bluuebunny/crossref_metadata_2025 huggingface dataset:
21-hydroxylase autoantibodies in adult patients with endocrine autoimmune diseases are highly specific for Addison's disease
Authors: FALORNI A , LAURETI S , NIKOSHKOV A , PICCHIO M L , HALLENGREN B , VANDEWALLE C L , GORUS F K ,   BELGIAN DIABETES REGISTRY, TORTOIOLI C , LUTHMAN H , BRUNETTI P , SANTEUSANIO F
Published: December 2003

The diagnostic specificity of recombinant 21-hydroxylase autoantibodies (21OH-Ab) for Addison's disease was tested in adult patients with either Graves' disease (GD), insulin-dependent diabetes mellitus (IDDM), or polyendocrinopathy, as well as in healthy controls. Using a radiobinding assay with in vitro translated recombinant human 21-hydroxylase, we found 21OH-Ab in 24/28 (86%) idiopathic Addison patients, and using an immunofluorescence assay we found adrenal cortex autoantibodies (ACA) in 12/28 (43%) patients (P =0.002). All the 12 ACA-positive sera were also positive for 21OH-Ab and ACA were found in 11/15 (73%) patients with less than 15 years and in 1/13 (8%) patients with 15–38 years of disease duration (P = 0.002). 21OH-Ab were present in 3/92 (3%) patients with GD, in 1/180 (0.6%) with IDDM and in 0/106 healthy subjects. The 21OH-Ab-positive GD and IDDM patients were also positive for ACA. None of 17 patients with polyendocrinopathy, but without Addison's disease, had 21OH-Ab. None of the 180 Belgian IDDM patients had Addison's disease or developed an adrenal insufficiency at follow up. In two out of three Graves patients, the presence of 21OH-Ab was associated with clinical and biochemical signs of adrenal insufficiency. Of the 89 21OH-Ab-negative patients with GD none had Addison's disease at the time of blood sampling, and 79 were followed up for 5.6–7.5 years and none developed clinical signs of adrenal insufficiency. We conclude that the presence of 21OH-Ab in patients with endocrine autoimmune diseases is highly specific for Addison's disease.
Anti-neutrophil monoclonal antibody therapy inhibits the development of adjuvant arthritis
Authors: SANTOS L L , MORAND E F , HUTCHINSON P , BOYCE N W , HOLDSWORTH S R
Published: December 2003

The aim of this study was to determine the contribution of neutrophils to adjuvant arthritis (AA) by in vivo depletion of peripheral blood neutrophils. Specific anti-neutrophil MoAb, RP3 (10 mg), or a control antibody was given twice daily on days 8–11 after injection of Mycobacterium tuberculosis in inbred male Sprague-Dawley rats. RP3 treatment inhibited the neutrophil leukocytosis associated with AA (3.3 ± 0.6 × 103/mm3versus 21.2 ± 6.9 × 103/mm3; P < 0.001). On day 12, control animals exhibited severe arthritis as assessed by articular index (AI) (9.2 ± 1.3), increase in paw volume (149.3 ± 10.6%), and synovial fluid (SF) cell count (5.3 ± 0.5 × 105). RP3 treatment significantly reduced AI (1 ± 0.1; P < 0.001), paw volume (103.6 ± 5.8%; P < 0.001) and SF cells (0.6 ± 0.1 × 105; P < 0.001) without affecting cutaneous DTH (treated 0.6 ± 0.1 mm change in thickness, control 0.8 ± 0.2 mm; NS). Additional experiments demonstrated that CD4+ cell depletion but not decomplementation inhibited AA development and synovial neutrophil accumulation. Depletion of circulating neutrophils prevented joint inflammation and synovial leucocyte influx in AA, suggesting a pivotal role for neutrophils in the effector phase of AA. Inhibition of neutrophil accumulation by CD4+ cell depletion and not by decomplementation suggests that neutrophil accumulation in AA is T cell-dependent.
Different Trypanosoma cruzi strains promote neuromyopathic damage mediated by distinct T lymphocyte subsets
Authors: MIRKIN G A , CELENTANO A M , MALCHIODI E L , JONES M , GONZÁLEZ CAPPA S M
Published: December 2003

The proliferative response of CD4 and CD8 T lymphocytes obtained from C3H/HeN mice chronically infected with Trypanosoma cruzi strains that differ in virulence, tropism and immunogenicity, was assayed against skeletal muscle, sciatic nerve and spinal cord homogenates. Although both CD4 and CD8 T lymphocytes from mice infected with the RA strain strongly proliferated against the nervous system, no response against skeletal muscle antigens was detected. CD4 and CD8 T lymphocytes from mice infected with the K-98 clone (from CA-I strain) showed low proliferative response against all the antigens assayed. To determine whether the proliferation patterns showed correlation with T cell-mediated neuromuscular damage, passive cell transfer studies were performed. Fifteen days after transfer of CD4 T cells from RA-infected donors (CD4-RA), normal syngeneic recipients displayed exclusively nervous tissue damage, such as perineural, endoneural and/or meningeal inflammatory infiltrates, with predominance of CD4 T cells. Fifteen days after transfer of CD4 T lymphocytes from mice infected with K-98 (CD4-K98), recipients showed inflammatory infiltrates only in skeletal muscle, where CD4 T lymphocytes and macrophages were predominant cells. Recipients of CD8 T cells from RA-infected mice (CD8-RA) showed lesions in both spinal cord and sciatic nerves. Higher percentages of CD8 T cells were observed in comparison with the recipients of CD4-RA or CD4-K98. In contrast, CD8 T cells from K-98-infected donors (CD8-K98) did not induce tissue damage. These results provide evidence that mice infected with T. cruzi populations that differ in their biological characteristics show diverse immune mechanisms that may be involved in the pathogenesis of peripheral nervous system damage.
Effects of interferon-alpha (IFN-α) administration on leucocytes in healthy humans
Authors: CORSSMIT E P M , HEIJLIGENBERG R , HACK C E , ENDERT E , SAUERWEIN H P , ROMIJN J A
Published: December 2003

Plasma concentrations of IFN-α are increased in several inflammatory conditions. Several lines of evidence indicate that IFN-α has anti-inflammatory properties. To study the effects of IFN-α on leucocyte subsets and activation and on cytokines, we administered IFN-α (rhIFN-α2b; 5 × 106 U/m2) to eight healthy human subjects in a randomized controlled cross-over study and analysed changes in circulating leucocytes and parameters for neutrophil and monocyte activation. After administration of IFN-α, neutrophil counts increased, monocyte counts decreased transiently, whereas the number of lymphocytes, basophils and eosinophils showed a sustained decrease. IFN-α administration was also associated with neutrophil activation, reflected in an increase in the plasma concentrations of elastase–α1-antitrypsin complexes and lactoferrin. Serum neopterin, a marker for monocyte activation, was significantly increased 10 h after administration of IFN-α. IFN-α significantly increased plasma concentrations of IL-6, IL-8 and IL-10. Although IL-1 and tumour necrosis factor (TNF) remained undetectable, plasma concentrations of soluble TNF receptors p55 and p75 increased after IFN-α administration. We conclude that IFN-α induces multiple alterations in the distribution and functional properties of leucocytes. IFN-α exerts pro- as well as anti-inflammatory effects within the cytokine network.
Identification and characterization of cells infiltrating the graft and aqueous humour in rat corneal allograft rejection
Authors: LARKIN D F P , CALDER V L , LIGHTMAN S L
Published: December 2003

In a rat model of corneal transplantation, Fischer 344 (RT1lv1) rats received orthotopic corneal isografts or Wistar-Furth (RT1u) donor allografts. Rejection was observed in 25 of 26 allograft recipients, at a median time of 18 days, with all isografts surviving > 100 days. Flow cytometric analysis of aqueous humour identified cellular infiltration of the aqueous at the time of allograft rejection, in contrast to the acellular aqueous found in isografts at corresponding times following transplantation. A higher proportion of CD8+ than CD4+ cells was found at days 1–3 following rejection, whereas there was a higher proportion of CD4+ cells at days 5–8. No changes in peripheral blood T cell subsets were found at the time of rejection. Immunohistochemical analysis of cells infiltrating recipient iris and grafted cornea undertaken at days 1–2, 4 and 7–10 following onset of rejection, demonstrated inflammatory cells in the graft epithelium, stroma and aggregated on the endothelium. Large numbers of macrophages, T cells (CD4+ > CD8+ at all time points), natural killer (NK) cells and neutrophils were detected in graft tissue at days 1–2 and 4, diminishing after that time. Most infiltrating cells expressed MHC class II antigen, and a smaller number expressed IL-2R. Expression of the co-stimulatory marker B7 was identified in a few cells at day 4 in the region of the graft-host wound. The immune response in graft rejection was characterized at day 4 also by expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells of iris and corneal vessels, demonstration of interferon-gamma on mononuclear cells in the peripheral (recipient) cornea, and tumour necrosis factor-alpha on aggregated mononuclear cells on the graft, but not recipient, endothelium. Only sparse cellular infiltrates were found in isograft controls, with inflammation located at the graft-host wound. These findings suggest that inflammatory cells reach a corneal allograft by two routes—from vessels in the peripheral recipient cornea, and from vessels in the recipient iris via the aqueous humour. Different aqueous and intragraft T cell subset proportions were seen early in rejection, although a preponderance of CD4+ cells was found in both aqueous and graft at later times.
HIV infection of CD45RA+ and CD45RO+ CD4+ T cells
Authors: HELBERT M R , WALTER J , L'AGE J , BEVERLEY P C L
Published: December 2003

HIV preferentially infects the RO+ memory subset of CD4+ lymphocytes, and these cells are lost earlier in HIV infection than their RA+ counterparts. Although both populations express similar amounts of CD4 and bind the HIV envelope glycoprotein (gp120) equally well, calcium signals and CD4 down-regulation subsequent to gp120 binding are not the same in both populations. Data suggest these disparities are mediated by differential tyrosine kinase (TK) regulation. Syncytium formation is enhanced in RO+ cells, partly a consequence of increased leucocyte function antigen-1 (LFA-1) expression and, again, partly due to altered TK regulation. After in vitro HIV infection, reverse transcription is not detected in RA+ cells, is minimal in the RO+ class II− population, but progresses well in RO+ class II+. Infection followed by mitogen stimulation permits reverse transcription in all cells. HIV infection of RO+ cells is enhanced moderately at multiple points in the virus life cycle.
Immunoprecipitation of steroidogenic enzyme autoantigens with autoimmune polyglandular syndrome type I (APS I) sera; further evidence for independent humoral immunity to P450c17 and P450c21
Authors: PETERSON P , UIBO R , PERA¨NEN J , KROHN K
Published: December 2003

Three steroidogenic P450 cytochromes, steroid 17α-hydroxylase (P450c17), steroid 21-hydroxylase (P450c21) and side-chain cleavage enzyme (P450scc), have been described as autoantigens in APS I. In this study we report an immunoprecipitation assay for the detection of autoantibodies to these three enzymes using in vitro35S-labelled antigens. Overall, 33 out of 46 (72%) patients with APS I had autoantibodies to at least one of the three proteins and each protein was recognized by patient sera with equal frequency. A higher rate of autoantibody positivity was observed in APS I patients with Addison's disease compared with patients without Addison's disease (85% versus 39%). All 11 patients with ovarian failure had anti-P450c17 or anti-P450scc antibodies. The immunoprecipitation results with P450c17, P450c21 and P450scc correlated well with the results obtained by immunoblotting assays. In addition, the steroidogenic enzymes 11β-hydroxylase (P450c11β), aromatase (P450arom), 3β-hydroxysteroid dehydrogenase (3βHSD) and adrenodoxin were studied by immunoprecipitation assay, but no reaction was found either with 46 APS I or with 26 healthy control sera. To study the suggested immunological cross-reactivity between P450c17 and P450c21 enzymes, nine APS I patient sera were preabsorbed with bacterially expressed P450c17 or P450c21 and subsequently used in immunoprecipitation assay. The absorption experiments clearly indicated that the preincubation inhibited only the reactivity of corresponding antigen, suggesting independent autoantibody response to the two enzymes. Our results suggest that the immune response to some but not to all steroidogenic enzymes is a specific feature of APS I that may be pathogenically significant.
A boy with X-linked hyper-IgM syndrome and natural killer cell deficiency
Authors: ØSTENSTAD B , GILIANI S , MELLBYE O J , NILSEN B R , ABRAHAMSEN T
Published: December 2003

We present a boy with hyper-IgM syndrome with a previously not reported mutation in the CD40 ligand gene. He also had a concomitant natural killer (NK) cell deficiency. He had no CD56+ or CD16+ cells and no NK activity as determined in 4 h chromium release cytotoxicity assay. After 5 days in culture with IL-2-containing medium, however, his peripheral blood mononuclear cells lysed both NK-sensitive and NK-resistant targets, showing that he had lymphokine-activated killer cell precursors in the circulation. Due to the associated neutropenia, he was treated with granulocyte colony-stimulating factor (G-CSF) and responded well. In the same period we observed a transient increase in the number of NK cells. Isolated NK cell deficiencies are extremely rare. We suggest that the defect in our patient is part of the hyper-IgM syndrome, probably representing the phenotype of the new mutation described. Thus, it is possible that both the neutropenia and the NK cell deficiency are due to lack of growth-promoting signals normally delivered by the CD40 ligand.
Neutralization of tumour necrosis factor (TNF) but not of IL-1 reduces inflammation in chronic dextran sulphate sodium-induced colitis in mice
Authors: KOJOUHAROFF G , HANS W , OBERMEIER F , MA¨NNEL D N , ANDUS T , SCHO¨LMERICH J , GROSS V , FALK W
Published: December 2003

The cytokines TNF and IL-1 have been implicated as mediators of the inflammatory processes in patients with inflammatory bowel disease (IBD). To investigate the role of these cytokines in mucosal inflammation we used anti-cytokine strategies in a mouse model of acute and chronic colitis. Mice which received 5% dextran sulphate sodium (DSS) in their drinking water showed signs of acute colitis on day 4, with severe weight loss and bloody diarrhoea. Chronic colitis was established after four cycles of feeding 5% DSS for 7 days and water for 10 days, with the mice showing diarrhoea but no weight loss. In acute colitis, treatment with anti-IL-1 reagents, anti-TNF MoAb, or dexamethasone (DEX) led to aggravation. By contrast, in chronic colitis, treatment of mice with several IL-1 activity-inhibiting reagents failed to show significant effects, whereas anti-TNF MoAb or DEX significantly reduced the colitis. We conclude that in acute colitis IL-1 and TNF are beneficial, whereas in chronic colitis, TNF but not IL-1 seems to play a major role in perpetuation of chronic inflammation.
Normal human immunoglobulins for intravenous use (IVIg) delay hyperacute xenograft rejection through F(ab′)2-mediated anti-complement activity
Authors: LATREMOUILLE C H , GENEVAZ D , HU M C , SCHUSSLER O , GOUSSEF N , MANDET C , BRUNEVAL P , HAEFFNER-CAVAILLON N , CARPENTIER A , GLOTZ D
Published: December 2003

Xenotransplantation between discordant species leads to a hyperacute rejection mediated by natural antibodies, both of the IgG and IgM isotypes, activation of complement and endothelial cell activation. The combination of these mechanisms leads to a transplant survival of minutes to a few hours. Polyclonal human immunoglobulins for intravenous use (IVIg) from normal donors have proved effective in a number of antibody-mediated disorders, as well as in inflammatory disorders. We demonstrate that administration of IVIg in a guinea pig to rat model of cardiac xenografting can effectively delay hyperacute rejection. This effect is mediated by the F(ab′)2 fragments of IVIg, and is correlated to an anti-complementary activity.
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

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

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 < 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

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

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

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

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

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

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

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

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.
A case of intestinal obstruction following transperitoneal laparoscopic colposuspension
Authors: Govind A. , Cox C. W. F. M.
Published: December 2003

We present the case of a patient who underwent a seemingly uneventful laparoscopic colposuspension. She appeared to bleed from one of the laparoscopic ports postoperatively and her haemoglobin level dropped. She became unwell on the eighth postoperative day. A diagnosis of small bowel obstruction was made from a plain X‐ray film and the cause of this was revealed only at laparotomy. This case highlights a previously unreported cause of small bowel obstruction secondary to haematoma.
Disinfection and sterilization in gynaecological endoscopy: problems and costs
Authors: Franchini M. , Cianferoni L. , Appicciafuoco A. , Marseglia A. R.
Published: December 2003

Objective

To determine and compare the total costs of two low‐temperature sterilization systems.

Design

The 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.

Results

Hydrogen peroxide plasma sterilization represented a cost saving after 95 units of sterilization.

Conclusions

Gas 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

Objective

To assess the value and limitations of aspiration cytology in the diagnosis of cystic lesions of the ovary which were predicted sonographically as benign.

Design

A 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.

Results

Between 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.

Conclusion

Cytological 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

Objective

To investigate the prevalence of hysteroscopically observed abnormalities and anomalies in a population without gynaecological complaints.

Design

Analysis of the hysteroscopic observations in 503 patients who consented to have a hysteroscopic tubal occlusion attempt for sterilization (OvablocR procedure).

Setting

Outpatient department of a general hospital.

Results

The 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.

Conclusions

In 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.
The effect of cryoprotectants during freezing or freeze drying upon properties of washed mechanically recovered broiler meat
Authors: Kijowski Jacek , Richardson R. Ian
Published: December 2003

Mechanically recovered meat (MRM) from broilers was washed three times with water and subjected to either slow or rapid freezing or freeze‐drying with, or without, the presence of cryoprotectants. Both freezing and freeze‐drying reduced the functionality of the MRM when no cryoprotectants were used. Sorbitol/sucrose showed some protection of gel forming ability of frozen samples whilst sorbitol/sucrose with tripolyphosphate gave stronger gels after freezing or freeze‐drying than fresh samples. Most of the loss of functionality during freezing or freeze‐drying was caused by loss of solubility of myosin and to a lesser extent actin. This was supported by DSC studies. The combined presence of sorbitol/sucrose/tripolyphosphate restored most functional properties of the frozen or freeze‐dried material to that of the fresh material.
Compression characteristics, firmness, and texture perception of heat treated and unheated apples
Authors: Lurie Susan , Nussinovitch Amos
Published: December 2003

Two cultivars of apple fruits, Malus domestica cvs. ‘Golden Delicious’ and ‘Granny Smith’, were heated for 4 days at 38°C and then held for a week at 20°C or at 0°C. At the end of this period texture, firmness and organoleptic tests were made on these apples and the results were compared with those for unheated apples. The heated apples were found by a taste panel to be crispier and sweeter than the unheated apples. Flesh firmness, tested with a Magness‐Taylor penetrometer correlated well with crispiness for ‘Golden Delicious’ apples and less well with ‘Granny Smith’. Instron compression tests of strength and stiffness correlated with crispiness in both varieties. Instron measurement of brittleness was not correlated with crispiness. We suggest that the properties of apple flesh sensed during mastication are most closely related to the properties derived from the compression test of strength and stiffness.
Reducing the coumarin content of tonka bean extracts using supercritical CO2
Authors: Ehlers Dorothea , Pfister Michael , Gerard Dieter , Quirin Karl‐Werner , Bork Wolf‐Rainer , Toffel‐Nadolny Peter
Published: December 2003

By supercritical fluid CO2 extraction of tonka beans a lipophilic top phase and a crystalline base phase were obtained. These were analysed by gas chromatography‐mass spectrometry (GC/MS) and high‐performance liquid chromatography (HPLC) and compared with an ethanolic extract of the same batch of tonka beans. It was shown that the three samples differed considerably in their composition and that the bulk of the main compound coumarin was present in the base phase of the CO2 extraction.
Influence of cleansers on a polysulphone membrane used for milk ultrafiltration
Authors: Nwuha Victor O.
Published: December 2003

Membrane stress and apparent water flux were measured as a function of time, pressure and milk concentration during unstirred ultrafiltration of milk with a polysulphone membrane. Membrane properties changed considerably after exposure to six common membrane cleanser's with notable changes in the rate of declines in milk flux (Q), increase (inorganic and organic cleansers) and decrease (surfactants) in relative hydraulic resistance (RHR) values.
Physical, chemical and sensory characteristics of cooked meat emulsion style products containing vegetable oils
Authors: Ambrosiadis John , Vareltzis Kyriakos P. , Georgakis Spyros A.
Published: December 2003

Beef frankfurters and cooked salamis (containing 19.5% pork back fat) were compared with samples containing vegetable oils. The pork back fat was replaced with Soya‐seed oil (19.5%), sunflower oil (19.5%, 24%, 27.5%), cotton‐seed oil (19.5%), corn‐seed oil (19.5%) or palmine (19.5%). The emulsion stability of the products containing vegetable oil was good, even if the temperature of the batters reached 20°C. However, firmness, lightness of internal colour and flavour intensity were reduced in the vegetable oil specimens. In terms of flavour, panellists scored the acceptability of the experimental products as follows: control best; sunflower, corn‐seed and palmine next and soya‐ and cotton‐seed worst.
Liquid‐to‐particle heat transfer in continuous tube flow: Comparison between experimental techniques
Authors: Balasubramaniam V.M. , Sastry Sudhir K.
Published: December 2003

The liquid‐to‐particle convective heat transfer coeffcient (hfp) is a critical parameter in the design of safe continuous thermal processes for particulate foods. Three methods of measuring hfp values during continuous tube flow were compared: moving thermocouple, liquid crystal, and relative velocity. A model error analysis of the heat transfer methods (moving thermocouple and liquid crystal) indicated that measurement of the temperature and particle velocity were important sources of error. For the relative velocity method, the measurement of relative velocity, the rheological properties of the carrier medium, and thermal conductivity of the fluid were found to be most important. The liquid crystal method yielded the highest values of all techniques, largely because of the freedom of rotation allowed to particles under test conditions. The moving thermocouple and relative velocity methods yielded results that were in agreement with each other, the principal reason being the restriction of rotation in the former, and neglect of rotation in the latter. The moving thermocouple approach can be used for conservative but realistic estimation of hfp in continuous flow through holding tubes. The relative velocity method does not stand on its own, but can be used to provide a measure of verification for the other methods.
Crossflow microfiltration of gum arabic solutions: Comparison of the classical system with the co‐current permeate flow system
Authors: Decloux Martine , Dornier Manuel , Gratius Isabelle
Published: December 2003

Gum arabic is a natural gum exuded mainly by the trees Acacia senegal, currently used in the food industries for its emulsifying, thickening and stabilizing properties. Its present processing includes various operations providing a quite turbid product. Crossflow microfiltration could be interesting for the clarification and the cold‐pasteurization of the gum arabic solutions. Several experiments were therefore made with the crossflow microfiltration unit at ENSIA, using two different systems: the classical one (without permeate circulation), and the co‐current permeate flow system (CCPF) allowing the exploration of the low transmembrane pressures range. With gum arabic solutions of 0.17g solids g−1 solution and 70°C, the best results after 60 min of filtration (105.7 L h−1 m−2, 4.4% of solids retention and 83.4% of clarification) were obtained with the CCPF system at low transmembrane pressure and high crossflow velocity (0.3 bar and 7.5ms−1).
The air drying behaviour of fresh and osmotically dehydrated banana slices
Authors: Sankat Clement K. , Castaigne Francois , Maharaj Rohanie
Published: December 2003

Ripe banana, cut to 10mm thick slabs were osmotically treated in sugar solutions of 35, 50 and 65° Brix for 36h. The initial moisture content fell from a value of 3.13kg H2O DM to 2.19, 1.63 and 1.16kg H2O kg−1 for treatment in the three solutions, respectively. These slabs, with Total Soluble Solids (TSS) contents of 26, 34 and 39° Brix, respectively, as well as freshly cut but untreated slabs (15° Brix) were air dried in a cabinet type tray drier to near equilibrium conditions at fixed temperatures from 40 to 80°C and at a constant air speed of 0.62m s−1. Drying was found to occur in the falling rate period only for both banana types and two drying constants K1 and K2 were established for a first and second falling rate period of drying. Increasing the drying air temperature significantly enhanced the drying rate and the K‐values, except at 80°C when the rates fell, possibly because of case hardening of the slabs. Reducing the slab thickness also improved the drying rate, but increasing the air speed to 1.03m s−1 did not have any profound effect. As the sugar content of the banana slabs increased through the osmotic treatment, drying rates fell. Calculated apparent moisture diffusivities at 60°C ranged from 34.8× 10−10 m2 s−1 (fresh slab) to 8.8×10−10 m2 s−1 for dried (39° Brix) slabs. The moisture diffusivity was significantly lowered as the moisture content dropped in drying and with increased levels of sugar. Previously osmosed and then air dried banana slabs showed appealing colour and texture compared to the fresh banana.
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

Objective  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

Objective  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.