bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD10 and Bcl10 expression in diffuse large B‐cell lymphoma: CD10 is a marker of improved prognosis
Authors: Ohshima K , Kawasaki C , Muta H , Muta K , Deyev V , Haraoka S , Suzumiya J , Podack E R , Kikuchi M 
Published: March 2003

CD10 and Bcl10 expression in diffuse large B‐cell lymphoma: CD10 is a marker of improved prognosis Aims: Diffuse large B‐cell lymphoma (DLBCL), the most common subtype of non‐Hodgkin’s lymphoma, is clinically and pathologically heterogeneous. The Bcl10 gene was recently isolated from the breakpoint region of t(1;14)(p22;q32) in mucosa‐associated lymphoid tissue (MALT) lymphomas, and is considered to be an apoptosis‐associated gene. CD10 is considered to be a marker of follicular centre B‐cell differentiation. To assess the clinical significance and roles of CD10 and Bcl10 in DLBCL, we analysed 138 cases, using immunohistochemical methods. Methods and results: CD10 expression was limited to the cytoplasm, whereas Bcl10 expression was detected in the cytoplasm and/or nuclei. CD10 expression was detected in 39 of 138 cases (28.2%), cytoplasmic Bcl10 in 68 cases (49.2%), and nuclear Bcl10 in 34 cases (24.6%). Nuclear Bcl10 was detected in 14 of 28 cases (50%) of extranodal DLBCL, but only 20 of 110 cases (18.2%) of nodal DLBCL. Cytoplasmic Bcl10 was detected in 19 of 28 cases (67.8%) of extranodal DLBCL and 49 of 110 cases (44.5%) of nodal DLBCL. CD10 expression closely correlated with improved survival (68% overall survival (OS) vs. 48% OS), but not with site of disease. A high International Prognostic Index (IPI) was considered to be a poor prognostic factor associated with a shorter OS. CD10 expression was detected in 27 of 84 cases (32.1%) with low‐risk IPIs, and in 12 of 54 cases (22.2%) with high‐risk IPIs. In the low‐risk group, cases expressing CD10 carried a better prognosis than CD10− cases (93% OS vs. 71% OS), whereas this was not the case in the high‐risk group (25% vs. 20%). Conclusions: Bcl10 expression was associated with extranodal DLBCL, but not with prognosis. CD10 expression was closely associated with improved survival, but not with risk as predicted by IPI. Overall, our results suggest that CD10 expression may be useful, in combination with clinical parameters, for determining the prognosis of DLBCL.
Intratumoral hypoxia resulting in the presence of a fibrotic focus is an independent predictor of early distant relapse in lymph node‐negative breast cancer patients
Authors: Colpaert C , Vermeulen P , Van Beest P , Goovaerts G , Weyler J , Van Dam P , Dirix L , Van Marck E 
Published: March 2003

Intratumoral hypoxia resulting in the presence of a fibrotic focus is an independent predictor of early distant relapse in lymph node‐negative breast cancer patients Aims: To examine the importance of a fibrotic focus—a scar‐like area in a carcinoma—as a marker of intratumoral hypoxia that correlates with angiogenesis and with clinical outcome in node‐negative breast cancer. Methods and results: One hundred and four T1–2N0M0 breast carcinoma patients were divided into two groups: group 1 (n=46) showing early distant relapse (median disease‐free survival 25 months) and group 2 (n=58) showing no evidence of disease (median follow‐up 91.5 months). All tumours were evaluated for medial/lateral location, size, histological grade, mitotic activity, necrosis, fibrotic focus, angiogenesis, vascular permeation and growth pattern. Multiple regression analysis showed that only histological grade and the presence of a fibrotic focus were independent predictors of early distant relapse. A fibrotic focus was present in 53% of the tumours. The relative size (fibrotic focus/tumour ratio) was significantly correlated with an unfavourable outcome. The presence of necrosis inside the fibrotic focus and the absolute and relative size of the fibrotic focus were significantly correlated with angiogenesis. A fibrotic focus was significantly associated with large, expansively growing tumours with high histological grade and numerous mitoses. Conclusion: A fibrotic focus can be used as a surrogate for quantifying angiogenesis and is an independent predictor of early metastasis in lymph node‐negative breast cancer.
A unique basal pattern of p53 expression in ulcerative colitis is associated with mutation in the p53 gene
Authors: Noffsinger A E , Belli J M , Miller M A , Fenoglio‐Preiser C M 
Published: March 2003

A unique basal pattern of p53 expression in ulcerative colitis is associated with mutation in the

p53

gene Aims: The p53 protein is implicated in the control of cell proliferation, differentiation, and death. As part of a study characterizing p53 alterations in colonic mucosa of patients with ulcerative colitis, we identified a unique pattern of basal p53 immunoreactivity. Methods and results: Tissue samples (n=180) from 42 ulcerative colitis patients were evaluated for p53 alterations by immunohistochemistry, loss of heterozygosity analysis, polymerase chain reaction‐single‐strand conformation polymorphism and direct sequencing. In addition, the expression of the p53‐ associated proteins p21waf1/cip1 and MDM2 was evaluated immunohistochemically. Three basic patterns of p53 immunoreactivity were observed: (i) isolated immunoreactive cells in the crypt bases; (ii) strongly positive cells confined to the basal half of the glands; and (iii) diffusely staining cells. The basal staining pattern was observed in both non‐neoplastic tissues and in some areas of dysplasia, and was associated with normal expression of p21waf1/cip1 in all cases, and with p53 mutation in seven of 11 cases. Conclusions: The basal pattern of p53 expression is associated with mutation in the p53 gene, and appears to be an early change in a subgroup of ulcerative colitis patients. The significance of this pattern of immunoreactivity and the mechanism by which it develops are discussed.
Combined examination of p27Kip1, p21Waf1/Cip1 and p53 expression allows precise estimation of prognosis in patients with gastric carcinoma
Authors: Liu X P , Kawauchi S , Oga A , Suehiro Y , Tsushimi K , Tsushimi M , Sasaki K 
Published: March 2003

Combined examination of p27Kip1, p21Waf1/Cip1 and p53 expression allows precise estimation of prognosis in patients with gastric carcinoma Aims: In order to estimate the prognostic values of p27Kip1, p21Waf1/Cip1, and p53, alone and in combination, we investigated immunohistochemically the expression of p27Kip1, p21Waf1/Cip1, and p53 proteins in gastric carcinomas. Methods and results: The expression of p27Kip1, p21Waf1/Cip1, and p53 was immunohistochemically examined in 140 gastric carcinomas. Positive expression of p27Kip1 and p21Waf1/Cip1 correlated significantly with a favourable prognosis (P < 0.05), whereas, positive expression of p53 tended to correlate with poor prognosis. Multivariate survival analysis revealed that TNM stage of tumour (P < 0.001), lymph node state (P=0.005), and p27Kip1 expression (P=0.006) were independent prognostic factors. A striking stratification of mortality rate was found when patients were divided into four groups according to the expression of p21Waf1/Cip1 and p27Kip1. The mortality rate was higher in patients with both p21Waf1/Cip1‐ and p27Kip1‐negative gastric carcinoma than in patients with one or both positive carcinomas (P < 0.01). In addition, if the four p21Waf1/Cip1/p27Kip1 groups were compared based on p53 status, p53+ cases tended to have a higher mortality rate than p53‐ cases. Conclusion: Our results suggest that low expression of both p27Kip1 and p21Waf1/Cip1 could be useful as markers of poorer prognosis, and the combined examination of p27Kip1, p21Waf1/Cip1 and p53 expression allows reliable estimation of prognosis for patients with gastric carcinoma.
Expression of angiogenic factors and hypoxia inducible factors HIF 1, HIF 2 and CA IX in non‐Hodgkin's lymphoma
Authors: Stewart M , Talks K , Leek R , Turley H , Pezzella F , Harris A , Gatter K 
Published: March 2003

Expression of angiogenic factors and hypoxia inducible factors HIF 1, HIF 2 and CA IX in non‐Hodgkin's lymphoma Aims: Angiogenesis in solid tumour pathology is well established but less is known about its role in haematological malignancies. Our study investigated the immunohistochemical expression of a variety of angiogenic and hypoxic factors and microvessel densities on 110 cases of high‐ and low‐grade non‐Hodgkin's lymphomas and reactive lymphoid tissues. Methods and results: Expression of vascular endothelial growth factor (VEGF) was present in 82 (96%) of the non‐Hodgkin's cases and 35 (100%) of the reactive lymphoid tissue cases. Both hypoxia inducible factors 1α and 2α (HIF 1α, 2α) were weakly expressed in the majority of high‐ and low‐grade lymphomas. Carbonic anhydrase IX (CA IX), a HIF‐inducible membrane‐bound enzyme, expression was not abundant with membranous staining being present in seven (8%) of the lymphoma cases and none of the reactive cases. Thymidine phosphorylase (TP) was distributed amongst macrophages and follicular dendritic cells but was not present in the neoplastic population. The vasculature was stained using CD34 which gave rise to a distinct vascular, predominantly paracortical network present in low‐grade lymphomas and reactive lymphoid tissue but which was lost in high‐grade lymphomas. Conclusion: Our results suggest that non‐Hodgkin's lymphomas may be less angiogenic and hypoxically driven than most solid tumours, which has implications for possible future therapies.
Can pulmonary sclerosing haemangioma be accurately diagnosed by intra‐operative frozen section?
Authors: Chan A C L , Chan J K C 
Published: March 2003

Aims:  Pulmonary sclerosing haemangioma is a rare benign tumour with a characteristic variegated histological pattern. In this retrospective study we aimed to identify features that can aid in making a correct diagnosis and avoiding potential pitfalls at the time of intra‐operative frozen section.Methods and results:  Twenty cases of pulmonary sclerosing haemangioma with intra‐operative frozen section were reviewed. The four major histological patterns (solid, sclerotic, papillary and haemorrhagic) were found in various combinations in the frozen sections. In 17 cases, three or more patterns were present. There could be focal areas mimicking epithelioid haemangioendothelioma or carcinoid tumour. Intra‐operative imprint/scrape cytology served as a helpful adjunct in confirming the cytological blandness, although occasional atypical cells could be present. An intra‐operative frozen section diagnosis of ‘sclerosing haemangioma’ or ‘benign tumour’ was given in 14 cases; the diagnosis was deferred in six cases. Retrospective analysis of the deferred cases showed that a definitive intra‐operative diagnosis could have been made in three, because three or more major histological patterns were present. One case showed a pure papillary pattern at frozen section, mimicking the appearance of papillary adenocarcinoma (primary or secondary), bronchioloalveolar carcinoma, epithelioid mesothelioma or papillary adenoma; two tumours from a patient with multicentric disease showed widespread significant cytological atypia in the tumours raising a serious consideration of malignancy.Conclusion:  A diagnosis of pulmonary sclerosing haemangioma can be made at intra‐operative frozen sections in most cases based on the tumour circumscription and variegated histological patterns. When only a single histological pattern is identified or when there is significant cytological atypia, distinction from other tumours can be problematic, and the diagnosis is best deferred.
Unusual sclerosing haemangiomas and sclerosing haemangioma‐like lesions, and the value of TTF‐1 in making the diagnosis
Authors: Nicholson A G , Magkou C , Snead D , Vohra H A , Sheppard M N , Goldstraw P , Beddow E , Hansell D M , Travis W D , Corrin B 
Published: March 2003

Aims:  Sclerosing haemangiomas typically comprise a mixture of four architectural patterns (papillary, sclerotic, solid and haemorrhagic) and two cell types, eosinophilic cuboidal epithelial lining cells and sheets of rounded cells with either eosinophilic or clear cytoplasm. In most instances, recognition of these architectural and cytological features provides sufficient evidence for diagnosis. This study presents and discusses the histogenesis of four cases where difficulties in diagnosis were encountered, and reports the value of the antibody TTF‐1 in making the diagnosis.Methods and results:  Four cases with focal areas reminiscent of sclerosing haemangioma were reviewed and immunostained with an antibody panel including antibodies to TTF‐1 and surfactant apoprotein A. Of these, one case was classified as sclerosing haemangioma combined with typical carcinoid, in which there was a mediastinal lymph node metastasis solely comprising the solid component of sclerosing haemangioma. The second was classified as an alveolar adenoma with sclerosing haemangioma‐like areas. In the remaining two cases, diagnosis was confounded by presentation with predominantly cystic masses, the largest 70 mm in diameter. Immunohistochemically, TTF‐1 was of greater value than surfactant apoprotein, in particular in identifying the solid component of sclerosing haemangioma when this was solely present.Conclusion:  Sclerosing haemangiomas should be considered in the differential diagnosis of cystic pulmonary masses. They may also present histologically as combined tumours and metastasize to mediastinal nodes, indicating an, albeit low, malignant potential. TTF‐1 is a valuable antibody in identifying the presence of a sclerosing haemangioma when typical features are absent.
The value of ‘mesothelium‐associated’ antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas
Authors: Osborn M , Pelling N , Walker M M , Fisher C , Nicholson A G 
Published: March 2003

Aims: Despite increasing usage of mesothelium‐associated antibodies in diagnosis, a meta‐analysis of studies analysing these antibodies in relation to distinguishing mesothelioma from renal cell carcinoma shows a paucity of published data. Given the clinical importance of elucidating this differential diagnosis, we compared the phenotypes of these two tumours using a panel of antibodies comprising recently described ‘mesothelium‐associated’ antibodies and the more established ‘epithelium‐associated’ antibodies.Methods and results: We applied an antibody panel comprising calretinin, cytokeratin (CK)5/6, thrombomodulin, carcinoembryonic antigen (CEA), BerEP4 and BCA225 to 37 cases of pleural mesotheliomas and 40 cases of renal cell carcinoma (27 primary tumours and 13 metastatic to the pleura). All mesotheliomas were either purely epithelioid or of mixed type. Cases of renal cell carcinoma were graded and classified as to cell type and architecture. For mesotheliomas, 0% stained for CEA, 16% for BerEP4, 83% for BCA225, 78% for CK5/6, 86% for thrombomodulin and 97% showed nuclear staining for calretinin. For renal cell carcinomas, 0% stained for CEA, 50% for BerEP4, 88% for BCA225, 5% for CK5/6, 32% for thrombomodulin and 10% showed nuclear staining for calretinin.Conclusion: Calretinin, CK5/6 and BerEP4 appear the most useful antibodies in helping to distinguish between renal cell carcinomas and mesotheliomas, although BerEP4 was not particularly sensitive for renal cell carcinomas. Thrombomodulin was not as specific as the other ‘mesothelium‐associated’ antibodies in this study, reflecting how staining for mesothelium‐associated antibodies varies in carcinomas from different primary sites, and such variations should be taken into account when assessing the differential diagnosis of mesothelioma. In cases where doubt remains over distinguishing metastatic renal cell carcinoma from mesothelioma, data from such a panel should be viewed with caution and assessed in association with clinical, imaging and morphological features.
Intestinal IgA plasma cells of the B1 lineage are IL‐5 dependent
Authors: Bao S. , Beagley K. W. , Murray A. M. , Caristo V. , Matthaei K. I. , Young I. G. , Husband A. J. 
Published: March 2003

Two lineages of B cells, designated B1 and B2 cells, have been identified based upon their origins, anatomical distribution, cell surface markers, antibody repertoire and self‐replenishing potential. B1 cells are maintained by self‐renewal of cells resident in the peritoneal cavity (PerC) and they utilize a limited repertoire of germline V‐region genes, mostly directed against ubiquitous bacterial antigens such as phosphoryl choline (PC). B2 cells are replenished from bone marrow precursors and use a larger repertoire of immunoglobulin V‐region genes. Whereas most immunoglobulin A (IgA) plasma cells in the intestine derive from B2 lineage precursors in the Peyer’s patch, a subpopulation of Per C‐derived B1 cells populate the intestinal lamina propria where they mature into IgA plasma cells. In previous in vivo studies we have shown that whereas IgA+ B2 cells are interleukin (IL)‐6 dependent, B1 cells are IL‐6 independent. In view of the in vitro evidence that IL‐5 is also involved in IgA expression, in the studies reported here we have used IL‐5‐deficient mice to evaluate the role of IL‐5 in vivo in IgA expression in the gut. The results demonstrate that although total IgA cell numbers are only marginally depressed in IL‐5‐deficient mice, there is a marked selective depletion of IgA+ cells of the B1 lineage in the gut and a corresponding depression in the capacity of these mice to mount an intestinal response to a B1 antigen (PC) but not to a B2 antigen (oralbumin; OVA), reflecting intact B2‐derived IgA cell function but a defect in the B1 cell contribution to IgA responses in IL‐5 deficient mice. Collectively these data demonstrate differential cytokine regulation of subsets of IgA+ cells in the gut in that IgA+ cells of the B2 lineage are IL‐6 dependent but IL‐5 independent, but B1‐derived IgA+ cells are IL‐5 dependent and IL‐6 independent.PerC, peritoneal cavity OVA, ovalbumin Ars, arsanilic acid HBBS, Hanks balanced salt solution LPL, lamina propria lymphocytes PE, phycoerythrin AOCC, anti‐OVA containing cells IPP, intra‐Peyer’s patch.
C57BL/6 mice are more susceptible to antigen‐induced pulmonary eosinophilia than BALB/c mice, irrespective of systemic T helper 1/T helper 2 responses
Authors: Morokata T. , Ishikawa J. , Ida K. , Yamada T. 
Published: March 2003

SummaryInflammatory response differences between C57BL/6 and BALB/c mice following ovalbumin (OVA) sensitization and a single challenge were investigated. Serum immunoglobulin (Ig)E and IgG1 levels were higher in C57BL/6 mice than in BALB/c mice. In contrast, IgG2a levels in C57BL/6 mice were lower than in BALB/c mice. Furthermore, the number of eosinophils infiltrating into lungs in C57BL/6 mice was significantly higher than in BALB/c mice after OVA challenge. The levels of the T helper 2 (Th2)‐type cytokines interleukin (IL)‐4 and IL‐5, generated in challenged C57BL/6 lung tissue, were also higher than in BALB/c lung tissue. The participation of IL‐4 and IL‐5 in the induction of eosinophil infiltration into the lungs was confirmed in both strains of mice by injection of anti‐IL‐4 and anti‐IL‐5 monoclonal antibodies (mAbs). However, following OVA stimulation, in vitro IL‐4 and IL‐5 production in splenocyte cultures from C57BL/6 mice was lower than in splenocyte cultures from BALB/c mice. These results indicate that C57BL/6 mice induce Th2‐type responses in the lungs, while BALB/c mice induce T helper 1 (Th1)‐type responses in the lungs, despite considerable production of IL‐4 and IL‐5 from splenocytes. Therefore, local immune responses are more important in the induction of allergic inflammation in the lungs and are different from systemic immune responses, which are thought to depend on genetic background.
Mice transgenic for a soluble form of murine cytotoxic T lymphocyte antigen 4 are refractory to murine acquired immune deficiency sydrome development
Authors: De Leval L. , Debrus S. , Lane P. , Boniver J. , Moutschen M. 
Published: March 2003

SummaryInteractions between B and CD4+ T cells are central to the pathogenesis of retrovirus‐induced murine acquired immune deficiency virus (MAIDS). Prompted by previous work showing that treatment with cytotoxic T lymphocyte antigen 4 immunoglobulin (CTLA4Ig) partly inhibited the disease, we studied the course of infection in mice deficient for CD28–B7 interactions (mCTLA4‐Hγ1 transgenic mice). Despite a relative viral load identical to that of non‐transgenic mice, the transgenic mice did not develop any of the major MAIDS symptoms (i.e. lymphoproliferation and immune anergy). The mCTLA4‐Hγ1 did not however, completely inhibit B‐cell activation as indicated by a slight hypergammaglobulinaemia and microscopic blastic transformation. Absence of MAIDS in transgenic mice was associated with much lower levels of both interleukin‐4 and interferon‐γ transcripts following viral infection. These results support the theory that the CD28/B7 costimulatory pathway is a critical determinant to MAIDS development.
Regulation of murine dendritic cell functions in vitro by taurine chloramine, a major product of the neutrophil myeloperoxidase–halide system
Authors: Marcinkiewicz J. , Nowak B. , Grabowska A. , Bobek M. , Petrovska L. , Chain B. 
Published: March 2003

SummaryTaurine chloramine (TauCl) is a major chloramine generated in activated neutrophils as a result of the reaction of highly toxic hypochlorous acid and taurine, the most abundant free amino acid in cytosol. In this study we have tested the influence of TauCl on the properties of murine dendritic cells (DC), the major cell population involved in the initiation of an adaptive immune response against pathogenic organisms. N418+, MHC II+, B7‐2+ dendritic cells, generated from the mouse bone marrow cells cultured in the presence of granulocyte–macrophage colony‐stimulating factor, were stimulated by interferon‐γ and lipopolysaccharide to produce nitric oxide, reactive oxygen species, interleukin‐6 (IL‐6), tumour necrosis factor‐α, and IL‐12, in the presence of different doses of TauCl. TauCl differently inhibited the generation of these inflammatory mediators in a dose‐dependent manner. Furthermore, TauCl selectively modulated the ability of DC to induce the release IL‐2 and IL‐10 from T cells. These results suggest that neutrophil‐derived mediators, such as TauCl, at a site of inflammation, may affect the functions of sentinel DC and macrophages, and play a role in maintaining the balance between the inflammatory response and the induction of an antigen‐specific immune response.
Lack of activation induced cell death in human T blasts despite CD95L up‐regulation: protection from apoptosis by MEK signalling
Authors: Walker L. S. K. , Mcleod J. D. , Boulougouris G. , Patel Y. I. , Ellwood C. N. , Hall N. D. , Sansom D. M. 
Published: March 2003

SummaryThe generation of effective immunity requires that antigen‐specific T cells are activated, clonally expanded and ultimately eliminated by apoptosis. The involvement of CD95‐mediated apoptosis in T‐cell elimination is well established, but the conditions which regulate the death pathway under normal circumstances are still emerging. Using superantigen‐activated human T cells, we found that whilst T‐cell receptor (TCR) signalling triggered up‐regulation of CD95 ligand (CD95L), the majority of T cells were resistant to apoptosis induction, despite co‐expressing high levels of CD95. Resistance was maintained following direct antibody‐mediated cross‐linking of CD95 and was not confined to early time periods following activation. Our data implicate TCR‐derived signals in protection from apoptosis and reveal a role for the mitogen‐activated protein (MAP) kinase pathway by use of a MAP kinase kinase (MEK) inhibitor. Collectively these data demonstrate that resistance to activation‐induced cell death in human T cells is prolonged rather than transient, is not attributable to a lack of CD95L up‐regulation and is due, at least in part, to signalling via the MEK pathway.