Restriction site polymorphism at the LPA (Lp(a) apoliprotein; apoliprotein(a)) locus

A restriction site polymorphism in the Lp(a) apolipoprotein gene (the LPA gene) is reported. The basis for the polymorphism is presence or absence of an MspI restriction site that appears to be 3' to the last kringle IV structure of the gene. The "1" gene (presence of the restriction site) has a frequency of 0.316 and the "2" gene (absence of the restriction site) has a frequency of 0.684. Both members of each of 67 monozygotic (MZ) twin pairs had the same genotype and there was Mendelian segregation of the DNA variants in 40 families with a total of 75 children. There was a lower proportion of people with genotype 1-1 in the top quartile than in the 3 bottom quartiles of the population distribution of Lp(a) lipoprotein levels but the difference did not reach statistical significance.     

Evaluation of Gianturco Coils for Closure of Large (≥3.5 mm) Patent Ductus Arteriosus

Objectives. This report evaluates the use of Gianturco coils to close large patent ductus arteriosus (PDAs) (≥3.5 mm) and describes transvenous delivery of 0.052-in. (0.132-cm) Gianturco coils.

Background. Coil closure of PDAs has become increasingly popular. However, the technique has significant limitations when used to close large PDAs. This report evaluates patient characteristics, PDA anatomy, hemodynamic variables, delivery technique and coil geometry to determine predictors of success.

Methods. Between January 1995 and January 1997, 16 of 118 patients undergoing catheterization for PDA closure were found to have large PDAs. Their median age and weight were 14 months (range 3 months to 43 years) and 8.5 kg (range 3.5 to 73), respectively. The mean PDA diameter was 4.3 mm (range 3.5 to 5.9). Closure of PDAs was attempted using transcatheter delivery of 0.038-in. (0.096-cm) and 0.052-in. coils. Differences in clinical, anatomic, hemodynamic and technical variables between successes and failures were compared.

Results. Eleven (69%) of 16 patients had successful closure of their PDA. Failures occurred only in patients <8 months of age with an indexed PDA diameter >7 mm/m and a pulmonary/systemic flow ratio ≥2.8:1. Use of 0.052-in. coils tended to reduce the incidence of embolization and the number of coils needed for closure.

Conclusions. Patients >8 months of age can have successful closure of large PDAs with currently available Gianturco coils. The 0.052-in. Gianturco coils can be used safely to close large PDAs in infants as small as 6 kg. Increased experience and improved coil design may improve closure rates of large PDAs in infants.     

Inhibitory effects of lysophosphatidic acid receptor-5 on cellular functions of sarcoma cells

Abstract

Lysophosphatidic acid (LPA) is a bioactive lipid that interacts with G protein-coupled LPA receptors (LPA receptor-1 (LPA₁) to LPA₆). Here, we investigated the effects of LPA signaling via LPA₅ on cellular functions of sarcoma cells by generating Lpar5 overexpressing and Lpar5 knockdown cells from rat osteosarcoma and malignant fibrous histiocytoma cells, respectively. The cell motility activity of Lpar5 overexpressing cells was significantly lower, while Lpar5 knockdown cells showed high cell motility, compared with respective controls. Gelatin zymography showed that LPA₅ suppressed the activation of matrix metalloproteinase-2. LPA₅ also inhibited the cell motility activity of endothelial cells, correlating with the expression levels of vascular endothelial growth factor genes. These results suggest that LPA signaling via LPA₅ negatively regulates the cellular functions of rat sarcoma cells.     

Diagnostic and prognostic significance of lysophosphatidic acid in malignant pleural effusions

Background

Lysophosphatidic acid (LPA) is an important extracellular signal transmitter and intracellular second messenger in body fluids. It can be detected in the ascitic fluid of patients with ovarian cancer. Increasing evidence shows that LPA can stimulate cancer cell proliferation and promote tumor invasion and metastasis. Our study aimed to evaluate the diagnostic value of LPA in differentiating between malignant pleural effusions (MPEs) and benign pleural effusions (BPEs) and to evaluate the association between the level of LPA in MPE and the prognosis of lung cancer patients.

Patients and methods

The level of LPA in the pleural effusions (PEs) of 123 patients (94 MPE, 29 BPE) with lung cancer was evaluated using an enzyme-linked immunosorbent assay. The performance of LPA was analyzed by standard Receiver operator characteristic curve (ROC) analysis methods, using the area under the curve (AUC) as a measure of accuracy. Overall survival (OS) curves and progression-free survival (PFS) curves were based on the Kaplan-Meier method, and the survival differences between subgroups were analyzed using the log-rank or Breslow test (SPSS software). A multivariate Cox proportional hazards model was used to assess whether LPA independently predicted lung cancer survival.

Results

The levels of LPA differed significantly between MPE (22.08±8.72 µg/L) and BPE (14.61±5.12 µg/L) (P<0.05). Using a cutoff point of 18.93 µg/L, LPA had a sensitivity of 60% and a specificity of 83% to distinguish MPEs from BPEs with an AUC of 0.769±0.045 (SE) (P=0.000) (95% CI, 0.68-0.857). In the three pathological types of lung cancer patients with MPE, there were no significant associations between LPA levels and the length of PFS and OS (P=0.58 and 0.186, respectively). Interestingly, in the patients with MPE caused by lung adenocarcinoma there were significant associations between the LPA levels and the PFS and OS (P=0.018 and 0.026, respectively). Multivariate analysis showed that the LPA level was an independent prognostic factor for PFS in lung adenocarcinoma.

Conclusions

Our results indicate that LPA can be used as a new biomarker for the diagnosis of MPE caused by lung cancer and that higher levels of LPA are related to shorter PFS in adenocarcinoma of the lung.     

川芎清脑颗粒联合硫酸软骨素治疗偏头痛的临床研究

目的探讨川芎清脑颗粒联合硫酸软骨素治疗偏头痛的临床疗效。方法选取2017年3月—2018年3月在陕西省核工业二一五医院治疗的偏头痛患者76例,根据用药的差别分为对照组(38例)和治疗组(38例)。对照组口服硫酸软骨素钠片,0.6 g/次,3次/d;治疗组在对照组基础上口服川芎清脑颗粒,10 g/次,3次/d。两组患者均治疗4周。观察两组患者临床疗效,同时比较治疗前后两组患者临床症状评分、血清学指标和脑血流情况。结果治疗后,对照组临床有效率为81.58%,显著低于治疗组的97.37%,两组比较差异具有统计学意义(P0.05)。治疗后,两组头痛发作次数、头痛发作持续时间和头痛发作程度评分均明显降低(P0.05),且治疗组患者临床症状评分明显低于对照组(P0.05)。治疗后,两组患者血清高敏C反应蛋白(hs-CRP)、基质金属蛋白酶-9(MMP-9)、血管内皮生长因子(VEGF)和溶血磷脂酸(LPA)水平均显著降低(P0.05),且治疗后治疗组这些血清学指标明显低于对照组(P0.05)。治疗后,两组患者大脑前动脉(ACA)、大脑中动脉(MCA)、大脑后动脉(PCA)、基底动脉(BA)、椎动脉(VA)的平均血流速度(Vm)均显著降低(P0.05),且治疗后治疗组脑血流情况明显优于对照组(P0.05)。结论川芎清脑颗粒联合硫酸软骨素治疗偏头痛可有效改善患者临床症状,降低血清hs-CRP、MMP-9、VEGF、LPA水平,有利于脑血流速度改善。     

The DSM-5 dissociative-PTSD subtype: Can levels of depression,anxiety, hostility,and sleeping difficulties differentiate between dissociative-PTSD and PTSD in rape and sexual assault victims?

The DSM-5 currently includes a dissociative-PTSD subtype within its nomenclature. Several studies have confirmed the dissociative-PTSD subtype in both American Veteran and American civilian samples. Studies have begun to assess specific factors which differentiate between dissociative vs. non-dissociative PTSD. The current study takes a novel approach to investigating the presence of a dissociative-PTSD subtype in its use of European victims of sexual assault and rape (N = 351). Utilizing Latent Profile Analyses, we hypothesized that a discrete group of individuals would represent a dissociative-PTSD subtype. We additionally hypothesized that levels of depression, anger, hostility, and sleeping difficulties would differentiate dissociative-PTSD from a similarly severe form of PTSD in the absence of dissociation. Results concluded that there were four discrete groups termed baseline, moderate PTSD, high PTSD, and dissociative-PTSD. The dissociative-PTSD group encompassed 13.1% of the sample and evidenced significantly higher mean scores on measures of depression, anxiety, hostility, and sleeping difficulties. Implications are discussed in relation to both treatment planning and the newly published DSM-5.     

Lysophosphatidic acid-induced IL-8 secretion involves MSK1 and MSK2 mediated activation of CREB1 in human fibroblast-like synoviocytes

Lysophosphatidic acid (LPA) is a pleiotropic lipid mediator that promotes motility, survival, and the synthesis of chemokines/cytokines such as interleukin-8 (IL-8) and interleukin-6 by human fibroblast-like synoviocytes from patients with rheumatoid arthritis (RAFLS). In those cells LPA was reported to induce IL-8 secretion through activation of various signaling pathways including p38 mitogen-activated protein kinase (p38 MAPK), p42/44 MAPK, and Rho kinase. In addition to those pathways we report that mitogen- and stress-activated protein kinases (MSKs) known to be activated downstream of the ERK1/2 and p38 MAPK cascades and CREB are phosphorylated in response to LPA. The silencing of MSKs with small-interfering RNAs and the pharmacological inhibitor of MSKs SB747651A shows a role for both MSK1 and MSK2 in LPA-mediated phosphorylation of CREB at Ser-133 and secretion of IL-8 and MCP-1. Whereas CREB inhibitors have off target effects and increased LPA-mediated IL-8 secretion, the silencing of CREB1 with short hairpin RNA significantly reduced LPA-induced chemokine production in RAFLS. Taken together the data clearly suggest that MSK1 and MSK2 are the major CREB kinases in RAFLS stimulated with LPA and that phosphorylation of CREB1 at Ser-133 downstream of MSKs plays a significant role in chemokine production.