Adopting a family approach to theory and practice: measuring distress in cancer patient-partner dyads with the distress thermometer

Objective: Significant others are central to patients' experience and management of their cancer illness. Building on our validation of the Distress Thermometer (DT) for family members, this investigation examines individual and collective distress in a sample of cancer patients and their matched partners, accounting for the aspects of gender and role. Method: Questionnaires including the DT were completed by a heterogeneous sample of 224 couples taking part in a multisite study. Results: Our investigation showed that male patients (34.2%), female patients (31.9%), and male partners (29.1%) exhibited very similar levels of distress, while female partners (50.5%) exhibited much higher levels of distress according to the DT. At the dyad level just over half the total sample contained at least one individual reporting significant levels of distress. Among dyads with at least one distressed person, the proportion of dyads where both individuals reported distress was greatest (23.6%). Gender and role analyses revealed that males and females were not equally distributed among the four categories of dyads (i.e. dyads with no distress; dyads where solely the patient or dyads where solely the partner is distressed; dyads where both are distressed). Conclusion: A remarkable number of dyads reported distress in one or both partners. Diverse patterns of distress within dyads suggest varying risks of psychosocial strain. Screening patients' partners in addition to patients themselves may enable earlier identification of risk settings. The support offered to either member of such dyads should account for their role- and gender-specific needs. Copyright © 2010 John Wiley ; Sons, Ltd.

Whole-exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow-up of a large family.

Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We utilized whole-exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPα. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mutant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow-up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-α to bind DNA and reduces transactivation, leading to acute myeloid leukemia.

Knock-out of Arabidopsis metal transporter gene IRT1 results in iron deficiency accompanied by cell differentiation defects

IRT1 and IRT2 are members of the Arabidopsis ZIP metal transporter family that are specifically induced by iron deprivation in roots and act as heterologous suppressors of yeast mutations inhibiting iron and zinc uptake. Although IRT1 and IRT2 are thought to perform redundant functions as root-specific metal transporters, insertional inactivation of the IRT1 gene alone results in typical symptoms of iron deficiency causing severe leaf chlorosis and lethality in soil. The irt1 mutation is characterized by specific developmental defects, including a drastic reduction of chloroplast thylakoid stacking into grana and lack of palisade parenchyma differentiation in leaves, reduced number of vascular bundles in stems, and irregular patterns of enlarged endodermal and cortex cells in roots. Pulse labeling with 59Fe through the root system shows that the irt1 mutation reduces iron accumulation in the shoots. Short-term labeling with 65Zn reveals no alteration in spatial distribution of zinc, but indicates a lower level of zinc accumulation. In comparison to wild-type, the irt1 mutant responds to iron and zinc deprivation by altered expression of certain zinc and iron transporter genes, which results in the activation of ZIP1 in shoots, reduction of ZIP2 transcript levels in roots, and enhanced expression of IRT2 in roots. These data support the conclusion that IRT1 is an essential metal transporter required for proper development and regulation of iron and zinc homeostasis in Arabidopsis.