bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune response of the coeliac nasal mucosa to locally-instilled gliadin
Authors: TORRE P , FUSCO S , QUAGLIA F , ROTONDA M L L A , PAPARO F , MAGLIO M , TRONCONE R , GRECO L 
Published: March 2003

SUMMARYWe previously demonstrated a specific gluten-induced response in the rectal mucosa of coeliac patients. In the present study, we have evaluated the immune response to local gliadin challenge in the nasal mucosa of coeliac patients preliminary to exploring the feasibility of immune modulation by the nasal route. The local response to gliadin was evaluated on non-invasive scrapings of nasal mucosa. Cells harvested from the nasal scrapings of 21 coeliac patients and 12 healthy controls were counted after immunohistochemical staining. Six hours after gliadin challenge, the total number of cells was increased in coeliacs but not in controls. The increase was due principally to lymphoid cells and granulocytes. CD3+ cells doubled after gliadin challenge, but not after albumin control challenge. There was a similar rise in CD25+ cells, whereas the number of ICAM-expressing cells did not increase significantly. In control subjects, both gliadin and albumin induced a moderate but not significant increase in total cell number. In conclusion, the gliadin antigen provokes a mild inflammatory response in coeliac nasal mucosa.
Antigen presentation by macrophages is enhanced by the uptake of necrotic, but not apoptotic, cells
Authors: BARKER R N , ERWIG L-P , HILL K S K , DEVINE A , PEARCE W P , REES A J 
Published: March 2003

SummaryThe aim of this study was to determine whether phagocytosis of necrotic or apoptotic cells affects antigen presentation by murine bone marrow-derived macrophages. After uptake of necrotic neutrophils, macrophages were able to stimulate significantly higher T cell proliferation in vitro against both the recall antigen albumin and the mitogen concanavalin A. No such effect was seen following phagocytosis of apoptotic neutrophils. Flow cytometry revealed that, within 4h of ingestion, macrophages that had taken up the necrotic cells expressed higher levels of CD40 than those that had phagocytosed apoptotic cells. Macrophage cultures pulsed with apoptotic, but not necrotic, neutrophils contained higher levels of transforming growth factor β1, but lower concentrations of tumour necrosis factor α, compared to untreated controls. Our interpretation of these results is that macrophages that have taken up necrotic neutrophils co-stimulate T cells with greater efficiency due to rapid CD40 up-regulation, whereas those that have ingested apoptotic cells are not only ineffective in co-stimulation, but also secrete inhibitory cytokine.
Proteinase 3 and dihydrolipoamide dehydrogenase (E3) are major autoantigens in hepatitis C virus (HCV) infection
Authors: Wu Y-Y , Hsu T-C , Chen T-Y , Liu T-C , Liu G-Y , Lee Y-J , TSAY G J 
Published: March 2003

SUMMARY
Hepatitis C virus (HCV) infection has been found to be strikingly associated with autoimmune phenomena. The aim of the present study was to investigate the presence of various autoantibodies in patients with HCV infection. Anti-neutrophil cytoplamic antibody (ANCA), anti-dihydrolipoamide dehydrogenase (anti-E3), rheumatoid factor (RF), anti-dihydrolipoamide acetyltransferase (anti-E2), anti-SS-A/Ro (60 kD), anti-SS-A/Ro (52 kD), anti-SS-B/La, anti-topoisomerase II (anti-topo II), anti-cardiolipin (aCL), anti-dsDNA, anti-ssDNA, anti-nuclear antibodies (ANA), anti-proteinase 3 (anti-Pr3) and anti-myeloperoxidase (anti-MPO) were determined in sera from 516 patients with HCV infection, 11 with primary biliary cirrhosis (PBC) and 44 healthy controls. Assays employed were indirect immunofluoresence, the particle latex agglutination test, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. ANCA, anti-E3 antibody and RF were positive in 278/516 (55·6%), 276/516 (53·3%) and 288/516 (56%) patients with HCV infection, respectively. Positivity for ANA was present in 15·8%, anti-ssDNA in 15·6%, anti-dsDNA in 8·5%, aCL in 5%, anti-SS-B/La in 4·1%, anti-SS-A/Ro (60 kD) in 3·9%, anti-E2 in 3·3% and anti-SSA/Ro (52 kD) in 1·2%, anti-MPO in 4·8%, anti-Topo II and anti-actinin in 0%. All sera with ANCA showed c-ANCA patterns and contained anti-PR3 specificity. HCV patients with ANCA showed a higher prevalence of skin involvement, anaemia, abnormal liver function and α-Fetoprotein (α-FP). HCV patients with anti-E3 antibodies showed a higher prevalence of liver cirrhosis, arthritis, abnormal liver function and elevated α-FP levels. The prevalence of autoantibodies was not affected by treatment with interferon-alpha (IFN-α). In conclusion, autoantibodies are commonly found in patients with HCV infection. There is a high prevalence of anti-E3, ANCA and RF in these patients. Proteinase 3 and E3 are the major target antigens in HCV infection. HCV may be regarded as a possible causative factor in ANCA-related vasculitis.
Predictors of HIV-specific lymphocyte proliferative immune responses induced by therapeutic vaccination
Authors: MOSS R B , WALLACE M R , STEIGBIGEL R T , MORRISON S A , GIERMAKOWSKA W K , NARDO C J , DIVELEY J P , CARLO D J 
Published: March 2003

SUMMARY
We treated a cohort of 38 HIV-infected individuals with a therapeutic vaccine (remune, HIV-1 Immunogen) in an open label study. We then determined whether baseline parameters, such as CD4 cell count, viral load and IgG levels, were predictive of the magnitude of the HIV-specific lymphocyte proliferative responses (LPRs). We demonstrate herein that there is a significant enhancement from baseline for both HIV and p24 antigen-stimulated LPRs after immunization. Using a responder definition of a stimulation index of &gt;5 on at least two post-immunization time-points, 29/38 (76%) responded to HIV-1 antigen while 27/38 (71%) responded to native p24 antigen. Viral load and total IgG were negatively correlated, while CD4 cell counts were positively associated with the magnitude of the HIV antigen LPR. In a multivariable analysis, baseline CD4 was the best predictor of HIV antigen LPR post-immunization.
Transmural pressure induces IL-6 secretion by intestinal epithelial cells
Authors: KISHIKAWA H , MIURA S , YOSHIDA H , HIROKAWA M , NAKAMIZO H , HIGUCHI H , ADACHI M , NAKATSUMI R C , SUZUKI H , SAITO H , ISHII H 
Published: March 2003

SUMMARYAlthough intestinal epithelial cells (IECs) are known as an important source for IL-6, it is not known whether mechanical forces affect IL-6 production. We investigated how transmural pressure modulates IL-6 synthesis and activation of transcription factors in IECs. Pressure was loaded onto IEC-18 cells by introducing compressed helium gas into the cell culture flask for 1–48 h. IL-6 release into the culture media was determined by cell proliferation bioassay using an IL-6-dependent mouse hybridoma cell line (7TD1). Exposure to pressure (80 mmHg) significantly enhanced IL-6 release into the culture media from IEC-18 cells at 12 h. Under control conditions, IL-6 secretion was directed to the basolateral side, but after exposure to pressure IL-6 secretion was increased in both the apical and basolateral sides. A nuclear factor kappa B (NF-κB) decoy reversed completely the pressure-induced increase of IL-6 secretion by IEC-18 cells. Pressure treatment enhanced IL-6 mRNA expression in IECs within 6 h. Pressure loading significantly enhanced the activation of both NF-κB and NF-IL-6 from 1h in the nuclear protein of IEC-18 cells as assessed by the electrophoretic mobility shift assay using FITC-conjugated specific primers. Increased phosphorylation of I-kappa B was also demonstrated in the cytosol of IEC cells within 1h by Western blot analysis. These results suggest a possible role for pressure loading in immune modulation of the intestinal mucosa by the stimulation of IL-6 release from intestinal epithelial cells.
T-cell specificity in murine autoimmune haemolytic anaemia induced by rat red blood cells
Authors: BARKER R N , SHEN C-R , ELSON C J 
Published: March 2003

SUMMARY
Autoimmune haemolytic anaemia (AIHA) can be induced in mice by repeated injections with rat red blood cells (RBC). Here we describe the identification of rat and murine RBC antigens recognized by T-cells from mice with this disease. Splenic T-cells from mice with AIHA proliferated in response to multiple murine RBC membrane components, each of which is recognized by rat RBC induced autoantibodies. Thus, there were responses to murine autoantigen fractions that correspond in apparent molecular mass with the anion channel Band 3, with spectrin from the membrane skeleton and with the high and low molecular mass glycophorins, and the equivalent fractions from rat RBC also stimulated proliferation by T-cells. It was confirmed that purified Band 3 from murine and rat RBC also elicited responses. In contrast with the results in AIHA, T-cells from healthy control mice failed to respond to the antigens from either species, with the exception of proliferation induced by murine spectrin in one experiment and weak responses elicited by rat Band 3. It is suggested that T-cells activated by multiple cross-reactions between rat and murine RBC proteins, and by epitope spreading, are necessary to drive autoantibody production in this model of AIHA.
Coupling complement regulators to immunoglobulin domains generates effective anti-complement reagents with extended half-lifein vivo
Authors: HARRIS C L , WILLIAMS A S , LINTON S M , MORGAN B P 
Published: March 2003

SUMMARYComplement activation and subsequent generation of inflammatory molecules and membrane attack complex contributes to the pathology of a number of inflammatory and degenerative diseases, including arthritis, glomerulonephritis and demyelination. Agents that specifically inhibit complement activation might prove beneficial in the treatment of these diseases. Soluble recombinant forms of the naturally occurring membrane complement regulatory proteins (CRP) have been exploited for this purpose. We have undertaken to design better therapeutics based on CRP. Here we describe the generation of soluble, recombinant CRP comprising rat decay accelerating factor (DAF) or rat CD59 expressed as Fc fusion proteins, antibody-like molecules comprising two CRP moieties in place of the antibody Fab arms (CRP-Ig). Reagents bearing DAF on each arm (DAF-Ig), CD59 on each arm (CD59-Ig) and a hybrid reagent containing both DAF and CD59 were generated. All three reagents inhibited C activation in vitro. Compared with soluble CRP lacking Fc domains, activity was reduced, but was fully restored by enzymatic release of the regulator from the Ig moiety, implicating steric constraints in reducing functional activity. In vivo studies showed that DAF-Ig, when compared to soluble DAF, had a much extended half-life in the circulation in rats and concomitantly caused a sustained reduction in plasma complement activity. When given intra-articularly to rats in a model of arthritis, DAF-Ig significantly reduced severity of disease. The data demonstrate the potential of CRP-Ig as reagents for sustained therapy of inflammatory disorders, including arthritis, but emphasize the need for careful design of fusion proteins to retain function.
Increased expression of the secretory leukocyte proteinase inhibitor in Wegener's granulomatosis
Authors: OHLSSON S , FALK R , YANG J J , OHLSSON K , SEGELMARK M , WIESLANDER J 
Published: March 2003

SUMMARY
The secretory leucocyte proteinase inhibitor (SLPI) is a low molecular weight, tissue-specific inhibitor of proteases, such as elastase and cathepsin G. It is the major local protease inhibitor in the upper airways. Proteinase 3, the main autoantigen in Wegener's granulomatosis (WG), can degrade SLPI proteolytically. In addition, SLPI is sensitive to oxidative inactivation by myeloperoxidase-generated free oxygen radicals. SLPI also has an antimicrobial capacity that can be of interest, as infection is considered to play a role in the pathogenesis of WG. This study focuses on SLPI expression in patients suffering from WG, something that to our knowledge has not been explored hitherto. Serum samples and nasal biopsies were obtained from 12 Swedish WG patients, while buffy coats were obtained from 33 American WG patients. SLPI levels in serum were measured by means of ELISA and the protein was detected by means of immunohistochemistry in nasal biopsies. mRNA expression was studied by means of in situ hybridization on nasal biopsies and RT-PCR on leucocytes. IL-6 or ESR were measured as markers of inflammatory activity. Cystatin C or creatinine was measured as a marker of renal filtration. White blood cell counts were registered. In serum, we found close to normal SLPI levels, without any correlation to IL-6. Two patients had greatly elevated values, both of them suffering from severe renal engagement. Strong SLPI mRNA expression was found in nasal biopsies. RT-PCR on leucocyte mRNA showed normal or greatly elevated expression of SLPI mRNA, correlating with disease activity. Leukocyte SLPI expression seems to be up-regulated in active WG. Serum levels were measured in a small number of patients and were found to be close to normal. Lack of correlation to the acute phase response indicates a specific regulation. This might be linked to an altered protease/antiprotease balance. These findings could indicate that SLPI locally participates in the anti-inflammatory and perhaps antimicrobial response in WG.
Chlamydia trachomatis heat shock protein-60 induced interferon-γand interleukin-10 production in infertile women
Authors: KINNUNEN A , SURCEL H-M , HALTTUNEN M , TIITINEN A , MORRISON R P , MORRISON S G , KOSKELA P , LEHTINEN M , PAAVONEN J 
Published: March 2003

SUMMARYChlamydia trachomatis-associated tubal factor infertility (TFI) involves enhanced humoral and cell-mediated immune response to the chlamydial 60 kDa heat shock protein (CHSP60). We evaluated the role of CHSP60-induced immune response in TFI by studying lymphocyte proliferation and cytokine (interferon (IFN)-γ, interleukin (IL)-12 and IL-10) secretion in response to C. trachomatis elementary body (EB) and CHSP60 antigens in 57 women with TFI and in 76 women with other causes of infertility. Positive proliferative response of PBMC to CHSP60 was more common in the TFI group (20/57; 36%) than in the other groups (17/76; 22%) although the frequency or the median responses did not differ significantly (1·6, range 0·2–22·1 versus 1·4; 0·2–24·4). C. trachomatis EB induced significantly higher IFN-γ and lower IL-10 secretion in the TFI group compared to the other groups. The EB and CHSP60 induced IL-12 secretion was similar in all study groups and correlated with IFN-γ secretion in the other but not in the TFI group. The lack of correlation between EB-induced IL-12 and IFN-γ production and simultaneously found prominent IL-10 secretion in response to CHSP60 in the TFI group suggests that the CHSP60 may have a specific role in regulating the immune reactions during chlamydial infection and may consequently contribute to the immunopathogenesis of TFI.
Monocyte-derived RANTES is intrinsically elevated in periodontal disease while MCP-1 levels are related to inflammation and are inversely correlated with IL-12 levels
Authors: FOKKEMA S J , LOOS B G , VAN DER VELDEN U 
Published: March 2003

SummaryBacteria colonizing tooth surfaces are essential in the induction of an inflammatory response in the periodontal tissues, but do not cause periodontitis in everyone, implicating differences in the host immune response. These possible differences were studied using lipopolysaccharide (LPS)-stimulated whole blood cell cultures (WBCC), which revealed a down regulation of monocyte derived interleukin-12 (IL-12p70) in untreated periodontitis patients and an up regulation after therapy. IL-12p70 is a crucial factor in the differentiation of Th1 cell responses. Since CC chemokines are able to influence the T cell differentiation via cytokine secretion in antigen-presenting cells, the production of CC chemokines in periodontitis was evaluated. Therefore WBCC were stimulated with LPS from Escherichia coli for 18 h and the levels of IL-12p70 and CC chemokines were measured in the supernatants by ELISA. Untreated periodontitis patients released 2 fold more RANTES (regulated on activation normal T cell expressed and secreted) (P = 0·01) and lower levels of IL-12p70 in comparison to controls (P &lt; 0·05). A trend towards higher levels of macrophage chemoattractant protein-1 (MCP-1) (P = 0·07) was also seen in untreated periodontitis patients; while similar levels of monocyte derived chemokine (MDC) and macrophage inflammatory proteins-1α and -1β (MIP-1α and -1β) were found. After periodontal therapy no changes were seen with regard to MDC, MIP-1α, MIP-1β and RANTES, whereas the MCP-1 levels decreased (P &lt; 0·05) and the IL-12p70 levels strongly increased (P &lt; 0·01). The data showed a consistent inverse correlation between the levels of MCP-1 and IL-12p70, and their proportional changes after therapy correlated with the clinical inflammatory response after therapy. This indicates that the disease state regulates the release of IL-12p70 and MCP-1 in E. coli LPS-stimulated WBCC. In contrast, the persistent augmented levels of RANTES after therapy are suggestive for an intrinsic behaviour.
The antibody response to HBs antigen is regulated by coordinated Th1 and Th2 cytokine production in healthy neonates
Authors: JAFARZADEH A , SHOKRI F 
Published: March 2003

SummaryA proportion of healthy neonates fail to produce protective levels of anti-HBs antibody following vaccination with recombinant hepatitis B vaccine. This study was undertaken to investigate contribution of Th1 and Th2 responses to anti-HBs antibody production and to explore the mechanism(s) of unresponsiveness to HBsAg in human neonates. Peripheral blood manonuclear cells (PBMCs) were isolated form 28 nonresponder (anti-HBs antibody &lt;10 IU/l) and 25 responder neonates. The cells were stimulated in vitro with recombinant HBsAg and PHA mitogen and concentrations of IL-4, IL-10 and IFN-γ were quantified in culture supernatants by sandwich ELISA. Our results demonstrated significantly increased production of all cytokines, including IL-4 (P &lt; 0·001), IL-10 (P &lt; 0·002) and IFN-γ (P &lt; 0·01) in responder compared to nonresponder vaccinees. No significant differences, however, were observed between the two groups of neonates in the levels of cytokines induced by PHA or secreted in absence of antigen and mitogen. Our findings suggest that unresponsiveness to recombinant HBsAg in healthy neonates is linked to inadequate secretion of both Th1 and Th2 cytokines.
Long‐term therapy with long‐acting octreotide (Sandostatin‐LAR®) for the management of acromegaly
Authors: Davies Peter H. , Stewart Susan E. , Lancranjan Ioana , Sheppard Michael C. , Stewart Paul M. 
Published: March 2003

OBJECTIVESTo evaluate the efficacy and safety of a long‐acting preparation of the somatostatin analogue octreotide, Sandostatin‐LAR® (SMS‐LAR) for the treatment of acromegaly.DESIGN AND PATIENTSThirteen patients with acromegaly received intramuscular injections of SMS‐LAR 20–40 mg at 4–6‐week intervals for a period of up to 3 years.MEASUREMENTSSerial measurement of serum GH and IGF‐1 concentrations were obtained. Symptoms related to acromegaly were scored by patients at baseline and following each injection. Serial gallbladder ultrasound and pituitary imaging was performed throughout the study.RESULTSOne patient was withdrawn from the study after 6 months because of continued gastrointestinal side effects; 4 patients were treated with monthly injections for 12 months and 8 patients with injections at either 1 month or 6‐week intervals for 36 months; hence data is presented for n = 12 for up to 12 months and thereafter n = 8. SMS‐LAR significantly reduced serum GH and IGF‐1 values: for the whole group GH concentrations fell from 24.8 ± 4.2 mU/l (mean ± SE) at baseline to 5.2 ± 0.8 mU/l at 12 months (P < 0.01, n = 12). In the 8 patients treated for 3 years GH fell from 27.8 ± 6.1 mU/l at baseline to 4.2 ± 0.8 mU/l at the end of 3 years (P < 0.01, n = 8). GH fell to <10 mU/l in all subjects and was <5 mU/l in 50% after both 1 and 3 years. IGF‐1 concentrations fell from 95 ± 13 nmol/l at baseline to 63 ± 13 nmol/l after 1 year (P < 0.01, n = 12; reference range <65 nmol/l). In the 8 patients treated for 3 years IGF‐1 concentrations fell from 119 ± 14 nmol/l at baseline to 60 ± 13 nmol/l after 3 years (P < 0.001, n = 8). IGF‐1 was <65 nmol/l in 60% of patients after 1 year and 75% after 3 years. Treatment resulted in trends towards improvement in symptoms of acromegaly and statistically significant improvement in sweating. There was no evidence of tachyphylaxis or evidence to suggest development of glucose intolerance. Only 2 patients (15%) developed gallbladder sludge which was asymptomatic; no patient developed gallstones.CONCLUSIONSWe conclude that SMS‐LAR is a safe, effective and well tolerated treatment, making it an important therapeutic option in the management of acromegaly.
TSH suppression combined with carbimazole for Graves' disease: effect on remission and relapse rates
Authors: Pujol Pascal , Osman Abdul , Grabar Sophie , Daurès Jean‐Pierre , Galtier‐Dereure Florence , Boegner Catherine , Baldet Line , Raye Regine , Bringer Jacques , Jaffiol Claude 
Published: March 2003

OBJECTIVEWe studied the influence of TSH suppressive therapy combined with carbimazole (CBZ) on treatment outcome in Graves' disease.DESIGNOpen non‐randomized prospective study.SETTINGUniversity Hospital of Montpellier, France.SUBJECTSSixty‐six consecutive patients without prior treatment were included. All the patients were treated initially with 30 mg of CBZ. After 1 month of treatment, one group continued CBZ alone (n = 23), another group received a combination of CBZ plus T3 (n = 19) and a third group received CBZ and 3,5,3′‐triiodothyroacetic acid (Triac, n = 24). Therapy was stopped when remission was obtained based on clinical euthyroidism, normalization of FT4 and of early radioiodine uptake. Nine patients with medical treatment failure or major side effects requiring to stop antithyroid drugs underwent surgery or radioiodine therapy. Nine patients were lost to follow‐up. The remaining 48 patients were available for analysis of both remission and relapse.RESULTSThe median duration of therapy was 18 months (range, 4–41 months). Based on clinical examination, goitre size at 4 months decreased more in the CBZ + T3 and CBZ + Triac groups than in the CBZ group (P = 0.02). The overall remission rate tended to be higher in the groups treated with CBZ + T3 and CBZ + Triac than in the group treated with CBZ alone, but the difference did not reach statistical significance (P = 0.17). No difference in the relapse rate was observed between the three groups.CONCLUSIONTSH suppression combined with CBZ has little or no effect on remission and relapse rates in Graves' disease patients.