A novel RUNX1 mutation in familial platelet disorder with propensity to develop myeloid malignancies

We describe a Japanese family with familial platelet disorder with propensity to develop myeloid malignancies (FPD/MM). Among the three affected individuals, two members developed myeloid malignancies. Sequence studies demonstrate that all affected individuals of the pedigree display a heterozygous single nucleotide deletion in exon 8 of the RUNX1 gene.     

Dosage of inactivated influenza vaccine for infants

BACKGROUND: In Japan, the inoculation dosage of inactivated influenza vaccine for children under 1 year old is 0.1 mL per dose. The dosage is not half as much as that in Europe and the U.S.A. We considered that low efficacy fate of influenza vaccine in children under 1 year old results from its less dosage. So we designed this study to verify this hypothesis. MATERIALS AND METHODS: This study was prospective in design. Subjects were divided into two groups by age: 8 to 11 months old (n = 26) and 12 to 16 months old (n = 22). Infants received 0.1 mL of inactivated influenza vaccine and over 1 year, 0.2 mL. Forty-eight children were inoculated twice at intervals of over 4 weeks. Serum samples were drawn before the first inoculation and 1 month after the second vaccination. Pre- and post-immunization antibody titers were measured. The titers of hemaglutinatinin inhibiting antibodies to the 3 viral strains were assayed. Antibody titers were determined using HAI. RESULTS: The post-vaccination proportions of children with protective HAI antibody titers were significantly smaller in infants than those in children over 1 year old (A/H1N1; 23% vs. 77%, A/H3N2; 39% vs. 73%, B; 0% vs. 32%). The number of children with >four-fold increased antibodies were significantly smaller in infants than that in 1 year old (A/H1N1; 74% vs. 91%, B; 0% vs. 39%). In the mean antibody titer, there were signficant differences between infants and children over 1 year old (A/H1N1; 19 times vs. 56 times, B; 8 times vs. 14 times). CONCLUSION: We consider that significant differences in antibody titers between infants and children over 1 year old were caused by the difference of dosage in influenza vaccines. To obtain protective levels of antibodies by influenza vaccines in infants, they must be inoculated with enough dosage.     

Association of human T-cell leukemia virus type 1 with prevalent rheumatoid arthritis among atomic bomb survivors: A cross-sectional study

Previous studies have suggested that human T-cell leukemia virus type 1 (HTLV-1) might act as a pathogen in rheumatoid arthritis (RA), but epidemiological evidence of an association is scarce. We measured anti-HTLV-1 antibodies among Nagasaki atomic bomb survivors to determine whether HTLV-1 is related to RA and whether radiation exposure is associated with HTLV-1 and RA prevalence.This is a cross-sectional study among atomic bomb survivors who participated in biennial health examinations from 2006 to 2010. Serum levels of anti-HTLV-1 antibodies were measured using a chemiluminescent enzyme immunoassay and confirmed by Western blotting. Association between HTLV-1 and RA was analyzed by a logistic regression model.Of 2091 participants (women 61.5%; median age, 73 years), 215 (10.3%) had anti-HTLV-1 antibodies. HTLV-1 prevalence was higher among women (13.1% vs 5.8%; P < .001). Twenty-two participants (1.1%) were diagnosed with RA. HTLV-1 prevalence among RA participants was significantly higher than that among non-RA participants (27.3% vs 10.1%; P = .020). After adjustment for age, sex, and hepatitis C virus infection, HTLV-1 was significantly associated with prevalent RA (odds ratio, 2.89; 95% confidence interval, 1.06, 7.03). There was no association between radiation dose and either the prevalence of HTLV-1 or RA.This study, among a well-defined group of atomic bomb survivors, suggests that HTLV-1 is associated with RA.     

Deciphering Subtype-Selective Modulations in TRPA1 Biosensor Channels

The transient receptor potential (TRP) proteins are a family of ion channels that act as cellular sensors. Several members of the TRP family are sensitive to oxidative stress mediators. Among them, TRPA1 is remarkably susceptible to various oxidants, and is known to mediate neuropathic pain and respiratory, vascular and gastrointestinal functions, making TRPA1 an attractive therapeutic target. Recent studies have revealed a number of modulators (both activators and inhibitors) that act on TRPA1. Endogenous mediators of oxidative stress and exogenous electrophiles activate TRPA1 through oxidative modification of cysteine residues. Non-electrophilic compounds also activate TRPA1. Certain non-electrophilic modulators may act on critical non-cysteine sites in TRPA1. However, a method to achieve selective modulation of TRPA1 by small molecules has not yet been established. More recently, we found that a novel N-nitrosamine compound activates TRPA1 by S-nitrosylation (the addition of a nitric oxide (NO) group to cysteine thiol), and does so with significant selectivity over other NO-sensitive TRP channels. It is proposed that this subtype selectivity is conferred through synergistic effects of electrophilic cysteine transnitrosylation and molecular recognition of the non-electrophilic moiety on the N-nitrosamine. In this review, we describe the molecular pharmacology of these TRPA1 modulators and discuss their modulatory mechanisms.     

Pediatric myositis ossificans mimicking osteosarcoma

Myositis ossificans (MO) is a rare benign cause of heterotopic bone formation in soft tissue that most commonly affects young adults, typically following trauma. We report the case of an 11‐year‐old girl who developed MO mimicking osteosarcoma in her right shoulder. Plain radiography and computed tomography showed poorly defined flocculated densities in the soft tissue and a periosteal reaction along the proximal humerus. On magnetic resonance imaging, the mass displayed an ill‐defined margin and inhomogeneous signal change. Histologically, the mass had a pseudosarcomatous appearance. Based on these findings, the patient was initially misdiagnosed with osteosarcoma at another hospital. The diagnosis was difficult because the patient was 11 years old and had no trauma history, with atypical radiographic changes and a predilection for the site of origin for osteosarcomas. We finally made the correct diagnosis of MO by carefully reviewing and reflecting on the pathological differences between stages.     

Knockdown of macrophage migration inhibitory factor disrupts adipogenesis in 3T3-L1 cells

Obesity is a condition in which adipose tissue mass is expanded. Increases in both adipocyte size and number contribute to enlargement of adipose tissue. The increase in cell number is thought to be caused by proliferation and differentiation of preadipocytes. Macrophage migration inhibitory factor (MIF) is expressed in adipocytes, and intracellular MIF content is increased during adipogenesis. Therefore, we hypothesized that MIF is associated with adipocyte biology during adipogenesis and focused on the influence of MIF on adipogenesis. To examine the effects of MIF on adipocytes, MIF expression in 3T3-L1 preadipocytes was inhibited by RNA interference, and cell differentiation was induced by standard procedures. The triglyceride content of MIF small interfering RNA (siRNA)-transfected 3T3-L1 cells was smaller than that of nonspecific siRNA-transfected cells. In addition, MIF knockdown apparently abrogated increases in adiponectin mRNA levels during differentiation. Gene expression of peroxisome proliferator-activated receptor (PPAR)gamma, CCAAT/enhancer binding protein (C/EBP)alpha, and C/EBPdelta decreased with MIF siRNA transfection, but C/EBPbeta expression increased. Cell number and incorporation of 5-bromo-2-deoxyuridine into cells decreased from 1-3 d and from 14-20 h, respectively, after induction of differentiation in MIF siRNA-transfected cells, thus suggesting that MIF siRNA inhibits mitotic clonal expansion. Taken together, these results indicated that MIF regulates differentiation of 3T3-L1 preadipocytes, at least partially, through inhibition of mitotic clonal expansion and/or C/EBPdelta expression.     

Hypoxic ventilatory depression in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes

We describe a case of a 21-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who presented with hypoxic ventilatory depression. He had chronic hypoventilation, which was not explained by weakness of respiratory muscles. His hypercapnic ventilatory response was not impaired. In contrast, hypoxic ventilatory depression was observed in the isocapnic progressive hypoxic response test. After exposure to hypoxic conditions, his respiratory frequency decreased and tidal volume was unchanged. The hypoxic ventilatory depression was partially blocked by pretreatment with aminophylline. In conclusion, we need to be careful with patients with MELAS who are hypoxaemic because a vicious circle of hypoxia and hypoventilation can occur.     

Effect of post-transplant double filtration plasmapheresis on recurrent focal and segmental glomerulosclerosis in renal transplant recipients

In the present study, we reviewed the effect of post-transplant double filtration plasmapheresis (DFPP) on recurrent focal segmental glomerulosclerosis (FSGS) in the transplanted kidney allograft. Sixteen patients with post-transplant recurrent FSGS were enrolled in this study. Out of 16 patients with recurrent FSGS after transplantation, five did not receive DFPP and lost their grafts, while 11 did receive DFPP and four of these patients lost their grafts. Seven patients were able to maintain normal renal function for an average observation period of 57.1 +/- 40.7 months (range 7-125 months). In five patients who had a significant reduction in urinary protein after DFPP, the urinary protein level decreased from 26.60 +/- 23.05 g/day (range 3.34-62.6 g/day) to 2.95 +/- 3.42 g/day (range 0.02-8.64 g/day) and renal function was maintained. The beneficial effects of DFPP on graft outcome were more likely to occur if the patients experienced a marked drop in urinary excretion. Thus, post-transplant DFPP appears to be effective for reducing urinary protein levels and improving long-term graft survival. With the small numbers in this trial, however, none of the findings were statistically significant. We recommend the use of post-transplant DFPP to prevent the progression of recurrent FSGS.