bluuebunny/crossref_metadata_2025_split huggingface dataset:
The transmembrane form of TNF-αdrives autoantibody production in the absence of CD154: studies using MRL/Mp-Faslprmice
Authors: FUJII T , OKADA M , MIMORI T , CRAFT J 
Published: March 2003

SummaryIt is generally accepted that the interaction between CD40 and its ligand (CD154) plays a decisive role in contact-dependent help for T and B cells. In CD154-deficient MRL/Mp-Faslpr (MRL/lpr) mice, however, high titres of IgG2a-type autoantibodies against small nuclear ribonucleoproteins (snRNPs) are observed. We successfully isolated two CD154-deficient MRL/lpr Th1 lines, which could provide B cell help for anti-snRNP antibody production. The proliferative responses of the Th1 cell lines were MHC class II (I-Ek)-restricted. Although syngeneic B cell proliferation was induced by Th1 lines in both a contact-dependent and -independent manner, the soluble form of TNF-α (sTNF-α) was not involved in contact-independent B cell proliferation. On the other hand, both anti-TNF-α and TNF-receptor 2 (TNF-R2, p75) monoclonal antibody (MoAb) blocked contact-dependent B cell proliferation, suggesting that the transmembrane form of TNF-α (mTNF-α)–TNF-R2 co-stimulation participates in B cell activation. Similarly, anti-TNF-α and TNF-R2 MoAb inhibited anti-snRNP antibody production in vitro, but anti-CD154 or TNF-R1 MoAb did not. These results indicate that the interaction of mTNF-α on activated Th1 cells with TNF-R2 on B cells may be involved in the autoimmunity seen in MRL mice, and that the blockade of  CD40-CD154  co-stimulation  may  not  always  be  able  to  suppress  some  Th1-related  manifestations of lupus.
Loss of ileal IgA+ plasma cells and of CD4+ lymphocytes in ileal Peyer's patches of vitamin A deficient rats
Authors: BJERSING J L , TELEMO E , DAHLGREN U , HANSON L Å 
Published: March 2003

SummaryChild mortality in diarrhoeal disease is increased significantly by vitamin A deficiency in poor countries. The pathological mechanisms are not known in detail. However, in this paper we report that vitamin A-deficient Wistar rats had much reduced IgA+ plasma cells in the ileal lamina propria (eightfold reduction from 470 cells/mm2, P = 0·009), as well as a prominent reduction of CD4+ cells in the parafollicular regions of ileal Peyer's patches (reduction from 7200 to 105 cells/mm2, P = 0·009). IL-2Ralpha-chain (CD25) positive lymphocytes in the ileal Peyer's patches were also reduced significantly in vitamin A deficiency (from 1400 to 300 cells/mm2, P = 0·009). The density of CD8 cells tended to be increased relative to the control animals (from 5100 to 6000 cells/mm2, not statistically significant). In conclusion, the marked decrease of lamina propria IgA+ plasma cells may be one cause of the high diarrhoeal mortality in vitamin A deficiency. This, in turn, appears to be related to reduced numbers of activated or regulatory CD4+ T cells in Peyer's patches.
Selective reduction of intestinal trefoil factor in untreated coeliac disease
Authors: CIACCI C , DI VIZIO D , SETH R , INSABATO G , MAZZACCA G , PODOLSKY D K , MAHIDA Y R 
Published: March 2003

Summary
The trefoil factor family (TFF) encompasses small peptides of which intestinal trefoil factor (ITF) is expressed specifically in goblet cells of the small and large intestine. Previous studies have shown that ITF plays an important role in mucosal protection and repair. Coeliac disease represents a model of immune-mediated small intestinal inflammation and damage, with recovery on gluten-free diet. The aim of this study was to investigate the expression of ITF in the distal duodenal mucosa of subjects with coeliac disease, before and after treatment with a gluten-free diet. Expression of ITF and mucin in the distal duodenal biopsies from treated (n = 11) and untreated (n = 9) coeliac subjects and controls (n = 8) was investigated by immunohistochemistry and semiquantitative PCR. In untreated coeliac disease, there was reduction of ITF immunoreactivity in goblet cells but mucin expression was preserved. Mucosal recovery on gluten-free diet was associated with increased ITF immunoreactivity in goblet cells. There was also reduction in the expression of ITF transcripts, relative to MUC2 mRNA, in untreated coeliac duodenal samples, with recovery on gluten-free diet. Our study suggests that there is a selective reduction in the expression of the ITF gene in untreated coeliac disease. Recovery of ITF expression on a gluten-free diet suggests that the mucosal immune system regulates goblet cell differentiation and ITF expression in the human intestinal mucosa.
Prevalence of non-organ specific autoantibodies in HCV-infected subjects in the general population
Authors: MURATORI P , MURATORI L , STROFFOLINI T , PAPPAS G , TERLIZZI P , FERRARI R , LOFFREDA S , CASSANI F , RAPICETTA M , GUADAGNINO V , BIANCHI F B , LENZI M 
Published: March 2003

SUMMARY
The significance of non-organ specific antibodies (NOSAs) in HCV-related chronic hepatitis is largely unclear. In this study we evaluated the prevalence of NOSAs in a non-selected population of HCV-infected subjects. One hundred and seventy anti-HCV positive and 192 anti-HCV negative sex and age-matched subjects (median age 64 years, range 7–91 years, female 68%) enrolled from the general population of a small Italian town were evaluated for NOSAs by indirect immunofluorescence on rat tissue sections and HEp-2 cells, and by counterimmunoelectrophoresis with thymus and spleen extracts as the antigen source. One hundred and sixty-three (96%) HCV-infected subjects had normal ALT serum levels and no evidence of liver disease. NOSAs were found in 31 out of 170 (18%) anti-HCV positive subjects and in 20 out of 192 (10%) controls (P = NS), with similar median titre (1:40) and range (1:40 to 1:160). Neither liver/kidney microsomal antibody type 1 nor antiactin reactivity were detected. No significant association between NOSAs and HCV genotypes was observed. In the general population, HCV-infected subjects and healthy controls have a similar prevalence of NOSAs. Without continuous liver damage HCV infection is unlikely to induce the appearance of NOSAs.
In vitrodendritic cell-induced T cell responses to B cell chronic lymphocytic leukaemia enhanced by IL-15 and dendritic cell–B-CLL electrofusion hybrids
Authors: GODDARD R V , PRENTICE A G , COPPLESTONE J A , KAMINSKI E R 
Published: March 2003

SUMMARYHLA class II-restricted proliferative and cytotoxic T cell (CTL) responses to B cell chronic lymphocytic leukaemia (B-CLL) can be generated using autologous dendritic cells (DCs) pulsed with tumour cell lysate. In this study a number of different approaches were used to optimize further the in vitro system. First, the effects of a variety of maturation agents were studied. The addition of TNF-α, polyriboinosinic polyribocytidylic acid (Poly(I:C)) and LPS to autologous DCs resulted in the emergence of only a small percentage of CD83+ DCs, IFN-α having no demonstrable effect. Only the addition of Poly(I:C) to DCs resulted in modestly increased specific cytotoxicity to B-CLL targets, IFN-α and LPS having no effect. Secondly, T cells were pretreated with IL-15, prior to culturing with lysate-pulsed autologous DCs. A significant increase in T cell activation (P = 0·038), IFN-γ secretion (P = 0·030) and specific cytotoxicity to B-CLL targets (P = 0·006) was demonstrated compared to untreated T cells. Thirdly, monocyte derived DCs electrofused with B-CLL B cells were compared with lysate-pulsed DCs. T cells stimulated by fused DCs generated higher levels of specific cytotoxicity to autologous B-CLL B cell targets than those stimulated by lysate pulsed DCs (P = 0·013). Blocking studies demonstrated inhibition of this cytotoxicity by both anti-CD4 (P = 0·062) and anti-CD8 monoclonal antibodies (P = 0·018), suggesting the generation of both HLA class I- and HLA class II-restricted CTL responses. In summary, in vitro B-CLL-specific T cell responses can be enhanced further by preincubating T cells with IL-15 and using autologous fused DC–B-CLL hybrids instead of autologous lysate-pulsed DCs. These preliminary data require confirmation with larger numbers of patients. Such an approach, however, may eventually provide effective immunotherapy for treatment of B-CLL.
Respiratory syncytial virus infection suppresses IFN-γproduction ofγδT cells
Authors: AOYAGI M , SHIMOJO N , SEKINE K , NISHIMUTA T , KOHNO Y 
Published: March 2003

SUMMARYThe immunological mechanisms by which respiratory syncytial virus (RSV) contributes to the development of asthma are poorly understood. γδ T cells are important in mucosal defence, and may contribute to the establishment of primary immune responses by producing cytokines early during respiratory infections. Thus, we used flow cytometry and intracellular cytokine staining to investigate the expression of interferon (IFN)-γ and interleukin (IL)-4 by mitogen-stimulated γδ T cells from the peripheral blood of 15 hospitalized infants with RSV bronchiolitis, seven rotavirus-infected infants and eight normal controls. γδ T cells from RSV-infected infants had a lower proportion of IFN-γ-producing cells (median, 4.00%; range, 0.58–6.60%) and a slightly but significantly higher proportion of IL-4-producing cells (median, 0.40%; range, 0.13–2.76%) than rotavirus-infected infants (median, 32.10%; range, 14.43–61.21%; P &lt; 0·01, median, 0.00%; range, 0.00–0.00%; P &lt; 0·05) in the acute phase. By contrast, differences in cytokine production by total CD3+ T cells did not differ significantly between patient groups. Thus, reduced IFN-γ-production by γδ T cells in the peripheral blood of RSV-infected infants is accompanied by increased Th2 cytokine production during the acute phase of disease. At follow-up, eight children had recurrent episodes of wheezing. The frequencies of IFN-γ-producing γδ T cells were significantly lower in patients who developed recurrent wheezing (median, 0.65%; range, 0.02–1.75%) than in patients without recurrent wheezing (median, 6.90%; range, 5.25–10.98%; P &lt; 0·005). Cytokine production by γδ T cells may therefore be important in the pathogenesis of acute RSV disease, and play a part in the development of recurrent childhood wheezing after bronchilolitis.
Selective up-regulation of functional CXCR4 expression in erythroid cells by HIV-1 Tat protein
Authors: GIBELLINI D , RE M C , VITONE F , RIZZO N , MALDINI C , LA PLACA M , ZAULI G 
Published: March 2003

SummaryCXCR4 is the high affinity receptor for the SDF-1α chemokine and represents the main coreceptor for HIV-1 T-tropic strains. The surface expression of CXCR4 was analysed in CD34+ haematopoietic progenitors, induced to differentiate along the erythroid or granulocytic lineages, in liquid cultures supplemented or not with HIV-1 Tat protein. At concentrations as low as 1–10 ng/ml, synthetic Tat protein significantly increased the surface expression of CXCR4 in erythroid but not in granulocytic cells. The Tat-mediated up-regulation of surface CXCR4 was accompanied by a concomitant increase of CXCR4 mRNA and total CXCR4 protein content in cells developing along the erythroid lineage after 6–10 days of culture. Moreover, addition of SDF-1α (200 ng/ml) induced a significant higher rate of apoptosis in Tat-treated erythroid cells in comparison with control cells. These results demonstrated for the first time a direct positive role in haematopoietic gene regulation of Tat protein, and suggest the possible involvement of Tat in HIV-1-induced anaemia.
The octreotide suppression test and [111In‐DTPA‐D‐Phe1]‐octreotide scintigraphy in neuroendocrine tumours correlate with responsiveness to somatostatin analogue treatment
Authors: Shi  , Buchanan  , Johnston  , Larkin  , Ong  , Ferguson  , Laird  
Published: March 2003

OBJECTIVEThe somatostatin analogue octreotide (Sandostatin, Novartis, Basle) significantly improves the syndromes suffered by most patients with neuroendocrine tumours (NETs). The use of [111In‐DTPA‐D‐Phe1]‐octreotide scintigraphy ([111In]‐pentetreotide) to predict the response to octreotide treatment has been described. Short‐term hormone inhibition by a single injection of octreotide has also been reported. This study aimed to compare the effects of the suppression test with the response to long‐term somatostatin analogue treatment, and to seek a correlation between the short‐term suppression test, [11In]‐pentetreotide observations and long‐term somatostatin analogue treatment.DESIGN AND MEASUREMENTSShort octreotide suppression test and octreotide scintigraphy. Blood samples were collected before (0900, 0930 h), at (1000 h), and after (1030, 1100, 1200, 1300 h) the injection of 50 μg octreotide subcutaneously. Plasma hormones relevant to the syndrome were analysed by radioimmunoassay. The short suppression effects, the [111In]‐pentetreotide observations and the response to long‐term treatment with somatostatin analogue were evaluated and compared.PATIENTSTwenty‐six patients with metastatic NETs were evaluated, including 14 carcinoid tumours, 10 pancreatic endocrine tumours and 2 medullary carcinomas of thyroid (MCTs). Twelve patients had received octreotide treatment before the study, another 4 patients were treated subsequently with somatostatin analogue.RESULTSDuring the short suppression test, hormones relevant to the syndromes were suppressed in 24 patients (those with carcinoids and pancreatic endocrine tumours). There was no suppression in the 2 patients with MCT. [111In]‐pentetreotide observations closely correlated with the short suppression response to octreotide. Fourteen patients were treated with somatostatin analogue, and responded clinically; they had a positive short inhibition test and positive tumour uptake. Two patients with MCT did not respond to the treatment and had a negative suppression test and a negative [111In]‐pentetreotide.CONCLUSIONOur results suggest that a consistent relationship exists between the short suppression test and the response to somatostatin analogue treatment in the majority of the patients with neuroendocrine tumours. The octreotide suppression test and octreotide scintigraphy together will be helpful in selecting appropriate patients for clinical treatment with somatostatin analogues.
Plasma sex hormones are significantly associated with plasma leptin concentration in healthy subjects
Authors: Paolisso Giuseppe , Rizzo Maria Rosaria , Mone Concetta Maria , Tagliamonte Maria Rosaria , Gambardella Antonio , Riondino Mariangela , Carella Carlo , Varricchio Michele , D'Onofrio Felice 
Published: March 2003

OBJECTIVEIn humans a sexual dimorphism of plasma leptin concentration has been demonstrated but its significance remains to be established. Sex hormones may have a role.PATIENTSEighty healthy, non‐obese subjects (41M/39F) were studied.MEASUREMENTSIn the whole group of subjects plasma sex hormones, leptin and insulin concentrations were determined, body fat content assessed by bioimpedance analysis, body fat distribution evaluated and insulin‐mediated glucose uptake measured by euglycemic hyperinsulinemic glucose.RESULTSAfter adjustment for age, gender, amount of body fat, waist/hip ratio (WHR) and fasting plasma insulin concentration, fasting plasma leptin was still significantly correlated with plasma DHEAS (r =−0.30, P < 0.006), oestradiol (r = 0.53, P < 0.001) and testosterone (r = −0.43, P < 0.001) in all subjects (n = 80). Independently of age, amount of body fat and WHR, fasting plasma leptin concentration correlated with plasma oestradiol (r = 0.38, P < 0.01) and total testosterone (r = −0.58, P < 0.001) in males (n = 41) and with fasting plasma oestradiol (r = 0.48, P < 0.002) in females (n = 39). To investigate the independent contribution of anthropometric and hormonal variables to fasting plasma leptin concentration, a multivariate stepwise regression analysis with fasting plasma leptin concentration as dependent variable was made. In the entire group (n = 80), the whole model explained 43% of fasting plasma leptin concentration with fasting plasma insulin, total testosterone and oestradiol concentrations significantly and independently associated with plasma leptin concentration. In this model, fasting plasma DHEAS, testosterone and oestradiol explained 25% of the variability in plasma leptin concentration.CONCLUSIONOur study demonstrates that plasma sex hormone concentrations are associated with plasma leptin concentration.
Positive association between circulating free thyroxine and insulin‐like growth factor I concentrations in euthyroid elderly individuals
Authors: Seck Thomas , Scheidt‐Nave Christa , Ziegler Reinhard , Pfeilschifter Johannes 
Published: March 2003

OBJECTIVEPrevious studies have shown marked changes in circulating insulin‐like growth factor‐I (IGF‐I) levels in hypo‐ and hyperthyroid patients. In this study we examined whether the circulating concentration of IGF‐I may also be affected by normal thyroid hormone levels.DESIGNA cross‐sectional study of thyroid hormones and plasma IGF components in a population‐based sample.PATIENTS50–80 year‐old men (n = 262) and women (n = 218) with normal concentrations of serum free thyroxine (f T4), free triiodothyronine (f T3) and thyrotrophin (TSH).MEASUREMENTSPlasma concentrations of IGF‐I, IGF‐II and IGFBP‐3, and serum concentrations of TSH, f T3 and f T4.RESULTSSerum f T4 values were weakly positively correlated and serum TSH levels were inversely correlated with circulating IGF‐I concentrations. The associations persisted after adjustment for age and ideal body weight.CONCLUSIONSOur data demonstrate that thyroid hormones are positively correlated to IGF‐I plasma levels even under physiological conditions. However, thyroid hormones explain only 1–2% of the normal variability of circulating IGF‐I.
TSH receptor antibody‐associated thyroid dysfunction following subacute thyroiditis
Authors: Iitaka Makoto , Momotani Naoko , Hisaoka Toshihiko , Noh Jaeduk Yoshimura , Ishikawa Naofumi , Ishii Jun , Katayama Shigehiro , Ito Kunihiko 
Published: March 2003

OBJECTIVEAutoimmunity plays an important role in the development of thyrotrophin (TSH) receptor antibodies and the pathogenesis of Graves' disease and Hashimoto's thyroiditis. On the other hand, subacute thyroiditis is a self‐limited inflammatory disease of presumed viral aetiology. The aim of this study was to examine whether subacute thyroiditis triggers TSH receptor antibody‐associated thyroid disorders.PATIENTSWe reviewed 1,697 patients with subacute thyroiditis seen between 1985 and 1995.DESIGN AND MEASUREMENTSWe measured antibodies which inhibit the TSH binding to the TSH receptor (TBIAb), thyroid stimulating antibodies (TSAb) and antibodies that block TSH action (TBAb). Other thyroid autoantibodies were also determined.RESULTSTBIAb became positive in 38 patients following subacute thyroiditis. Thyroid function after the development of TBIAb appeared to be influenced by the bioactivity of the antibody. Hyperthyroidism developed in the presence of TSAb, and so did hypothyroidism in the presence of TBAb, although 21 patients did not have thyroid dysfunction despite high titres of TBIAb. Fifteen out of 17 patients recovered from hyperthyroidism or hypothyroidism after the disappearance of TBIAb sometimes even without medication. TBIAb‐positive patients had a high incidence of a family history of thyroid disease and positive anti‐thyroid microsomal antibodies. An ophthalmopathy similar to Graves' disease was also observed in 3 patients.CONCLUSIONSSubacute thyroiditis may trigger autoreactive B cells to produce TSH receptor antibodies, resulting in TSH receptor antibody‐associated thyroid dysfunction in some patients.
Dose response with fluticasone propionate on adrenocortical activity and recovery of basal and stimulated responses after stopping treatment
Authors: Wilson Andrew M. , Sims Erika J. , Lipworth Brian J. 
Published: March 2003

OBJECTIVETo evaluate the dose–response relationship for adrenocortical activity with fluticasone propionate (FP) and to assess basal and dynamic markers after stopping treatment for 3 days.PATIENTS AND DESIGNFourteen asthmatic patients were recruited: mean age 33.3 years, forced expiratory volume in 1 s (FEV1): 91.3% predicted, forced mid expiratory flow rate (FEF25–75): 58.1% predicted. A single blind study design was used comparing a placebo run‐in with sequentially low, medium and high doses of FP and a placebo washout. All active treatments, placebo and washout were each for 3 days. FP was given at steady‐state with twice daily divided dosing at 0800 h and 2200 h at doses of 375 μg, 875 μg, and 1750 μg per day.MEASUREMENTSA 100 μg iv bolus hCRF test was performed at 0800h after the run‐in and washout periods. Blood samples were taken for 0800h serum cortisol and osteocalcin as well as an overnight 10 h urine collection for cortisol/creatinine excretion after the run‐in period, each dose of active treatment and washout.RESULTSFor serum cortisol (pre and post hCRF stimulation) there was no significant difference between placebo and washout values. Mean (SE) cortisol (nmol/1) values pre hCRF were run‐in: 644.5 (59.7), washout: 550.3 (42.8) and post hCRF were run‐in: 690.9 (42.9), washout: 719.1 (43.8). There was a significant (P < 0.05) difference between run‐in vs medium and high doses for 0800 h serum cortisol, overnight urinary cortisol and overnight urinary cortisol/creatinine excretion; and vs high dose for serum osteocalcin. The fold difference (95% CI for difference) between run‐in and high dose was: 2.2 (1.5–3.2) for overnight urinary cortisol, 2.5 (1.5–4.1) for overnight urinary cortisol/creatinine, 2.0 (1.1–3.6) for serum cortisol, and 1.2 (1.1–1.3) for serum osteocalcin.CONCLUSIONFluticasone propionate exhibited dose related adrenal suppression with treatment. The suppressive effects of fluticasone propionate on adrenocortical activity were greater than those observed on osteocalcin.
Cardiac function at rest in hypothyroidism evaluated by equilibrium radionuclide angiography
Authors: Tielens Emile T. , Pillay Marrmuthoo , Storm Corstiaan , Berghout Arie 
Published: March 2003

OBJECTIVEPrevious studies have suggested that hypothyroidism affects both systolic and diastolic cardiac function. We have applied equilibrium radionuclide angiography to the study of heart function at rest in hypothyroidism.DESIGNA prospective study, evaluating cardiac function at rest in primary hypothyroidism.METHODSCardiac function was studied by means of equilibrium radionuclide angiography. Screening echo‐Doppler examinations were performed on each patient.PATIENTSTwenty‐six consecutive untreated hypothyroid patients without clinical or echocardiographic cardiac disease and 20 healthy matched controls.RESULTSBetween patients and controls, the time to peak emptying rate (161 ± 6 msec vs. 144 ± 6 msec, P < 0.05) and the time to peak filling rate (188 ± 6 msec vs. 170 ± 5 msec, P < 0.05), were the only discriminatory parameters. In hypothyroid patients, a trend towards a decrease in diastolic cardiac function, expressed as peak filling rate, was observed: 2.6 ± 0.1 End Diastolic Volume (EDV)/s vs. 3.0 ± 0.1 EDV/s, P = 0.06. Within the hypothyroid patient group, the time to peak emptying rate was more prolonged in patients with lower free thyroxine levels (R = − 0.60, F = 13.5, P < 0.001). Peak filling rate was decreased in patients with lower free thyroxine levels (R = 0.51, F = 8.4, P < 0.01) whereas the time to peak filling rate was more prolonged (R = − 0.62, F = 15, P < 0.001).CONCLUSIONIn a large group of consecutive patients presenting with primary hypothyroidism, even in the absence of clinical cardiac disease and echocardiographic abnormalities, clear changes in myocardial performance at rest were observed. The most obvious effect of thyroid hormone deficiency on the heart was a lengthening of both systolic and early diastolic time characteristics. Diastolic rather than systolic cardiac function was influenced by hypothyroidism.