bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of IL-15 in HIV-1-associated hypergammaglobulinaemia
Authors: KACANI L , STOIBER H , DIERICH M P 
Published: November 2003

SUMMARY
IL-15 is a novel cytokine, produced by monocytes/macrophages, with biological activities similar to IL-2 but with no significant sequence homology. IL-15 also stimulates human B cells to proliferation and immunoglobulin secretion. We measured serum levels of IL-15 in 84 HIV-1-infected individuals at different stages of disease in reference to 41 healthy blood donors. Our results show a marked elevation of IL-15 serum levels during HIV-1 infection. Moreover, we found that this increase correlated with serum levels of IgG (r=0.376, P&lt;0.0001), and partly with serum IgM (r=0.265, P&lt;0.0015). A significant increase of IL-15 production by cultured peripheral blood mononuclear cells (PBMC) and purified monocytes in the presence of HIV-1 virus suggests that monocytes/macrophages may be a source of higher IL-15 serum levels in HIV-1-infected individuals. These findings indicate a participation of IL-15 in the hypergammaglobulinaemia frequently associated with HIV-1 infection.
Role of leucocyte adhesion molecules in aminonucleoside of puromycin (PAN)-associated interstitial nephritis
Authors: MARTÍN A , ESCUDERO E , MAMPASO F 
Published: November 2003

SUMMARY
Rats receiving a single dose (10 mg/100 g body wt) of PAN develop severe proteinuria and acute interstitial nephritis. To investigate the mechanisms involved in interstitial leucocyte accumulation, we examined the expression of adhesion molecules on kidney tissue sections as well as on endothelial cell cultures. We also performed in vivo treatments with antibodies against adhesion molecules. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) was found on day 7 of the disease, when interstitial nephritis was first detected. Also, rat endothelial cells in culture showed maximal expression of ICAM-1 in the presence of 10−9–10−11 m PAN. Adhesion of peripheral blood mononuclear cells (PBMC) on kidney sections from PAN-treated rats was highest on day 7 (3·05±0·7 (mean±s.e.m.); controls 0·75±0·5). Such increased adhesion was notably blocked after PAN-treated rat kidney sections were incubated with anti-ICAM-1 MoAb (0·9±0·4). In addition, adhesiveness of PBMC to PAN-stimulated endothelial cells in culture was enhanced (25±2·5%; non-stimulated cells 13±3·1%). The addition of specific MoAbs against ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) produced a high blockage of adhesiveness induced by exposure to PAN (inhibition 58±3%; non-stimulated cells 40±7%). Simultaneous administration to PAN-treated rats of anti-LFA-1 and anti-ICAM-1 MoAbs reduced the number of interstitial cells by 70% compared with the 30% of reduction obtained when anti-very late antigen-4 (VLA-4) MoAb and anti-vascular cell adhesion molecule-1 (VCAM-1) antibodies were used. Our results suggest that the LFA-1/ICAM-1 pathway plays a principal role in the interstitial nephritis occurring in rats with PAN-nephrosis.
Rapid cytotoxicity of human B lymphocytes induced by VH4-34 (VH4.21) gene-encoded monoclonal antibodies, II
Authors: BHAT N M , BIEBER M M , HSU F J , CHAPMAN C J , SPELLERBERG M , STEVENSON F K , TENG N N H 
Published: November 2003

SUMMARY
We have previously described complement-independent killing of human B lymphocytes by two IgM MoAbs derived from the VH4-34 (VH4.21) gene. Analysis of 17 independently derived VH4-34-encoded MoAbs shows that B cell toxicity is not limited to the two described MoAbs, but is a general property shared by a subset of MoAbs derived from the VH4-34 gene. As observed by two independent microscopy techniques, giant membrane pores were formed on target B cells within 10–15 min of exposure to cytotoxic VH4-34-derived MoAbs. Toxicity by individual MoAb correlated directly to its B cell binding intensity measured by FACS, i.e. stronger the binding greater the killing. Sequence analysis showed that VH region in germ-line or in near germ-line configuration was necessary but not sufficient for B cell binding. In addition, a particular sequence motif enriched in basic amino acids in the CDR3 may be required to supplement the reactivity mediated by the VH region of the MoAb molecule. VH4-34-encoded antibodies that fulfil the above sequence requirements have cold agglutinin activity towards the i antigen of cord erythrocytes. In vivo, such anti-i/anti-B cell antibodies are rarely detected in healthy adults, but serum levels are dramatically elevated in selective pathological conditions, such as systemic lupus erythematosus and infectious mononucleosis. This strict regulation may be related to the novel and rapid mechanism of human B cell toxicity demonstrated by antibodies encoded by a single human VH gene.
Down-regulatory role of surface CD4 molecules on autoreactive helper T cells during B cell activation
Authors: AIZAWA K , HAMANO T , IWASAKI T , KAKISHITA E 
Published: November 2003

SUMMARY
MS202 is an IL-2-dependent Th2 clone reactive to auto-MHC class II antigens as previously reported. It expresses CD4, TCR-αβ, Thy 1.2 and H-2k on the cell membrane, as well as CD40 ligand. In order to investigate a functional role of surface CD4 molecules on Th2 cells during B cell activation, we attempted to establish a CD4− variant subclone derived from the CD4+ MS202, and its effect on B cell activation was examined. Briefly, MS202 was incubated with ethyl methanesulfonate to induce mutation followed by extensive treatment with anti-CD4 MoAb and complement. MS1.1.2, a representative subclone of resulting cell lines, was shown to lack CD4 molecules on the cell membrane, although it possessed almost the same amount of surface molecules other than CD4 compared with the original MS202 by analysis with flow cytometry. Interestingly, MS1.1.2 induced the maturation of B cells into IgM-producing cells more potently than MS202. This differentiative effect was markedly greater on activated B cells than resting B cells; each population was prepared from splenic B cells by a gradient separation method, but after treatment with anti-IgM antibodies, resting B cells responded to MS1.1.2, resulting in the secretion of a comparative amount of IgM. Furthermore, the effect of MS1.1.2 on DNA synthesis of activated B cells was much greater than that of MS202. The present results suggest that surface CD4 molecules on Th2 cells may not be substantially required for B cell activation, and rather mediate a down-regulation signal to B cells.
Synergistic mechanisms by which sirolimus and cyclosporin inhibit rat heart and kidney allograft rejection
Authors: STEPKOWSKI S M , TIAN L , NAPOLI K L , GHOBRIAL R , WANG M E , CHOU T C , KAHAN B D 
Published: November 2003

SUMMARY
The studies presented herein examined the mechanism(s) whereby sirolimus (SRL) and cyclosporin (CsA) act synergistically to block allograft rejection. Combination index (CI=1 reflects additive, CI&lt;1 antagonistic, and CI&lt;1 synergistic, effects) analysis documented potent synergism between SRL and CsA to block allograft rejection. Combinations of the two drugs produced synergistic prolongation of heart (CI=0.001–0.2) or kidney (CI=0.03–0.5) allograft survival at SRL/CsA ratios ranging from 1:12.5 to 1:200. Pharmacokinetic analysis of the individual drugs showed that CsA does not affect the blood levels of SRL, and SRL mildly increases the levels of CsA in SRL/CsA-treated rats. Quantitative polymerase chain reaction analysis was used to document that both subtherapeutic (1.0 mg/kg) and therapeutic (2.0 or 4.0 mg/kg) CsA doses inhibited the expression of interferon-gamma (IFN-γ) (P&lt;0.03) and IL-2 (P&lt;0.003) mRNA produced by T helper (Th) 1 cells, as well as IL-10 (P&lt;0.001), but not IL-4 (NS) mRNA produced by Th2 cells. Contrariwise, all tested SRL doses (0.02, 0.04 or 0.08 mg/kg) did not affect cytokine mRNA expression. However, heart allografts from rat recipients treated with synergistic SRL/CsA doses displayed reduced levels of IFN-γ (P&lt;0.01), IL-2 (P&lt;0.001) and IL-10 (P&lt;0.001) mRNA. Thus, because subtherapeutic doses of CsA reduce Th1/Th2 activity, thereby facilitating the inhibition of signal transduction by low does of SRL, the two agents act synergistically to inhibit allograft rejection.
Production of interleukins 10 and 12 by peripheral blood mononuclear cells (PBMC) in chronic hepatitis C virus (HCV) infection
Authors: KAKUMU S , OKUMARA A , ISHIKAWA T , IWATA K , YANO M , YOSHIOKA K 
Published: November 2003

SUMMARY
We previously reported that interferon-gamma (IFN-γ) production by PBMC in response to HCV core protein was increased in patients with type C chronic liver disease. To understand better the pathophysiology of this disease, we evaluated production of IL-10 and IL-12 by PBMC from 41 patients with chronic HCV infection, including asymptomatic HCV carriers with persistently normal serum ALT values. IL-10 is known to inhibit many effector functions of the immune system, suppressing Th1-type cell development, while IL-12 stimulates differentiation of Th1-type cells, facilitating cell-mediated immunity. IL-10 production was determined by culturing lymphocytes with concanavalin A (Con A), while IL-12 was produced by monocytes in the presence of Staphylococcus aureus Cowan 1 (SAC) with or without recombinant HCV core protein, respectively. The cytokine levels in culture supernatants were measured by ELISA. Spontaneous IL-10 production was greater in patients with chronic hepatitis (CH) (229±119 pg/ml, P&lt;0·01) and liver cirrhosis (LC) (185±88 pg/ml, P&lt;0·05) than in controls (119±27 pg/ml), while it was decreased during IFN treatment (70±25 pg/ml). Both HCV core protein and Con A enhanced IL-10 production by cells from HCV-infected patients. IL-12 was not detectable in medium alone cultures, and SAC-induced IL-12 production did not differ between various patient groups and controls. Simultaneous addition of HCV protein resulted in an increase of IL-12 production in chronic liver disease compared with SAC-alone cultures. Addition of IL-10 to the cultures equally suppressed IFN-γ production for both controls and patient groups, but the enhancing effect of IL-12 on IFN-γ production was significantly less in LC than in controls and other patient groups. The findings suggest that secretion of IL-10/IL-12 by cells from control individuals and various patient groups may be different, and that the cytokines might show different effects on IFN-γ production by some cells.
Induction of oral tolerance with effects on numbers of IgE-carrying mast cells and on bystander suppression in young rats
Authors: DAHLMAN-HÖGLUND A , HANSON L Å , AHLSTEDT S 
Published: November 2003

SUMMARY
The presence of IgE+ mast cells in the small intestine, bystander suppression of DTH and antibody responses to human serum albumin (HSA) were studied in young rats, made tolerant to ovalbumin (OA) by feeding an OA-containing diet for 1–4 weeks starting from weaning, and in sensitized control rats. One week after finishing the OA diet, both groups of rats were immunized with a mixture of OA and HSA in Freund's complete adjuvant (FCA) at one site on the back. The animals were then colonized for 5 days with a genetically manipulated Escherichia coli producing OA. Immunohistochemical staining of the small intestine of the rats fed the OA diet for 4 weeks showed significantly fewer IgE+ mast cells in the lamina propria, a lower level of MHC class antigen was found in the epithelial cells and in the lamina propria, and the villus crypt depth was also significantly less in tolerant compared with sensitized rats (P&lt;0.003, 0.007, 0.003, respectively). Sensitized rats showed a mild diarrhoea during the colonization in contrast to tolerant rats. All rats fed OA showed a significantly reduced IgE anti-OA antibody and DTH response to OA before colonization compared with the sensitized rats. Bystander suppression of IgG and IgE anti-HSA antibody responses was also seen, but only in the rats fed OA for either 1 or 4 weeks. Rats fed the OA-containing diet for 1, 3, or 4 weeks showed bystander suppression of the DTH response to HSA. After colonization with E. coli producing OA, rats tolerant to OA after either 1 or 4 weeks on an OA diet maintained tolerance to OA and bystander suppression HSA. These results suggest that oral tolerance to OA down-regulates signs of local inflammatory response by IgE, IgG antibody and T cell responses to OA, but also provides bystander suppression to an unrelated antigen, HSA.
Antigen presentation by common variable immunodeficiency (CVID) B cells and monocytes is unimpaired
Authors: THON V , EGGENBAUER H , WOLF H M , FISCHER M B , LITZMAN J , LOKAJ J , EIBL M M 
Published: November 2003

SUMMARY
CVID is a primary immunodeficiency syndrome comprising a heterogeneous group of patients with hypogammaglobulinaemia and defective formation of specific antibodies. Previous studies demonstrated defective T cell responsiveness to antigen in a major subgroup of patients. In the present study we investigated the capacity of peripheral blood monocytes and Epstein–Barr virus (EBV)-transformed B cell lines from seven patients with CVID, including two patients expressing an extended MHC haplotype described to be associated with CVID, to present antigen (Tet. Tox.) to CD4+ antigen-specific T cell lines from healthy controls. The results presented show an unimpaired capacity of peripheral blood monocytes to present antigen in all patients studied. In addition, the present study demonstrates for the first time that CVID B cells function normally as antigen-presenting cells (APC). These findings indicate that expression of a certain MHC phenotype in CVID is not associated with a defect in the presentation of recall antigen by monocytes and B cells. Based on these studies, uptake, processing and re-expression of recall antigen in association with MHC class II molecules on the APC surface are functional and there is no indication for structural abnormalities of the MHC class II molecules expressed by the patients studied that could be essential for their function in antigen binding and presentation.
Lack of specific antibody response in common variable immunodeficiency (CVID) associated with failure in production of antigen-specific memory T cells
Authors: KONDRATENKO I , AMLOT P L , WEBSTER A D B , FARRANT J 
Published: November 2003

SUMMARY
Several T cell defects have been described in the antibody deficiency disease, CVID, but there have been few data on the generation of responses of specific T cell populations to primary neoantigens. We have now used immunization with the neoantigens, keyhole limpet haemocyanin (KLH) and DNP-Ficoll, to evaluate immune responses in CVID patients and normal donors. B and T cell responses were examined 2 and 4 weeks post-immunization. Sera were examined for IgM and IgG anti-KLH responses by ELISA and for anti-DNP-Ficoll activity by haemagglutination. The frequency of KLH-responsive T cells was measured by DNA synthesis in a limiting dilution culture system. Low density cells enriched for dendritic cells were pulsed with KLH and cultured with different numbers of autologous T cells. T cells from normal donors and from patients showed a low frequency of antigen-specific precursor T cells (≤1:200 000). After KLH immunization the frequency increased in normal donors (1:60 000 and 1:30 000 at 2 and 4 weeks, respectively), while in CVID patients it did not change from the pre-immunization level. The defect may extend to a dysfunction of antigen-specific cells, rather than being solely due to the reduced numbers of cells, since mean responses of ‘positive’ wells were also reduced. The serum-specific antibody response paralleled the T cell data, in that all normal donors but none of the CVID patients generated IgG KLH-specific antibodies. CVID patients did produce IgM antibodies against the T-independent DNP-Ficoll, but at a lower level than normal controls. These data show that both T and B cells from CVID patients have defective responses to specific antigen, implicating both lineages in the antibody deficiency.
Characterization of HIV-related periodontitis in AIDS patients: HIV-infected macrophage exudate in gingival crevicular fluid as a hallmark of distinctive etiology
Authors: SUZUKI T , TAI H , YOSHIE H , JEANNEL D , FOURNIER S , DUPONT B , DE THÉ G , HARA K 
Published: November 2003

SUMMARY
In an attempt to clarify the immunobiological events featuring periodontitis lesions of AIDS patients in the late stage of the disease, peripheral blood (PB) and gingival crevicular fluid (GCF) leucocytes from periodontitis lesions of 23 late-stage AIDS patients were analysed by three-colour flow cytometry for detection and identification of intracytoplasmic p24+ cell fractions. The cells were reacted with CD14 and CD68 for mononuclear phagocytes or with CD4 and CD14 for Th cells, then with anti-p24 MoAb. To detect HIV proviral sequences and intracellular p24 RNA sequences, genomic DNA and cellular RNA from leucocytes were extracted for semi-nested polymerase chain reaction (PCR) amplification. CD68+/p24+ and CD14+/CD68+/p24+ fractions were larger in GCF than in PB (P &lt; 0·0001; P &lt; 0·003). CD14+/p24+ fraction was lower in GCF than in PB (P &lt; 0·05). The fluorescence intensities (FI) for intracellular p24 in CD68+ and CD14+/CD68+ cells were higher in GCF than in PB (P &lt; 0·003; P &lt; 0·02), whereas those of CD14+ macrophages did not differ. The p24 FI of CD68+ macrophages in GCF correlated with CD4+ lymphocyte counts in PB (P &lt; 0·005). p24 FI levels of CD14+ monocytes in GCF and PB significantly correlated (P &lt; 0·02), whereas that of CD68+ macrophages did not. PCR and reverse transcriptase (RT)-PCR of cellular DNA and RNA yielded positive signals, demonstrating viral integration and production in GCF leucocytes. These results show that periodontitis lesions in AIDS patients can be characterized by a rapid macrophage turnover, and these HIV-infected macrophage exudates in GCF may be considered as a within-mouth source of virus.
Decreased expression of 20-kD homologous restriction factor (HRF20, CD59) on T lymphocytes in Epstein–Barr virus (EBV)-induced infectious mononucleosis
Authors: KAWANO M , TSUNODA S , KONI I , MABUCHI H , MURAMOTO H , YACHIE A , SEKI H 
Published: November 2003

SUMMARY
HRF20 (CD59) is one of the membrane-associated complement regulatory proteins. The characteristic function of CD59 is to prevent membrane attack complex (MAC) formation on the cell surface and to protect the cell from complement-mediated cell lysis. We examined the expression of CD59 antigen on T cell subpopulations in patients with acute infectious mononucleosis (IM) and analysed the relationship between the amount of CD59 expression and activation-induced cell death of mature T cells with apoptosis. Decreased expression of CD59 on CD8+ T cells, especially on CD45RO+ and HLA-DR+ activated T cells, was marked in acute IM patients. In contrast, activated CD4+ T cells from IM patients expressed as much CD59 antigen as CD4+ T cells from healthy volunteers. After incubation-induced cell death, viable CD8+ T cells showed normal amounts of CD59 antigen on their surface. CD59dim CD8+ T cells were more susceptible to apoptosis than CD59bright CD8+ T cells. These findings suggest that decreased expression of CD59 on CD8+ T cells may discriminate the susceptibility of activated CD8+ T cells to activation-induced cell death in IM.
Characteristics of the pituitary gland in elderly subjects from magnetic resonance images: relationship to pituitary hormone secretion
Authors: Terano Takashi , Seya Akira , Tamura Yasushi , Yoshida Sho , Hirayama Toshio 
Published: November 2003

OBJECTIVE Physiological changes in the pituitary gland with age have not been fully evaluated. The aim of this study was to clarify the morphological characteristics of the pituitary gland by magnetic resonance imaging(MRI) in elderly subjects and to relate them to pituitary hormone secretion. DESIGN AND PATIENTS We investigated the pituitary MRI in 59 elderly (15 males, 44 females; median 82 years) and 41 young (13 males, 28 females; median 34 years) healthy subjects. RESULTS Pituitary height, width and volume in the elderly subjects were less than those in the young subjects. Empty sella was more frequently observed in the elderly subjects (19%), especially women, than in the young ones. However, no relation was observed between the pituitary size or volume and basal levels of anterior pituitary hormones. Posterior pituitary bright signal(PBS) on T1‐weighted MRI, which is thought to reflect its storage of the neurophysin‐peptide complex, was not detected in 29% of the elderly subjects while it could be detected in all the young subjects. None of the elderly subjects showed clinical signs or symptoms of diabetes insipidus. Fasting plasma osmolarity and AVP in the elderly subjects were significantly higher than in the young subjects. Moreover, plasma AVP was significantly higher in the elderly subjects without the PBS than in those with the PBS. CONCLUSIONS It is suggested that the excessive release of AVP from the posterior pituitary as a result of persistently raised plasma osmolality in the elderly subjects may lead to depletion of the neurosecretory granules in the posterior pituitary gland and may result in disappearance of the posterior pituitary bright signal on T1‐weighted MRI. As these morphological changes might relate to the normal physiological occurrence of ageing, we should be cautious in evaluating MRI of the pituitary gland in elderly subjects.
A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism
Authors: Page S. R. , Sheard C. E. , Herbert M. , Hopton M. , Jeffcoate W. J. 
Published: November 2003

OBJECTIVE The optimal dosage regimen for carbimazole (CBZ) in the treatment of hyperthyroidism remains uncertain, despite clinical use of the drug for approximately fifty years. We have compared the early clinical and biochemical responses to 20 or 40 mg/day of CBZ given as initial treatment for hyperthyroidism. DESIGN Prospective open multicentre trial. PATIENTS Sixty‐three patients presenting with hyperthyroidism. MEASUREMENTS Serum total and free thyroid hormones, serum TSH and SHBG were measured at baseline and at 4 and 10 weeks after start of therapy. Weight, pulse and a symptom questionnaire were also monitored at 6 and 12 weeks. RESULTS Patients randomized to a starting dose of 40 mg/day CBZ had lower total (98 ± 10 it 158 ± 11 nmol/l, P < 0.001) and free T4 (19.4 ± 2.6 vs 35.2 ± 3.7 pmol/l, P < 0.001) and total (2.6 ± 0.3 vs 4.3 ± 0.4 nmol/l, P < 0.001 and free T3 (8.3 ± 1.0 vs 13.7 ± 1.2 pmol/l, P < 0.01) at 4 weeks than those receiving 20 mg/day. Clinical responses at 6 and 12 weeks (weight, pulse, symptom score) and SHBG concentrations were similar. Drug‐related hypothyroidism was less likely to occur at 4 and 10 weeks in those patient who initially received 20 mg CBZ/day, but this dose was less effective at controlling hyperthyroidism in those with more severe hyperthyroidism with baseline TT4 > 260 nmol/l. CONCLUSIONS In treating hyperthyroidism, 20 mg/day carbimazole is effective, convenient and has a lower risk than 40 mg/day of iatrogenic hypothyroidism in patients with mild or moderate hyperthyroidism. Higher doses are required for those with severe hyperthyroidism.