bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific increases in urinary excretion of anti-DNA antibodies in lupus mice induced by lysozyme administration: further evidence for DNA-anti-DNA immune complexes in the pathogenesis of nephritis
Authors: YAMAMOTO T , NAGASE M , HISHIDA A , HONDA N 
Published: July 2010

SUMMARYWe previously reported that lysozyme electrostatically inhibits the fibronectin-mediated DNA binding to the glomerular basement membrane (GBM) and reduces in situ DNA-anti-DNA complex formation in the GBM in NZB/W F1 mice [I]. In this study, we further noticed significant increases in urinary excretion of anti-DNA antibodies and immune complexes (IC) in lysozyme-treated NZB/W F1 mice. Their clearance ratios of IgG anti-DNA antibody to whole IgG were markedly high compared with those of saline-treated animals. A large number of IgG and C3 positive granules were observed in the tubular cells of NZB/W F1 mice treated with lysozyme. On the contrary, nil or only small amounts of anti-DNA antibodies were detected in the urine of NZB/W F1 mice without lysozyme administration despite a large amount of proteinuria, suggesting entrapment of the antibodies in lupus glomeruli. Lysozyme neither inhibited the binding of anti-DNA antibodies to DNA or heparan sulphate nor did it displace anti-DNA antibodies and IC from the kidney homogenates of lupus mice. It thus appears that the inhibition of DNA binding to the GBM due to lysozyme reduced the entrapment of anti-DNA antibodies in the GBM, resulting in urinary excretion of the antibodies.
Effect of chlorpromazine on kinetics of injected monoclonal antibody in MoAb-induced glomerular injury
Authors: TAKASHIMA N , KAWACHI H , OITE T , NISHI S , ARAKAWA M , SHIMIZU F 
Published: July 2010

SUMMARYThe effect of chlorpromazine, one of several calmodulin antagonists that inhibit cytoskeletal movement, on the local kinetics of injected proteinuria-inducing MoAb 5–1–6 was examined to test the hypothesis that proteinuria is inhibited if the antigen recognized by MoAb 5–1–6 or injected MoAb remains on the surface of epithelial foot processes. MoAb 5–1–6 was injected into both chlorpromazine-treated (5 mg/100 g body weight) and untreated rats. As a positive control for the chlorpromazine treatment, anti-Fx 1A serum was also injected into other chlorpromazine-treated and untreated rats. Chlorpromazine inhibited neither the change in localization of injected MoAb 5–1–6 nor proteinuria, although it showed an inhibitory effect on redistribution of immune complex and the fixation of complement in passive Heymann glomerulonephritis induced by injection of anti-Fx 1A serum. We conclude that the kinetics of bound MoAb 5–1–6 are regulated by a system different from that operating in passive Heymann glomerulonephritis.
Asp57-negative HLA DQβ chain and DQA1*0501 allele are essential for the onset of DQw2-positive and DQw2-negative coeliac disease
Authors: MANTOVANI V , CORAZZA G R , BRAGLIANI M , FRISONI M , ZANIBONI M G , GASBARRINI G 
Published: July 2010

SUMMARY
The genetic predisposition to coeliac disease is associated with the HLA DQw2 allele. Coeliac patients lacking the DQw2 allele are very rare and always exhibit the DR4-DQw3 haplotype. We performed oligotyping of polymerase chain reaction (PCR)-amplified DQA1 and DQB1 genes in six DQw2-negative and 30 DQw2-positive coeliac patients. The DQB analysis showed that all six DQw2-negative patients possessed the DQB 1*0302 allele. The other DQB alleles found in five of these patients were DQB1*0501, DQB1*0604 and DQB1*0302. The DQβ chains encoded from all these alleles have the replacement of aspartic acid residue at position 57 (Asp57), as well as the DQB 1 *0201 allele which was found in all 30 DQw2-positive coeliac patients. The DQw2-negative proband who lacked the homozygous Asp57 replacement exhibited the DQA1*0501 allele in the DQA1 gene. The DQA1 *0501 allele was also found in 27 of the 30 DQw2-positive coeliac patients. Among this group of coeliacs, the four cases lacking the DQA1*0501 allele exhibited the homozygous Asp57 replacement in the DQβ chain. Our results indicate that Asp57-negative DQβ alleles are involved in both DQw2-positive and -negative coeliac patients. Moreover, when the Asp57-negative DQβ chain is encoded from only one of the two DQB1 genes the DQA1*0501 allele is always present.
Activation of the immune system of cancer patients by continuous i.v. recombinant IL-2 (rIL-2) therapy is dependent on dose and schedule of rIL-2
Authors: GRATAMA J W , BRUIN R J , LAMERS C H J , OOSTEROM R , BRAAKMAN E , STOTER G , BOLHUIS R L H 
Published: July 2010

SUMMARYThe effect of dose and schedule of continuous i.v. rIL-2 infusions on leucocyte subset counts, activation status of CD56+CD3- natural killer (NK) and CD3+ T lymphocytes, and cytolytic activities of peripheral blood mononuclear cells (PBMC) was studied. A single 4-day course of rIL-2 in escalating doses (0.9-11.5 × 106 U/m2 per day) was given to 18 patients with various types of metastatic cancer. The serum IL-2 concentration during rIL-2 Iherapy ranged between 23 and 64 U/ ml and was proportional to ihe administered rIL-2 dose, as was the rebound lympbocytosis following therapy. Before therapy, the CD56+CD3- NK cells expressed low levels of the p75 chain of the IL-2 receptor (IL-2R) and virtually no IL-2R(p55). Most CD3+ T cells were IL-2R(p55,p75). Between 2 and 4 days following therapy, i.e. at the time of lymphocytosis, the percentage of CD56+, CD3 NK cells among tbe lymphocytes had increased proportional to tbe administered rIL-2dose. The levels of IL-2R(p75) expression by the CD56+, CD3 NK cells had increased. The percentages of CD3+ T cells expressing IL-2R(p55). H LA-DR and CD45RO had increased proportional to the administered rIL-2 dose. The level of lymphokine- activated killer (LAK) activity against Daudi cells was also positively correlated with rIL-2 dose. Subsequently, seven patients received 4-weekly cycles of rIL-2 (2.9-4.4 × 106 U/m2 per day) during 4 consecutive weeks. This schedule led to marked increments in lymphocyte and eosinopbil counts, and to increased cytolytic activities compared with pretreatment. We conclude that CD56+, CD3- NK and CD3+ T cells are activated differentially by continuous i.v. rIL-2 proportional to dose and duration of treatment.
Serum and salivary responses to oral tetravalent reassortant rotavirus vaccine in newborns
Authors: FRIEDMAN M G , SEGAL B , ZEDAKA R , SAROV B , MARGALITH M , BISHOP R , DAGAN R 
Published: July 2010

SUMMARY
Serum and salivary responses of 95 infants to either a standard (4 ± 104 plaque-forming units (PFU), 47 neonates) or a high dose (4 ± 105 PFU, 48 neonates) of tetravalent reassortant rhesus rotavirus vaccine (administered at 2 days and at 6 weeks of age) were evaluated in a double-blind clinical trial. Serum and salivary IgA antibodies to the rotavirus group A common antigen were determined by ELISA and radioimmunoassay (RIA). Serum neutralizing antibodies to rhesus rotavirus were determined by fluoreseent foeus reduction assay. No significant differences in responses to the high versus standard dose were noted in serum or saliva. Response was influenced by cord blood antibodies. All infants who were cord blood-negative for rhesus rotavirus neutralizing antibodies (nine who received the standard dose and 20 who received the higher dose) had serum responses, compared with 42-70% of those who were cord blood-positive. The serum response rate recorded for babies with cord blood neutralizing titres &gt; 1000 was 44%. Infants being bottle fed had a higher serum response rate than did babies being breast fed exclusively. If serum and salivary responses were combined, the response rate reached 80% for bottle fed infants. Thus, determination of serum responses alone underestimates vaccine ‘take’ in infants, and more so in highly endetnie areas thati in areas subject only to sporadic outbreaks. However, determination of salivary responses in newborn breastfed infants may be inaccurate, due to possible persistence of antibodies derived frotn colostrum or breast milk.
Lymphocyte changes associated with prolongation of cardiac allograft survival in adult mice using anti-CD4 monoclonal antibody
Authors: PEARSON T C , BUSHELL A R , DARBY C R , WEST L J , MORRIS P J , WOOD K J 
Published: July 2010

SUMMARYThis study investigated the effect of anti-CD4 MoAb treatment on lymphocyte phenotype and function and correlated these changes with the prolongation of cardiac allograft survival in adult mice. Indefinite survival of hcterotopic cardiac aliografts was obtained in several fully allogencie strain combinations when two doses of the anti-CD4 MoAb, YTS 191.1, were given at the time of transplantation, A dose response analysis in the C57BL/10 to C3H/He strain combination showed that very low doses of YTS 191.1 (25 μg/dose) were able to induce prolonged allograft survival when administered perioperatively. At the time of transplantation the immunosuppression induced by administration of the anti-CD4 MoAb is not antigen-specific, as heart grafts from different donor strains, mismatched for both major and minor histoeompatibility antigens, showed prolonged survival in treated recipients. Immunocompetence was restored by 6 weeks after MoAb treatment, as recipients regained the ability to reject a cardiac allograft transplanted at this time point. However, while recovery of immunocompetence could be demonstrated in civo, leucocytes isolated from the peripheral lymphoid organs of treated mice continued to be hyporesponsive in mixed leucocyte culture (MLC), Phenotypic analysis of the peripheral lymphoid tissues showed that C3H/He recipients treated with 25 μg/dose of YTS 191.1 had a marked, but not complete, elimination of the CD4+ subset al the time of transplantation, which was gradually restored to 50% of normal by 6 weeks after treatment. Thus, complete elimination of the CD4+ subset was not required to achieve indefinite allograft survival, and immunocompetence, as assessed in vivo, returned even when the CD4+ subset was present at half the normal level. Low doses of anti-CD4 MoAb (25 μg) had no effect on the expression of the CD4 molecule by thymocytes, and yet thymocytes were hyporesponsive to alloantigen in vitro. At higher doses of YTS 191.1, immature CD4+ 8+ thymoeytcs were selectively depicted. These results suggest that anti-CD4 MoAb therapy may modulate the intrathymic T cell selection process. These studies provide further insight into the mechanism of action of low dose, depleting anti-CD4 MoAb therapy in allograft rejection, and form a basis from which rational modifications to therapeutic protocols in transplantation models can be made.
Therapeutic effect of granulocyte colony-stimulating factor and cephem antibiotics against experimental infections in neutropenic mice induced by cyclophosphamide
Authors: WAKIYAMA H , TSURU S , HATA N , SHINOMIYA M , SHINOMIYA N , NORITAKE M , UMEZAWA Y , ROKUTANDA M 
Published: July 2010

SUMMARYEffects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) against severe infections in cyclophosphamide (CY)-induced neutropenic mice were investigated by its single use or by its combination with cephem antibiotics. Treatment with rhG-CSF increased the number of peripheral blood leucocytes and strikingly shortened the duration of the neutropenic state. Most of the regained population in the peripheral blood leucocytes were neutrophils. Functions of neutrophils, such as phagocytic activity, superoxide release, and expression of Mac-1 molecules, were remarkably enhanced by administration of rhG-CSF. When rhG-CSF was administered to CY-induced neulropenic mice before infection, protective effects against various kinds of bacteria were remarkable. On the other hand, such remarkable effects were not observed when rhG-CSF was administered after infections. However, even in the case of post-infectious treatment, a combination therapy of rhG-CSF with cephem antibiotics, particularly with Cefodizime (CDZM), showed a significant improvement in the survival rate and a decrease in the number of viable bacteria in the liver. These results suggest that a combination therapy of rhG-CSF with cephem antibiotics, especially with CDZM, is an efficient regime against severe infections in patients with ncutropenia induced by a heavy anti-tumour chemotherapy.
Isotype-specific cross-linking of select human FcγR isoforms triggers release of IL-6
Authors: DUITS A J , AARDEN L A , ERNST L K , CAPEL P J A , van de WINKEL J G J 
Published: July 2010

SUMMARYAnti-CD3 MoAbs arc widely used in T cell activation studies, and are effective in immunosuppressive therapy. We used a panel of mouse (m) anti-CD3 switch variant MoAbs of five different isotypes to study IL-6 release from accessory cells. Incubation of human (h) mononuelear cells with anti-CD3 MoAbs resulted in increased IL-6 levels with MoAbs of mIgG 1 and mIgG2a isotypes. with no effect of mlgG2b or mIgA. This suggested involvement of IgG Fc receptors (FcγR) in triggering IL-6 production. To evaluate the role of different FcγR molecules individually we used a panel of hFcγR-transfeeted mouse fibroblasts, and Jurkat T cells as a model. IL-6 secretion by CD32 transfectants expressing the hFcγRIIa high-responder (HR) allelic form was triggered by mIgG1 anti-CD.3 MoAb. with no effect of four other isotypes. None of the anti-CD3 MoAbs induced IL-6 secretion by CD32 transfectants expressing either a variant of this receptor, containing only a single intracellular amino acid (CT-), the hFcγRIIa low-responder (LR) allelic form, or hFcγRIIbl. hFcγRI (CD64) transfectants exhibited IL-6 production after incubation with mlgG2a anti-CD3 MoAb, and to a lesser extent with mlgG2b. and mlgG I MoAb. Indirect involvement of T cells in triggering IL-6 secretion could be excluded by experiments in which transfectants were cultured with immobilized anti-CD3 MoAb. These data indicate that cross-linking of cither hFcγRI, or hFcγRIIaHR by appropriate anli-CD3 MoAbs triggers IL-6 production of accessory cells, and not T cells. This may also take place in vivo during immunosuppressive therapy with anti-CD3 MoAbs, and related antibody-mediated immune responses.
The anti-lipid A antibody HA-IA binds to rough Gram-negative bacteria, fixes complement and facilitates binding to erythrocyte CRl (CD35)
Authors: TONOLI M , DAVIES K A , NORSWORTHY P J , COHEN J , WALPORT M J 
Published: July 2010

SUMMARYMoAbs to bacterial cell wall Iipopolysaccharidc arc currently under evaluation for the treatment of Gram-negative sepsis. The mode of action of these reagents remains poorly understood. In this study we examined the ability of radiolabelled HA-IA (an IgM anti-lipid A MoAb) to bind in vitro to Salmonella minnesota (Re 595), Escherichia coli, and Streptococcus pyogenes. HA-1A was able to bind specifically to the “rough” mutant Stilm. minnesota. but not to a ‘smooth’E. coli, or Strep, pvogenes. Binding to Salm. minnesota led to complement fixation which resulted in bacterial adherence to erythrocyte CR1, suggesting a possible mechanism whereby the antibody might enhance clearance of bacteria by facilitating delivery to the fixed mononuclear phagocytic system. We were not able to demonstrate the formation of immune complexes between free lipopolysaccharide and HA-IA in the presence of serum, nor the enhancement of complement-mediated binding of HA-1 A:Salm. minnesota immune complexes to erythrocytes by antibiotic treatment. Binding of HA-IA to small bacterial fragments was, however, demonstrable after in vitro treatment with a β-lactam antibiotic, which disrupts the bacterial cell wall, but not with gentamicin, an aminoglycoside antibiotic which blocks protein synthesis.
Synovial fluid antigen-presenting cell function in rheumatoid arthritis
Authors: VINER N J , GASTON J S H , BACON P A 
Published: July 2010

SUMMARYWe have previously demonstrated enhanced synovial fluid (SF) antigen-presenting cell (APC) function in inflammatory arthritis patients selected on the basis of marked SF mononuclcar cell (MNC) responsiveness to reactive arthritis-associated bacteria (Clin Exp Immunol 1990; 79:189-94). In this study we have assessed whether similarly enhanced synovial APC function is present in other inflammatory arthritis patients by using two assay systems to study 18 rheumatoid arthritis patients whose MNC responsiveness had not been determined in advance. We demonstrate that rheumatoid SF APC are much more potent than peripheral blood (PB) APC in stimulating the responses of autologous PB T cells to a range of recall antigens. In addition, SF APC are shown to be efficient stimulators of the antigen-specific responses of MHC-compatible, cloned T cells. Enhanced synovial APC function is thus likely to be a general feature of inflammatory arthritis and may play an important role in its pathogenesis.
γσ Lymphocytes in endocrine autoimmunity: evidence of expansion in Graves' disease but not in type 1 diabetes
Authors: ROURA-MIR I C , ALCALDE L , VARGAS F , TOLOSA E , OBIOLS G , FOZ M , JARAQUEMADA D , PUJOL-BORRELL R 
Published: July 2010

SUMMARY
Endocrine autoimmune disorders are mediated by T cell-dependent responses to organ-specific antigens, but the mechanisms initiating the process remain unknown. Lymphocytes whieh use the γδ heterodimer as T ceii receptor (TCR) for antigen constitute a distinct subset of T cells whose function remains elusive. In order to investigate their possible involvement in endocrine auloimmunity we have determined the proportion of γδ T cells in the peripheral biood of 23 patients with type 1 (insulin-dependent) diabetes mellitus (type-1 DM) and 30 patients with autoimmune thyrotoxicosis (Graves’ disease). T lymphocyte TCR expression was assessed by fluorescence-activated flow eytometry on peripheral blood mononuclear cells using MoAbs UCHTI (CD3), TCR 51 (γδ TCR), WT31 and βF1 (αβ TCR) and both the percentage of T cells expressing γδ and the ratio γδ/αβ were calculated. In the diabetie patients γδ cells were not significantly different from (he control group (7·7 ± 54%versus 8·0 ± 5·5%) of T eells, P NS). There was no relation between the proportion of γδ lymphoeytes and the presence ol’ islet cell antibodies (ICA) in the sera. The Graves’ patients showed a tendency towards a higher proportion of γδ T lymphocytes than the controls (γδ/αβ ratios: 0·095 ± 0·047 versus 0·063 ± 0·022, P= 0·03). In 14 Graves’ patients the number of γδ were measured in paired samples of peripheral and inlrathyroidal lymphocytes, demonstrating an expansion of γδ within the thyroid glands (0·21 ± 0·3 versus 0·095 ± 0·047, P= 0·032). Immunohistochemical studies showed that γδ celts were scattered among the predominant αβ lymphoeytes infiltrating the thyroid gland and that they aeeount for 10% of intraepitheliai lymphocytes. No relation was found between the increase of γδ lymphocytes and any clinieai features.
Trafficking of inflammatory macrophages from the kidney to draining lymph nodes during experimental glomerulonephritis
Authors: LAN H Y , NIKOLIC-PATERSON D J , ATKINS R C 
Published: July 2010

SUMMARYMacrophage accumulation within the glomerulus and renal interstitium is a prominent feature of most forms of glomerulonephritis, but the fate of these inflammatory cells is unknown. Macrophage trafficking to the draining kidney lymph nodes (KLN) was assessed in a detailed kinetic analysis of accelerated antiglomerular basement membrane (GBM) disease in the rat. Leucocytes draining to KLN via lymphatic vessels were identified within the marginal sinus by MoAb labelling of tissue sections. In anti-GBM disease, there was a significant increase in the weight of the KLN due to both lymphoproliferation within the nodes and increased lymphatic drainage from the inflamed kidney, as evidenced by prominent dilation of the marginal sinus and increased numbers of cells within the sinus. In non-inflamed lymph nodes, few ED1+ macrophages were present within the marginal sinus (3·0±0·6/100 nucleated cells). However, in anti-GBM disease, macrophages became the major cell type within the dilated marginal sinus of the KLN, as shown by labelling with ED1, ED2 and ED3 MoAbs, peaking at 74±2·6 ED1+ cells/100 nucleated cells at day 14. These changes were not simply due to systemic antigen administration, since in the axillary lymph node (ALN) there was no obvious dilation of the marginal sinus and macrophages accounted for a maximum of only 15±4·6 ED1+ cells/100 nucleated cells. In conclusion, this study provides indirect evidence that there is significant trafficking of the renal macrophage infiltrate to the KLN during experimental glomerulonephritis. This may be a mechanism whereby nephritogenic antigens, released as a consequence of the local inflammatory response, may be presented to T and B lymphocytes within lymph nodes, resulting in the amplification of the immune response in glomerulonephritis.
Quantitative study of mesangial injury with proteinuria induced by monoclonal antibody 1-22-3
Authors: KAWACHI H , OITE T , SHIMIZU F 
Published: July 2010

SUMMARYMurine MoAb 1-22-3 has already been reported to bind to the mesangial cell surface and to cause transient proteinuria and mesangial morphological changes characterized by mesangiolysis. subsequent mesangial cell proliferation and mesangial matrix increase by a single i.v. injection. In this study, MoAb-induced glomerulopathy was quantitatively analysed. No correlation between the severity of mesangial morphological changes and the degree of proteinuria was detected (r= 0·190). The minimum dose injected to induce abnormal proteinuria was 25 μg. This dose corresponded to 1·79 μg/2 kidneys 30 min after MoAb injection. The highest average level of proteinuria was observed in rats injected with 500 μg of MoAb, and less proteinuria was observed in rats injected with 10·0, 5·0 and 2·0mg. Although the amounts of kidney-fixing MoAb and the subsequent deposition of rat C3 in the high-dose-injected group were larger than in the 500 ng injected group, the numbers of infiltrating inflammatory cells were the same in both groups. No correlations between the degrees of such mediators and proteinuria were observed.
Mucosal macrophage subsets of the gut in HIV: decrease in antigen-presenting cell phenotype
Authors: LIM S G , CONDEZ A , POULTER L W 
Published: July 2010

SUMMARYThe effect of HIV infection on intestinal lamina propria macrophage subsets was investigated in 41 patients at various stages of HIV infection (asymptomatic HIV infection, n= 17; AIDS, n= 24). Duodenal biopsies taken from HIV patients at endoscopy were snap frozen and cryostat sections cut for immunohistochemical staining. MoAbs CD68 (EBM11. pan-macrophage marker). RFD1 (antigen-presenting cells) and RFD7 (mature phagocytic macrophages) were used to identify cell subsets using indirect immunoperoxidase or alkaline phosphatase. Double immunofluoresccncc using MoAbs to HIV proteins (p24, p17 and gp120) and RFD1 were used to identify HIV-infected antigen-presenting cells. Double immunofluoresccncc was also used to identify macrophages that expressed both RFD1 and RFD7 (‘suppressor’ macrophages). Intensity of HLA-DR expression in lamina propria cells was investigated using a MoAb to HLA-DR directly conjugated to glucose oxidase. The results show that there was no difference in overall density of macrophages, but there was a significant decrease in dendritic cells (RFD1+) in all clinical stages of HIV. There was no difference in the density of RFD7+ macrophages, nor was there a difference in intensity of HLA-DR expression in lamina propria cells. Only four HIV-infected cells were positively identified in the 41 patients. This result suggests that the antigen-presenting arm of mucosal immune defences may be seriously compromised in HIV infection, and represents a further insult to mucosal immunity already impaired as a result of loss of CD4+ T lymphocytes. This may contribute to development of opportunist infection in the gut.