bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spindle cell squamous carcinoma of the oesophagus: an analysis of 17 cases, with new immunohistochemical evidence for a clonal origin
Authors: Handra‐Luca A , Terris B , Couvelard A , Molas G , Degott C , Flejou J‐F 
Published: March 2003

Spindle cell squamous carcinoma of the oesophagus: an analysis of 17 cases, with new immunohistochemical evidence for a clonal origin Aims: To study the morphological and immunohistochemical characteristics of spindle cell squamous carcinoma of the oesophagus, in order better to understand the histogenesis of this tumour. Methods and results: In this study we analysed the morphological and immunohistochemical characteristics of 17 cases of spindle cell squamous carcinoma of the oesophagus. Most tumours were polypoid, but tumours with an ulcerated and infiltrative pattern were also observed. Histologically, most tumours were of superficial type, with a characteristic morphological aspect consisting of two types of tumour cells, i.e. differentiated squamous cells, and spindle cells with transition zones between the two components. On immunohistochemistry, the squamous cells were positive for cytokeratin and the spindle cells showed variable expression of cytokeratin, vimentin and smooth muscle actin. p53 protein was over‐expressed in 10 cases, both tumour cell types showing strong nuclear positivity. In most tumours, E‐cadherin was expressed in the squamous cells and absent in the spindle cells. Conclusions: The similar pattern of p53 protein expression in the two tumour cell types of spindle cell squamous carcinoma of the oesophagus suggests their common origin. The change in adhesion molecule expression with loss of E‐cadherin expression may be associated with the acquisition of spindle cell morphology by the squamous tumour cells.
Malignant peripheral nerve sheath tumours: high Ki67 labelling index is the significant prognostic indicator
Authors: Watanabe T , Oda Y , Tamiya S , Kinukawa N , Masuda K , Tsuneyoshi M 
Published: March 2003

Malignant peripheral nerve sheath tumours: high Ki67 labelling index is the significant prognostic indicator Aims: We investigated p53, Ki67, MDM2, and p21WAF1/CIP1 in order to evaluate its relationship with prognosis in malignant peripheral nerve sheath tumours (MPNST). Methods and results: In 49 cases of MPNSTs, the immunohistochemical studies of Ki67, p53, MDM2, p21WAF1/CIP1 and polymerase chain reaction single‐strand conformation polymorphism (PCR‐SSCP) with direct sequencing of p53 were performed with the formalin‐fixed paraffin‐embedded tissue. In 43 cases with survival data available, an evaluation of the prognostic significance of clinicopathological factors was also carried out. A high Ki67 labelling index (LI) (>25%) was correlated with a reduced survival rate in the 43 cases of MPNST (P=0.0106, log‐rank test). Furthermore, there was a significant correlation between the Ki67 LI and the immunohistochemical expression of p53 or MDM2. In 17 MPNST cases, PCR amplification of exons 5 through 8 of the p53 gene was successful. One case showed a base change of codon 240 (AGT→AGC), but translated amino acid (Ser) remained unchanged. Multivariate Cox analysis of our series showed that the association of von Recklinghausen’s disease, tumour depth, and the presence of rhabdomyoblasts (malignant triton tumour) each had an independent negative impact on overall survival. Conclusion: High Ki67 LI (>25%) was of significant prognostic value in MPNST.
Evidence for local immunosuppression and demonstration of c‐myc amplification in pyothorax‐associated lymphoma
Authors: Yamato H , Ohshima K , Suzumiya J , Kikuchi M 
Published: March 2003

Evidence for local immunosuppression and demonstration of c‐myc amplification in pyothorax‐associated lymphoma Aims: Pyothorax‐associated lymphoma (PAL) develops in the pleural cavity of patients with a long history of pyothorax. Epstein–Barr virus (EBV) is also involved in PAL, similar to lymphomas in immunodeficient patients. Here we examined T‐lymphocyte subsets as well as c‐myc and REL gene amplification in PAL tissues. Methods and results: We determined the number and distribution of CD4+ and CD8+ T‐lymphocytes, to evaluate T‐cells in the host immune reaction in seven cases of PAL. As controls, we also studied 10 cases of extranodal diffuse large B‐cell lymphoma (DLBL) and 10 cases of nodal DLBL. Chromosomal imbalances in PAL were determined by using comparative genomic hybridization (CGH) analysis. The mean numbers of CD4+ and CD8+ and their ratio were significantly lower in PAL than in nodal DLBL. CGH analysis of PAL showed amplification of the 8q24 chromosomal region. In addition, c‐myc amplification was found in four cases of PAL by Southern blot analysis. Conclusions: Our results suggest that the development of PAL may involve a local immunosuppressive environment and that amplification of c‐myc might promote tumour progression, as has been described in the development of Burkitt’s lymphoma.
Immunohistochemical localization of CEA, CA19‐9 and DU‐PAN‐2 in hepatitis C virus‐infected liver tissues
Authors: Kitagawa Y , Iwai M , Muramatsu A , Tanaka S , Mori T , Harada Y , Okanoue T , Kashima K 
Published: March 2003

Immunohistochemical localization of CEA, CA19‐9 and DU‐PAN‐2 in hepatitis C virus‐infected liver tissues Aims: We investigated expression of CEA, CA19‐9 and DU‐PAN‐2 in liver tissues of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, measuring their serum value to clarify their clinical significance, and proliferating cell nuclear antigen (PCNA) was assessed in serial sections to determine whether expression of these molecules in chronic liver disease was related to regeneration of biliary ducts. Methods and results: Liver tissues were biopsied under peritoneoscopy or echo‐guidance and resected surgically among 63 patients with anti‐hepatitis C virus‐positive sera. There were 26 cases of chronic hepatitis, 21 cases of liver cirrhosis and 16 cases of hepatocellular carcinoma (four cases of mixed type). They were simultaneously used for immunocytochemistry for CEA, CA19‐9 and DU‐PAN‐2, and PCNA was demonstrated in serial liver tissues by immunohistochemistry. Serum CEA, CA19‐9 and DU‐PAN‐2 were measured by radioimmunoassay or enzyme immunoassay. In chronic hepatitis and liver cirrhosis CEA immunoreactivity was seen on membranes facing bile canaliculi and in bile ductules. Both CA19‐9 and DU‐PAN‐2 immunoreactivity were observed in bile ductules in chronic hepatitis liver cirrhosis and non‐neoplastic areas surrounding hepatocellular carcinoma, and CA19‐9 was also present in interlobular bile ducts. PCNA immunoreactivity was not detected in marker‐positive bile ductules or interlobular bile ducts. In hepatocellular carcinoma CEA immunoreactivity was seen on membrane facing dilated bile canaliculi in glandular structures, and CEA, CA19‐9 and DU‐PAN‐2 immunoreactivity was observed in cholangiolar areas in mixed type of hepatocellular carcinoma. Conclusions: CEA in chronic hepatitis and liver cirrhosis is expressed not only in bile ductules but also on membrane facing bile canaliculi, and both CA19‐9 and DU‐PAN‐2 were seen in different levels of biliary ducts. These molecules were expressed in bile ductules in surrounding non‐neoplastic areas of hepatocellular carcinoma, and their expression was not associated with regeneration of biliary ducts. CEA expression was present in the trabecular type of hepatocellular carcinoma, and CA19‐9 and DU‐PAN‐2 were observed in cholangiolar areas in mixed type of hepatocellular carcinoma.
Abnormal α‐catenin expression in invasive breast cancer correlates with poor patient survival
Authors: Nakopoulou L , Gakiopoulou‐Givalou H , Karayiannakis A J , Giannopoulou I , Keramopoulos A , Davaris P , Pignatelli M 
Published: March 2003

Abnormal α‐catenin expression in invasive breast cancer correlates with poor patient survival Aims: α‐Catenin is a member of the E‐cadherin‐catenin family of adhesion molecules whose role is essential for the function of the E‐cadherin complex. In this study, we have evaluated the expression of α‐catenin but also of the other catenins (β‐, γ‐ and p120‐catenin) and E‐cadherin in invasive breast cancer and statistically analysed these expressions with known clinicopathological parameters, c‐erbB‐2 oncoprotein expression and patient survival. Methods and results: Abnormal E‐cadherin and β‐catenin expression, especially loss of expression, was associated with lobular histological type of breast carcinomas (P=0.03 and P=0.01, respectively). Abnormal E‐cadherin and α‐catenin expression was associated with high histological grade ductal carcinomas (P=0.01 and P=0.03, respectively). Abnormal E‐cadherin and β‐catenin expression was correlated with lymph node metastases (P=0.02 and P=0.05, respectively), while abnormal α‐ and β‐catenin were correlated with the advanced stage of the disease (P=0.04 and P=0.05, respectively). Abnormal p120‐catenin expression was associated with loss of PR (P=0.008). Survival analysis demonstrated a statistically significant association between abnormal α‐catenin expression and poor patient survival (P=0.02). When survival analysis was performed according to the different patterns of abnormal expression, statistically significant associations were seen between cytoplasmic α‐ and β‐catenin expression and poor survival (P=0.006 and P=0.04, respectively). Conclusions: α‐Catenin, especially its cytoplasmic expression, seems to be a more sensitive prognostic marker than the other members of the E‐cadherin complex in invasive breast cancer.
Putative role for interleukin‐7 in the maintenance of the recirculating naive CD4+ T‐cell pool
Authors: Webb L. M. C. , Foxwell B. M. J. , Feldmann M. 
Published: March 2003

SummaryThe capacity of the immune system to respond efficiently to new antigens depends upon a continuous source of naive CD4+ T cells. Such cells exit from the thymus and join the recirculated T‐cell pool. Factors present at the sites of naive CD4+ T‐cell circulation must be responsible for their survival, since upon removal from their host, naive CD4+ T cells die. However, such factors remain unknown. The presence of the cytokine interleukin‐7 (IL‐7) in secondary lymphoid organs and the continuous expression of its receptor on naive CD4+ T cells prompted us to examine the possibility that IL‐7 might be a survival factor for naive CD4+ T cells. Using naive CD4+ T cells isolated from cord blood we show that IL‐7, but not IL‐2, can maintain naive CD4+ T‐cell viability in vitro for at least 15 days. In addition, we find that IL‐7 can induce modest proliferation of naive CD4+ T cells without affecting either their cell surface phenotype or their ability to respond to antigenic stimulation. We also find that after anti‐CD3 stimulation, naive CD4+ T cells lose that ability to respond to IL‐7. However, if cells are primed with IL‐7 prior to antigenic stimulation, their proliferative responses are enhanced. Together, these data suggest a novel and important role for IL‐7 in the maintenance and maturation of naive CD4+ T cells, ensuring that they can respond maximally when they first meet antigen in secondary lymphoid tissue.
Decay accelerating factor in guinea‐pig reproductive organs
Authors: He C. , Nonaka M. , Tada T. , Koji T. , Li W. , Okada N. , Okada H. 
Published: March 2003

SummaryDecay accelerating factor (DAF, CD55) expressed in human reproductive organs and gametes is thought to play a pivotal role in protection against autologous complement activation in the genital tract. To further investigate the role of DAF in reproduction, we analysed DAF distribution in reproductive organs using guinea‐pigs that express multiple DAF isoforms. In males, significant staining was observed in testis on the elongated spermatids and spermatozoa. Levels of DAF mRNA with a shorter 3′ untranslated region were significantly enhanced in testis from 9 weeks of age, indicating the presence of DAF mRNA and protein synthesis of spermatozoa DAF in late haploid germ cells. Epididymal spermatozoa appeared to express DAF on the inner acrosomal membrane as well as over their entire surface. Significant DAF expression was also observed on the epithelium of seminal vesicles from 4 weeks of age, with no increase thereafter in the mRNA. C3 mRNA was not detected in this tissue. In females, DAF was detected on the plasma membranes of oocytes through follicle development and on the apical region of uterine epithelium, although the levels of DAF mRNA in these tissues were low. In addition, DAF was selectively expressed on the apical region of ciliated oviductal epithelial cells. The apical region of the ciliated cells comprising the efferent ductule epithelium was also stained significantly, even at 12 days of age, while other epididymal epithelial cells were hardly stained at any age, suggesting that DAF is constitutively expressed on cilia.
Increased resistance to mycobacterial infection in the absence of interleukin‐10
Authors: Jacobs M. , Brown N. , Allie N. , Gulert R. , Ryffel B. 
Published: March 2003

SummaryInterleukin‐10 (IL‐10) down‐regulates T helper type 1 cell and macrophage functions. As IL‐10 is induced along with tumour necrosis factor (TNF) and IL‐12 in mycobacterial infection, we asked whether endogenous IL‐10 plays a role in the antimycobacterial response. We demonstrate here that IL‐10‐deficient mice eliminate Mycobacterium bovis Calmette–Guérin bacillus faster than wild‐type mice. Granulomas are significantly larger, containing more CD‐11b‐ and CD11c‐positive antigen‐presenting cells and T cells, and the expression of major histocompatibility complex class II and intracellular adhesion molecule‐1 is increased. Macrophages in granulomas of IL‐10‐deficient mice express high levels of TNF, acid phosphatase and inducible nitric oxide synthase (iNOS). Finally, an increased cutaneous delayed‐type hypersensitivity reaction to mycobacterial proteins is further evidence of an augmented cell‐mediated immune response. In conclusion, the cell‐mediated immunity is enhanced in the absence of IL‐10, resulting in a robust granuloma response, which accelerates the clearance of mycobacteria. Therefore, endogenous IL‐10 attenuates mycobacterial immunity.
Intestinal lymphocyte number, migration and antibody secretion in young and old rats
Authors: Thoreux K. , Owen R. L. , Schmucker D. L. 
Published: March 2003

SummaryThis study demonstrates that the mucosal immune response to cholera toxin (CT) is compromised in old rats in comparison with young animals. The total number of immunoglobulin A (IgA)‐secreting cells is similar or higher in the intestinal inductor and effector sites in old animals. However, the number of specifically induced anti‐CT IgA antibody‐secreting cells is lower in these tissues in comparison with those in young animals. The kinetics of this immune response in the different gut‐associated lymphoid tissues studied suggests that the age‐associated decline in the number of anti‐CT IgA‐secreting cells in the intestinal mucosa reflects impaired IgA immunoblast migration. Our data from lymphocyte adoptive transfer studies indicate that factors intrinsic to both the donor cells and the host recipient influence the migration of immunoblasts from the Peyer's patches to the effector site. For example, donor cells from old donors transferred to either young or old recipient rats migrate slower than young donor lymphocytes transferred into old host animals. In vitro studies clearly indicate that ageing does not impair antibody secretion by intestinal mucosal plasma cells. Therefore, the age‐related decline in the intestinal mucosal immune response, e.g. diminished specific antibody titres in intestinal lavage, reflects fewer antibody‐secreting cells in the mucosa.
Major histocompatibility complex class II– fetal skin dendritic cells are potent accessory cells of polyclonal T‐cell responses
Authors: Elbe‐Bürger, A. , Mommaas A. M. , Prieschl, E. E. , Fiebiger, E. , Baumruker T. , Stingl G. 
Published: March 2003

SummaryWhereas dendritic cells (DC) and Langerhans cells (LC) isolated from organs of adult individuals express surface major histocompatibility complex (MHC) class II antigens, DC lines generated from fetal murine skin, while capable of activating naive, allogeneic CD8+ T cells in a MHC class I‐restricted fashion, do not exhibit anti‐MHC class II surface reactivity and fail to stimulate the proliferation of naive, allogeneic CD4+ T cells. To test whether the CD45+ MHC class I+ CD80+ DC line 80/1 expresses incompetent, or fails to transcribe, MHC class II molecules, we performed biochemical and molecular studies using Western blot and polymerase chain reaction analysis. We found that 80/1 DC express MHC class II molecules neither at the protein nor at the transcriptional level. Ultrastructural examination of these cells revealed the presence of a LC‐like morphology with indented nuclei, active cytoplasm, intermediate filaments and dendritic processes. In contrast to adult LC, no LC‐specific cytoplasmic organelles (Birbeck granules) were present. Functionally, 80/1 DC in the presence, but not in the absence, of concanavalin A and anti‐T‐cell receptor monoclonal antibodies stimulated a vigorous proliferative response of naive CD4+ and CD8+ T cells. Furthermore, we found that the anti‐CD3‐induced stimulation of naive CD4+ and CD8+ T cells was critically dependent on the expression of FcγR on 80/1 DC and that the requirement for co‐stimulation depends on the intensity of T‐cell receptor signalling.
HLA‐G has a concentration‐dependent effect on the generation of an allo‐CTL response
Authors: Kapasi K. , Albert S. E. , Yie S.‐M. , Zavazava N. , Librach C. L. 
Published: March 2003

SummaryHuman leucocyte antigen (HLA) ‐G is expressed on trophoblast cells during pregnancy, suggesting a role in protection of the semiallogeneic fetus. Published data suggest that HLA‐G protects a cell against natural killer cell lysis. It has been hypothesized that HLA‐G may also protect the fetus by preventing allo‐cytotoxic T lymphocyte (CTL) responses. To test this hypothesis, we assayed the effects of various concentrations of purified HLA‐G on CTL response in a mixed lymphocyte culture (MLC) system. We found that concentrations ≥ 0·1 µg/ml of HLA‐G suppressed the allo‐CTL response by 30–100% over the control, but, paradoxically, concentrations of 0·01–0·05 µg/ml of HLA‐G augmented the allo‐CTL response by 25–50% over the control. Concentrations ≤ 0·001 µg/ml HLA‐G had no effect. Addition of HLA‐G to preprimed allo‐CTL effector cells did not affect their killing ability. Allo‐CTL suppressive doses of HLA‐G induced a T helper type 2 (Th2) cytokine response, whereas allo‐CTL‐enhancing doses of HLA‐G induced a Th1‐type cytokine response. HLA‐G purified from first‐trimester placenta does not affect allo‐proliferative responses nor does it alter the percentage of CD4+ or CD8+ T cells in MLCs. These findings support a potential role for HLA‐G‐mediated suppression of allo‐CTL formation in normal pregnancies. In addition, the effects observed at lower concentrations of HLA‐G may have interesting implications for the condition of pre‐eclampsia in which concentrations of this HLA class I molecule are reduced.
The calcium‐independent protein kinase C participates in an early process of CD3/CD28‐mediated induction of thymocyte apoptosis
Authors: Asada A. , Zhao Y. , Komano H. , Kuwata T. , Mukai M. , Fujita K. , Tozawa Y. , Iseki R. , Tian H. , Sato K. , Motegi Y. , Suzuki R. , Yokoyama M. , Iwata M. 
Published: March 2003

SummaryThymocyte negative selection eliminates self‐reactive clones and involves both a T‐cell receptor (TCR)/CD3‐mediated signal and a costimulatory signal, which can be delivered via CD28. Anti‐CD3/anti‐CD28‐triggered apoptosis in isolated CD4+CD8+ thymocytes in vitro provides a basic model for negative selection. Effects of isoform‐selective and non‐isoform‐selective inhibitors of protein kinase C (PKC) on this apoptotic process suggest that activation of Ca2+‐independent PKC isoforms during the first 2–3 hr of culture is essential for inducing apoptosis, and that Ca2+‐dependent PKC isoforms may be influential, but not essential, for apoptosis. To assess the CD3/CD28‐mediated activation of PKC in the apoptotic process, we prepared CD4+CD8+ thymocytes (without contamination with cells that had received negative or positive selection signals in vivo) by establishing TCR‐transgenic mice with RAG‐2‐deficient and non‐selecting major histocompatibility complex (MHC) backgrounds, in addition to a CD4+CD8+ thymocyte‐enriched population from normal mice. Translocation of Ca2+‐independent PKC from the cytosolic fraction to the particulate fraction of CD4+CD8+ thymocytes was induced by CD3/CD28‐mediated stimulation, but not by CD3‐ or CD28‐mediated stimulation alone, and peaked 2 hr after the start of culture. The kinase activity of the translocated Ca2+‐independent PKC was dependent on cofactors in vitro, indicating that novel (n)PKC, but not atypical (a)PKC or a proteolytic PKC fragment, was responsible for the activity. Immunoblotting analysis indicated that the nPKC‐θ isoform was the major contributor among nPKC isoforms, and that the classical (c)PKC‐α isoform was the major contributor among cPKC isoforms. These results suggest that activation of nPKC (especially the θ isoform) in CD4+CD8+ thymocytes is involved in a pathway for negative selection.
Induction of T helper 1‐ and T helper 2‐type immune responses duringHaemonchus contortus infection in sheep
Authors: Gill H. S. , Altmann K. , Cross M. L. , Husband A. J. 
Published: March 2003

SummaryThe production of cytokines by lymphoid cells, isolated from non‐infected and Haemonchus contortus‐infected lambs, was investigated. Particular attention was paid to differences in T helper 1‐ (Th1) and Th2‐type immune profiles between genetically resistant and random‐bred animal groups. Non‐infected resistant and random‐bred lambs produced equivalent levels of interferon‐γ (IFN‐γ) and interleukin‐5 (IL‐5), from isolated abomasal lymph node cells (ALN), mesenteric lymph node cells (MLN) and spleen cells (SC), in response to in vitro stimulation with T‐cell mitogen (concanavalin A) or larval parasite antigen. ALN and MLN cells derived from infected resistant and random‐bred lambs produced relatively lower levels of IFN‐γ, following in vitro stimulation with parasite antigen, when compared with their uninfected counterparts. In contrast, infected lambs of both groups showed enhanced mitogen‐ and antigen‐stimulated production of IL‐5, in comparison with uninfected controls, at days 5 and 28 postinfection (p.i.). Mitogen‐ and antigen‐stimulated IL‐5 responses were higher among resistant lambs compared with random‐bred lambs, with the highest overall production of IL‐5 by parasite antigen‐stimulated ALN and MLN cells. Among day 28 p.i. lambs, levels of cell culture‐derived parasite‐specific immunoglobulin G1 (IgG1) and IgE antibodies were higher in resistant lambs than in random‐bred lambs, following in vitro stimulation of SC or ALN cells with parasite antigen. Finally, after 28 days p.i., histological examination of abomasal tissue revealed higher densities of mast cells and eosinophils in the mucosa of resistant lambs than in random‐bred lambs. Taken together, these data support the notion of a strong Th2‐type immune response to Haemonchus infection in genetically resistant sheep, and support the claim for a Th1/Th2 dichotomy in ruminants.