Publications (8)40.07 Total impact
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Article: Large-cell transformation of a composite lymphoma.
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ABSTRACT: Composite lymphoma is a rarely reported entity, defined as two or more morphologically distinct types of lymphoma at the same anatomic site, occurring either synchronously or metachronously. Since 1978, about 100 case reports of composite lymphoma have been cited, many involving combinations of low-grade B-cell lymphomas. To our knowledge, no cases of large-cell transformation of composite lymphoma have yet been described. We report the case of a patient who presented with diffuse large B-cell lymphoma (DLBCL) fifteen years after successful treatment for a mature B-cell lymphoma. Reassessment of the patient's lymph node from 1995, using techniques not previously available, resulted in a revised diagnosis of composite lymphoma, comprising both follicular lymphoma (FL) and small lymphocytic lymphoma (SLL). Analysis of B-cell gene rearrangement studies using BIOMED-2-based PCR, and of t(14;18) rearrangements by both FISH and PCR, provided evidence that the DLBCL evolved from transformation of the composite lymphoma, specifically from its FL component. B-cell gene rearrangement studies also supported a clonal relationship between the FL and SLL components of the composite lymphoma.Experimental and Molecular Pathology 12/2010; 89(3):260-7. · 2.42 Impact Factor -
Article: Ménétrier's disease associated with Kaposi's sarcoma.
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ABSTRACT: Ménétrier's Disease is a giant fold gastropathy whose precise etiology has remained enigmatic. However, mucosal changes characteristic of Ménétrier's Disease have been linked to diverse pathologies, both infectious and malignant. Here, we describe a novel association: Ménétrier's mucosa developing on top of underlying Kaposi's Sarcoma. Two male patients, ages 24 and 31, with HIV/AIDS underwent gastric biopsies that demonstrated Kaposi's Sarcoma. When the former patient expired, a more complete postmortem histologic examination of his stomach was undertaken. For each patient, endoscopic findings at the time of biopsy revealed thickened gastric mucosa overlying the Kaposi's changes. Microscopically, this thickened mucosa comprised hyperplastic foveolar cells that extended to the muscularis mucosa, characteristic of Ménétrier's mucosa. In both cases, special stains confirmed this impression. Dissection of the 24 year-old patient's stomach at autopsy demonstrated that the Ménétrier's mucosa was limited to areas where there was underlying Kaposi's Sarcoma, and that this mucosa was not present when the underlying stroma was normal. Our findings indicate, therefore, an association between Ménétrier's mucosal changes and Kaposi's Sarcoma; such an association has not, to our knowledge, been described previously in the literature.Experimental and Molecular Pathology 10/2008; 85(3):160-4. · 2.42 Impact Factor -
Article: Metastatic patterns of cancers: results from a large autopsy study.
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ABSTRACT: Many studies have addressed metastatic patterns seen among various cancers. No recent studies, however, provide quantitative analyses of such patterns arising from a broad range of cancers based primarily on postmortem tissue analyses. To provide a quantitative description of metastatic patterns among different primary cancers based on data obtained from a large, focused autopsy study. Review of data from 3827 autopsies, performed between 1914 and 1943 on patients from 5 affiliated medical centers, comprising 41 different primary cancers and 30 different metastatic sites. Testicular cancers were most likely to metastasize (5.8 metastases per primary cancer), whereas duodenal cancers were least likely to do so (0.6 metastases per primary cancer). Preferred metastatic sites varied among the primary cancers analyzed. Overall, regional lymph nodes were the most common metastatic target (20.6% of total), whereas testes were the least common (0.1% of total). Not surprisingly, different primary cancers tended to metastasize, with differing frequencies, to different sites. These varying metastatic patterns might be helpful in deducing the origins of cancers whose primary sites are unclear at presentation.Archives of pathology & laboratory medicine 07/2008; 132(6):931-9. · 2.58 Impact Factor -
Article: CADASIL Notch3 mutant proteins localize to the cell surface and bind ligand.
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ABSTRACT: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a vascular dementia arising from abnormal arteriolar vascular smooth muscle cells. CADASIL results from mutations in Notch3 that alter the number of cysteine residues in the extracellular epidermal growth factor-like repeats, important for ligand binding. It is not known whether CADASIL mutations lead to loss or gain of Notch3 receptor function. To examine the functional consequences of CADASIL mutations, we engineered 4 CADASIL-like mutations into rat Notch3 and have shown that the presence of an unpaired cysteine does not impair cell-surface expression or ligand binding.Circulation Research 04/2002; 90(5):506-8. · 9.49 Impact Factor -
Article: Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2
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ABSTRACT: Proteins encoded by the fringe family of genes are required to modulate Notch signalling in a wide range of developmental contexts. Using a cell co-culture assay, we find that mammalian Lunatic fringe (Lfng) inhibits Jagged1-mediated signalling and potentiates Delta1-mediated signalling through Notch1. Lfng localizes to the Golgi, and Lfng-dependent modulation of Notch signalling requires both expression of Lfng in the Notch-responsive cell and the Notch extracellular domain. Lfng does not prevent binding of soluble Jagged1 or Delta1 to Notch1-expressing cells. Lfng potentiates both Jagged1- and Delta1-mediated signalling via Notch2, in contrast to its actions with Notch1. Our data suggest that Fringe-dependent differential modulation of the interaction of Delta/Serrate/Lag2 (DSL) ligands with their Notch receptors is likely to have a significant role in the combinatorial repertoire of Notch signalling in mammals.Nature Cell Biology 07/2000; 2(8):515-520. · 19.49 Impact Factor -
Article: Expression Patterns ofJagged, Delta1, Notch1, Notch2,andNotch3Genes Identify Ligand–Receptor Pairs That May Function in Neural Development
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ABSTRACT: Notchgenes encode receptors for a signaling pathway that regulates neurogenesis. TheDSL(Delta/Serrate/lag-2) genes encode ligands that bind and activate Notch.In situhybridization was used to determine the spatiotemporal expression of Notch1, Notch2, and Notch3, and the DSL ligands, Jagged and Delta1, in an effort to identify potential ligand–receptor pairs that function during development of the rat nervous system. Here we describe both distinct and overlapping expression patterns for these genes in neural progenitors that form both the central and the peripheral nervous systems. The punctate expression patterns we detected for Jagged and Delta1 are consistent with their role in mediating lateral inhibition, a process proposed to regulate neural determination. Furthermore, within the ventricular zone of the neural tube and retina, Jagged and Delta1 were expressed in complementary regions, suggesting that different DSL–Notch combinations may direct the development of distinct neural subtypes.Molecular and Cellular Neuroscience 8(1):14-27. · 3.66 Impact Factor -
Article: Fringe differentially modulates Jagged1 and Delta1 signalling throughNotch1 and Notch2
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Article: Ligand-Induced Signaling in the Absence of Furin Processing of Notch1
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ABSTRACT: Notch is a conserved cell surface receptor that is activated through direct contact with neighboring ligand-expressing cells. The primary 300-kDa translation product of the Notch1 gene (p300) is cleaved by a furin-like convertase to generate a heterodimeric, cell-surface receptor composed of 180- (p180) and 120- (p120) kDa polypeptides. Heterodimeric Notch is thought to be the only form of the receptor which is both present on the cell surface and able to generate an intracellular signal in response to ligand. Consistent with previous reports, we found that disruption of furin processing of Notch1, either by coexpression of a furin inhibitor or by mutation of furin target sequences within Notch1 itself, perturbed ligand-dependent signaling through the well-characterized mediator of Notch signal transduction, CSL (CBF1, Su(H), and LAG-1). Yet contrary to these reports, we could detect the full-length p300 Notch1 product on the cell surface. Moreover, this uncleaved form of Notch1 could suppress the differentiation of C2C12 myoblasts in response to ligand. Taken together, these data support our previous studies characterizing a CSL-independent Notch signaling pathway and identify this uncleaved isoform of Notch as a potential mediator of this pathway. Our results suggest a novel paradigm in signal transduction, one in which two isoforms of the same cell-surface receptor could mediate two distinct signaling pathways in response to ligand.Developmental Biology.
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Institutions
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2008
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Harbor-UCLA Medical Center
Torrance, CA, USA
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2000
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University of California, Los Angeles
- Department of Biological Chemistry
Los Angeles, CA, USA
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