bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination chemo-immunotherapy: kinetics ofin vivoandin vitrogeneration of natural killer cells and lymphokine-activated killer cells in the rat
Authors: STEWART L S , SEWELL A F , THOMSON A W 
Published: July 2010

SUMMARYRats received a single high dose of cyclophosphamide (Cy) (150 mg/kg). followed 48 h later (on day 0) by immunization with a T cell-dependent soluble antigen, ovalbumin in Freund's complete adjuvant (FCA). The effect of this treatment on lymphoid cell subpopulalions in the spleen, natural killer (NK) cell and interieukin-2 (IL-2) induced lymphokine-activated killer (LAK) cell activity was examined. Cy (with and without ovalbumin) caused a large relative increase (by day 14) in splenic OX 8+, OX 19-cells with NK morphology. A marked relative increase in fresh NK cell activity was noted after Cy+ovalbumin, but not consistently after Cy alone. Elevated NK activity was Cy dose- and time-dependent, was evident within 7 days post Cy/ovalbumin and persisted for at least 28 days. Pooled splente mononuclear cells (MNC), obtained 14 days after Cy/ovulbumin, lost all cytolytic activity against YAC-I cells when cultured in the absence of human recombinant IL-2 (rIL-2). In contrast, similarly maintained cells from normal rats displayed NK activity higher than normal‘fresh’levels. Upon culture in medium containing 500 U/ml rIL-2, however,‘augmented’NK. activity was equivalent, on a per-cell basis, in both normal and Cy/ovaibumin-pretreuted groups. LAK activity generated in vitro (i.e. against NK.-resistant target cells) was significantly lower in the latter group, and the overall yield of cells was reduced. By day 21 after Cy/ovaibumin, augmented NK activity was significantly greater lhan controls, on a per-cell and total culture yield basis. Moreover, LAK activity was now similar between groups. It is concluded that the chemotherapy/immunization protocol which we have used can greatly enhance NK activity in vitro and that these cells are responsive to induction of LAK activity by IL-2 in ritro.
Reduced natural cytotoxic cell activity in patients receiving cisplatin-based chemotherapy and in mice treated with cisplatin
Authors: POWELL C B , MUTCH D G , KAO M -S , COLLINS J L 
Published: July 2010

SUMMARYIn mice natural cytotoxic (NC) cells are known to play a role in the rejection of tumours that are sensitive to NC-mediated lysis. We have recently shown that in vitro human and murine tumour cells become more sensitive to lysis mediated by NC cells in the presence of the anti-cancer drug cisplatin. If NC activity plays a role in tumour surveillance in humans, then the ability of NC cells to eliminate tumours in patients treated with cisplatin would not only be dependent on cisplatin increasing the sensitivity of tumours to NC mediated lysis, but would also depend on the maintenance of high levels of NC activity during chemotherapy. Here we report that patients receiving chemotherapy that included cisplatin showed a time-dependent reduction in NC activity. NC activity was normal I day after treatment; however, 15 days after treatment patients had an eight- to 16-fold reduction in NC activity that returned to normal levels by day 21. The reduction in NC activity of patients was coincident with a reduction in circulating monocytes. Mice treated with only cisplalin showed a similar reduction in NC activity. Mice treated with cisplalin had a reduced level of NC activity that was first apparent 8 days after treatment, reached a nadir on day 15, and returned to normal levels on day 22.
Antibodies to mouse laminin in patients with systemic sclerosis (scleroderma) recognize galactosyl (αl-3)-galactose epitopes
Authors: GABRIELLI A , CANDELA M , RICCIATTI A M , CANIGLIA M L , WIESLANDER J 
Published: July 2010

SUMMARYEmploying radioimmunoinhibition assays with distinct oligosaccharides as inhibitors, this study demonstrates that the epitope recognized on mouse laminin by sera from patients with systemic sclerosis (scleroderma) is a terminal galactosyl (α1–3)-galactose disaccharide. The reaction with this α-digalactose was further confirmed when the sera were tested in radioimmunoassay (RIA) binding assay and in ELISA with synthetic galactose α1–3 galactosc coupled to human serum albumin. The circulating antibody appeared restricted to the IgG class and mostly to the subclass IgG3 and IgG4. Antibodies with the same specificity can be found in patients with American cutaneous leishmaniasis and Chagas disease: however, whilst in these diseases the antibody production is triggered by antigenic determinants present on the surface of the parasites, the events eliciting their appearance in systemic sclerosis are unknown.
Heart-specific autoantibodies can be eluted from the hearts of Coxsackievirus B3-infected mice
Authors: NEUMANN D A , LANE J R , LAFOND-WALKER A , ALLEN G S , WULFF S M , HERSKOWITZ A , ROSE N R 
Published: July 2010

SUMMARYThis study was undertaken to determine if immunoglobulin G (IgG) antibodies could be eluted from the hearts of mice with Coxsackievirus B3-induced autoimmune myocarditis and to characterize the immunorcactivity of any elutable autoantibodies. Susceptible (A/J) and resistant (B10.A) mice were administered the virus or the control treatment and killed at various times after treatment. Acid eluates from pooled heart tissue from each treatment group and each time were tested for IgG reactivity with normal heart tissue by immunohistochemistry and with normal heart extracts by Western immunostaining. Eluates from infected A/J mice reacted strongly with syngeneic heart and modestly with syngeneic skeletal muscle tissue. Eluates from infected B10.A or control mice of either strain exhibited little reactivity with either tissue. Tissue reactivity was similar when allogeneic tissue was used as the substrate. Eluates from infected A/J mice recognized the heavy chain of cardiac myosin and several other cardiac antigens by Western immunostaining while eluates from the other treatment groups exhibited little or no reactivity with any normal heart constituents. These results indicate that in vivo IgG deposition occurs in the hearts of mice with post-infectious autoimmune myocarditis and that the specificity of these antibodies is similar to that reported for serum from animals with this disease. The mechanism(s) leading to myocardial IgG deposition and its possible role in pathogenesis remain to be elucidated.
Inhibition of autoimmune diabetes in NOD mice with serum from streptococcal preparation (OK-432)-injected mice
Authors: SEINO H , SATOH J , SHINTANI S , TAKAHASHI K , ZHU X P , MASUDA T , NOBUNAGA T , SAITO M , TERANO Y , TOYOTA T 
Published: July 2010

SUMMARYWe have recently reported that systemic and chronic administration of recombinant tumour necrosis factor alpha (TNF-α), as well as streptococcal preparation (OK-432), inhibits development of insulin-dependent diabetes mellitus (IDDM) in NOD mice and BB rats, models of IDDM. In this study we examined whether serum containing endogenous TNF induced by OK-432 injection could inhibit IDDM in NOD mice. Treatment twice a week from 4 weeks of age with OK-432-injected mouse serum, which contained endogenous TNF (75U), but not IL-1, IL-2 and interferon-gamma (IFN-γ) activity, reduced the intensity of insulitis and significantly inhibited the cumulative incidence of diabetes by 28 weeks of age in NOD mice, as compared with the incidence in non-treated mice (P&lt;0.01) and in mice treated with control serum (P&lt;002). This inhibitory effect of the serum was diminished, although not significantly, by neutralization of serum TNF activity with anti-mouse TNF antibody. In the mice treated with the serum from OK-432-injected mice, Thy-1.2+ or CD8+ spleen cells decreased (P&lt;0.01) and surface-Ig+ (S-Ig+) cells increased (P&lt;0.05), whereas the proliferative response of spleen cells to concanavalin A (P&lt; 0.01) and lipopolysaccharide (P&lt;0.05) increased. The results indicate that the inhibition by OK-432 treatment of IDDM in NOD mice was partially mediated by serum factors including endogenous TNF.
Antibodies toMycobacterium tuberculosis-specificepitopes in lepromatous leprosy
Authors: BOTHAMLEY G , BECK J S , BRITTON W , ELSAGHIER A , IVANYI J 
Published: July 2010

SUMMARYSera from patients with leprosy or tuberculosis and healthy subjects have been analysed for the presence of antibodies to four species-specific mycobacterial epitopes, four different viruses and five autoantigens. Antibodies to the Mycobacterium leprae-specific 35-kD protein and phenolic glycolipid I epitopes were not present in patients with active pulmonary tuberculosis. In contrast, antibody levels to species-specific epitopes of the 38-kD and 14-kD antigens M. tuberculosis were significantly elevated in patients with lepromatous leprosy. Neither of the two antigens is cross-reactive with M. leprae at the B cell level. However, it was considered that cross-reactive helper T cells could recall the response of M. tuberculosis-specific memory B cells, which had been primed through prior self-healing tuberculous infection. As an alternative explanation, the possible role of polyclonal B cell stimulation was considered. This seemed unlikely, however, since: (i) antibody levels to autoantigens, except anti-smooth muscle, were not elevated, and (ii) antibody levels to four distinct viruses, unlike those to all mycobacterial epitopes, showed no correlation with litres, to M. tuberculosis-specific epitopes.
Suppression of human lymphocyte responses to specific and non-specific stimuli in human onchocerciasis
Authors: ELKHALIFA M Y , GHALIB H W , ALLA T DAFA , WILLIAMS J F 
Published: July 2010

SUMMARYCharacterization of in vitro lymphocyte responsiveness was performed on selected groups of onchocerciasis patients from Sudan and Sierra Leone. These patients manifested a very broad range of clinical signs and showed widely divergent parasite infection intensities. Lymphocyte proliferative responses to soluble Onchocerca volvulus antigen (sAg) were poor in infected persons; mitogen and PPD responses were maintained in the normal range in one group of patients from southwestern Sudan, but were profoundly depressed in a group from N.E. Sudan. Proliferative responses and interferon-gamma (INF-γ) secretion were very significantly depressed in the presence of live microfilariae of O. volvulus or secretions/excretions (S/E) from microfilariae (mf) or from female, but not male, adult parasites. Lymphocyte responses were maintained near normal when exogenous IL-2 was added to these cultures. The results indicate that O. volvulus infection and its clinical consequences arc not consistently associated with systemic deficits in immune responsiveness. However, suppression of lymphocyte reactivity by mf and S/E in vitro suggests that direct parasite intervention in host cell responses could be taking place in vivo, perhaps at the local micro-environment level, mediated by effects on cytokine production.
T cell receptor γδ bearing cells are decreased in the peripheral blood of patients with atopic diseases
Authors: SCHAUER U , DIPPEL E , GIELER U , BRÄUER J , JUNG T , HEYMANNS J , RIEGER C H L 
Published: July 2010

SUMMARYThe biological role of T cell receptor (TCR) γδ bearing cells is currently not fully understood. Recently, a monoclonal antibody (TCRδ1) reacting against the whole molecule became available which facilitates the direct analysis of TCR-γδ+ cells. We studied 11 children with atopic dermatitis, 20 children with atopic asthma, 18 adults with atopic dermatitis and 38 healthy age matched controls aged 4–51 years. Lymphocytes were isolated from heparinized peripheral blood and the proportion of TCR-γδ+ lymphocytes was determined by FACS analysis. Patients with atopic diseases yielded a significantly (P&lt;0.01) lower proportion of TCR-γδ+ cells compared with normal controls (median 4.8%versus 7.1%). The percentage of TCR-γδ+ cells showed an age-dependent decline in both the patient group (r=—0.49, P&lt;0.01) and the control group (r=–-0.40, P&lt;0.01). In addition, the proportion of cells which expressed CD8, TCR-γδ or CD4, TCR-γδ simultaneously was determined by double labelling immunofluorescence. Whereas CD4+, TCR-γδ+ cells could be identified in only a few individuals, CD8+, TCR-γδ+ cells were found in nearly all controls (median 2.4%, range 0.0–10.8%); atopic patients displayed significantly (P &lt; 0.01) lower proportions of CD8+, TCR-γδ+ cells.
Vascular deposition of complement-split products in kidney allografts with cell-mediated rejection
Authors: FEUCHT H E , FELBER E , GOKEL M J , HILLEBRAND G , NATTERMANN U , BROCKMEYER C , HELD E , RIETHMÜLLER G , LAND W , ALBERT E 
Published: July 2010

SUMMARYComplement activation in 73 renal transplant biopsies was investigated by indirect immunoperoxidase staining using MoAbs reactive with complement-split products. Intense deposition of complement fragments C4d and C3d in peritubular capillaries, indicating activation of the classical pathway, could be detected in the majority of transplanted kidneys with cell-mediated rejections. Abundant deposition of complement-split products was observed in 22 early biopsies from patients with high ‘immunological risk’ (i.e. previous, rejected transplants and/or circulating antibodies against HLA-antigens). Despite negative results in the crossmatch before transplantation and paucity of immunoglobulins in transplant biopsies, antibodies directed against endothelial cell antigens should be considered as a possible cause of classical complement activation.
Peripheral blood neutrophils in inflammatory bowel disease: morphological evidence ofin vivoactivation in active disease
Authors: MCCARTHY D A , RAMPTON D S , LIU Y-C 
Published: July 2010

SUMMARYMorphological evidence of activation in vivo of circulating neutrophils in patients with inflammatory bowel disease (IBD) was sought by quantitative light microscope examination of toluidine bluestained leucocyte preparations made from peripheral venous bloods that had been fixed immediately ex vivo. The proportion of spherical (unactivated) circulating neutrophils was reduced in active Crohn's disease (73%; 46–96 (median; range), n= 11) compared with inactive Crohn's (90%; 45–99; n= 18, P&lt;0.01) and normal subjects (94%; 44–98; n=13, P&lt;0.05). There tended to be fewer spherical neutrophils in active ulcerative colitis (77%; 13–96; n= 17) than in quiescent colitis (88%; 57–99, n= 13, P&lt;0.1) or normal subjects (P&lt;0.05). Activated neutrophils occur in the circulating pool of patients with active IBD and can be detected by light microscopy of peripheral venous blood leucocyte preparations.
Cytotoxicity against human peripheral blood mononuclear cells and T cell lines mediated by anti-T cell immunotoxins in the absence of added potentiator
Authors: FISHWILD D M , STASKAWICZ M O , WU H-M , CARROLL S F 
Published: July 2010

SUMMARYSeveral in vitro assays have indicated that anti-T cell immunotoxins (IT), composed of monoclonal antibodies (MoAbs)conjugated to ricin A chain (RTA), are maximally effective against T cells only in the presence of potentiators. It was thought that such IT might not be sufficiently cytotoxic to deplete T cells in vivo upon administration to patients. Therefore, we have re-evaluated the in vitro assays and report herein that even with a short exposure lime (2 h), the two anti-T cell IT, H65-RTA (anti-CD5 MoAb coupled to RTA) and 4MRTA (anti-CD7 MoAb coupled to RTA30), were specifically cytotoxic for peripheral blood mononuclear cells(PBMC)in the absence of potentiators. Moreover, as has been reported for IT when tested against T cell lines, prolonging the exposure lime of the IT with PBMC from 2 h to as long as 90 h, without added potentiators, enhanced their cytotoxicity from 2- to 40-fold. In contrast, most T cell lines were more sensitive to IT in the presence of potentiator, and IT cytotoxicity was much less enhanced by prolonging the exposure time. Thus, T cell lines may not serve as accurate models to determine the efficacy of IT against PBMC in vitro or in vivo. We conclude that IT-induced cytotoxicity of PBMC can be demonstrated in vitro at pharmacologically achievable concentrations in the absence of added potentiators.
Defective control of Epstein-Barr virus-infected B cell growth in patients with X-linked lymphoproliferative disease
Authors: YASUDA N , LAI P K , ROGERS J , PURTLO D T 
Published: July 2010

SUMMARYWe studied the cellular function and lymphokine production of T cells from patients with X-linked lymphoproliferative disease (XLP) when activated by the challenge with Epstein-Barr virus (EBV) infection. We used an assay system in which T cells were stimulated with membrane antigens of autologous EBV-infected B lymphoblastoid cell lines (B-LCL) and we examined cellular and humoral factors derived from the stimulated T cells which control the growth of EBV-inlected B-LCL. Immunoglobulin secretion from the autologous B-LCL was suppressed with radiosensitive suppressor cells in the patients with XLP. The degree of suppression was correlated with the immunoglobulin levels in the serum of the patients with acquired hypogammaglobulinaemia (P&lt;0.05). In addition, T cells from the patients with XLP failed to produce interferon-gamma (IFN-γ) (P &lt; 0.001). Moreover, the T cell supernatants from the patients with XLP were less potent to inhibit the B-LCL growth. This diminished inhibition of the B-LCL growth was correlated well with the decreased concentration of IFN-γ in the T cell supernatants. These findings suggest that suppressor cells may be activated in the patients with the hypogammaglobulinaemia phenotype of XLP. but the frequent development of B cell lymphoma in hypogammaglobulinaemia indicate that immunoglobulin suppression may not exert enough pressure on the in vivo growth of EBV-infected B cells. The defective secretion of IFN-γ may be, at least partially, responsible for the abnormal cytotoxic T cell and natural killer activities found in the patients with XLP, and may indicate the clinical evaluation about the preventive injection of IFN-γ against the development of malignant lymphoma.
Human cartilage is degraded by rheumatoid arthritis synovial fluid but not by recombinant cytokines in vitro
Authors: HOLLANDER A P , ATKINS R M , EASTWOOD D M , DIEPPE P A , ELSON C J 
Published: July 2010

SUMMARY
Rheumatoid arthritis (RA) synovial fluid (SF) stimulated significant loss of glycosaminoglycans (GAG) from normal and pathological human cartilage biopsies over 2 days as compared with normal human serum. By contrast, 15 RA SFs failed to degrade killed normal cartilage, and degraded killed RA cartilage less effectively than living RA cartilage. Four RA SFs were treated with neutralizing anti-cytokine antisera prior to incubation with normal cartilage. The degrading effects of two of the fluids were reversed by anti-interleukin-1α (IL-1α) while degradation by the third and fourth fluids were reversed by anti-intcrleukin-1β (IL-1β) and anti-tumour necrosis factor-alpha (TNF-α). respectively. However, recombinant human IL-1α. 1L-1β. TNFα or a combination of all three cytokines had no degrading effect in this 2-day culture system. It is concluded that RA SF degrades cartilage by a mechanism involving a synergistic interaction between cytokines and some other component of SF.
Cytomegalovirus-specific antibodies to an immediate early antigen and a late membrane antigen and their possible role in controlling secondary cytomegalovirus infection
Authors: VAN ZANTEN J , VAN DER GIESSEN M , VAN DER VOORT L H M , VAN SON W J , VAN DER BIJ W , THE T H 
Published: July 2010

SUMMARY
In 24 renal transplant recipients who had a secondary cytomegalovirus (CMV) infection, the magnitude and development of CMV-specific antibodies directed against two different antigens were studied in relation to the presence of CMV-immediate early antigen-positive peripheral blood leucocytes (CMV antigenaemia). These antibodies were measured in an antigen-capture ELISA using two monoclonal antibodies: one directed against the major immediate early antigen (IEA) and a second one directed against the CMV-encoded glycoprotein B (gB). A statistically significant inverse relationship between the level of anti-IEA antibodies present at the time of transplantation as well as the magnitude of the increase of these antibodies during CMV infection and the maximum number of IEA-positive cells during infection was shown. In contrast, both anti-gB and anti-total CMV antibodies did not give any correlation with the CMV antigenaemia. This may indicate that the anti-IEA immune response plays a role in defence mechanisms against a CMV infection.
IgM anti-idiotypes that block anti-HLA antibodies: naturally occurring or immune antibodies?
Authors: URLACHER A , TONGIO M M , PASQUALI J L 
Published: July 2010

SUMMARYUsing dithiothreitol (DTT) technique, IgM anti-HLA anti-idiotypic antibodies were detected in a multiparous multitransfused woman. These antibodies were able to inhibit the binding of specific IgG anti-HLA antibodies on their corresponding antigen. The recognized determinants were crossrcactive determinants since they were partially found on anti-HLA antibodies from unrelated individuals. By studying the patient's sera over a period of 2 years, no IgM-IgG switch was observed bui the presence of these antibodies was stable in time, despite the disappearance of the idiotypes (anti-HLA antibodies). However, when looking at the patient's earlier serum, it was shown that these IgM anti-idiotypic antibodies were absent from the first available serum. Thus, these anti-idiotypic antibodies seem to behave both like natural and immune antibodies. The incidence of such antibodies in pretransplant patients is discussed.
Human rib bone marrow mononuclear cells spontaneously synthesize and secrete IgEin vitro
Authors: MACDERMOTT R P , JENDRLSAK G A S , NASH G S , SCHREIBER S , BERTOVICH M J , NAHM M , NONAKA M , FITZGERALD P , KATZ D H , MARCELLETTI J F 
Published: July 2010

SUMMARYWe have examined spontaneous secretion of IgE by human rib bone marrow mononuclear cells (MNC). Bone marrow MNC from nine out of 12 rib specimens synthesized and secreted substantial amounts of IgE during 14 days of in vitro culture. The 14-day supernatants from these bone marrow MNC contained a mean of 2589 pg/ml of IgR (n= 12) with a maximum production of 1540K pg/ml of IgE compared with small amounts of IgE 80–200 pg/ml) produced by similarly cultured normal and inflammatory bowel disease intestinal lamina propria MNC. Using two rib specimens, time-course studies revealed spontaneous secretion of IgE to be minimal during the first 2 days of culture (152 pg/ml), followed by a steady increase between days 4 (517 pg/ml) and 14 (3588 pg/ml). The addition of pokeweed mitogen resulted in 72% suppression of spontaneous IgE production by bone marrow MNC. The bone marrow MNC isolated from the ribs consisted of 22% Leu 12+ (B) cells of which 3.2% were surface IgE positive. Staining for cytoplasmic immunoglobulin revealed 1% of the bone marrow MNC to be cytoplasmic IgE+. The presence of IgE-bearing and IgE-secreting MNC in human bone marrow is consistent with the observation that allergen-specific IgE-mediated hypersensitivity is adoptively transferred by human bone marrow transplantation and demonstrates the usefulness of human bone marrow MNC for examination of IgE secretory and regulatory events.