bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nickel-induced IL-10 down-regulates Th1- but not Th2-type cytokine responses to the contact allergen nickel
Authors: Minang J T , Areström I , Zuber B , Jönsson G , Troye-Blomberg M , Ahlborg N 
Published: February 2006

SummaryWhereas the involvement of Th1- and Th2-type cytokines in contact allergy to nickel (Ni) is well documented, the role of the regulatory cytokine IL-10 is less clear. We therefore investigated the impact of IL-10 on Ni-induced Th1- (IFN-γ) and Th2-type (IL-4 and IL-13) cytokine responses in human peripheral blood mononuclear cells (PBMC). PBMC from 15 blood donors with reactivity to Ni (Ni-PBMC) and 8 control donors devoid of reactivity (control PBMC) were stimulated with Ni and the frequency of cytokine-producing cells and the levels of secreted cytokines were analysed by ELISpot (IL-4, IL-13 and IFN-γ) and ELISA (IL-10, IL-13 and IFN-γ), respectively. The Ni-induced response was further assessed in the presence of recombinant IL-10 (rIL-10) or neutralizing antibody to IL-10 and the phenotype of the Ni-specific cytokine-producing cells regulated by IL-10 was determined by cell depletion experiments. Ni induced IL-10 production in Ni-PBMC (mean, (range); 33·1 pg/ml (0–93·4 pg/ml)) but not control PBMC (2·2 pg/ml (0–14·9 pg/ml)) (P = 0·002). Ni also induced significant production of IL-4, IL-13 and IFN-γ that correlated with the IL-10 response. Addition of rIL-10 down-regulated the Ni-induced production of all cytokines but with a more pronounced effect on IFN-γ. However, neutralization of Ni-induced IL-10 enhanced the levels of IFN-γ induced by Ni (P = 0·004) but did not affect the number of IFN-γ-producing cells or the production of other cytokines. Cell depletion experiments suggested that the Ni-specific IFN-γ (and Th2-type cytokine) producing cells were CD4+ T cells. The impact of IL-10 on Ni-induced IFN-γ responses by CD4+ T cells suggests that an important role of IL-10 in vivo is to counteract the allergic reactions mediated by Th1-type cytokines.
The local immune response in ulcerative lesions of Buruli disease
Authors: Kiszewski A E , Becerril E , Aguilar L D , Kader I T A , Myers W , Portaels F , Hernàndez Pando R 
Published: February 2006

SummaryBuruli disease (BU) is a progressive necrotic and ulcerative disease of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. BU is considered the third most common mycobacterial disease after tuberculosis and leprosy. Three clinical stages of the cutaneous lesions have been described in BU: pre-ulcerative, ulcerative and healed lesions. In this study we used immunohistochemistry and automated morphometry to determine the percentage of macrophages and of CD4/CD8 lymphocytes and their expression of interferon (IFN)-γ, interleukin (IL)-10, tumour necrosis factor (TNF)-α and transforming growth factor (TGF)-β. Expression of these cytokines was correlated with the inflammatory response evaluated by histopathology. All the studied BU ulcerative cases showed extensive necrosis and chronic inflammation. The most important feature was the presence or absence of granulomas co-existing with a mixed pro-inflammatory/anti-inflammatory cytokine balance. When granulomas were present significantly higher expression of IFN-γ was seen, whereas in ulcerative lesions without granulomas there was increased expression of IL-10 and significantly higher bacillary counts. These features correlated with the chronicity of the lesions; longer-lasting lesions showed granulomas. Thus, granulomas were absent from relatively early ulcerative lesions, which contained more bacilli and little IFN-γ, suggesting that at this stage of the disease strong suppression of the protective cellular immune response facilitates proliferation of bacilli.
Human autoantibodies to diacyl-phosphatidylethanolamine recognize a specific set of discrete cytoplasmic domains
Authors: Laurino C C F C , Fritzler M J , Mortara R A , Silva N P , Almeida I C , Andrade L E C 
Published: February 2006

Summary
The aim of this study was to characterize a novel human autoantibody–autoantigen system represented as cytoplasmic discrete speckles (CDS) in indirect immunofluorescence (IIF). A distinct CDS IIF pattern represented by 3–20 discrete speckles dispersed throughout the cytoplasm was identified among other cytoplasmic speckled IIF patterns. The cytoplasmic domains labelled by human anti-CDS-1 antibodies did not co-localize with endosome/lysosome markers EEA1 and LAMP-2, but showed partial co-localization with glycine–tryptophan bodies (GWB). CDS-1 sera did not react with several cellular extracts in immunoblotting and did not immunoprecipitate recombinant GW182 or EEA1 proteins. The typical CDS-1 IIF labelling pattern was abolished after delipidation of HEp-2 cells. Moreover, CDS-1 sera reacted strongly with a lipid component co-migrating with phosphatidylethanolamine (PE) in high performance thin-layer chromatography (HPTLC)-immunostaining of HEp-2 cell total lipid extracts. The CDS-1 major molecular targets were established by electrospray ionization–mass spectrometry (ESI-MS), HPTLC-immunostaining and chemiluminescent enzyme-linked immunosorbent assay as diacyl-PE species, containing preferentially a cis-C18 : 1 fatty acid chain at C-2 of the glycerol moiety, namely 1,2-cis-C18 : 1-PE and 1-C16 : 0-2-cis-C18 : 1-PE. The clinical association of CDS-1 sera included a variety of systemic and organ-specific autoimmune diseases but they were also observed in patients with no evidence of autoimmune disease.
Leptin, soluble interleukin-6 receptor, C-reactive protein and soluble vascular cell adhesion molecule-1 levels in human coronary atherosclerotic plaque
Authors: Karaduman M , Oktenli C , Musabak U , Sengul A , Yesilova Z , Cingoz F , Olgun A , Sanisoglu S Y , Baysan O , Yildiz O , Taslipinar A , Tatar H , Kutlu M , Ozata M 
Published: February 2006

Summary
The aim of the present study was to explore the relationship between tissue levels of leptin, soluble interleukin-6 receptor (sIL-6R), high-sensitive-C-reactive protein (hs-CRP) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in atherosclerotic plaques, and traditional risk factors. Coronary artery specimens were obtained from 35 consecutive patients (26 men and nine women) who underwent coronary artery bypass grafting procedure. The mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in patients with diabetes mellitus than without diabetes mellitus. When patients were classified according to the smoking status, the mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in current smokers than both former smokers and non-smokers. In addition, the mean tissue levels of leptin and sIL-6R were significantly higher in former smokers than non-smokers. There was a positive association between leptin and hs-CRP, sIL-6R and plasma glucose in all patients. Plasma HDL levels were associated negatively with atherosclerotic tissue levels of leptin. Tissue levels of sIL-6R were associated significantly in a positive manner with leptin, hs-CRP and plasma glucose, while tissue levels of hs-CRP were associated with both leptin and sIL-6R. In conclusion, it is attractive to speculate that hs-CRP, sIL-6R and leptin could act synergistically in course of local inflammatory activity and those molecules may not be just markers of inflammation and cardiovascular risk but are also likely to play a pathogenic role in atheromatous plaque. In addition, atherosclerotic tissue levels of CRP, sIL-6R and leptin were significantly higher in current smokers and patients with diabetes.
Cancer immunotherapy using dendritic/tumour-fusion vaccine induces elevation of serum anti-nuclear antibody with better clinical responses
Authors: Homma S , Sagawa Y , Ito M , Ohno T , Toda G 
Published: February 2006

SummaryDendritic cell (DC) vaccines might induce both anti-tumour immunity and autoimmunity. In this report, we demonstrate elevated levels of anti-nuclear antibody (ANA) in the sera of patients with cancer who had received immunotherapy with a dendritic/tumour-fusion vaccine. Twenty-two patients were treated with DC vaccine of fusion cells composed of autologous DCs and tumour cells (DC/tumour-fusion vaccine), which was generated by treating each cell type with polyethylene glycol. Nine of the 22 patients were treated with both the DC/tumour-fusion vaccine and systemic administration of recombinant human interleukin (rhIL)-12. Serum levels of ANA were examined with an enzyme-linked immunosorbent assay kit. One patient with gastric carcinoma (patient 1, DC/tumour-fusion vaccine alone), one patient with breast cancer (patient 2, DC/tumour-fusion vaccine alone) and one patient with ovarian cancer (patient 3, DC/tumour-fusion vaccine + rhIL-12) showed significant elevations of serum ANA levels during treatment. In patient 1 malignant ascitic effusion resolved and serum levels of tumour markers decreased. Patients 2 and 3 remained in good physical condition during treatment for 24 and 9 months, respectively. Immunoblot analysis indicated antibody responses to autologous tumour cells after vaccination in patient 2. None of the treated patients showed clinical symptoms suggesting autoimmune disease. Patients with elevated serum levels of ANA had significantly longer treatment periods than those without it. Elevated serum levels of ANA after DC/tumour-fusion cell vaccine might be associated with anti-tumour immune response induced by the vaccination.
Reduction of tissue transglutaminase autoantibody levels by gluten-free diet is associated with changes in subsets of peripheral blood lymphocytes in children with newly diagnosed coeliac disease
Authors: Agardh D , Lynch K , Brundin C , Ivarsson S-A , Lernmark Å , Cilio C M 
Published: February 2006

SummaryTissue transglutaminase (tTG) autoantibodies decline after gluten-free diet in patients with coeliac disease. We tested the hypothesis that gluten-free diet-induced change in tTG autoantibody levels affects subsets of peripheral blood lymphocytes. Peripheral blood was obtained from 20 children with biopsy-proven active coeliac disease. Gluten-free diet was initiated and the children examined again after three and six months. tTG autoantibodies were measured in radioligand binding assays and lymphocyte subsets by flow cytometry. IgA-tTG levels at diagnosis, 2204 U/ml (median, range 113–24990), were reduced over six months to 76 U/ml (median, range 1–1261) (P &lt; 0·001). At six months, 12/20 (60%) children had reduced their IgA-tTG levels to &lt; 100 U/ml and these children showed a decrease in B cells (mean change −3·8%, P = 0·014), CD4+ T cells (mean −4·32%, P = 0·011) and CD4+ T cells expressing CD25high (mean change −0·62%, P = 0·036). In contrast, the CD4+CD25highCCR4+ T cell population increased during the same period (mean change 11·5%, P = 0·0036). The decline in IgA-tTG levels correlated to the decrease in B cells (r = 0·56, P = 0·01), CD4+ T cells (r = 0·66, P = 0·004) as well as CD4+CD25high T cells (r = 0·59, P = 0·01). A negative correlation was found between the decline in IgA-tTG and CD4+CD25high T cells expressing CD45RO (r = –0·49, P = 0·03) and CCR4 (r = –0·54, P = 0·01). This is the first observational study on the effect of gluten-free diet on concurrent changes of tTG autoantibodies and specific peripheral blood lymphocyte subsets. Our data suggest that flow cytometry may be a useful complement to tTG autoantibodies when studying the effects of gluten-free diet in children with coeliac disease.
Quality of glucocorticoid replacement in adrenal insufficiency: clinical assessment vs. timed serum cortisol measurements
Authors: Arlt Wiebke , Rosenthal Carmen , Hahner Stefanie , Allolio Bruno 
Published: February 2006

SummaryObjective  Evaluation of glucocorticoid replacement quality in adrenal insufficiency (AI) relies primarily on clinical judgement and thus largely depends on the physician's expertise. It is a matter of debate whether cortisol day curves are of value in assessing glucocorticoid replacement quality. Here we compared the results of a structured clinical assessment to the outcome of repeated, timed serum cortisol measurements.Design  Cross‐sectional study in the outpatient department of a university teaching hospital.Patients  Forty‐six patients (19 men, 27 women, age range 16–76 years) with primary (n = 23) and secondary (n = 23) AI on stable replacement with a median dose of 37·5 mg cortisone acetate (range 25–50 mg) since 10 ± 7 years (range 1–31 years).Measurements  Clinical performance was scored by structured assessment of signs and symptoms, physical examination and routine biochemical tests. Serum cortisol was measured on two to three separate occasions in three timed samples after the morning glucocorticoid dose. Bone mineral density was measured in 15 patients with long‐standing glucocorticoid replacement.Results  Thirty‐seven patients were considered well replaced, whereas clinical scores suggested over‐ or under‐replacement in five and four, respectively. There was no correlation of the clinical score with total or body weight‐adjusted glucocorticoid dose. The mean z score of serum cortisol differed significantly between under‐ and over‐replaced patients (P < 0·05) but neither group differed significantly from well‐replaced patients. Bone mineral density was normal in all patients studied.Conclusions  Our results suggest that serum cortisol day curves are of limited value in the monitoring of glucocorticoid replacement. Bone mineral density in AI is generally normal and does not require routine follow‐up.
Phenotypic variability in children with growth hormone deficiency associated with posterior pituitary ectopia
Authors: Simon Dominique , Hadjiathanasiou Charalambos , Garel Catherine , Czernichow Paul , Léger Juliane 
Published: February 2006

SummaryObjective  The cause of posterior pituitary ectopia (PPE) with anterior pituitary hormone deficiencies is unknown. This disease is usually considered sporadic. The objective of this study was to improve the phenotypic characterization of children with PPE and growth hormone deficiency (GHD) to seek insight into the mechanisms underlying abnormal pituitary‐gland development.Patients and design  Sixty children with GHD and PPE were evaluated in this retrospective chart review (1988–2003).Results  Known extra‐pituitary birth defects (BD) were present in 31 patients (BD+, 52%) and absent in 29 patients (BD–). Among BD+ patients, seven had well‐defined syndromes (Fanconi anaemia, n = 2; Pallister–Hall, n = 1; Currarino, n = 2; or Stilling–Duane, n = 2) and the other 24 had 53 BDs, mainly involving the brain, eyes and the craniofacial structures (n = 27, 51%) but also affecting the heart, skeleton, kidneys, gastrointestinal tract and skin. Of the 60 patients, seven (12%) were born to consanguineous parents (five sporadic and two familial cases). There were seven (12%) familial cases, with wide variations in clinical presentation, endocrine profiles and magnetic resonance imaging (MRI) findings within families and various patterns consistent with autosomal dominant, recessive or X‐linked transmission.Conclusion  The high rate of extra‐pituitary BDs and of familial components supports a role for genetic factors in the pathogenesis of this heterogeneous disorder. A detailed record of phenotypic abnormalities in patients with GHD and PPE might produce useful hypotheses for genetic studies.
Ewing's sarcoma of bone: the detection of specific transcripts in a large, consecutive series of formalin‐fixed, decalcified, paraffin‐embedded tissue samples using the reverse transcriptase‐polymerase chain reaction
Authors: Mangham D C , Williams A , McMullan D J , McClure J , Sumathi V P , Grimer R J , Davies A M 
Published: February 2006

Aims : (i) To report on the routine use of the reverse transcriptase‐polymerase chain reaction (RT‐PCR) technique on decalcified or non‐decalcified, formalin‐fixed, paraffin‐embedded tissue (FFPET) for translocation detection, with particular emphasis on improved RNA extraction methodology and the use of PCR primers designed to generate small amplicons. (ii) To report on the relative incidences of translocation types and transcript variants in a large, single institution series of Ewing's sarcoma of bone.Methods and results : Using RT‐PCR to detect specific transcript variants, we analysed FFPET from 54 consecutive cases of Ewing's sarcoma of bone. We used ‘gold standard’ detection methods on corresponding fresh and fresh frozen tissue to validate the technique. We have demonstrated the effective use of RT‐PCR on decalcified and non‐decalcified FFPET samples for sarcoma‐specific translocation detection (96% sensitivity, 100% specificity). Tissue decalcification did not affect the detection rate. The relative incidence of Ewing's sarcoma‐specific translocation types and transcript variants was entirely consistent with previously published data.Conclusions : With equal effectiveness, RT‐PCR can be applied to both acid decalcified and non‐decalcified FFPET for (Ewing's sarcoma) translocation detection and the technique can be introduced into routine practice in histopathology departments.
Finding of conjunctival melanocytic pigmented lesions within pterygium
Authors: Perra M T , Colombari R , Maxia C , Zucca I , Piras F , Corbu A , Bravo S , Scarpa A , Sirigu P 
Published: February 2006

Aims : Conjunctival pigmented lesions have characteristic clinical and histopathological appearances. Melanocytic pigmented lesions commonly occur in the conjunctiva, although they have not been previously reported in pterygium, a common lesion which originates from conjunctiva. Our aim was to evaluate the possibility of an association between pterygium and conjunctival melanocytic pigmented lesions.Methods and results : A total of 80 samples of pterygium excised from Ecuadorian patients in 2002 were collected. Clinical data were available regarding age, sex, race and place of residence. Histological sections were evaluated for the presence of melanocytic pigmented lesions. Nine cases of conjunctival melanocytic, pigmented lesions within pterygium were found and were classified according to the histopathological criteria previously published for pigmented lesions of the conjunctiva, as naevi and primary acquired melanosis (PAM) with varying degrees of atypia. Five of the nine cases showed primary acquired melanosis without atypia, while two cases had atypia; one case showed features of compound naevus and one lesion was designated as subepithelial naevus.Conclusions : Our findings suggest that conjunctival melanocytic, pigmented lesions occasionally occur in pterygium. All surgically removed pterygia should undergo careful histopathological examination.
Granular cell tumours of the gastrointestinal tract: expression of nestin and clinicopathological evaluation of 11 patients
Authors: Parfitt J R , McLean C A , Joseph M G , Streutker C J , Al‐Haddad S , Driman D K 
Published: February 2006

Aims : Granular cell tumours (GCTs) in the gastrointestinal (GI) tract are rare, with few series reported in the literature. Nestin is a recently identified intermediate filament protein that is expressed in neuroectodermal stem cells and skeletal muscle progenitor cells and has been shown to be expressed in gastrointestinal stromal tumours (GISTs) and GI schwannomas. Herein, we describe the clinicopathological and immunohistochemical features of 11 GI GCTs, introducing nestin as an additional marker that identifies these tumours.Methods and results : The archives of the departments of pathology at London Health Sciences Centre (London, Ontario) and St Michael's Hospital (Toronto, Ontario) were searched for GCTs occurring in the GI tract, yielding 11 cases. Histological features were assessed and immunohistochemistry was performed with S100 protein, nestin, glial fibrillary acidic protein (GFAP), CD34, desmin, CD117, and inhibin‐α. Charts were reviewed for clinical information. Ages at diagnosis ranged from 31 to 73 years; there were six males and four females. All GCTs were solitary, six in the oesophagus, three in the caecum, one in the rectum and one perianal. Most lesions were discovered incidentally. The size of the GCTs ranged from 4 mm to 30 mm. All were submucosal, typically firm, with a white‐yellow appearance. Histologically, the GCTs showed moderate cellularity, predominantly solid growth with areas of nesting. While lesional cells were mainly plump and polygonal, areas of spindling were present in several tumours, more frequently in the colorectum. Margins were circumscribed. Nuclei were round to oval, with even chromatin and small nucleoli. Mitoses were rare to absent and necrosis was absent in all cases. Staining with periodic acid–Schiff, with diastase predigestion, showed globular and diffuse positivity within the cytoplasm. Moderate to strong expression of S100 protein and nestin was observed in 11 of 11 and seven of seven tumours, respectively. GFAP, CD34, desmin, CD117 and inhibin‐α were negative. While patients were variably managed with resection or observation, all remain clinically well, without disease progression.Conclusions : Although rare, GI GCTs have characteristic clinicopathological features. Nestin may be a useful immunohistochemical marker for identifying these tumours; the presence of this persistent stem cell cytoskeletal filament within GI GCTs suggests that these lesions may arise from a multipotential stem cell in the GI tract.
Duodenal intraepithelial lymphocytosis during Helicobacter pylori infection is reduced by antibiotic treatment
Authors: Nahon S , De Serre N Patey‐Mariaud , Lejeune O , Huchet F‐X , Lahmek P , Lesgourgues B , Traissac L , Bodiguel V , Adotti F , Tuszynski T , Delas N 
Published: February 2006

Aim : To evaluate clinical, biological and immunological features of patients with increased duodenal intraepithelial lymphocytes (IELs), and its relation to Helicobacter pylori (HP) and coeliac disease (CD).Methods : We have studied all patients accrued over a 4‐year period with increased duodenal IELs. Those patients were recalled for biological and immunological evaluation and a second endoscopy.Results : Twenty‐three from a total of 639 patients were identified and 17 of them were included in the study. The median duodenal IEL count was 59 per 100 epithelial cells. Twelve (71%) patients were HP+; eight of them received HP eradication. At the second endoscopy the duodenal IEL count was significantly lower 2 months after HP eradication (73 versus 28), while the IEL count was unchanged in those patients seronegative for HP (n = 5) or those in whom it was not eradicated (n = 4) (55 versus 55). No patient had coeliac antibodies, four expressed HLA‐DQ2, lower than in the general population, and the prevalence of CD was 2% (12/639 patients).Conclusion : In some cases an increased duodenal IEL count may be due to an inappropriate host response to HP. HP screening and eradication should be considered before recommending a gluten‐free diet.