bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum
Authors: Attanoos R L , Webb R , Dojcinov S D , Gibbs A R 
Published: March 2003

Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum Aims: To evaluate the role of mesothelial markers (calretinin, thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal carcinoembryonic antigen, Leu‐M1, CA‐125 and Ber‐EP4) in distinguishing diffuse peritoneal malignant mesothelioma from primary serous papillary adenocarcinoma of the ovary and peritoneum. Methods and results: Paraffin‐embedded formalin‐fixed blocks from 32 diffuse peritoneal mesotheliomas of epithelial subtype (all females), 20 serous papillary ovarian carcinomas and three primary peritoneal serous papillary carcinomas were studied. Calretinin and Ber‐EP4 appeared to be the best positive mesothelial and carcinoma marker, respectively. Nuclear calretinin expression was identified in 28 of 32 malignant mesotheliomas with no nuclear immunoreactivity in the cohorts of serous papillary ovarian and peritoneal carcinomas, thus yielding 88% sensitivity and 100% specificity. Ber‐EP4 showed 95% sensitivity and 91% specificity for serous papillary ovarian carcin‐ oma. Thrombomodulin, cytokeratin 5/6 and CD44H immunoreactivities were seen in 18 (56%), 17 (53%) and 15 (47%) of peritoneal mesotheliomas, respectively, and in six (30%), five (25%) and five (25%) of the ovarian tumours, respectively. None of the three primary peritoneal serous papillary carcinomas expressed calretinin, thrombomodulin, cytokeratin 5/6 or CD44H. Polyclonal and monoclonal CEA, and Leu‐M1 were expressed by two (10%), one (5%) and seven (35%) serous papillary ovarian carcinomas, respectively. None of the serous papillary peritoneal carcinomas expressed polyclonal CEA, monoclonal CEA or Leu‐M1. CA‐125 was positive in 19 (95%) and two (67%) ovarian and peritoneal carcinomas, respectively, and in eight (25%) peritoneal mesotheliomas. Conclusions: Calretinin and Ber‐EP4 are useful discriminant markers in distinguishing peritoneal mesothelioma in women from serous papillary ovarian and peritoneal carcinoma. The other mesothelial markers (thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal CEA, and Leu‐M1) yielded a too low sensitivity for practical use.
Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression: a multicentre immunohistochemical study in the Asia–Pacific region
Authors: Putti T C , To K F , Hsu H C , Chan A T C , Lai G M , Tse G , Lee Y S , Whang‐Peng J , Millward M , Lin L , Lin X , Lee C S 
Published: March 2003

Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression: a multicentre immunohistochemical study in the Asia–Pacific regionAims:  With ongoing efforts to target the epidermal growth factor receptor (EGFR)‐mediated tumour growth in the treatment of selected human malignancies, there is a need to determine the expression levels of EGFR and to evaluate its prognostic value in various malignancies in the Asia–Pacific region.Methods and results:  A total of 172 patients with head and neck squamous cell carcinomas from Australia, Hong Kong, Singapore, and Taiwan were selected for EGFR detection. Immunohistochemical staining was performed to evaluate EGFR expression. EGFR expression was present in 88.4% (152/172) of all cases tested. Specifically, EGFR expression was found in 91.3% (42/46), 84.6% (22/26), 84.1% (37/44), 96.0% (24/25), and 87.1% (27/31) cases of head and neck squamous cell carcinomas from the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx, respectively. The results demonstrate a stronger EGFR expression in T4 tumours (P=0.017) and later clinical stages (P=0.016). No significant correlation was seen with risk factors, primary tumour site and ethnicity.Conclusions:  The majority of head and neck squamous cell carcinomas express EGFR, indicating the importance of studying the efficacy of anti‐cancer therapy through this pathway. The results also show similar rates of receptor expression in head and neck squamous cell carcinoma patients from our region compared with other parts of the world.
Non‐HTLV‐1‐associated primary gastric T‐cell lymphomas show cytotoxic activity: clinicopathological, immunohistochemical characteristics and TIA‐1 expression in 31 cases
Authors: Hatano B , Ohshima K , Katoh A , Kanda M , Kawasaki C , Tsuchiya T , Shimazaki K , Haraoka S , Sugihara M , Suzumiya J , Kikuchi M 
Published: March 2003

Aims:  Most primary gastrointestinal lymphomas are of B‐cell origin and T‐cell origin is very rare. Recent studies have suggested that human T‐cell lymphotrophic virus type 1 (HTLV‐1) may be involved in the development of primary gastric T‐cell lymphoma. We analysed 31 patients with primary gastric T‐cell lymphoma in south‐west Japan, an area endemic for HTLV‐1, and determined their phenotypes, genotypes, and HTLV‐1 status.Methods and results:  Here we present 31 cases of primary gastric T‐cell lymphoma in a HTLV‐1‐endemic area in Japan and analyse the clinical status, histology, phenotype and virus status. The median age at onset of primary gastric T‐cell lymphoma was 57 years with a gender ratio of M:F = 1.58:1. Six of the 31 primary gastric T‐cell lymphoma cases had HTLV‐1 proviral DNA (five males, one female), nine of the 31 cases were positive for anti‐adult T cell leukaemia antibody, without examination of HTLV‐1 proviral DNA (five males, four females), eight were non‐HTLV‐1‐associated primary gastric T‐cell lymphoma (four males, four females) and the other eight cases were unknown. Primary gastric T‐cell lymphoma usually presented as a large ulcerated tumour at the corpus to the antrum and histologically consisted of anaplastic large cell type (n = 2), pleomorphic large cell type (n = 3), pleomorphic medium and large cell type (n = 14), pleomorphic medium cell type (n = 11), and angioimmunoblastic T‐cell lymphoma type (n = 1). There were no clear macroscopic and microscopic differences between HTLV‐1‐associated and non‐HTLV‐1‐associated primary gastric T‐cell lymphoma. Most patients died within 2 years of diagnosis, and both types of primary gastric T‐cell lymphoma (with and without HTLV‐1) were associated with poor prognosis. Cytotoxic marker analysis showed that HTLV‐1‐associated lymphomas were negative for TIA‐1, while non‐HTLV‐1‐associated lymphomas were positive for TIA‐1.Conclusions:  Our results suggest that in HTLV‐1‐endemic areas, patients with HTLV‐1‐associated primary gastric T‐cell lymphoma should be managed carefully and that TIA‐1 seems to be useful for identifying the aetiology of this lesion.
Contribution of mast cells to the T helper 2 response induced by simultaneous subcutaneous and oral immunization
Authors: Aoki I. , Itoh S. , Yokota S. , Tanaka S.‐I. , Ishii N. , Okuda K. , Minami M. , Klinman D. M. 
Published: March 2003

SummaryThis work examines the contribution of mast cells to the synergistic enhancement of the T helper 2 (Th2) immune response elicited following simultaneous oral and subcutaneous (s.c.) immunization. The s.c. route induced a Th1‐biased immune response, characterized by increased interferon‐γ (IFN‐γ) and immunoglobulin G2a (IgG2a) antibody production. In contrast, oral immunization stimulated a primarily Th2‐type response in which interleukin‐4 (IL‐4) and IgG1 antibody production were dominant. Simultaneous immunization also triggered a Th2‐biased response, the magnitude of which exceeded the additive effects of s.c. and oral immunization alone by greater than threefold. To analyse whether mast cells in gut‐associated lymphoid tissue contributed to this synergistic response, mast cell‐deficient mice WBB6F1‐w/wv were studied. Whereas the primary response following simultaneously antigen administration was reduced only twofold in these animals compared with wild type controls WBB6F1‐+/+ (suggesting that mast cells were not needed to initiate Th2 immunity), reconstitution with bone‐marrow‐derived mast cells from WBB6F1‐+/+ mice resulted in a superoptimal response (suggesting that mast cells contribute to the magnitude and perpetuation of these Th2‐biased responses).
l‐selectin expression on thymic emigrants defines two distinct tissue‐migration pathways
Authors: Holder J. E. , Kimpton W. G. , Washington E. A. , Cahill R. N. P. 
Published: March 2003

SummaryWe have studied the appearance and phenotype of recent thymic emigrants in blood, spleen and lymph nodes (LN) of neonatal lambs. Using in situ labelling of thymocytes with fluoroscein isothiocyanate (FITC), we examined the expression of the LN homing receptor
l‐selectin on αβ and γδ subsets of recent thymic emigrants 24 hr after labelling. There were marked differences in the proportions of CD4+, CD8+ and γδ T‐cell receptor (TCR+) cells exported from the thymus to spleen compared to lymph nodes. Spleen was enriched in CD8+ and γδ TCR+ emigrants while LN were enriched in CD4+ emigrants. There were also marked differences in the expression of
l‐selectin by emigrants homing to spleen compared with those homing to lymph nodes. While the majority of thymic emigrants in LN expressed
l‐selectin, considerably fewer emigrants in spleen were
l‐selectin+. The presence of large numbers of CD8+ l‐selectin– and γδ TCR+ l‐selectin– thymic emigrants homing to spleen raises the possibility that unique homing receptor specificities underpin the migration of T cells to spleen as distinct from lymph nodes.
Identification of cation‐independent mannose 6‐phosphate receptor/insulin‐like growth factor type‐2 receptor as a novel target of autoantibodies
Authors: Tarrago D. , Aguilera I. , Melero J. , Wichmann I. , Nuñez‐roldan A. , Sanchez B. 
Published: March 2003

SummaryTwo human monoclonal autoantibodies, B‐33 and B‐24, were generated from the B cells of a patient with scleroderma. Both monoclonal antibodies (mAbs) were composed of µ and λ chains, and recognized cytoplasmic vesicular structures by indirect immunofluorescence on Hep‐2 cell line slides, although mAb B‐24 showed an additional diffuse cytoplasmic staining pattern. By Western blot, mAb B‐24 exhibited a polyreactive‐like binding pattern, whereas mAb B‐33 failed to recognize any electroblotted Hep‐2 antigen. The polyreactive versus monospecific behaviour of mAbs B‐24 and B‐33 was further confirmed by enzyme‐linked immunosorbent assay (ELISA) with a variety of foreign and autoantigens. The N‐terminal sequence of a protein band isolated by affinity chromatography with mAb B‐33 was identical to that of cation‐independent mannose 6‐phosphate receptor (CI‐MPR), also known as the insulin‐like growth factor type‐2 receptor (IGF‐2R). Immunofluorescence experiments on Hep‐2 cell line slides demonstrated a striking co‐localization between the staining pattern exhibited by these mAbs and the pattern obtained using a goat anti‐CI‐MPR serum, indicating the recognition by B‐24 and B‐33 of a structure located predominantly in late endosomes. Sequence analysis of the V‐region gene segments of B‐33 and B‐24 showed both to be identical, except for the existence of a point mutation in B‐33 located in the H‐complementarity‐determining region 3 (H‐CDR3) (position 100D), which produces a non‐conservative replacement of Gly by Ser. This single replacement appears to be responsible for the dramatic change in reactivity of human mAb B‐33. The data shown here provide new evidence of the critical role played by the H‐CDR3 region in distinguishing a polyspecific from a monospecific antibody. A population study demonstrated the existence of immunoglobulin G (IgG) reactivity against CI‐MPR/IGF‐2R in serum specimens from five individuals with different pathological conditions, thus indicating that this molecule is a potential target for the human autoimmune response.
Large clonal expansions of human virus‐specific memory cytotoxic T lymphocytes within the CD57+ CD28– CD8+ T‐cell population
Authors: Weekes M. P. , Wills M. R. , Mynard K. , Hicks R. , Sissons J. G. P. , Carmichael A. J. 
Published: March 2003

SummaryThe proportion of human peripheral blood CD8+ T cells that are CD57+ CD28– is low at birth but increases with age and in individuals infected with human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV). These CD57+ CD28– CD8+ T cells contain large oligoclonal T‐cell expansions whose antigen specificity is unknown. We identified clonal expansions of virus‐specific memory cytotoxic T‐lymphocyte precursors (CTLp) in both healthy carriers of HCMV and in asymptomatic HIV‐infected subjects. In each subject, from the T‐cell receptor (TCR) β‐chain hypervariable sequence of each immunodominant CTL clone, we designed complementary oligonucleotide probes to quantify the size and phenotypic segregation of individual virus‐specific CTL clones in highly purified populations of peripheral blood CD8+ T cells. We found large clonal expansions of virus‐specific CTL clonotypes in CD57+ CD28– CD8+ T cells. Using limiting dilution analysis, we found functional peptide‐specific CTLp at high frequency in CD57+ CD28– cells. Thus, memory CTL specific for persistent viruses account for many oligoclonal expansions within CD57+ CD28– CD8+ T cells.
Naturally occurring polyphenolic antioxidants modulate IgE‐mediated mast cell activation
Authors: Chen S.‐S. , Gong J. , Liu F.‐T. , Mohammed U. 
Published: March 2003

SummaryReactive oxygen species (ROS) are known to modulate activities of a host of kinases, phosphatases and transcription factors. Rutin and chlorogenic acid (CGA) are the major polyphenolic antioxidants present in the small molecular fraction of smokeless tobacco leaf extracts, as ascertained by reverse‐phase high‐pressure liquid chromatography (HPLC) and mass spectrometry. Levels of intracellular ROS in resting versus antigen–immunoglobulin E (IgE)‐challenged murine mast cells were measured at 510 nm by fluorescence‐activated cell sorting (FACS) using carboxy‐dichlorofluorescein (DCFH‐DA). Enhanced ROS production was observed in IgE‐sensitized mast cells following antigenic challenge. Rutin and CGA reduced ROS levels in antigen–IgE‐activated mast cells. Concomitantly, they also profoundly inhibited histamine release by these activated mast cells. In contrast, rutin and CGA augmented the inducible cytokine messages, i.e. interleukin (IL)‐10, IL‐13, interferon‐γ (IFN‐γ), IL‐6 and tumour necrosis factor‐α (TNF‐α) in IgE‐sensitized mast cells following antigen challenge. This study indicates that tobacco polyphenolic antioxidants that quench intracellular ROS, differentially affect two effector functions of antigen–IgE‐activated mast cells. This model system may be employed to determine the molecular target of polyphenols. The potential role of these polyphenolic antioxidants on IgE‐mediated allergy in vivo depends on a balance of their differential effects on mast cell activation.
Induction of functional CD154 (CD40 ligand) in neonatal T cells by cAMP‐elevating agents
Authors: Suárez A. , Mozo L. , Gayo A. , Simó A. , Gutiérrez C. 
Published: March 2003

SummaryA deficiency of neonatal T lymphocytes to express CD154 antigen in response to ionomycin and phorbol 12‐myrsistate 13‐acetate (PMA) stimulation or after CD3 cross‐linking has been described. In the present report we describe that CD45RA+ newborn cells are able to synthesize and express CD154 at similar or even higher levels than adult cells in response to ionomycin and cAMP‐elevating agents which trigger the protein kinase A (PKA) ‐mediated metabolic pathway. Peak CD154 protein concentrations in newborn cells were found between 4 and 8 hr after stimulation with ionomycin and dibutyryl cAMP. These agents, however, did not induce expression of the early activation antigen CD69. Surface levels of CD154 did not correlate with specific mRNA concentration, indicating that dibutyryl cAMP up‐regulates CD154 by acting at a post‐transcriptional stage. The CD154 antigen induced by PKA activation of newborn cells was functional, since upon binding to CD40 on B lymphocytes in the presence of interleukin‐4 (IL‐4), it promoted immunoglobulin heavy‐class switching to IgE. We also found a different pattern of cytokine production between neonatal and adult CD4+ T cells. In response to ionomycin and dibutyryl cAMP, cord blood cells were more prone than adult lymphocytes to secrete the T helper type 2‐derived immunosuppressive cytokines IL‐4 and IL‐10. Taking into account that the feto–maternal environment is rich in cAMP‐elevating agents, the reduced risk of graft versus host disease associated with cord blood trasplantation, as compared with the risk with adult bone marrow cell transplants, may be due to the bias of neonatal cells to differentiate towards the T helper type 2 functional cell subset.
Failure to remove autoreactive Vβ6+ T cells in Mls‐1a newborn mice attributed to the delayed development of B cells in the thymus
Authors: Touma M. , Mori K. J. , Hosono M. 
Published: March 2003

SummaryClonal deletion of autoreactive T cells in the thymus is one of the major mechanisms for establishing tolerance to self‐antigens, and self‐reactive T cells bearing Vβ6 T‐cell receptors are usually deleted before their maturation in Mls‐1a mice. However, these T cells develop transiently in the neonatal thymus, and migrate to the periphery. In order to understand the mechanisms which permit these potentially auto‐toxic T cells to generate, we investigated in vivo the physiological or functional properties of the elements involved, such as neonatal T cells, antigens and antigen‐presenting cells (APC). Confirming the previous findings that each of these elements per se is already completed in function in neonates, we investigated the possibility of the absence or immaturity of particular APC with Mls antigens of their own products in the neonatal thymus. In the search for the cellular and histological changes occurring in the newborn thymus, we found that the elimination of Vβ6+ T cells progressed in parallel with the development of thymic B cells. Involvement of B cells in purging the autoreactive T cells from the newborn thymus was shown by prevention of the deletion of Vβ6+ T cells after the removal of B cells by the treatment of neonates with anti‐immunoglobulin M antibodies. The restricted and stable expression of CD5 on the thymic B cells, but not on the splenic cells, suggests that these B cells are not postnatal immigrants from the periphery. Finally, it is concluded that the deficiency in the deletion of self‐reactive T cells in the thymus of Mls‐1a neonates is due to the delayed development of B cells.
Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus
Authors: Han S. N. , Wu D. , Ha W. K. , Beharka A. , Smith D. E. , Bender B. S. , Meydani S. N. 
Published: March 2003

SummaryCompared with young mice, old mice infected with influenza virus have significantly higher pulmonary viral titres, although these can be reduced significantly with dietary vitamin E supplementation. T helper 1 (Th1) cytokines, especially interferon‐γ (IFN‐γ), play an important role in defending against influenza infection. However, there is an age‐associated loss of Th1 cytokine production. Prostaglandin E2 (PGE2) production, which increases with age, can modulate the T helper cell function by suppressing Th1 cytokine production. To investigate the mechanism of vitamin E supplementation on reduction of influenza severity in old mice, we studied the cytokine production by splenocytes, and PGE2 production by macrophages (Mφ), in young and old C57BL mice fed semipurified diets containing 30 (control) or 500 parts per million (ppm) (supplemented) vitamin E for 8 weeks, and then infected with influenza A/PC/1/73 (H3N2). Old mice fed the control diet had significantly higher viral titres than young mice; old mice fed the vitamin E‐supplemented diet had significantly lower pulmonary viral titres than those fed the control diet (P = 0·02 and 0·001 for overall age and diet effect, respectively). Following influenza infection, interleukin (IL)‐2 and IFN‐γ production was significantly lower in old mice than in young mice. Vitamin E supplementation increased production of IL‐2 and IFN‐γ in old mice; higher IFN‐γ production was associated with lower pulmonary viral titre. Old mice fed the control diet showed significantly higher lipopolysaccharide (LPS)‐stimulated Mφ PGE2 production than old mice fed the vitamin E diet or young mice fed either diet. There was no significant age difference in IL‐6, IL‐1β, or tumour necrosis factor‐α (TNF‐α) production by splenocytes. Young mice fed the vitamin E‐supplemented diet had significantly lower IL‐1β (day 7) and TNF‐α production (day 5) compared with those fed the control diet. Old mice fed the vitamin E‐supplemented diet had significantly lower TNF‐α production (day 2) than those fed the control diet. Our results indicate that the vitamin E‐induced decrease in influenza viral titre is mediated through enhancement of Th1 cytokines, which may be the result of reduced PGE2 production caused by vitamin E.
Activation of T‐cell receptor‐γδ+ cells in the intestinal epithelia of KN6 transgenic mice
Authors: Kawaguchi‐Miyashita M. , Shimada S. , Matsuoka Y. , Ohwaki M. , Nanno M. 
Published: March 2003

SummaryWe analysed the properties of intraepithelial lymphocytes of small intestine (SI‐IEL) in KN6‐transgenic (Tg) mice expressing cDNA of T‐cell receptor (TCR)‐γδ specific for the T22b molecule. While most splenic Tg TCR‐γδ+ cells from KN6‐Tg mice with H‐2d/d background (Tgd/d mice) were Thy‐1+ CD8α– CD44dull+ CD45RB+ CD69–, Tg TCR‐γδ+ cells in SI‐IEL (Tg γδ‐IEL) were heterogeneous in the expression of Thy‐1, CD8α and CD44 molecules and predominantly CD45RB+ CD69+. Tg γδ‐IEL exhibited a much reduced proliferative response to the antigen (irradiated H‐2b splenocytes) than splenic Tg TCR‐γδ+ cells; the CD44+ subset, but not the CD44– subset, in Tg γδ‐IEL responded to the antigen. Furthermore, Tg γδ‐IEL, but not splenic Tg TCR‐γδ+ cells, displayed cytolytic activity whether they were prepared from conventional or germ‐free KN6‐Tg mice. Comparative analysis of young and aged KN6‐Tg mice revealed that the proportion of CD44+ cells in Tg γδ‐IEL increased but the proliferative response of Tg γδ‐IEL to the antigen attenuated in association with ageing. Moreover, although Tg γδ‐IEL from Tgb/d mice contained a higher proportion of CD44+ cells than Tgd/d mice, they did not respond to the antigen. These results demonstrate that Tg TCR‐γδ+ cells lose the ability to recognize the antigen following activation in the intestinal epithelia.