bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of respiratory mucins in fatal status asthmaticus and mild asthma
Authors: Groneberg D A , Eynott P R , Lim S , Oates T , Wu R , Carlstedt I , Roberts P , McCann B , Nicholson A G , Harrison B D , Chung K F 
Published: March 2003

Expression of respiratory mucins in fatal status asthmaticus and mild asthma Aims: The airways of patients with asthma are characterized by chronic inflammatory changes comprising mainly T‐cells and eosinophils, and airway remodelling with goblet cell metaplasia and submucosal gland hyperplasia. Mucus hypersecretion is often a marked feature, particularly in status asthmaticus. The matrix of airway sputum consists of high molecular glycoproteins and mucins. In this study, the expression and distribution of the major gel‐forming mucins MUC5AC and MUC5B were studied in fatal status asthmaticus tissues and bronchial biopsies of mild asthmatic patients. The effect of inhaled corticosteroids on the expression of these mucins was also investigated. Methods and results:  Polyclonal antibodies specific for MUC5AC and MUC5B, and a monoclonal antibody for MUC5B were used to stain lung tissues and airway mucosal biopsies obtained from patients who died of status asthmaticus (n=5) and from mild asthmatics (n=4), respectively. Immunohistochemistry for MUC5AC revealed abundant staining of goblet cells situated in the epithelial surface lining and glandular ducts of tissues from patients with fatal asthma. MUC5B immunoreactivity was restricted to mucous cells of submucosal glands and to epithelial cells. In mild asthmatics, large amounts of MUC5B, but not MUC5AC, positive extracellular mucus was found in the airway lumen as plugs, adjacent to the epithelial lining and in the necks of glandular secretory ducts of mild asthmatics. The distribution of MUC5AC and MUC5B in bronchial biopsies of mild asthmatics was similar before and after inhaled steroid treatment. Conclusions: The expression of MUC5AC and MUC5B shares a similar distribution to normal airways in different states of asthma. The distribution is not affected by topical corticosteroid therapy.
Keratin expression in human tissues and neoplasms
Authors: Chu P G , Weiss L M 
Published: March 2003

Keratin expression in human tissues and neoplasms Keratin filaments constitute type I and type II intermediate filaments (IFs), with at least 20 subtypes named keratin 1–20. Since certain keratin subtypes are only expressed in some normal human tissues but not others, and vice versa, various tissues have been subclassified according to the pattern of keratin staining. Simple epithelia generally express the simple epithelial keratins 7, 18, 19, and 20, while complex epithelia express complex epithelial keratins 5/6, 10, 14, and 15. When an epithelium undergoes malignant transformation, its keratin profile usually remains constant. The constitution and expression patterns of keratin filaments in human epithelial neoplasms are complex and often distinctive. In this article, we first briefly review the molecular and cell biology of keratin filaments. We then focus on the expression patterns of keratin filaments in various human neoplasms.
Mixed ductal–pancreatic polypeptide‐cell carcinoma of the pancreas
Authors: Chatelain D , Parc Y , Christin‐Maitre S , Parc R , Flejou J‐F 
Published: March 2003

Mixed ductal–pancreatic polypeptide‐cell carcinoma of the pancreasAims:  Mixed ductal‐endocrine carcinomas of the pancreas are rare tumours with 10 cases reported in the English literature. We report the first case with a polypeptide‐cell component.Methods and results:  The tumour was fortuitouslydiscovered in a 72‐year‐old woman during the exploration of an endometrial adenocarcinoma. It measured 100 mm and was located in the tail of the pancreas. On microscopic examination two intermingled endocrine and exocrine components were present. The endocrine component consisted of trabeculae and solid nests composed of cells immunoreactive for chromogranin A, synaptophysin and pancreatic polypeptide, but negative for p53 and Bcl‐2 proteins. The exocrine component was composed of tubules lined by atypical cylindrical cells immunoreactive for CK19, CEA, p53 and Bcl‐2. The stroma of the endocrine component contained amyloid deposits.Conclusion:  Mixed ductal–endocrine carcinomas of the pancreas are often described in middle‐aged patients. The tumours are usually large and located in the head of the pancreas. An endocrine syndrome is rare and the prognosis is often unfavourable. We report the first case of mixed endocrine–exocrine carcinoma of the pancreas with a pancreatic polypeptide‐cell component. The histogenesis of mixed carcinoma of the pancreas is still uncertain but the over‐expression of p53 and Bcl‐2 could play a major role in the neoplastic progression of the ductal component.
Expression of cytokeratins 7 and 20 in carcinomas of the gastrointestinal tract
Authors: Kende A I , Carr N J , Sobin L H 
Published: March 2003

Aims:  The differential expression of cytokeratin (CK) 7 and 20 by carcinomas may help in determining the primary site of a metastatic tumour. The aim of this study was to extend the published data on CK7 and CK20 expression in epithelial neoplasms of the gastrointestinal tract by considering the degree of differentiation and including some unusual neoplasms.Methods and results:  Cases referred to the Armed Forces Institute of Pathology were studied prospectively for immunohistochemical expression of CK7 and CK20. Lesions from 105 patients were analysed. Adenocarcinomas of the upper gastrointestinal tract were positive for both CK7 and CK20 in 78% of cases; only poorly differentiated lesions were CK7–. Well‐differentiated and moderately differentiated adenocarcinomas of the large intestine, including appendix, were CK7–/CK20+ in the great majority of cases, as were goblet cell carcinoids, but half of the poorly differentiated adenocarcinomas exhibited aberrant expression, as did most of the mixed goblet cell carcinoid/adenocarcinomas. All five high‐grade neuroendocrine carcinomas were negative for both CK7 and CK20.Conclusions:  Not only the site but also the grade and histological type of a gastrointestinal carcinoma should be considered when assessing cytokeratin phenotype.
Alteration of E‐cadherin‐mediated adhesion protein is common, but microsatellite instability is uncommon in young age gastric cancers
Authors: Lim S , Lee H S , Kim H S , Kim Y I , Kim W H 
Published: March 2003

Aims:  Gastric adenocarcinoma in young patients has been considered to differ in many ways from gastric carcinoma in older patients. This study was designed to determine the clinicopathological features and molecular mechanisms.Methods and results:  Based on 4123 patients of gastric cancer in Seoul National University Hospital, 135 patients (3.3%) were chosen by the age of 30 years or younger. Expression of E‐cadherin, β‐catenin, p53 and Epstein–Barr virus (EBV) was analysed using the tissue array method in formalin‐fixed paraffin‐embedded specimens and microsatellite instability (MSI) was determined. As a control, 320 cases of older patients were compared. Gastric adenocarcinoma of young patients revealed significant female predominance, type IV gross type, proximal location, diffuse type and frequent lymph node metastasis. In‐situ hybridization for EBV showed higher positivity in young patients (9/78, 11.5%) than in older ones, but not statistically significant. In EBV+ cases, p53 over‐expression was significantly higher in young patients than older patients (P < 0.05). Alteration of E‐cadherin or β‐catenin was significantly higher in younger patients than in older patients (P < 0.05). Overall survival was significantly poorer in younger patients than older ones. The frequency of MSI was rare (1.3%, P < 0.05) in young patients compared with older patients (9.3%).Conclusions:  These data indicate that gastric adenocarcinoma of young patients has a poor prognosis, possesses aggressive histopathological features, exhibits reduced expression of E‐cadherin and β‐catenin, and demonstrates lower MSI than tumours in older patients.
Bacterial lipopolysaccharide acts as an adjuvant to induce autoimmune arthritisin mice
Authors: Yoshino S. , Sasatomi E. , Ohsawa M. 
Published: March 2003

SummaryWe investigated the ability of lipopolysaccharide (LPS) as an adjuvant to induce autoimmune arthritis. LPS from Escherichia coli was intraperitoneally injected into DBA/1J mice together with the joint cartilage component type II collagen (CII) on day 0. Thereafter, the injection of CII and LPS was continued every 2 weeks up to day 56. The results showed that mice injected with CII plus LPS had signs of arthritis on day 55 and the joint inflammation reached a peak on day 75. Injection of CII or LPS alone induced no arthritis. Histologically, marked oedema of synovium and intense infiltration of inflammatory cells, including neutrophils, were observed 3 days after the onset of joint inflammation. Twenty‐one days later, there were marked proliferation of synovial tissues with many mononulear cells and destruction of cartilage. Anti‐CII immunoglobulin G (IgG) and IgG2a antibodies were markedly produced in mice injected with CII plus LPS. Pronounced secretion of cytokines, including interleukins‐12 and ‐1β, interferon‐γ and tumour necrosis factor‐α, was also observed in these animals. Arthritis was passively transferred into naive syngeneic mice with sera but not with lymphoid cells from mice given CII with LPS. Other types of LPS from Salmonella enteritidis, Salmonella typhimurium and Klebsiella pneumoniae as well as lipid A from E. coli, induced inflammation in joints when administered with CII. Polymixin B sulphate mixed with LPS or lipid A blocked the induction of joint inflammation. These results indicate that LPS appears to play an important role as an adjuvant in the induction of arthritis in which autoimmunity to CII is involved.
Decreased expression of FcγRIII (CD16) by γδ T cells in patients withrheumatoid arthritis
Authors: Bodman‐smith M. D. , Anand A. , Durand V. , Youinou P. Y. , Lydyard P. M. 
Published: March 2003

SummarySome γδ T cells express a receptor for the Fc portion of immunoglobulin G (FcγRIII – CD16). The relevance of this Fc receptor to γδ T‐cell function is at present unclear. Our previous studies have shown that γδ T cells express activation markers in patients with rheumatoid arthritis (RA). In this study we have examined the relative proportions of CD16+γδ T cells in the blood and synovial fluid of these patients compared with control blood. CD16+γδ T cells from RA patients were significantly reduced in synovial fluid compared with the circulation. That this was due to blocking of antibody binding to CD16 was unlikely as treatment of blood γδ T cells with RA synovial fluid (known to contain immune complexes) failed to alter expression of CD16. Treatment of blood γδ T cells with phytohaemagglutinin in vitro, resulted in a time‐dependent decrease in expression of CD16, with a concomitant increase in expression of human leucocyte antigen‐DR, at the single cell level. We conclude that expression of CD16 by γδ T cells is lost in the synovial compartment as the result of activation.
γδ T‐cell anergy in human immunodeficiency virus‐infected persons with opportunistic infections and recovery after highly active antiretroviral therapy
Authors: Martini F. , Urso R. , Gioia C. , De Felici A. , Narciso P. , Amendola A. , Paglia M. G. , Colizzi V. , Poccia F. 
Published: March 2003

Summaryγδ T lymphocytes recognize non‐peptidic microbial antigens without antigen processing and major histocompatibility complex (MHC) restriction, representing an early defence mechanism against invading pathogens. As a defective response to non‐peptidic antigens was observed in human immunodeficiency virus‐positive (HIV+) persons, the aims of this study were twofold: to analyse the incidence of γδ T‐cell anergy in HIV+ patients with opportunistic infections/co‐infections (HIV‐OIC), and to investigate the role of highly active antiretroviral therapy (HAART) on γδ T‐cell functions. Peripheral γδ T‐cell distribution and in vitro reactivity to a non‐peptidic mycobacterial antigen, isopentenyl pyrophosphate (IPP), were analysed. γδ T‐cell subset distribution was altered more in HIV‐OIC patients than in asymptomatic HIV+ subjects (HIV‐ASY). Specifically, the Vδ2/Vδ1 ratio was inverted as a consequence of a decrease in Vδ2 T‐cell number. Moreover, IPP‐stimulated Vδ2 T cells from the HIV‐OIC group displayed a major defect in interferon‐γ (IFN‐γ) production. Interestingly, HAART induced a sustained recovery of naive CD45RA+ and CD62L+ T cells and restored γδ T‐cell function. Accordingly, in vitro CD45RA depletion resulted in γδ T‐cell hyporesponsiveness. Altogether, the incidence of γδ T‐cell anergy was increased in HIV‐OIC patients and dependent on CD45RA helper function. Moreover, HAART was able to restore γδ T‐cell reactivity, extending the immune recovery to non‐peptidic microbial antigens.
Feline leukaemia virus: protective immunity is mediated by virus‐specific cytotoxic T lymphocytes
Authors: Flynn J. N. , Hanlon L. , Jarrett O. 
Published: March 2003

SummaryFeline leukaemia virus (FeLV) nucleic acid vaccination of domestic cats affords protection against viraemia and the development of latency without inducing antiviral antibodies.1To determine the contribution of cell‐mediated immunity to the control of virus replication and clearance from the host, FeLV‐specific cytotoxic T lymphocyte (CTL) responses were compared in vaccine‐protected, transiently viraemic, and persistently viraemic cats. Vaccinal immunity was associated with the detection of higher levels of virus‐specific effector CTL in the peripheral blood and lymphoid organs to FeLV Gag/Pro and Env antigens than those observed in unvaccinated control, persistently viraemic cats (P < 0·001). Likewise, higher levels of virus‐specific CTLs were also observed in transiently viraemic cats which recovered following exposure to FeLV. In cats that controlled their infection, recognition of Gag/Pro antigens was significantly higher than the recognition of Env antigens. This is the first report highlighting the very significant role that virus‐specific CTL have in determining the outcome of FeLV infection in either vaccinated cats or cats recovering naturally from FeLV exposure.
Immunoglobulin A cell distribution in the human small intestine: phenotypic and functional characteristics
Authors: Farstad I. N. , Carlsen H. , Morton H. C. , Brandtzaeg P. 
Published: March 2003

SummaryWe compared B‐cell phenotypes in Peyer's patches and solitary lymphoid follicles (organized gut‐associated lymphoid tissue, GALT) with those in jejunal or ileal lamina propria. In situ, immunostaining showed that small B cells of naive [surface immunoglobulin D‐positive (sIgD+) CD27–] and memory (sIgD± CD27+) phenotypes occurred almost exclusively in GALT, whereas the lamina propria contained only scattered sIgA+ CD27+ memory cells. In contrast, B‐cell blasts and plasma cells negative for CD20 and often also for CD19 but with strong expression of CD38, CD27 and cytoplasmic IgA (cIgA), dominated in the lamina propria but were scarce in GALT. By flow cytometry, the proportion of dispersed CD19+ B lymphocytes varied from 4 to 42% among jejunal mucosal samples; between 5 and 50% of these were sIgD+, suggesting a variable contamination with GALT cells. B‐cell blasts and plasma cells, identified by their large size and strong expression of CD38, were regularly found (25–35% of the total mononuclear cell population). Distinction between B‐cell blasts and mature plasma cells was made by the presence or absence of human leucocyte antigen (HLA) class II molecules, CD45RA, CD19 and surface immunoglobulin. No CD19+ B cells outside GALT expressed CD5, but a very small portion of the lamina propria B‐cell blasts were positive for CD28. Dispersed sIgA+ lamina propria cells expressed low levels of CD40, proliferated on CD40 ligation and constitutively secreted IgA in vitro. We concluded that the lamina propria B‐cell compartment consists mainly of B‐cell blasts and plasma cells but also has scattered, small sIgA+ cells that can proliferate in response to CD40 ligation and may therefore function as local memory cells for recall antigens.
An αβ T‐cell‐independent immunoprotective response towards gut coccidia is supported by γδ cells
Authors: Smith A. L. , Hayday A. C. 
Published: March 2003

SummaryAlthough γδ cells are commonly hypothesized to provide a ‘first line of defence’, γδ‐cell‐deficient mice are generally only marginally more susceptible to pathogens. Because γδ cells are enriched within epithelia, it is important to resolve whether immunoprotective capacity towards epithelial‐tropic pathogens is absent from the γδ‐cell compartment, or whether such activity is present but simply redundant with that of αβ T cells. In this work, following infection of the intestinal epithelium of αβ T‐cell‐deficient mice with the coccidian parasite, Eimeria vermiformis, γδ cells were shown to support the rapid activation of other lymphoid cells and to confer a transferable antipathogen effect that could be eradicated by neutralization of interferon‐γ. However, unlike αβ T cells, these effects of γδ cells showed no evidence of functional immunological memory. These results are directly relevant to coccidiosis, an economically significant disease of livestock, and should have general relevance to infections involving αβ T‐cell deficiencies, e.g. cryptosporidiosis in patients with acquired immune deficiency syndrome (AIDS).
T helper 1‐type cytokine transcription in peripheral blood mononuclear cells of pseudorabies virus (Suid herpesvirus 1)‐primed swine indicates efficient immunization
Authors: Fischer T. , Büttner M. , Rziha H.‐J. 
Published: March 2003

SummaryThe induction of porcine cytokines, which are believed to be important for the regulation of T helper (Th)1‐ and Th2‐specific immune responses of pigs, was analysed after in vitro restimulation with a herpesvirus, Suid herpes 1 (pseudorabies virus [PRV]), in peripheral blood mononuclear cells (PBMC). To this end, quantitative, competitive reverse transcription–polymerase chain reaction (RT–qcPCR) was established using constructed heterologous DNA MIMICS, which contain cytokine‐ or glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH)‐specific primer‐binding sites. This is a simple method that allows reliable determination of the differing regulation of cytokine mRNAs specific for porcine interleukin (IL)‐2, ‐4 and ‐10, interferon gamma (IFN‐γ) and the housekeeping gene, GAPDH, as an endogenous control. PBMC derived from naive (innate response) and PRV‐primed (memory response) outbred swine were analysed comparatively. The results demonstrated that restimulation with PRV significantly enhanced the transcription of Th1‐type cytokines (IL‐2 and IFN‐γ) but not of Th2‐type cytokines (IL‐4 and IL‐10). This virus‐specific cytokine response was only found with PBMC from swine protected against lethal PRV challenge infection, but not with naive PBMC or with PBMC from pigs immunized with plasmid DNA encoding PRV glycoprotein gC. Notably, PBMC derived from immune and naive pigs constitutively produced relatively high amounts of IL‐10‐specific mRNA, exceeding that of GAPDH mRNA, independently of the addition of viral antigen or the mitogen concanavalin A (Con A). The results of this work should help to provide a better understanding of the effector cell/cytokine network response to infection with, or vaccination against, PRV. Additionally, the simple, reliable and sensitive RT–qcPCR, when used to determine the porcine cytokine pattern, might be of prognostic value for the induction of protective immunity.
Natural autoantibodies against heat‐shock proteins hsp70 and gp96: implications for immunotherapy using heat‐shock proteins
Authors: Ménoret A. , Chandawarkar R. Y. , Srivastava P. K. 
Published: March 2003

SummaryImmunization of mice with cognate cancer‐derived heat‐shock protein (hsp) preparations leads to protection from cancer growth. As hsp used for vaccination or therapy are derived from autologous cancers, questions of pathological autoimmunity are of immense significance for the ongoing translation of this approach to therapy of human cancer. Employing the sera of normal adult mice as the first antibody, highly sensitive immunoblotting revealed the presence of anti‐hsp natural autoantibodies in healthy animals. Natural autoantibodies of the immunoglobulin D (IgD) isotype bind to gp96, whereas hsp70 was recognized by IgD and IgM autoantibodies. Neither hsp was recognized by the IgA, IgE or IgG immunoglobulins contained in the serum. The antigen–antibody recognition was titratable and dependent on the integrity of the IgD molecule. Sera from only a subset of the animals tested were found to be positive for autoantibodies against gp96 and hsp70, and individual and strain‐specific variations were detected. Injection of gp96 into healthy mice did not show sustained or consistent anti‐gp96 IgD antibody response, class switching, toxicity or pathological autoimmunity. IgD autoantibodies against gp96 and hsp70 were also not detected in the autoimmune lpr mice. These observations show the existence of a measured and tightly regulated natural immune response to hsp.
Modulation of delayed‐type hypersensitivity during the time course of immune response to a protein antigen
Authors: Jacysyn J. F. , Abrahamsohn I. A. , Macedo M. S. 
Published: March 2003

SummaryDelayed‐type hypersensitivity reactions elicited in the footpad of ovalbumin‐sensitized mice after challenge with aggregated ovalbumin on day 4 or 8 of immunization are distinct. The former was characterized by a dense mononuclear infiltrate and, macroscopically, the reaction peaked at 48 hr after antigen challenge; the latter was preceded by immediate‐type reactions, reached the maximum at 24 hr and faded drastically later. Histologically, oedema and a mixed granulocytic–lymphocytic infiltrate was found at this time‐point. Immunoglobulin G1 (IgG1), IgG2a and IgE antibodies were detected only in plasma obtained after 8 days of immunization. Regarding the cytokines produced by draining lymph node cells after in vitro restimulation, interleukin‐4 (IL‐4) and IL‐10 were predominant after 4 days and interferon‐γ and IL‐2 after 8 days of immunization. These two types of delayed‐type hypersensitivity (DTH) were used to study the influence of antibody‐mediated responses on the inductive and effector phases of cell‐mediated immunity. The effector phase of DTH was not affected by immediate‐type reactions, as abrogation of these reactions by mediators' antagonists on day 8 or induction of passive reactions by transfer of immune serum on day 4 did not change the extent or kinetics of either type of DTH. Only transfer, before immunization, of whole or T‐cell‐enriched spleen cells, but not sera, from hyperimmunized donors (high antibody producers) abolished the induction of pure DTH in 4‐day immunized recipient mice and changed their cytokine profile to a T helper 2 type. These results indicate that in a non‐polarized immune response to a protein antigen there is initially a bias towards cell‐mediated immunity, which is gradually dampened by the development of antibody‐mediated immunity.