bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary signet ring cell adenocarcinomas of the lung: a clinicopathological study of 15 cases
Authors: Castro C Y , Moran C A , Flieder D G , Suster S 
Published: March 2003

Primary signet ring cell adenocarcinomas of the lung: a clinicopathological study of 15 cases Aims: We describe the clinicopathological characteristics of 15 cases of primary signet ring cell adenocarcinoma of the lung and highlight the importance of recognizing that not all adenocarcinomas with signet ring cell features represent metastatic adenocarcinomas. Methods and results: We evaluated the clinicopathological and immunohistochemical features of 15 cases of signet ring cell adenocarcinoma of the lung. The patients were 12 men and three women, age 30–75 years (mean 52.5 years). No evidence of a primary tumour elsewhere could be found on thorough clinical examination. Nine patients underwent resection and the remainder were biopsied. The tumours ranged from 18 to 80 mm in greatest dimension. Microscopically, two distinct patterns of growth were recognized: acinar and diffuse. The tumours were characterized by the presence of >75% signet ring cells. Periodic acid–Schiff and mucicarmine showed strong intracellular positive staining. Immunohistochemical stains for TTF‐1 (6/6) and CEA (9/9) showed strong positive reaction in all cases evaluated. Three out of six cases were also positive for cytokeratin 7. All the tumours (6/6) were negative for cytokeratin 20, ER, PR and GCDFP‐15. Follow‐up information was obtained in 11 patients; six patients died within 1 year and five patients were alive from 3 to 36 months after initial diagnosis. Conclusion: These cases highlight an unusual histological growth pattern of primary lung adenocarcinoma that may be mistaken for a metastasis from an occult primary. The recognition of this pattern of lung tumours is important for proper treatment.
Loss of CD30 expression in metastatic embryonal carcinoma: the effects of chemotherapy?
Authors: Berney D M , Shamash J , Pieroni K , Oliver R T D 
Published: March 2003

Loss of CD30 expression in metastatic embryonal carcinoma: the effects of chemotherapy? Aims: CD30 has been shown to be consistently strongly expressed in embryonal carcinomas. Our aim was to examine changes in CD30 expression in embryonal carcinomas before and after treatment with chemotherapy. Methods and results: One hundred and eighteen retroperitoneal lymph node dissections from patients with metastatic germ cell tumours were reviewed. Seventeen contained embryonal carcinoma deposits. In nine cases, the matching pre‐chemotherapy orchidectomy specimens were available. The cases were immunohistochemically stained for CD30. All nine pre‐ chemotherapy orchidectomy specimens showed embryonal carcinoma and stained strongly positively for CD30. However, only four out of nine of the matched post‐chemotherapy retroperitoneal lymph node dissection specimens and a total of six out of 17 (35%) with embryonal carcinoma deposits stained for CD30. Ten seminomas were negative for CD30. Loss of CD30 did not appear to influence the relapse rate of the patients. Conclusions: Loss of CD30 expression occurs frequently in metastatic embryonal carcinomas after chemotherapy. This finding has implications in the use of CD30 in the diagnosis of metastatic non‐seminomatous germ cell tumours and suggests that chemotherapy may alter the immunophenotype of embryonal carcinoma while retaining its characteristic histological appearances.
Arthroplasty‐associated malignant fibrous histiocytoma: two case reports
Authors: Lucas D R , Miller P R , Mott M P , Kronick J L , Unni K K 
Published: March 2003

Arthroplasty‐associated malignant fibrous histiocytoma: two case reports Aims: Sarcoma localized to the site of an arthroplasty procedure is a rare occurrence, and detailed histological depictions and descriptions are limited. We report the clinicopathological findings in two cases of arthroplasty‐associated malignant fibrous histiocytoma (MFH) and review the literature. Methods and results: The patients were an elderly man and woman. Medical histories, radiographs and slides were reviewed. Immunohistochemistry, electron microscopy, cytogenetics, and electron dispersion spectroscopy were performed in one case. Both were destructive femoral bone tumours that appeared 2 and 8 years post‐total hip arthroplasty, and pursued aggressive clinical courses. The histology was similar in both tumours, consisting of high‐grade, pleomorphic sarcoma with numerous osteoclastic giant cells, prominent phagocytic activity, and entrapped particles of bone cement. Literature review disclosed 14 previous reports of arthroplasty‐associated MFH, representing the most common phenotype. A number of materials and factors related to arthroplasty procedure, such as metal corrosion, wear debris, osteonecrosis, and chronic inflammation, have been implicated as causative agents. Conclusions: Arthroplasty‐associated MFH is a rare and aggressive tumour. Although the aetiology remains unclear, the small number of arthroplasty‐associated sarcomas compared with the large number of joint replacement operations performed over the past four decades suggests a coincidental as opposed to a causal relation.
Mucinous (colloid) adenocarcinomas secrete distinct O‐acylated forms of sialomucins: a histochemical study of gastric, colorectal and breast adenocarcinomas
Authors: Sáez C , Japón M A , Poveda M A , Segura D I 
Published: March 2003

Mucinous (colloid) adenocarcinomas secrete distinct O‐acylated forms of sialomucins: a histochemical study of gastric, colorectal and breast adenocarcinomas Aims: Mucinous (colloid) adenocarcinomas represent a distinct group of tumours defined by the presence of large amounts of extracellular mucins. By using histochemical methods, we analysed mucins secreted by mucinous versus non‐mucinous adenocarcinomas and looked for differential secretion profiles. Methods and results: Sixty‐four adenocarcinomas were studied (23 colorectal, 17 gastric, and 24 breast tumours). Thirty‐two tumours were of the colloid type. The following methods were applied to paraffin tissue sections: (i) Alcian blue (pH 2.5) and periodic acid–Schiff (PAS); (ii) high iron diamine and Alcian blue (pH 2.5); (iii) periodic acid borohydride, potassium hydroxide, and PAS; (iv) periodic acid–thionine Schiff, potassium hydroxide, and PAS; and (v) periodic acid–borohydride and PAS. Most adenocarcinomas secreted acidic mucins, with sialomucins predominating over sulfomucins, except for non‐mucinous adenocarcinomas of the breast which showed predominant neutral mucins. All mucinous adenocarcinomas contained C9‐O‐acyl sialic acid as mono, di(C8,C9)‐, or tri(C7,C8,C9)‐O‐acyl forms. Acidic mucins secreted by the majority of non‐colloid adenocarcinomas consisted of non‐O‐acylated sialomucins. Conclusions: C9‐O‐acylation of sialic acid is a characteristic feature of mucinous adenocarcinomas and can be readily detected by histochemical methods.
A study of eleven cutaneous malignant melanomas in adults with small‐cell morphology: emphasis on diagnostic difficulties and unusual features
Authors: Hanson I M , Banerjee S S , Menasce L P , Prescott R J 
Published: March 2003

A study of eleven cutaneous malignant melanomas in adults with small‐cell morphology: emphasis on diagnostic difficulties and unusual features Aims: To describe the clinicopathological and immunohistochemical features of cutaneous malignant melanomas with a pure or mixed small‐cell pattern in 11 adult patients, and to discuss the diagnostic difficulties encountered. Methods and results: Haematoxylin and eosin‐stained sections of each case of cutaneous small‐cell malignant melanoma, together with locally recurrent skin lesions and, where available, metastatic deposits, were re‐examined. Available immunohistochemical sections were evaluated. Clinical follow‐up data were obtained in each case. One patient presented with metastatic disease, the others presented with cutaneous lesions. Suggested initial diagnoses included malignant melanoma, non‐Hodgkin's lymphoma, Merkel cell carcinoma and sarcoma. All the tumours were in the vertical growth phase. Nine had a junctional component, often inconspicuous. The lesions showed either a pure small‐cell pattern or a mixed pattern with more conventional areas. In one case, there was colonization of a basal cell carcinoma by invasive malignant melanoma. Variable retention of small‐cell morphology in local recurrences and metastases was observed, although in some cases more typically pleomorphic cells were present. In the cases tested, there was strong immunostaining for S100 protein and NKI‐C3, and variable immunostaining for HMB45 and Melan‐A. Non‐melanocytic markers were negative. Conclusions: The possibility of a small‐cell malignant melanoma should be considered in the assessment of cutaneous and non‐cutaneous small‐cell neoplasms. The correct diagnosis requires careful evaluation for junctional activity, melanin production and the use of a panel of melanocytic markers.
CD44 is involved in selective leucocyte extravasation during inflammatory central nervous system disease
Authors: Brennan F. R. , O'Neill J. K. , Allen S. J. , Butter C. , Nuki G. , Baker D. 
Published: March 2003

SummaryClinical signs of experimental autoimmune encephalomyelitis (EAE) are associated with the selective recruitment of CD4+ memory (CD45RBlow CD44high) T cells into the central nervous system (CNS). However, we have found that many of these recently recruited memory cells are CD44low, suggesting that the CD44 antigen may be involved in, and transiently lost during, the extravasation process. Indeed, administration of a CD44‐specific antibody (IM7.8.1) induced leucocyte CD44 shedding and both prevented the development and ameliorated the severity of established EAE by inhibiting mononuclear cell infiltration into the CNS. Trafficking of cells into lymph nodes, however, a property mainly of naïve cells, was essentially unaffected. In contrast, treatment with antibody to very late activation antigen‐4 (VLA‐4) prevented homing to both the CNS and to lymph nodes. This study contests previous reports that dismissed a role for CD44 in inflammation of the CNS and, coupled with observations in murine dermatitis and arthritis, suggests that CD44 is involved in the homing of primed lymphocytes to sites of inflammation. CD44 should therefore be considered a target for immunotherapy of T‐cell‐mediated inflammatory diseases, such as multiple sclerosis.
In vivo selective expansion of a tumour‐specific cytotoxic T‐cell clone derived from peripheral blood of a melanoma patient after vaccination with gene‐modified autologous tumour cells
Authors: Sun Y. , Möller P. , Berking C. , Schlüpen E.‐M. , Volkenandt M. , Schadendorf D. 
Published: March 2003

SummaryMelanoma‐specific cytotoxic T lymphocytes (CTL) can be generated from peripheral blood lymphocytes (PBL) by mixed lymphocyte–tumour cell cultures. Analysis of CTL precursor frequencies in peripheral blood of melanoma patients is generally used for immunomonitoring purposes to evaluate vaccination efficacy. At present, it is unclear whether PBL‐derived CTL generated in vitro are indicative of an anti‐tumour immune response in vivo. Three tumour‐specific human leucocyte antigen (HLA)‐B/C‐restricted CTL clones were derived from peripheral blood of a melanoma patient immunized with interleukin‐7 (IL‐7) gene‐modified tumour cells. CTL clones differing in their T‐cell receptor‐γ (TCRγ) rearrangement produced interferon‐γ, IL‐4 and/or IL‐10. On the basis of their unique TCRγ gene rearrangements clone‐specific primers were generated for detection of clone‐specific DNA by polymerase chain reaction. One CTL clone (E5) of the three was found to be selectively expanded in one of seven metastases obtained at autopsy, as determined by Southern blot hybridization. However, the presence of E5 in only one of seven metastases at death indicates that the in vivo accumulation of the specific CTL clone was not sufficient to contain tumour progression. Nevertheless, our data support the proposition that analysis of anti‐tumour activity of PBL‐derived CTLs may reflect an anti‐tumour immune response in vivo.
Adhesion to fibronectin promotes the activation of the p125FAK/Zap‐70 complex in human T cells
Authors: Bearz A. , Tell G. , Formisano S. , Merluzzi S. , Colombatti A. , Pucillo C. 
Published: March 2003

SummaryThe β1 integrins are a family of heterodimeric adhesion receptors involved in cell‐to‐cell contacts and cell‐to‐extracellular matrix interactions. Through their adhesive role, integrins participate in transduction of outside/inside signals and contribute to trigger a multitude of cellular events such as differentiation, cell activation, and motility. The fibronectin integrin receptors, α4β1 and α5β1, can function as costimulatory molecules in T‐cell receptor (TCR)‐dependent T‐cell activation. In the current study the Jurkat T‐cell line was used as a model system to investigate the TCR‐independent role of cell adhesion to fibronectin in the activation of Zap‐70, a central molecule in the signalling events in T cells. Upon adhesion to plastic immobilized fibronectin but not to bovine serum albumin (BSA) the phosphorylation of p125FAK, a protein kinase that localizes to focal adhesion sites, was induced. Moreover, clustering of fibronectin receptors led to the detection of a p125FAK/Zap‐70 complex. Finally, while the complex between fak‐B, another protein kinase localized to focal adhesion sites, and Zap‐70 was detected in cells plated either on BSA or on fibronectin, the formation of the p125FAK/Zap‐70 complex appeared specifically induced following fibronectin‐mediated integrin clustering. These data suggest the existence of a high degree of specificity when the members of the β1 integrin family mediate signalling pathways in T cells.
A novel function of B lymphocytes from normal mice to suppress autoimmunity in (NZB × NZW)F1 mice
Authors: Ono S. , Shao D.‐Z. , Yamada S. , Yang Y. , Yamashita M. , Hamaoka T. 
Published: March 2003

SummaryIn systemic autoimmune‐prone (NZB × NZW)F1 (NZB/W F1) mice, B‐cell abnormalities characterized by hypergammaglobulinaemia accompanying autoantibodies have been thought to be a main cause of the disease. To examine a possible regulatory role of B cells in the disease manifestations, we injected, intravenously (i.v.), normal or autoimmune B cells into non‐irradiated NZB/W F1 mice. The injection of splenic B cells from major histocompatibility (MHC)‐matched or allogeneic normal mice caused a marked decrease in serum immunoglobulin G (IgG) levels of autoantibodies, delayed the appearance of proteinuria and prolonged life span, whereas treatment with splenic B cells from NZB/W F1 or X‐linked immunodeficient (Xid) mice failed to suppress the autoimmunity. Moreover, in vitro polyclonal antibody responses to lipopolysaccharide (LPS) of NZB/W F1‐derived B cells from the treated mice were markedly reduced. Interestingly, the treatment of NZB/W F1 mice at 16, 18 and 20 or at 20, 22 and 24 weeks of age was more effective than that at 6, 8 and 10 weeks. The treatment also inhibited the development of surface IgG+ (sIgG+) B cells and splenomegaly, prominent in aged NZB/W F1 mice. In addition, when untreated NZB/W F1 responding B cells were precultured with normal B cells in vitro for 3 days, they also diminished the autoantibody production to subsequent LPS stimulation. Hence, the present results imply a novel function of normal B cells to ameliorate autoimmune disease in NZB/W F1 mice by correcting their B‐cell abnormalities, and indicate that NZB/W F1 and Xid mice possess defects in this regulatory B‐cell function.
2B4 stimulation of YT cells induces natural killer cell cytolytic function and invasiveness
Authors: Chuang S. S. , Kim M. H. , Johnson L. A. , Albertsson P. , Kitson R. P. , Nannmark U. , Goldfarb R. H. , Mathew P. A. 
Published: March 2003

Summary2B4 is a surface molecule found on all human natural killer (NK) cells, a subset of CD8+ T cells, monocytes and basophils. It was originally identified on mouse NK cells and the subset of T cells that mediate non‐major histocompatibility complex (MHC)‐restricted killing. Recently,
9 we have cloned the human homologue of 2B4 (h2B4) and found h2B4 to also mediate non‐MHC‐restricted cytotoxicity. In this study, we examine h2B4 in regulating various functions of NK cells using a human NK cell line YT, with monoclonal antibody (mAb) C1.7, an antibody that specifically recognizes h2B4. Ligation of surface 2B4 with mAb C1.7 increases YT's ability to destroy tumour cells. In the presence of mAb C1.7, the production of interferon‐γ (IFN‐γ) by YT cells is greatly enhanced. Engagement of surface 2B4 by mAb C1.7 downregulates the expression of h2B4 at the cell surface as well as the expression of h2B4 mRNA. Also, signalling through h2B4 causes the increased expression of matrix metalloproteinase‐2, a member of the matrix degrading proteinase family. Thus, in addition to modulating cytolytic function and cytokine production of NK cells, activation through surface 2B4 may play a role in upregulating the machinery for degradation of extracellular matrices to promote invasion of the tumour by NK cells.
SHP‐1/immunoreceptor tyrosine‐based inhibition motif‐independent inhibitory signalling through murine natural killer cell receptor Ly‐49A in a transfectedB‐cell line
Authors: Motoda K. , Takata M. , Kiura K. , Nakamura I. , Harada M. 
Published: March 2003

SummaryLy‐49A is a member of the Ly‐49 family of mouse natural killer cell receptors that inhibit cytotoxicity upon recognition of their ligands, the major histocompatibility complex (MHC) class I molecules, on the target cell surface. Although Ly‐49A has an immunoreceptor tyrosine‐based inhibition motif (ITIM) in its cytoplasmic tail, relatively little is known about the mechanisms underlying its inhibitory function. We report here that antibody‐mediated co‐ligation of the B‐cell receptor (BCR) with the transfected Ly‐49A molecule results in abrogation of BCR‐induced interleukin‐2 (IL‐2) secretion and mild reduction in activation of Erk1/2 and p38 mitogen‐activated protein (MAP) kinases in the B‐cell line A20. Surprisingly, BCR‐induced calcium mobilization was unaffected by cross‐linking of BCR with Ly‐49A. Furthermore, substitution of the single tyrosine residue in ITIM with phenylalanine, did not result in a complete loss of inhibitory function, as measured by BCR‐induced IL‐2 secretion. Deletion of the N‐terminal 37 amino acid peptide, which includes the ITIM, did abrogate the inhibitory activity. Co‐immunoprecipitation experiments revealed that, upon induction of tyrosine phosphorylation, Ly‐49A recruits tyrosine phosphatase src‐homology 2 (SH2) containing tyrosine phosphatases‐1 (SHP‐1), but not inositol phosphatase src‐homology 2 (SH2) containing inositol phosphatase (SHIP), and that the tyrosine residue in the ITIM is critical for this interaction. These results suggest that transfected Ly‐49A utilizes two different inhibitory mechanisms in B‐cell signalling: ITIM‐dependent and ITIM‐independent.
Selection and characterization of MUC1‐specific CD8+ T cells from MUC1 transgenic mice immunized with dendritic‐carcinoma fusion cells
Authors: Gong J. , Apostolopoulos V. , Chen D. , Chen H. , Koido S. , Gendler S. J. , Mckenzie I. F. , Kufe D. 
Published: March 2003

SummaryMice transgenic for the human MUC1 carcinoma‐associated antigen (MUC1.Tg) are tolerant to immunization with MUC1 antigen. Recent studies, however, have demonstrated that immunization of MUC1.Tg mice with fusions of MUC1‐positive tumour and dendritic cells (FC/MUC1) reverses MUC1 unresponsiveness and results in rejection of established MUC1‐positive pulmonary metastases. Here we demonstrate that lymph node cells from MUC1.Tg mice immunized with the FC/MUC1 fusion cells proliferate in response to MUC1 antigen by a mechanism dependent on the function of CD4, major histocompatibility complex (MHC) class II, B7‐1, B7‐2, CD28, CD40 and CD40 ligand. The findings demonstrate that stimulation of lymph node cells with MUC1 results in selection of MUC1‐specific CD8+ T cells. We show that the CD8+ T cells exhibit MUC1‐specific cytotoxic T lymphocyte (CTL) activity by recognition of MUC1 peptides presented in the context of MHC class I molecules Kb and Db. The MUC1‐specific CD8+ T cells also exhibit antitumour activity against MUC1‐positive metastases, but with no apparent reactivity against normal tissues. These results indicate that immunization of MUC1.Tg mice with FC/MUC1 reverses immunological unresponsiveness to MUC1 by presentation of MUC1 peptides in the presence of costimulatory signals and generates MHC‐restricted MUC1‐specific CD8+ T cells.
DNase I footprinting of the human interleukin‐5 gene promoter
Authors: Cousins D. J. , Richards D. , Kemeny D. M. , Romagnani S. , Lee T. H. , Staynov D. Z. 
Published: March 2003

SummaryA characteristic feature of allergic asthma is the overexpression of the T helper type 2 (Th2) cytokines interleukin‐4 (IL‐4), IL‐5 and IL‐13 by T lymphocytes. Of these cytokines, IL‐5 is critical for the growth, survival and recruitment of eosinophils which are thought to be responsible for the tissue damage observed in asthmatic airways. The expression of human IL‐5 is primarily regulated at the transcriptional level; however, little is known about the mechanisms that control its transcription. Using nuclear extracts from allergen‐specific human T‐cell clones we have performed DNase I footprinting of the human IL‐5 promoter in order to establish sites occupied by transcription factors. We show footprints covering the conserved lymphokine element 0 [(CLE0) – 60 to – 44 base pairs (bp)] and GATA (– 73 to – 62 bp) elements, which have previously been identified to be important in the regulation of the murine IL‐5 promoter. We also describe a footprint covering a considerably extended Octamer binding site (– 249 to – 217 bp), which encompasses two hitherto unidentified CCAAT/enhancer binding protein consensus binding sites. We have also identified a previously unknown Ets binding site (– 274 to – 264 bp). These novel data on the regions of the human IL‐5 promoter that are bound by transcription factors should allow dissection of the regulatory mechanisms involved in the transcription of IL‐5 in the T‐helper lymphocytes of asthmatics.
Antiviral protection after DNA vaccination is short lived and not enhanced by CpG DNA
Authors: Oehen S. , Junt T. , López‐macías C. , Kramps T. A. N. 
Published: March 2003

SummaryIn this study, we investigated the potential of a DNA vaccine expressing the minimal cytotoxic T lymphocyte (CTL) epitope gp33 of the lymphocytic choriomeningitis virus glycoprotein to protect against infection of a non‐lymphoid organ and compared this to protection against a systemic infection. Furthermore, since immune stimulatory sequences have been shown to augment CTL responses, we examined the capacity of CpG DNA to enhance CTL memory. The data show that DNA vaccination with a gp33‐based gene construct induced short‐lived gp33‐specific CTL which protected against a systemic infection but not against a peripheral infection. Immune stimulatory sequences were incapable of either prolonging CTL memory or promoting protection against infection of a peripheral organ.