Morphology of human T lymphocyte clones

Six human T lymphocyte clones, characterized as to cytolytic activities and several surface markers, were investigated for possible morphologic correlates of function. Cytotoxic T lymphocyte clones and natural killer-like clones had basically similar morphology, but cytotoxic T lymphocytes tended to cluster in groups and had many more lipid bodies, whereas natural killer-like cells had fewer intercellular contacts and had more and larger electron-dense bodies. Dense bodies were also quite prominent in noncytotoxic clones. The latter were distinctive in having a minority of very large cells (10 to 16 microns) with many microvilli, scattered among the majority of 5- to 8-microns diameter cells.     

6q deletions define distinct clinico-pathologic subsets of non- Hodgkin's lymphoma

Commonly observed in lymphoid neoplasms, deletions of 6q have been correlated with histologic and clinical subsets of non-Hodgkin's lymphoma (NHL). Our recent analysis of loss of heterozygosity of 6q loci in NHL showed two regions of minimal molecular deletion (RMD), an RMD1 at 6q25-27 and an RMD2 at 6q21-23. To establish correlations between these RMDs and regions of minimal cytogenetic deletions (RCDs) on 6q, and to define associations between RCDs and clinico-pathologic features, we have analyzed chromosome 6 abnormalities in 459 consecutively ascertained, karyotypically abnormal cases of NHL. Among these, 126 (27.5%) cases had structural abnormalities of chromosome 6, of which 94 were deletions. Analysis of these deletions identified three RCDs. An RCD1 encompassing 6q25-27 was seen in 45 intermediate- grade NHL. An RCD2 at 6q21 was observed in 11 high-grade NHL, 9 of which were of the immunoblastic subtype. An RCD3 at 6q23 was noted in 18 low-grade NHL lacking a t(14;18) translocation. Of these 18 cases, 12 were small lymphocytic NHL and, in 2 of these, del(6q) was the sole karyotypic abnormality. In 20 cases of low-grade NHL with t(14;18), the deletions spanned both RCD1 and RCD3. These data suggested the presence of at least 3 tumor suppressor genes on 6q within RCD1, RCD2, and RCD3; they also showed associations between RCDs in 6q and subsets of NHL, including a specific association between a group of well-differentiated lymphoid neoplasms and RCD3. The apparent heterogeneity of breakpoints when all NHLs are considered together explains the inability of previous studies to reliably establish correlations between recurring 6q deletions and histologic and clinical features of NHL.     

A gradient in the duration of the G1 phase in the murine neocortical proliferative epithelium

Neuronogenesis in the neocortical pseudostratified ventricular epithelium (PVE) is initiated rostrolaterally and progresses caudo- medially as development progresses. Here we have measured the cytokinetic parameters and the fractional neuronal output parameter, Q, of laterally located early-maturing regions over the principal embryonic days (E12-E15) of neocortical neuronogenesis in the mouse. These measures are compared with ones previously made of a medial, late- maturing portion of the PVE. Laterally, as medially, the duration of the neuronogenetic interval is 6 days and comprises 11 integer cell cycles. Also, in both lateral and medial areas the length of G1 phase (TG1) increases nearly 4-fold and is the only cell cycle parameter to change. Q progresses essentially identically laterally and medially with respect to the succession of integer cell cycles. Most importantly, from E12 to E13 there is a steeply declining lateral to medial gradient in TG1. The gradient is due both to the lateral to medial graded stage of neuronogenesis and to the stepwise increase in TG1 with each integer cycle during the neuronogenetic interval. To our knowledge this gradient in TG1 of the cerebral PVE is the first cell biological gradient to be demonstrated experimentally in such an extensive proliferative epithelial sheet. We suggest that this gradient in TG1 is the cellular mechanism for positionally encoding a protomap of the neocortex within the PVE.      

Outcomes of coronary artery bypass grafting versus percutaneous coronary intervention and medical therapy for multivessel disease with and without left ventricular dysfunction

Multiple randomized trials support the treatment of patients with multivessel coronary artery disease (CAD) and relatively normal left ventricular (LV) ejection fraction (EF) by either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). However, there has been a paucity of trials in the recent literature that have compared the outcomes of patients with multivessel CAD and low EF who undergo PCI or CABG. This review examines some of the clinical trials and series in this subgroup of patients and also compares the outcome of patients undergoing either procedure in the absence and presence of LV dysfunction. These trials and series support the notion that PCI can be successfully performed in patients with low EF with relatively low mortality, but that CABG is associated with greater freedom from repeat revascularization and from angina or congestive heart failure symptoms. In addition, most of the data published thus far indicate a long-term survival advantage among patients with ventricular dysfunction who have undergone CABG. Further studies, including randomized trials incorporating the evolving techniques of CABG and the recent advances in PCI, will be needed to assess the proper role and outcome of these two interventions.     

WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP)

Wiskott-Aldrich syndrome protein (WASP) is in a complex with WASP-interacting protein (WIP). WASP levels, but not mRNA levels, were severely diminished in T cells from WIP(-/-) mice and were increased by introduction of WIP in these cells. The WASP binding domain of WIP was shown to protect WASP from degradation by calpain in vitro. Treatment with the proteasome inhibitors MG132 and bortezomib increased WASP levels in T cells from WIP(-/-) mice and in T and B lymphocytes from two WAS patients with missense mutations (R86H and T45M) that disrupt WIP binding. The calpain inhibitor calpeptin increased WASP levels in activated T and B cells from the WASP patients, but not in primary T cells from the patients or from WIP(-/-) mice. Despite its ability to increase WASP levels proteasome inhibition did not correct the impaired IL-2 gene expression and low F-actin content in T cells from the R86H WAS patient. These results demonstrate that WIP stabilizes WASP and suggest that it may also be important for its function.