Estrogen receptor alpha and imprinting of the neonatal mouse ventral prostate by estrogen

Exposure to estrogen in the neonatal period affects prostatic growth and leads to an increased incidence of prostatic intraepithelial neoplasia in later life. The effects of neonatal estrogen are clearly dependent on estrogen receptor (ER) alpha because they do not occur in ERalpha-knockout mice. Because ERalpha is expressed in the stroma, but not in the epithelium, of the adult ventral prostate, the concept of indirect estrogen effects through stromal signaling has been proposed. Here, we show that during the first 4 weeks of life, there are profound and rapid changes in the ER profile in the mouse ventral prostate. ERalpha is abundant in the stroma during week 1, but by week 2 it is exclusively epithelial, and then by week 4, ERalpha is lost and ERbeta is dominant in the prostatic epithelium. The presence of ERalpha is associated with a high proliferation index, and ERbeta is associated with quiescence. Branching morphogenesis was altered in ERalpha-/-, but not in ERbeta-/-, mice. We conclude that imprinting and branching morphogenesis of the ventral prostate are mediated by estrogen acting directly on epithelial and stromal ERalpha during the first 2 weeks of life.     

Technical and biologic sources of variability in the mapping of aortic, mitral and tricuspid color flow jets

The quantification of valvular regurgitation by 2-dimensional Doppler imaging depends on identifying and minimizing variability. Aortic, mitral and tricuspid regurgitant jet areas were measured in 50 patients with sinus rhythm or atrial fibrillation to analyze the variables of reading error, valve site, jet size, rhythm and frame rate. One technician recorded jet velocities at 1 frame/cycle at a triggered interval after the electrocardiographic R wave and at frame rates of 7.5 and 15 frames/s. Jet areas from 5 consecutive beats were measured by planimetry by 1 observer. Coefficients of variation between and among groups were compared by analysis of variance; mean values were 14 to 22%. Jets grouped less than 2.5, 2.5 to 5 and greater than 5 cm2 showed the variance of small jets exceeding that of medium and large jets. Aortic regurgitant jets were largest and had smaller variance than mitral tricuspid jets. Variability due to atrial fibrillation and the slower frame rate was marginal. Intraobserver error was 4.3% and interobserver 15.4%. Thus, reproducing jet areas carries a minimum variability of 15% or higher, depending on jet size. Valve site could not be excluded as a separate variable. Comparative quantification is best limited to 1 observer.     

Wound,pressure ulcer and burn guidelines – 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.     

A study of arteriosclerosis in healthy subjects with HBV and HCV infection

Background It is unclear whether infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) affects arteriosclerosis. We performed a cross-sectional study to clarify the effect of HBV and HCV infection on arteriosclerosis. Methods The study subjects were 1806 healthy individuals who visited Shimane Environment and Health Public Corporation for routine medical check-ups. Serum levels of total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, and blood glucose were investigated in all subjects. The degree of arteriosclerosis was assessed using systolic blood pressure, the bilateral ankle brachial index (ABI), the heart-carotid pulse wave velocity (HCPWV), and the heart-ankle PWV (HAPWV). These cardiovascular parameters were compared between control subjects and subjects with HBV and HCV infection, using analysis of covariance to adjust for confounding factors (sex, age, body mass index, and smoking and drinking). Results Of the 1806 subjects, 39 and 31 were diagnosed as positive for HBV and HCV infection, respectively. The remaining 1736 were considered to be the controls. Adjusted serum lipid levels in the subjects with HBV and those with HCV infection tended to be lower than those in the control subjects. Adjusted arteriosclerotic parameters in the subjects with HBV and HCV infection were similar to those in the control subjects, even after adjusting for serum lipid levels. Conclusions Infection with HBV or HCV does not influence the severity of arteriosclerosis in healthy subjects.     

Leflunomide-related lung injury in patients with rheumatoid arthritis: imaging features

Imaging findings of 26 cases of leflunomide (Arava)-related acute lung injury were analyzed. Thirteen cases had pre-existing interstitial pulmonary disease on chest X-ray or computed tomography. The main features of clinically determined leflunomide-induced acute lung injury were similar to those caused by other drugs: diffuse or widespread patchy ground-glass opacities and/or consolidation, frequently accompanied by septal thickening and intralobular reticular opacities. We categorized these findings into four patterns: diffuse alveolar damage (DAD), acute eosinophilic pneumonia, hyperreaction, and cryptogenic organizing pneumonia. The DAD group had a higher mortality rate, but statistically not a significant one. It is impossible to exclude infectious disease such as pneumocystis carinii pneumonia based on imaging findings, and detailed correlation of imaging findings with clinical and laboratory findings is essential in order to make a correct diagnosis.     

A Comprehensive Functional Analysis of NTRK1 Missense Mutations Causing Hereditary Sensory and Autonomic Neuropathy Type IV (HSAN IV)

Hereditary sensory and autonomic neuropathy type IV (HSAN IV) is an autosomal recessive disorder characterized by a complete lack of pain perception and anhidrosis. Here, we studied a cohort of seven patients with HSAN IV and describe a comprehensive functional analysis of seven novel NTRK1 missense mutations, c.1550G >A, c.1565G >A, c.1970T >C, c.2096T >C, c.2254T >A, c.2288G >C, and c.2311C >T, corresponding to p.G517E, p.G522E, p.L657P, p.I699T, p.C752S, p.C763S, and p.R771C, all of which were predicted pathogenic by in silico analysis. The results allowed us to assess the pathogenicity of each mutation and to gain novel insights into tropomyosin receptor kinase A (TRKA) downstream signaling. Each mutation was systematically analyzed for TRKA glycosylation states, intracellular and cell membrane expression patterns, nerve growth factor stimulated TRKA autophosphorylation, TRKA‐Y496 phosphorylation, PLCγ activity, and neurite outgrowth. We showed a diverse range of functional effects: one mutation appeared fully functional, another had partial activity in all assays, one mutation affected only the PLCγ pathway and four mutations were proved null in all assays. Thus, we conclude that complete abolition of TRKA kinase activity is not the only pathogenic mechanism underlying HSAN IV. By corollary, the assessment of the clinical pathogenicity of HSAN IV mutations is more complex than initially predicted and requires a multifaceted approach.