bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental immunization with anti-rheumatic bacterial extract OM-89 induces T cell responses to heat shock protein (hsp)60 and hsp70; modulation of peripheral immunological tolerance as its possible mode of action in the treatment of rheumatoid arthritis (RA)
Authors: BLOEMENDAL A , VAN DER ZEE R , RUTTEN V P M G , VAN KOOTEN P J S , FARINE J C , VAN EDEN W 
Published: December 2003

SUMMARY
OM-89 is a bacterial (Escherichia coli) extract used for oral administration in the treatment of RA. Given the evidence that immunity to bacterial heat shock antigens plays a critical role in the immunomodulation of arthritis and possibly inflammation in general, the purpose of the present studies was to evaluate the presence and immunogenicity of hsp in OM-89. Furthermore, we studied the effects of OM-89 in an experimental arthritis, where hsp are known to have a critical significance in disease development. In rats immunization with OM-89 was found to lead to proliferative T cell responses to hsp60 and hsp70 of both E. coli and mycobacterial origin. Conversely, immunization with hsp antigens was also found to induce T cell reactivity specific for OM-89. Based on this and the antigen specificity analysis of specific T cell lines, hsp70 (DnaK) turned out to be one of the major immunogenic constituents of OM-89. Parenteral immunization with OM-89 was found to reduce resistance to adjuvant arthritis (AA), whereas oral administration was found to protect against AA. Given the arthritis-inhibitory effect of oral OM-89 in AA, it is possible that peripheral tolerance is induced at the level of regulatory T cells with specificity for hsp. This may also constitute a mode of action for OM-89 as an arthritis-suppressive oral drug.
IL-5 production by allergen-stimulated T cells following grass pollen immunotherapy for seasonal allergic rhinitis
Authors: TILL S , WALKER S , DICKASON R , HUSTON D , O'BRIEN F , LAMB J , KAY A B , CORRIGAN C , DURHAM S 
Published: December 2003

SUMMARY
Grass pollen immunotherapy for the treatment of seasonal allergic rhinitis (‘summer hayfever’) results in improvement in symptoms, a reduction in the early and late phase responses to allergen provocation and decreased tissue eosinophilia. Immunotherapy may act by altering the pattern of cytokine production by allergen-specific T cells from a ‘Th2-type’ (IL-4 and IL-5) profile to a ‘Th1-type’ (interferon-gamma (IFN-γ)) profile. We set out to determine whether clinical improvement following specific allergen immunotherapy is accompanied by reduced production of the pro-eosinophilic and archetypal ‘Th2-type’ cytokine, IL-5. Peripheral blood mononuclear cells (PBMC) were isolated from (i) 13 patients who had received 6 or 7 years' continuous conventional immunotherapy with timothy grass pollen (Phleum pratense); (ii) 14 patients who had received 3 or 4 years of conventional immunotherapy followed by 3 years of placebo treatment; (iii) 12 matched seasonal rhinitic patients who had never received immunotherapy; and (iv) 17 non-atopic normal controls. PBMC were stimulated with 20 μg/ml and 200 μg/ml P. pratense extract, or 10 μg/ml of Mycobacterium tuberculosis purified protein derivative (PPD), at 2 × 106 cells/ml and 5 × 106 cells/ml. IL-5 concentrations in culture supernatants collected after 6 days' culture were measured by ELISA. IL-5 production in response to stimulation with P. pratense extract was highly reproducible and was elevated in both of the immunotherapy treated groups and the untreated rhinitics relative to non-atopic controls (P &lt; 0.005 for each group relative to non-atopic controls, under each of the four conditions tested). However, no significant reduction was observed in IL-5 production when immunotherapy treated patients were compared with untreated rhinitic controls. Moreover, abrogation of the cutaneous late-phase responses to allergen following treatment was not associated with reduced IL-5 production by allergen-stimulated peripheral blood T cells. Reduced IL-5 production by peripheral blood T cells may not be necessary for immunotherapy to be effective. Local immunodulation of T cell responses may play a role in this form of treatment.
Anti-neutrophil cytoplasmic antibody (ANCA) in malaria is directed against cathepsin G
Authors: YAHYA T M , BENEDICT S , SHALABI A , BAYOUMI R 
Published: December 2003

SUMMARY
Autoantibodies of diverse specificities are detected in sera of patients with acute malaria. The clinical relevance of these autoantibodies is not clear, though there are reports associating some autoantibodies with specific disease manifestations. We have investigated the occurrence of ANCA in the sera of 93 patients during episodes of acute malaria. Sera were tested by indirect immunofluorescence (IIF) and by ELISA for antibodies to neutrophil cytoplasmic components proteinase 3 (PR3), myeloperoxidase (MPO), cathepsin G (CG), human leucocyte elastase (HLE), and lactoferrin (LF). Forty-seven sera samples (50.5%) were positive by IIF, all except one with the atypical ANCA pattern (a-ANCA). When screened by ELISA, anti-CG antibodies were detected in 52 samples (56%), while anti-PR3 and anti-MPO antibodies were detected in three and one samples, respectively. Antibody binding to HLE and LF was not significant. Anti-CG antibodies were detected in 93% of the IIF-positive sera. A combination of anti-CG and anti-PR3 antibodies was noted in three samples. Our study demonstrates the presence of ANCA in sera from patients with acute malaria, almost all with the a-ANCA pattern on IIF. The antibody specificity, noted for the first time in our study, appears to be predominantly directed against CG. The significance of CG and CG-ANCA in the pathogenesis and clinical manifestations of malaria has yet to be elucidated.
Antibodies against dengue virus E protein peptide bind to human plasminogen and inhibit plasmin activity
Authors: HUANG Y H , CHANG B I , LEI H Y , LIU H S , LIU C C , WU H L , YEH T M 
Published: December 2003

SUMMARY
Both mice and rabbits immunized with dengue virus E protein peptide spanning amino acids 100–119 (D4E) produced antibodies that reacted not only with the D4E peptide itself but also with human plasminogen, as shown by ELISA and Western blot. Sera from dengue virus-hyperimmunized mice and dengue patients also contained antibodies against D4E and plasminogen. Furthermore, such sera all contained plasmin inhibitory activity. Using affinity-purified anti-D4E antibodies and free D4E peptide for competitive inhibition, we demonstrated that the inhibition of plasmin activity was due to anti-D4E antibodies rather than other substances in the sera. Taken together, these results suggest dengue virus E protein amino acids 100–119 are a cross-reactive immunogenic region, and antibodies against this region may interfere with human fibrinolysis.
Chemoattractant-induced release of elastase by lipopolysaccharide (LPS)-primed neutrophils; inhibitory effect of the anti-inflammatory drug nimesulide
Authors: OTTONELLO L , BARBERA P , DAPINO P , SACCHETTI C , DALLEGRI F 
Published: December 2003

SUMMARY
Human neutrophils, pre-exposed to low concentrations (1–10 ng/ml) of bacterial LPS in the presence of 1% autologous serum, released elastase activity in response to n-formyl-met-leu-phe (fMLP). Both cell incubation with LPS without subsequent fMLP stimulus and fMLP stimulation without prior exposure to LPS failed to promote significant elastase release. Therefore, LPS primes neutrophils for the subsequent release of elastase in response to fMLP. Compared with fMLP, human recombinant C5a had a slight although not significant activity, whereas other chemoattractants such as IL-8, platelet-activating factor and leukotriene B4 were ineffective. The fMLP-induced response of LPS-primed neutrophils was susceptible to suppression by the methane-sulphonanilide anti-inflammatory drug nimesulide and RO 20-1724, which selectively inhibit cAMP-catabolizing phosphodiesterase type IV. This suggests that the elastase release by LPS-primed neutrophils is likely to be controlled by intracellular cAMP, and raises the possibility of limiting pharmacologically the elastase-mediated tissue injury during neutrophilic inflammation.
Artificial antigen-presenting cells engineered by recombinant vaccinia viruses expressing antigen, MHC class II, and costimulatory molecules elicit proliferation of CD4+ lymphocytes in vitro
Authors: OERTLI D , MARTI W R , NORTON J A , TSUNG K 
Published: December 2003

SUMMARY
The current study was designed to test the ability of recombinant Vaccinia virus (rVV) encoding essential components of an artificial antigen-presenting cell to activate antigen-specific T cells in vitro. We have constructed a set of rVV encoding separately or in combination a CD4+ T cell-specific epitope (the 133–145 peptide of chicken conalbumin), the MHC class II molecule I-Ak, and costimulatory molecules (mB7-1 and mB7-2). Cultured cells infected with rVV encoding both the antigen and the presenting MHC, but not either one alone, could activate cloned CD4+ T cells specific for the virus-encoded epitope. Additional co-expression of mB7-1 and mB7-2 resulted in further enhancement of T cell response. Thus, our rVV vector expressing four different foreign gene products elicited the highest proliferation rates of antigen-specific cloned T cells.
Differential distribution of B7.1 (CD80) and B7.2 (CD86) costimulatory molecules on mucosal macrophage subsets in human inflammatory bowel disease (IBD)
Authors: RUGTVEIT J , BAKKA A , BRANDTZAEG P 
Published: December 2003

SUMMARY
The molecules B7.1 and B7.2 deliver costimulatory signals of critical importance to naive T cells, and may thus be involved in abrogation of oral tolerance in IBD. Functional disparity apparently exists among antigen-presenting cells in vivo. We wanted to examine if differential B7 expression occurs on mucosal macrophage subsets. Cryosections of bowel specimens from patients with IBD and normal controls were subjected to immunofluorescence and immunoperoxidase staining. In normal mucosa, selective subepithelial accumulation of B7.2+ cells was found. In inflamed IBD mucosa, however, subsets appeared consisting of both B7.2hi and B7.1hi cells as well as CD14hi macrophages. Notably, outside lymphoid aggregates the prominent fraction of recently recruited CD14hi macrophages comprised most (≈ 80%) of the B7.1hi cells, whereas most (≈ 70%) B7.2hi cells were identified as resident mucosal macrophages (CD14lo or CD14−). Differential expression of B7.1 and B7.2 on two functionally different subsets of intestinal macrophages implies separate immunoregulatory roles for the two molecules. This finding is in keeping with recent experimental data demonstrating that monocyte-derived cells are crucial for immune responses at mucosal surfaces. Preferential B7.1 up-regulation might be critical in breaking the immunological tolerance to luminal antigens in IBD, but it cannot be excluded that it is a secondary pathogenic event.
Clinical outcome of hypogammaglobulinaemic patients following outbreak of acute hepatitis C: 2 year follow up
Authors: CHRISTIE J M L , HEALEY C J , WATSON J , WONG V S , DUDDRIDGE M , SNOWDEN N , ROSENBERG W M C , FLEMING K A , CHAPEL H , CHAPMAN R W G 
Published: December 2003

SUMMARY
In 1994, an outbreak of hepatitis C virus (HCV) infection, genotype 1a, occurred in 30 hypogammaglobulinaemic patients in the UK from one batch of contaminated anti-HCV screened intravenous immunoglobulin. This study aimed to study prospectively the outcome of HCV in hypogammaglobulinaemic patients, and to assess the response to early treatment with interferon-alpha, 6 million units three times weekly for 6 months. Data were collected using standardized questionnaires. Five patients with secondary hypogammaglobulinaemia due to lymphoid malignancy were not treated and all have died of their primary malignancy. Of 25 patients with primary hypogammaglobulinaemia, one resolved HCV infection before treatment, 17 commenced on treatment, and seven declined or treatment was contra-indicated. Thirteen of 17 patients completed therapy and seven (54%) have a sustained response (normal transaminases, negative serum HCV RNA) at 6 and 12 months after treatment. Two of the 12 patients with primary hypogammaglobulinaemia, who were not treated or failed to complete treatment, have cleared the virus. Liver biopsy was performed in patients not clearing HCV and was abnormal in all. Four patients developed liver failure within 2 years, of whom three have died and one has been successfully transplanted. In conclusion, HCV can cause rapid severe liver disease in hypogammaglobulinaemic patients. Early treatment with high-dose interferon-alpha results in a high clearance of HCV.
Cell-mediated immune responses to mycobacterial antigens in patients with pulmonary tuberculosis and HIV infection
Authors: SILVEIRA H , ORDWAY D , DOCKRELL H , JACKSON M , VENTURA F 
Published: December 2003

SUMMARY
Lymphocyte proliferation and cytokine responses induced by a panel of mycobacterial antigens were compared in Portuguese donors with pulmonary tuberculosis (TB) with or without HIV co-infection, HIV+ patients and healthy Mantoux-positive controls. Control donors showed stronger proliferative responses than any of the patient groups, with secreted antigens (Mycobacterium tuberculosis (Mtb) 30 kD and short-term culture filtrate proteins (ST-CFP)), purified protein derivative (PPD) and Mtb H37Rv Sonicate (MtbS) inducing the strongest proliferation. Patients with pulmonary TB showed lower proliferation to PPD or to the 30-kD antigen. Responses to all the antigens (PPD, ST-CFP, MtbS, 70 kD, 65 kD, 38 kD, 30 kD and 10 kD) were higher in TB/HIV patients with CD4 counts  200 CD4+ T cells/mm3 compared with HIV alone (CD4  200 T cells/mm3), but were lost in both TB/HIV and HIV patients when CD4 counts fell below 200 T cells/mm3. Measurements of interferon-gamma (IFN-γ) in culture supernatants revealed that PPD, 30 kD, MtbS and ST-CFP induced the strongest Th1 response. Analysis of mRNA for IFN-γ, IL-4 and IL-10 confirmed that IFN-γ production was maintained in patients with pulmonary TB without any concomitant increase in IL-4 or IL-10 mRNA expression, although expression of IL-10 mRNA was increased if HIV infection was present. These results reveal that IFN-γ production is retained in pulmonary TB patients to a broad range of mycobacterial antigens, and that no switch to IL-4 production is seen even with HIV infection. Secreted antigens, and in particular ST-CFP, were the best inducers of IFN-γ secretion, confirming their role in protective responses to Mtb.
Local therapy with soluble complement receptor 1 (sCR1) suppresses inflammation in rat mono-articular arthritis
Authors: GOODFELLOW R M , WILLIAMS A S , LEVIN J L , WILLIAMS B D , MORGAN B P 
Published: December 2003

SUMMARY
Complement activation has been implicated in the pathogenesis of human rheumatoid arthritis. We sought to determine whether inhibition of complement (C) using sCR1 could influence the development and progression of antigen arthritis in the rat, a recognized model of human chronic synovitis. The effect of C inhibition, systemically and locally, on three different stages of disease was examined: (i) prophylaxis, (ii) treatment of established inflammation, and (iii) prevention of antigen-induced flares of disease. Arthritis was assessed by knee swelling and by histological examination. Our results show that intra-articular injection of sCR1 prior to disease onset reduced joint swelling and development of arthritis, whereas systemic administration was ineffective. Treatment of established arthritis with intra-articular sCR1 3 days after disease onset caused a transient reduction in swelling, but treatment 7 days after disease onset had no effect on disease. An intra-articular dose of sCR1 given at the time of disease flares had a small, yet significant effect on knee swelling. We conclude that complement activation is important in the initiation and maintenance of inflammation in antigen arthritis. The potent effect of local C inhibition suggests that C biosynthesis and activation within the joint contributes to inflammation in this model of arthritis.
Disinfection and sterilization in gynaecological endoscopy: problems and costs
Authors: Franchini M. , Cianferoni L. , Appicciafuoco A. , Marseglia A. R. 
Published: December 2003

ObjectiveTo determine and compare the total costs of two low‐temperature sterilization systems.DesignThe direct and indirect costs of ethylene oxide and hydrogen peroxide plasma sterilization were recorded over a 6‐month period. Break‐even point analysis was performed to establish when the use of the gas plasma system represented a cost saving.ResultsHydrogen peroxide plasma sterilization represented a cost saving after 95 units of sterilization.ConclusionsGas plasma sterilization was shown to be a valid method in hospital procedures with respect to both economy and quality.
Laparoscopic aspiration of ovarian cysts: an unreliable technique in primary diagnosis of (sonographically) benign ovarian lesions
Authors: Jansen F. W. , Tanahatoe S. , Veselic M. , Trimbos J. B. 
Published: December 2003

ObjectiveTo assess the value and limitations of aspiration cytology in the diagnosis of cystic lesions of the ovary which were predicted sonographically as benign.DesignA prospective study. All patients, pre‐ and postmenopausal, who were going to have a laparoscopic cystectomy or oöphorectomy had a laparoscopic aspiration of the cyst. Without knowledge of the patient's clinical history or the histology of the lesion, cytological evaluation was performed. Cytomorphological evaluation and prediction of the subsequent histological diagnosis was made.ResultsBetween July 1994 and August 1996 60 aspirates were evaluated. Of the aspirates, 16 (27%) were not evaluable, according to our cytological criteria. The predictive value for discrimination between functional or neoplastic cysts was 65% (95% CI, 52–77%). Sensitivity and specificity were 91% (95% CI, 80–97%) and 67% (95% CI, 22–96%), respectively. The predictive value for the correct histological diagnosis was 42% (95% CI, 29–55%). The size of the cyst had no significant predictive value for the histological diagnosis.ConclusionCytological evaluation of aspirates of ultrasonographically benign ovarian cysts gives no additional information regarding the histology of the lesion. Because the therapeutic significance of this method is also low, aspiration of ovarian cysts should be abandoned.
Prevalence of hysteroscopic abnormalities and anomalies observed in a population without gynaecological complaints
Authors: Van Der Leij G. , Lammes F. B. 
Published: December 2003

ObjectiveTo investigate the prevalence of hysteroscopically observed abnormalities and anomalies in a population without gynaecological complaints.DesignAnalysis of the hysteroscopic observations in 503 patients who consented to have a hysteroscopic tubal occlusion attempt for sterilization (OvablocR procedure).SettingOutpatient department of a general hospital.ResultsThe prevalence of polyps was found to be 0.032, of fibroids 0.034, of intrauterine adhesions 0.040 and all Müllerian variations 0.152. The prevalence of fibroids and intrauterine adhesions was found to be age dependent. The incidence of Müllerian variations decreased as parity increased. Post‐delivery and abortion curettage were a cause of intrauterine adhesions in only a minority of our patients.ConclusionsIn the hysteroscopic work‐up of patients presenting with fertility problems and patients with abnormal uterine bleeding, one should consider the prevalence of intrauterine abnormalities and anomalies in asymptomatic women. Adhesions around the tubal orifices could be indicative of a tubal obstruction.
Randomised controlled clinical trial of stapled haemorrhoidectomy vs conventional haemorrhoidectomy; a three and a half year follow up
Authors: Au‐Yong I. , Rowsell M. , Hemingway D. M. 
Published: December 2003

AbstractObjective  This article presents the results of a three and a half year follow up of patients recruited to a randomised controlled clinical trial comparing circumferential mucosectomy (stapled haemorrhoidectomy) vs conventional haemorrhoidectomy.Methods  Patients were assessed in an outpatient setting to examine a number of outcome measures.Results  Our data suggest that at the three and a half year follow up, there are no significant differences in outcome between the two groups.Conclusions  It will be important to review the long‐term results of larger trials.
Penile and clitoral stimulation for faecal incontinence: external application of a bipolar electrode for patients with faecal incontinence
Authors: Frizelle F. A. , Gearry R. B. , Johnston M. , Barclay M. L. , Dobbs B. R. , Wise C. , Troughton W. D. 
Published: December 2003

AbstractObjective  The aim of this study was to assess the effect of a novel pudendal nerve stimulator on clinical and anorectal manometric parameters in patients with faecal incontinence.Method  Retrospective cohort analysis of consecutive patients presenting with faecal incontinence who had failed initial conservative treatment and were not suitable for surgical intervention in a university hospital incontinence clinic. Biofeedback using a pudendal nerve stimulator comprising a bipolar electrode applied to the base of the clitoris or penis. Electrical pulse voltage was self‐titrated and defined periods of treatment were prescribed. Anorectal manometry and Cleveland incontinence scores were assessed.Results  There was a significant reduction in incontinence symptom score after pudendal nerve stimulator treatment in the 42 patients treated and who had a complete set of data (median age 57 years (range 37–81); 39 female, 3 male). This was accompanied by significant improvements (P < 0.05) in anal sphincter tone, maximal tolerated rectal volume and the sustained rectoanal inhibitory reflex.Conclusions  An externally applied pudendal nerve stimulator improves symptoms and physiological evidence of faecal incontinence but long‐term follow up is not available for these patients.
Proctocolectomy and pelvic pouch – Is a diverting stoma dangerous for the patient?
Authors: Gunnarsson U. , Karlbom U. , Docker M. , Raab Y. , Påhlman L. 
Published: December 2003

AbstractObjective  A diverting loop ileostomy was previously considered mandatory for minimizing the effects of septic complications in pelvic pouch surgery. During the past decade there has been a trend towards omission of the loop ileostomy without obvious signs of increased numbers of pouch complications or impaired long‐term function. The aim of the present study was to evaluate the risk of complications associated with the construction and closure of the loop ileostomy itself.Patients and methods  Complications following diverting loop ileostomies in 143 patients subjected to restorative pelvic pouch surgery during the period 1983–97 were studied retrospectively by evaluation of case records.Results  In the period between discharge after pelvic pouch surgery and closure of the loop ileostomy, 20 (14%) patients were hospitalized because of excessive stoma flow and 19 (13%) patients were treated for other surgical complications, of whom 10 (7%) required surgical intervention. In the early postoperative period (within 30 days) after closure of the loop ileostomy, 18 (13%) patients suffered complications necessitating surgery. Another 12 (8%) patients were hospitalized because of intestinal obstruction that could be treated conservatively.Conclusion  The proportion of complications associated with diverting loop ileostomies in pelvic pouch surgery was considerable. A randomised controlled multicentre study is ethically defensible and is recommended.