Genetic and epigenetic alterations of the EGFR and mutually independent association with BRCA1, MGMT,and RASSF1A methylations in Vietnamese lung adenocarcinomas

Genetic and epigenetic alterations importantly contribute to the pathogenesis of lung cancer. In the study, we measured the frequency and distribution of molecular abnormalities of EGFR as well as the aberrant promoter methylations of BRCA1, MGMT, MLH1, and RASSF1A in Vietnamese lung adenocarcinomas. We investigated the association between genetic and epigenetic alteration, and between each abnormality with clinicopathologic parameters. Somatic EGFR mutation that was found in 49/139 (35.3%) lung adenocarcinomas showed a significant association with young age, female gender, and non-smokers. EGFR overexpression was identified in 82 tumors (59.0%) and statistical relationships with EGFR or BRCA1 methylation but not EGFR mutation. In addition, EGFR, BRCA1, MGMT, MLH1, and RASSF1A methylations were found in 33 (23.7%), 41 (29.5%), 46 (33.1%), 28 (20.1%), and 41 (29.5%) cases of a total of 139 lung adenocarcinomas, respectively. The RASSF1A methylation was found to be linked to the smoking habit. Methylations in MGMT and RASSF1A were also found to correlate with metastasis status. Furthermore, the distribution of EGFR mutation and that of BRCA1, MGMT or RASSF1A methylation were significantly exclusive in lung adenocarcinomas. The main finding of our study demonstrate that epigenetic abnormalities might play a critical role for the lung tumorigenesis in patients with smoking history and metastasis, and partly affect the predictive value of EGFR mutations through blocking expression due to promoter EGFR hypermethylation. Mutually exclusive distribution of genetic and epigenetic alterations reflects differently biological characteristics in the etiology of lung adenocarcinomas.     

Vers un rapprochement du syndrome de Klinefelter et de la psychopathie en psychiatrie légale

Klinefelter syndrome (KS) (47,XXY) is the most common aneuploidy (1/650) of sexual chromosome among male (0,1 à 0,2 % of male population) (Hong and Reiss, 2014). Because its large physical phenotypic variability (high tall, sparse hairiness, gynecomastia), this syndrome is largely underdiagnosed (less than 25 % of affected persons) (Samango-Sprouse et al., 2018). Nevertheless, cognitive variability is smaller. Normal to low average total IQ, low verbal IQ, social problems and high levels of psychiatric comorbidities including early aggressiveness are commonly described (Hong and Reiss, 2014). In Denmark, higher risks of committing sexual crime and arson (compared to criminal controls) was recently reported (Stochholm et al., 2012). Quite a few clinically relevant cases reports scattered in the literature, suggests the presence of a pattern of a specific subtype of KS inpatients among forensic population (Bénézech, 1975). However, very few studies provide quantitative or qualitative pertaining to robust results. KS well-documented neurobiological (van Rijn, 2018) (e.g. low levels of testosterone), neuropsychological (Bénézech, 1975; Hong and Reiss, 2014; Samango-Sprouse et al., 2018; Savic, 2012; Seara-Cardoso et al., 2016; Senon, 2005; Stochholm et al., 2012; van Rijn, 2018; van Rijn et al., 2008; van Rijn et al., 2018; van Rijn et al., 2014; van Rijn et al., 2012) [29] (e.g. alterations of both complex cerebral — attention, empathy — and behavioral regulation functions - inhibition, mental flexibility, emotional response modulation, control of own actions) and neuroanatomical (Hong and Reiss, 2014; Itti et al., 2003; Savic, 2012; van Rijn et al., 2008; van Rijn et al., 2012) [29] (e.g. limbic system and temporal lobe abnormal volume, hemispheric specialization shortcoming) features may be helpful to understand comorbid symptoms psychopathology. Numbers of recent studies conduct on KS pediatric or adult population provide interesting results on conduct, anxiety, psychotic and autism spectrum disorders. In addition, some authors use genetic and epigenetic specific features of sex chromosome aneuploidies (e.g. X genes neurodevelopmental role; imprinting) in order to clarify genotype-phenotype links of comorbid symptoms (Bruining et al., 2011; Zitzmann et al., 2004;). With Belgian colleagues from the Social Defense Research Center (CRDS, Tournai, Belgium), we are currently recruiting KS inpatients from security hospitals or psychiatric units in Belgium and France. We aim to assess psychopathic traits with the Psychopathy Checklist Revised (PCL-R, Hare) (Hare, 2003). Our first results concerning 3 KS males outline that PCL-R is useful for the characterization of clinical phenotype among KS forensic sample. While three of them present psychopathic traits, two of them present categorical double diagnose “psychopathy-KS” (total PCL-R score > = 30/40 (Delannoy et al., 2017)). Moreover, dimensional analysis support our hypothesis of a higher prevalence of “explosive profile” in comparison to other psychopathic profiles in our sample (Delannoy et al., 2017). The present article summarizes historic background (e.g. “psychopathy” disappearance of mental disorder reference classification schemes, “crime chromosome” (Bénézech, 1975)) and current context argues (e.g. French psychiatrists court experts widely refer to psychopathy concept despite a lack of consensual definition (Senon, 2005), weak knowledge and training of PCL-R and its related biopsychological recent findings (Blair, 2013; de Oliveira-Souza et al., 2008; Dotterer et al., 2017; Glenn and Raine, 2014; Hosking et al., 2017; Korponay et al., 2017; Pham, 1995; Pham, 2005; Raine, 2008; Raine et al., 2003); stigma and discrimination apprehensions of KS and psychopath) that motivate our research project. Finally, we discuss the advantages of our research protocol on KS participants assessed with PCL-R, such as tackling stigma and discrimination, better understanding psychopathology, and clarifying murky interactions of biological, psychological and social factors entangled in the development of these two fascinating troubles.     

Increased ratio of saturated to unsaturated C18 fatty acids in colonic adenocarcinoma: Implications for cryotherapy and lipid raft function

Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of human malignancies including colonic adenocarcinoma. Since FASE synthesizes only saturated fatty acids, we hypothesized that cancer cells have a greater proportion of long-chain saturated fatty acids. We studied and found an unequivocal increase in saturated C18 fatty acid (stearic acid) in colonic adenocarcinoma compared to adjacent normal colonic mucosa. The increase is even more striking when measured as a ratio of stearic acid to the unsaturated C18 fatty acids (oleic acid and linoleic acid). This change in fatty acid composition of the cancer cells should significantly alter their physical and biological properties. The increase in relative proportion of saturated fatty acids should make the cancer cells more susceptible to cryodamage and measurement of fatty acid composition of cancer cells may help individualize the temperature for cryotherapy. Also, the lipid alterations may affect the structure and functions of lipid rafts, which may enable the cancer cells to affect signaling mechanisms such as those involved in cell growth and apoptosis. Dietary or therapeutic interventions targeting lipid rafts may thus be an option for cancer treatment.     

Pathology of falciparum malaria in Vietnam.

Autopsy samples from the brains of 20 patients who died of falciparum malaria were examined by light microscopy and by an immunohistologic method. Particular attention was paid to a comparison of the pathologic features of the white matter and the cortex. In the high-sequestration (greater than 50%) group (n = 8), the mean +/- SD percentage of cerebral microvessels that showed parasitized red blood cell (PRBC) sequestration was 71.2 +/- 8.1% in the cortex and 84.0 +/- 6.7% in the white matter. The difference in the PRBC sequestration rate between cortex and white matter was statistically significant (P less than 0.01). Perivascular and ring hemorrhages were seen more frequently in the white matter than in the cortex. Deposition of IgG and Plasmodium falciparum antigen in the cerebral microvessels was more highly significant in the white matter than in the cortex (P less than 0.01). Our study demonstrated that the localized concentration of PRBC sequestration in the brain correlated with the marked immunohistologic differences in the microvessels of cortex and white matter.     

Orale Antikoagulation bei symptomatischen intrakraniellen Stenosen

SummarySymptomatic intracranial stenoses display an increased risk for ischemic stroke. Until now, only retrospective studies have demonstrated a positive effect of oral anticoagulation for prevention of further ischemic strokes. However, this therapy is widely used. The aim of the present study was to examine the efficacy and safety of oral anticoagulation for patients with symptomatic intracranial stenoses in clinical practice. Sixty-one patients with the diagnosis of symptomatic intracranial stenosis between 1992 and 1998 and who received oral anticoagulation were interviewed and examined in 2000. Ten patients suffered ischemic strokes (eight TIA, two completed strokes), and a subdural hematoma occurred in one patient. Six patients died during the observation period. In none of these cases was the death related to oral anticoagulation. Eight extracerebral bleedings occurred. An annual rate of 3% per year for ischemic strokes could be calculated. The annual rates for intracerebral and extracerebral bleeding amounted to less than 1% per year and 2.6% per year, respectively. Thus, oral anticoagulation in patients with symptomatic intracranial stenoses seems to be safe. Although the results suggest its efficacy, this cannot be proven due to the small number of patients examined and due to the design of the study.     

Nasolacrimal injuries. Evaluation and management

The tear drainage system is disrupted in 17% to 21% of nasoethmoidal fractures and, to a lesser degree, other midfacial fractures. When epiphora or dacryocystitis occurs, evaluation should include the Jones dye tests, probing of the ductal system, or dacryography. Dacryocystorhinostomy is the treatment of obstruction distal to the common canaliculus.     

鹿茸有效成分对小鼠肝脏RNA和蛋白质合成的影响

多次给小鼠po鹿茸多胺30mg/kg,对[³H]leucine和[³H]uridine掺入肝组织蛋白和RNA有明显的促进作用,而庸茸非多胺则无此作用;当腐胺剂量为21mg/kg时,不仅促进[³H]leucine和[³H]uridiae掺入肝组织蛋白和RNA,也促进[³H]uridine掺入肝细胞核的RNA中,并增强RNA聚合酶的活性;精脒在剂量为8mg/kg时,仅对[³H]leucine掺入肝组织蛋白有促进;而精胺在1mg/kg时,没有观察到上述各种现象。此结果提示,鹿茸多胺类物质是鹿茸中刺激小鼠肝组织蛋白和RNA合成的主要活性物质,这 种刺激小鼠肝组织蛋白和RNA合成效应是由于鹿茸多胺能够显著地增强RNA聚合酶的活性。     

鹿茸多肽的纯化和鉴定(英文)

应用凝胶过虑和离子交换层析等技术,从鹿茸(pilose antler or Cervus nipponTemminck)中分离纯化出一种多肽(peptide of pilose antler,PAP)。经高效液相色谱和N-末端氨基酸分析鉴定为单一多肽,氨基酸组成分析证明,PAP是由68个氨基酸组成,分子是为7200。药理研究证明,PAP对大鼠角叉菜胶性足肿胀具有明显的抑制作用并呈现良好的量—效关系。