bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 proviral DNA copy number in peripheral blood leucocytes and bronchoalveolar lavage cells of AIDS patients
Authors: CLARKE J R , GATES A J , COKER R J , DOUGLASS J A , WILLIAMSON J D , MITCHELL D M 
Published: July 2010

SUMMARYIn this study we have determined by polymerase chain reaction (PCR) the quantity of HIV-1 proviral DNA in cells obtained by bronchoalveolar lavage (BAL) from the lung of HIV-1+ individuals. This has been compared quantitatively with the proviral DNA in peripheral blood leucocytes (PBL) obtained simultaneously from the same patients. The mean HIV DNA copy number per 106 cells was 391 for PBL, with a range of 1–9000, and 2971 for BAL cells, with a range of &lt; 1–70000. The quantity of HIV DNA detected in BAL cells was higher than that detected in the corresponding PBL samples in 44 out of 78 (56%) individuals, whilst more HIV DNA was detected in the PBL compared with BAL cells in 14 out of 78 (18%) patients. In both BAL and PBL higher levels of HIV DNA were detected in the adherent (monocyte/macrophage) enriched cell populations compared with other non-adherent cells (leucocytes). A direct relationship between HIV DNA copy number and ability to recover infectious HIV progeny in vitro by cultivation with cord blood leucocytes was found for both PBL and BAL cells. Individuals known to be receiving azidothymidine treatment had a lower mean HIV DNA load in all cell fractions compared with those patients on no antiretroviral therapy.
Nerve and skin damage in leprosy is associated with increased intralesional heat shock protein
Authors: KHANOLKAR-YOUNG S , YOUNG D B , COLSTON M J , STANLEY J N A , LOCKWOOD D N J 
Published: July 2010

SUMMARYLeprosy is frequently complicated by the development of reversal reactions in which peripheral nerve and skin lesions become inflamed and irreversible nerve damage may ensue. Increased expression of proteins belonging to the 70-kD heat shock family (hsp70) occurs in cells of the central nervous system exposed to hyperthermia, physical damage or drug-induced trauma. In the present study we have used immunocytochemical staining to monitor hsp70 levels in peripheral nerves infected by Mycobacterium leprae. Hsp70 was detected in skin and nerve lesions from all leprosy patients, but was particularly prominent in lesions from patients undergoing reversal reactions. Hsp70 immunocytochemistry can thus be used as a marker of neural injury in the peripheral as well as in the central nervous system. The cellular dynamics of nerve damage in leprosy are currently poorly understood, and we postulate that the immunopathology of leprosy may be partly due to an autoimmune response to heat shock proteins.
Activation of macrophages and expansion of specific T lymphocytes in the lungs of mice intratracheally inoculated withCryptococcus neoformans
Authors: KAWAKAMI K , KOHNO S , MORIKAWA N , KADOTA J , SAITO A , HARA K 
Published: July 2010

SUMMARYA quantitative and qualitative change in inflammatory cells in the lungs of mice after intratracheal inoculation of heat-killed Cryptococcus neoformans was examined by direct analysis of the pulmonary intraparenchymal leucocytes. Macrophages and T and B lymphocytes increased, peaked at day 7, and then gradually decreased to the basal level, Macrophages were activated 7 days after the inoculation, as indicated by the enhanced expression of MHC class II, intercellular adhesion molecule-1 (ICAM-I)and Fc receptor (FcR), which have been known as their activation markers. T cells were also activated, as indicated by the induction of IL-2 receptor (IL-2R) and the enhanced expression of leucocyte function-associated molecule-1 (LFA-1) and ICAM-1, a pair of adhesion molecules which have also been regarded as T cell activation markers. CD4+ T cells preferentially accumulated in lungs, and proliferated in vitro by stimulation with heat-killed whole yeast cells, suggesting that at least some of the infiltrated T cells expand locally in response to the organisms. These results demonstrate that the activation of macrophages and T cells reactive to C. neoformans is induced in lungs after intratracheal inoculation of heat-killed organisms, and suggest that these cells interact to eliminate organisms more efficiently from the host.
Defective CD2 T cell pathway activation in common variable immunodeficiency (CVID)
Authors: ZIELEN S , DENGLER T J , BAUSCHER P , MEUER S C 
Published: July 2010

SUMMARYClonal T cell expansion requires simultaneous activation of the TCR and secondary signals, e.g. CD2, CD4, CD28, Interference of CD2/CD58 interaction with MoAbs abrogates the primary immune response and antibody production. Given this functional importance of CD2/CD58 interaction for the generation of specific immune responses, we demonstrate for the first time a defective CD2 pathway activation in patients with CVID (seven children and four adults). The co-stimulatory effect of monocytes upon CD2-triggered proliferation was significantly impaired in CVID patients: 4·080 ct/min versus 20·769 ct/min in controls (F&lt;0·05), Second, IL-1, which is a strong comitogenic factor for activation via CD2 in normal T cells, showed a defective amplifier function of the CD2 pathway in most patients (median 1·714ct/min in patients versus 17·521 ct/min in controls; P&lt;0·05). In addition, by using a mitogenic combination of CD2 plus CD45 MoAb, median proliferation of T cells was severely depressed in patients: 10·577 ct/min versus 34·685 ct/min in controls (p= 0·005). In conclusion, the marked dysfunction seen in responsiveness to phytohaem-agglutinin (PHA) (median 24·594 ct/min in patients versus 52·229 ct/min in controls; P&lt;0·001) and after CD2 triggering, together with the unaffected response to TCR-CD3, suggest that the T cell deficiency in CVID is in part due to deficiencies in the CD2 pathway. Since direct activation of protein kinase C (PKC) by phorbol ester restores defective T cell responses to normal, our results suggest that an early signal-transducing defect might exist at a step proximal to PKC activation in patients with CVID.
Percutaneous exposure of adjuvant oil causes arthritis in DA rats
Authors: KLEINAU S , ERLANDSSON H , KLARESKOG L 
Published: July 2010

SUMMARY
The arthritogenic properties of adjuvant oil upon percutaneous administration in DA rats was investigated. Groups of rats were administered single or repeated percutaneous applications of Freund's incomplete adjuvant (FIA) or olive oil on shaved skin with or without prior abrasion of the skin. Control rats were shaved and abrased only. A transient arthritis developed in 8/16 animals after repeated applications of FIA on abrased skin. The incidence of arthritis increased to 7/8 animals when FIA was repeatedly administered via filter paper on abrased skin and covered with a bandage. Histological examination of the arthritic joints showed proliferation of the synovial lining layer, infiltration of mononuclear cells and polymorphonuclear cells in the subsynovial tissue. Some bone and cartilage destruction was also seen. Repeated treatment with olive oil on abrased skin induced joint swelling in 3/15 animals, which did not, however, correspond to any microscopically observable signs of inflammation. Also, a single application of FIA on abrased skin or repeated applications of FIA without abrasion induced arthritis, although with low penetration, whereas control animals had no clinical signs of joint involvement. These findings demonstrate that percutaneous administration of adjuvant oil can cause arthritis in genetically susceptible animals.
Profiles of immunoregulatory cytokine productionin vitroin patients with IgA nephropathy and their kindred
Authors: SCIVITTARO V , GESUALDO L , RANIERI E , MARFELLA C , SCHEWN S A , EMANCIPATOR S N , SCHENA F P 
Published: July 2010

SUMMARYWe hypothesized that the altered immunoglobulin synthesis and/or lymphocyte function apparent in patients with IgA nephropathy (IgAN) is due to a primary defect in lymphokine regulation. In addition, we reasoned that such changes in lymphokine production might be, at least partially, genetically determined. To assess the extent of lymphocyte abnormalities, we investigated the profile of cytokine production from peripheral blood mononuclear cells (PBMC) in 34IgAN patients and 44 of their first degree relatives, 10 of whom had persistent microhaematuria. Compared with healthy volunteers (n=34), PBMC from patients showed increased IL-2 production both spontaneously or after phytohaemagglutinin (PHA) (20 μ/ml) stimulation, whereas IL-4 and interferon-gamma (IFN-γ) production were significantly higher only after stimulation. Microhaematuric relatives had a similar pattern of cytokine production, whereas non-microhaematuric relatives showed no significant difference versus normals. The altered pattern of cytokine production appeared to be quite specific to IgAN patients and their microhaematuric relatives, because patients with other forms of primary glomerulonephritis (n= 17) did not differ from normal individuals. Patients and relatives that hyperproduced IL-4 were also hyperproducers of IL-2. No such congruence was seen in any other group or with any other pairing of cytokines. We propose that a subpopulation of IgAN patients bear lymphocytes intrinsically hyper responsive. Among those individuals such hyperresponsiveness may be causally related to the pathogenesis and/or character of IgAN.
Autoantibodies from mixed cryoglobulinaemia patients bind glomerular antigens
Authors: DOLCHER M P , MARCHINI B , SABBATINI A , LONGOMBARDO G , FERRI C , RIENTE L , BOMBARDIERI S , MIGLIORINI P 
Published: July 2010

SUMMARYMixed cryoglobulinaemia (MC) is a disorder characterized by the presence of large amounts of cryoprecipitating IgM-IgG complexes. An immune complex glomerulonephritis develops in one third of all patients, but its occurrence docs not seem related to the amount of cryoglobulins in the sera, nor to their complement-fixing ability. In this study we investigated the presence of IgG antibodies reactive with kidney antigens in 33 MC patients (11 with glomerulonephritis, 22 without renal involvement). A total glomerular extract was run on a 10% acrylamide gel, blotted to nitrocellulose and probed with the patients'sera. Sera from half of the patients without renal involvement reacted with several glomerular antigens whose molecular weight ranged between 200 and 29 kD. In the group with renal involvement, sera from 7/11 patients reacted with an antigen of 50 kD, which is also expressed in thymus, but not in the heart or liver. In a follow-up study of four patients with renal involvement, the amount of serum antibody specific for the 50-kD antigen fluctuated, either spontaneously or in response to therapy. These results show that antibodies specific for glomerular antigens are detectable in MC sera. The immune response against a 50-kD antigen expressed in the kidney and thymus seems to be restricted to a subset of MC patients with renal involvement. Circulating autoantibodies specific for glomerular antigens might contribute to the induction of glomerulonephritis in MC forming immune complexes in situ.
Modulation of immune response toLol pI by pretreatment with anti-idiotypic antibody is not restricted to the idiotypic expression
Authors: BOUTIN Y , HÉBERT J 
Published: July 2010

SUMMARYTo study the role of anti-idiotypic antibodies in the regulation of the immune response to Lol p I (the major allergenic component of rye grass pollen), we have recently generated a panel of three MoAbs directed against distinct epitopes of Lol p I and an anti-idiotypic MoAb directed against the idiotype borne by one of the anti-Lol p I MoAbs (290A-167). The effects of pretreatment with this anti-idiotypic MoAb in BALB/c mice before immunization with the antigen have been examined. The anti-idiotypic MoAb or unrelated MoAb were given weekly for 8 weeks intraperitoneally. Mice then received the antigen (2 μg) adsorbed with alum (2 mg) at weeks 9, 11 and 13. Serum anti-Lol p I antibodies (IgG or IgE) and specific idiotypic responses were measured. Anti-Lol pI IgG antibodies could be detected before immunization with Lol p I only in mice pretreated with anti-idiotypic MoAb. Immunization with Lol p I induced an anti-Lol p I IgG response in both groups, but this response was higher in mice that received anti-idiotypic MoAb. Similar profiles were seen for specific IgE antibodies and idiotypic responses. Surprisingly, idiotypes borne by other anti-Lol p I MoAbs (539A-6 and 348A-6) had also been enhanced after pretreatment with the anti-290A-167 MoAb. These observations suggested that the pretreatment with this anti-idiotypic MoAb modulates not only the expression of the respective idiotype, but also affects other idiotype responses.
Biological and clinical significance of neutralizing and binding antibodies to interferon-alpha (IFN–α) during therapy for chronic hepatitis C
Authors: GIANNELLI G , ANTONELLI G , FERA G , DEL VECCHIO S , RIVA E , BROCCIA C , SCHIRALDI O , DIANZANI F 
Published: July 2010

SUMMARYIt is known that IFN therapy can induce the development of anti-IFN antibodies. In order to evaluate the biological and clinical significance of both neutralizing (NA) and non-neutralizing (binding) antibodies, 123 patients with chronic hepatitis C treated with recombinant IFN-α were examined. Among them, 15 were positive for NA and 24 for binding antibodies. The kinetics of NA appearance show that, in general, they develop early during the first 3 months of treatment. Moreover, NA seem to be clinically relevant, since they may be responsible for non-responsiveness to treatment in 53% of patients who develop them. The evaluation of the clinical significance of binding antibodies is more difficult. They appear significantly earlier in non-responders than in responders, but no differences were observed in the overall percentage of seroconversion between responders and non-responders. Thus, it is not possible at the moment to establish their possible role in inducing non-responsiveness.
Co-expression of the CD45RA and CD45RO antigens on T lymphocytes in chronic arthritis
Authors: SUMMERS K L , O'DONNELL J L , HART D N J 
Published: July 2010

SUMMARYThe site of T lymphocyte activation in chronic arthritis is unknown. Peripheral blood (PB) lymphocytes from chronic arthritis patients are in a ‘naïve’ or non-activated state, as defined by expression of the CD45RA antigen and lack of HLA class II expression. In contrast, most synovial fluid (SF) T lymphocytes express a ‘memory’ or activated phenotype, as defined by the CD45RO antigen and high HLA class II expression. Following stimulation, naive cells lose CD45RA and gain CD45RO expression to become memory cells with a transitional stage of dual CD45RA, CD45RO antigen expression. To localize where this change in phenotype occurs we used dual colour immunofluorescence labelling to compare the percentage of dual CD45RA, CD45ROpositive T lymphocytes in PB and SF from chronic arthritic patients and from normal PB, assuming this population would be increased at the primary site of T lymphocyte activation. Expression of the intermediate and late activation marker. HLA-DR, was also analysed using dual colour immunofluorescence labelling. The percentage of dual positive T lymphocytes was similar between arthritic PB, SF. and normal PB, as was the density of both CD45RA and CD45RO antigens. Thus, CD45 isoform expression did not indicate where T lymphocytes were activated. However, we identified a previously unreported population of CD45RA+ CD45RO+ HLA-DR- T lymphocytes in arthritic and normal PB. In SF, this population was absent, but a substantial number of dual CD45RA, CD45RO-positive HLA-DR+ T lymphocytes were identified. This population would not be predicted by the current model of T lymphocyte activation. Division of T lymphocytes into functional groups on the basis of CD45 isoform expression is likely to be more complicated than previously thought. Based on our findings we propose an alternative model of T lymphocyte differentiation.
Nitric oxide synthesis in patients with advanced HIV infection
Authors: EVANS T G , RASMUSSEN K , WIEBKE G , HIBBS J B 
Published: July 2010

SUMMARYThe discovery that humans produce nitric oxide and that this molecule plays an important role in cell communication, host resistance to infection, and perhaps in host defence to neoplastic disease, has created much interest in further research on its function in the body. A cytokine-inducible high output L-arginine/nitric oxide pathway was recently detected in patients with advanced malignancy treated with IL-2. The production of nitric oxide was thus examined in patients with advanced HIV infection and in intensive care unit control patients. Extrinsic nitrate and nitrite consumption were carefully controlled in the diet or through the use of total parenteral nutrition. Seven of eight HIV+ patients were placed into positive nitrogen balance. Nitric oxide synthesis was found to be within the normal human range. In contrast, nitric oxide synthesis in extremely ill intensive care unit patients was low normal to depressed.
Assessment of the correlation between nitrite concentration and Listericidal activity in cultures of resident and elicited murine macrophages
Authors: HIGGINBOTHAM J N , PRUETT S B 
Published: July 2010

SUMMARYReactive nitrogen intermediates (RNI) derived from L-arginine have been implicated as important anti-bacterial agents in the control of Listeria monocytogenes by murine macrophages. However, not all evidence is consistent with this conclusion. In the present study, this issue was examined using a simple experimental system to assess the correlation between macrophage Listericidal activity and production of nitrite (a stable end product of RNI) in culture. Various levels of nitrite production were achieved by activating macrophages with interferon-gamma (IFN-γ) (20 or 500 U/ml) with or without lipopolysaccharide (LPS) (10 ng/ml) for 20 h before the Listericidal assay, and by using normal and arginine-free culture medium during the Listericidal assay. Nitrite concentration was measured for the same wells used to assess Listericidal activity. There was essentially no correlation between initial or final nitrite concentration and Listericidal activity in resident peritoneal macrophages. Significant correlations were noted between initial and final nitrite concentration and Listericidal activity in proteose peptone-elicited peritoneal macrophages. However, the correlation coefficients (0·34 and 0·52) suggested marginal biological relevance. In addition, no correlation was noted when LPS-activated macrophages were omitted from analysis. A previous study suggested that the enhanced Listericidal activity of LPS-treated macrophages could be accounted for by an enhanced rate of phagocytosis during the initial phase of the assay. These results suggest RNI are probably not the predominant bactericidal agents used by macrophages from female CD-I mice to kill L. monocytogenes. However, it remains possible that RNI are important anti-bacterial agents in highly activated (LPS-treated) macrophages, and that there are other mechanisms whereby RNI contribute to host resistance to L. monocytogenes.
Adoptive transfer of an autoimmunological labyrinthitis in the guinea pig; animal model for a sympathetic cochleolabyrinthitis
Authors: GLODDEK B , ROGOWSKI M , ARNOLD W 
Published: July 2010

SUMMARY
Sensorineural hearing loss is a common problem in the otolaryngologist's practice, with autoimmune disease of the inner ear being one possible cause. The restoration of auditory function in some patients following immunosuppressive therapy has created a desire to define and understand this disease better. Because of the lack of a well defined detection method to identify this entity clinically, this study was undertaken in order to provide an animal model for autoimmune disease of the inner ear. Previous studies with guinea pigs have demonstrated that sensitized lymphocytes from the systemic circulation migrate to the labyrinth during an immune response in the inner ear. The aim of this study was to prove the capacity of sensitized lymphocytes to transfer autoimmune inner ear disease, and to describe the resulting morphological and physiological changes. Therefore two groups of sensitized lymphocytes partially labelled with a radioactive marker from inbred guinea pigs with an immune response within the inner ear were injected into the bloodstream of naive recipient animals. Most of the labelled cells were observed in the apical turn of the experimental cochlea, while only few cells were detectable in the control cochleas. In addition, the absence of otoacoustic emissions and the loss of outer hair cells observed by electron microscopy were interpreted as a sign of damage caused by the provoked immunopathologic mechanism. The results are discussed as a possible model for a sympathetic cochleolabyrinthitis.
Neonatal injections of cyclosporin enhance autoimmune diabetes in non-obese diabetic mice
Authors: SAÏ P , SENECAT O , MARTIGNAT L , GOUIN E 
Published: July 2010

SUMMARYSince the modulation of the immune system at birth may influence the course of insulin-dependent (type 1) diabetes, we investigated whether neonatal injections of cyclosporin (CsA) to newborn non-obese diabetic (NOD) mice influence diabetes during later life. Two groups of 90 mice (45 female, 45 male) were injected intraperitoneally for the first 6 days of life with CsA (l0mg/kg per day) or with vehicle. In female NOD mice, the onset of diabetes was earlier and cumulative incidence was higher after neonatal treatment with CsA (P &lt; 0·01). The incidence of diabetes was also dramatically enhanced in male NOD mice (P &lt; 0·01), which normally display a very low disease incidence. Concomitantly, the severity of lymphocytic infiltration of the pancreatic islets was higher in female NOD mice neonatally treated by CsA (P &lt; 0·02), and to a lesser extent in males, than in control mice. After administration of CsA to newborn NOD mice, there was a reduction (P &lt; 0·01) of both CD4+CD8+ and CD4+CD8+ thymocytes, whereas the number of double positive CD4+CD8+ thymocytes was increased. Concomitantly, Thy 1–2+ cells in spleen were decreased (P &lt; 0·01), and spleen cells expressing either CD3 molecule or αβ TCR complex were diminished (P &lt; 0·01). Both CD4+ and CD8+ spleen T cells were depleted. By contrast, the low percentage of γδ TCR-expressing splenocytes was not modified. Numbers of MHC class 1+ or MHC class 2+ spleen cells were also depressed (P &lt; 0·01). After neonatal injections of CsA, spleen cells showed a reduced response to concanavalin A (Con A) (P &lt; 0·01). On the contrary, stimulation indices of splenocytes incubated with xenogeneic insulin-producing cell extracts were enhanced (P &lt; 0·03). Proliferation indices of splenocytes to self class 2 antigens, generating suppressor cell activity, during syngeneic mixed lymphocyte reaction (SMLR) were significantly reduced (P &lt; 0·01). Irradiated NOD mice were used as recipients for spleen cells from CsA -neonatally treated NOD mice. They displayed enhanced insulitis 2 weeks after transfer, and diabetes was successfully produced by 1 month after transfer in 50% of the recipients. By contrast, NOD mice which received control syngeneic spleen cells remained normoglycaemic, with only moderate islet infiltration which would be expected of NOD mice of this age. Thus, neonatal injections of CsA markedly enhance diabetes in both female and male NOD mice. The mechanisms behind the clinical effect are at least related to arrest of thymocytopoiesis at the double positive stage and to attenuation of suppressor cell activity during the completion of immune selftolerance, leading to enhancement of autoreactive T lymphocytes directed against insulin-secreting cells. This could be a useful tool for gaining insight into both the mechanisms underlying the thymic generation of autoreactive T lymphocytes against islet cells and the peripheral immunoregulatory device that controls expansion of the disease already initiated.