Brief Report: Highly motile cells are metabolically responsive to collagen density

Altered tissue mechanics and metabolism have gained significant attention as drivers of tumorigenesis, and mechanoresponsive metabolism has been implicated in migration and metastasis. However, heterogeneity in cell populations makes it difficult to link changes in behavior with metabolism, as individual cell behaviors are not necessarily reflected in population-based measurements. As such, the impact of increased collagen deposition, a tumor-associated collagen signature, on metabolism remains ambiguous. Here, we utilize a wide range of collagen densities to alter migration ability and study the bioenergetics of individual cells over time. Sorting cells based on their level of motility revealed energetics are a function of collagen density only for highly motile cells, not the entire population or cells with low motility. Changes in migration with increasing collagen density were correlated with cellular energetics, where matrix conditions most permissive to migration required less energy usage during movement and migrated more efficiently. These findings reveal a link between matrix mechanics, migratory phenotype, and bioenergetics and suggest that energetic costs are determined by the extracellular matrix and influence cell motility.     

老年子宫颈癌患者生存情况及其影响因素分析

目的:探讨影响老年子宫颈癌患者术后生存的影响因素.方法:对1980年1月～1998年12月诊治的老年子宫颈癌243例临床资料和随访结果进行回顾性分析.采用Kaplan-Meier法计算累积生存率,用Log-Rank法比较各因素不同水平生存分布的差异,进一步应用COX回归模型进行预后因素分析.结果:全组子宫颈癌术后5、10、15年累积生存率分别为87％、81％、75％,Log-Rank分析结果显示不同临床分期、不同组织分化程度、有无淋巴结转移、不同治疗方法患者生存差异存在明显差异(x2=23.172,P＜0.05;x2=32.766,P＜0.05;x2 =25.086,P＜0.05;x2 =28.906,P＜0.05).年龄、不同生长方式、肿瘤直径、有无辅助治疗水平间生存差异无统计学意义(P＞0.05),COX模型多因素分析表明:临床分期、组织分化程度、淋巴结转移是影响预后的独立因素(P＜0.01).结论:临床分期、淋巴结转移、组织分化是影响老年子宫颈癌预后的独立危险因素,及早发现和合理降低临床分期是治疗老年子宫颈癌以及提高预后的关键手段.     

子宫内膜微创技术对体外受精和胚胎移植妊娠结局影响的研究

目的探讨子宫内膜微创术对不孕症妇女体外受精-胚胎移植(IVF-ET)妊娠结局的影响。方法选择2010年1月-2012年6月在新疆医科大学第一附属医院生殖助孕中心74例接受IVF-ET/卵胞浆内单精子注射(ICSI)的不孕症患者,以采用子宫内膜微创术的41例患者作为治疗组,在促排周期月经来潮24h内进行子宫内膜微创术;以未进行子宫内膜微创术的33例为对照组,比较两组的胚胎种植率及临床妊娠率。结果治疗组与对照组胚胎种值率分别26.51%和11.43%,差异有统计学意义(P<0.05);治疗组与对照组临床妊娠率分别为43.90%和21.21%,差异有统计学意义(P<0.05)。结论不孕症妇女进行子宫内膜微创术后能够显著提高IVF-ET/ICSI周期的胚胎种植率及临床妊娠率,改善妊娠结局。     

米非司酮对不同月经周期异位和在位子宫内膜雌激素受体α和孕激素受体表达的影响

目的 探讨米非司酮对雌激素受体α(ERα)和孕激素受体(PR)在不同月经周期的子宫腺肌症中表达的影响.方法 47例行全子宫切除术的子宫腺肌症患者分为米非司酮组(n=24)和未用药组(n=23);无腺肌症的正常子宫内膜作为对照组(n=15).运用免疫组化的方法测定异位和在位子宫内膜及正常子宫内膜在不同月经周期的腺上皮及间质细胞中ERα和PR水平.结果 未用药组ERα和PR在异位子宫内膜腺上皮及间质细胞中的表达均低于在位内膜及对照组正常内膜(P<0.05).对照组及未用药组ERα和PR在在位内膜腺上皮细胞中的表达,增生期高于分泌期(P<0.05),而在未用药组异位内膜,差异无统计学意义(P>0.05).ERα和PR在异位和在位子宫内膜中的表达,米非司酮组低于未用药组(P<0.05).结论 ERα和PR在异位子宫内膜中的表达与在位子宫内膜不同;异位内膜丧失了正常内膜的周期性变化规律;米非司酮通过下调其性激素受体(ERα和PR)含量治疗子宫腺肌症.     

Semi-mechanistic Modeling of the Interaction Between the Central and Peripheral Effects in the Antinociceptive Response to Lumiracoxib in Rats

The model-based approach was undertaken to characterize the interaction between the peripheral and central antinociceptive effects exerted by lumiracoxib. The effects of intraplantar and intrathecal administrations and of fixed ratio combinations of lumiracoxib simultaneously administered by these two routes were evaluated using the formalin test in rats. Pain-related behavior data, quantified as the number of flinches of the injected paw, were analyzed using a population approach with NONMEM 7. The pain response during the first phase of the formalin test, which was insensitive to lumiracoxib, was modeled using a monoexponential decay. The second phase, which was sensitive to lumiracoxib, was described incorporating synthesis and degradation processes of pain mediators that were recruited locally after tissue injury. Upregulation at the local level and in the central nervous system (CNS) was set to be proportional to the predicted levels of pain mediators in the local (injured) compartment. Results suggest a greater role of upregulated COX-2_Local in generating the pain response compared to COX-2_CNS. Drug effects were described as inhibition of upregulated COX-2. The model adequately described the time course of nociception after formalin injection in the absence or presence of lumiracoxib administered locally and/or spinally. Data suggest that the overall response is the additive outcome of drug effects at the peripheral and central compartments, with predominance of peripheral mechanisms. Application of modeling opens new perspectives for understanding the overall mechanism of action of analgesic drugs.     

Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report

This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional.     

Aplastic anemia: analysis of stromal cell function in long-term marrow cultures

Marrow samples from 89 patients with aplastic anemia (AA) were evaluated for their ability to grow stromal layers in standard long- term marrow cultures (LTMCs). Results were highly variable: 6.8% failed to grow any stromal cells (group I); 42.5% either failed to grow to confluency or appeared to have a decreased number of adipocytes and/or macrophages (group II); and 52.8% appeared as normal confluent cultures with fibroblasts, adipocytes, and macrophages (group III). Analyses of patient data suggested that group I patients had a longer disease duration and poorer survival (P = .07). Enzyme-linked immunosorbent assay analysis of cytokine production was performed on 20 of the normal- appearing AA LTMCs and 12 LTMCs established from normal donors. Significant differences between the AA and control groups were apparent for macrophage inflammatory protein-1 alpha (MIP-1 alpha), interleukin- 1 receptor antagonist (IL-1ra), granulocyte-macrophage colony- stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G- CSF), and leukemia-inhibitory factor (LIF). The most dramatic differences observed were elevated levels of MIP-1 alpha and GM-CSF and decreased levels of IL-1ra, particularly after IL-1 alpha stimulation. In contrast, IL-1 alpha stimulation of AA LTMCs produced levels of IL- 6, LIF, and G-CSF comparable with those of controls. These data suggest that defects exist within the microenvironment of some AA marrows. Whether the majority of these defects are the cause or consequence of aplasia is not clear. However, we speculate that some of these abnormalities may contribute to the maintenance of the hypoplastic state and, in extreme cases, prevent engraftment of donor marrow.     

FEMALE GENITAL MUTILATION AND PUBLIC HEALTH: LESSONS FROM THE BRITISH EXPERIENCE

The author addresses the public health policy challenge posed by the increasing numbers of immigrant girls and women in the United States affected by female genital mutilation (FGM), a traditional ritual health practice in which part or all of the external genital structures are removed from females, usually during childhood. The practice is common today in 26 African nations and affects 100 to 126 million women and girls worldwide. The significant lifelong negative health impact of FGM has been documented. Recent developments in British domestic health and social policy are reviewed to provide insights. The definition of FGM, prevalence, health impact, and history of the practice are presented. Implications for the development of health and social services policies and programs in the United States are drawn.     

Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis

We have localized the molecular alteration in the membrane skeleton of two of four kindreds with hereditary spherocytosis (HS) to an alteration in the spectrin-protein-4.1 interaction due to a defective spectrin molecule. The defective spectrin-protein-4.1 interaction in these kindreds (referred to as type I HS) leads to a weakened spectrin- protein-4.1-actin ternary complex, which in turn may lead to the friable membrane skeleton and suggested membrane instability related to this disorder. Type I HS spectrin binds approximately 63% as much protein-4.1 as normal spectrin (with equal affinity). This defect does not correlate with splenic function or erythrocyte age in the circulation. However, the approximately 37% reduction in binding of protein-4.1 to HS spectrin approaches the theoretical value of 50% expected in this autosomal dominant disorder. All other type I membrane skeletal interactions (spectrin-syndein, spectrin heterodimer- heterodimer, syndein-band-3) were found to be normal. It would appear therefore that the defective HS spectrin-protein-4.1 interaction in type I hereditary spherocytosis may be the primary molecular defect rather than a secondary phenomena.