bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Th1/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reversed transcribed polymerase chain reaction (RT-PCR)
Authors: Niessner M , Volk B A 
Published: July 2010

SUMMARYCytokines serve a central function as key factors in the regulation of the intestinal immune response and mediation of tissue damage in inflammatory bowel disease (IBD). Abnormalities in the expression of immunoregulatory cytokines such as IL-2, IL-4, IL-10 and interferon-gamma (IFN-γ) may indicate a dysregulation of intestinal immunity probably associated with pathogenic events. Therefore, cytokine mRNA concentrations were determined in the mucosa of patients with IBD at sites of active (n= 13) and inactive (n= 12) ulcerative colitis (UC), active (n= 11) and inactive (n= 11) Crohn's disease (CD) and in control patients (n= 14) using quantitative RT-PCR. IL-10 mRNA concentrations were significantly increased in patients with both active UC (P &lt; 0.001) and active CD (P &lt; 0.005) compared with control patients. IFN-γ mRNA concentrations were also significantly increased both in patients with active UC (P &lt; 0.02) and active CD (P &lt; 0.05) compared with control patients, whereas IL-2 mRNA levels were significantly (P &lt; 0.02) increased only in active CD. IL-4 mRNA expression in the intestinal mucosa was frequently below the detection limit. Our results demonstrate that chronic intestinal inflammation in patients with CD is characterized by an increase of Th1-like cytokines. Furthermore, the increased IL-10 mRNA expression at sites of active IBD suggests that IL-10 is an important regulatory component involved in the control of the inflammatory response in inflammatory bowel disease.
Increased dimeric IgA-producing B cells in tonsils in IgA nephropathy determined byin situhybridization for J chain mRNA
Authors: Harper S J , Allen A C , BÉNÉ M-C , Pringle J H , Faure G , Lauder I , Feehally J 
Published: July 2010

SUMMARYThe origin of mesangial IgA deposits in IgA nephropathy (IgAN) remains obscure. A significant proportion of deposited immunoglobulin is dimeric (J chain-positive). Previous studies of J chain expression within lymphoid tissue in IgAN have utilized antibodies which other investigators have found to be non-specific. To address this problem, we have developed an in situ hybridization (ISH) method for the detection of J chain mRNA within IgA plasma cells. Tonsils from 12 patients with IgAN and 12 controls were studied using (i) non-isotopic ISH for J chain mRNA, and (ii) combined immunofluorescence (IF) and fluorescent ISH. J chain mRNA-positive cells were identified in germinal centres, and within the subepithelial and interfollicular zones. A greater number of J chain mRNA-positive cells were found in the germinal centres of patients (mean 57.7±4.6 cells/105μm2) compared with controls (mean 36.9±3.5 cells/105μm2) (P &lt; 0.001). Combined IF and fluorescent ISH showed a greater proportion of J chain mRNA-positive interfollicular IgA cells in patient tonsils (3.2±3.4%) compared with controls (21±2.3%; P &lt; 0.02). These results indicate a shift towards dimeric IgA production in the tonsils in IgAN. In addition, the finding of excess numbers of J chain-positive IgA-negative cells within germinal centres suggests that an abnormality may be present at the B cell differentiation stage before IgA switching. These results further highlight immune abnormalities within the tonsil as a central feature of abnormal polymeric IgA biology in this common form of glomerulonephritis.
Hydrocortisone enhances total IgE levels—but not the synthesis of allergen-specific IgE—in a monocyte-dependent manner
Authors: Bohle B , Willheim M , Baier K , Stadler B , Spitzauer S , Scheiner O , Kraft D , Ebner C 
Published: July 2010

SUMMARYRecently, hydrocortisone (HC), when combined with human IL-4, has been reported to increase IgE levels in supernatants (SN) of in vitro cultured leucocytes. In this study we investigated the influence of HC on allergen-specific IgE synthesis. Moreover, we examined the relevance of different cell types in this respect. Peripheral blood mononuclear cells (PBMC), T cell-depleted PBMC, CD14-depleted PBMC and highly purified B cells from 10 allergic (birch pollen and/or grass pollen) patients and five non-allergic individuals were investigated. The cells were incubated with HC and/or recombinant human IL-4 (rIL-4) for 8 days. A considerable increase of total IgE was observed in HC/rIL-4-stimulated cultures compared with rIL-4 alone, HC alone or non-stimulated cultures. We demonstrate that this effect depends on the presence of monocytes in in vitro cultures. These results were seen in every experiment, irrespective of healthy or atopic state of the blood donor. The increase of IgE could not be attributed to a rise of birch pollen- and/or grass pollen-specific IgE in patients allergic to these allergens, as shown by IgE-immunoblot. Radioallergosorbent test (RAST) investigations of HC/rIL-4-stimulated cell cultures from allergic and non-allergic patients confirmed that HC/rIL-4-induced elevated IgE production was also not due to increased production of IgE, specific for important aero-allergens (pollens, house dust mite or animal dander). Therefore we conclude that newly synthesized IgE is not specific for allergens, but that sequential isotype switching in human B cells leads to increased polyclonal IgE production.
Depression in caregivers of demented patients is associated with altered immunity: impaired proliferative capacity, increased CD8+, and a decline in lymphocytes with surface signal transduction molecules (CD38+) and a cytotoxicity marker (CD56+ CD8+)
Authors: Castle S , Wilkins S , Heck E , Tanzy K , Fahey J 
Published: July 2010

SUMMARYChanges in relevant immune parameters, including function, were found to be associated with depression in elderly caregiver wives of demented patients. We studied the relationship between immune cell phenotype and T cell proliferative capacity of such caregivers to levels of stress and depression over the course of a support group intervention. The data indicate the strongest association between depression (of all stress parameters) and impaired T cell proliferative capacity. Depression was also most strongly (of stress parameters) associated with a shift in T cell populations with an increase in CD8+ T cells, and a reduced percentage of CD38+ cells in both CD8+ and CD4+ T cell populations. Since CD38 is a signal transduction factor, it was interesting that a decreased percentage of CD38+ cells correlated with impaired T cell function (proliferation). Another significant difference was the reduction in natural killer (NK) cells as well as the percentage of the CD56+ component of the CD8+ population. This latter subset is important in MHC-unrestricted cytotoxicity, and has been found expanded in healthy centenarians. This study shows that both chronic stress, and depression in particular, and age have deleterious effects on T cells, and together could significantly contribute to the higher risk of disease and mortality associated with being a caregiver of a demented individual.
The development of a novel immunotherapy model of human ovarian cancer in human PBL-severe combined immunodeficient (SCID) mice
Authors: Walker W , Gallagher G 
Published: July 2010

SUMMARYThe reported ability of SCID mice to accept xenografts of both human tumours and peripheral blood lymphocytes (PBL) provides the potential for the development of novel immunotherapy models in these animals. This study describes the development of a novel small animal model of human ovarian cancer. This was achieved by engrafting a human ovarian cancer cell line (Ovan-4) into the peritoneal cavity of immunodeficient SCID and immune reconstituted human PBL-SCID mice. When transplanted to SCID mice this cell line exhibited growth characteristics similar to the clinical disease observed in patients with Implantation of metastatic nodules onto the interior surface of the peritoneal wall. Reconstituted human PBL-SCID mice challenged with identical numbers of Ovan-4 cells exhibited a significant increase in survival time, suggesting a role for cells of the human immune system in preventing the development of this type of malignancy in vivo. Furthermore, vaccination of human PBL-SCID mice against Ovan-4 produced tumour-specific human antibodies in the serum of these animals. Animals reconstituted with CD8-depleted PBL exhibited increased serum immunoglobulin levels and produced enhanced anti-Ovan-4 activity after vaccination. Subsequent challenge of these animals with Ovan-4 revealed a further increase in survival time. These results suggest that human antibodies may have a role in immunity against ovarian cancer and could be of therapeutic value in this type of disease.
A systematic study of neutrophil degranulation and respiratory burstin vitroby defined immune complexes
Authors: Zhang W , Voice J , Lachmann P J 
Published: July 2010

SUMMARYDefined immune complexes (IC) were used to compare the effect of antibodies of different classes and subclasses on neutrophil respiratory burst and degranulation. IC were made from 5-iodo-4-hydroxy-3-nitrophenacetyl (NIP) conjugated to bovine serum albumin (BSA) and chimaeric mouse-human anti-NIP monoclonal antibodies including lgA2, IgE and all four IgG subclasses. The activation of neutrophils by IC depended on antibody class and subclass, on antigen epitope density, on antigen : antibody ratio and on the medium used. The ability to generate the respiratory burst showed a different pattern to the ability to give rise to degranulation. Compared with other IC, IgA2 IC provided the strongest stimulus for neutrophil activation. IgG1 IC, IgG2 IC and IgG4 IC activated neutrophils moderately or weakly. IgG3 IC were unable to stimulate the respiratory burst, but could cause strong degranulation. IgE IC could hardly cause any neutrophil response. Neutrophil degranulation in response to IgG3 IC in serum-free medium or heat-inactivated serum was fast, and it quickly reached maximum. Degranulation caused by IgA IC was relatively slow. but gradually increased during incubation. The activity of IgG1 IC. IgG2 IC and IgG4 IC generated a respiratory burst increased with antibody excess and decreased with antigen excess. The activity of IgA2 IC, however, was not affected by change of antigen and antibody ratio. A specific role of serum, possibly due to complement, was found in enhancing degranulation. both temporally and quantitatively, by lgA2 IC.
Autoantibodies in human anti-Ro sera specifically recognize deproteinized hY5 Ro RNA
Authors: Boulanger C , Chabot B , MÉNard H A , BOIRE G 
Published: July 2010

SUMMARYWe report the existence of a Novel autoantibody specificity linked to anti-Ro antibodies. Sera from two patients with anti-Ro ribonucleoprotein (RNP) antibodies also contained antibodies that immunoprecipitated specifically either the deproteinized RNA component of the RohY5 RNP particle, or intact in vitro transcribed hY5 RNA. No serum recognized specifically the other hY RNAs. A mutant hY5 RNA with additional nucleotides (nt) at both extremities was not immunoprecipitated, possibly because of altered secondary structure. Following digestion of hY5 RNA with ribonuclease TI, the smallest immunoprecipitable RNA fragments were 27 and 31 nt long, and respectively mapped to the 5′and 3′ends of hY5 RNA, excluding the La-binding region. Base pairing between the 27 and 31 nt long fragments was required for recognition by antibodies. Our data indicate that the epitope bound by anti-hY5 RNA antibodies is conformational. We have previously reported that most anti-Ro sera contain a population of antibodies specific for the RohY5 RNP. Since antibodies to the deproteinized hY RNAs within anti-Ro sera are also restricted to anti-hY5 RNA, a direct role for the human-specific RohY5 particles in the immunization process leading to the production of anti-Ro antibodies is suggested.
Lysis of human macrophages by cytolytic CD4+ T cells fails to affect survival of intracellularMycobacterium bovis-bacille Calmette-Guérin (BCG)
Authors: Fazal N , Lammas D A , Rahelu M , Pithie A D , Gaston J S H , Kumararatne D S 
Published: July 2010

SUMMARYHuman CD4+, mycobacteria-specific, cytolytic T cell clones were used to lyse BCG-infected macrophages. and the effect on the subsequent growth and viability of the organisms was examined. The survival of released bacteria following cell lysis was assessed by both 3H-uridine labelling and colony-forming unit (CFU) estimation. The results indicate that even when effective antigen-specific or lectin-mediated cytolysis of the infected macrophages was achieved, there was no evidence for a direct mycobactericidal effect on the intracellular bacteria. This remained the case even if the period of co-culture of T cells and macrophages was extended up to 48 h. Pretreatment of the macrophages with interferon-gamma (IFN-γ) was not able to act together with T cell-mediated lysis to produce inhibition of mycobacterial growth.
A rare mediastinal tumour presenting with systemic effects due to IL-6 and tumour necrosis factor (TNF) production
Authors: Davies K A , Cope A P , Schofield J B , Chu C-Q , Mason J C , Krausz T , Smith P , Denman A M , Walport M J 
Published: July 2010

SUMMARYPatients presenting with prolonged systemic illnesses with no specific clinical or serological defining features may be diagnosed as having atypical systemic vasculitides, but often turn out to have occult malignancies. Cytokines have been implicated in causing many of the systemic effects in such cases. In this study we describe a patient presenting after 2 years of a severe systemic illness with a marked acute phase response, due to an occult mediastinal angiomatoid malignant fibrous histiocytoma. Tumour resection was curative. We evaluated in detail the local and systemic production of cytokines induced by this tumour. Blood samples were taken pre- and postoperatively for cytokine studies. In vitro production of IL-2, IL-2R, IL-1β, IL-6 and TNF-α by cultured monocytes from the patient, as well as plasma cytokine levels, were measured by ELISA. Tumour cytokine production was also evaluated immunocytochemically, and by in situ hybridization with specific cDNA probes. Plasma IL-2R and IL-6, and IL-6 and TNF-α production by peripheral blood monocytes were markedly elevated before tumour resection, normalizing postoperatively. Most tumour cells and infiltrating lymphocytes stained with antibodies to IL-6, IL-6R and TNF-α, and expressed HLA class II. IL-6 and TNF- α mRNA production in the tumour was confirmed by in situ hybridization studies. We have described the first case of an occult angiomatoid malignant fibrous histiocytoma in the mediastinum. Studies of cytokine expression suggested that chronic TNF, IL-6, and IL-2 production by leucocytes and tumour cells in this patient was responsible for the severe systemic illness with which she presented.
IL-1 is expressed in human adrenal glandin vivo.Possible role in a local immune-adrenal axis
Authors: GonzÁLez-HernÁNdez J A , Bornstein S R , Ehrhart-Bornstein M , Gschwend J E , Gwosdow A , Jirikowski G , Scherbaum W A 
Published: July 2010

SUMMARYIL-1 is an important mediator in the dialogue between the immune system and the hypothalamo-pituitary-adrenal axis. A direct influence of IL-1 upon adrenal steroidogenesis has been demonstrated in experimental animals. We therefore designed a study to see if IL-1 is expressed within the normal human adrenal gland. The combination of in situ hybridization and specific immunostaining to IL-1β was eminently suited to demonstrate both mRNA and protein production. The specific immunostaining of the different cells combined with in situ hybridization (IL-1) allowed us to identify the exact cellular source of IL-1. IL-1 mRNA occurred in the zona reticularis in 17α-hydroxyiase positive steroid cells surrounding the adrenomedullary cells. Some CD68+ macrophages in this zona showed a positive signal. A weak signal was seen to IL-1 mRNA in few chromaffin cells, while IL-1-like immunoreactivity was more frequent. We conclude that in the normal situation in man IL-1 is mainly expressed in specialized cortical cells. The occurrence of the major glucocorticoid inducing factor in the normal human adrenal gland itself provides evidence for an autocrine or paracrine reaction under physiological conditions.
Non-muscle myosin as target antigen for human autoantibodies in patients with hepatitis C virus-associated chronic liver diseases
Authors: VON MÜHLEN C A , CHAN E K L , PEEBLES C L , IMAI H , KIYOSAWA K , TAN E M 
Published: July 2010

SUMMARYThree patients with hepatitis C virus (HCV)-related chronic liver disease were shown to have autoantibodies strongly reacting with cytoskeletal fibres of non-muscle cells. The heavy chain of non-muscle myosin microfilament was the main target for those autoantibodies, as determined by (i) cell and tissue immunofluorescence studies showing colocalization with an anti-myosin antibody prototype; (ii) primary reactivity in immunoblotting with a 200-kD protein, using either MOLT-4 cells, human platelets, or affinity-purified non-muscle myosin as antigen extract; and (iii) immunoblotting of similar immunoreactive fragments in papain-digested MOLT-4 cell extracts, by using those human sera and antibody prototype. Autoantibodies to non-muscle myosin heavy chain were not previously reported in patients with chronic liver diseases, especially in those associated with HCV infection.
Combined effects of FK506 (tacrolimus) and cyclophosphamide on atypical B220+ T cells, cytokine gene expression and disease activity in MRL/MpJ-lpr/lprmice
Authors: WOO J , WRIGHT T M , LEMSTER B , BOROCHOVITZ D , NALESNIK M A , THOMSON A W 
Published: July 2010

SUMMARYGroups of female MRL/MpJ-lpr/lpr mice received either saline or FK506 (tacrolimus; 2mg/kg intraperitoneally) three times weekly, cyclophosphamide (CY; 20mg/kg) once monthly, or both drugs from 8 weeks of age. Median survival for untreated and CY-treated mice was 26 weeks, and for FK506- and FK5O6 + CY-treated groups was ± 44 weeks. Severity of skin lesions and lymph node hyperplasia was markedly reduced by the drug combination, whereas either drug alone was less effective. FK506 or CY alone delayed the onset of proteinuria, but by 24 weeks all of these animals were positive. In contrast, drug combination reduced the prevalence of proteinuria to ± 60% throughout the 44 weeks of study. Sequential monitoring of peripheral blood lymphocytes revealed that combination therapy but not monotherapy markedly reduced the proportion of atypical CD3+ B220+ and CD3+CD4-CD8- T cells. Neither FK506 nor CY affected the reduction in IL-2 and IL-4 mRNA levels observed in lymph nodes of diseased animals compared with normals. Although the drug combination also did not affect IL-2 mRNA levels, IL-4 mRNA transcripts were increased six-fold compared with saline-treated controls. IL-10 and interferon-gamma (IFN-γ) mRNAs were induced by FK506, CY and by the drug combination. Serum levels of anti-dsDNA antibodies were reduced in all treatment groups. These data demonstrate improved efficacy of combined T and B cell-directed immunosuppression in murine lupus, associated with marked inhibition of atypical T cells and selective augmentation of IL-4 within the affected lymphoid tissue.
Peritoneal lavage fluids stimulate NIH3T3 fibroblast proliferation and contain increased tumour necrosis factor and IL-6 in experimental silica-induced rat peritonitis
Authors: LEE H G , CHOI I , PYUN K H , PARK K W 
Published: July 2010

SUMMARY
Fibroblast proliferation is one of the earliest features of fibrosis, preceding collagen deposition in wound. The response to tissue injury is characterized by the infiltration of acute inflammatory cells, followed by persistence of macrophages. In vitro, macrophages are known to secrete monokines and growth factors which affect fibroblast proliferation and collagen synthesis. To investigate in vivo kinetics of fibroblast proliferating activity and monokine production in experimental peritonitis, silica was instilled intraperitoneally into rats, and peritoneal lavage fluids (PLF) and the culture supernatants of macrophages were analysed for NIH3T3 fibroblast proliferating activity and monokine production. NIH3T3 fibroblast proliferating activity in PLF was markedly elevated 3–5 days after intraperitoneal silica instillation, and peritoneal macrophages also spontaneously released these factors in vitro. Tumour necrosis factor (TNF) and IL-6 were also markedly increased after 3–5 days, and macrophages spontaneously released these monokines. PLF-induced fibroblast proliferation was blocked by anti-TNF antibody, and fibroblast proliferation was stimulated by the external addition of TNF or TNF and IL-6 in vitro. These results show high influx of fibroblast proliferating factors and monokines in peritoneal lavage fluid after 3–5 days of silica-induced experimental peritonitis, providing further evidence of involvement of macrophages, TNF, and possibly IL-6 in peritoneal fibrosis.
Do IgE-IgG complexes occur in the circulation?
Authors: BOLUDA L , BERRENS L 
Published: July 2010

SUMMARYIgG anti-IgE autoantibodies in human allergic sera have been investigated using an enzyme immunoassay on microplates coated with anti-human IgE MoAb. After incubation with serum, the plates were developed with peroxidase-labelled anti-human IgE MoAb for the determination of total IgE levels, or with anti-IgG MoAb for evaluating IgG anti-IgE autoantibodies. Using this methodology, no correlation was found between total IgE and IgG anti-IgE levels in groups of sera of allergic individuals. Although the results obtained with enzyme-labelled anti-IgG are often interpreted as indicative of IgE-IgG complexes captured from the serum, molecular sieving on gel columns as well as direct ultrafiltration experiments through 300-kD membranes demonstrate that such complexes do not occur preformed in the circulation, but arise de novo on the anti-IgE-coated solid phase during in vitro incubation with human serum. It is suggested that IgG anti-IgE autoantibodies react with IgE only after the latter has undergone a conformational change, either by colloidal manipulation or after reaction with allergen.
Localization and identification of granzymes A and B-expressing cells in normal human lymphoid tissue and peripheral blood
Authors: KUMMER J A , KAMP A M , TADEMA T M , VOS W , MEIJER C J L M , HACK C E 
Published: July 2010

SUMMARYCytoplasmic granules from activated natural killer (NK) and cytotoxic T lymphocytes (CTL) contain a pore-forming protein, perforin, and several homologous serine proteinases called granzymes. Expression of these proteins correlates with the cytolytic potential of cytotoxic lymphocytes. Using a panel of MoAbs specific for human granzyme A and B, respectively, expression of these proteinases in non-pathological lymphoid tissue and peripheral blood lymphocyte (PBL) subpopulations was investigated. Using immunohistochemistry and double stainings, the phenotype of granzyme-expressing cells in lymphoid tissue was investigated. Granzyme-positive cells were detected in all lymphoid tissues tested. No large differences in the number and distribution between granzyme A- and granzyme B-positive cells were observed. The highest number of positive cells was located in the red pulp of the spleen. Significant numbers were detected in tonsil, lymph nodes, liver and thymus. Low numbers were present in the lamina propria of non-inflamed stomach, small intestine and colon. Phenotypic analysis and cell sorting showed that most of the granzyme-positive cells in lymphoid tissue and PBL consisted of CD3+ CD16+CD56+ lymphocytes. Hardly any granzyme-positive CD3+CD8+ CTL were present in peripheral blood. The synthesis of granzyme A as well as B by both CD3 CD16+ CD56+ and CD3+CD8+ cells in peripheral blood was increased upon IL-2 stimulation. These results indicate that in normal lymphoid tissue the predominant cytolytic cell population is formed by the NK cells, and activated CTL are rare.