bluuebunny/crossref_metadata_2025_split huggingface dataset:
Passive transfer of flt-3L-derived dendritic cells delays diabetes development in NOD mice and associates with early production of interleukin (IL)-4 and IL-10 in the spleen of recipient mice
Authors: MORIN J , FAIDEAU B , GAGNERAULT M-C , LEPAULT F , BOITARD C , BOUDALY S 
Published: December 2004

SUMMARYCD11c+/CD11b+dendritic cells (DC) with high levels of major histocompatibility complex (MHC) class II and co-stimulatory molecules have been derived from spleen cells cultured with granulocyte-macrophage colony stimulating factor (GM-CSF) + flt-3L + interleukin (IL)-6 (flt-3L-DC). Investigating in vivo the function of DC in non-obese diabetic mice (NOD), we showed that a single injection of this in vitro-derived subset of DC prevents the development of diabetes into prediabetic female mice. In contrast, DC derived from bone marrow cells cultured with GM-CSF + IL-4 [bone marrow (BM)-DC] induced no protection. Moreover, protection against diabetes following injection of flt-3L-DC was associated with IL-4 and IL-10 production in the spleen and the pancreatic lymph nodes of recipient mice, indicating that this DC population is able to polarize the immune response towards a Th2 pathway. As we shown previously, NOD BM-DC exhibit an enhanced capacity to produce IL-12p70 in response to lipopolysaccharide (LPS) and anti-CD40 stimulation compared to BM-DC from control mice. In contrast, NOD flt-3L-DC, as their control mouse counterpart, produced no IL-12p70 to these stimuli. Our findings show that a subset of DC, characterized by a mature phenotype and the absence of IL-12p70 production can be derived from NOD mouse spleen favouring IL-4 and IL-10 regulatory responses and protection from diabetes development.
Functional responses of human neonatal B lymphocytes to antigen receptor cross-linking and CpG DNA
Authors: TASKER L , MARSHALL-CLARKE S 
Published: December 2004

SUMMARYHuman neonates are immunologically immature and consequently are highly susceptible to infection. The cellular basis for the dysfunctional immune responses of neonates is not clear, but is likely to reflect the immaturity of both B and T cell populations. Here we have examined the ability of human cord blood B cells to respond to antigen receptor cross-linking and also to CpG containing oligodeoxynucleotides (ODN), and compared their responses with those of adult peripheral blood B cells. Antigen receptor cross-linking with soluble F(ab′)2 anti-IgM antibodies, induced HLA-DR and CD86 up-regulation and proliferation to a similar extent in adult and cord blood B cells. Both interleukin (IL)-2 and IL-4 co-stimulated anti-IgM-induced proliferation, but cord blood B cells were less sensitive than adult B cells to the co-stimulatory effects of IL-2. Antigen receptor cross-linking induced secretion of the chemokines macrophage inflammatory protein-1α (MIP-1α) and MIP-1β in adult and cord blood B cells, and secretion was enhanced by IL-2 or IL-4. CpG-ODN induced up-regulation of HLA-DR and CD86 expression and proliferation of adult and cord blood B cells, and anti-IgM and CPG-ODN synergized in the induction of proliferation. CpG-ODN also induced MIP-1α and MIP-1α secretion in adult and cord blood B cells. In addition to functional studies we examined the expression of CD62L (l-selectin), CCR7 and CXCR5. Our data show that surface expression of CD62L and CCR7 is lower on cord blood B cells than on adult B cells, suggesting that human cord blood B cells may exhibit homing defects.
Leptin stimulates the oxidative burst in control monocytes but attenuates the oxidative burst in monocytes from HIV-infected patients
Authors: SÁNCHEZ-POZO C , RODRIGUEZ-BAÑO J , DOMÍNGUEZ-CASTELLANO A , MUNIAIN M A , GOBERNA R , SÁNCHEZ-MARGALET V 
Published: December 2004

SUMMARYLeptin, the 16 kDa product of the ob gene, is a an adipocyte-secreted hormone that centrally regulates weight. However, the physiological role of leptin is not limited to the regulation of food intake and energy expenditure, and leptin has a variety of effects in peripheral tissues, such as a regulatory role modulating the immune system. Thus, leptin receptor is expressed in human peripheral blood mononuclear cells, mediating the leptin stimulation of proliferation and activation, the production of proinflammatory cytokines from cultured monocytes, and the prevention of apoptotic death in serum-deprived monocytes. Because leptin can stimulate monocytes and the production of reactive oxygen species (ROS) are the result of monocyte activation, we investigated the effect of leptin on ROS production by human monocytes in vitro. Oxidative burst was measured by oxidation of the redox-sensitive dye 2′,7′-dichlorofluorescein diacetate, and analysed by flow cytometry. We have found that stimulation with leptin produces oxygen radical formation by monocytes. This effect is dependent on the dose and maximal response is achieved at 10 nm leptin. Because HIV infection induces the production of ROS, we next investigated the effect of leptin on ROS production in monocytes from HIV-positive (HIV+) subjects. We have also found that monocytes from HIV+ subjects spontaneously produced increased amounts of free radicals. In contrast, leptin stimulation of monocytes from these patients partially inhibited the production of ROS. This effect of leptin was also dependent on the dose and maximal effect was achieved at 10 nm. The effect of leptin stimulating the production of ROS is consistent with the proinflammatory role in the immune system. On the other hand, the inhibitory effect on monocytes from HIV+ subjects may be explained by the attenuation of the oxidative burst by a delayed activation of monocytes in a hyperinflammatory state.
Comparativein vitrostudy of the immunomodulatory activity of humanized and chimeric anti-CD25 monoclonal antibodies
Authors: KIRCHER B , LÄTZER K , GASTL G , NACHBAUR D 
Published: December 2004

SUMMARYHumanized or chimeric monoclonal antibodies (MoAbs) directed against the interleukin-2 (IL-2) receptor α-chain, CD25, are promising immunosuppressive agents due to improved pharmacokinetic profiles and less toxicity. These MoAbs have been used effectively in preventing and/or treating rejection in solid organ transplantation and are currently under investigation for prevention/treatment of graft-versus-host disease (GvHD) in stem cell transplantation. We analysed the in vitro activities of the chimeric anti-CD25 MoAb basiliximab and the humanized anti-CD25 MoAb daclizumab in various test systems for alloimmune response and T cell activation in comparison to cyclosporin A (CsA) and prednisolone. Anti-CD3- and alloantigen-induced T cell proliferation were decreased significantly by the anti-CD25 MoAbs in a dose-dependent fashion. At a concentration of 10 ng/ml daclizumab and CsA synergistically decreased T cell proliferation of mixed lymphocyte cultures, whereas basiliximab showed only subadditive activity. Simultaneous addition of the anti-CD25 MoAbs and prednisolone did not result in combined activity. Addition of exogenous IL-2 completely overcame the inhibitory effect on T cell proliferation of both anti-CD25 MoAbs, but not that of CsA and prednisolone. Anti-CD25 MoAbs inhibited the generation of antigen-specific cytotoxic T lymphocytes in a limiting dilution assay, whereas they showed no effect on the cytolytic activity of established antigen-specific T cell clones. This in vitro study demonstrates strong immunosuppressive activity by both chimeric and humanized MoAbs against CD25. The combined activity with CsA justifies their early use for prevention rather than treatment of GvHD.
Association of interleukin 1 gene family polymorphisms with duodenal ulcer disease
Authors: GARCIA-GONZALEZ M A , LANAS A , SAVELKOUL P H M , SANTOLARIA S , BENITO R , CRUSIUS J B A , PEÑA A S 
Published: December 2004

SUMMARY
Cytokine genes taking part in the immunological response to Helicobacter pylori infection are good candidates to study for genetic predisposition to duodenal ulcer disease (DU). Among cytokines, interleukin (IL)-1β and its natural specific inhibitor, the interleukin-1 receptor antagonist, are cytokines that play a key role in regulating gastric acid secretion and modulating the immune response in the gastrointestinal mucosa. We aimed to investigate whether polymorphisms in the IL-1B and IL-1RN genes are involved in the susceptibility to duodenal ulcer. DNA from 131 unrelated Spanish Caucasian patients with DU and 105 ethnically matched healthy controls was typed for the IL-1B-511, IL-1B-31, and IL-1B + 3954 gene polymorphisms, and the VNTR polymorphism in intron 2 of the IL-1RN gene by polymerase chain reaction (PCR)-based methods and TaqMan assays. H. pylori status and non-steroidal anti-inflammatory drugs (NSAIDs) use was determined in all patients and controls. Logistic regression analysis identified H. pylori infection (OR: 9·74; 95%CI = 3·53–26·89) and NSAIDs use (OR: 8·82; 95%CI = 3·51–22·17) as independent risk factors for DU. In addition, the simultaneous carriage of IL-1RN*2, IL-1B-511*C, IL-1B-31*T and IL-1B + 3954*C alleles was a genetic risk factor for DU in patients with H. pylori infection (OR: 3·22; 95%CI = 1·09–9·47). No significant differences in IL-1RN and IL-1B genotypes were found when patients were categorized according to gender, age of onset, smoking habit, NSAIDs use, type of complication and positive family history. Our results provide further evidence that host genetic factors play a key role in the pathogenesis of duodenal ulcer.
Identical twins discordant for multiple sclerosis have a shift in their T-cell receptor repertoires
Authors: HAEGERT D G , GALUTIRA D , MURRAY T J , O'CONNOR P , GADAG V 
Published: December 2004

SUMMARYCD4 T-cells have an important role in the autoimmune response in multiple sclerosis (MS). We investigate the possibility that a shift occurs in the T-cell receptor (TR) repertoire of identical twins discordant for MS. We compare the CDR3 spectratype distributions of 24 different TR V beta (TRBV) segments in naïve CD4 T-cells from discordant MS twins and from healthy identical twins. We also compare the CDR3 spectratype distributions in unrelated healthy pairs, formed by combining members of different healthy twins, with the CDR3 spectratype distributions in unrelated pairs of MS patients and in unrelated pairs of their apparently healthy cotwins, formed by combining members of different discordant twins. We use the correlation coefficient (r-value) as a measure of similarity of CDR3 spectratypes in each pair, and we test for the significance of the difference between r-values from the different pairs. We observe that the r-value for the CDR3 spectratype distributions among discordant twins differs significantly from the corresponding r-value for the healthy twins for two TRBV segments. Further, the r-values, for both the unrelated MS patient pairs and the unrelated pairs of their apparently healthy cotwins, differ significantly from the r-values for healthy unrelated pairs of individuals. We conclude that both the MS patients and their apparently healthy cotwins have shifts in their CDR3 repertoires. Because we study naïve CD4 T-cells, we postulate that CDR3 repertoire shifts precede MS and predispose to MS, but are unlikely to be sufficient to cause MS.
Loss of the CD56hiCD16− NK cell subset and NK cell interferon-γproduction during antiretroviral therapy for HIV-1: partial recovery by human growth hormone
Authors: GOODIER M R , IMAMI N , MOYLE G , GAZZARD B , GOTCH F 
Published: December 2004

SUMMARYPrevious studies have shown that human natural killer (NK) cells are lost from the periphery and are functionally suppressed during HIV-1 infection, and that the administration of highly active antiretroviral therapy (HAART) results in a recovery of NK cell numbers in HIV-1-infected individuals. However, despite this recovery, interleukin (IL)-2 + IL-12-driven interferon (IFN)-γ production by NK cells has been shown to remain suppressed after HAART. Here we show that the innate immune factor IL-15 in combination with IL-12 is also unable to recover NK cell IFN-γ production in HAART-treated individuals. Furthermore, we also demonstrate an imbalance in the distribution of CD56loCD16hi and CD56hiCD16– NK subsets after successful HAART, CD56hiCD16– cells being reduced substantially in HIV-1 patients on HAART. Treatment of patients with combined human growth hormone and antiretroviral therapy resulted in further enhancement in the absolute numbers and the proportion of NK cells in some individuals in the absence of parallel effects on CD4+ T cells. Furthermore, in these individuals HAART with growth hormone resulted in an enhancement of cytokine-driven NK cell activation and IFN-γ production compared to the HAART-only baseline.
Adipokine levels in Cushing's syndrome; elevated resistin levels in female patients with Cushing's syndrome
Authors: Krsek Michal , Silha Josef V. , Jezková Jana , Hána Václav , Marek Josef , Weiss Vladimír , Stepán Jan J. , Murphy Liam J. 
Published: December 2004

Summarybackground  Cushing's syndrome (CS) is associated with central adiposity, insulin resistance and impaired glucose homeostasis. Adipose tissue is thought to regulates glucose homeostasis via circulating adipokines, such as resistin, leptin and adiponectin, although their role in the insulin resistance associated with CS has not been established.design  We examined the relationship between insulin resistance and adipokine levels in CS patients. We compared plasma levels of resistin, leptin and adiponectin in 10 women and four men patients with CS, with 14 health subjects matched for age, gender and body mass index. A subgroup of three women and four men with pituitary‐dependent CS were re‐examined at least 9 months after curative surgery.results  CS patients had significantly more truncal fat and less lean body mass as assessed by DEXA compared to control subjects. Total cholesterol, triglycerides and insulin resistance, as calculated using the homeostasis model assessment of insulin resistance (HOMA‐R), was significantly increased in CS patients. Of the adipokines measured, only resistin was significantly different between female CS patients and female control subjects (5·05 ± 0·56 vs. 2·91 ± 0·39 µg/l, P = 0·015). Curative surgery significantly reduced total body fat and truncal fat, leptin, total and low‐density lipoprotien (LDL) cholesterol, glucose and HOMA‐R. A reduction in both resistin and adiponectin was also observed but the differences between pre‐ and post‐treatment levels did not achieve statistical significance.conclusion  Here we report for the first time that resistin levels are significantly elevated in CS patients and may be important in the insulin resistance associated with glucocorticoid excess.
The first homozygous mutation (S226I) in the highly‐conserved WSXWS‐like motif of the GH receptor causing Laron syndrome: supression of GH secretion by GnRH analogue therapy not restored by dihydrotestosterone administration
Authors: Jorge Alexander A. L. , Souza Silvia C. A. L. , Arnhold Ivo J. P. , Mendonca Berenice B. 
Published: December 2004

Summaryobjective  The study describes for the first time, a homozygous mutation in the WSXWS‐like motif of the human GH receptor (GHR) in a patient with Laron syndrome and describe laboratory data during treatment with GnRHa to suppress puberty and dihydrotestosterone (DHT).patients  A 16‐year‐old boy at Tanner puberty stage 2 with Laron syndrome was born SGA to consanguineous parents, presented severe growth retardation, obesity and micropenis.methods and measurements  GHR coding region was sequenced. GH, GHBP, IGF‐I and IGFBP‐3 were determined before, during and after GnRHa and DHT treatment.results  A homozygous mutation in exon 7, replacing serine by isoleucine in codon 226 was identified. S226 is the last serine belonging to the WSXWS‐like motif in GHR. No specific effect of S226I mutation in heterozygous state was observed. Laboratory data at the prepubertal age showed markedly high GH, low GHBP, IGF‐I and IGFBP‐3 levels. Re‐evaluation at pubertal age showed normal basal serum IGFBP‐3 levels and low but near normal IGF‐I levels. We also noticed a sustained decrease in GH, IGF‐I and IGFBP‐3 levels after blocking puberty, which was not affected by short‐ and long‐term DHT treatment. Pubertal hormonal profile was re‐established after the GnRHa therapy was discontinued to allow the reactivation of the gonadal axis.conclusion  The homozygous mutation S226I in WSXWS‐like motif of GHR causes GH insensitivity. The decrease in IGF‐I and IGFBP‐3 levels after GnRHa therapy, which was not reversed with DHT administration, suggests that sex steroids have, through oestradiol, a GH‐independent action on IGF‐I and IGFBP‐3 levels. A direct effect of GnRHa on GH secretion cannot be excluded.
Growth hormone replacement in adults and bone mineral density: a systematic review and meta‐analysis
Authors: Davidson Peter , Milne Ruairidh , Chase Deborah , Cooper Cyrus 
Published: December 2004

Summarybackground  The effect of GH replacement on bone mineral density (BMD) in adults with GH deficiency (GHD) is uncertain. We carried out a systematic review of randomized trials that compared GH to no active treatment, with BMD as an outcome.methods  We searched electronic databases to identify articles, abstracts and conference proceedings to March 2002. We also checked reference lists in included studies and expert reviews. Two reviewers independently extracted the data on study design and change in BMD. The results of individual trials were combined by fixed effects model meta‐analysis using weighted mean difference (WMD) of change in BMD at the lumbar spine (our primary outcome) and other sites.findings  Eighteen trials that included 700 patients met the inclusion criteria. Maximum follow‐up was for 12 weeks (1 trial), 6 months (14 trials), 12 months (1 trial), 18 months (1 trial) and 24 months (1 trial). Reporting quality of both study design and results was poor. Ten trials (458 subjects) were included in the meta‐analysis. We excluded those eight trials from which sufficient data could not be extracted. We found a mean change in BMD, at the lumbar spine with GH treatment, of 0·01 g/cm2 after 6 and 12 months, 0·02 g/cm2 after 18 months and 0·03 g/cm2 after 24 months. Statistical significance at the 0·05 level was just achieved at 6 and 12 months but was significant at 18 and 24 months. These changes are small and may be influenced by bias.conclusion  There is evidence of a small effect of GH replacement on bone mineral density in adults with GH deficiency. The clinical importance of this is uncertain.
Serum paraoxonase activity before and after treatment of thyrotoxicosis
Authors: Raiszadeh Farbod , Solati Mehrdad , Etemadi Arash , Azizi Fereidoun 
Published: December 2004

Summaryobjective  Antioxidant effects of paraoxonase, a high density lipoprotein (HDL)‐associated enzyme that inhibits low density lipoprotein cholesterol (LDL‐C) oxidation in human serum, have been reported. Patients with thyroid dysfunction are more susceptible to oxidative stress, and may show enhanced LDL‐C oxidation. The purpose of this study was to evaluate serum paraoxonase activity in patients with hyperthyroidism before and after treatment with methimazole (MMI).design and patients  Twenty‐four hyperthyroid patients (15 women and nine men, aged 43·0 ± 12·9 years) and 23 age‐ and sex‐matched healthy controls were studied. Serum paraoxonase activity, lipid, lipoprotein and apolipoprotein levels were measured in fasting samples. Patients were treated with MMI 20–30 mg daily for the first month, and 5–10 mg daily thereafter, and re‐evaluated after 6–9 months of treatment.results  Significantly lower serum paraoxonase activity was present in hyperthyroid patients before treatment compared with the controls (43·4 ± 21·9 vs. 72·6 ± 41·2 U/ml, P < 0·005). After a mean follow‐up of 7·3 months, 15 patients became euthyroid (treated) and nine were still hyperthyroid. After follow‐up, serum paraoxonase activity had increased to 62·2 ± 37·4 U/ml in those who became euthyroid (P < 0·05 compared with baseline). In patients who were still hyperthyroid serum paraoxonase was unchanged from baseline, at 43·2 ± 23·2 U/ml.conclusion  Serum paraoxonase is reduced in patients with hyperthyroidism and reverts to normal after euthyroidism is attained. Reduced serum paraoxonase activity in thyrotoxicosis might predispose lipids to oxidation.
Association between ghrelin and cardiovascular indexes in healthy obese and lean men
Authors: Tritos Nicholas A. , Kissinger Kraig V. , Manning Warren J. , Danias Peter G. 
Published: December 2004

Summaryobjective  Obesity is an increasingly common condition and is associated with excess morbidity and mortality, including clinical and subclinical cardiac dysfunction. The role of hormones involved in energy homeostasis, including ghrelin and leptin, in cardiovascular function remains incompletely understood. Therefore, we sought to evaluate the association between systemic ghrelin and leptin levels with indexes of cardiovascular structure and function.design and measurements  We measured serum ghrelin and leptin levels in 25 clinically healthy obese men and 25 lean controls, using commercially available immunoassays. We also assessed right and left ventricular structure and function using cardiac magnetic resonance imaging. We then investigated the association between serum ghrelin and leptin levels with cardiac indexes, using univariate and multivariate analysis.results  There was an independent association between serum ghrelin levels and height‐adjusted right ventricular mass (r = −0·324, P = 0·026), right ventricular end‐diastolic volume (r = −0·363, P = 0·017) and right ventricular end‐systolic volume (r = −0·398, P = 0·009) as well as right ventricular ejection fraction (r = 0·317, P = 0·050). There was no significant association between serum ghrelin and indexes of left ventricular structure or function. We also identified an association between serum leptin levels and resting heart rate (r = 0·391, P = 0·002). There was an association between serum leptin and height‐adjusted left ventricular mass on univariate, but not on multivariate, analysis.conclusions  Serum ghrelin is associated with right ventricular cardiovascular indexes and serum leptin is associated with resting heart rate. These associations indicate a close interaction between the endocrine and cardiovascular systems in obesity.