bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of collagen-induced arthritis (CIA) by treatment with polyethylene glycol-conjugated type II collagen; distinct tolerogenic property of the conjugated collagen from the native one
Authors: ITO H-O , SO T , UEDA T , IMOTO T , KOGA T 
Published: November 2003

SUMMARY
Administration of a soluble protein into animals prior to challenge immunization induces immunological tolerance which is specific for the protein. In addition, chemical modification of proteins with polyethylene glycol (PEG) has been reported to convert the immunogenic proteins to become tolerogenic. However, differences in tolerogenic properties between PEG-modified proteins and the native counterparts have never been analysed. The ability of PEG-conjugated type II collagen (PEG-CII) to attenuate CIA, an animal model for rheumatoid arthritis, was compared with the native unconjugated CII. Groups of DBA/1 J mice were treated weekly with i.p. injections with PEG-CII, native CII, or vehicle alone for 3 weeks, before they were challenged with CII in adjuvants. The induction of tolerance was confirmed in both PEG-CII- and CII-pretreated mice when suppression of lymph node T cell proliferation in response to CII was noted. The degrees of suppression of T cell proliferation were comparable between the two pretreated groups. However, induction of arthritis and production of IgG anti-CII antibody were more markedly suppressed in PEG-CII-pretreated mice than in native CII-pretreated mice, although the severity of arthritis and antibody levels in the latter group were also lower than in control mice. IgG2a and IgG2b antibody levels were equally suppressed in the two pretreated groups, whereas the IgG1 level was significantly lower in the PEG-CII-pretreated group than in the native CII-pretreated group. The results provide the first evidence that attachment of PEG to CII renders the protein more tolerogenic.
Thalidomide therapy of established collagen-induced arthritis (CIA) not accompanied by an evident Th2 shift
Authors: HAUSCHILD A , KROEGER H , MITCHISON N A , UGRINOVIC S , ZWINGENBERGER K 
Published: November 2003

SUMMARY
Thalidomide, a drug likely to affect the cytokine pattern, was administered orally to mice at various stages of CIA. Treatment (150mg/kg per day by gavage, 5 days/week), started 6 weeks post-immunization, i.e. at the height of the disease, significantly reduced arthritis, and appeared also to reduce the level of inflammation as judged by neutrophil chemiluminescence. With treatment started 9 weeks post-immunization the effect on arthritis was no longer statistically significant, and when started at 14 weeks was lost. Over a dose range of up to 150mg/kg per day the treatment had no effect on either interferon-gamma (IFN-γ) or IL-4 mRNA levels. The treatment is therefore not likely to have operated via a shift in the Th1/Th2 balance.
Age-related changes in serum immunoglobulins in patients with familial IgA deficiency and common variable immunodeficiency (CVID)
Authors: JOHNSON M L , KEETON L G , ZHU Z-B , VOLANAKIS J E , COOPER M D , SCHROEDER H W 
Published: November 2003

SUMMARY
The concentration of serum immunoglobulins in individuals with IgA deficiency (IgAD) and CVID can vary with age to have practical implications for evaluation, therapy, and genetic analysis. Most IgAD and CVID patients in our clinic population in the Southeastern United States have inherited part or all of two extended MHC haplotypes, referred to as haplotype 1 (HLA-DQB1 0201, HLA-DR3, C4B-Sf, C4A-0, G1-15, Bf-0.4, C2-a, HSP-7.5, TNFα-5, HLA-B8, HLA-A1) and haplotype 2 (HLA-DQB1 0201, HLA-DR-7, C4B-S, C4A-L, G11-4.5, Bf-0.6, C2-b, HSP-9, TNFα-9, HLA-B44, HLA-A29). In the present study, the clinic records of 68 CVID patients and 73 IgAD patients were reviewed to determine whether patients with familial or MHC-associated IgAD or CVID experience changes in serum immunoglobulin concentrations. An increase in serum immunoglobulin to the normal range was associated with clinical improvement in one patient with CVID and haplotype 2, two patients with IgAD and haplotype 2, and one IgAD patient whose haplotype was not determined. Two patients with haplotype 1 and one with haplotype 2 had a significant decline in serum immunoglobulin: one progressed from normal to IgAD associated with IgG subclass deficiencies, and two progressed from IgAD to CVID. Five of the seven patients with notable changing serum immunoglobulin levels have a family member with either IgAD or CVID. The findings suggest that familial, MHC-associated IgAD and CVID may be either progressive or reversible disorders, and emphasize the value of monitoring immunoglobulin levels in affected individuals and their family members.
Circulating soluble selectins in Kawasaki disease
Authors: TAKESHITA S , DOBASHI H , NAKATANI K , KOIKE Y , TSUJIMOTO H , HIRAYAMA K , KAWAMURA Y , MORI K , SEKINE I , YOSHIOKA S 
Published: November 2003

SUMMARY
To investigate the significance of circulating adhesion molecules associated with leucocyte–endothelial cell interaction in Kawasaki disease (KD), serum levels of soluble E-, P-, L-selectin (sE-, sP-, sL-selectin), and vascular cell adhesion molecule-1 (VCAM-1) were measured in 16 patients with KD, eight with other febrile diseases, six with Henoch–Schönlein purpura (HSP), and 10 healthy children using an ELISA. Serum sE-selectin levels from patients in the acute phase of KD were significantly higher than from those in other groups (P&lt;0.01). The levels of sP-selectin in the subacute phase of KD were significantly higher than in other groups (P&lt;0.01). Serum sL-selectin levels tended to rise in the convalescent phase of KD. There were also significant correlations between sE-selectin levels and C-reactive protein (r=0.80, P&lt;0.0001), and between sP-selectin levels and platelet counts (r=0.57, P&lt;0.0001) in KD patients. These data indicate that circulating soluble forms of three selectins may have different kinetics during the clinical course of KD, suggesting that they may reflect its inflammatory process.
Th1-like responses to peptides from peripheral nerve myelin proteins in patients with polyneuropathy associated with monoclonal gammopathy
Authors: EKERFELT C , ERNERUDH J , VRETHEM M 
Published: November 2003

SUMMARY
Polyneuropathy associated with monoclonal gammopathy is usually regarded as an immune-mediated disorder with autoantibody activity against myelin glycoproteins. The pathogenic mechanisms are, however, not fully understood. Several reports have indicated an additional involvement of T cells. We investigated the occurrence of myelin-specific T cells as well as their functional characteristics. Cytokine responses generated after stimulation of peripheral blood mononuclear cells with selected peptides of myelin proteins P0 and P2 were investigated with an ELISPOT method. Three P0 peptides caused significantly elevated levels of interferon-gamma (IFN-γ)-secreting cells in patients with polyneuropathy associated with monoclonal gammopathy (n=8) compared with controls (n=8), whereas none of the peptides caused elevated levels of IL-4-secreting cells. Patients with non-immunological types of neuropathy (n=4) did not reveal any cytokine responses to myelin peptides. Our results indicate that a Th1-like response against myelin proteins occurs in polyneuropathy associated with monoclonal gammopathy.
Positive and negative associations of distinct HLA-DR2 subtypes with ulcerative colitis (UC)
Authors: DE LA CONCHA E G , FERNANDEZ-ARQUERO M , SANTA-CRUZ S , LOPEZ-NAVA G , FIGUEREDO M A , DIAZ-RUBIO M , GARCIA-PAREDES J 
Published: November 2003

SUMMARY
In UC, as in many other diseases with a suspected autoimmune etiology or pathogenesis, an association with certain HLA class II specificities has been investigated. In the Japanese, several studies have shown a positive association with DR2, but in Caucasian populations the results are conflicting. Therefore we undertook a study of HLA class II gene association with UC in a large group of white Madrid patients and ethnically matched controls, using molecular biology techniques to investigate whether any allelic subspecificity within the HLA-DR2 group is associated with susceptibility to or protection against UC. Patients with ulcerative colitis (n=107) and 200 controls were typed using molecular, DNA-based techniques for HLA-DRB1, DQA1 and DQB1 alleles. Those HLA-DR2+ were then specifically typed for the individual alleles within the HLA-DR2 group. We observed a positive association with HLA-DR15 (P=0.021) and its subtype DRB1*1501 (P=0.018). HLA-DRB1*1502 was also increased, although its frequency both in patients and controls was very low. When the HLA-DR2+ population was studied, HLA-DRB1*1601 was significantly decreased in patients (P=0.026). Both HLA-DR3 (P=0.002) and HLA-DQB1*02 (P=0.001) were also negatively associated with the disease, the latter especially with pancolitis. Therefore, HLA class II association with UC is complex, and separate alleles confer either susceptibility or resistance. Conflicting results with HLA-DR2 appear to be due to the presence in this group of both positively associated (HLA-DRB1*1501 and DRB1*1502) and negatively associated (HLA-DRB1*1601) subspecificities. Moreover, HLA-DR3 and HLA-DQB1*02 are associated negatively.
Combined immunodeficiency phenotype associated with inappropriate spontaneous and activation-induced apoptosis
Authors: PIGNATA C , FIORE M , SCOTESE I , COSENTINI E , SPERANDEO M P , TURCO C , PETRELLA A , NOTARANGELO L , VENUTA S 
Published: November 2003

SUMMARY
Programmed death of T cells has been proposed as one of the mechanisms by which HIV induces a decline in the number and functions of T cells in advanced AIDS. In this study we report on a patient affected by a congenital form of combined immunodeficiency presenting as a profound T cell activation deficiency. Subsequently, a gradual loss of T cells occurred, eventually resulting in a classical form of severe combined immunodeficiency (SCID). In this patient a sizeable fraction of apoptotic cells was documented in the first phase of the disease by either propidium iodide staining or DNA fragmentation analysis. The presence of anergic T cells of maternal origin and engrafted in the child was excluded by analysis of DNA polymorphic regions. At 4 years of age the patient died of disseminated interstitial pneumopathy, while still awaiting an HLA-matched bone marrow transplantation. On the occasion of a new pregnancy in the mother, the prenatal immunological evaluation of the female fetus revealed a T− B+ SCID phenotype. This is the first observation of a primary immunodeficiency associated with inappropriate apoptosis.
Differential susceptibility to Mycoplasma pulmonis intranasal infection in X-linked immunodeficient (xid), severe combined immunodeficient (scid ), and immunocompetent mice
Authors: SANDSTEDT K , BERGLÖF A , FEINSTEIN R , BÖLSKE G , EVENGÅRD B , SMITH C I E 
Published: November 2003

SUMMARY
Mice with the scid mutation are highly susceptible to Mycoplasma pulmonis infection and develop a disseminated disease. In order to study the contribution of humoral immunity to the immune response, M. pulmonis was inoculated intranasally to X-linked immunodeficient (xid) mice. Severe combined immunodeficient (scid) and immunocompetent CBA mice were used as controls. The mice were killed and necropsied at day 30 or 37 post-infection. Samples from the nose, lungs and joints were taken for bacteriological and histological examination. Rhinitis was observed in all mouse strains. Chronic purulent bronchopneumonia was diagnosed in some of the CBA mice. Xid mice did not show severe lung lesions, despite the presence of numerous mycoplasma organisms in the lungs, in contrast to immunocompetent mice, which developed lung pathology. Scid mice showed less signs of pneumonia, but unlike in xid and CBA mice, there was spread of mycoplasmas from the respiratory tract and severe pathological changes in the joints. Our results indicate that B and/or T lymphocytes protect against dissemination of M. pulmonis from the airways. Innate immune reactions and/or bacterial virulence factors seem to contribute to the development of joint lesions, whereas IgG3 and IgM antibodies might be involved in lung pathology.
Premature removal of uninfected erythrocytes during malarial infection of normal and immunodeficient mice
Authors: SALMON M G , DE SOUZA J B , BUTCHER G A , PLAYFAIR J H L 
Published: November 2003

SUMMARY
Anaemia during blood-stage plasmodial infections is known to be due to at least three mechanisms: direct destruction of erythrocytes by the intra-erythrocytic parasite, inhibition of erythropoiesis, and premature removal of uninfected erythrocytes. The removal of the uninfected erythrocytes is considered by many to be dependent on an antibody-mediated mechanism. Our investigations involving normal, severe combined immunodeficient (SCID) and nude BALB/c mice and the murine malaria parasite Plasmodium yoelii, indicate that this mechanism is unlikely. The process of removal of uninfected erythrocytes was reduced in SCID mice but could not be enhanced by the passive transfer of serum from infected immunocompetent mice. Macrophage activation, as judged by the removal of xenogeneic erythrocytes, did not differ in the three strains of mice. Changes in the erythrocytes themselves may be responsible for their shortened lifespan.
Jak3 activation in human lymphocyte precursor cells
Authors: SHARFE N , DADI H K , O'SHEA J J , ROIFMAN C M 
Published: November 2003

SUMMARY
Although expression of the Jak3 tyrosine kinase in T lymphocytes has been thought to be restricted to mature, activated cells, mutations of Jak3 can lead to the development of a human severe combined immunodeficiency (SCID) characterized by an absence of peripheral T lymphocytes. We therefore examined in detail the expression of Jak3 throughout human T cell differentiation and show that Jak3 is in fact present throughout the entire developmental process, with high levels expressed in thymocytes. Jak3 is highly expressed in double negative (CD4−CD8−) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 receptor. IL-7 is known to stimulate thymocyte proliferation and initiate re-arrangement of the T cell receptor (TCR) β gene, suggesting that the failure of mutated Jak3 proteins to transduce this signal may be responsible for failures in T cell development. While Jak3 SCID patients possess mature peripheral B cells, we demonstrate that the Jak3 tyrosine kinase is also expressed in human pre-B cells and can be activated by the pre-B cell growth factor IL-7.
IL-5 expressed by CD4+ lymphocytes from Echinococcus multilocularis-infected patients
Authors: JENNE L , KILWINSKI J , SCHEFFOLD W , KERN P 
Published: November 2003

SUMMARY
IL-5 is a major factor inducing differentiation of B lymphocytes into immunoglobulin-producing cells as well as a main regulator of eosinophils. Recently, we have shown that peripheral blood mononuclear cells (PBMC) from patients with alveolar echinococcosis (AE) express IL-5 mRNA after stimulation with crude Echinococcus multilocularis (E.m.) antigen. To characterize the observed response in lymphocyte subpopulations, we cultured patients' PBMC in the presence of E.m. crude antigen for 18 h. PBMC were separated from seven patients by fluorescence-activated cell sorting (EPICSorter) into CD4+ and CD8+ subpopulations and from an additional seven patients by magnetic cell sorting (MACS) into CD4+, CD8+ and the CD4+/CD8+ depleted fractions. mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) for the cytokines IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, as well as for β-actin as control. IL-4 and IFN-γ expression was positive in all of the patients in the stimulated CD4+ subgroup. IL-5 mRNA expression was detected in eight out of 14 CD4+ samples (58%) and not observed in the other subpopulations, or the unstimulated and healthy controls. Co-expression of other Th2 cytokines in the eight patients expressing IL-5 mRNA was found in five patients for IL-3 and in seven for IL-10. Expression of IL-5 and both Th2 cytokines (IL-3 and IL-10) was only observed in patients judged as critically ill. Out of the six patients who were regarded as cured after radical operation or as stabilized with or without chemotherapy, only two expressed IL-5. Out of those eight patients considered as critically ill, six expressed IL-5 mRNA and five of these co-expressed IL-3 and IL-10. Thus, we conclude that specific antigenic challenge of PBMC from patients with active or previous AE induces an IL-5 response of CD4+ lymphocytes. The expression of Th2-type interleukin mRNA is significantly more frequent in patients clinically judged as progressive. Furthermore, IgE was elevated only in patients regarded as critically ill (six out of eight). In none of the patients were eosinophils elevated. These data support a Th2-type immune response in patients with chronic E. multilocularis infection.
Binding and internalization of human IgG by living cultured endothelial cells
Authors: RONDA N , GATTI R , ORLANDINI G , BORGHETTI A 
Published: November 2003

SUMMARY
Interactions between circulating IgG and endothelial cells (EC) in humans have been described only in conditions associated with pathologic immunoglobulins and/or activated or damaged EC. In this study we provide evidence that normal human IgG includes one/some antibody species that bind to and are internalized by living EC in culture. This novel function of EC and natural autoantibodies is of potential importance for the understanding of physiologic interactions between vessels and the immune system and for the clarification of pathogenesis of vasculitis and mechanisms of action of pooled IgG used in the therapy of such conditions.
A new approach to cytochrome CYP2D6 antibody detection in autoimmune hepatitis type-2 (AIH-2) and chronic hepatitis C virus (HCV) infection: a sensitive and quantitative radioligand assay
Authors: YAMAMOTO A M , JOHANET C , DUCLOS-VALLEE J-C , BUSTARRET F A , ALVAREZ F , HOMBERG J-C , BACH J-F 
Published: November 2003

SUMMARY
Antibodies specific for cytochrome CYP2D6, formally known as liver-kidney-microsome type-1 antibodies (LKM-1), are characteristically found in a subgroup of patients presenting autoimmune hepatitis. They are also found in some patients with chronic HCV infection. These autoantibodies are usually detected by indirect immunofluorescence, immunoblotting and ELISA tests. In an attempt to set up a more sensitive detection assay we developed a quantitative immunoprecipitation radioligand assay using a 35S-methionine-labelled CYP2D6 antigen obtained by in vitro transcription and translation synthesis. All 16 sera from AIH-2 patients strongly bound to this CYP2D6 antigen. Two of the nine sera (22%) from AIH-2 patients that presented only liver cytosol-1 antibodies also bound to CYP2D6. All 24 sera from HCV patients that were positive for LKM-1 antibodies by indirect immunofluorescence were also positive using this CYP2D6 radioligand assay. Lastly, all 15 sera from HCV patients negative for LKM-1 antibodies were negative by this test. The present results support the view that this quantitative radioligand assay is more sensitive than immunoblotting and ELISA CYP2D6 assays, and that it could be used in combination with indirect immunofluorescence assay.
Isolation of human anti-c-erbB-2 Fabs from a lymph node-derived phage display library
Authors: CLARK M A , HAWKINS N J , PAPAIOANNOU A , FIDDES R J , WARD R L 
Published: November 2003

SUMMARY
An immunoglobulin phage display library constructed from a tumour-associated pericolic lymph node was panned against the extracellular domain of the oncoprotein c-erbB-2. Sixteen independent clones were confirmed as positive binders based on ELISA analysis of soluble Fabs. Nucleotide sequencing demonstrated that the VH region of 12 clones belonged to four different V gene families, and the clones demonstrated varying degrees of somatic mutation compared with germ-line sequences. Fab fragments were examined for cross-reactivity by ELISA and shown to be negative against a panel of irrelevant self and non-self antigens, including bovine serum albumin (BSA), mouse immunoglobulin, tetanus toxoid, heregulin-PE40-FLAG and insulin. Reactivity of Fabs in vitro was verified by immunocytochemistry, which showed binding to the c-erbB-2 over-expressing breast cancer cell line SKBR3 but not to the low-expressing cell line MDA-MB-231. We conclude that a single lymph node library of moderate diversity (2 × 107κ light chain and γ heavy chain clones), when derived from an individual whose colorectal tumour over-expressed c-erbB-2, can be successfully panned to isolate a number of unique Fabs specific for this antigen. The nature of the anti-c-erbB-2 Fabs recovered from this library suggests that they may have resulted from a humoral immune response in the individual, and that in vivo antibody responses to tumour-associated antigens may be exploited in vitro for the production of tumour-specific recombinant antibodies.
Protective effect of granulocyte colony-stimulating factor (G-CSF) in a granulocytopenic mouse model of Pseudomonas aeruginosa lung infection through enhanced phagocytosis and killing by alveolar macrophages through priming tumour necrosis factor-alpha (TNF-α) production
Authors: SHIRAI R , KADOTA J , TOMONO K , OGAWA K , IIDA K , KAWAKAMI K , KOHNO S 
Published: November 2003

SUMMARY
We investigated the effects of G-CSF in a granulocytopenic mouse model of Pseudomonas aeruginosa lung infection. The model was prepared by intratracheal instillation of the bacteria, while granulocytopenia was induced by intraperitoneal injection of 4.0 mg of cyclophosphamide (CPA). There was no difference in the survival rate between G-CSF-treated animals and the normal group, and the number of neutrophils in the blood and lung recovered to normal in the former group. However, the phagocytic and killing activities of neutrophils were lower in G-CSF-treated mice than in controls. Interestingly, the mortality rate increased significantly when anti-TNF-α antibody was combined with G-CSF, although it was intermediate between CPA alone and CPA–G-CSF-treated mice. However, the improved mortality was not associated with a change in the number of neutrophils in the circulation and lung. Administration of anti-TNF-α antibody resulted in a significant suppression of TNF-α in bronchoalveolar lavage fluid and of enhanced alveolar macrophage function (phagocytic and bactericidal activity) against P. aeruginosa in G-CSF-treated granulocytopenic mice. We showed also increased TNF-α mRNA expression and TNF-α production in vitro using G-CSF-pretreated alveolar macrophages compared with control untreated macrophages. Our results are the first evidence to suggest that G-CSF provides a synergistic protective effect against lethal P. aeruginosa lung infection in the granulocytopenic host. This effect is probably due to enhancement of alveolar macrophage function through endogenous TNF-α production, in addition to increasing the number of circulating neutrophils.