Incidence of 17p deletions and TP53 mutation in myelodysplastic syndrome and acute myeloid leukemia with 5q deletion

TP53 mutations are frequent in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with complex karyotype that include del(5q) and are often associated with deletion of 17p. They have also recently been observed in MDS with isolated del(5q). We assessed the incidence of 17p deletion detected by fluorescence in situ hybridization (FISH) and of TP53 mutations detected by direct sequencing and their correlation and prognostic value in 26 MDS and 17 AML with del(5q). In the 20 cases with isolated del(5q) or one additional abnormality, no 17p deletion was found and 3 of the 18 cases analyzed (17%) had TP53 mutation. In the 23 patients with complex karyotype, 17p deletion was suspected by conventional cytogenetics in 15 cases and confirmed by FISH in 10 of them, while TP53 mutation was found in 8 of the 15 patients tested (53%), only five of whom had 17p deletion. In the whole patient series, TP53 mutations were associated with shorter survival (P = 0.07). We confirm the existence of TP53 mutations in 17% of MDS with isolated del(5q). In patients with del(5q) and complex karyotype, FISH and direct sequencing are complementary techniques to analyze TP53 abnormalities. Our findings also suggest that sequencing of the TP53 gene should be included in the study of patients with del(5q) as a single abnormality or in complex karyotype before lenalidomide treatment. © 2012 Wiley Periodicals, Inc.     

Brain-derived neurotrophic factor gene Val66Met polymorphism and cognitive function in obsessive-compulsive disorder

In the present study, we have tested the hypothesis that brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism is associated with obsessive-compulsive disorder (OCD) and also investigated the association between the BDNF Val66Met polymorphism and the performance on tests measuring executive functions in a sample of patients with OCD. A total of 100 patients diagnosed with OCD according to DSM-IV criteria and 110 control subjects were included in this study. Single nucleotide polymorphism (G/A) leading to Val to Met substitution at codon 66 in BDNF was screened in the DNA samples of all participants. The genotype frequencies of BDNF Val66Met polymorphism were compared in OCD patients and healthy controls. The four subgroups of OCD and healthy control subjects, determined according to being Val homozygous or carrying a Met allele, were also compared according to their performance in a battery of neuropsychological tests of executive functions and verbal memory. There was no significant difference for the allele and genotype distributions of BDNF Val66Met polymorphism between the OCD and healthy control groups. Compared to the other three subgroups, OCD-Met carriers were slower on Trail-Making Test part A (TMT A), part B (TMT B) score and its speed-corrected score (TMT B-A). OCD-Met carriers had also poor performance on verbal fluency tasks and several CVLT measures compared only to the healthy control-Met carriers. These results demonstrate that the BDNF Val66Met polymorphism does not appear to be a risk factor for OCD. However, the presence of a BDNF Met allele, which is a known attenuator of BDNF activity, may be associated with a poorer executive functioning in OCD. ? 2012 Wiley Periodicals, Inc.     

Processing of emotional reactivity and emotional memory over sleep

Sleep enhances memories, particularly emotional memories. As such, it has been suggested that sleep deprivation may reduce posttraumatic stress disorder. This presumes that emotional memory consolidation is paralleled by a reduction in emotional reactivity, an association that has not yet been examined. In the present experiment, we used an incidental memory task in humans and obtained valence and arousal ratings during two sessions separated either by 12 h of daytime wake or 12 h including overnight sleep. Recognition accuracy was greater following sleep relative to wake for both negative and neutral pictures. While emotional reactivity to negative pictures was greatly reduced over wake, the negative emotional response was relatively preserved over sleep. Moreover, protection of emotional reactivity was associated with greater time in REM sleep. Recognition accuracy, however, was not associated with REM. Thus, we provide the first evidence that sleep enhances emotional memory while preserving emotional reactivity.     

Comparing cisplatin plus etoposide with combination of mitomycin, ifosfamide and cisplatin in advanced non-small cell lung cancer patients

Cisplatin-etoposide (CE) and mitomycin, ifosfamide and cisplatin (MIC) combinations are active conventional regimens in non-small cell lung cancer (NSCLC). In this retrospective study, we compared response rates, survival, duration of response, time-to-progression and toxicity of CE with MIC regimens in treatment of previously untreated patients with stage IIIB and IV NSCLC. We first determined the patients with NSCLC who had stage IIIB or IV and received CE or MIC between January 1997 and December 2002 in our clinic. Out of the eligible patients, 45 received MIC, 167 received CE. In addition 45 MIC patients, we included 46 of the 167 CE patients in the study by selecting one patient of every three patient randomly. In CE protocol, cisplatin 80 mg/m(2) on day 1 and etoposide 100 mg/m(2) on days 1, 2, 3 (every three weeks); in MIC protocol, mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), cisplatin 50 mg/m(2) on day 1 (every three weeks) were performed. For statistical analysis, chi-square, t-test, Kaplan-Meier survival analysis, Cox regression analysis and logistic regression analysis were used by SPSS 11.5 computer program. The overall response rate was 33.3% in the MIC arm and 34.8% in the CE arm. A respective median survival was 28 weeks for the MIC arm and 35 weeks for the CE arm. Median duration of response and time to progression in each groups were 23 and 14 weeks in MIC arm and 32 and 22 weeks respectively. There was no statistical difference for response rates, duration of survival and response, time top progression and toxicity between the two arms. We consider that the combinations of MIC and CE have similar activity and they can be used confidently in advanced NSCLC.     

Relationship of Q angle and joint hypermobility and Q angle values in different positions

Patellar malalignment is the most important reason for anterior knee pain. Patellar alignment is commonly determined by the measurement of the quadriceps (Q) angle. In this study, our primary aim was to investigate the Q angle difference between healthy individuals with and without joint hypermobility. The other objectives were to compare the Q angle values, which were measured in supine and upright positions, to determine hypermobility frequency among healthy males in a certain population, and to investigate the correlation between the existent skeletal deformities and Beighton score levels. Two hundred fifty-three healthy male college students were examined for hypermobility and skeletal deformities. According to the Beighton scoring system, three groups (n=20) were formed, and Q angle measurements were performed on the 60 individuals in both supine and upright positions. In the comparison of the groups, the mean Q angle values in healthy hypermobile individuals were found to be significantly higher than that of the nonhypermobile ones (p<0.05). No statistical difference was found between Q angle values in supine and upright positions (p>0.05). The frequency of joint hypermobility (Beighton score 4 or more) was found to be 29.25% in this population. No correlation was determined between existent skeletal deformities and Beighton score values (p>0.05). In conclusion, the Q angle evaluation among healthy hypermobile individuals may have a prognostic value for probable knee pathologies that may appear in the future.     

Beta-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury

Myelotoxic injury in the bone marrow (BM) as a consequence of total body irradiation (TBI) or granulocyte colony-stimulating factor (G-CSF) mobilization results in the deposition of iC3b on BM stroma (stroma-iC3b). In the present study, we have examined how stroma-iC3b interacts with hematopoietic progenitor cells (HPCs) and the role of complement (C) and complement receptor 3 (CR3) in BM injury/repair. We demonstrate here that stroma-iC3b tethers HPCs via the inserted (I) domain of HPC complement receptor 3 (CR3, CD11b/CD18, Mac-1). Following irradiation, stroma-iC3b was observed in the presence of purified IgM and normal mouse serum (NMS), but not serum from Rag-2(-/-) mice, implicating a role for antibody (Ab) and the classic pathway of C activation. Furthermore, a novel role for soluble yeast beta-glucan, a ligand for the CR3 lectin-like domain (LLD), in the priming of CR3(+) HPC is suggested. Soluble yeast beta-glucan could enhance the proliferation of tethered HPCs, promote leukocyte recovery following sublethal irradiation, and increase the survival of lethally irradiated animals following allogeneic HPC transplantation in a CR3-dependent manner. Taken together, these observations suggest a novel role for C, CR3, and beta-glucan in the restoration of hematopoiesis following injury.