Repeated Necrotizing Lymphadenitis with MEFV Gene Mutations

We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient''s chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis.     

Continuing Medical Education Activity in Echocardiography

Article Title: Speckle Tracking Global Strain Rate E/E’ Predicts LV Filling Pressure More Accurately Than Traditional Tissue Doppler E/E’ (Echocardiography, 2012;29:403)     

Occupational Factors and Problem Drinking among a Japanese Working Population

Problem drinking is a serious public health problem in the workplace. However, fewJapanese epidemiological studies have investigated the occupational characteristics ofproblem drinking. The purpose of this study is to clarify the occupational risk factorsfor problem drinking among a Japanese working population. We used data from arandom-sampling survey about mental health and suicide, conducted among Hamamatsu Cityresidents aged 15 to 79 yr old during May and June in 2008. The relation betweenoccupational factors and problem drinking was analyzed with multiple logistic regressionmodels stratified by gender. CAGE questionnaire was used to assess problem drinking. Withregard to employment types, problem drinkers were more prevalent among self-employedwomen. With regard to occupational types, clerical and service professions had moreproblem drinkers of either sex, while administrative/managerial and sales professions hadmore women with such problem. With regard to company size, male problem drinkers were moreprevalent in smaller companies than in larger ones. These results indicate that theprevalence of problem drinkers in the workplace depends on where one works. It isnecessary to consider these characteristics to provide effective measures to addressproblem drinking in the workplace.     

Determinants of Bronchodilator Responsiveness in Patients with Controlled Asthma

Short-term bronchodilator responsiveness to an inhaled β 2 adrenergic agonist was assessed by changes in forced expiratory volume in 1 second (FEV₁) in nonsmoking adults with controlled asthma (mild disease, 20 patients; moderate disease, 20 patients; severe disease, 18 patients). Responsiveness correlated significantly with age and with percent of predicted FEV₁ (%FEV₁) except in patients with severe asthma, who showed significantly less responsiveness than others. Thus, responsiveness is closely associated with degree of airflow limitation in patients with controlled asthma and is significantly influenced by severity of disease and by aging.     

Accurate diagnosis and treatment of Vibrio vulnificus infection: a retrospective study of 12 cases

Background and aimsVibrio vulnificus causes an infectious disease that has extremely poor convalescence and leads to necrotic fasciitis. In this study, we sought to define the characteristic epidemiology of V. vulnificus infection and clarify its diagnosis at the global level.MethodsOver a period of 10 years, we investigated the appearance of symptoms, underlying conditions, treatment, and mortality in 12 patients (eight men, four women; >50 years old; average age, 66 years,) infected with V. vulnificus.ResultsThe development of symptoms occurred primarily between June and September, a period during which seawater temperature rises and the prevalence of V. vulnificus increases. All patients had underlying diseases, and seven patients reported a history of consuming fresh fish and uncooked shellfish. The patients developed sepsis and fever with sharp pain in the limbs. Limb abnormalities were observed on visual examination. All patients underwent debridement; however, in the survival group, the involved limb was amputated early in 80% patients. The mortality rate was 58.3%.ConclusionRecognition of the characteristic epidemiology and clinical features of this disease is important, and positive debridement should be performed on suspicion. When the illness reaches an advanced stage, however, amputation should be the immediate treatment of choice.     

Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients

Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of systemic autoinflammatory disorders in which the majority of patients have mutations in the cold-induced autoinflammatory syndrome (CIAS)1 gene. Despite having indistinguishable clinical features, some patients lack CIAS1 mutations by conventional nucleotide sequencing. We recently reported a CAPS patient with mosaicism of mutant CIAS1, and raised the possibility that CIAS1 mutations were overlooked in "mutation-negative" patients, due to a low frequency of mosaicism. To determine whether there were latent mutant cells in "mutation-negative" patients, we sought to identify mutation-associated biologic phenotypes of patients' monocytes. We found that lipopolysaccharide selectively induced necrosis-like cell death in monocytes bearing CIAS1 mutations. Monocyte death correlated with CIAS1 up-regulation, was dependent on cathepsin B, and was independent of caspase-1. Cell death was intrinsic to CIAS1-mutated monocytes, was not mediated by the inflammatory milieu, and was independent of disease severity or anti-IL-1 therapy. By collecting dying monocytes after lipopolysaccharide treatment, we succeeded in enriching CIAS1-mutant monocytes and identifying low-level CIAS1-mosaicism in 3 of 4 "mutation-negative" CAPS patients. Our findings reveal a novel effect of CIAS1 mutations in promoting necrosis-like cell death, and demonstrate that CIAS1 mosaicism plays an important role in mutation-negative CAPS patients.     

Trib1 and Evi1 cooperate with Hoxa and Meis1 in myeloid leukemogenesis

Cooperative activation of Meis1 and Hoxa9 perturbs myeloid differentiation and eventually leads myeloid progenitors to leukemia, yet it remains to be clarified what kinds of subsequent molecular processes are required for development of overt leukemia. To understand the molecular pathway in Hoxa9/Meis1-induced leukemogenesis, retroviral insertional mutagenesis was applied using retrovirus-mediated gene transfer. The mice that received Hoxa9/Meis1-transduced bone marrow cells developed acute myeloid leukemia (AML), and Trib1, Evi1, Ahi1, Raralpha, Pitpnb, and AK039950 were identified as candidate cooperative genes located near common retroviral integration sites. Trib1 and Evi1 were up-regulated due to retroviral insertions, and coexpression of these genes significantly accelerated the onset of Hoxa9/Meis1-induced AML, suggesting that Trib1 and Evi1 are the key collaborators. Furthermore, Trib1 by itself is a novel myeloid oncogene, enhancing phosphorylation of ERK, resulting in inhibition of apoptosis. These results demonstrate the importance of specific oncogene interaction in myeloid leukemogenesis.     

Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure

Deficiency of ADAMTS13 is found in patients with thrombotic thrombocytopenic purpura (TTP), and the genetic defects in the ADAMTS13 gene or the autoantibody against ADAMTS13 is thought to be responsible for the development of TTP. The clinical correlation and mechanisms of secondary ADAMTS13 deficiency in other disease states were investigated. In addition to TTP, ADAMTS13 levels were severely decreased in patients with sepsis-induced disseminated intravascular coagulation (DIC). The incidence of acute renal failure and serum creatinine levels in patients with ADAMTS13 activity levels lower than 20% (incidence, 41.2%; creatinine, 160 +/- 150 microM [1.81 +/- 1.70 mg/dL]) (P < .05) were significantly higher than they were in patients with ADAMTS13 activity levels higher than 20% (incidence, 15.4%; creatinine, 84 +/- 67 microM [0.95 +/- 0.76 mg/dL]) (P < .01). Additionally, unusually large von Willebrand factor multimers were detected in 26 (51.0%) of 51 patients with ADAMTS13 activity levels lower than 20%. Lower molecular weight forms of ADAMTS13 were found in the plasma of patients with sepsis-induced DIC, suggesting that the deficiency of ADAMTS13 was partially caused by its cleavage by proteases in addition to decreased synthesis in the liver. These data suggested that severe secondary ADAMTS13 deficiency can be associated with sepsis-induced DIC and may contribute to the development of renal failure.     

Rapid electrical stimulation of contraction modulates gap junction protein in neonatal rat cultured cardiomyocytes: involvement of mitogen-activated protein kinases and effects of angiotensin II-receptor antagonist

OBJECTIVES: The aim of this study was to investigate the effects of rapid electrical stimulation (RES) of contraction on the expression of connexin (Cx)43 gap junction in neonatal rat cultured ventricular myocytes and the consequent changes of conduction properties. BACKGROUND: The expression and distribution of gap junctions in cardiac muscle can be changed readily under a variety of pathological conditions because of dynamic turnover of Cxs. The effects of RES of contraction on gap junction remodeling are not well understood. METHODS: Neonatal rat ventricular myocytes cultured for five days were subjected to RES (field stimulation) at 3.0 Hz for up to 120 min. RESULTS: Rapid electrical stimulation resulted in a significant upregulation of Cx43 (by approximately 1.5-fold in protein and by approximately 1.9-fold in messenger ribonucleic acid at 60 min). Immunoreactive signal of Cx43 was also increased. Angiotensin II (AngII) content was increased significantly by RES >15 min. Phosphorylated forms of extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinases, and p38 mitogen-activated protein kinases (MAPKs) were all increased dramatically by RES with peaks at 5 - 60 min. Propagation of excitation was visualized by extracellular potential mapping by using a multiple electrode array system. Conduction velocity was increased significantly by RES for 60 to 90 min (25% - 27% increase). Treatment of myocytes with losartan (100 nmol/l) prevented most of these effects of RES; RES-induced upregulation of Cx43 was also prevented by specific inhibitors for ERK and p38 MAPKs. CONCLUSIONS: A short-term RES causes upregulation of Cx43 in cardiomyocytes and a concomitant increase of conduction velocity, mainly through an autocrine action of AngII to activate ERK and p38 MAPKs.     

Three adult cases with Corynebacterium propinquum respiratory infections in a community hospital

Corynebacterium propinquum, which is included in Corynebacterium group ANF-3, exists as a commensal in the oral flora. This organism has not yet been fully recognized as a respiratory pathogen. We previously reported that the first case with respiratory infection caused by C. propinquum. On the other hand, Corynebacterium pseudodiphtheriticum is recognized as a causative organism in respiratory infections. Recently we experienced two cases with C. propinquum respiratory infections in our hospital. Three types of the onset such as a community-acquired infection, a hospital-acquired infection, and a nursing home acquired infections were observed. Our analysis indicated that gram staining of the purulent sputum is an essential tool to evaluate whether C. propinquum is a respiratory pathogen or not, because this organism is a commensal bacteria.