Diagnostic accuracy of ultrasonic examination in suspected craniosynostosis among infants

The current study was performed to assess the diagnostic accuracy of ultrasound compared to CT scan as a gold standard in the diagnosis of craniosynostosis. 44 infants (17 girls) under 1 year old, clinically suspected to have craniosynostosis, were first sonographically examined by a pediatric radiologist and were later referred to another blinded pediatric radiologist to examine CT scan with 3D reconstructed images of skull. Sensitivity, specificity, positive and negative predictive values of ultrasound versus CT scan were 96.9%, 100%, 100%, and 92.3%, respectively. The high specificity of ultrasound helps to correctly rule out craniosynostosis in clinically suspected cases and thus, can prevent unnecessary exposure of healthy infants to CT scan ionizing radiation.     

Ongoing immunoglobulin somatic mutation in germinal center B cell-like but not in activated B cell-like diffuse large cell lymphomas

B cell diffuse large cell lymphoma (B-DLCL) is a heterogeneous group of tumors, based on significant variations in morphology, clinical presentation, and response to treatment. Gene expression profiling has revealed two distinct tumor subtypes of B-DLCL: germinal center B cell-like DLCL and activated B cell-like DLCL. In a separate study, we determined that B-DLCL can also be subdivided into two groups based on the presence or absence of ongoing Ig gene hypermutation. Here, we evaluated the correlation between these B-DLCL subtypes established by the two different methods. Fourteen primary B-DLCL cases were studied by gene expression profiling using DNA microarrays and for the presence of ongoing mutations in their Ig heavy chain gene. All seven cases classified as germinal center B cell-like DLCL by gene expression showed the presence of ongoing mutations in the Ig genes. Five of the seven cases classified by gene expression as activated B cell-like DLCL had no ongoing somatic mutations, whereas, in the remaining two cases, a single point mutation was observed in only 2 of 15 and 21 examined molecular clones of variable heavy (V(H)) chain gene, respectively. These two cases were distantly related to the rest of the activated B cell-like DLCL tumors by gene expression. Our findings validate the concept that lymphoid malignancies are derived from cells at discrete stages of normal lymphocyte maturation and that the malignant cells retain the genetic program of those normal cells.     

The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile

Recently we have identified subgroups of de novo primary diffuse large B-cell lymphoma (DLBCL) based on complementary DNA microarray-generated gene expression profiles. To correlate the gene expression profiles with cytogenetic abnormalities in these DLBCLs, we examined the occurrence of the t(14;18)(q32;q21) in the 2 distinctive subgroups of DLBCL: one with the germinal center B-cell gene expression signature and the other with the activated B cell-like gene expression signature. The t(14;18) was detected in 7 of 35 cases (20%). All 7 t(14;18)-positive cases had a germinal center B-cell gene expression profile, representing 35% of the cases in this subgroup, and 6 of these 7 cases had very similar gene expression profiles. The expression of bcl-2 and bcl-6 proteins was not significantly different between the t(14;18)-positive and -negative cases, whereas CD10 was detected only in the group with the germinal center B-cell expression profile, and CD10 was most frequently expressed in the t(14;18)-positive cases. This study supports the validity of subdividing DLBCL into 2 major subgroups by gene expression profiling, with the t(14;18) being an important event in the pathogenesis of a subset of DLBCL arising from germinal center B cells. CD10 protein expression is useful in identifying cases of DLBCL with a germinal center B-cell gene expression profile and is often expressed in cases with the t(14;18).     

Intra-familial prevalence of hepatitis B virologic markers in HBsAg positive family members in Nahavand, Iran

AIM: To determine the prevalence of hepatitis B in Nahavand and evaluate the HBsAg positive prevalence in families with a member who was confirmed to have HBV infection. METHODS: This study was performed in two phases. In the first phase, 1 824 subjects in Nahavand city were selected. The interviewers visited the houses of chosen families to fill the questionnaire and take the blood samples. All subjects signed an informed consent before interviews and blood sampling. The samples were evaluated for HBV virologic markers. In the second phase, 115 HBsAg-positive cases were enrolled and evaluated for HBV virologic markers. RESULTS: The prevalence of positive HBsAg in Nahavand was 2.3%. The most frequent relatives of index cases were sons and daughters (32.2% and 23.5% respectively). Twelve (11%) of all family members were HBsAg positive. Fifty (56.2%) were isolated HBsAb positive and only one person (2,5%) was isolated HBcAb positive. The higher rates of HBsAg marker were detected in the brothers (1-25%) and fathers (1-12.5%). The infection rate in husbands and wives of index cases was 10%. Only two (16.7%) of all HBsAg-positive participants reported previous HBV vaccination. CONCLUSION: The prevalence of intra-familial HBV infection is lower in Nahavand of Iran compared to other studies. More attention should be paid to HBV vaccination and risk-lowering activities.     

Fludarabine treatment of patients with chronic lymphocytic leukemia induces a p53-dependent gene expression response

Fludarabine, the current standard treatment for B-cell chronic lymphocytic leukemia (CLL), can induce apoptosis in CLL cells in vitro, and a number of molecular mechanisms contribute to its cytotoxicity. Using gene expression profiling, we investigated the molecular consequences of fludarabine treatment of patients with CLL in vivo. In 7 patients with CLL, a consistent gene expression signature of in vivo fludarabine exposure was identified. Many of the fludarabine signature genes were known p53 target genes and genes involved in DNA repair. In vitro treatment of CLL cells with fludarabine induced the same set of genes as observed in vivo, and many of these genes were also induced by in vitro exposure of CLL cells to ionizing radiation. Using isogenic p53 wild-type and null lymphoblastoid cell lines, we confirmed that many of the fludarabine signature genes were also p53 target genes. Because in vivo treatment with fludarabine induces a p53-dependent gene expression response, fludarabine treatment has the potential to select p53-mutant CLL cells, which are more drug resistant and associated with an aggressive clinical course. These considerations suggest that fludarabine treatment should be given in strict accordance to the current National Cancer Institute (NCI) guidelines that have established criteria of disease activity that warrant treatment.     

The effects of quercetin on the gene expression of the GABA<Subscript>A</Subscript> receptor α5 subunit gene in a mouse model of kainic acid-induced seizure

The flavonoid quercetin has recently been reported to have neuroprotective effects, and the role of the gamma-aminobutyric acid A alpha 5 subunit (GABA_A α5) receptor has been determined in some nervous system disorders. The aim of this study was to identify the molecular mechanism of the effect of quercetin administered at anticonvulsive doses on the expression of the GABA_A α5 receptor gene in kainic acid (KA)-induced seizures in mice. The experimental animals were divided into four groups: control, KA, and KA + quercetin at 50 or 100 mg/kg, respectively. The results showed a dose-dependent reduction in the behavioral seizure score with quercetin pre-treatment in the KA mouse model. Two hours after the end of the 7-day treatment regimen, expression of the GABA_A α5 receptor gene in the hippocampus was found to be increased in the KA group, but this increase was reduced in the KA + quercetin 50 or 100 mg/kg treatment groups. These results suggest that expression of the GABA_A α5 receptor could be a mechanism for reducing seizure severity or may be a marker of seizure severity. Further studies are necessary to clarify quercetin’s mechanism of action and the relation of GABA_A α5 receptor gene expression to seizure severity.