bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell receptor usage in patients with non-progressing HIV infection
Authors: BODMAN-SMITH M D , WILLIAMS I , JOHNSTONE R , BOYLSTON A , LYDYARD P M , ZUMLA A 
Published: March 2003

SUMMARYIt is still unclear why some patients with HIV progress more slowly than others to developing full blown AIDS. In this study using flow cytometry we have investigated the TCRBV repertoire of peripheral blood T lymphocytes in 17 long-term non-progressing HIV patients (LTNP) to determine if there is a biased usage of T cell receptor V gene products. Patients were identified from hospital records and entered into the study. Three colour flow cytometry was used to determine the expression of the TCRBV3S5, BV5S1, BV5S2, BV5S3, BV6S1, BV7S1, BV9, BV11, BV12, BV13, BV14, BV16, BV17, BV18, BV20, BV21S3, BV22, and BV23 by CD8 and CD4 positive cells isolated from the peripheral blood of patients and controls. Increases in the absolute numbers of CD8+ T cells expressing TCRBV2 and 8 were observed in the HIV-LTNP population (P &lt; 0·05 in both cases). No differences were seen in numbers of CD8+ T cells expressing other TCRBV or in any TCRBV within the CD4+ T cell popu-lation. At follow up (1–2 years later), those patients in which CD4 levels were below 500 × 106/l were those initially found to have lower levels of TCRBV8 +ve CD8 cells. A significant increase in the absolute numbers of T cells coexpressing the gamma delta (γδ) T cell receptor and CD8 were also seen in the HIV-LTNP patients compared with controls (P = 0·002). The increase in CD8+ T cells in the HIV-LTNP patients may be interpreted as either an antigen specific, or group of antigen specific responses to viral antigen, or less likely a viral superantigen. A low level of TCRBV8, CD8+ T cells might be predictive of a more rapid disease progression and might indicate a protective role for this population in HIV infected patients. The increase in γδT cells bearing the CD8 coreceptor suggests a role for this cell type in the response to HIV infection.
Abnormal expression of intracellular cytokines and chemokine receptors in peripheral blood T lymphocytes from patients with systemic sclerosis
Authors: FUJII H , HASEGAWA M , TAKEHARA K , MUKAIDA N , SATO S 
Published: March 2003

SummaryIn patients with systemic sclerosis (SSc), there are conflicting findings regarding which is predominant between type 1 and type 2 immune responses. To determine the balance between type 1 and type 2 T lymphocytes in peripheral blood from SSc patients, we investigated the expression of intracellular cytokines, such as interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-13, and chemokine receptors such as CXCR3 and CCR4 by flow cytometry. The frequency of IFN-γ-producing cells among CD8+ cells was significantly increased in patients with diffuse cutaneous SSc (n = 11, P &lt;  0·0001) and limited cutaneous SSc (lSSc; n= 16, P &lt; 0·0001) compared with normal controls (n = 17) while there was no significant difference in the frequency of IL-4- or IL-13-producing cells. In contrast, the frequency of IFN-γ- or IL-4-producing cells among CD4+ cells was similar between the three groups. Similar results were obtained when absolute numbers were assessed. The frequency of IFN-γ-producing cells among CD8+ cells inversely correlated with percentage DLco in SSc patients (r = − 0·650, P &lt; 0·005). CXCR3+ CD8+ cells selectively produced IFN-γ, and the frequency of CXCR3+ CD45RO+ cells among CD8+ cells was higher in lSSc patients (n = 14, P &lt; 0·01) than in normal controls (n = 22). In contrast, there was no significant difference in the frequencies of CXCR3- or CCR4-expressing CD45RO+ cells among CD4+ cells. These results demonstrate the predominance of type 1 cytokine-producing cells (Tc1 cells) in peripheral blood CD8+ T cells from SSc patients, but no definite Th1/Th2 imbalance in CD4+ T cells. Tc1 cells may be associated with pulmonary vascular damage in SSc.
Evidence for lack of cross-genotype protection of CD4+ T cell responses during chronic hepatitis C virus infection
Authors: HARCOURT G C , LUCAS M , GODKIN A J , KANTZANOU M , PHILLIPS R E , KLENERMAN P 
Published: March 2003

SUMMARYCD4+ T lymphocyte responses are thought to play a major role in control of the hepatitis C virus (HCV). Few, however, have been mapped down to the level of peptide and HLA restriction. Furthermore, the ability of such T cells to respond to viruses which differ in genotype has not been addressed in detail. In most cases of persistent infection with HCV, CD4 proliferative responses are weak or absent. From a large cohort of persistently infected patients, we identified an individual with unusually robust and persistent responses in the face of chronic infection. We firstly mapped two peptide epitopes to regions of the nonstructural protein NS4 (aa1686–1705 and aa 1746–1765). However, in contrast to the genotype 1a derived antigens used for mapping, the infecting virus was identified as genotype 3a. Strikingly, the patient's CD4 response to these epitopes were specific only for the genotype 1a sequence, and did not recognize genotype 3a synthetic peptides. Serologic assays indicated that prior exposure to HCV of genotype 1 had occurred. This patient therefore maintains strong CD4 proliferative responses which are genotype specific and not cross-reactive. The apparent ‘misdirection’ of these nonprotective responses has important implications for the role of natural and vaccine induced CD4 responses in the face of variable viruses.
Autoantibodies against complement receptor 1 (CD35) in SLE, liver cirrhosis and HIV-infected patients
Authors: SADALLAH S , HESS C , TRENDELENBURG M , VEDELER C , LOPEZ-TRASCASA M , SCHIFFERLI J A 
Published: March 2003

SUMMARYThe acquired loss of CR1 (CD35) on erythrocytes in specific autoimmune diseases and chronic infections may be due to autoAb against CR1. An ELISA using rCR1 was established to measure antiCR1 IgG autoAb. Plasma containing alloAb to polymorphism on CR1 (Knops blood group Ab) reacted strongly against rCR1 and were used as positive controls. AntiCR1 Ab was found in 3/90 (3·5%) plasma samples from healthy blood donors. The binding of these Ab was not inhibited by high salt concentrations. AntiCR1 Ab were present in the IgG fractions of plasma, and they bound to rCR1 on Western Blot. Affinity chromatography on rCR1-sepharose depleted the plasma of antiCR1, and the acid-eluted fractions contained the antiCR1 Ab. An increased frequency of antiCR1 autoAb was found in patients with SLE (36/78; 46%), liver cirrhosis (15/41; 36%), HIV infection (23/76; 30%) (all P &lt; 0·0001), and in patients with anticardiolipin Ab (4/21; 19%, P &lt; 0·01) multiple sclerosis (7/50; 14%, P &lt; 0·02), and myeloma (autoAb (8/56; 14%, P &lt; 0·02), but not in those with acute poststreptococcal glomerulonephritis (1:32; 3%). Because C1q binds to CR1, antiC1q Ab were analysed in the same patients. There was no correlation between levels of antiC1q and antiCR1 autoAb. In HIV patients, levels of antiCR1 did not correlate with low CR1 levels expressed on erythrocytes or soluble CR1 in plasma.The binding of antiCR1 autoAb to rCR1 fixed on ELISA plates was not inhibited by soluble rCR1 or by human erythrocyte CR1, in contrast to alloAb and one SLE serum, which induced partial blockade. Thus, antiCR1 autoAb recognize mostly CR1 epitope(s) not present on the native molecule, suggesting that they are not directly involved in the loss of CR1. Rather antiCR1 autoAb might indicate a specific immune response to denatured CR1.
Monocyte-derived cytokines in multiple sclerosis
Authors: FILION L G , GRAZIANI-BOWERING G , MATUSEVICIUS D , FREEDMAN M S 
Published: March 2003

SUMMARYMS is an inflammatory, presumably autoimmune, disease mediated by the activation of T cells, B cells and monocytes (MO). Inflammation is thought to occur early during the relapsing-remitting phase of MS (RRMS), whereas in the later phases of MS such as secondary progressive MS (SPMS), inflammation tends to diminish. Our objective was to compare the types and amounts of proinflammatory and regulatory cytokines produced by MO from relapsing–remitting patients with or without treatment with IFN-β (RRMS+ therapy, RRMS− therapy), respectively, from secondary progressive patients (SPMS) and from healthy controls (HC). MO were isolated by a density-gradient technique and three different techniques (RNase protection assay, ELISA and intracellular cytokine staining) were used to assess cytokine levels. An increase in IL6, IL12 and TNF-α was observed by all three methods for RRMS– therapy and for SPMS patients compared to HC and RRMS+ therapy patients. We conclude that proinflammatory and regulatory monokines can be derived from MO of MS patients and that these levels are modulated by IFN-β therapy. Although it is believed that inflammation tends to diminish in SPMS patients, our data show that inflammatory cytokines continue to be released at high levels, suggesting that IFN-β or IL10 treatment may be beneficial for this group.
Antigens shared by malignant plasma cells and normal B cells may be involved in graftversusmyeloma
Authors: HOLLOWAY P A , KALDENHOVEN N , KOK-SCHOEMAKER H M , VAN KESSEL B , VAN BLOKLAND W T M , BLOEM A C , LOKHORST H M 
Published: March 2003

SUMMARYCytotoxic T cells play an important role in graft-versus-host-disease (GvHD) and graft-versus-leukaemia/myeloma, which may occur in patients treated with an allogeneic stem cell transplantation (ASCT). Here, we describe the selection of a myeloma reactive CD4+ cytotoxic T cell-line (CTL) and two CD4+ clones from this CTL. The CTL was generated from the blood from a patient with multiple myeloma (MM) with graft versus myeloma/GvHD, following an ASCT. The CTL was stimulated using irradiated peripheral blood mononuclear cells and EBV transformed B cells from the myeloma patient (EBVp), both of which were obtained prior to ASCT. Both the CTL and the two T cell clones specifically lysed EBVp and secreted IFN-γ after coculture with EBVp and autologous myeloma tumour cells in a class II restricted fashion. These results show that myeloma tumour cells and autologous B cells present a common polymorphic peptide that functions as a target for graft derived cytotoxic T cells. Identification of these proteins will give insight into the relationship between graft versus myeloma (GvM) and GvHD and may provide immunotherapeutical targets in the treatment of MM.
Flow cytometric determination of glucocorticoid receptor (GCR) expression in lymphocyte subpopulations: lower quantity of GCR in patients with post-traumatic stress disorder (PTSD)
Authors: GOTOVAC K , SABIONCELLO A , RABATI´C S , BERKI T , DEKARIS D 
Published: March 2003

SUMMARY
Assessment of the intracellular glucocorticoid receptor (GCR) level may be useful in monitoring functional disturbances of the hypothalamic-pituitary-adrenocortical axis or effects of prolonged steroid therapy. Cytosolic ligand binding assays have recently been supplemented by flow cytometric determination of receptor expression in individual cells. A method based on multiparametric analysis of whole blood by simultaneous labelling of intracellular GCRs and surface markers of lymphocyte subsets is described. We examined 25 healthy male volunteers and 35 age- and sex-matched post-traumatic stress disorder (PTSD) patients within 8 years from traumatic event. PTSD patients had a lower relative quantity of GCR in all lymphocyte populations tested as compared with healthy volunteers. NK cells of both groups showed higher expression of GCR than other lymphocyte subsets. In PTSD patients, the expression of GCR in B lymphocytes was also higher than in T cell. Although serum cortisol level was lower in PTSD patients, there was no correlation between cortisol level and GCR expression. Multiparameter flow cytometric determination of GCR expression in lymphocyte subpopulations may provide a useful tool for monitoring immunoregulatory action of glucocorticoids.
Enhanced chemokine response in experimental acuteEscherichia colipyelonephritis in IL-1β-deficient mice
Authors: HERTTING O , KHALIL A , JAREMKO G , CHROMEK M , LI Y-H , BAKHIET M , BARTFAI T , TULLUS K , BRAUNER A 
Published: March 2003

SUMMARYThe aim of the present study was to investigate the effects of IL-1β and Escherichia coli on the expression and secretion of MIP-2, the mouse equivalent to human IL-8, MCP-1 and RANTES in the kidneys of mice with acute pyelonephritis. Female Bki NMRI, as well as IL-1β deficient mice and their wild-type littermates, were transurethrally infected with either E. coli CFT 073 or injected with NaCl 0·9% (w/v) and thereafter obstructed for 6 h. The Bki NMRI mice were killed at 0, 24, 48 h and 6 days and the IL-1β-deficient mice at 48 h. Chemokine mRNA and protein levels peaked at 24 h for the tested chemokines with the mRNA expression localized in the tubular epithelial cells and for MIP-2 also in neutrophils. Obstruction per se, also induced a chemokine expression similar to E. coli infection although at a lower level. Interestingly, MIP-2 levels were higher in the IL-1β deficient mice as compared with the wild-type littermates. Likewise, the inflammatory changes were more frequent and, when present, more widespread in the IL-1β-deficient mice than in the wild-type mice. Stimulation of a human renal tubular epithelial cell line (HREC), A498 and of primary human mesangial cells (HMC) with the same bacterial antigen depicted gene expression of the same chemokines. A rapid release of IL-8 and MCP-1 was observed from both cell types. RANTES response was delayed both in the HREC and the HMC. We conclude that acute E. coli pyelonephritis induces a MIP-2/IL-8, MCP-1 and RANTES expression and secretion localized primarily to the epithelial cells and that this production is confirmed after in vitro stimulation with the same bacterial antigen of human epithelial and mesangial cells. Blockade of induction of chemokine response may thus be an attractive target for possible therapeutic intervention.
Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients
Authors: Modigliani Elisabeth , Cohen Régis , Campos José‐Marie , Conte‐Devolx Bernard , Maes Béatrice , Boneu Andrée , Schlumberger Martin , Bigorgne Jean‐Claude , Dumontier Philippe , Leclerc Laurence , Corcuff Bernard , Guilhem Isabelle 
Published: March 2003

BACKGROUNDPrognostic factors of sporadic or inherited medullary thyroid carcinoma (MTC) are still controversial and have been assessed in old and small series. A better knowledge of these factors would improve patient management.OBJECTIVETo evaluate factors involved in the prognosis of MTC in a large series of cases, using uni‐ and multivariate analysis.DESIGN AND PATIENTSClinical, biological, surgical and epidemiological data on 899 MTC patients, diagnosed between 1952 and 1996, were collected by the French Calcitonin Tumors Study Group (GETC) with a standardized questionnaire, and processed in a national database.MEASUREMENTSSurvival and biochemical cure (i.e. normal basal post‐operative serum calcitonin levels) were analysed with Kaplan and Meier and log‐rank test statistical procedures. Data are presented as adjusted rather than observed survival, to consider only patients who died of MTC. Cox's forward‐stepping proportional hazard model was used to analyse factors with a significant influence on survival by univariate analysis.RESULTSApart from the large proportion of familial forms (43%), the general characteristics of our population were similar to those in other studies: mean age at surgery = 43.4 years; sex ratio = 1 male/1.35 female; stage I = 20.8%; stage II = 21.2%; stage III = 46.5% and stage IV = 11.5%. 863 (96%) patients underwent surgery; 43% of operated patients were biochemically cured. Adjusted survival was 85.7 ± 1.5% at 5 years and 78.4 ± 2.1% at 10 years. Multivariate analysis showed that age and stage were independent predictive factors of survival. Gender, type of surgery, type of familial form were predictive only in univariate analysis. Biochemical cure predicts a survival rate of 97.7% at 10 years. Authentic recurrence, that is subsequent elevation of calcitonin (CT) after post‐operative normalization, was found in 4.9%. In non‐cured patients (57%), survival was still good: 80.2% (±2.2%) and 70.3% (±2.9%) at 5 and 10 years, respectively. Similarly, prediction of biochemical cure was solely dependent on stage.CONCLUSIONSurvival of these medullary thyroid carcinoma patients appears better than expected even in non‐cured patients. Considering the strong impact of stage, the necessity for pre‐operative diagnosis of MTC is obvious.
Long‐term follow‐up of bone mineral density and bone metabolism in transsexuals treated with cross‐sex hormones
Authors: Van Kesteren Paul , Lips Paul , Gooren Louis J. G. , Asscheman Henk , Megens Jos 
Published: March 2003

OBJECTIVEIt is unknown whether long term cross‐sex hormone treatment affects the human skeleton. We monitored bone mineral density and biochemical markers of bone turnover for 28–63 months in 20 male‐to‐female transsexuals (M → F) treated with anti‐androgens and oestrogens, and 19 female‐to‐male transsexuals (F → M) treated with androgens. They underwent gonadectomy 13–35 months after the start of cross‐sex hormone administration.DESIGNBone mineral density (BMD) and the markers of bone turnover osteocalcin, alkaline phosphatase, fasting urinary calcium/creatinine and hydroxyproline/creatinine, were measured at baseline, after 1 year and after 28–63 months of cross‐sex hormone administration.RESULTSIn oestrogen‐treated M → F, variables of bone turnover decreased significantly with consecutive measurements. BMD had increased significantly after 1 year, but decreased again to baseline levels after 28–63 months of cross‐sex hormones.In F → M, alkaline phosphatase levels increased during the first year. BMD did not change during the first year but had decreased significantly after 28–63 months following ovariectomy. In both M → F and F → M, the change of BMD correlated inversely with serum LH and FSH levels. Of all biochemical variables LH levels appeared to be the best predictor of loss of BMD; in the long‐term LH levels were more elevated in testosterone‐treated F → M than in oestrogen‐treated M → F transsexuals.CONCLUSIONIn M → F, oestrogen treatment prevented bone loss after testosterone deprivation. In F → M the testosterone dosage used, associated with a decline in serum oestradiol levels, was unable to maintain bone mass fully in all subjects in the longer term. The inverse relationship between BMD and serum LH levels suggests that the dose of hormone replacement has been too low in subjects with a decline in their BMD. Its cause might be underdosing or non‐compliance in some patients. We propose that serum LH levels may be used as a measure of the adequacy of replacement with sex steroids.
Tuberculous Addison's disease: lack of normalization of adrenocortical function after anti‐tuberculous chemotherapy
Authors: Bhatia Eesh , Jain Sunil K. , Gupta Rakesh K. , Pandey Rakesh 
Published: March 2003

OBJECTIVETuberculosis of the adrenal glands is a common cause of Addison's disease in developing countries. We conducted a study to determine if treatment of such patients with modern anti‐tuberculous chemotherapy would lead to an improvement in plasma cortisol and aldosterone levels.DESIGNProspective study.PATIENTS5 patients with Addison's disease secondary to tuberculosis.MEASUREMENTSBasal and ACTH stimulated plasma cortisol and aldosterone levels were measured prior to instituting anti‐tuberculous chemotherapy, as well as one month after its conclusion. Four patients were again studied over the next 2–5 years.RESULTSPeak plasma cortisol levels prior to treatment were markedly reduced (range, < 14–110 nmol/l). There was no improvement one month (< 14–143 nmol/l) or 2–5 years (< 14–69 nmol/l) after completing anti‐tuberculous chemotherapy. Peak plasma aldosterone at diagnosis was < 56–210 pmol/l; it was undetectable in 4 patients. No improvement was observed one month (< 56–210 pmol/l), or 2–5 years (< 56–389 pmol/l) after stopping anti‐tuberculous chemotherapy. Plasma aldosterone levels at both these time points were far lower than those in control subjects (median 763 pmol/l, 560–1512 pmol/l; p < 0.01). One patient had an increase in peak aldosterone from < 56 pmol/l to 389 pmol/l, though peak cortisol actually declined in this subject (from 110 nmol/l to 69 nmol/l).CONCLUSIONSTreatment of tuberculous Addison's disease with anti‐tuberculous chemotherapy does not lead to normalization of ACTH stimulated plasma cortisol or aldosterone levels during the 2–5 year period of study. However, prolonged follow up with regular adrenal function tests is warranted in all such patients.
Radioiodine treatment in unsuspected pregnancy
Authors: Evans  , Webster  , Evans  , Bevan  , Scanlon  
Published: March 2003

OBJECTIVERadioiodine is being used increasingly as first line therapy for hyperthyroidism. Our aim is to highlight some of the difficulties which can occur following the use of 131I to treat hyperthyroidism in fertile women.PATIENTSWe present 3 cases of young women to whom radioiodine was given, only to find some weeks later that they had been pregnant at the time of treatment.CONCLUSIONSThese cases serve as a reminder of the importance of obtaining an accurate and full menstrual and contraceptive history. Guidelines advocate the application of the ten day rule with the further recommendation that pregnancy testing may be undertaken as an alternative.
Serum follistatin concentrations are increased in patients with septicaemia
Authors: Michel Uwe , Shintani Yasumi , Nau Roland 
Published: March 2003

OBJECTIVEFollistatin (FS) is the specific binding protein of activin, a growth and differentiation factor of many cell types. Both factors have almost ubiquitous tissue distributions. In vitro, FS is secreted by vascular endothelial cells and this can be stimulated by bacterial compounds. For this reason, serum FS levels were examined in patients with septicaemia.PATIENTSFive male and four female patients of different age with various forms of septicaemia and different clinical outcome.MEASUREMENTSSerum concentrations of FS, C‐reactive protein (CRP) and blood leucocyte counts were determined repeatedly in all nine patients; samples from age‐ and sex‐matched healthy volunteers served as controls.RESULTSThe median of the maximum FS concentrations of septicaemic patients was threefold higher than in healthy controls (P = 0.008). The highest increase observed was approximately 40 times normal. Serum FS levels in patients with septicaemia showed large variations between individuals. Serum FS levels parallelled those of CRP but were not correlated to the leucocyte counts.CONCLUSIONserum follistatin concentrations in humans are elevated during septicaemia and appear to parallel serum C‐reactive protein levels.