Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status

B-cell chronic lymphocytic leukemia (CLL) consists of 2 prognostic entities where cases with mutated immunoglobulin V(H) genes have better outcome than unmutated cases. V(H)-mutated CLLs display longer telomeres compared with unmutated cases and telomere length has been indicated to predict outcome, although the prognostic value of telomere length has not been fully established in CLL. We analyzed telomere length, V(H) gene mutation status, and clinical parameters in a large series of CLL. Telomere length was assessed by quantitative polymerase chain reaction (PCR), giving a very good correlation to telomere length estimated by Southern blotting (P < .001). The prognostic information given by mutation status (n = 282) and telomere length (n = 246) was significant (P < .001, respectively). Telomere length was a prognostic factor for stage A (P = .021) and stage B/C (P = .018) patients, whereas mutation status predicted outcome only in stage A patients (P < .001). Furthermore, mutated CLLs were subdivided by telomere length into 2 groups with different prognoses (P = .003), a subdivision not seen for unmutated cases (P = .232). Interestingly, the V(H)-mutated group with short telomeres had an overall survival close to that of the unmutated cases. Thus, by combining V(H) mutation status and telomere length, an improved subclassification of CLL was achieved identifying previously unrecognized patient groups with different outcomes.     

Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia

We recently identified a chronic lymphocytic leukemia (CLL) subgroup using the immunoglobulin variable heavy-chain (V(H)) gene V(H)3-21 with almost identical heavy-chain complementarity determining region 3s (HCDR3s) and preferential variable light-chain (V(L)) gene usage, suggesting recognition of a common antigen epitope in this subset. To further explore the B-cell receptors (BCRs) in CLL, we characterized 407 V(H) rearrangements amplified from 346 CLLs regarding V(H), diversity (D), and joining (J(H)) gene usage and performed multiple alignment of the HCDR3 sequences. These analyses revealed 3 small subsets (2 V(H)1-69 groups, 7 cases; and 1 V(H)1-2 group, 5 cases) with highly restricted HCDR3 features including identical V(H)/D/J(H) usage, HCDR3 lengths, and shared N-sequences, in addition to the V(H)3-21 group (22 cases). Furthermore, another 3 groups (9 V(H)1-3(+) cases, 3 V(H)1-18(+) cases, and 5 V(H)4-39(+) cases) had essentially identical V(H)/D/J(H) use and similar HCDR3 lengths but less conserved N-regions. Analysis in all 6 of these subgroups showed restriction in V(L) gene use, whereas no association between V(H) and V(L) usage was found in cases without HCDR3 similarities. Altogether, structurally similar HCDR3s associated with preferential V(L) gene usage implies selection of BCRs, especially in subsets showing high HCDR3 similarities, thus pointing to restricted antigen recognition sites and possibly involvement of specific antigens in CLL development.     

Echocardiographic detection of intimo-intimal intussusception in a patient with acute Stanford type A aortic dissection

Intimo-intimal intussusception is a very rare and unusual complication of type A dissections, typically noted on TEE exam. It has been reported in a few cases in the cardiothoracic surgical and radiology literature, and even more rarely in the cardiac anesthesia/TEE literature. This uncommon variation occurs in severe, acute, type A dissections when the ascending aortic intima circumferentially strips and detaches from the media and forms a tube-like structure which may either prolapse antegrade into the ascending aortic lumen or retrograde into the left ventricular (LV) outflow tract and LV cavity. Antegrade intussusceptions may be severe enough to partially or completely occlude the ostia of the innominate, left common carotid, and left subclavian arteries producing acute neurologic symptoms. Retrograde intussusceptions may severely impair LV filling in diastole, can worsen aortic insufficiency, mitral regurgitation, as well as produce occlusion of the coronary ostia and acute coronary ischemia. Here, we describe the incidental finding of a retrograde intussusception that was not visualized on computed tomography scan but by intraoperative TEE examination, in a patient with a severe, extensive type A dissection.     

Changes in human regional cerebral blood flow following hypertonic saline induced experimental muscle pain: a positron emission tomography study

Synphilin-1 interacts with alpha-synuclein, which has been implicated in the pathogenesis of Parkinson's disease (PD). By examination of their interactions quantitatively, with the use of the yeast two-hybrid beta-galactosidase assay, we find that the synuclein amino acid (aa) 1-65 region is sufficient for an interaction. A central domain of synphilin-1, aa 349-555, is both necessary and sufficient for an interaction with alpha-synuclein. We did not observe an effect of the synuclein A53T mutation, which causes one familial form of PD, on interactions with synphilin-1. However, the A30P mutation caused an increase in the interaction between the synuclein aa 1-65 fragment and the synphilin-1 central domain.     

Proximal muscle weakness and selenium deficiency associated with long term parenteral nutrition

A 33-yr-old white female with short bowel syndrome secondary to trauma was maintained on home parenteral nutrition for 4 yr when her plasma, red cell, white cell, and platelet glutathione peroxidase (GSHPx) activities were found to be extremely low, as were her plasma and red cell selenium levels. During her first year on parenteral nutrition she noted the onset of an inability to rise from a squatting position, rapid tiring when stair climbing, and weakness when attempting to lift large or moderately heavy objects. Treatment with 400 micrograms/d of selenious acid intravenously was associated with a disappearance of her symptoms and an increase in proximal muscle strength within 6 wk. The plasma and red cell selenium levels, and the plasma and white cell GSHPx activities rose to normal levels within 6 wk. Red cell GSHPx activity returned to normal by 3 mo.     

Assessment of left ventricular function from M-mode measurement of circumflex artery motion recorded by coronary angiography

OBJECTIVE: To evaluate the usefulness of M-mode measurement of circumflex artery motion (CAM) for assessment of left ventricular (LV) function. DESIGN: Seventy-two patients referred for coronary angiography and LV angiography were included. Ejection fraction (EF) was calculated from LV angiography and systolic and diastolic parameters of CAM were measured by M-mode from coronary angiography. Twenty-three patients, examined by echocardiography of mitral annulus motion (MAM) within 24 h before the angiographic examination, formed a subgroup for comparison between angiographic M-mode of CAM and echocardiographic M-mode of MAM. RESULTS: In addition to previous reported CAM amplitude and longitudinal fractional shortening (FSL) the maximal systolic velocity of CAM can be reliably recorded by M-mode. The diastolic indices, atrial contribution to the total amplitude and maximal early and late diastolic velocities, are also well monitored by M-mode of CAM in comparison with echocardiographic MAM. CONCLUSION: LV systolic and diastolic function can be assessed by M-mode of CAM.