bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous deletion enhances movement of a cucumber necrosis virus based chimera expressing the red clover necrotic mosaic virus movement protein gene†
Authors: Reade Ron , Delroux Karine , Macdonald Kim , Sit Tim L. , Lommel Steven A. , Rochon D’Ann 
Published: March 2003

SummaryThe 35‐kDa movement protein (MP) gene of red clover necrotic mosaic virus (RCNMV) and 3′ flanking sequence were inserted in a cucumber necrosis virus (CNV) deletion mutant lacking a large portion of the coding region for the MP. Nicotiana benthamiana plants inoculated with chimeric synthetic transcripts of the resulting hybrid cDNA clone (M5/RM2) developed both local and systemic symptoms and accumulated high levels of chimeric viral RNA. Reverse transcriptase polymerase chain reaction (RT‐PCR) and sequence analysis of viral RNA extracted from systemically infected leaves of four different plants revealed that in each plant a large portion (305, 308, 315 or 127 nts) of the 3′ terminus of the inserted sequence spontaneously deleted during infection. In three of the deletion derivatives, the truncated RCNMV MP open reading frame (ORF) was fused in‐frame with the remaining portion of the 3′ terminal region of CNV MP ORF. The movement efficiencies of M5/RM2, a cloned copy of one of the deletion derivatives (ClM5/RM2dd1), and a stop codon mutant of ClM5/RM2dd1 (ClM5/RM2dd1stop), which prevents translational fusion to the CNV MP, were compared and it was determined that deletion of RCNMV MP sequences in conjunction with fusion to CNV MP sequences increases the movement efficiency of the chimeric virus genome. Absence of the C‐terminal region of the RCNMV MP in RCNMV RNA‐2 abolished RCNMV movement. However, movement could be complemented in trans if cells were coinoculated with ClM5/RM2dd1. Complementation of RCNMV movement did not occur using ClM5/RM2dd1stop, suggesting a role for appended CNV MP sequences in movement of the RCNMV genome. The ability of the CNV replicase to delete unnecessary or deleterious RCNMV sequences and to append the required CNV MP sequences reinforces the role of RNA recombination in the adaptation and evolution of viral genomes.
De novo generation of Lettuce infectious yellows virus defective RNAs in protoplasts
Authors: Rubio Luis , Tian Tongyan , Yeh Hsin‐Hung , Livieratos Yannis , Falk Bryce W. 
Published: March 2003

Summary Lettuce infectious yellows virus (LIYV)‐infected plants contain a heterogeneous population of defective RNAs (D RNAs) derived from LIYV genomic RNA 2. To partly address how LIYV D RNAs are generated, in vitro synthesized transcripts corresponding to the LIYV genomic RNAs 1 and 2 were inoculated to protoplasts, and these were analysed for genomic and D RNAs. De novo generated D RNAs were readily detected by 48 h post‐inoculation. Furthermore, when separate aliquots from the same protoplast preparation were separately inoculated with aliquots of the same LIYV RNA 1 and RNA 2 transcript preparations, different D RNA populations were detected in each. Thus, different D RNAs arose de novo within separate protoplast samples. Nucleotide sequence analysis of some de novo LIYV D RNAs revealed that they have a similar structure to the LIYV D RNAs described previously from whole plants, and to those of other plant viruses, consisting of one large internal deletion of the LIYV genomic RNA 2, but retaining 5′ and 3′ terminal sequences. However, one of the LIYV D RNAs had two non‐contiguous internal deletions.
Expression of CD44 in premalignant and malignant Barrett's oesophagus
Authors: Lagorce‐Pages  , Paraf  , Dubois  , Belghiti  , FLÉjou  
Published: March 2003

Aims: To establish the prevalence of CD44 protein expression in a large surgical series of Barrett's adenocarcinoma and associated preneoplastic lesions and to correlate this expression with clinicopathological data and prognosis.Methods and results:CD44H and variants (V4/V5,V6) expression was detected by immunohistochemistry in formalin‐fixed, paraffin wax tissue samples of Barrett's mucosa (50) and Barrett's adenocarcinoma (73) obtained from surgical resections from 73 patients. This expression was correlated with pathological features of the tumour and prognosis. CD44H and V6 expression was found in 62% and 55% of Barrett's specialized mucosa negative for dysplasia and in 70% and 63% of Barrett's adenocarcinoma, respectively. CD44H and V6 expression was restricted to the lower part of the crypts in Barrett's specialized mucosa negative for dysplasia and reached the upper part of the crypts in high‐grade dysplasia. A significant relation was found between CD44V6 expression and depth of tumour invasion in the oesophageal wall (P = 0.05), neoplastic vascular invasion (P = 0.0001), neoplastic perineural invasion (P = 0.0004) and stage in Rosenberg's classification (P = 0.02). Cancers with CD44V6 expression had a significantly poorer prognosis (5‐year survival: 17%) than those without (5‐year survival: 44%) (P = 0.02) in univariate analysis. However, multivariate analysis showed that CD44V6 expression had no independent prognostic value when tumour invasion and lymph node involvement were taken as explanatory variables.Conclusion:CD44H and V6 are frequently expressed in Barrett's oesophagus. The pattern of expression that we observed from mucosa negative for dysplasia to adenocarcinoma suggests that CD44H and V6 may be involved in the carcinogenesis of Barrett's mucosa. CD44V6 expression in adenocarcinoma is correlated to aggressive pathological features.
Epithelioid cell granulomas in chronic hepatitis C: immunohistochemical character and histological marker of favourable response to interferon‐α therapy
Authors: Harada K , Minato H , Hiramatsu K , Nakanuma Y 
Published: March 2003

Aims: The clinicopathological significance of intrahepatic epithelioid cell granulomas in chronic hepatitis C was determined.Method and resultsGranulomatous lesions were surveyed in 542 liver biopsy specimens and were immunohistochemically examined. We also tested whether this lesion is a marker of response to interferon‐α therapy in chronic hepatitis C. Granulomatous lesions in hepatic lobules and/or portal tracts were identified in 11/542 (2%) cases with chronic hepatitis C. Granulomas were positive for HLA‐DR and β2‐microglobulin, and were surrounded by T‐cells. Among them, three chronic hepatitis C cases showed portal granulomas with mild biliary epithelial damage. Bile ducts showing mild epithelial damage in chronic hepatitis C were positive for β2‐microglobulin, but negative for HLA‐DR, while both antigens were frequently expressed in damaged bile ducts in primary biliary cirrhosis (PBC). All five cases of chronic hepatitis C with granulomas who had interferon‐α therapy and were followed up and were found to have responded well.ConclusionGranulomas showed the same immunohistochemical phenotypes, though the expression of HLA‐DR on bile ducts in PBC but not in chronic hepatitis C suggests a different pathogenesis. Granulomas may predict a favourable response to interferon‐α therapy in chronic hepatitis C.
Loss of laminin‐5 in the epithelium–stroma interface: an immunohistochemical marker of malignancy in epithelial lesions of the breast
Authors: Henning  , Berndt  , Katenkamp  , Kosmehl  
Published: March 2003

AimsTo demonstrate immunohistochemically the α3 and γ2 chain of laminin‐5 in benign epithelial and malignant lesions of the human breast.Methods and resultsThe α3 chain was identified by the monoclonal antibody BM165 and the γ2 chain by GB3 in shock frozen samples using APAAP (alkaline phosphatase monoclonal anti‐alkaline phosphatase) technique. The pre‐existing breast epithelium, the 12 benign ductal and lobular proliferations and the three fibroadenomas showed a continuous immunostaining in the basement membrane region. In contrast to benign epithelial lesions, the 44 cases of invasive breast carcinoma showed a loss of the laminin‐5 chains in more than 50% of the carcinoma stroma interface. Twenty‐four out of the 44 invasive carcinomas revealed a complete loss of laminin‐5 immunostaining. Focal defects of the laminin‐5 immunostaining were also found in ductal carcinoma in situ in its pure form.ConclusionsAs recently described, the malignant transformation of breast epithelium with expression of an invasive phenotype is associated with a decrease of hemidesmosomes. The reduced immunostaining of laminin‐5 is in line with this finding because laminin‐5 represents the major component of the anchoring filaments attaching hemidesmosomes to the basement membrane. We feel that immunohistochemical demonstration of laminin‐5 may serve as a marker of benignity in epithelial breast lesions. While other carcinoma types exhibit an increased laminin‐5 deposition, which has been suggested as an invasion promoting factor, the loss of laminin‐5 in breast cancer supports the view that breast carcinomas do not utilize laminin‐5 for invasion.
Blastic transformation of mantle cell lymphoma: genetic evidence for a clonal link between the two stages of the tumour
Authors: László  , Matolcsy  
Published: March 2003

AimsThe blastic variant of mantle cell lymphoma (MCL‐BV) may develop through histological transformation of mantle cell lymphoma (MCL). However, the clonal link between the tumour cells of MCL and transformed MCL‐BV has not been established at the genetic level. To investigate this link longitudinal molecular genetic studies have been performed in two cases of MCL that showed morphological transformation to MCL‐BV.Methods and resultsPolymerase chain reaction (PCR) and nucleotide sequence analyses of the complementary determining region 3 (CDR) of the immunoglobulin (Ig) heavy chain (H) gene were performed to identify clone‐specific rearrangements. In both cases, nucleotide sequence analysis revealed common clone‐specific IgH gene rearrangements in MCL and subsequent MCL‐BV.ConclusionsThese results provide genetic evidence for the common clonal origin of MCL and subsequently developed MCL‐BV.
The fraction of fields showing neoplastic tubules: a practical estimate of tubular differentiation in breast cancer
Authors: Kronqvist  , Kuopio  , Pirvu  , Collan  
Published: March 2003

AimsThe purpose of the study is to evaluate histological measurement methods for quantitative assessment of the degree of tubular differentiation in breast cancer.Methods and resultsWe evaluated tubular differentiation in 20 cases of invasive breast cancer by four different assessment methods. Method 1 was the traditional subjective evaluation of the amount of malignant tubules in each sample. Method 2 evaluated the fraction of fields presenting tubular differentiation by registering the presence or absence of neoplastic tubular structures in each microscopic field. In method 3 the area fraction of malignant epithelial cells presenting tubular differentiation was assessed field‐by‐field and expressed as an average of the whole tumour area. Method 4 applied point counting for evaluating the fraction of malignant epithelial cells in tubular structures. By correlation and reproducibility analyses, method 1 was inferior to the other methods. Method 4 was accurate but too laborious and time‐consuming for clinical use. Methods 2 and 3 were both efficient and reproducible and could be used interchangeably. With the time and effort used in the measurements taken into consideration method 2 was best applicable to clinical practice.ConclusionAccurate evaluation of tubular differentiation in breast cancer is possible by defining the presence or absence of tubular differentiation in microscopic fields of a histological section. Assessment of the fraction of fields with tubular differentiation (FTD) is simple, unambiguous, objective and fast − even a large sample can be screened in less than 10 min. In our results, FTD has clear advantages over subjective or point counting‐based evaluation methods of tubular differentiation.
Frequent presence of neuroendocrine small cells in thymic carcinoma: a light microscopic and immunohistochemical study
Authors: Kuo T‐t 
Published: March 2003

AimsNeuroendocrine differentiation has been described in conventional carcinomas of various organs. Small cells postulated to be neuroendocrine cells were observed previously in some thymic carcinomas. This study was conducted to confirm and characterize the presence of neuroendocrine small cells in thymic carcinomas by light microscopy and immunohistochemistry.Methods and resultsTwenty‐two thymic carcinomas were studied by light microscopy to detect the presence of small neuroendocrine‐like cells. They were found in four of 10 squamous cell carcinomas (SCC) and seven of eight adenosquamous carcinomas (ASC). No small cells were observed in three lymphoepithelioma‐like carcinomas (LELC) and one adenocarcinoma. The small cells were located within the tumour nests and constituted less than 1% of the entire tumour. In one case, small cells also extended outside the tumour nests. Rosette formation was seen in three cases. They were proved to be neuroendocrine cells by their immunoreactivity to neuron‐specific enolase, chromogranin A, and/or synaptophysin. A few scattered neuroendocrine small cells were found only by immunohistochemistry in one case each of SCC, ASC, and LELC. The small cells were also strongly positive for cytokeratin (CK) 8 and CK18 but negative for CK19 and CK20. The predominant carcinoma cells other than the neuroendocrine small cells also displayed neuroendocrine markers in 68% of the cases studied.ConclusionsNeuroendocrine small cells can be recognized by light microscopic examination in approximately 61% of thymic SCC and ASC. Neuroendocrine markers, CK8 and CK18 can aid in confirming their presence. The neuroendocrine small cells present in thymic carcinomas are different from the main carcinoma cells displaying immunohistochemical neuroendocrine markers. The presence of neuroendocrine small cells could be an useful marker for the differentiation of thymic carcinomas from thymomas and carcinomas of other sites.
Interrelationship between Epstein–Barr virus infection in gastric carcinomas and the expression of apoptosis‐associated proteins
Authors: Ishii H , Gobé G , Kawakubo Y , Sato Y , Ebihara Y 
Published: March 2003

Aims:Epstein–Barr virus (EBV) and its associated proteins may be protective against the occurrence of apoptosis that would normally inhibit cancer development and progression. Alternatively, the viral infection may cause altered or mutated expression of oncogenes or tumour suppressor genes that are necessary for tumour development, an action that may also involve apoptosis. In this study, a relationship was sought between occurrence of EBV infection, expression of apoptosis‐associated proteins (tumour suppressor gene p53 and oncogenes c‐myc and bcl‐2) and levels of cell death (apoptosis or necrosis) in 119 cases of gastric carcinoma.Methods and results:The EBV status of the gastric carcinomas (using the EBV‐encoded small RNA I (EBER‐1) and in‐situ hybridization), stage and grade of tumour and sex of patients were compared for bcl‐2, p53 and c‐myc expression patterns. EBER‐1 was detected in approximately 20% of cases studied. There was no significant correlation between levels of cell death in the tumour tissue and EBV status. In the protein analyses, development and progression of gastric carcinoma, with or without EBV infection, was independent of bcl‐2 expression. However, in gastric cancers with EBV infection, p53 overexpression was inhibited and c‐myc expression was increased in early stage cancers, in comparison with decreased c‐myc expression in late stage cancers.Conclusions:The p53 and c‐myc expression patterns indicate that EBV‐infected gastric carcinomas are less likely to have a natural regression via apoptosis at an early stage and explain, in part, the resistance to treatment of late stage of gastric cancers.
Increased microvessel density in malignant and borderline mammary phyllodes tumours
Authors: Tse G M K , Ma T K F , Chan K‐F , Law B K B , Chen M‐H , Li K‐H , Chan E C K , Mak M K F 
Published: March 2003

Increased microvessel density in malignant and borderline mammary phyllodes tumours Aims: Tumour vascularity is considered a prognostic indicator in breast carcinoma, but its utility in mammary phyllodes tumour has not been explored. The authors report the correlation between intratumoral microvessel density and the histological grade of phyllodes tumour. Methods and results: Forty cases of phyllodes tumour were reviewed for stromal cellularity, overgrowth, cytological pleomorphism, mitotic count and margin pattern. Using established criteria, these were diagnosed as benign (n=28), borderline (n=10) and malignant (n=2). Microvessel density was counted on CD31‐stained slides as the number of vessels per high power field. For benign phyllodes tumour, the range was 7–26.2 (mean 13.1); for borderline phyllodes tumour the range was 17.2–32.5 (mean 22.4); for malignant phyllodes tumour the range was 25.9–33.3 (mean 29.6). The difference between the benign and borderline groups was significant (P < 0.0001) but that between the borderline and malignant groups was not, due to the small number of malignant cases. Conclusions: There is a significant difference in stromal microvessel density between benign and borderline phyllodes tumour. Although the small number of cases of malignant phyllodes tumour limits further interpretation, we believe that microvessel density can be used as an additional objective histological parameter in the evaluation of phyllodes tumour.
Morphometric assessment of gastric antral atrophy: comparison with visual evaluation
Authors: Ruiz B , Garay J , Johnson W , Li D , Rugge M , Dixon M F , Fiocca R , Genta R M , Hattori T , Lechago J , Price A B , Sipponen P , Solcia E , Watanabe H , Correa P 
Published: March 2003

Morphometric assessment of gastric antral atrophy: comparison with visual evaluation Aims: As part of a multinational effort to reach a consensus in the definition and evaluation of atrophic gastritis, we applied morphometric techniques to 22 antral biopsy specimens examined visually by 12 experienced gastrointestinal pathologists. Methods and results: Atrophy was defined as loss of glands. Each pathologist graded atrophy with both non‐standardized and standardized approaches. Discriminant function analyses of morphometric measurements were conducted to validate and grade atrophy. Kappa statistics were used to compare the performance of each pathologist against the group mode and against the discriminant functions’ grading of atrophy. Three morphometric indexes showed significant differences among categories of atrophy utilizing non‐standardized as well as standardized visual atrophy grades: (i) the ratio of glandular length to total mucosal thickness; (ii) the proportion of the secretory compartment area occupied by glands; and (iii) the number of glandular cross sections per 40× microscopic field. The discriminant function analyses verified all cases classified visually as either non‐atrophic, or moderately/severely atrophic; it verified as mildly atrophic 40% of the cases classified visually as mildly atrophic; and classified the remaining 60% as moderately or severely atrophic. The κ statistics were good or excellent for the majority of pathologists. Conclusions: The evaluation of antral atrophy, simply defined as loss of glands, can be reliable and reproducible. The visual grading of atrophy as absent, moderate and severe is entirely consistent with objective morphometric observations.
Capsular intravascular endothelial hyperplasia: a peculiar form of vasoproliferative lesion associated with thyroid carcinoma
Authors: Tse L L Y , Chan I , Chan J K C 
Published: March 2003

Capsular intravascular endothelial hyperplasia: a peculiar form of vasoproliferative lesion associated with thyroid carcinoma Aims: Florid vasoproliferative processes are uncommon in the thyroid gland. We report three cases of an unusual vasoproliferation involving the capsular blood vessels of thyroid carcinoma. Methods and results: The histological diagnoses of the three cases were made on conventional histological sections. Two cases were minimally invasive follicular carcinomas and one case was an encapsulated variant of papillary carcinoma. Some blood vessels in the tumour fibrous capsule were filled with spindly cellular proliferations forming irregular vascular clefts and papillae. Immunohistochemical studies for CD31, CD34 and muscle‐specific actin confirmed that the spindly cells were mostly endothelial cells variably supported by pericytes. Conclusion: This peculiar intravascular endothelial hyperplasia by itself should not be mistaken for vascular invasion by tumour, but evidence of malignancy must be diligently sought by extensive sampling because the lesion has thus far been consistently associated with malignant thyroid neoplasms.
Prichard’s structures of the fossa ovalis are not histogenetically related to cardiac myxoma
Authors: Acebo E , Val‐Bernal J F , Gómez‐Román J J 
Published: March 2003

Prichard’s structures of the fossa ovalis are not histogenetically related to cardiac myxoma Aims: Cardiac myxomas are neoplasms of unknown histogenesis. They are thought to arise from hypothetical subendothelial vasoformative reserve cells or from primitive cells which reside in the fossa ovalis and surrounding endocardium. In 1951 Prichard described a kind of microscopic endocardial structure with a predilection for the interatrial septum, which were suggested to be related to cardiac myxomas. To confirm the existence of Prichard’s structures and to clarify their role in the genesis of cardiac myxomas, we examined histologically the fossa ovalis and we performed an immunohistochemical study of the endocardial abnormalities that were found. Methods and results: A prospective histological study of 100 interatrial septa and an immunohistochemical study of three out of the 12 endocardial abnormalities that were detected, as well as of four conventional cardiac myxomas were accomplished. Antibodies were used to vimentin, CD31, CD34, α‐smooth muscle actin, S100 protein, thrombomodulin, calretinin and c‐kit (CD117), a tyrosine kinase growth factor receptor for stem cell factor usually expressed by embryonic/fetal endothelium. Structures similar to the ones described by Prichard were found in 12% of septa, most of them in the left side of the fossa ovalis. The hearts with these structures were from patients 10 years older than the ones without them (72 ± 10 versus 62 ± 16 years, P=0.006). Immunohistochemically the cells comprising Prichard’s structures were positive for vimentin, CD31, CD34 and thrombomodulin, and negative for α‐smooth muscle actin, S100 protein, calretinin and c‐kit. Therefore these cells seem to be mature endothelial cells, but not primitive multipotential mesenchymal cells. Furthermore, these cells were not found in the atrial tissue from the bases of any of the conventional cardiac myxomas. Conclusions: Our study suggests that there is no apparent relation between Prichard’s structures and cardiac myxomas, and that Prichard’s minute endocardial deformities are age‐related phenomena.