The multiple drug resistance gene,MDR1: Expression at the protein and RNA levels

A comparison of three different approaches to detect MDR₁ expression in myeloid leukemia cells was undertaken. With respect to the 4 different antibodies studied, a high proportion of false positive reactions were detected. Substantial discordance between MDR₁ expression as indicated by Northern blot analysis, PCR, and immunohistochemistry was found. These findings complicate the clinical interpretation of data derived from these methods.     

Darier's disease following radiotherapy for carcinoma of cervix

Darier-White disease is due to a defect in the ATP2A2 gene encoding the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2b). We report a case of carcinoma cervix in whom Darier's disease manifested after the initiation of radiation therapy. Conventional cytogenetics on peripheral blood revealed non-clonal constitutional autosomal and X chromosome abnormalities suggesting radiation induced gene toxicity. Occurrence of Darier's disease in our case could be due to treatment induced sustained differentiation in the Darier's affected skin by an unknown mechanism. Late onset or sporadic Darier's disease is the other possibility.     

Feeding Problems and Nutrient Intake in Children with and without Autism: A Comparative Study

Objective

To compare parent reported feeding difficulties and nutritional adequacy of children with Autism Spectrum Disorders (ASD) to an age and socio-economically matched group of typically developing children.

Methods

The scores on Children’s Eating Behavior Inventory (CEBI), three-day food records, anthropometric measures and adequacy of micro- and macro- nutrients were compared for 63 children diagnosed with ASD and 50 typically developing children enrolled from the department of pediatrics of a tertiary care teaching hospital from North India.

Results

The majority (79%) of the parents of ASD children reported some concern regarding their feeding behavior as compared to 64% of the parents of typically developing children. As compared to controls, ASD children had significantly higher CEBI scores (97.28 vs. 89.48, t = 3.15, P = 0.002) and more feeding problems (6.42 vs. 2.70, t = 3.74, P = 0.001). Relative to controls, ASD children consumed fewer number of food items (P = 0.022), particularly fruits (P = 0.004), vegetables (P = 0.011), and proteins (P = 0.015); had significantly lower daily intake of potassium (P = 0.001), copper (P = 0.007), and folate (P = 0.001). Although children with autism did not differ significantly from controls on intake of calories, height, weight, or body mass index, significantly greater proportion of ASD children failed to meet the estimated average requirement of thiamine (P = 0.039), vitamin C (P = 0.013), and copper (P = 0.005).

Conclusions

The findings underscore the need for comprehensive assessment and empirically-supported interventions for eating problems and dietary deficiencies found in ASD children.

     

Impact of parent and teacher concordance on diagnosing attention deficit hyperactivity disorder and its sub-types

Objective  This study examines the extent to which parents and teachers agree on the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) and its subtypes, as per the DSM IV criteria. It assesses whether the extent of agreement between informants improves by making the ADHD criteria more flexible. Methods  Parents and teachers of 119 clinic-referred sample of children (mean age=8.4 years, S.D= 2.48) with disruptive behavioral symptoms completed the Vanderbilt Attention Deficit Hyperactivity Disorder Diagnostic Parent and Teacher Rating Scales, respectively. Concordance of parent and teacher reports for the presence or absence of diagnosis of ADHD and type of ADHD was examined by percent agreement and the kappa statistics. Results  Of the 119 children referred for disruptive behavior disorders, 96 (80.6%) met criteria for any type of ADHD according to the parents’ report; and only 68 (57.1%) met criteria according to the teachers’ report. Parent and teacher agreement for the diagnosis of any type of ADHD was only 52% :(k= .11, n.s); and the agreement regarding diagnosis of sub-type was even poorer. Making the criteria more flexible vis-à-vis impairment or number of symptoms did not improve agreement between the informants. Conclusion  Clear guidelines are needed to reconcile the differences between informants in order to promote uniform diagnostic practices among clinicians working with children having ADHD.     

Over expression of brain and acute leukemia,cytoplasmic and ETS-related gene is associated with poor outcome in acute myeloid leukemia

The high expression of brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) has been reported to influence the outcome in acute myeloid leukemia (AML), but due to limited prospective studies, their role as prognostic factors is unclear. At diagnosis, the prognostic value of BAALC and ERG expression with respect to other cytogenetic and molecular markers was analyzed in 149 AML patients. Patients were divided into quartiles which resulted in the formation of four groups (G1–G4) based on expression values of BAALC and ERG and clinical response defined across groups. Groups with similar survival probabilities were merged together and categorized subsequently as high versus low expressers. Patients with high BAALC and ERG expression had significantly lower overall survival (OS; BAALC: p = 0.001 at 5 years 29.4% vs. 69.8%; ERG: p < 0.0001 at 5 years 4% vs. 50.4%) and disease-free survival (BAALC: p = 0.001 at 5 years 19.5% vs. 69.8%; ERG: p < 0.0001 at 5 years 4.2% vs. 47%). Patients were further stratified combining BAALC and ERG expression in an integrative prognostic risk score (IPRS). After a median follow-up of 54 months (95% CI 45–63 months) among survivors, IPRS for high versus low expressers was a significant predictor for OS (BAALC + ERG: 4% vs. 71.6%, p < 0.0001) and DFS (BAALC + ERG: 4.5% vs. 74.1%, p < 0.0001). In a multivariate model, IPRS of BAALC + ERG expression retained prognostic significance for OS (hazard ratio [HR] 2.96, 95%CI 1.91–4.59, p < 0.001) and DFS (HR 3.61, 95%CI 2.26–5.76, p < 0.001).     

Identification of a novel homozygous UNC80 variant in a child with infantile hypotonia with psychomotor retardation and characteristic facies-2 (IHPRF2)

Metabolic Brain Disease - The UNC80 gene encodes for a large component of the NALCN sodium-leak channel complex that regulates the basal excitability of the nervous system. In this study, we report...     

Autoimmunity against the β2 adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome

Complex regional pain syndrome (CRPS) is a painful condition affecting one or more extremities of the body, marked by a wide variety of symptoms and signs that are often difficult to manage because the pathophysiology is incompletely understood. Thus, diverse treatments might be ineffective. A recent report revealed the presence of autoantibodies against differentiated autonomic neurons in CRPS patients. However, it remained unclear how the antibodies act in the development of CRPS. We therefore aimed to characterize these antibodies and identify target antigens. Functional properties of affinity-purified immunoglobulin G of control subjects or CRPS patients were assessed using a cardiomyocyte bioassay. Putative corresponding receptors were identified using antagonistic drugs, and synthesized peptide sequences corresponding to segments of these receptors were used to identify the target epitopes. Chinese hamster ovary cells were transfected with putative receptors to ensure observed binding. Further, changes in the intracellular Ca²⁺ concentration induced by agonistic immunoglobulin G were measured using the Ca²⁺-sensitive fluorescent dye fura-2 assay. Herein, we demonstrate the presence of autoantibodies in a subset of CRPS patients with agonistic-like properties on the β₂ adrenergic receptor and/or the muscarinic-2 receptor. We identified these autoantibodies as immunoglobulin G directed against peptide sequences from the second extracellular loop of these receptors. The identification of functionally active autoantibodies in serum samples from CRPS patients supports an autoimmune pathogenesis of CRPS. Thus, our findings contribute to the further understanding of this disease, could help in the diagnosis in future, and encourage new treatment strategies focusing on the immune system.     

Ohtahara syndrome with biotinidase deficiency

Ohtahara syndrome is a rare epileptic encephalopathy in infants; the underlying etiology is generally thought to be structural brain malformations. The authors present a rare case of this type of epileptic encephalopathy in which a treatable metabolic condition such as biotinidase deficiency was suspected and diagnosed, and early institution of appropriate therapy led to a good clinical outcome.