bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down-regulation on CD8+ T cells from HIV-infected subjects
Authors: VINGERHOETS J H , VANHAM G L , KESTENS L L , PENNE G G , COLEBUNDERS R L , VANDENBRUAENE M J , GOEMAN J , GIGASE P L , DE BOER M , CEUPPENS J L
Published: July 2010

The CD28 receptor on CD4+ and CD8+ T cells interacts with B7 molecules on antigen-presenting cells (APC) to generate essential costimulatory signals. The cytolytic potential of CD8+ T cells could be linked to CD28 expression. Since HIV induces dysfunction of both CD4+ and CD8+ T cells, we evaluated CD28 expression and function in both subsets during HIV infection. CD28 expression on CD8+ T cells from HIV+ subjects was strongly reduced in a disease stage-related fashion. CD28-CD8+ T cells preferentially expressed CD57 and CD11b, but lacked CD26 and IL-2Rα. The CD8+ T cells from the patients showed a significantly reduced proliferative response to co-stimulation with cell-bound anti-CD3 and B7. Nevertheless, when stimulated with plate-fixed anti-CD3, CD8+ T cells from HIV-infected subjects proliferated normally, and normal levels of IL-2Rα nod transferrin-receptor could be induced on CD28-CD8+ T cells from the patients. In addition, stimulation with plate-fixed anti-CD3 induced proliferative responses in highly purified CD28-CD8+ T cells from both HIV- and HIV+ persons. Furthermore, the increased cytotoxic activity of peripheral blood mononuclear cells (PBMC) from HIV+ subjects, measured in an anti-CD3 redirected assay, was predominantly exerted by CD28-CD57+ T cells. CD4+ T cells from the patients showed a slight but significant CD28 down-regulation and were slightly hyporesponsive to B7 co-stimulation. Decrease of CD28 on CD8+ T cells from HIV+ subjects is associated with an impaired response to co-stimulation via B7. CD28-CD8+ T cells from seropositives, however, are not completely inert, since they contain in vivo activated CTL and they can be additionally activated through a B7-independent stimulation.
Fulminant meningococcal septic shock in a boy with combined inherited properdin and protein C deficiency
Authors: Fijen C A P , Derkx B H F , Kuijper E J , Mannens M , Poort S R , Peters M , Daha M R , Dankert J
Published: July 2010

A 7-year-old patient with fulminant septic shock, due to Neisseria meningitidis of the uncommon serogroup Y developed extensive gangrene of the limbs. Multiple amputations were necessary and a pulmonary embolism occurred within 2 days post-operatively. Complement and haemostatic system studies, done after recovery, showed a complete absence of properdin antigen and a low protein C antigen and activity level in plasma. Defective haemolytic activity in gel by the alternative pathway of complement activation could be restored with purified properdin, indicating a properdin deficiency type 1. Protein C antigen level as well as activity were in agreement with a protein C deficiency type I. The polymerase chain reaction (PCR) product of exon five of the protein C gene showed a substitution of 72Gly by Arg. Both deficiencies were traced among relatives of the patient. Serum of the father of the patient's mother was also properdin-deficient. Microsatellite haplotyping of the X-chromosome of the patient and his relatives showed that a distinct haplotype cosegregated with the properdin deficiency (Lodscore 2·25; four informative meioses). The protein C type I deficiency was present in the patient's mother and her mother and cosegregated with the mutation found. So far as is known, this is the first patient described with combined inherited properdin deficiency and protein C deficiency.
Cytotoxic T cell responses in patients with chronic hepatitis B virus infection undergoing HBe antigen/antibody seroconversion
Authors: Waters J A , O'rourke S , Schlict H-J , Thomas H C
Published: July 2010

Cytotoxic T cells have been identified in the peripheral blood of patients with acute hepatitis B virus infections for a short period after clinical presentation. However, in patients in whom the virus persists these have been difficult to demonstrate. In the chronic infection during HBe antigen clearance, when there has been an exacerbation of the disease, we have been able to demonstrate MHC class I-restricted cytolytic response directed against the nucleocapsid antigens. In an HLA-A2 patient this was induced in vitro with the peptide pl8-27, previously described as an HLA-A2-restricted T cell epitope. In patients of other HLA types, recombinant core antigen was used to induce antigen-specific lysis: statistical analysis of the cytolytic responses of chronically infected patients demonstrated a nucleocapsid antigen-specific lysis in patients who were seroconverting. Removal of CD4+ cells reduced non-MHC-restricted cytolysis, allowing an MHC class I-restricted cytolytic component to be demonstrated.
Antibody and clinical responses in volunteers to immunization with malaria peptide–diphtheria toxoid conjugates
Authors: Ramasamy R , Wijesundere DA , Nagendran K , Ramasamy MS
Published: July 2010

Twenty residue peptides from the 185–200-kD and 45-kD merozoite surface antigens of the malaria parasite Plasmodium falciparum were covalently linked to diphtheria toxoid as a carrier and used to immunize human volunteers with aluminium hydroxide as an adjuvant. Significant antibody levels were elicited by two boosting injections. The antibodies reacted with acetone-methanol fixed merozoite membranes in an immunofluorescence assay, but no inhibition of merozoite reinvasion could be detected in in vitro cultures containing the antibodies. Antibody levels against the immunizing peptides declined markedly within 77 days after the third injection. No hypersensitivity was observed against the peptides. However, the volunteers developed hypersensitivity against diphtheria toxoid, and in particular a pronounced type III (Arthus) hypersensitivity after three injections with the toxoid. This effect might appear to limit the use of peptide–diphtheria toxoid conjugates for human immunization. Several biochemical, haematological and immunological tests done on the volunteers showed no other adverse effects from the immunizations.
Tumour necrosis factor-alpha (TNF-α) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions
Authors: Khanolkar-Young S , Rayment N , Brickell P M , Katz D R , Vinayakumar S , Colston M J , Lockwood D N J
Published: July 2010

Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (reversal reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-α mRNA and TNF-α protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-α mRNA are significantly increased in reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-α mRNA and TNF-α protein levels are higher in reactional nerves then reactional skin. In both reactional skin and nerve TNF-α mRNA is more abundant than TNF-α protein; this may reflect the rapid turnover of TNF-α protein in an immunologically dynamic situation, such as is seen in reversal reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy reversal reaction may be regarded as a useful model of tissue immunopathology in which TNF-α is generated as part of the host response to infection, but also produces local tissue damage.
Changes in urinary cytokines and soluble intercellular adhesion molecule-1 (ICAM-1) in bladder cancer patients after Bacillus Calmette—Guérin (BCG) immunotherapy
Authors: Jackson A M , Alexandroff A B , Kelly R W , Skibinska A , Esuvaranathan K , Prescott S , Chisholm G D , James K
Published: July 2010

Intravesical immunotherapy for carcinoma in situ of the bladder is arguably the most effective form of tumour immunotherapy described to date. Following repeated instillations of BCG organisms into the bladder, large quantities of cytokines are detected in patients’ urine. This study concerns the production of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and soluble ICAM-1 (sICAM-1) throughout the six weekly instillations which comprise a therapeutic course. Sequential instillations of BCG induced secretion of IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α, IFN-γ and sICAM-1 into urine. The responses were heterogeneous between patients and cytokines, but some general trends were evident. Although cytokine levels were initially low, their concentration increased with repeated instillation of BCG. Certain cytokines (e.g. IL-6, IL-8 and IL-10) could be detected after the first instillation, whilst others (e.g. IL-2 and IFN-γ) were not detected until after the third or fourth instillation. Interestingly, IL-4 was not detected, perhaps suggesting a differential effect on Th2-like responses. Some patients produced particularly elevated or non-detectable levels of cytokines, and a positive correlation was found between the production of various cytokines. The production of a particular cytokine did not correspond with lack of production of another species. Whether monitoring the production of cytokines following therapy may be of prognostic value will be determined in a larger series of patients. However, as these potent immunomodulators are thought t o be important for the 75% complete clinical response observed with BCG therapy, there remains the possibility that detection of the products of an activated immune system may correlate with eventual clinical outcome. This study is a necessary forerunner to full prognostic evaluation of such immunological data.
B cells from a distinct subset of patients with common variable immunodeficiency (CVID) have increased CD95 (Apo-1/fas), diminished CD38 expression, and undergo enhanced apoptosis
Authors: Saxon A , Keld B , Diaz-Sanchez D , Guo B-C , Sidell N
Published: July 2010

We investigated the role of apoptosis in the differentiation failure of B cells from a selected subpopulation of patients with CVID delineated by B cell surface marker analysis, in vitro. IgE response, and molecular markers of B cell VH gene repertoire. These patients had altered display of B cell surface molecules that play a role in apoptosis. The patients' ‘B cells had a 4.5 250-fold increase in CD95 (Apo-I. fas) expression and increased CD95 display on their T cells. CD38. a molecule important in preventing germinal centre B cell apoptosis. was reduced on the patients’ B cells. The expression of this molecule was inducible on the CVID lymphocytes with retinoic acid. Increased spontaneous apoptosis in vitro. was observed with the patients’B (23%) and T ceils (10%) compared with normal cells (13% and 3%, respectively). Stimulation in vitro. with IL-4 and CD40 rescued the B cells from apoptosis and allowed for their differentiation. However, IL-4 plus aCD40-driven immunoglobulin production was not quantitatively or qualitatively normal. Failure to overcome apoptosis, a normal step in germinal centre B cell development, may be involved in the lack of differentiation seen in this subset of CVID patients.
HLA-DR-restricted T cell lines from newly diagnosed type 1 diabetic patients specific for insulinoma and normal islet beta cell proteins: lack of reactivity to glutamic acid decarboxylase
Authors: Huang G C , Tremble J , Bailyes E , Arden S D , Kaye T , Mcgregor A M , Banga J P
Published: July 2010

T cells reacting with pancreatic islet beta cell proteins play a pivotal role in the pathogenesis of type I diabetes in experimental animal models and man, although the islet cell autoantigens against which these T cells are directed remain to be characterized. We have previously shown the presence of disease-related antigens residing in the transplantable RIN insulinoma membranes which are recognized by T ceils from diabetic NOD mice. We now report on the establishment of CD4+, T cell lines reacting with insulinoma membranes from six newly diagnosed type 1 diabetic patients. Detailed examination of T cell lines from two patients revealed that both the lines continued to react with normal islet cell proteins and. interestingly, were also stimulated by antigens present in brain microsomes. The two T cell lines showed reactivity with different molecular weight proteins of the insulinoma membranes and both the lines were histocompatibility-linked antigen (HL A)-DR restricted. Although the insulinoma membrane preparation is known to contain glutamic acid decarboxylase (GAD), none of the six T cell lines proliferates in response to purified GAD. These T cell tines will be valuable in characterizing novel islet beta cell antigens which are likely to be implicated in type 1 diabetes.
Immune tolerance induction in patients with IgA anaphylactoid reactions following long-term intravenous IgG treatment
Authors: Ahrens N , Höflich C , Bombard S , Lochs H , Kiesewetter H , Salama A
Published: July 2010

To date, there is very little information regarding the pathomechanism of IgA anaphylactoid reactions and the management of affected patients. Five adult patients with common variable immunodeficiency (CVID) and a history of anaphylactic reactions due to the administration of immunoglobulin preparations were studied. The activity of anti-IgA was determined by the gel agglutination technique using IgA-coated beads. Antibodies to IgA were detected in the serum of all five patients. Initially, IgA ‘depleted’ intravenous (i.v.) IgG preparations were infused carefully into the patients until the activity of anti-IgA was decreased significantly or became undetectable. Subsequently, unselected i.v. IgG preparations were infused, and the activity of anti-IgA was abolished in all cases. Intravenous IgG long-term administration results in tolerance induction in patients with IgA anaphylactoid reactions. This tolerance appears to be related to antibody blockage in the circulation and an inhibition of antibody production. Most importantly, IgA appears to play an important role in the treatment of CVID. Patients with IgA anaphylactoid reactions can be treated safely with IgA containing i.v. IgG preparations following tolerance induction.
Differential inhibition of autoreactive memory- and alloreactive naive T cell responses by soluble cytotoxic T lymphocyte antigen 4 (sCTLA4), CTLA4Ig and LEA29Y
Authors: Huurman V A L , Unger W W J , Koeleman B P C , Oaks M K , Chandraker A K , Terpstra O T , Roep B O
Published: July 2010

Cytotoxic T lymphocyte antigen 4 (CTLA4) is a potent inhibitory co-stimulatory molecule believed to be involved in type 1 diabetes and other autoimmune diseases. An association has been reported of both mRNA expression and serum levels of the soluble splice variant of CTLA4 (sCTLA4) with type 1 diabetes. Furthermore, recombinant fusion proteins CTLA4Ig and LEA29Y have been proposed as therapies for type 1 diabetes. We studied the role of (s)CTLA4 in islet autoimmunity. Binding capacity of the proteins to antigen-presenting cells was determined by flow cytometry in competition and binding assays. Functionality of sCTLA4 as well as the therapeutic inhibitory fusion proteins CTLA4Ig and LEA29Y was measured in a dose–response lymphocyte stimulation test, using a panel of diabetes-associated T cell clones reactive to islet autoantigens. As controls, mixed lymphocyte reactions (MLR) were performed to assess functionality of these proteins in a primary alloreactive setting. All three CTLA4 molecules were able to bind to antigen-presenting cells and inhibit the expression of CD80/CD86. sCTLA4 was able to suppress proliferation of different committed autoreactive T cell clones in a dose-dependent manner, whereas CTLA4Ig and LEA29Y were not. Conversely, CTLA4Ig and LEA29Y, rather than sCTLA4, were able to suppress naive alloreactive proliferation in a MLR. Our results indicate a differential role for sCTLA4, CTLA4Ig and LEA29Y proteins in memory versus primary immune responses with implications for efficacy in intervention therapy.
Recent thymic emigrants in lymphoma patients with and without human immunodeficiency virus infection candidates for autologous peripheral stem cell transplantation
Authors: Pratesi C , Simonelli C , Zanussi S , Talamini R , Bortolin M T , Tedeschi R , Marus A , Caffau C , Michieli M , Tirelli U , De Paoli P
Published: July 2010

Signal joint T cell receptor excision circles (sjTRECs) have been reported as a clinical marker to measure the potential for recovery of the immune system after immunosuppressive treatments. The aim of this study was to investigate the thymic regenerative potential in 55 human immunodeficiency virus (HIV)-1 infected (HIV+) and non-infected (HIV-) lymphoma patients, candidates for autologous stem cell transplantation (ASCT). Moreover, the possible associations between sjTRECs and other immunological and clinical parameters were examined. SjTRECs levels in peripheral blood mononuclear cells (PBMCs) were quantified by real-time polymerase chain reaction and T lymphocyte subsets were analysed by flow cytometry. Our data showed that sjTRECs were reduced in lymphoma patients compared to healthy controls, although a weak significant association between low sjTRECs levels and increasing age was maintained [odds ratio (OR) = 4·00; 95% confidence interval (CI) 1·09–17·17]. We found that different chemotherapeutic treatments seem to induce similar effects on the thymic reservoir, independently from their intensity (type and number of cycles of previous chemotherapy). Results from multivariate models including adjustment for patients' sex, type of lymphoma and type of chemotherapy showed that thymic output was independent from HIV infection (OR, 0·95; 95% CI 0·20–4·48). SjTRECs levels correlated with naive T cell subsets in overall lymphoma patients and after stratification by HIV infection (r > 0·37). HIV replication should be maximally suppressed to properly evaluate thymic output by sjTREC markers. Our results suggested that de novo T cell generation is maintained partially in pretreated recurrent lymphoma patients, candidates for ASCT, and could contribute to restore the immune function after transplantation.
Respiratory Deleted in Malignant Brain Tumours 1 (DMBT1) levels increase during lung maturation and infection
Authors: Müller H , End C , Weiss C , Renner M , Bhandiwad A , Helmke B M , Gassler N , Hafner M , Poustka A , Mollenhauer J , Poeschl J
Published: July 2010

Deleted in Malignant Brain Tumours 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds and aggregates various bacteria and viruses in vitro. Studies in adults have shown that DMBT1 is expressed mainly by mucosal epithelia and glands, in particular within the respiratory tract, and plays a role in innate immune defence. We hypothesized that respiratory DMBT1 levels may be influenced by various developmental and clinical factors such as maturity, age and bacterial infection. DMBT1 levels were studied in 205 tracheal aspirate samples of 82 ventilated preterm and full-term infants by enzyme-linked immunosorbent assay. Possible effects of various clinical parameters were tested by multiple regression analysis. DMBT1 levels increased significantly with lung maturity (P < 0·0001 for both gestational and postnatal age) and in small-for-gestational-age infants (P = 0·0179). An increase of respiratory DMBT1 levels was detected in neonatal infections (P < 0·0001). These results were supported by Western blotting. Immunohistochemical analyses of archived newborn lung sections (n = 17) demonstrated high concentrations of DMBT1 in lungs of neonates with bacterial infections. Our data show that preterm infants are able to up-regulate DMBT1 in infection as an unspecific immune reaction.
Translational Mini-Review Series on Complement Factor H: Therapies of renal diseases associated with complement factor H abnormalities: atypical haemolytic uraemic syndrome and membranoproliferative glomerulonephritis
Authors: Noris M , Remuzzi G
Published: July 2010

OTHER ARTICLES PUBLISHED IN THIS TRANSLATIONAL MINI-REVIEW SERIES ON COMPLEMENT FACTOR H

Genetics and disease associations of human complement factor H. Clin Exp Immunol 2008; 151: doi:10.1111/j.1365-2249.2007.03552.x

Structural and functional correlations for factor H. Clin Exp Immunol 2008; 151: doi:10.1111/j.1365-2249.2007.03553.x

Renal diseases associated with complement factor H: novel insights from humans and animals. Clin Exp Immunol 2008; 151: doi:10.1111/j.1365-2249.2007.03574.x

Genetic and acquired abnormalities in complement factor H (CFH) have been associated with two different human renal diseases: haemolytic uraemic syndrome and membrano proliferative glomerulonephritis. The new genetic and pathogenetic findings in these diseases and their clinical implications for the management and cure of patients are reviewed in this paper.
A mutant HBs antigen (HBsAg)183–191 epitope elicits specific cytotoxic T lymphocytes in acute hepatitis B patients
Authors: Liu H-G , Fan Z-P , Chen W-W , Yang H-Y , Liu Q-F , Zhang H , Tien P , Wang F-S
Published: July 2010

HBs antigen (HBsAg)183–191 (FLLTRILTI, R187 peptide) is a dominant human leucocyte antigen-A2 (HLA-A2)-restricted epitope associated with hepatitis B virus (HBV) infection in Caucasian populations. However, its prevalence is poorly understood in China, where there is a high incidence of HBV infection. In this report, we sequenced the region of HBsAg derived from 103 Chinese patients. Approximately 16·5% of the patients bore a mutant HBsAg183–191 epitope in which the original arginine (R187) was substituted with a lysine (K187 mutant peptide). Importantly, K187 still bound to HLA-A2 with high affinity, and elicited specific cytotoxic T lymphocyte (CTL) responses in HLA-A2/Kb transgenic mice. K187-specific CTLs were also generated successfully in acute hepatitis B (AHB) patients, indicating that this mutant epitope is processed and presented effectively. Our findings show that R187-specific CTLs can cross-react with the K187 peptide. These findings reveal that K187 still has the property of an HLA-A2 restricted epitope, and elicits a protective anti-HBV CTL response in humans.
Decreased serum lipocalin-2 levels in human immunodeficiency virus-infected patients: increase during highly active anti-retroviral therapy
Authors: Landrø L , Damås J K , Flo T H , Heggelund L , Ueland T , Tjønnfjord G E , Espevik T , Aukrust P , Frøland S S
Published: July 2010

Although neutrophil gelatinase-associated lipocalin (NGAL) may play a pivotal role in the innate immune response, there are currently no data on NGAL levels in human immunodeficiency virus (HIV)-infected patients. In this study we aimed to examine the regulation of NGAL in HIV infection. The regulation of NGAL in HIV infection was examined by different experimental approaches, including studies in peripheral blood and mononuclear cells (MNC) from bone marrow aspirates before and during highly active anti-retroviral therapy (HAART). We found that: before initiating HAART, HIV-infected patients (n = 37) had significantly decreased serum NGAL levels compared with healthy controls (n = 26); (ii) during HAART, there was a gradual and significant increase in NGAL concentrations reaching levels comparable to those in healthy controls after 12 months; (iii) this increase was seen primarily in virological responders to HAART (HIV RNA level <200 copies/ml after 24 months); (iv) phytohaemagglutinin-stimulated NGAL release in MNC cells from bone marrow aspirates was decreased in untreated HIV-infected patients compared with healthy controls, but increased after 26 weeks on HAART; and (v) there was a significant positive correlation between neutrophil counts and NGAL levels at all time-points during HAART. We have shown decreased NGAL levels in HIV-infected patients, potentially reflecting decreased number and function of neutrophils as well as impaired bone marrow myelopoiesis. These abnormalities were reversed by successful HAART. Our findings underscore further the involvement of neutrophils and innate immunity in HIV-related immunodeficiency.
Human leucocyte antigen class II association in idiopathic bronchiectasis, a disease of chronic lung infection, implicates a role for adaptive immunity
Authors: Boyton R J , Smith J , Jones M , Reynolds C , Ozerovitch L , Chaudhry A , Wilson R , Rose M , Altmann D M
Published: July 2010

The aetiology of idiopathic bronchiectasis, a lung disease where chronic inflammation and bacterial infection leads to progressive lung damage, is unknown. A possible role for natural killer cells has been highlighted previously. However, a role for adaptive immunity is suggested by the presence of CD4 and CD8 T cells in diseased lung tissue. Evidence of a human leucocyte antigen (HLA) class II disease association would further implicate a role for adaptive immunity. To establish if there is any HLA association, we analysed HLA-A, HLA-B, HLA-DQA1, HLA-DQB1 and HLA-DRB1 alleles in patients with idiopathic bronchiectasis and controls. Genomic DNA from 92 adults with idiopathic bronchiectasis and 101 healthy controls was analysed by polymerase chain reaction with sequence-specific primers. We found an increase in the prevalence of HLA-DRB1*01 DQA1*01/DQB1*05 genes in idiopathic bronchiectasis; that is, the HLA-DR1, DQ5 haplotype (odds ratio 2·19, 95% confidence interval 1·15–4·16, P = 0·0152) compared with control subjects. The association with HLA-DR1, DQ5 implicates a role for CD4 T cells restricted by these molecules in susceptibility to the progressive lung damage seen in this disease. This may operate either through influencing susceptibility to specific pathogens or to self-reactivity and requires further investigation.
Prevention of graft-versus-host disease by intrabone marrow injection of donor T cells: involvement of bone marrow stromal cells
Authors: Miyake T , Inaba M , Fukui J , Ueda Y , Hosaka N , Kamiyama Y , Ikehara S
Published: July 2010

We have developed a new and effective method for bone marrow transplantation (BMT): bone marrow cells (BMCs) are injected directly into the bone marrow (BM) cavity of recipient mice. The intrabone marrow injection of BMCs (IBM-BMT) greatly facilitates the engraftment of donor-derived cells, and IBM-BMT can attenuate graft-versus-host reaction (GVHR), in contrast to conventional intravenous BMT (i.v.-BMT). Here, we examine the mechanisms underlying the inhibitory effects of IBM-BMT on GVHR using animal models where GVHR is elicited. Recipient mice (C57BL/6) were irradiated and splenic T cells (as donor lymphocyte infusion: DLI) from major histocompatibility complex-disparate donors (BALB/c) were injected directly into the BM cavity (IBM-DLI) or injected intravenously (i.v.-DLI) along with IBM-BMT. The BM stromal cells (BMSCs) from these recipients were collected and related cytokines were examined. The recipient mice that had been treated with IBM-BMT + i.v.-DLI showed severe graft-versus-host disease (GVHD), in contrast to those treated with IBM-BMT + IBM-DLI. The suppressive activity of BMSCs in this GVHD model was determined. The cultured BMSCs from the recipients treated with IBM-BMT + IBM-DLI suppressed the proliferation of responder T cells remarkably when compared with those from the recipients of IBM-BMT + i.v.-DLI in mixed leucocyte reaction. Furthermore, the level of transforming growth factor-β and hepatocyte growth factor in cultured BMSCs from IBM-BMT + IBM-DLI increased significantly when compared with those from the recipients of IBM-BMT + i.v.-DLI. Thus, the prevention of GVHD observed in the recipients of IBM-BMT + IBM-DLI was attributable to the increased production of immunosuppressive cytokines from BMSCs after interaction with host reactive T cells (in DLI).
Live probioticBifidobacterium lactisbacteria inhibit the toxic effects induced by wheat gliadin in epithelial cell culture
Authors: Lindfors K , Blomqvist T , Juuti-Uusitalo K , Stenman S , Venäläinen J , Mäki M , Kaukinen K
Published: July 2010

Wheat gliadin induces severe intestinal symptoms and small-bowel mucosal damage in coeliac disease patients. At present, the only effective treatment for the disease is a strict life-long gluten-free diet. In this study we investigated whether probiotics Lactobacillus fermentum or Bifidobacterium lactis can inhibit the toxic effects of gliadin in intestinal cell culture conditions. The ability of live probiotics to inhibit peptic-tryptic digested gliadin-induced damage to human colon cells Caco-2 was evaluated by measuring epithelial permeability by transepithelial resistance, actin cytoskeleton arrangements by the extent of membrane ruffling and expression of tight junctional protein ZO-1. B. lactis inhibited the gliadin-induced increase dose-dependently in epithelial permeability, higher concentrations completely abolishing the gliadin-induced decrease in transepithelial resistance. The same bacterial strain also inhibited the formation of membrane ruffles in Caco-2 cells induced by gliadin administration. Furthermore, it also protected the tight junctions of Caco-2 cells against the effects of gliadin, as evinced by the pattern of ZO-1 expression. We conclude thus that live B. lactis bacteria can counteract directly the harmful effects exerted by coeliac-toxic gliadin and would clearly warrant further studies of its potential as a novel dietary supplement in the treatment of coeliac disease.
Immunological efficacy of heat shock protein 60 peptide DiaPep277TM therapy in clinical type I diabetes
Authors: Huurman V A L , Van Der Meide P E , Duinkerken G , Willemen S , Cohen I R , Elias D , Roep B O
Published: July 2010

An immunogenic peptide (p277) from the 60-kDa heat shock protein (hsp60) arrested beta-cell destruction in non-obese diabetic mice. A randomized, double-blind, phase Ib/II clinical trial of DiaPep277 peptide treatment was performed in recent-onset type 1 diabetes patients with remaining insulin production. We studied the immunological efficacy of this peptide therapy and correlated this with clinical outcome. Forty-eight C-peptide-positive patients were assigned subcutaneous injections of 0·2, 1·0 or 2·5 mg p277 (n = 12 per dosage) at entry, and 1, 6 and 12 months, or four placebo injections (n = 12). T cell autoimmunity to hsp60, DiaPep277, glutamic acid decarboxylase and tetanus toxoid (recall response control) were assayed by proliferation and cytokine secretion assays (enzyme-linked immunospot) at regular intervals until 18 months after the first injection. All treated patients at each dosage of peptide demonstrated an altered immune response to DiaPep277, while the majority of placebo-treated patients remained non-responsive to treatment (P = 0·00001), indicating a 100% efficacy of immunization. Cytokine production in response to therapy was dominated by interleukin (IL)-10. IL-10 production before therapy and decreasing autoantigen-specific T cell proliferation were associated with beta-cell preservation. Third-party control immune responses were unaffected by therapy. No potentially adverse immunological side effects were noted. DiaPep277 is immunogenic in type 1 diabetic subjects and has immune modulating properties. Immunological monitoring distinguished therapy from placebo treatment and could determine immunological efficacy. Declining or temporary proliferative responses to peptide DiaPep277 treatment may serve as an immunological biomarker for clinical efficacy.
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Epstein–Barr virus and multiple sclerosis: epidemiological evidence
Authors: Ascherio A , Munger K L
Published: July 2010

While the causes of multiple sclerosis (MS) are unknown, there is strong evidence that infection with Epstein–Barr virus (EBV) is an important factor. In this review, we discuss the epidemiological evidence and argue for a causal role of EBV in MS aetiology. One of the most striking and consistent observations is that MS is extremely rare among EBV-negative individuals. Further, the timing of EBV infection appears to be critical, with individuals who are infected during adolescence and young adulthood, when the infection is more likely to manifest as mononucleosis, having a two- to threefold greater risk of MS compared to individuals infected in early life. These observations challenge the hygiene hypothesis which states that being in a high hygiene environment in early life increases future risk of MS – if this general formulation were true, EBV-negative individuals would be expected to have an increased risk of MS. Additional support for the causal role of EBV comes from longitudinal, prospective studies which show remarkable consistency, in that antibodies against EBV are elevated prior to MS onset. However, while infection with EBV is consistent with many observations of MS epidemiology, there are some that remain unexplained, suggesting that other factors are also involved in determining risk.
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Microbes, apoptosis and TIM-1 in the development of asthma
Authors: Umetsu D T , DeKruyff R H
Published: July 2010

Asthma is a complex disorder which has increased dramatically in prevalence over the past three decades. Current therapies, based on the T helper type 2 (Th2) paradigm, have not been able to control this disease. Epidemiological studies have demonstrated an association between infection with the hepatitis A virus (HAV) and protection against the development of asthma, and genetic studies have shown that the HAV receptor, TIM-1 (T cell, immunoglobulin domain and mucin domain), is an important atopy susceptibility gene. Furthermore, recent studies indicate that TIM-1 is a receptor for phosphatidylserine, an important marker of apoptotic cells. These studies together suggest that HAV and TIM-1 may potently regulate asthma through novel non-Th2-mediated mechanisms. Further study of the immunobiology of TIM-1 and its involvement in the clearance of apoptotic cells is likely to provide important insight into the mechanisms that lead to, and those that protect against, asthma, and how infection affects immunity and the development of asthma.
Shortened lifespan of paroxysmal nocturnal haemoglobinuria‐affected RBC estimated from differences in ratios of CD59‐negative populations between reticulocytes and whole RBC
Authors: NINOMIYA H. , SATO S. , HASEGAWA Y. , NAGASAWA T.
Published: July 2010

Paroxysmal nocturnal haemoglobinuria (PNH) is a haemolytic disease characterized by complement‐sensitive red blood cells (RBC). PNH‐affected RBC (PNH‐RBC) should have a shortened mean lifespan (MLS); however, direct measurement is difficult. We have recently developed a sensitive flow cytometric assay to analyse PNH‐affected reticulocytes that may closely correspond to the PNH clone‐derived erythropoiesis. Naturally, the CD59‐negative populations in reticulocytes were larger than those in whole RBC in PNH. We estimated the MLS of PNH‐RBC in six PNH patients from the differences in the ratios of CD59‐negative populations between reticulocytes and whole RBC. The MLS of PNH‐RBC was calculated using the following formula: W/100 = R × M/[(100 − R) × 120 + R × M], where W, percentage CD59‐negative whole RBC; R, percentage CD59‐negative reticulocytes; M, MLS (days) of CD59‐negative RBC. The MLS of PNH‐RBC, estimated as 16–45 days in the PNH patients, showed a weak positive and a weak negative relation with RBCs and percentage reticulocytes, respectively, among the patients. The MLS, in individual patients, altered irrespective of RBC and percentage reticulocytes. The MLS calculated from our methods may be a parameter that evaluates the haemolytic conditions in PNH.
Prostate cancer cell proliferation and angiogenesis in different obese mice models
Authors: Ribeiro Andreia M. , Andrade Sara , Pinho Filipa , Duarte Monteiro J. , Costa Madalena , Lopes Carlos , Aguas Artur P. , Monteiro Mariana P.
Published: July 2010

Obesity has been associated with increased incidence and aggressiveness of prostate cancer. Although controversial, several studies suggest that leptin could influence tumour cell growth and proliferation. The main goal of this study was to assess cellular growth of prostate adenocarcinoma cells in obese mice with different endogenous hormonal environments in what relates to leptin circulating levels and sensitivity. Four groups of mice (n = 6/group) were used, namely obese mice with congenital non‐functioning leptin receptor OBR (db/db), obese mice with congenital leptin deficiency (ob/ob), mice with diet induced obesity (DIO) and normal weight C57BL/6J mice (control). All groups of mice were injected subcutaneously with 3.0 × 105 RM1 cells/500 μl PBS (murine prostate carcinoma androgen insensitive cells) and tumour growth and angiogenesis were evaluated 14 days after inoculation. The tumours induced in ob/ob and DIO mice were significantly larger (P < 0.001) while those induced in db/db mice were significantly smaller (P = 0.047), when compared with controls. Morphometric analysis revealed that mitotic index and Ki‐67 positive nuclear density, both cell proliferation markers, were also significantly lower in the tumours of db/db mice (P < 0.001) when compared to controls. An inverse correlation was observed between leptin plasma levels and tumour weight (r = −0.642, P < 0.001), mitotic index (r = −0.646, P < 0.01) and Ki‐67 positive nuclear density (r = −0.795, P < 0.001). These results suggest that high leptin concentrations are not favourable to RM1 cell growth and proliferation. On the contrary, high plasma leptin levels were associated with less cellular proliferation and angiogenesis in vivo.
Water‐ and air‐thawing of frozen lamb shoulders
Authors: VANICHSENI S. , HAUGHEY D. P. , NOTTINGHAM P. M.
Published: July 2010

The effects of temperature and other factors on the thawing of frozen lamb shoulders in both water and air were evaluated by determining thawing time and changes in bacterial count, appearance and palatability characteristics.

Water thawing is suitable for a short‐time batch or continuous process immediately prior to boning and gives a net weight gain which partially offsets the previous weight loss during cooling and freezing. The optimum conditions are immersion in water at 45 ± 3°C (113 ± 5°F) for 2–2.5 hr, followed by equilibration and surface drying for 0.5 hr in air at 10°C (50°F) prior to boning. Provided a high standard of hygiene is maintained the water can be reused for up to 4 hr.

Air thawing is suitable for a batch process with a cycle time between 8 and 60 hr, which determines the air temperature required in the range 2–18°C (35–65°F). A high relative humidity is required to minimize weight loss.

Thawing times in both water and air can be theoretically predicted by a modified form of Plank's freezing equation.
Quantitative identification of soya protein in fresh and heated meat products
Authors: PARSONS A. L. , LAWRIE R. A.
Published: July 2010

A method based on laser densitometry of polyacrylamide electrophoretograms of proteins extractable in 10 m urea is described for the quantitative identification of soya protein in fresh meat products and in those heat processed at 100°C for over 1 hr. Qualitative identification of soya protein remains possible in products heated to the level of commercial sterility (127°C for 24 min). It is suggested that the method could also be used for the assessment of other non‐meat proteins in meat products.
The degradation of anthocyanins in canned strawberries
Authors: ADAMS J. B. , ONGLEY M. H.
Published: July 2010

The effect of sugars, acids, alkalis, antioxydants and sodium sulphite on the retention of pelargonidin‐3‐glucoside during the storage of canned strawberries (cv. Senga Sengana) has been investigated.
Microbial growth response to water sorption preparation
Authors: ACOTT K. M. , LABUZA T. P.
Published: July 2010

Intermediate moisture food systems were prepared by both an adsorption and desorption method to similar aws. Hysteresis occurred above an aw of 0.86. Four organisms, Candida cypolytica, Pseudomonas fragi, Staphylococcus aureus and Aspergillus niger, when inoculated in a pork system, showed more rapid growth in systems prepared by a desorption process than by an adsorption process at the same aw. In a solid chicken cube system, the same effect was found but the difference was less between the adsorption and the desorption systems. These results indicate that the method of addition of water to a food system as well as the aw is important in determining the response to growth.
Effect of processing on ascorbic acid in different varieties of cassava (Manihot esculenta, Crantz)
Authors: OGUNSUA A. O. , ADEDEJI G. T.
Published: July 2010

The ascorbic acid content of cassava tubers decreased during storage at room temperature. Pressure cooking led to a loss of 20% in ascorbic acid. Steaming resulted in a loss of 50% in ascorbic acid. The loss in the ascorbic acid content in fermented products was about 95%. There was a conversion of a large part of the ascorbic acid to dehydroascorbic acid during processing.
The use of low temperatures and radiation to destroy Enterobacteriaceae and Salmonellae in broiler carcasses
Authors: MULDER R. W. A. W.
Published: July 2010

Experiments were carried out to determine the effect of a radiation dose of 2.5 kGy (250 krad) on the Enterobacteriaceae and Salmonellae contamination of broiler carcasses when applied at two radiation temperatures (+5°C and ‐18°C). After the treatments the carcasses were stored for 4 months at ‐18°C. The storage period proved to have a considerably lethal effect on Enterobacteriaceae and Salmonellae. Salmonellae could be detected in the starting samples material as well as in the carcasses after 1 month of storage at ‐18°C. After a 1 month storage period no Salmonella was found in one of the two groups of low temperature and radiation‐treated carcasses.
Chemical and sensory changes in iced Nephrops norvegicus as indices of spoilage
Authors: STROUD G. D. , EARLY J. C. , SMITH G. L.
Published: July 2010

Changes in trimethylamine (TMA), total volatile bases (TVB), hypoxanthine and pH, and in cooked odour, flavour and texture have been followed during the iced storage of Nephrops norvegicus at approximately monthly intervals in order that seasonal variations could be investigated. None of the chemical methods investigated could give a prediction of age‐in‐ice to a standard error of less than 2 days. Initial TMA and TVB figures were significantly higher than other published figures.
Effect of salting and roasting on the carbohydrates and proteins of Iranian pistachio kernels
Authors: KASHANI GHASSEM G. , VALADON L. R. GUY
Published: July 2010

The free sugars which make up 2.7% of Iranian pistachio cv Badami were identified as fructose, glucose, sucrose, maltose, isomaltose, cellobiose, raffinose and stachyose. Both protein and free amino acids contained the same seventeen amino acids but lacked tryptophan, asparagine and glutamine. After salting and roasting, total available carbohydrates, total starches and dextrins, and total free sugars all decreased compared to controls, as did a number of individual sugars, especially the reducing sugars. While free amino acids had severely decreased, total protein amino acids and individual protein amino acid were not affected at all. The decreases in reducing sugars and in free amino acids may be due in part to their taking part in Maillard reactions.
Physico‐chemical studies on sugar glasses.
Authors: HERRINGTON THELMA M. , BRANFIELD ANTHONY C.
Published: July 2010

The rates of progress of the nucleation front of sucrose glasses containing various proportions of dextrose, fructose or confectioner's glucose have been measured and considered in relation to their water contents. At high water contents samples containing dextrose had lower rates than samples containing the same amount of glucose syrup solids. It was also found that there was a value of the water content below which crystallization did not occur for samples prepared from glucose syrups, but not from samples prepared from dextrose or fructose.
Potential value of the Limulus lysate assay for the measurement of meat spoilage
Authors: FALLOWFIELD H. J. , PATTERSON J. T.
Published: July 2010

Using a microtitre plate method the Limulus lysate endotoxin assay was shown to be capable of detecting Pseudomonas spp. at viable cell concentrations of 102‐l03/ml. The changes in endotoxin concentration, microbial flora, pH and ERV of laboratory‐produced minced beef and minced pork stored at 4°C were monitored. The endotoxin concentration was shown to increase with the onset of spoilage. Factors were derived enabling an estimate of AMC to be made from the endotoxin concentration determined by the Limulus lysate assay. The use of the microtitre plate system significantly reduces the cost of the Limulus lysate assay.
Perception of sugar‐acid mixtures in lemon juice drink
Authors: McBRIDE R. L. , JOHNSON R. L.
Published: July 2010

Acid was removed from lemon juice by selective adsorption on to a weak‐base resin. Four levels each of sucrose and citric acid were combined factorially and dissolved in the low‐acid juice, providing sixteen stimulus combinations. Using graphic‐rating scales, assessors evaluated the stimuli for intensities of overall flavour, sweetness, and acidity; the relation of each of these intensities to ideal; and general acceptability. The various acceptability responses proved to be internally consistent, and the experiment suggested an optimum sugar‐acid blend from the sixteen combinations. Ratings of overall flavour strength followed a compressed pattern in a factorial plot, with increasing concentrations of sugar and acid exerting a diminishingly small effect. In the perception of individual components, sucrose clearly suppressed the perceived intensity of citric acid, but only the highest concentration of acid unequivocally suppressed sweetness. There was a striking similarity between each set of intensity responses and the corresponding ideal‐relative responses, suggesting a link between intensity and hedonics.
Changes in individual carotenoids on processing and storage of mango (Mangifera indica) slices and purée
Authors: GODOY HELENA T. , RODRIGUEZ‐AMAYA DELIA B.
Published: July 2010

Susceptibility of different carotenoids to degradation during thermal processing and storage of two mango cultivars was investigated. The carotenoid composition was practically maintained on processing mango (cultivar Tommy Atkins) slices. The only significant change was the increase in luteoxanthin, compatible with the conversion of 5,6‐ to 5,8‐epoxide. More evident transformations occurred on processing mango (cultivar Golden) purée. The major pigment β‐carotene decreased 13%, resulting in a corresponding reduction of the vitamin A value. Auroxanthin, not found in the fresh fruit, appeared while violaxanthin and luteoxanthin decreased. During storage of mango slices in lacquered (epoxy) or plain tin‐plate cans, no appreciable loss of β‐carotene was observed during 10 months. Between the tenth and fourteenth month, about 50% reduction of β‐carotene occurred. The degradation continued, resulting in a total loss of 84% after 24 months. A tendency of violaxanthin to decrease, and auroxanthin to increase, during storage was also noted. β‐carotene showed a greater susceptibility to degrade in bottled mango purée (18% loss after 10 months) than in the canned product. As in the case of mango slices, however, both bottled and canned purée suffered 50% loss of β‐carotene after the tenth month, and a total loss of 83% after 24 months. Violaxanthin and luteoxanthin tended to decrease while auroxanthin maintained a comparatively high level throughout storage. The vitamin A values reflected the degradation trend of β‐carotene, a pattern that appears to agree with a free radical mechanism.