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61.
Abraham SC Wu TT Hruban RH Lee JH Yeo CJ Conlon K Brennan M Cameron JL Klimstra DS 《The American journal of pathology》2002,160(3):953-962
Acinar cell carcinomas (ACCs) are rare malignant tumors of the exocrine pancreas. The specific molecular alterations that characterize ACCs have not yet been elucidated. ACCs are morphologically and genetically distinct from the more common pancreatic ductal adenocarcinomas. Instead, the morphological, immunohistochemical, and clinical features of ACCs overlap with those of another rare pancreatic neoplasm, pancreatoblastoma. We have recently demonstrated a high frequency of allelic loss on chromosome arm 11p and mutations in the APC/beta-catenin pathway in pancreatoblastomas, suggesting that similar alterations might also play a role in the pathogenesis of some ACCs. We analyzed a series of 21 ACCs for somatic alterations in the APC/beta-catenin pathway and for allelic loss on chromosome 11p. In addition, we evaluated the ACCs for alterations in p53 and Dpc4 expression using immunohistochemistry, and for microsatellite instability (MSI) using polymerase chain amplification of a panel of microsatellite markers. Allelic loss on chromosome 11p was the most common genetic alteration in ACCs, present in 50% (6 of 12 informative cases). Molecular alterations in the APC/beta-catenin pathway were detected in 23.5% (4 of 17) of the carcinomas, including one ACC with an activating mutation of the beta-catenin oncogene and three ACCs with truncating APC mutations. One ACC (1 of 13, 7.6%) showed allelic shifts in four of the five markers tested (MSI-high), two (15.4%) showed an allelic shift in only one of the five markers tested (MSI-low), and no shifts were detected in the remaining 10 cases. The MSI-high ACC showed medullary histological features. In contrast, no loss of Dpc4 protein expression or p53 accumulation was detected. These results indicate that ACCs are genetically distinct from pancreatic ductal adenocarcinomas, but some cases contain genetic alterations common to histologically similar pancreatoblastomas. 相似文献
62.
Yin CC Lin P Carney DA Handy BC Rassidakis GZ Admirand JH Keating MJ Medeiros LJ 《American journal of clinical pathology》2005,123(4):594-602
We studied the clinicopathologic, immunophenotypic, and cytogenetic features of 26 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) associated with serum IgM paraprotein. The study group (16 men; 10 women; median age, 64 years; range, 40-82 years) represents approximately 2.5% of CLL/SLL cases at our institution. The paraprotein level ranged from 1 to 14 g/L (median, 4 g/L). Neoplasms in bone marrow were composed of small round lymphocytes arranged in nodular (n = 6), diffuse (n = 5), interstitial (n = 5), or mixed (n = 10) patterns. All cases were positive for monotypic surface immunoglobulin light chain, IgM/IgD, CD5, CD19, CD20, and CD23. CD11c (14/20 [70%]), CD79b (11/19 [58%]), FMC-7 (11/26 [42%]), CD22 (8/20 [40%]), and ZAP-70 (6/19 [32%]) were expressed in subsets of cases. Of 17 bone marrow specimens assessed by conventional cytogenetics, 6 were abnormal and 11 were diploid. The overall survival of this group (median follow-up, 24 months) was not significantly different from that for an age-, sex-and stage-matched group of 52 CLL/SLL patients without IgM paraprotein (P = .60). We conclude that CLL/SLL cases with serum IgM paraprotein are similar to other CLL/SLL cases in their clinicopathologic and immunophenotypic features. 相似文献
63.
Akari Inada Cameron Nienaber Sonya Fonseca Susan Bonner-Weir 《Developmental dynamics》2006,235(6):1571-1577
In the search for genetic markers for assessing the role of duct cells in pancreas growth, we examined whether carbonic anhydrase II (CAII) has ductal cell specificity. We determined the distribution and timing of CAII expression in mouse pancreas from embryonic stage to adult. The pancreatic ducts only start expressing CAII at embryonic day (E) 18.5, with increases after birth. Around E15.5, glucagon-positive cells, but not insulin-positive cells, also express CAII, with further increases by adult. CAII expression was restricted to cells within ductal structures and glucagon-positive cells with no colocalization with any insulin-positive cells at any time. In the human pancreas, CAII expression is restricted to the ducts. Furthermore, the activity of a 1.6-kb fragment of the human promoter with Luciferase assays was moderately strong compared with the cytomegalovirus promoter in human pancreatic duct cell line (PANC-1). Thus, we believe that the CAII gene could serve as a useful pancreatic duct cell marker. 相似文献
64.
Generation, annotation, evolutionary analysis, and database integration of 20,000 unique sea urchin EST clusters 总被引:2,自引:0,他引:2
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Poustka AJ Groth D Hennig S Thamm S Cameron A Beck A Reinhardt R Herwig R Panopoulou G Lehrach H 《Genome research》2003,13(12):2736-2746
Together with the hemichordates, sea urchins represent basal groups of nonchordate invertebrate deuterostomes that occupy a key position in bilaterian evolution. Because sea urchin embryos are also amenable to functional studies, the sea urchin system has emerged as one of the leading models for the analysis of the function of genomic regulatory networks that control development. We have analyzed a total of 107,283 cDNA clones of libraries that span the development of the sea urchin Strongylocentrotus purpuratus. Normalization by oligonucleotide fingerprinting, EST sequencing and sequence clustering resulted in an EST catalog comprised of 20,000 unique genes or gene fragments. Around 7000 of the unique EST consensus sequences were associated with molecular and developmental functions. Phylogenetic comparison of the identified genes to the genome of the urochordate Ciona intestinalis indicate that at least one quarter of the genes thought to be chordate specific were already present at the base of deuterostome evolution. Comparison of the number of gene copies in sea urchins to those in chordates and vertebrates indicates that the sea urchin genome has not undergone extensive gene or complete genome duplications. The established unique gene set represents an essential tool for the annotation and assembly of the forthcoming sea urchin genome sequence. All cDNA clones and filters of all analyzed libraries are available from the resource center of the German genome project at http://www.rzpd.de. 相似文献
65.
Active maintenance of sentence meaning in working memory: evidence from EEG coherences. 总被引:3,自引:0,他引:3
The active maintenance of sentence meaning in working memory was investigated using event-related electroencephalogram (EEG) coherences. Participants read a sentence, retained it for 2.5 s, and then verified a statement about its meaning. The sentences contained either three semantically related nouns or unrelated nouns and started either with a what phrase (WH sentences) or not (non-WH sentences), imposing either a high or low demand on verbal working memory. Comprehension accuracy showed an interaction of semantic relatedness and sentence type due to the presence of a relatedness effect (lower accuracy in the unrelated condition) in WH sentences but not in non-WH sentences. During the post-sentence retention interval, EEG coherences also displayed this interaction of relatedness and sentence type. A semantic relatedness effect was obtained in the WH sentences (high demand) but not in the non-WH sentences (low demand). In addition, compared to a pre-sentence baseline and sentence presentation, coherences increased in the 10-14 Hz band during retention and decreased in the 4-6 Hz band. These coherence changes spanned prefrontal and posterior brain regions, possibly reflecting increased synchronization in projection loops between attention control systems in prefrontal cortex and activated meaning representations in semantic memory in posterior cortex. These findings suggest that short-term retention of the meaning of a sentence involves active maintenance in a capacity-limited working memory, accompanied by a heightened inner direction of attention after sentence presentation. 相似文献
66.
D. K. Peters Angela Martin A. Weinstein J. S. Cameron T. M. Barratt C. S. Ogg P. J. Lachmann 《Clinical and experimental immunology》1972,11(3):311-320
Detailed studies of the complement system were carried out in fifteen patients with membranoproliferative glomerulonephritis. The findings of reduced levels of C3 and C7 and of circulating breakdown products of C3 in fresh plasma suggested in vivo complement activation. Low C3 levels were associated with the presence of a serum factor (the C3 nephritic factor C3NeF) which was capable of breaking down C3 in normal serum in vitro. Metabolic studies using radioactive iodine labelled C3 showed no evidence of accelerated in vivo breakdown of parenterally administered C3 suggesting that hypocomplementaemia is either maintained by diminished C3 synthesis or that accelerated catabolism is occurring in a pool that does not freely exchange with parenterally given C3. The C3 nephritic factor has so far only been identified in patients with membranoproliferative nephritis and is therefore of major diagnostic significance in patients with glomerular disease. 相似文献
67.
The contribution of synaptic input to input resistance was examined in 208 developing genioglossal motoneurons in 3 postnatal age groups (5-7 day, 13-16 day, and 18-24 day) using sharp electrode recording in a slice preparation of the rat brain stem. High magnesium (Mg(2+); 6 mM) media generated significant increases (21-38%) in both the input resistance (R(n)) and the first time constant (tau(0)) that were reversible. A large percent of the conductance blocked by high Mg(2+) was also sensitive to tetrodotoxin (TTX). Little increase in resistance was attained by adding blockers of specific amino acid (glutamate, glycine, and GABA) transmission over that obtained with the high Mg(2+). Comparing across age groups, there was a significantly larger percent change in R(n) with the addition of high Mg(2+) at postnatal days 13 to 15 (P13-15; 36%) than that found at P5-6 (21%). Spontaneous postsynaptic potentials were sensitive to the combined application of glycine receptor antagonist, strychnine, and the GABA(A) receptor antagonist, bicuculline. Application of either 10 microM strychnine or bicuculline separately produced a reversible increase in both R(n) and tau(0). Addition of 10 microM bicuculline to a strychnine perfusate failed to further increase either R(n) or tau(0). The strychnine/bicuculline-sensitive component of the total synaptic conductance increased with age so that this form of neurotransmission constituted the majority (>60%) of the observed percent decrease in R(n) and tau(0) in the oldest age group. The proportion of change in tau(0) relative to R(n) following strychnine or high magnesium perfusate varied widely from cell to cell and from age to age without pattern. Based on a model from the literature, this pattern indicates a nonselective distribution of the blocked synaptic conductances over the cell body and dendrites. Taken together, the fast inhibitory synapses (glycine, GABA(A)) play a greater role in determining cell excitability in developing brain stem motoneurons as postnatal development progresses. These findings suggest that synaptically mediated conductances effect the membrane behavior of developing motoneurons. 相似文献
68.
Endothelin receptor expression in human decidua 总被引:3,自引:1,他引:3
Kohnen G; Campbell S; Irvine GA; Church HJ; MacLachlan F; Titterington M; Cameron IT 《Molecular human reproduction》1998,4(2):185-193
The endothelins are signalling peptides that act via two receptors, ET(A)
and ET(B). In the human endometrium, endothelin receptors have been
demonstrated in glands and stroma and have been shown to vary during the
course of the menstrual cycle. The present study was undertaken to
determine whether or not expression of endothelin receptors changes during
pregnancy or after administration of exogenous progestagens. The expression
of the receptors was correlated with the appearance of basement membrane
components during decidualization of the endometrial stroma. Decidual
specimens (n = 15) were obtained during the first trimester of pregnancy
and 10 at term. Sixteen pairs of endometrial biopsies were obtained from
women with menorrhagia before and after exposure to exogenous progestagens.
A total of 15 hysterectomy specimens were used as controls for the
expression of stromal basement membrane proteins in the absence of
decidualization. Autoradiography was carried out with selective ligands for
ET(A) ([125I]-PD 151242) and ET(B) ([125I]-BQ3020). The distribution of
ligand binding was then compared with the distribution of laminin alpha2
light chain and collagen IV. ET(A), ET(B), laminin alpha2 light chain, and
collagen IV were expressed in stromal decidual cells in the first trimester
of pregnancy. ET(B) was also found on endometrial glandular epithelium.
Quantitative macro-autoradiography and multiple regression analysis
demonstrated a highly significant positive correlation (P < 0.001)
between expression of ET(B) and laminin alpha2 light chain. In the third
trimester qualitative examination suggested a reduction of ET(A) in the
stroma. Progestagen-induced decidua exhibited a similar pattern to that
found in first trimester decidua. This study has demonstrated up-regulation
of ET(B) during the progesterone- dependent process of decidualization and
suggests a paracrine or autocrine role for endothelins in the decidua.
相似文献
69.
Dominantly inherited tubular aggregate myopathy. 总被引:1,自引:0,他引:1
We report an unusual familial myopathy characterized morphologically by the presence of large tubular aggregates in all fibre types. Two patients, a father and daughter, presented with slowly progressive proximal weakness, limitation of eye movement, and Achilles tendon contractures. Serum creatine kinase was 5-10 times normal. Light microscopy revealed type I fibre predominance. Basophilic accumulations, which stained intensely with the NADH-TR reaction, were present in both fibre types. Electron microscopy revealed that these consisted of tightly packed parallel tubular arrays. These varied somewhat in their ultrastructural appearance and were classified accordingly as type I, II, and III tubular structures. The tubular aggregates appear to be derived from the sarcoplasmic reticulum. This report further supports the evidence of a distinct clinico-pathological entity of genetic origin. 相似文献
70.
Podocytic cytoskeletal disaggregation and basement-membrane detachment in puromycin aminonucleoside nephrosis. 总被引:8,自引:4,他引:8
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Puromycin aminonucleoside--(PAN) treated rats develop acute nephrotic syndrome, mimicking human minimal lesion disease. In PAN nephrosis, podocyte detachment from the glomerular basement membrane (GBM) is the most likely cause of massive proteinuria in this model. To elucidate further the mechanisms of PAN-induced cellular dysfunction, new methods were employed to visualize podocyte cytoskeletal aggregation and to measure fibrillar attachment to the GBM. Adult Sprague-Dawley rats (n = 4/group) received a single tail-vein injection of PAN (75 mg/kg). On days 1, 2, 3, and 5 following injection, 24-hour urine collections were obtained for creatinine clearance, albuminuria, and total proteinuria. Then kidneys from each group were fixed by perfusion. Podocytic cytoskeleton was visualized by scanning electron microscopy. Subepithelial GBM staining and attachment fiber number, observed on digitized images of transmission electron micrographs, were quantitated with computer-based density analysis. A significant reduction in attachment fiber number in the GBM lamina rara externa occurred by day 5. On scanning electron micrographs, the secondary and tertiary podocytic processes were observed to be formed by highly aggregated cytoskeleton, which became partially disaggregated by day 3, was totally absent by day 5, and normalized by day 20. Immunogold staining revealed that actin and vinculin localized to the tertiary podocytic processes in the normal state were dispersed into the cell body following PAN. Podocyte cytoskeletal disaggregation precedes, and detachment from the GBM occurs simultaneously with, the onset of massive proteinuria in the PAN model. 相似文献