大地震创伤后应激障碍患者的心理与神经内分泌变化

目的 :研究唐山大地震所致慢性创伤后应激障碍患者基础血清皮质醇浓度和地塞米松抑制试验。方法 :唐山大地震所致创伤后应激障碍 3 5例 (研究组 )和 3 3例正常人 (对照组 )接受了基础血清皮质醇水平的测定和地塞米松抑制试验。结果 :两组基础血清皮质醇水平比较差异无统计学显著性 ,各组男女之间基础血清皮质醇水平分别比较差异亦无统计学显著性。两组服用相同剂量的地塞米松后 ,研究组血清皮质醇水平低于对照组和对血清皮质醇的抑制作用高于对照组 ,差异均有统计学显著性。各组男女之间的基础血清皮质醇水平、服用地塞米松后血清皮质醇水平和对地塞米松的抑制率比较差异无统计学显著性。结论 :唐山大地震所致慢性PTSD患者对糖皮质激素的敏感性增高而导致PHA轴负反馈抑制增强 ,无性别差异     

重组人表皮生长因子防治乳腺癌放射性皮肤反应的临床研究

目的 观察重组人表皮生长因子(rhEGF)局部外用对乳腺癌放疗皮肤反应的防治作用。方法 将30例乳腺癌根治术后放疗的患者,随机分为2组,每组15人,以胸壁出现的放疗反应及用药后的变化作为观察指标。结果 A组:使用rhEGF治疗Ⅱ°湿性皮肤反应的平均愈合时间为5.2±1.1天,使用常规治疗方法(氢地油)平均愈合时间为12.4±2.2天(P<0.01)。B组:胸壁上1/2使用rhEGF的患者仅1例出现Ⅱ°湿性放射性皮肤反应,而下1/2不用药者有6例出现Ⅱ°湿性反应(P<0.05)。结论 使用rhEGF可使乳腺癌放疗中出现的Ⅱ°湿性皮肤反应的愈合时间明显缩短,在乳腺癌术后放疗期间尽早使用rhEGF能有效防止放射性皮肤反应的发生。     

大黄蒽醌含量测定方法的研究

目的：测定大黄中游离蒽醌和总蒽醚的含量。方法：采用甲醇冷浸法，利用蒽醌衍生物在碱性条件下呈红色的特点，用可见分光光度法测定其含量。结果：该法测定平均回收率为100．2％，RSD＝2．96％(n＝5)，线性范围为5μg一30μg，r＝0．9999。结论：用本法检测大黄中的蒽醌含量，方法简便，结果可靠。     

Blood leukocytes recapitulate diabetogenic peptide–MHC-II complexes displayed in the pancreatic islets

Assessing the self-peptides presented by susceptible major histocompatibility complex (MHC) molecules is crucial for evaluating the pathogenesis and therapeutics of tissue-specific autoimmune diseases. However, direct examination of such MHC-bound peptides displayed in the target organ remains largely impractical. Here, we demonstrate that the blood leukocytes from the nonobese diabetic (NOD) mice presented peptide epitopes to autoreactive CD4 T cells. These peptides were bound to the autoimmune class II MHC molecule (MHC-II) I-A^g7 and originated from insulin B-chain and C-peptide. The presentation required a glucose challenge, which stimulated the release of the insulin peptides from the pancreatic islets. The circulating leukocytes, especially the B cells, promptly captured and presented these peptides. Mass spectrometry analysis of the leukocyte MHC-II peptidome revealed a series of β cell–derived peptides, with identical sequences to those previously identified in the islet MHC-II peptidome. Thus, the blood leukocyte peptidome echoes that found in islets and serves to identify immunogenic peptides in an otherwise inaccessible tissue.     

Social networks and alcohol use disorders: findings from a nationally representative sample

Background: While some argue that social network ties of individuals with alcohol use disorders (AUD) are robust, there is evidence to suggest that individuals with AUDs have few social network ties, which are a known risk factor for health and wellness. Objectives: Social network ties to friends, family, co-workers and communities of individuals are compared among individuals with a past-year diagnosis of alcohol dependence or alcohol abuse to individuals with no lifetime diagnosis of AUD. Method: Respondents from Wave 2 of the National Epidemiologic Survey on Alcohol Related Conditions (NESARC) were assessed for the presence of past-year alcohol dependence or past-year alcohol abuse, social network ties, sociodemographics and clinical characteristics. Results: Bivariate analyses showed that both social network size and social network diversity was significantly smaller among individuals with alcohol dependence, compared to individuals with alcohol abuse or no AUD. When social and clinical factors related to AUD status were controlled, multinomial logistic models showed that social network diversity remained a significant predictor of AUD status, while social network size did not differ among AUD groups. Conclusion: Social networks of individuals with AUD may be different than individuals with no AUD, but this claim is dependent on specific AUD diagnosis and how social networks are measured.     

Film dosimetry calibration method for pulsed-dose-rate brachytherapy with an 192Ir source

192Ir sources have been widely used in clinical brachytherapy. An important challenge is to perform dosimetric measurements close to the source despite the steep dose gradient. The common, inexpensive silver halide film is a classic two-dimensional integrator dosimeter and would be an attractive solution for these dose measurements. The main disadvantage of film dosimetry is the film response to the low-energy photon. Since the photon energy spectrum is known to vary with depth, the sensitometric curves are expected to be dependent on depth. The purpose of this study is to suggest a correction method for silver halide film dosimetry that overcomes the response changes at different depths. Sensitometric curves have been obtained at different depths with verification film near a 1 Ci 192Ir pulsed-dose-rate source. The depth dependence of the film response was observed and a correction function was established. The suitability of the method was tested through measurement of the radial dose profile and radial dose function. The results were compared to Monte Carlo-simulated values according to the TG43 formalism. Monte Carlo simulations were performed separately for the beta and gamma source emissions, using the EGS4 code system, including the low-energy photon and electron transport optimization procedures. The beta source emission simulation showed that the beta dose contribution could be neglected and therefore the film-depth dependence could not be attributed to this part of the source radioactivity. The gamma source emission simulations included photon-spectra collection at several depths. The results showed a depth-dependent softening of the photon spectrum that can explain the film-energy dependence.     

The Association Between Park Facilities and Duration of Physical Activity During Active Park Visits

Public parks provide places for urban residents to obtain physical activity (PA), which is associated with numerous health benefits. Adding facilities to existing parks could be a cost-effective approach to increase the duration of PA that occurs during park visits. Using objectively measured PA and comprehensively measured park visit data among an urban community-dwelling sample of adults, we tested the association between the variety of park facilities that directly support PA and the duration of PA during park visits where any PA occurred. Cross-classified multilevel models were used to account for the clustering of park visits (n?=?1553) within individuals (n?=?372) and parks (n?=?233). Each additional different PA facility at a park was independently associated with a 6.8% longer duration of PA bouts that included light-intensity activity, and an 8.7% longer duration of moderate to vigorous PA time. Findings from this study are consistent with the hypothesis that more PA facilities increase the amount of PA that visitors obtain while already active at a park.     

The moderating role of social networks in the relationship between alcohol consumption and treatment utilization for alcohol-related problems

Many individuals wait until alcohol use becomes severe before treatment is sought. However, social networks, or the number of social groups an individual belongs to, may play a moderating role in this relationship. Logistic regression examined the interaction of alcohol consumption and social networks as a predictor of treatment utilization while adjusting for sociodemographic and clinical variables among 1,433 lifetime alcohol-dependent respondents from wave 2 of the National Epidemiologic Survey on Alcohol Related Conditions (NESARC). Results showed that social networks moderate the relationship between alcohol consumption and treatment utilization such that for individuals with few network ties, the relationship between alcohol consumption and treatment utilization was diminished, compared to the relationship between alcohol consumption and treatment utilization for individuals with many network ties. Findings offer insight into how social networks, at times, can influence individuals to pursue treatment, while at other times, influence individuals to stay out of treatment, or seek treatment substitutes.     

Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal

Directed migration of diverse cell types plays a critical role in biological processes ranging from development and morphogenesis to immune response, wound healing, and regeneration. However, techniques to direct, manipulate, and study cell migration in vitro and in vivo in a specific and facile manner are currently limited. We conceived of a strategy to achieve direct control over cell migration to arbitrary user-defined locations, independent of native chemotaxis receptors. Here, we show that genetic modification of cells with an engineered G protein-coupled receptor allows us to redirect their migration to a bioinert drug-like small molecule, clozapine-N-oxide (CNO). The engineered receptor and small-molecule ligand form an orthogonal pair: The receptor does not respond to native ligands, and the inert drug does not bind to native cells. CNO-responsive migration can be engineered into a variety of cell types, including neutrophils, T lymphocytes, keratinocytes, and endothelial cells. The engineered cells migrate up a gradient of the drug CNO and transmigrate through endothelial monolayers. Finally, we demonstrate that T lymphocytes modified with the engineered receptor can specifically migrate in vivo to CNO-releasing beads implanted in a live mouse. This technology provides a generalizable genetic tool to systematically perturb and control cell migration both in vitro and in vivo. In the future, this type of migration control could be a valuable module for engineering therapeutic cellular devices.The ability of many cell types to migrate long distances within the body and specifically localize to target sites of action is critical for their proper function. For example, immune cells rapidly home to sites of infection, concentrating their powerful cytotoxic and proinflammatory activities for maximum efficacy while limiting damage to healthy tissue. In morphogenesis, cells undergo a complex stereotyped process involving migration as well as proliferation, differentiation, and programmed cell death to produce fully developed multicellular structures. In wound healing and regenerative processes, stem and progenitor cells home to injured tissues from nearby sites—as well as from distant locations including the bone marrow—to provide a stream of new cells to replenish and provide trophic support to old and damaged cells.Cell migration is also an important factor to consider in the use of cells as therapeutic agents. The use of cells for the treatment of a growing array of diseases including cancer, autoimmunity, and chronic wounds is currently being explored (1–6). The appropriate and efficient localization of therapeutic cells to sites of disease has been identified as an important factor for successful cell-based therapy (7–17). However, preclinical studies and clinical trials to date have shown that the homing to sites of disease of many cell types commonly used as therapeutics is frequently impaired or limited, especially after ex vivo expansion of cells in culture (7, 12, 18, 19).The ability to redirect the migration of cells to any user-specified location in the body would be a powerful enabling technology for basic research as well as for future applications, but there are currently few easily generalizable strategies to accomplish this goal. We conceived of an approach to direct cellular homing to small molecules by expressing, in motile cells, engineered G protein-coupled receptors (GPCRs) called receptors activated solely by a synthetic ligand (RASSLs) (20, 21).RASSLs are engineered to be unresponsive to endogenous ligands but can be activated by pharmacologically inert orthogonal small molecules (Fig. 1A). Versions of these receptors exist for the three major GPCR signaling pathways (Gαs-, Gαi-, and Gαq-coupled receptors), and the design of a new arrestin-biased variant has recently been reported (21, 22). Because GPCRs control many important physiological functions, including cell migration, we hypothesized that, by expressing these engineered receptors in motile cells, we could develop a general strategy for establishing user control over cell homing (Fig. 1B). Here, we use a family of second-generation RASSLs, known as designer receptors exclusively activated by a designer drug (DREADDs), that are activated only by the small molecule clozapine-N-oxide (CNO), an inert metabolite of the FDA-approved antipsychotic drug clozapine (Fig. S1) (20). CNO is highly bioavailable in rodents and humans, lacks affinity for any known receptors, channels, and transporters, and does not cause any appreciable physiological effects when systemically administered in normal mice (20, 23, 24).Open in a separate windowFig. 1.Engineered Gαi-coupled GPCRs Di3 and Di mediate cytoskeletal changes and chemotaxis of HL-60 neutrophils in response to CNO. (A) RASSLs are engineered GPCRs that interact orthogonally with a bioinert small-molecule drug. Natural ligands do not interact with the engineered receptors, and the bioinert drug that activates the engineered receptors does not interact with native receptors. (B) We tested whether certain second-generation RASSLs known as DREADDs could mediate cell motility. (C) Changes in electrical impedance that result from cell spreading in response to drug or ligand are detected by an electrode array. HL-60 neutrophils transiently transfected to express engineered GPCRs were plated on fibronectin-coated impedance assay plates and stimulated with vehicle control, 100 nM fMLP (positive control chemoattractant) or 100 nM CNO. All cells responded to fMLP whereas only Di3- or Di-expressing cells responded to CNO. Mean ± SEM for n = 3 replicates is shown. (D) Cell migration of HL-60 neutrophils transiently transfected with engineered GPCRs was quantitated in a porous transwell Boyden-chamber assay. All cells migrated in response to fMLP whereas only Di3- or Di-expressing cells migrated in response to CNO. Drug concentrations used: 100 nM CNO, 100 nM fMLP. Mean ± SEM for n = 3 replicates is shown. (E) Polarization and cell migration in neutrophils involves Rac and PI3K activation. Di-expressing HL-60 neutrophils were treated with 100 nM fMLP or 100 nM CNO before immunoblotting for phosphorylated Akt and phosphorylated PAK as readouts for PI3K and Rac activity, respectively. Peak levels of phospho-Akt and phospho-PAK are shown for each condition. Both were increased by CNO stimulation in Di cells but not in control cells (P < 0.01 by Student t test). Stimulation with fMLP increased phospho-Akt and phospho-PAK levels in both Di and control cells (P < 0.01 by Student t test), but Di cells showed higher peak levels of phospho-Akt than did control cells (P < 0.01 by Student t test). Three (for CNO) or four (for fMLP) independent experiments were performed and mean ± SEM are shown.