bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary excretion of nitrite and nitrate in experimental glomerulonephritis reflects systemic immune activation and not glomerular synthesis
Authors: SEVER R , COOK T , CATTELL V 
Published: August 2010

SUMMARYIn immune-induced glomerulonephritis (gn), glomeruli (gl) synthesize nitric oxide (NO), and urinary nitrite (NO2−) excretion is increased. In mammals on a low nitrate (NO3−) diet, urinary NO3− is a measure of endogenous NO3− synthesis. Excretion is increased after administration of macrophage activators, reflecting induction of NO production. To determine whether increased urinary NO2− gn is due to glomerular synthesis we studied urinary NO2−/NO3− in accelerated nephrotoxic nephritis induced by preimmunization with rabbit immunoglobulin G (IgG), followed by rabbit anti-rat nephrotoxic globulin, and in control rats similarly preimmunized with rabbit IgG, but followed by normal rabbit serum. Both urinary NO2− and NO3− were increased by i.p. preimmunization with rabbit IgG (peak 463 ± 171 nmol NO2−/60·3 ± 9·4 nmol NO3/24 h, P&lt;0·001 for both NO2− and NO3− compared with preimmunization levels). Repeat immunization with i.v. rabbit anti-rat nephrotoxic globulin (nephritic rats) or normal rabbit globulin (control rats) again increased urinary NO2− and NO3−. There was no statistically significant difference in urinary NO2 and NO3− levels between nephritic rats where globulin had nephrotoxic activity and the control rats injected with normal rabbit globulin, despite increased NO2−synthesis in ex vivo nephritic glomeruli after nephrotoxic globulin (7·9 ± 1·9 nmol/2000 gl/48 h; controls 3·2 ± 1·0 nmol/2000 gl/48 h). Thus neither urinary NO2− nor NO3− levels reflect local activation of the NO pathway in glomeruli. As reported for other stimulants, we show here that systemic stimulation with foreign antigen increased NO synthesis.
Changes in circuIating B cells and immunoglobulin cIasses and subcIasses in a healthy aged popuIation
Authors: PAGANELLI R , QUINTI I , FAGIOLO U , COSSARIZZA A , ORTOLANI C , GUERRA E , SANSONI P , PUCILLO L P , SCALA E , COZZI E , BERTOLLO L , MONTI D , FRANCESCHI C 
Published: August 2010

SUMMARYThe study of 87 adults of different ages, including 15 centenarians, selected for their healthy status, showed that profound changes of humoral immunity occur throughout life. In particuIar, a statistically significant age-reIated increase of the serum level of immunoglobulin cIasses (IgG and IgA but not IgM) and IgG subcIasses (IgG1, 2 and 3, but not IgG4) was detected. A parallel age-related decrease of circuIating B cells was also observed. The hypothesis of a complex derangement of B cell function and/or compartmentalization with age is put forward, together with the proposal that healthy centenarians (as representative of successful ageing) may be helpful in identifying the physiological age-reIated modifications of the immune system.
Association of T cell and macrophage dysfunction with surface gp120-immunoglobulin-complement complexes in HIV-infected patients
Authors: DANIEL V , SÜSAL C , WEIMER R , ZIMMERMANN R , HUTH-KÜHNE A , OPELZ G 
Published: August 2010

SUMMARYThe mechanism of CD4+ cell depletion and functional T helper cell inhibition in HIV-infected individuals is poorly understood. The present study demonstrates that immune complex-covered CD4+ cells arc associated with T cell inhibition and macrophage stimulation. We studied 30 patients with ARC/AIDS and 35 asymptomatic HIV haemophilia patients. Overall, 20 ± 3% of peripheral CD4+ lymphocytes were covered with gp 120 (range 0–94%). Gp120+ cells also exhibited surfacebound IgG (P=0.0001). IgM (P= 0.0001), and complement (P= 0.0001). Decreased in vitro lymphocyte proliferation was associated with the immune complex load of CD4+ cells. The higher the percentage of CD4+ gp120+ cells in the blood, the lower the T cell response in vitro (P=0.00l). Moreover, an association was found between immune complex-positive cells and plasma neopterin (P=0.01). Patients with increased plasma neopterin levels had decreased in vitro responses to pokeweed mitogen (PWM) (P=0.006), phytohaemagglutinin (PHA) (P=0.004), concanavalin A (Con A) (P=0.09), and anti-CD3 MoAb (P=0.03), and decreased CD4+ cell counts in the blood (P=0.006). Since maximally 1% of CD4+ lymphocytes are infected with HIV, T cell dysfunction and T cell depletion in HIV-infected patients may also be caused by the release of free gp120 that binds to uninfected CD4+ cells. Our data suggest that the functional inhibition and subsequent elimination of uninfected CD4+ lymphocytes with surface gp120 immunoglobulin complement complexes may be a pathomechanism in the manifestation of AIDS.
Tumour necrosis factor productionin vivoandin vitroin response toParacoccidioides brasiliensisand the cell wall fractions thereof
Authors: FIGUEIREDO F , ALVES L M C , SILVA C L 
Published: August 2010

SUMMARYTumour necrosis factor (TNF) was detected in scrum from mice challenged with Paracoccidioides brasiliensis. The scrum TNF levels of mice challenged with an avirulent strain were significantly higher than those of mice challenged with a virulent strain, and the same was observed for the TNF levels of mice challenged with a cell wall fraction (F1) from the two fungal strains. Fraction F1 consisted of chitin and β-glucan; but although the chitin contents were similar for the two strains, the avirulcnt strain allowed a greater content of β-glucan. The β-glucan, purified from both strains, increased serum TNF levels in an identical dose-dependent manner, whereas purified chitin did not induce scrum TNF levels. P. brasiliensis, the F1 fractions and β-glucan induced macrophages to secrete TNF in vitro. The differences in TNF levels, induced by the different fungal strains, were correlated with the β-glucan concentrations in the cell walls of both the avirulent and virulent strains of P. brasiliensis. These findings support a role for TNF in the pathogenicity of P. brasiliensis.
Immunosuppressive property of bromocriptine on human B lymphocyte functionin vitro
Authors: MORKAWA K , OSEKO F , MORIKAWA S 
Published: August 2010

SUMMARYBromocriptine (BRC), a dopamine ergot alkaloid, inhibits the release of pituitary prolactin (PRL). Hypoprolactinaemia induced in rat by treatment with BRC produces a similar immunosuppressive effect as observed in hypophysectomized rats. The effect of immunosuppression by the administration of BRC has been interpreted as the result of hypoprolactinaemia produced by BRC. However, the direct effect of BRC on lymphocyte function has never been evaluated. The purpose of this study was to investigate the in vitro effect of BRC on human B cell functions. Highly purified B cells from tonsil samples were isolated by Percoll density gradient from non-rosctted cells, and were used as target cells. BRC significantly suppressed the proliferative response of resting and activated B cells in vitro. It suppressed immunoglobulin generation of activated B cells. The inhibition of BRC was manifested in the early stage of the proliferation and differentiation of B cells. The conditioned medium from the polyclonal B cell mitogcn-stimulated B cell cultures did not contain PRL as determined by immunoradiometric assay. Treatment with low-dose cyclosporin A or FK506 in conjunction with BRC has proved more effective than either drug alone in suppression of B cell proliferation. Thus, the combined therapy of BRC and immunosuppressants may be effective with decreased toxicity for clinical use.
Immunohistochemical detection of co-localizing cytokine and antibody producing cells in the extrafollicular area of human palatine tonsils
Authors: HOEFAKKER S , van't ERVE E H M , DEEN C , van den EERTWEGH A J M , BOERSMA W J A , NOTTEN W R F , CLAASSEN E 
Published: August 2010

SUMMARYIn vitro experiments have documented the role of cytokines in the regulation of the human humoral immune response. Which cytokines arc operative in vivo and in which lymphoid compartment interactions between cytokine-producing T cells and antibody-forming B cells occur is still unclear. For that reason we studied human tonsils using immunohistochemical techniques. In tissue sections from tonsils in a resting stage after recurrent tonsillitis we observed cells producing IL-1 α and tumour necrosis factor-alpha (TNF-α) which were exclusively localized in the mantle zone of the follicle and in the extrafollicular area. Furthermore, a high frequency of interferon-gamma (IFN-γ)-producing cells was detected in the extrafollicular area, but not inside the follicles. Occasional IL-2- and IL-4-producing cells were found in the extrafollicular area. Immunohistochemical detection of antibody isotypes revealed that B cells, IgM-membrane-positive, were localized inside the follicles and mantle zones, whereas IgD-membrane-positive cells were mainly found in the mantle zones of secondary follicles. In contrast, plasma cells producing IgGl-4 and IgAl-2 were found in the extrafollicular area. No IgD and IgE antibody-forming cells were detected in tonsils, whereas IgM antibody-forming cells were detected in the xtrafollicular area. The co-localization of cytokine-producing cells and antibody-forming cells in human tonsil suggests that T-B cell interactions, required for B cell differentiation and isotype switching, take place in the extrafollicular area.
Antimitochondrial autoantibodies in anti-glomerular basement membrane disease
Authors: MARRIOTT J B , OLIVEIRA D B G 
Published: August 2010

SUMMARYAnti-glomerular basement membrane (GBM) disease is characterized by the production of an autoantibody with very restricted specificity, with no evidence of polyclonal B cell activation. It was therefore surprising to find that in a solid-phase ELISA a proportion of anti-GBM sera showed significant binding to pyruvate dehydrogenase (PDH), a reactivity usually associated with the antimitochondrial autoantibodies (AMA) found in primary biliary cirrhosis (PBC). The specificity of this reactivity was confirmed by inhibition and competition experiments. The AMA found in anti-GBM sera were of much lower affinity than those found in PBC sera, and recognized a more restricted set of species (mainly the 55-kD and occasionally the 74-kD component of PDH). However, it was possible to block the binding in a Western blot of an anti-GBM serum to both the 55-kD and 74-kD species with F(ab')2 fragments prepared from a PBC serum. Although AMA have been found in diseases other than PBC, such diseases have usually been characterized by polyclonal B cell activation. The stimulus to the production of AMA in anti-GBM disease, and their significance in pathogenesis (if any), are unknown.
Surface expression of adenosine deaminase in mitogen-stimulated lymphocytes
Authors: MARTIN M , CENTELLES J J , HUGUET J , ECHEVARNE F , COLOMER D , VIVES-CORRONS J L , FRANCO R 
Published: August 2010

SUMMARYAdenosine deaminase (ADA) expression on the surface of mitogen-stimulated lymphocytes was studied by flow cytometry. The gate for lymphocytes was located by cell size (forward scatter), cytoplasmic complexity (side scatter) and by expression of the markers CD2, CD4. CD8 and CD19. After mitogenic proliferation two populations appeared, one corresponding to non-stimulated cells, and the other consisting of larger cells which showed relatively high expression of adenosine deaminase on their surface. The increase was similar to that observed for CD71 expression, and paralleled the increase in 3H-thymidine incorporation. There was a correlation between ADA and CD71 expression (r= 0.92 for phytohacmagglutinin (PHA) and 0.97 for pokeweed mitogen (PWM)). These results suggest a role for ecto-adenosine deaminase in lymphocyte proliferation and/or triggering.
Recombinant gp120 induces IL-10 in resting peripheral blood mononuclear cells; correlation with the induction of other cytokines
Authors: AMEGLIO F , CAPOBIANCHI M R , CASTILLETTI C , CORDIALI FEI P , FAIS S , TRENTO E , DIANZANI F 
Published: August 2010

SUMMARYImmutiological abnotmalities present in HIV-1-infected individuals often reflect an imbalance of cytokine production. The HIV-I gpl20 has the ability to induce a number of cytokines, and to enhance immunoglobulin release by normal peripheral blood mononuclear cells (PBMC) in vitro, in the absence of IL-2 production and of lymphoproliferation. This study provides evidence that gpl20 is a potent IL-10 inducer in normal PBMC cultures. The pattern of other cytokines induced by gp 120 includes interferon-alpha (IFN-a) and IFN-γ, tumour necrosis factor-alpha (TNF-α), IL-6, IL-Iα2 and IL-β, and not IL-2 and IL-4. These findings further define the pattern of cytokine release induced by gpl20 on human resting PBMC. Furthermore, the present findings roughly parallel those observed both in the sera of patients and in the mononuclear cells from HIV+ individuals early after infection, suggesting that gpl20 could be a good candidate as one of the agents responsible for cytokine dysregulation observed in HIV-1-infected individuals.
Increased CD45RO expression on T lymphocytes in mediastinal lymph node and pulmonary lesions of patients with pulmonary sarcoidosis
Authors: FAZEL S B , HOWIE S E M , KRAJEWSKI A S , LAMB D 
Published: August 2010

SUMMARYSarcoidosis is characterized by a cell-mediated response mediated by the activation of CD4′ T lymphocytes in an environment lacking adequate numbers of regulatory CD8 T lymphocytes. Immunohistological studies on frozen tissues have shown that sarcoid lesions have activated CD4 heiper/inducer T lymphocytes at the centre of granulomata, whereas lymphocytes at the periphery are mainly CD8 suppressor/cytotoxic cells. In this study we investigated the immunohistological distribution of CD45 isoforms of T cells in 29 paraffin-embedded sarcoid lesions in mediastinal and open lung biopsies. Ten of these were assessed quantitatively, with single-staining of serial sections demonstrating a predominance of CD45RO memory T lymphocytes in granulomata and intergranulomalous areas. Ratios of CD45RO;CD45RA T lymphocytes (or the ratio oi memory to naive T cells) were 420:1 for granulomata and 17-9:l for intergranulomatous areas of sarcoid lesions counted. This finding is compatible with the hypothesis that nearly all the lymphocytes present in sarcoid lesions have been previously activated, and selectively home to sarcoid lesions.
Immunosuppressive activity of bromocriptine on human T lymphocyte functionin vitro
Authors: MORIKAWA K , OSEKO F , MORIKAWA S 
Published: August 2010

SUMMARYBromocriptine (BRC), a dopamine type 2 agonist, prevents secretion of pituitary prolactin (PRL). BRC has been shown to impair lymphocyte responsiveness toward antigenic stimulation by decreasing serum PRL levels, Hypophyophysectomized induced by BRC produces a similar immunosuppressive effect, as observed in hypophysectomized rats, which is restored by the administration of PRL, Therefore, the immunosuppression induced by BRC has been interpreted as the result of hypoprolactinaemia. However, the direct mechanism of BRC in immune response has never been evoked. We recently reported that BRC has an immunosuppressive activity on human B lymphocyte function in vitro. In the present study we demonstrate that BRC suppresses T cell proliferation by means of blocking IL-2 production by T cells as well as mixed lymphocyte reaction (MLR) in a dosedependent manner. We could not detect the immunoreactive PRL activity in the conditioned medium from polyclonai T cell mitogen-stimulated T cell cultures. Then, the immunosuppressive activity of BRC on human T cell function appeared to be independent of its hypoprolactinaemic effect. Treatment with low-dose cyclosporin A(CsA) or FK506 in combination with BRC has proved more effective than either drug alone in suppression of T cell proliferation and CD25 antigen expression. Thus, the therapeutic applicalion of BRC in combination with immunosuppressants may enhance the immunosuppressive effect, while at the same time decreasing the toxicity.
IL-6 induces hepatic inflammation and collagen synthesisin vivo
Authors: CHOI I , KANG H-S , YANG Y , PYUN K-H 
Published: August 2010

SUMMARYIL-6 regulates the synthesis of a broad spectrum of acute phase proteins in the liver. Also, it is involved in the pathogenesis of many fibrogenic diseases. To study ihe inflammatory effects of IL-6 on the in vetro human rIL-6, produced in Escherichia coli. was injected intraperitoneally into rats (25 μ/100 g body weight). The major fractopm of injected 11-6 was accumulated in the liver within 40 min, and the number of platelets was increased during 72 hafter injection. After 5 weeks of injection. the levels of serum glutamine pyruvic transaminase (GPT) and glutamic oxaloacctic transaminase (GOT) were not changed, but they were significantly elevated at 13 weeks of treatment. Meanwhile, scrum albumin levels were slightly decreased compared with those of controls. The same phenomena were observed in carbon tetrachloride-treated rats. Collagen synthesis was increased in the liver tissues and in the culture supernatants of hepatic lipocyles isolated from the rats treated with lL-6for 13 weeks. Histological analysis correlated well with biochemical analysis. At 5 weeks of treatment, only mild pathological changes were observed, but severe hepatocyte necrosis and the accumulation of fibres in necrotic area were developed in the liver of IL-6-treated rats after 13 weeks of treatment, confirming that hepatic inflammation and fibrosis were developed. IL-6 activities in the sera and in the culture supernatants of lipocytes from IL-6-treated rats were elevated compared with those in controls. These biochemical and pathological data indicate that IL-6 can induce hepatic inflammation, and it has important roles in the pathogenesis of fibrosis and diseases of the liver in vivo. In addition, these results will provide useful information for ihc clinical trials of IL-6.
Constitutive c-fos expression in osteoblastic MC3T3-E1 cells stimulates osteoclast maturation and osteoclastic bone resorption
Authors: KUROKI Y , SHIOZAWA S , SUGIMOTO T , KANATANI M , KAJI H , MIYAUCHI A , CHIHARA K 
Published: August 2010

SUMMARYThe effect of culture supernatants of c-fos-transfectcd MC3T3-El osteob[aslic cells on osteoclastic bone resorption was studied. Human c-fos cDNA was integrated in the expression vector pH8. and the cells were transfected using the calcium phosphate precipitation technique. Osteoclastic bone resorplion was quantified by the pit formation assay, and the osteoclast maturation from precursor was assessed by the generation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNC). The culture supernatants of MC3T3-E1 transfectants constitulively expressing c-fos gene enhanced osteoclast-like MNC formation from haematopoietic blast cells compared with those of control transfectants (P&lt;0·01). The culture supernatants also promoted osteoclastic bone resorption: the pit number. 118·7±38·5, was significantly higher than 19·0±10·1 of the control (P&lt;0·05). The absorption area. 12394±3145 mm2, was significantly larger than 1646+314 mm2 of the control (p&lt;0-05). The culture supernatants also promoted bone resorption by purified chick osteoclasts (P&lt;0·05). The results show that constitutive expression of c-fos gene in osteoblastic MC3T3-EI cells stimulates osteoclast rnaturation and osteoclastic bone resorption by releasing humoral mediator(s).
Increased numbers of CD5+ B cells and T cell receptor (TCR) γδ+ T cells are associated with younger age of onset in rheumatoid arthritis (RA)
Authors: Hassan J , Yanni G , Hegarty V , Feighery C , Bresnihan B , Whelan A 
Published: August 2010

SUMMARY
Patients presenting with RA before the age of 45 years (younger onset) are known to have more aggressive disease compared with patients presenting after the age of 65 years (older onset). Coordinated expansion of circulating CD5+ B cell and TCR γδ+ T cell levels has been reported in patients with RA. This study assesses the peripheral blood levels of these two cell types in RA patients with younger and older onset of disease. CD5+ B cell levels were significantly elevated in the younger onset RA group (26±6 γδ+4±5%) compared with the older onset RA group (14±2 γδ+1±2%; P&lt;0±01). TCR γδ+ T cell levels were also significantly raised in the young patients (4±0 γδ+0±9%) compared with elderly patients (1±6 γδ+0±2%; P&lt;0±01). T cell levels (CD3+) were similar in both groups (young 66±4 γδ+3±3%; old 74±3 γδ+3±4% (mean γδ+s.e.m.); NS). Total B cell levels (CD19+) were also similar in these groups (7±7 γδ+0±7%versus 8±9 γδ+1±8%; NS). A significant positive correlation was observed between the CD5+ B and TCR γδ+ T cell types in the patients (r= 0±72, P&lt;0.05). Compared with age-matched normal controls, the younger onset patients had similar CD5+ B cell and TCR γδ+ T cell levels to the elderly controls (CD5+ B cells 30±2 γδ+3±0%; TCR γδ+ T cells 3±0 γδ+0±8%). Conversely, older onset RA patients had CD5+ B cell levels similar to the young controls (12±3 γδ+1±9%). Spontaneous in vitro synthesis of immunoglobulins (IgM, IgA and IgG) and rheumatoid factors (IgM and IgA isotypes) were not significantly different in both patient groups. The coordinate expansion of circulating CD5+ B cells and γδ+ T cells seen in patients with RA presenting before 45 years of age and not after 65 years of age may suggest a potential role for these cells in more aggressive disease states.
Therapeutic effects of estradiol benzoate on development of collagen-induced arthritis (CIA) in the Lewis rat are mediated via suppression of the humoral response against denatured collagen type II (CII)
Authors: Waksman Y , Hod I , Friedman A 
Published: August 2010

SUMMARYThe effects of estradiol benzoate (EB) on the development of anti-CII antibodies and their pathogenic potential were studied during the progress of established CIA in the rat. CIA was induced in mature female Lewis rats by two subcutaneous inoculations containing bovine native CII (BCIIn), emulsified in Freund’s incomplete adjuvant. Clinical arthritis fully developed by day 18 and then EB (1 mg/kg body wt per day, diluted in corn oil (CO)) was administered intramuscularly every second day thereafter. Antibodies binding four different CIIs (bovine or rat, either native or heat-denatured) were detected in sera and joint tissue extracts by means of solid-phase ELISA. Pharmacological doses of EB (&gt;0±2 mg/kg body wt per day) caused significant remission of established CIA 5-7 days after treatment, and selectively suppressed the production of antibodies specific for denatured CII. To evaluate the arthritogenic potential of circulating anti-CIId IgG, transfer experiments were performed. IgG anti-CIIn, purified from EB-treated CIA rats, was not arthritogenic, whereas IgG anti-denatured (CIId), purified from CO-treated CIA rats, caused severe passive arthritis. Furthermore, pretreatment with rat CIId protected against subsequent induction of CIA, and this protection was associated with suppressed antibody production against CIId. Collectively, our results indicate that antibodies specific for CIId are involved in the pathogenesis of CIA, and that oestrogen-related remission of clinical arthritis may be caused by a selective suppression of antibodies produced against degraded denatured CII.