bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alkali‐Treated LPS of Yersinia enterocolitica does not Induce Expression of E‐Selectin, ICAM‐1 or VCAM‐1 on Endothelial Cells but may Mediate Antibody‐ and Complement‐Dependent Cell Injury
Authors: REPO H. , RENKONEN R. , HELANDER I. M. , LEIRISALO‐REPO M. 
Published: July 2006

Lipopolysaccharide (LPS) prepared from a rough mutant of Salmonella typhimurium and deacylated enzymatically (dLPS) does not promote neutrophil adherence to human umbilical vein endothelial cells (HUVECs). This paper reports that similarly, a smooth form of LPS prepared from Yersinia enlerocolitica O:3, a serotype known to trigger reactive arthritis in humans, and treated with alkali (yersinia LPS‐OH) failed to augment neutrophil adherence to HUVECs. Studies of the mechanism underlying the poor augmentation revealed that neither enzymatically deacylated LPS from Escherichia coli J5 (J5 dLPS) nor yersinia LPS‐OH stimulated expression of endothelial cell adhesion molecules E‐selectin, VCAM‐1 and ICAM‐1, whereas both Intact J5 LPS and yersinia LPS were stimulatory. Impaired up‐regulation could not be explained by decreased binding of yersinia LPS‐OH to HUVECs. Furthermore, 51Cr‐labelled HUVECs treated with different concentrations of yersinia LPS‐OH released 51Cr in the presence of anti‐yersinia anti‐0 antibody and complement. J5 dLPS and yersinia LPS‐OH inhibited up‐regulation of the adhesion molecules induced by J5 LPS and yersinia LPS but not that induced by tumour necrosis factor alpha.Taken together, the results suggest that although yersinia LPS‐OH can depress development of acute inflammation by inhibiting up‐regulation of etidothelial‐cell adhesion molecules, sufiicient LPS‐OH is bound to induce cell injury and thereby inflammation in the prescence of specific antibody and complement. The findings may have pathogenetic implications in yersinia‐triggered reactive arthritis characterized by dissemination of yersinia LPS throughout the body.
Somatic Hypermutations in the Immunoglobulin Genes of Two New Human Lymphoma Lines of Lymphatic Follicle Origin
Authors: WU H. Y. , TUOMIKOSKI T. , ERAY M. , MATTILA P. , KNUUTILA S. , KAARTINEN M. 
Published: July 2006

Variable immunoglobulin heavy‐chain regions (VDJ) of two newly established human lymphoma cell lines (HF‐1 and HF‐4) were sequenced. The most homologous germline VH gene found for both the HF‐1 and HF‐4 sequences was VH26 of the VH3a (V gene) family (82% and 91 % homologies, respectively). The JH region of the HF‐4 heavy‐chain sequence contained two nucleotide differences compared to the published germline JH3 gene. The DHJH region of the HF‐1 gene had a record high number (20%) of somatic mutations.The numerous hypermutations found in the HF‐1 cell line support the hypothesis that in some human follicular lymphomas, mutations continue to accumulate in immunoglobulin genes during the malignant growth. Follicular lymphoma cell lines, which have an active mutational machinery, in future may help to solve the molecular events behind the somatic hypermutations modifying immunoglobulin genes of B lymphocytes.
Characterization of a 58‐ and a 78‐kD Monocytic Membrane Protein with Affinity to the Acetylcholine Receptor in Myasthenia Gravis Patients
Authors: STUHLMÜLLER B. , KALIES I. , KACHELRIES H. , DRUSCHKY K.‐F. , KALDEN J. R. 
Published: July 2006

The autoimmune disease myasthenia gravis (MG), caused by the effect of specific antibodies, directed towards the nicotinic acetylcholine receptor, is triggered by autoantigen‐specific T cells. In order to investigate cellular parts of the immune response in MG, the authors investigated the binding of the nicotinic acetylcholine receptor (AChR) to peripheral blood mononuclear cells (PBMC) from MG patients. AChR binding cells were identified by resetting experiments using AChR‐coated fluoresceine beads. Applying this technique, a significant percentage of PBMC (21.2 × 7.65%) from MG patients formed rosettes with AChR‐coated beads.Membrane preparations of nycodenz‐ or percoll‐separated monocytes from MG patients or T‐cell depleted monocytic subpopulations were applied to SDS‐PAGE under reducing conditions. Ligand‐blotting studies with biotinylated AChRs revealed two cell‐membrane proteins with molecular weights of 58‐ and 78‐kD. In parallel the same results were obtained by affinity chromatography of monocytic membrane proteins using AChR‐sepharose. A possible interference of anti‐AChR IgG was excluded. The 58‐ and the 78‐kD proteins are detectable under reducing conditions by ligand blotting with AChR‐biotin, while under non‐reducing conditions only the 58‐kD protein can be detected. Furthermore, in experiments using Endoglycosidase‐H, the 58‐kD protein appears to be non‐glycosylated, while the 78‐kD protein bears carbohydrates.These findings suggest that monocytes which bind the AChR via specific membrane proteins on their surface might act as antigen‐presenting cells and may lead to an induction of the T‐cell response, in the early phase of the disease.
Mannan‐Binding Protein and Bovine Conglutinin Mediate Enhancement of Herpes Simplex Virus Type 2 Infection in Mice
Authors: FISCHER P. B. , ELLERMANN‐ERIKSEN S. , THIEL S. , JENSENTUS J. C. , MOGENSEN S. C. 
Published: July 2006

A broad range of plant lectins have recently been shown to inhibit the infectivity of herpes simplex virus type I (HSV‐1) in viiro. We decided to investigate the role of mammalian Icctins in infection witb herpes simplex virus. Two lectins, conglutinin and mannan‐binding protein (also called mannose‐binding protein. MBP). belonging to the collectin family of lectins, were examined.Four week‐old BALB/c mice were injected subcutaneously with 100 μg bovine conglutinin or 50 μg human MBP 1 day before intravenous infection with 5 × 104 PFU of herpes simplex virus type 2 (HSV‐2). A three‐fold increase in virus titre of the liver was observed on day 3 of the infection in the mice pretreated with conglutinin or MBP. whereas no effect was seen on days I and 5.In a standard plaque assay using Vero cells we were not able to demonstrate reproducibly either infection inhibition or infection enhancement, when virus was pre‐incubated with differing concentrations ofthe collectins. Tbe concentrations used were similar to tbose used by us in livo, and by others in in vitro experiments showing inhibition of the infectivity of HSV‐1 with plant lectins.In an ELISA with HSV‐2 antigens captured on anti‐HSV‐2 antibodies, calcium‐dependent and carbohydrate inhibitabte binding of the collectins was observed. Our results indicate that the effect of endogenous mammalian collectins in vivo may not be neutralization as suggested by the data using plant lectins. Instead, the previously described opsonizing activity of the mammalian collectins may provide the virions witb an alternative port of entry into cells leading to infection enhancement.
Indirect Effects of Oral Tolerance in Mice
Authors: CARVALHO C. R. , VERDOLIN B. A. , DE SOUZA A. V. , VAZ N. M. 
Published: July 2006

Anti‐DNP antibody formation resulting from intraperitoneal (i. p.) immunization with DNP‐KLH may be blocked by simultaneous (i. p.) injection of DNP‐Ova or native Ova in mice orally tolerant to Ova, but not in normal mice. In Ova‐tolerant mice the inhibition of anti‐DNP antibody formation also occurred when DNP‐Ova and DNP‐KLH were given by separate routes of immunization: subcutaneous (s. c.) and i. p. A second exposure to Ova by gastric intubation (gavage) or intravenous administration simultaneously with i. p. immunization with DNP‐KLH failed to inhibit anti‐DNP antibody formation. There was inhibition of responses to DNP‐KLH i. p. by DNP‐Ova given 24 h before, but not 24 h after, and in the Ova‐tolerant mice, addition of DNP‐Ova only to the primary immunization with DNP‐KLH inhibited secondary and tertiary responses to DNP‐KLH in the absence of further exposures lo DNP‐Ova.These results suggest that the indirect effects of parenteral exposure of tolerant mice to the tolerated immunogen may inhibit unrelated immune responses. This inhibition is not due to ‘innocent bystanding’ suppression, i, e., to inhibitory cytokines provided locally by specific suppressor lymphocytes; it may derive from more durable perturbations of immune system.
IL‐1β‐Stimulated Leucocyte–Endothelial Adhesion is Regulated, in Part, by the Cyclic‐GMP‐Dependent Signal Transduction Pathway
Authors: LESZCZYNSKI D. , JOSEPHS M. D. , FOEGH M. L. 
Published: July 2006

It is well known that the exposure of endothelial cells to IL‐1β induces an increase in endothelial cell adhesiveness for leucocytes. Using rat heart endothelial cells we found that exposure of endothelial cells to IL‐1β (100U/ml) induces a 133‐fold increase in the intracellular concentration of cyclic‐GMP; from 11.5×0.2fm to 1530 × 117.8 fm (per 106 cells). Therefore, we examined whether cyclie‐GMP is involved in the regulation of endothelial adhesiveness for leucocytes. Cyclic‐GMP analogue, dibutyryl cyclic‐GMP (0.01–0.05mm), similarly to IL‐1β, increased endothelial cell adhesiveness for leucocytes. Methylene blue, an inhibitor of guanylate cyclase, and KT5823, a specific inhibitor of cyclic‐GMP‐dependent protein kinase, inhibited both basal as well as IL‐1β‐induced endothelial cell adhesiveness for leucocytes, and KT5823 abolished the dibutyryl‐cyclic‐GMP‐induced increase in endothelial adhesive ness. The effect of cyclic‐GMP, induced by IL‐1β treatment, on the endothelial adhesiveness may be either direct or indirect because of the time‐gap between the rise in cyclic‐GMP level and the increase of endothelial adhesiveness.IL‐1β (100 U/ml) and dibuthyryl‐cyclic‐GMP (0.01 mm) both induced an increase in the expression of intercellular adhesion molecule‐1 by endothelial cells. However, the fact that KT5823 failed to prevent this increase, suggests that, although the IL‐lγb‐induced increase in adhesiveness is caused by the increase in intracellular levels of cyclic‐GMP, it may not be mediated through intercellular adhesion molecule‐1.In conclusion, the results obtained indicate that endothelial cell adhesiveness for leucocytes is, in part, regulated by the cyclic‐GMP‐dependent signal transduction pathway.
Implanted Solid Human Tumours Grow Under the Renal Capsule of Cyclosporin‐Immunosuppressed Rats
Authors: KAARTINEN M. , ERAY M. , LEHTONEN E. , MATOSO‐FERREIRA A. , TIENARI J. 
Published: July 2006

Cyclosporin (CsA) is a potent immunosuppressive drug widely used in organ transplantation. We transplanted fresh surgical samples from human solid malignant tumours into 45 CsA‐immunosuppressed rats. Eight out of nine tumour types grew and remained viable for 5 weeks or more in at least two of the transplanted rats. In 29 rats (64%) a distinct growth of primary human tumours was recorded.Five malignancies (intestinal‐type gastric carcinoma, adenocarcinoma of the lung, lymph node metastasis of a testicular teratocarcinoma, soft tissue malignant fibrous histiocytoma (MFH), and small‐cell sarcoma) showed invasive and progressive growth. In all five cases the largest tumours were 0.9 cm or over in diameter when the rats were killed 5–9 weeks after transplantation. In three cases (adenocarcinoma of the colon, hypernephroma, and a second MFH) the growth of the implants under the kidney capsule was slow, but small living tumour transplants were still found 3–6 weeks later. In every case the microscopic morphology of the xenograft tumour was identical with the original tumour. In two cases the primary xenografts (teratocarcinoma and small‐cell sarcoma) were retransplanted into 11 CsA‐immunosuppressed rats. In both types the second passage tumours grew, and the take‐off and growth rates were comparable to the primary xenografts.Cyclosporin‐treated laboratory rats are an alternative to immunodeficient nude and SCID mice for growing fresh human tumour transplants in vivo. Although a few infections were encountered, most of the rats survived the CsA treatment well for up to 2 months.
Affinity Maturation and Isotype Switch in Clonally Related Anti‐Erythrocyte Autoantibodies
Authors: SCOTT B. B , SADIGH S. , ANDREW E. M. , MAINI R. N. , MAGEED R. A. 
Published: July 2006

The NZB mouse is genetically predisposed to develop, at approximately 6 months of age, a spontaneous and severe autoimmune anaemia caused by production of pathogenic anti‐mouse erythrocyte auto‐antibodies. Molecular analysis of a panel of five anti‐erythrocyte monoclonal antibodies (MoAb) derived from splenocytes of unimmunized NZB mice revealed that these autoantibodies all had functionally rearranged genes from the VH J558 family of immunoglobulin genes with closest homology to germline genes H10 and H30. Owing to clustering of nucleotide differences within the CDRs, compared with the germline, it was concluded that these antibodies were most likely generated by an antigen‐driven mechanism.We report here further molecular analysis of two (4.16.1 and B4.13.2) of the panel of five anti‐mouse erythrocyte producing hybridomas which are apparently clonally related. Nucleotide analysis of the light chain cDNA indicated that both antibodies had closest homology to germline gene Vk24 and use Jk2 gene. Determination of the functional affinities of the MoAb reveal that B4.13.2 (IgG2a) has a > 10‐fold higher affinity for mouse erythrocytes when compared to 4.16.1 (IgGl). This finding supports the view that these two autoantibodies are generated by an antigen‐driven mechanism. The proposed mechanism would involve the selection and expansion of a small population of B‐lymphocytes by antigen leading to isotype switch, somatic mutation and increased affinity. Our data also point to the possibility that some framework residues may be involved in the binding to antigen.
Real‐Time Biospecific Interaction Analysis of a Natural Human Polyreactive Monoclonal IgM Antibody and its Fab and scFv Fragments with Several Antigens
Authors: ROGGENBUCK D. , KÖNIG H. , NIEMANN B. , SCHOENHERR G. , JAHN S. , PORSTMANN T. 
Published: July 2006

Surface plasmon resonance (SPR) was used to investigate the kinetics of interactions between the human monoclonal polyreactive IgM antibody CB03, its Fab as well as its single‐chain variable fragment (scFv) and different antigens. From these experiments apparent binding constants were determined and compared with binding constants obtained by ELISA experiments. In SPR studies with the complete antibody, the polyreactivity of the CB03 antibody as derived from ELISA experiments was confirmed.Interaction of scFv with k casein and human myoglobin is strong evidence for the location of polyreactivity within the variable domains of the antibody.Apparent binding constants of the complete antibody to immobilized K casein (9.2 × 107 M−1) and to human myoglobin (1.6 × 107 M −1) are up to 83 times higher than those of Fab. The binding constants of the scFv to the above mentioned antigens are again about 10 times lower when compared with Fab, which is mainly due to the lower association rates of the complexes formed by the scFv.
Autoantibodies Against Ganglioside GM3 Represent a Portion of Anti‐Lymphocyte Antibodies in AIDS Patients
Authors: GRIGGI T. , BAUER R. , GAROFALO T. , KUKEL S. , LENTI L. , MASSETTI A. P. , MÜLLER C. , SORICE M. , PONTIERI G. M. 
Published: July 2006

In this study we analysed the relationship between anti‐lymphocytic ganglioside antibodies and anti‐lymphocyte antibodies in AIDS patients. Anti‐lymphocytic ganglioside antibodies were detected by thin layer chromatography (TLC) immunostaining; three colour flow cytometry was used to analyse circulating antibodies against different lymphocyte subsets.Anti‐lymphocytic ganglioside antibodies were detected in 23 out of 49 AIDS patient sera (46.9%). All positive sera reacted selectively with the GM3 comigrating band from AIDS lymphocytes. Twenty two out of the 23 anti‐lymphocytic GM3 positive sera also had antibodies against CD4+ T cells, versus 17/26 anti‐GM3 negative. Furthermore, patients with lymphocytic GM3 antibodies showed a significantly higher antibody reactivity against CD4+ T cells than patients in which these antibodies were not detected. The absorption tests revealed that preincubation of positive sera with GM3 was followed by a decrease in the reaction with target lymphocytes.These findings suggest that anti‐GM3 antibodies are a portion, but not the majority, of antibodies reacting with CD4+ T cells.
The Fifth Serum Amyloid A‐Related Gene Sequence, GSAA4, is SAA3
Authors: WATSON G. , FAULKES D. J. , WOO P. 
Published: July 2006

The human serum amyloid A (SAA) gene family consists of two acute phase genes, SAA1 and SAA2; a pseudogene, SAA3 and a fourth gene, SAA4. The existence of SAA4 was first described in this laboratory. Subsequently, Sack & Talbol isolated a clone, designated GSAA4, which had homology to SAA3. The clone was described as the same as SAA4 and was characterized as a pseudogene. However, our restriction site and sequence analyses of SAA4 demonstrated that SAA4 and GSAA4 are separate entities. SAA4 encodes a functional, constitutively expressed protein.Recently, the GSAA4 clone has been reported by Sellar & Whitehead as constituting a fifth SAA‐ related sequence. However, we have demonstrated that GSAA4 has striking homology with the 3′ terminus of SAA3 in the reverse orientation. Furthermore, computer analyses strongly indicate that the GSAA4 or fifth SAA‐related sequence is in fact, a clone from the SAA3 locus. We have amplified, isolated and sequenced fragments from genomic DNA which demonstrate that the GSAA4 sequence is the correct sequence of the 3′ region of SAA3. The SAA family must therefore still be viewed as consisting of four SAA loci at present.
Lymphocyte Transformation Test in Adult Patients with Minimal Change Nephrotic Syndrome
Authors: AL‐AZZAWI Y. H. M. , AL‐TAWIL N. G. , AL‐SHAMAA I. A. 
Published: July 2006

The lymphocyte transformation test was used to evaluate the cellular immune response in 31 adult patients with MCNS in comparison with 30 normal control and 49 patient (CRF, FSGN. MGN) control groups. The results showed that the stimulation indices of the lymphocytes in MCNS group were significantly lower than those of the normal control and patient control groups with the exception of CRF group.In cross studies, lymphocytes obtained from normal individuals were incubated in homologous serum obtaitied from MCNS patients in relapse, and lymphocytes from MCNS patients in relapse were incubated in normal homologous AB serum. In both circumstances there was a depressed lymphocyte function which indicates that there is a defect in lymphocyte itself as well as a serum inhibitory factor(s) during the active stage of the MCNS. This depressed cellular immune response returned to normal level during remission of the patients with MCNS.
Inhibitory Activity of Soluble IL‐2R in Sera, Ascites and Culture Supernatants from Murine Leukaemic Cells
Authors: WALDNER C. , MONGINI C. , ALVAREZ E. , ROIG I. , HAJOS S. E. 
Published: July 2006

The effect of sera from mice bearing a T cell lymphoid leukaemia (LB) and the supernatants from short term cultures of the tumour cells were studied on cell proliferation using syngeneic and allogeneic normal and tumour cells. An inhibitory activity was demonstrated in 24–48 h supernatants of LB cells in culture and disappeared after 4 days of culture. Inhibitory activity was cytostatic but not cytotoxic and was non‐specific since it inhibited the growth of both syngeneic and allogeneic normal and tumour cells. Such activity was found in the 105–1.3 × 105 Mr serum fraction after a Sephacryl S200 chromatography. Though sensitive to protease, trypsine or neuraminidase treatment, which indicated its glycoprotein nature, it remained stable after heating or freezing‐thawing cycles as well as after alkaline, acid or hyaluronidase treatment. Addition of exogenous IL‐2 abrogated inhibitory activity. ELISA showed the presence of soluble IL‐2R both in LB conditioned medium and in above serum fraction.It is demonstrated that the inhibitory factor, soluble IL‐2R, is produced by LB leukaemia cells, then secreted into blood and ascitic fluid or released into culture supernatants. Soluble IL‐2R exerts inhibitory activity blocking cell proliferation and modulating immune response by binding to free IL‐2.
Circulating Myeloperoxidase May Cause False Negative Findings in the Analysis of Myeloperoxidase Antibodies in Systemic Vasculitis
Authors: HAAPALA A.‐M. , SOPPI E. , HYÖTY H. 
Published: July 2006

In systemic vasculitis reliable detection of myeloperoxidase antibodies (MPO‐Abs) is of great clinical importance in the diagnosis and follow‐up of patients. We have studied whether circulating myeloperoxidase (MPO) could have an effect on MPO‐Ab findings. Serum MPO and MPO‐Abs were measured in 50 healthy individuals, 35 patients and in the follow‐up samples from two patients with Wegener's granulomatosis.Heating the sera at 56°C for 30min reduced the concentration of immunoreactive MPO both in control and patient sera. In 71% of the patient sera heating made initially negative MPO‐Abs detectable. In a few cases with severe vasculitis the antibody findings remained totally negative. These results, together with the data from the follow‐up samples from two patients with Wegener's granulomatosis, revealed that the serological diagnosis of vasculitis may be considerably delayed if only native samples are analysed for MPO‐Abs. These findings are of considerable clinical significance for the interpretation of MPO‐Ab results.Circulating myeloperoxidase affects MPO‐Ab measurements, causing false negative findings in MPO‐Ab assays. Therefore, it is recommended to denaturate circulating MPO by heating the sera before the analysis of MPO‐Abs and to re‐evaluate the cut off‐values.
IgG Subclass‐Associated Differences in Anti‐Schistosomal Antibody Specificity
Authors: Evengård B. , WOLOWCZUK I. , MARGUERITE M. , HAMMARSTRÖM L. , SMITH E. , AURIAULT C. 
Published: July 2006

Consecutive sera from before and after treatment were collected from 23 patients with a Schistosoma mansoni infection, seven of whom had an early infection. All sera were analysed for IgGl, IgG3 and IgG4 antibody activity against three peptides from the protein Sm 28 GST (24–43, 115–131 and 140–153 aa). In addition, sera from 14 patients, four with an early infection and 10 patients with a chronic infection, were analysed for IgG and IgA antibody activity using seven peptides derived from the protein Sm 28 GST. This molecule has previously demonstrated protective activity against infection in various experimental models.The results are indicative of a subclass‐related epitope specificity of the antibodies. Moreover, reactivity to one of the peptides (158–175 aa) was significantly associated with a chronic infectious status.
IgG Humoral Response Against the Antigen 85 Complex Homologues in Leprosy
Authors: DROWART A. , HUYGEN K. , LAUNOIS P. , JANN E. , NYABENDA J. , VAN VOOREN J. P. 
Published: July 2006

Antigen 85 complex is the major protein component present in M. bovis BCG culture filtrate (CF). It consists of a family of three proteins: 85A, 85B and 85C. Combining isoelectric focusing and Western blot analysis, we have previously identified different antigenically related proteins present in the CF of other mycobacteria (M. tuberculosis, M. kansasii, M. avium, M. gordonae, M. fortuitum and M. plilei) using monoclonal antibodies (MoAbs) directed against the antigen 85 complex of M. bovis BCG.Humoral immune response directed against these cross‐reactive homologues was analysed in sera from 20 patients with multibacillary leprosy (BL/LL), from 20 patients with paucibacillary leprosy (BT/ TT) and from 15 healthy leprosy contacts.All the antigen 85 homologues identified in the seven CFs by MoAbs were also recognized by IgG present in sera from multibacillary leprosy patients, but not or very faintly in sera from paucibacillary leprosy patients or from healthy subjects.These results suggest that some of the M. leprae epitopes inducing a significant humoral response in multibacillary leprosy are common to the various 85 antigenically related proteins present in all mycobacterial species.