Telomeric IGH losses detectable by fluorescence in situ hybridization in chronic lymphocytic leukemia reflect somatic VH recombination events

Routine interphase fluorescence in situ hybridization (FISH) analysis of chronic lymphocytic leukemia (CLL) with LSI IGH/CCND1 assay, applied to differentiate CLL from leukemic mantle cell lymphoma, identified a subset of cases (42/174) with translocation-like IGH signal pattern. To unravel the underlying 14q32/IGH aberrations, 14 of these cases were subjected to cytogenetic, detailed FISH, and V(H) mutation analyses. FISH identified cryptic losses of various portions of the IGHV region in all 14 cases. Fine mapping of these V(H) deletions revealed a strict correlation between their distal border and localization of the used VH gene, suggesting that they are not oncogenic but reflect physiological events accompanying somatic V-D-J assembly. This hypothesis was further supported by FISH analysis of 20 CLL and hairy cell leukemia cases with the known V(H) usage showing a constant loss of sequences proximal to the used gene, identification of V(H) deletions in normal B cells, and their exclusive demonstration in B cell malignancies, but not of T cell and myeloid linage. Given that these cryptic physiological VH losses in B cells may seriously complicate analysis of B cell leukemia/lymphoma and lead to false conclusions, FISH users should take them into consideration when interpreting IGH aberrations in these malignancies.     

Dislodgment of pacemaker electrode simulating focal motor seizure.

The unusual finding of dislocation of the electrode of a pacemaker in a patient caused repetitive twitching of the right leg. Initial confusion with focal motor seizure resulted in the administration of antiepileptic medication. Malposition of the electrode was confirmed by appropriate roentgenographic studies, and subsequent repositioning terminated the episode.     

Mantle cell lymphoma presenting as a breast mass.

Breast lymphoma accounts for less than 1% of all non-Hodgkin's lymphomas (NHLs) and approximately 0.1% of all breast neoplasms. Most breast lymphomas are classified as diffuse large B cell or mucosa associated lymphoid tissue (MALT) lymphomas. The case of a 53 year old woman presenting with a breast mass and found to have mantle cell lymphoma is described. Core biopsy of the breast lesion showed a B cell NHL, probably of large cell type and of high grade. Morphological and immunophenotypic analysis of peripheral blood and bone marrow samples suggested a mantle cell lymphoma (MCL). This was confirmed by the detection of a t(11;14) in the bone marrow aspirate and breast tissue by polymerase chain reaction analysis. There have been no previous reports of an MCL presenting as a breast lump. Because a diagnosis of MCL has prognostic and therapeutic implications, this case highlights the need for an awareness of MCL presenting in this way, and the requirement for specialised investigations in its detection.     

Multidrug resistance gene expression and ABCB1 SNPs in plasma cell myeloma

Multi-drug resistance (MDR) leads to impaired treatment efficacy in all forms of malignancy. The main forms of MDR are thought to be mediated by the substrate transporting actions of certain adenosine triphosphate binding cassette (ABC) transport proteins. The genes ABCB1, ABCB4, ABCC1, ABCG2 and LRP1 have been identified as the most prominent contributors to clinically significant MDR. To date, no study has investigated the expression of these genes in plasma cell myeloma (PCM), or attempted to relate their expression to the incidence of relapse and/or stage at presentation. Here, we show that ABCB4 may be a prominent mediator of tumour cell MDR within PCM. Additionally, there are three SNPs (rs1045642, rs2032582 and rs1128503) within the most widely studied of these genes, ABCB1, which have been suggested to have a potential impact on OS in PCM and which may form a haplotype in ABCB1. rs1045642 in ABCB1 appears to be the only SNP affecting OS within the PCM patients studied, with minimal linkage disequilibrium demonstrated between it and rs2032582 and rs1128503.     

Immunohistological studies of artiodactyl and teleost pituitaries with antisera to calcitonin

The pituitary glands of pigs, cows, sheep (artiodactyls), and trout and goldfish (teleosts) were studied by immunohistology for the presence of calcitonin with antisera specific for the respective thyroidal and ultimobranchial calcitonins of these species. The specificity of the antisera was demonstrated by the lack of reactivity with other pituitary hormones and by the lack of cross-reactivity among the three groups of biochemically distinct thyroidal or ultimobranchial calcitonins: (a) rat (and human), (b) artiodactyl, and (c) teleost. The antiserum to salmon (teleost) calcitonin demonstrated immunohistologically positive cells in the teleost pituitaries, but not in the pig, sheep, or cow pituitaries. The antiserum to porcine calcitonin demonstrated immunohistologically positive cells in the artiodactyl but not in the teleost (or rat) pituitaries. The human calcitonin antiserum, cross-reacting with rat thyroidal calcitonin and demonstrating immunohistologically positive cells in the rat pituitary gland, did not demonstrate immunohistologically positive cells in the artiodactyl or teleost pituitaries. These studies demonstrate the presence of immunoreactive pituitary calcitonin in teleosts and artiodactyls and the species and immunochemical specificity of this phenomenon.     

Demonstration by immunoperoxidase histochemistry of calcitonin in the anterior lobe of the rat pituitary.

We have demonstrated by a specific immunoperoxidase procedure the presence of calcitonin-containing cells in the rat pituitary gland. These cells are widely distributed throughout the anterior lobe and seem to constitute the entire population of cells of the intermediate lobe. No such cells were seen in the posterior lobe. The presence of calcitonin-containing cells in the pituitary provides novel implications about the physiological significance of this hormone.     

Hemispheric asymmetries in categorical perception of orientation in infants and adults

Orientation CP is the faster or more accurate discrimination of two orientations from different categories (e.g., oblique1 and vertical1) compared to two orientations from the same category (e.g., oblique1 and oblique2), even when the degree of difference is equated across conditions. Here, we assess whether there are hemispheric asymmetries in this effect for adults and 5-month-old infants. Experiment 1 identified the location of the vertical-oblique category boundary. Experiment 2, using a visual search task with oriented lines found that adult search was more accurate when the target and distractors were from different orientation categories, compared to targets and distractors of an equivalent physical difference taken from the same category. This effect was stronger for targets lateralized to the left visual field (LVF) than the right visual field (RVF), indicating a right hemisphere (RH) bias in adult orientation CP. Experiment 3, replicated the RH bias using different stimuli and also investigated the impact of visual and verbal interference on the category effect. Experiment 4, using the same visual search task, found that infant search was also faster when the target and distractors were from different orientation categories than the same, yet this category effect was stronger for RVF than LVF lateralized targets, indicating a LH bias in orientation CP at 5 months. These findings are contrasted to equivalent studies on the lateralization of color CP (e.g., Gilbert, Regier, Kay, & Ivry, 2005). The implications for theories on the contribution of the left and right hemispheres of the infant and adult brain to categorical computations are discussed.     

New complementary perspectives for inpatient physical function assessment: matched clinician-report and patient-report short form measures from the PROMIS adult physical function item bank

Quality of Life Research - To develop two item content-matched, precise, score-level targeted inpatient physical function (PF) short form (SF) measures: one clinician-reported, one...     

Regulation of P-fimbrial phase variation frequencies in Escherichia coli CFT073

Adherence of uropathogenic Escherichia coli to host tissue is required for infection and is mediated by fimbriae, such as pyelonephritis-associated pili (Pap). Expression of P fimbriae is regulated by phase variation, and to date, phase transition frequencies have been measured only for pap regulatory region constructs integrated into the E. coli K-12 chromosome. The aim of this work was to measure P phase transition frequencies in clinical isolates for the first time, including frequencies for the sequenced strain E. coli CFT073. P fimbriation and associated phase transition frequencies were measured for two E. coli clinical isolates and compared with levels for homologous pap constructs in E. coli K-12. Fimbriation and off-to-on transition frequencies were always higher in the clinical isolate. It was concluded that the regulatory inputs controlling papI expression are likely to be different in E. coli CFT073 and E. coli K-12 as (i) phase variation could be stimulated in E. coli K-12 by induction of papI and (ii) the level of expression of a papI::gfp(+) fusion was higher in E. coli CFT073 than in E. coli K-12. Furthermore, phase transition frequencies for the two E. coli CFT073 pap clusters were shown to be different depending on the culture conditions, indicating that there is a hierarchy of expression depending on signal inputs.