The BCR-ABL1 kinase bypasses selection for the expression of a pre-B cell receptor in pre-B acute lymphoblastic leukemia cells

The BCR-ABL1 kinase expressed in acute lymphoblastic leukemia (ALL) drives malignant transformation of human pre-B cells. Comparing genome-wide gene expression profiles of BCR-ABL1+ pre-B ALL and normal bone marrow pre-B cells by serial analysis of gene expression, many genes involved in pre-B cell receptor signaling are silenced in the leukemia cells. Although normal pre-B cells are selected for the expression of a functional pre-B cell receptor, BCR-ABL1+ ALL cells mostly do not harbor a productively rearranged IGH allele. In these cases, we identified traces of secondary VH gene rearrangements, which may have rendered an initially productive VH region gene nonfunctional. Even BCR-ABL1+ ALL cells harboring a functional VH region gene are unresponsive to pre-B cell receptor engagement and exhibit autonomous oscillatory Ca2+ signaling activity. Conversely, leukemia subclones surviving inhibition of BCR-ABL1 by STI571 restore responsiveness to antigen receptor engagement and differentiate into immature B cells expressing immunoglobulin light chains. BCR-ABL1 kinase activity is linked to defective pre-B cell receptor signaling and the expression of a truncated isoform of the pre-B cell receptor-associated linker molecule SLP65. Also in primary leukemia cells, truncated SLP65 is expressed before but not after treatment of the patients with STI571. We conclude that inhibition of BCR-ABL1 reconstitutes selection for leukemia cells expressing a functional (pre-) B cell receptor.     

Impact of Balance Confidence on Daily Living Activities of Older People with Knee Osteoarthritis with Regard to Balance,Physical Function,Pain, and Quality of Life – A Preliminary Report

Objectives: The objective of this study was to explore the impact of balance confidence on different activities of daily living (ADL) in older people with knee osteoarthritis (OA).

Methods: Forty-seven consecutive participants with knee OA were included in this cross-sectional study. They were divided according to the results of the Activities-specific Balance Confidence (ABC) Scale into a group with a low level of confidence in physical functioning (ABC < 50, n = 22) and a group with moderate and high levels of confidence (ABC ≥ 50, n = 25).

Results: In the ABC < 50 group, the effect of pain on ADL, the physician’s global assessment of the disease, and the Western Ontario and McMaster Universities Osteoarthritis Index scores were significantly higher, while quality of life (Short form-36) was lower compared to the ABC ≥ 50 group. No significant difference was found between the two groups regarding the static and dynamic balance measurements.

Conclusions: Older people with knee OA who were less confident in their daily physical activities had more physical difficulties and a greater effect of pain on ADL, lower quality of life, and a higher physician’s global assessment, but no differences were obtained in balance tests.

Clinical Implications: In people with knee OA, decreased balance confidence is associated with more physical difficulties, an increased effect of pain on ADL, and lower quality of life. An improved awareness of decreased balance confidence may lead to more effective management of older people with knee OA by improving their mobility and QOL through rehabilitation. Furthermore, future research in that direction is warranted.     

Prevalence of mood and anxiety disorder in self reported irritable bowel syndrome (IBS). An epidemiological population based study of women

Background  

Irritable bowel syndrome (IBS) is commonly regarded as a functional disorder, and is hypothesized to be associated with anxiety and depression. This evidence mainly rests on population-based studies utilising self-report screening instruments for psychopathology. Other studies applying structured clinical interviews are generally based on small clinical samples, which are vulnerable to biases. The extant evidence base for an association between IBS and psychopathology is hence not conclusive. The aim of this study was therefore to re-examine the hypothesis using population-based data and psychiatric morbidity established with a structured clinical interview.     

Area-based socioeconomic status and mood disorders: cross-sectional evidence from a cohort of randomly selected adult women

Objective

Data suggest there are established socio-economic disparities associated with mental health although most research has focused on individual-level indicators of socio-economic position. The aim of this study was to investigate the association between mood disorders and area-based socio-economic status (SES), and whether both ends of the SES continuum experienced increased odds for a mood disorder.

Methods

Using a clinical interview (SCID-I/NP), psychiatric history was ascertained in a population-based sample of 1095 women (20–93 years) from the Barwon Statistical Division, south-eastern Australia. SES was determined by cross-referencing residential addresses with Australian Bureau of Statistics 2006 census data for the region and categorised into three groupings of low, mid, and upper SES. The Index of Economic Resources (IER), Index of Education and Occupation (IEO), and Index of Relative Socioeconomic Advantage/Disadvantage (IRSAD) were utilised. Lifestyle factors were self-reported.

Results

For IER, the low SES group had a 2.0-fold increased odds of a current mood disorder compared to the mid group, after adjustment for physical activity and current anxiety (OR = 2.0, 95% CI 1.0–4.1, p = 0.05). This pattern was similarly observed for IEO (OR = 1.8, 95% CI 0.9–3.7, p = 0.1) and IRSAD (OR = 1.6 95% CI 0.8–3.4, p = 0.2). Those within the upper SES group showed a non-significant increase in the odds of a current mood disorder compared to the mid-group; IER (OR = 1.4, 95% CI 0.8–2.5, p = 0.3), IEO (OR = 1.2, 95% CI 0.07–2.3, p = 0.5) and IRSAD (OR = 1.2, 95% CI 0.7–2.1, p = 0.6).

Conclusions

Women in the low SES category were most likely to have a mood disorder. Furthermore, being in an upper SES group may not be protective against mood disorders.     

MDR1 polymorphisms and response to azathioprine therapy in patients with Crohn's disease

BACKGROUND: To investigate the contribution of multidrug resistance 1 (MDR1) gene pharmacogenetics (G2677T/A and C3435T) to the efficacy of azathioprine in inducing remission in patients with Crohn's disease (CD). METHODS: A cohort of 327 unrelated Spanish patients with CD recruited from a single center was studied. All patients were rigorously followed up for at least 2 years (mean time, 11.5 years). A case-control analysis of MDR1 G2677T/A and C3435T SNPs and 2 loci haplotypes in 112 steroid-dependent CD patients treated with azathioprine was performed. Patients were classified on the basis of response to azathioprine. RESULTS: A total 76 patients treated with azathioprine for longer than 3 months were included. Remission was achieved in 42 CD patients (55.3%). A higher frequency of the 2677TT genotype was found in nonresponders than in responders (17.65% versus 7.14%; OR = 2.8; 95% CI; 0.6-12.1; P = 0.11). Nonresponders to azathioprine were found to have a higher frequency of the 3435TT genotype than did CD patients who had achieved clinical remission (17.64% versus 4.76%; OR = 4.3; 95% CI, 0.8-22.8; P = 0.06). The 2677T/3435T haplotype was also more abundant in nonresponders (29.4% versus 20.2%), whereas the 2677G/3435C haplotype was more frequent in responders (58.3% versus 47.1%). Lack of response to azathioprine therapy in CD patients was 1.8-fold greater in carriers of the 2677T/3435T haplotype than in carriers of the 2677G/3435C haplotype (OR = 1.8; 95% CI, 0.82-3.9; P = 0.14). CONCLUSIONS: The results of our study indicate higher frequencies of the 2677TT and 3435TT genotypes and the 2677T/3435T haplotype in CD patients who did not respond to azathioprine. Additional replications in independent populations would confirm the real impact of these polymorphisms in response to azathioprine therapy.     

Family processes and adolescent problem behavior: integrating relationship narratives into understanding development and change

OBJECTIVE: Mothers' relational schemas (RSs) regarding their adolescents were assessed using the Family Affective Attitude Rating Scale for coding 5-minute speech samples. The internal consistency and validity of positive RS and negative RS scales were also evaluated. METHOD: Data were collected from a multiethnic subsample of early-starting antisocial (n = 20) and successful (n = 20) urban adolescents and their families, using direct observations of parent-adolescent interactions, 5-minute speech samples, and questionnaires. RESULTS: The negative RS and positive RS scales were internally consistent, correlated reliably with critical and positive dimensions of 5-minute speech samples expressed emotion and with observed parent-adolescent interactions, and discriminated between antisocial and successful adolescents. Negative RS accounted for unique variance in adolescent antisocial behavior when controlling for previous problem behavior and observed coercion. A significant interaction was also found between negative RS and observed parent-adolescent dynamics when escalations in adolescent problem behavior were added to the model. CONCLUSIONS: RS narratives provided unique information in the prediction of adolescent antisocial behavior. RSs should be considered in the assessment of family dynamics and the design of interventions to prevent and treat adolescent behavior problems.     

The role of illness perceptions in patients with medical conditions

PURPOSE OF REVIEW: In this article we summarize recent investigations into the influence of illness perceptions on outcomes in patients with medical conditions. RECENT FINDINGS: Developments in assessment include the publishing of a new brief scale to assess illness perceptions and the examination of the relationship between patient drawings of their illness and outcomes. Recent studies in primary care highlight the importance of patients' beliefs and emotional responses to their illness as being important in influencing their satisfaction with the consultation, reassurance following negative medical testing and future healthcare use. Recent research shows illness perceptions to have associations with a number of outcomes in chronic illness including self-management behaviours and quality of life. As yet, however, few interventions have been developed designed to change illness perceptions and improve illness outcomes. Emerging areas of research include the application of illness perceptions to mental illness and genetic and risk factor testing. SUMMARY: Research on illness perceptions has confirmed that patients' beliefs are associated with important outcomes in a broadening range of illnesses and risk factor testing. New interventions based on this model have the potential to improve patient outcomes but have yet to be widely developed and applied.