Does dye laser treatment with higher fluences in combination with cold air cooling improve the results of port‐wine stains?

BACKGROUND AND OBJECTIVE: The use of cold air cooling (CAC) and cryogen spray cooling during dye laser treatment of port-wine stains (PWS) has become a standard in recent years. Still unsolved is the question of which fluences are necessary in combination with CAC in order to achieve an optimum clearance and the lowest possible rate of side-effects. STUDY DESIGN: In a prospective study, we treated 11 patients with PWS with pulsed dye laser (Photogenica V, Cynosure, lambda = 585 nm, iota(p) = 0.5 ms, spot size = 7 mm). Each PWS was partitioned into three areas: (area 1) 6 J/cm(2) without CAC, (area 2) 6 J/cm(2) with CAC (level 4), (area 3) 9 J/cm(2) with CAC (level 4). RESULTS: Area 3 (mean, 59%) showed a slightly better clearance than area 1 (mean, 57%); in area 2, we observed a reduced clearance (mean, 45%). Compared with area 1, we achieved a reduction of pain through CAC in areas 2 and 3. The healing periods as well as the rate of side-effects were comparable in all areas. CONCLUSION: We observed a slight but not statistically relevant increase in clearance with the use of higher fluences and CAC compared with lower fluences without CAC. Because pain is lowered significantly when using CAC, and because this makes the treatment more comfortable for the patients, we tend to recommend the use of higher fluences (9 J/cm(2)) with simultaneous CAC for treating PWS.     

Availability of complement bound to Staphylococcus aureus to interact with membrane complement receptors influences efficiency of phagocytosis

Complement-mediated opsonization of encapsulated Staphylococcus aureus (CP+) of the predominant capsule types, 5 and 8, remains poorly understood. Our previous work showed that complement is important for mouse survival of CP+ type 5 bacteremia and that the type 5 capsule inhibits the binding of opsonic C3 fragments to the organism. The importance of complement-mediated opsonization of CP+ was tested by neutrophil phagocytosis assays. Complement-mediated opsonization of CP+ increased phagocytosis by 57% compared to opsonization in complement-inhibited serum. Agar-grown CP+, enhancing capsule expression, was phagocytosed only one-tenth as well as the capsule-negative organisms (CP-), supporting the belief that staphylococcal polysaccharide capsules impair phagocytosis. Despite relatively poor phagocytosis of CP+ compared to CP-, complement activation increased the phagocytosis of CP+ by 103%. Thus, complement in normal human serum may have an important role in opsonizing CP+, even when capsule expression is strong. The ability of bound C3 fragments to interact with complement receptor 1 (CD35) on the membrane of human erythrocytes was tested in an immune adherence assay. S. aureus capsule was able to mask C3 fragments on the organism from binding to complement receptor 1. The inhibition of C3 binding to CP+ and the masking of deposited C3 fragments caused by the presence of capsule was associated with markedly decreased phagocytosis. The addition of anti-capsule antibodies to normal human serum was found to markedly improve the recognition of deposited C3 fragments by complement receptor 1 even when the absolute number of C3 molecules bound to S. aureus was not increased.     

用于选择视觉的数据和智能控制神经网络系统(英文)

在这篇论文中,我们提出了用于选择视觉的数据和智能控制的动态网络系统的神经实现过程。模型由数个相互作用的子系统构成,用于不同的处理。所有的神经子系统与信息和控制流程的倒序和顺序紧密相关。     

Chlamydia pneumoniae inhibits apoptosis in human epithelial and monocyte cell lines

Chlamydia pneumoniae is an obligate intracellular pathogen with a tendency to cause persistent infections that has been associated with many chronic conditions such as asthma and coronary artery disease. However, its immunopathogenic mechanisms are poorly understood. When aiming to study the impact of C. pneumoniae infection on host cell apoptosis, we found that epithelial infected (HL) cells and macrophages (U937-line) were resistant to staurosporine and tumour necrosis factor (TNF)-alpha-induced physiological apoptosis 48, 72 or 120 h post-infection, as determined by flow cytometry, DNA fragmentation assay and fluorescence microscopy. The antiapoptotic influence was observed even at a late stage of the chlamydial life cycle and was dependent on the chlamydial protein synthesis. The mechanisms involved blockage of mitochondrial cytochrome c release and caspase 3 activation. We also found that during a persistent C. pneumoniae infection induced in vitro by penicillin treatment of cell cultures, the inhibition of apoptosis was extended for up to 120 h of follow-up post-infection and was restricted to the cells carrying chlamydial inclusions. Our findings suggest that inhibition of apoptosis may be one of the pathogenetic mechanisms by which C. pneumoniae infection can mediate the development of chronic diseases.     

Rare SP-A alleles and the SP-A1-6A(4) allele associate with risk for lung carcinoma

Next to cigarette smoking, genetic factors may contribute to lung cancer risk. Pulmonary surfactant components may mediate response to inhaled carcinogenic substances and/or play a role in lung function and inflammation. We studied associations between surfactant protein (SP) genetic variants and risk in lung cancer subgroups. Samples (n=308) were genotyped for SP-A1, -A2, -B, and -D marker alleles. These included 99 patients with small cell lung carcinoma (SCLC, n=31), or non-SCLC (NSCLC, n=68) consisting of squamous cell carcinoma (SCC, n=35), and adenocarcinoma (AC) (n=23); controls (n=99) matched by age, sex, and smoking status (clinical control) to SCLC and NSCLC; and 110 healthy individuals (population control). We found (a) no significant marker associations with SCLC, (b) rare SP-A2 (1A9) and SP-A1 (6A11) alleles associate with NSCLC risk when compared with population control, (c) the same alleles (1A9, 6A11) associate with risk for AC when compared with population (6A11) or clinical control (1A9), and (d) the SP-A1-6A4 allele (found in approximately 10% of the population) associates with SCC, when compared with population or clinical control. A correlation between SP-A variants and lung cancer susceptibility appears to exist, indicating that SP-A alleles may be useful markers of lung cancer risk.     

Respiratory exposure to diesel exhaust particles decreases the spleen IgM response to a T cell-dependent antigen in female B6C3F1 mice.

We investigated the systemic immunotoxic potential of respiratory exposure to diesel exhaust particles (DEP) in this study. Female B6C3F1 mice (approximately 8 weeks old) were exposed to increasing concentrations of DEP intratracheally, 3 times every two weeks, and sacrificed 2 or 4 weeks after the first exposure. The systemic toxicity and immune status in mice were evaluated. Mice exposed to DEP (1 to 15 mg/kg) showed no significant changes in body, spleen, or liver weights. Lung weights were increased in the mice exposed to 15 mg/kg DEP for 2 or 4 weeks. Except for a decreased platelet count, no significant alterations occurred in hematological parameters following DEP exposure. The number of splenic anti-sheep red blood cell (sRBC) IgM antibody-forming cells (AFC) decreased following DEP exposure for 2 weeks. This effect was less severe following 4 weeks of exposure and was only evident in the high dose group. Exposure to DEP also resulted in a significant decrease in the absolute numbers and the percentages of total spleen cells for total, CD4(+), and CD8(+) T cells, while the numbers of B cells and total nucleated cells in spleen were not significantly changed. The proliferative response of splenocytes to the T-cell mitogen, concanavalin A (ConA), as well as their production of IL-2 and IFN-gamma, was decreased dose-dependently following exposure of mice to DEP for 2 weeks, whereas proliferation was not changed in response to anti-CD3 monoclonal antibody. In summary, short-term respiratory exposure of mice to DEP resulted in systemic immunosuppression with evidence of T cell-mediated and possibly macrophage-mediated mechanisms.     

Glial cell-induced endothelial morphogenesis is inhibited by interfering with extracellular signal-regulated kinase signaling.

PURPOSE: Tumor vasculature provides the infrastructure by which malignant tissue can be nourished; therefore, targeting angiogenesis may be an effective means of treating cancer. We showed previously that SNB19 glioblastoma cells modulate bovine retinal endothelial cells in cocultures to form capillary-like network structures, that matrix metalloproteinase-9 (MMP-9) expression is critical for endothelial morphogenesis, and that MMP-9 expression in glioblastoma cells is regulated by extracellular signal-regulated kinase-1 (ERK-1). In the present study, we investigated whether interfering with the activation of this mitogen-activated protein (MAP) kinase would repress MMP-9 synthesis and inhibit capillary formation. EXPERIMENTAL DESIGN: Cocultures of bovine retinal endothelial and SNB19 cells were analyzed for MMP-9 secretion, and phospho- and total ERK levels. These cocultures were treated with PD98059, a specific inhibitor of MAP/ERK kinase 1, or transfected with dominant-negative ERK-1 mutant containing expression vector. Alterations in capillary-like structure formation, and actin cytoskeleton and secretion of vascular endothelial growth factor (VEGF), MMP-9, and tissue inhibitor of metalloproteinase-1 were determined by immunofluorescence, gelatin zymography, and Western blotting. RESULTS: We found that inhibition of the ERK-1/2 pathway with PD98059 abrogated glial cell-mediated capillary formation by the endothelial cells and reduced the levels of MMP-9 in the coculture. Strikingly, the abrogation of MAP kinase signaling by a dominant-negative ERK-1 mutant inhibited glial-induced capillary network formation by reducing VEGF levels and MMP-9 activity and increasing the levels of tissue inhibitor of metalloproteinase-1. Inhibition of ERK activity also disrupted the formation of the actin cytoskeleton, a prerequisite for endothelial cell migration. CONCLUSION: The mechanism underlying activation of ERK is involved in reorganization of the actin cytoskeleton, and induction of VEGF and MMP-9, thereby stimulating endothelial cell morphogenesis. These studies clearly provide experimental evidence that ERK inhibition diminishes glial-induced endothelial-cell morphogenesis; therefore, interfering with ERK signaling may be a viable approach to target angiogenesis.     

Retention and HIV seroconversion among drug users on methadone maintenance treatment in Yunnan,China

Setting: Thirteen methadone maintenance treatment (MMT) clinics across Yunnan, the province with the highest human immunodeficiency virus (HIV) burden in China.Objectives: To determine, among HIV-negative participants on MMT, the proportion lost to follow-up (defined as those who missed the 6-monthly follow-up examination), factors associated with loss to follow-up (LFU), HIV seroconversion rate and factors associated with seroconversion.Design: Prospective cohort study from October 2008 to April 2011. All participants were administered a pre-tested structured questionnaire to capture associated factors and offered HIV testing every 6 months. χ² test and log-binomial regression were used for data analysis.Results: Of 1146 participants, 541 (47%) were lost to follow-up in 2.5 years. Factors associated with higher LFU proportion include <6 months of previous MMT, inconvenient location of the MMT clinic and average methadone dose ⩽60 mg/day, with adjusted relative risks (RRs) of respectively 1.4 (95%CI 1.2–1.5), 1.2 (95%CI 1.0–1.4) and 1.1 (95%CI 1.0–1.3). The overall HIV seroconversion rate was 6.6 (95%CI 3.7–11.0) per 1000 person-years. Not living with a partner contributed to higher HIV rates, with an adjusted RR of 3.6 (95%CI 1.0–12.8).Conclusion: The retention rate of MMT participants in Yunnan was not satisfactory. Decentralising service delivery in the community and making directly observed treatment more convenient has the potential to improve retention.