophagy. The index case is a 52-year-old man with almost 40 years of progressive proximal muscle weakness. High urinary β2 microglobulin, normal serum β2 microglobulin, autophagic vacuoles with sarcolemmal features, and a hemizygous c.164–7T>G mutation in the VMA21 gene were found. His two maternal uncles had similar clinicopathological findings. High urinary β2 microglobulin without obvious renal dysfunction might result from decreased urine acidification in the distal convoluted tubules caused by the VMA21 gene mutation. These findings might prove to be useful as a preliminary marker suggestive of X-linked myopathy with excessive autophagy.     

Parameters affecting prognosis after hemodialysis withdrawal: experience from a single center

Clinical and Experimental Nephrology - Withdrawal from maintenance hemodialysis is unavoidable in some patients due to their poor general condition; however, their survival days vary depending on...     

Safety and effectiveness of ferric citrate hydrate in serum phosphorus management of patients with chronic kidney disease: a long-term,real-world,observational, post-marketing surveillance study

Clinical and Experimental Nephrology - Ferric citrate hydrate (FC) is an oral iron-based phosphate binder that is used to treat hyperphosphatemia in patients with chronic kidney disease (CKD). This...     

Acute effects of zolpidem on daytime alertness, psychomotor and physical performance

In a double-blind cross-over study, seven athletes received zolpidem (10mg) or placebo in two sessions over two nights. Residual effects on subsequent daytime functions were evaluated objectively by measuring psychomotor and physical performance using a combined test of finger dexterity, a simple discriminatory reaction test, critical flicker fusion test (CFF), vertical jump, and 50-m sprint, as well as subjectively, by visual analog scales. Zolpidem shortened self-estimated sleep latency and increased total sleep at nighttime. There was no change in alertness and fatigue scales on the following day in the zolpidem session, but realm of daytime well-being was slightly worsened. The CFF test showed significantly better results in the zolpidem group than in the placebo group. Zolpidem did not have effects in athletic evaluation. Zolpidem has a hypnotic activity without disturbing psychomotor and physical performance on the following day when given to healthy adults, suggesting zolpidem may be used in healthy athletes to adjust their extrinsic sleep disturbances and their consecutive psychomotor and physical impairments.     

Computing mammographic density from a multiple regression model constructed with image-acquisition parameters from a full-field digital mammographic unit

Breast density (the percentage of fibroglandular tissue in the breast) has been suggested to be a useful surrogate marker for breast cancer risk. It is conventionally measured using screen-film mammographic images by a labor-intensive histogram segmentation method (HSM). We have adapted and modified the HSM for measuring breast density from raw digital mammograms acquired by full-field digital mammography. Multiple regression model analyses showed that many of the instrument parameters for acquiring the screening mammograms (e.g. breast compression thickness, radiological thickness, radiation dose, compression force, etc) and image pixel intensity statistics of the imaged breasts were strong predictors of the observed threshold values (model R(2) = 0.93) and %-density (R(2) = 0.84). The intra-class correlation coefficient of the %-density for duplicate images was estimated to be 0.80, using the regression model-derived threshold values, and 0.94 if estimated directly from the parameter estimates of the %-density prediction regression model. Therefore, with additional research, these mathematical models could be used to compute breast density objectively, automatically bypassing the HSM step, and could greatly facilitate breast cancer research studies.     

Survey on changes in subjective symptoms,onset/trigger factors,allergic diseases,and chemical exposures in the past decade of Japanese patients with multiple chemical sensitivity

Background

Recently, with rapid changes in the Japanese lifestyle, the clinical condition of patients with multiple chemical sensitivity (MCS) may also have undergone change. Thus, we conducted a new survey for subjective symptoms, ongoing chemical exposures, the prevalence of allergic diseases, and presumed onset/trigger factors in patients with MCS and compared results with those of an old survey from ten years ago.

Uptake and intracellular activity of NM394, a new quinolone, in human polymorphonuclear leukocytes.

The uptake of NM394, a new quinolone, by and its subsequent elution from human polymorphonuclear leukocytes were studied and compared with those of ofloxacin and ciprofloxacin. The kinetics of the uptake of NM394 was similar to that of ciprofloxacin. The maximum intracellular-to-extracellular concentration ratio was 12.3, compared with 8.6 for ciprofloxacin and 4.9 for ofloxacin at the extracellular concentration of 20 micrograms/ml. The elution of NM394 from human polymorphonuclear leukocytes occurs relatively slowly; 5 min after the removal of extracellular NM394, nearly 100% still remained in polymorphonuclear leukocytes, compared with ofloxacin, which was so rapidly eluted that only 12% remained. The uptake of NM394 was significantly decreased at 4 degrees C and by the presence of NaCN but was not affected by the presence of L-glycine, L-leucine, L-serine, adenosine, or NaF. NM394 showed intracellular activity at a concentration of 0.1 microgram/ml that significantly reduced the number of phagocytosed Pseudomonas aeruginosa cells with 2 h of incubation. These results suggest that uptake of NM394 by human polymorphonuclear leukocytes occurs via an active transport system differing from that of ofloxacin, whose uptake is affected by the presence of L-glycine and L-leucine, and that once accumulated, NM394 remains intracellularly active and participates in protection against bacterial infection.     

MELAS phenotype associated with m.3302A>G mutation in mitochondrial tRNA gene

The m.3302A>G mutation in the mitochondrial tRNA^Leu(UUR) gene has been identified in only 12 patients from 6 families, all manifesting adult-onset slowly progressive myopathy with minor central nervous system involvement. An 11-year-old boy presented with progressive proximal-dominant muscle weakness from age 7 years. At age 10, he developed recurrent stroke-like episodes. Mitochondrial myopathy, encephalopathy, lactic acidosis, plus stroke-like episodes (MELAS) was diagnosed by clinical symptoms and muscle biopsy findings. Mitochondrial gene analysis revealed a heteroplasmic m.3302A>G mutation. Histological examination showed strongly SDH reactive blood vessels (SSVs), not present in previous cases with myopathies due to the m.3302A>G mutation. These findings broaden the phenotypic spectrum of this mutation.