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91.
Early-onset gastric carcinomas display molecular characteristics distinct from gastric carcinomas occurring at a later age 总被引:5,自引:0,他引:5
Carvalho R Milne AN van Rees BP Caspers E Cirnes L Figueiredo C Offerhaus GJ Weterman MA 《The Journal of pathology》2004,204(1):75-83
Gastric cancer is thought to result from a combination of environmental factors and accumulation of specific genetic alterations, and consequently mainly affects older patients (>50 years of age). Fewer than 10% of patients present with the disease before 45 years of age and these young patients are thought to develop carcinomas with a different molecular genetic profile from that of sporadic carcinomas occurring at a later age. Forty early-onset gastric carcinoma resection specimens were characterized for microsatellite instability (MSI) and loss of heterozygosity status using 22 polymorphic microsatellite markers. Twenty-four biopsies were additionally evaluated for the presence of MSI. No MSI was observed in any of the cases analysed. Losses were infrequent, but were most common for the D1S234 (26.1%) and D1S1676 (17.4%) markers, flanking the RUNX3 gene; for the p53ALU (23.1%) and TP53 (15.4%) markers, near the TP53 gene; and for the D16S2624 (17.2%) marker, near the E-cadherin (CDH1) gene. All cases with loss of CDH1, as well as 6/7 cases with loss of TP53, displayed aberrant staining of the corresponding proteins, pointing to a functional role for these proteins in early-onset gastric carcinogenesis. No germline CDH1, TP53 or RUNX3 mutations were detected in any of the cases analysed. No correlation was observed between non-functional E-cadherin and the histological type of the tumours analysed. Finally, Epstein-Barr virus was not detected in any of the cases analysed. On the basis of these results, early-onset gastric carcinomas appear to have characteristics distinct from gastric carcinomas occurring at a later age. 相似文献
92.
Patients with semantic dementia, the temporal variant of frontotemporal dementia, are relevant to both the neuroanatomical and neuropsychological debates in the category-specific literature. These patients present with a selective and progressive semantic deficit consequent on circumscribed atrophy of the inferolateral polar temporal lobes bilaterally, including the inferotemporal gyrus. In this study, a patient KH with a significant advantage for artefacts over living things was compared to five other semantic dementia patients with commensurate levels of semantic impairment. KH demonstrated a consistent category difference in favour of artefacts across all the expressive and receptive semantic tests. This difference was reliable even when familiarity, frequency, and other potential confounding factors were controlled. While KH demonstrated an association between poor knowledge of sensory attributes and a consistently greater impairment on living things than artefacts, the other patients did not. As observed in a number of previous studies, all five of the patients, contrasted to KH, exhibited an advantage for functional/associative over sensory attributes but without demonstrating the category-specific deficit that the sensory-functional theory (and the locus of their atrophy) might predict. The results of this and other studies are discussed in relation to four accounts of category specificity: the sensory-functional theory, domain-specific knowledge systems, intercorrelated features, and individual differences. 相似文献
93.
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
94.
A 38-kilobase pathogenicity island specific for Mycobacterium avium subsp. paratuberculosis encodes cell surface proteins expressed in the host
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Stratmann J Strommenger B Goethe R Dohmann K Gerlach GF Stevenson K Li LL Zhang Q Kapur V Bull TJ 《Infection and immunity》2004,72(3):1265-1274
We have used representational difference analysis to identify a novel Mycobacterium avium subsp. paratuberculosis-specific ABC transporter operon (mpt), which comprises six open reading frames designated mptA to -F and is immediately preceded by two putative Fur boxes. Functional genomics revealed that the mpt operon is flanked on one end by a fep cluster encoding proteins involved in the uptake of Fe(3+) and on the other end by a sid cluster encoding non-ribosome-dependent heterocyclic siderophore synthases. Together these genes form a 38-kb M. avium subsp. paratuberculosis-specific locus flanked by an insertion sequence similar to IS1110. Expression studies using Western blot analyses showed that MptC is present in the envelope fraction of M. avium subsp. paratuberculosis. The MptD protein was shown to be surface exposed, using a specific phage (fMptD) isolated from a phage-peptide library, by differential screening of Mycobacterium smegmatis transformants. The phage fMptD-derived peptide could be used in a peptide-mediated capture PCR with milk from infected dairy herds, thereby showing surface-exposed expression of the MptD protein in the host. Together, these data suggest that the 38-kb locus constitutes an M. avium subsp. paratuberculosis pathogenicity island. 相似文献
95.
Eltoum IA Eloubeidi MA Chhieng DC Tamhane A Crowe R Jhala D St John KD Wilcox CM Siegal GP Vickers S Jhala NC 《American journal of clinical pathology》2005,124(5):697-707
Our objectives were to devise a cytologic grading system and determine whether it would predict survival of patients with solid-type pancreatic adenocarcinoma. We evaluated 116 consecutive patients from July 2000 to November 2002; they were followed up until September 2003. We scored the following features on rapid Romanowsky-stained endoscopic ultrasound-guided fine-needle aspiration smears: cell group architecture, single cells, nuclear grade, mucus, bizarre cells, and necrosis. A cytologic grade (low vs high) was assigned. The Kaplan-Meier estimate of 6-month survival was 76% (SE, 7%) for patients with low-grade tumors vs 50% (SE, 6%) for patients with high-grade carcinoma. The median survival for patients with low-grade vs high-grade tumors was 1 year vs 6 months, respectively (chi2 = 4.45; P = .035). Cox proportional hazards regression showed tumor stage, cancer-specific treatment, and cytologic grade to be independent predictors of survival (P = .001). No other factors (age, mass location, placement of stent, presence of concomitant chronic pancreatitis, race, sex) predicted survival. We devised a grading system that independently predicted survival in patients with pancreatic adenocarcinoma. 相似文献
96.
DeBerardinis RJ Medne L Spinner NB Zackai EH 《American journal of medical genetics. Part A》2005,(2):155-159
The DiGeorge anomaly (DGA) is an etiologically heterogeneous developmental field defect in which cardiovascular malformations, hypocalcemia, thymic hypoplasia, and characteristic dysmorphisms are major clinical features. The 22q11.2 deletion is the most common single etiology of DGA, although a number of other chromosomal abnormalities and teratogens, including maternal diabetes, have been implicated as well. We present a patient, born to a diabetic mother, with interrupted aortic arch type B (IAA-B), neonatal hypocalcemia, thymic hypoplasia, and dysmorphic features including microcephaly, thick, overfolded helices, and anteriorly-placed anus. Cytogenetic studies showed the presence of a marker chromosome, identified by fluorescence in-situ hybridization (FISH) as an isochromosome 18p [i(18p)]. We did not detect a 22q11.2 deletion by FISH using a cosmid probe corresponding to locus D22S75. The patient is the first example of either DGA or IAA-B in a patient with i(18p). We review the genetic abnormalities associated with DGA, and discuss the potential contributions of maternal diabetes and i(18p) in our patient. 相似文献
97.
Functional defects in the fanconi anemia pathway in pancreatic cancer cells 总被引:17,自引:0,他引:17
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van der Heijden MS Brody JR Gallmeier E Cunningham SC Dezentje DA Shen D Hruban RH Kern SE 《The American journal of pathology》2004,165(2):651-657
Biallelic BRCA2-mutations can cause Fanconi anemia and are found in approximately 7% of pancreatic cancers. Recently, several sequence changes in FANCC and FANCG were reported in pancreatic cancer. Functional defects in the Fanconi pathway can result in a marked hypersensitivity to interstrand crosslinking agents, such as mitomycin C. The functional implications of mutations in the Fanconi pathway in cancer have not been fully studied yet; these studies are needed to pave the way for clinical trials of treatment with crosslinking agents of Fanconi-defective cancers. The competence of the proximal Fanconi pathway was screened in 21 pancreatic cancer cell lines by an assay of Fancd2 monoubiquitination using a Fancd2 immunoblot. The pancreatic cancer cell lines Hs766T and PL11 were defective in Fancd2 monoubiquitination. In PL11, this defect led to the identification of a large homozygous deletion in FANCC, the first cancer cell line found to be FANCC-null. The Fanconi-defective cell lines Hs766T, PL11, and CAPAN1 were hypersensitive to the crosslinking agent mitomycin C and some to cis-platin, as measured by cell survival assays and G(2)/M cell-cycle arrest. These results support the practical exploration of crosslinking agents for non-Fanconi anemia patients that have tumors defective in the Fanconi pathway. 相似文献
98.
Number of C-bands of human isochromosome Xqi and relation to 45,X mosaicism 总被引:1,自引:1,他引:1
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Lillian Y. F. Hsu Sophie Paciuc Karen David Steluta Cristian Ralph Moloshok Kurt Hirschhorn 《Journal of medical genetics》1978,15(3):222-226
With combination of C and G banding techniques, three morphologically different types of isochromosome for the long arm of X (Xqi) have been identified, i.e. those with one C-band and symmetrical banding patterns of both arms, those with two C-bands and symmetrical banding patterns of two arms, and those with two C-bands but with asymmetrical banding patterns of two arms. The last type is a heterogeneous group with various different asymmetrical patterns. We have studied 6 cases of Xqi with C, G, and Q banding: 3 showed one C-band and symmetrical arms and all these were without 45,X mosaicism; the other 3 cases showed two C-bands, 2 of the cases having symmetrical arms and being mosaic for 45X/46,XXqi/47,XXqiXqi (those 2 were a pair of identical twins). One other had asymmetrical arms and was mosaic for 45,X/46,XXqi. Including our 6 cases, there have been a total of 30 reported cases of Xqi with C and G banding studies. Two-thirds of Xqi's were found to have 2 C-bands and one-third to have 1 C-band. Mosaicism was found in 85% of Xqi's with 2 C-bands and in only 44% of Xqi's with 1 C-band. Apparently, Xqi's with 2 C-bands have a greater tendency for anaphase lag and mitotic nondisjunction. Several possible mechanisms for the formation of the different types of Xqi's are discussed. 相似文献
99.
Delorenzi M Sexton A Shams-Eldin H Schwarz RT Speed T Schofield L 《Infection and immunity》2002,70(8):4510-4522
About 2.5 million people die of Plasmodium falciparum malaria every year. Fatalities are associated with systemic and organ-specific inflammation initiated by a parasite toxin. Recent studies show that glycosylphosphatidylinositol (GPI) functions as the dominant parasite toxin in the context of infection. GPIs also serve as membrane anchors for several of the most important surface antigens of parasite invasive stages. GPI anchoring is a complex posttranslational modification produced through the coordinated action of a multicomponent biosynthetic pathway. Here we present eight new genes of P. falciparum selected for encoding homologs of proteins essential for GPI synthesis: PIG-A, PIG-B, PIG-M, PIG-O, GPI1, GPI8, GAA-1, and DPM1. We describe the experimentally verified mRNA and predicted amino acid sequences and in situ localization of the gene products to the parasite endoplasmic reticulum. Moreover, we show preliminary evidence for the PIG-L and PIG-C genes. The biosynthetic pathway of the malaria parasite GPI offers potential targets for drug development and may be useful for studying parasite cell biology and the molecular basis for the pathophysiology of parasitic diseases. 相似文献
100.
Elliott AM Gonzales M Hoeffel JC Le Merrer M Maroteaux P Encha-Razavi F Joye N Berchel C Fliegel C Aughton DJ Beaudry-Rodgers K Hasteh F Nerlich AG Wilcox WR Rimoin DL Lachman RS Freisinger P 《American journal of medical genetics》2002,109(2):139-148
Neu-Laxova Syndrome (NLS) is a severe disorder with intrauterine growth retardation, edema, and characteristic face (including microcephaly with receding forehead, protuberant eyes, a flattened nose, deformed ears, cleft palate, and micrognathia). Ichthyosis is often present. Limb anomalies include hypoplastic fingers and syndactyly of fingers and toes. Patients are usually stillborn or die shortly after birth. We report five unrelated patients--four with atypical NLS and one with typical NLS. All five patients were stillbirths. Clinically, the atypical NLS patients showed a large skull; rhizo-, meso-, and acromelia; and hypoplasia of the metacarpals and phalanges. The feet were similarly affected. Radiographically, the atypical patients showed interpediculate narrowing and hypoplastic vertebral bodies. The long bones were stick-like, showing diaphyseal widening that spared the metaphyses and was more pronounced in the lower extremities. The ilia had a half-moon configuration with widening of the sacrosciatic notches. The ischia were vertical and the pubic bone was absent. The typical NLS patient showed microcephaly, normal vertebral body, and long bone ossification, but a pelvic configuration similar to that of the atypical NLS patients. The common and distinguishing clinical and radiographic features are reviewed. Scott et al. [1981: Am J Med Genet 9:165-175] described two patients with NLS with radiographic and clinical findings similar to patients 1-4 reported here. Patients 1-4 of this report lack the typical findings of NLS and likely represent a distinct lethal skeletal dysplasia. 相似文献