bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement and interpretation of pneumococcal IgG levels for clinical management
Authors: BALMER P , NORTH J , BAXTER D , STANFORD E , MELEGARO A , KACZMARSKI E B , MILLER E , BORROW R 
Published: December 2004

SUMMARY
The detection of pneumococcal IgG antibodies is helpful for the evaluation of response to pneumococcal vaccination and need for revaccination. Results generated by the clinical assay which is currently used, in which the 23 valent polysaccharide vaccine is the antigen, were compared to those obtained by a capsular polysaccharide serotype-specific assay that measures IgG antibodies to 9 common serotypes causing invasive disease. Discrepancies in 21/47 (45%) of the results were observed in a direct comparison between the two assays. In each case a positive titre was obtained on the clinical assay but IgG levels on the serotype-specific assay were below the putative protective level of 0·2 µg/ml for at least one of the 9 serotypes assayed. The generation of false positives by the current clinical assay is due to its lack of specificity. Antibodies to C-polysaccharide and all of the 23 serotypes included in the pneumococcal polysaccharide vaccine are incorporated into the final titre whereas the serotype-specific assay adsorbs out noncapsular polysaccharide antibodies. The discrepancies between the two assays highlight the importance of standardized assays that measure putative correlates of protection and demonstrate the need to re-evaluate the current clinical assay. A tool that allows the interpretation of the results of the serotype-specific assay is provided and its potential for assessing individual susceptibility levels to vaccine preventable pneumococcal infection is discussed.
Humoral β-cell autoimmunity is rare in patients with the congenital rubella syndrome
Authors: VISKARI H , PARONEN J , KESKINEN P , SIMELL S , ZAWILINSKA B , ZGORNIAK-NOWOSIELSKA I , KORHONEN S , ILONEN J , SIMELL O , HAAPALA A-M , KNIP M , HYÖTY H 
Published: December 2004

SUMMARY
The congenital rubella syndrome (CRS) is associated with increased risk for diabetes and thyroid disease. However, the mechanisms by which the rubella virus may cause these diseases are poorly characterized. Previous studies were carried out before modern immunological methods were available. The present study aimed at evaluating whether autoimmune mechanisms are involved in the pathogenesis by analysing antibodies to biochemically characterized autoantigens. The incidence of clinical diabetes, thyroid disease, coeliac disease and related antibodies (islet cell antibodies, ICA; insulin autoantibodies, IAA; antibodies to the tyrosine phosphatase related IA-2 molecule, IA-2 A and glutamic acid decarboxylase, GADA; thyroid peroxidase, TPO; tissue transglutaminase, TTGA; and gliadin, AGA) and HLA risk genotypes were analysed in 37 subjects affected by or exposed to rubella during fetal life (mean age 22·5 years). One patient had diabetes and four patients had clinical hypothyroidism at the time of the examination. ICA, IAA, GADA or IA-2 A were not detected in any of the patients, while five patients tested positive for TPO antibodies. Coeliac disease or TTGA were not observed. Eight patients carried the HLA-DR3–associated HLA-DQB1*02-DQA1*05 haplotype. These results provide no evidence of an increased frequency of markers for humoral β-cell autoimmunity in patients with CRS suggesting that diabetes in CRS may be caused by other than autoimmune mechanisms.
Donor dependent, interferon-γinduced HLA-DR expression on human neutrophilsin vivo
Authors: REINISCH W , LICHTENBERGER C , STEGER G , TILLINGER W , SCHEINER O , GANGL A , MAURER D , WILLHEIM M 
Published: December 2004

SUMMARYNeutrophils are effector cells of innate immune responses. Stimulated by interferon-γ (IFN-γ) to express HLA-DR, neutrophils acquire accessory cell functions for superantigen-mediated T cell activation. In vitro HLA-DR induction on neutrophils varies in a functionally relevant way as levels of MHC class II expression and magnitude of neutrophil induced T cell responses are correlated functions. The aim of this study was to assess whether IFN-γ induces HLA-DR on human neutrophils in a donor dependent fashion in vivo and to define regulatory events operative in MHC class II expression of neutrophils. In vivo administration of rhIFN-γ in 55 patients with renal cell carcinoma resulted in a varying increase of HLA-DR on neutrophils. By setting a cut-off for response at&gt;10% HLA-DR positive neutrophils, HLA-DR responders (51%) were as frequent as nonresponders (49%). In vivo kinetic studies revealed a peak expression of HLA-DR on neutrophils 48 h after rhIFN-γ application, while nonresponders remained HLA-DR negative over a 72-h period. In vitro IFN-γ stimulated neutrophils recapitulated the response profiles observed in vivo. No differences in IFN-γ dependent CD64 and invariant chain expression, and IFN-γ serum levels were observed among the response subgroups. HLA-DR mRNA was detected in neutrophils from rhIFN-γ treated responders and nonresponders, HLA-DR protein solely in lysates of responder neutrophils. IFN-γ stimulated HLA-DR expression on neutrophils is subject to donor dependent variations in vivo, which result from rather post-transcriptional than transcriptional regulation. Due to their abundance in inflammatory reactions heterogeneous HLA-DR expression by neutrophils could determine the outcome of superantigen-driven diseases.
Abnormalities in the T and NK lymphocyte phenotype in patients with Nijmegen breakage syndrome
Authors: MICHAŁKIEWICZ J , BARTH C , CHRZANOWSKA K , GREGOREK H , SYCZEWSKA M , WEEMAES C M B , MADALIŃSKI K , DZIERŻANOWSKA D , STACHOWSKI J 
Published: December 2004

SUMMARYNijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by spontaneous chromosomal instability with predisposition to immunodeficiency and cancer. In order to assess the cellular basis of the compromised immune response of NBS patients, the distribution of functionally distinct lymphocyte subsets in peripheral blood was evaluated by means of double-colour flow cytometry. The study involved the 36 lymphopenic patients with a total lymphocyte count ≤1500 µl (group A) and seven patients (group B) having the absolute lymphocyte count comparable with the age-matched controls (≥3000 µl). Regardless of the total lymphocyte count the NBS patients showed: (1) profound deficiency of CD4+ and CD3/CD8+ T cell subsets and up to fourfold increase in natural killer (NK) cells, almost lack of naive CD4+ T cells expressing CD45RA isoform, unchanged percentage of naive CD8+ cell subset (CD8/CD45RA+) but bearing the CD8 receptor of low density (CD8low); (2) normal expression of CD45RA isoform in the CD56+ lymphocyte subset, profound decrease in αβ but up to threefold increase in γδ-T cell-receptor (TCR)-positive T cells; (3) shift towards the memory phenotype in both CD4+ and CD8+ lymphocyte subpopulations expressing CD45RO isoform (over-expression of CD45RO in terms of both the fluorescence intensity for CD45RO isoform and the number of positive cells); and (4) an increase in fluorescence intensity for the CD45RA isoform in NK cells population. These results indicate either a failure in T cell regeneration in the thymic pathway (deficiency of naive CD4+ cells) and/or more dominant contribution of non-thymic pathways in lymphocyte renewal reflected by an increase in the population of CD4+ and CD8+ memory cells, γδ-TCR positive T as well as NK cell subsets.
Bruton's tyrosine kinase defect in dendritic cells from X-linked agammaglobulinaemia patients does not influence their differentiation, maturation and antigen-presenting cell function
Authors: GAGLIARDI M C , FINOCCHI A , ORLANDI P , CURSI L , CANCRINI C , MOSCHESE V , MIYAWAKI T , ROSSI P 
Published: December 2004

SUMMARYX-linked agammaglobulinaemia (XLA) is a primary immunodeficiency disease characterized by very low levels or even absence of circulating antibodies. The immunological defect is caused by deletions or mutations of Bruton's tyrosine kinase gene (Btk), whose product is critically involved in the maturation of pre-B lymphocytes into mature B cells. Btk is expressed not only in B lymphocytes but also in cells of the myeloid lineage, including dendritic cells (DC). These cells are professional antigen presenting cells (APC) that play a fundamental role in the induction and regulation of T-cell responses. In this study, we analysed differentiation, maturation, and antigen-presenting function of DC derived from XLA patients (XLA-DC) as compared to DC from age-matched healthy subjects (healthy-DC). We found that XLA-DC normally differentiate from monocyte precursors and mature in response to lipopolysaccharide (LPS) as assessed by de novo expression of CD83, up-regulation of MHC class II, B7·1 and B7·2 molecules as well as interleukin (IL)-12 and IL-10 production. In addition, we demonstrated that LPS stimulated XLA-DC acquire the ability to prime naïve T cells and to polarize them toward a Th1 phenotype, as observed in DC from healthy donors stimulated in the same conditions. In conclusion, these data indicate that Btk defect is not involved in DC differentiation and maturation, and that XLA-DC can act as fully competent antigen presenting cells in T cell-mediated immune responses.
The diagnostic use of the rhTSH/thyroglobulin test in differentiated thyroid cancer patients with persistent disease and low thyroglobulin levels
Authors: Pellegriti Gabriella , Scollo Claudia , Regalbuto Concetto , Attard Marco , Marozzi Paola , Vermiglio Francesco , Violi Maria Antonella , Cianci Michelangela , Vigneri Riccardo , Pezzino Vincenzo , Squatrito Sebastiano 
Published: December 2004

Summarybackground Serum thyroglobulin (Tg) measurement after TSH stimulation, by either thyroid hormone withdrawal or recombinant human TSH (rhTSH) administration, is the most sensitive method for early detection of patients with persistent or recurrent differentiated thyroid cancer (DTC) after total thyroidectomy and 131I ablation. The use of rhTSH is now increasing because it avoids thyroid hormone suppressive therapy (THST) withdrawal and the consequent symptoms of severe hypothyroidism. Current guidelines suggest measurement of serum Tg 4 days after starting a 2‐day course of rhTSH injections, and assumes that Tg reaches maximum serum levels at that time.objective The present study was carried out to evaluate the accuracy of rhTSH/thyroglobulin test in DTC patients with persistent disease and low thyroglobulin levels.patients and measurements A series of 13 DTC patients was selected because they had proven persistent disease associated with low Tg levels (< 2·0 µg/l) under l‐thyroxine treatment. In all of them, serum Tg was > 5·0 µg/l at the last THST withdrawal. We measured serum Tg and TSH levels on days 0·5, 1, 1·5, 2, 4, 7, 10 and 15 after the first of a 2‐day course of intramuscular rhTSH injections.results Serum Tg values were variable in terms of both peak and time‐course. Detectable serum Tg levels were recorded on day 4 in all patients. However, among these 13 patients, the peak Tg value was reached earlier than day 4 in three patients and later in two others. In one patient, Tg level at day 2 was higher (3·0 µg/l) than at day 4 (1·8 µg/l). In six of the 13 patients studied we compared Tg values after rhTSH to those subsequently obtained after THST withdrawal: in five of them Tg values were two to three times higher after the latter stimulation. Serum Tg value variability after rhTSH was partially accounted for by variability of serum TSH levels, which were inversely related to patient body surface.conclusions In DTC patients with persistent disease and low Tg levels, optimization of the diagnostic use of Tg measurement after rhTSH may require rhTSH dose adjustment to the patient body surface area and repeated blood sampling, in order to improve diagnostic accuracy. In these patients not even a TSH‐stimulated serum Tg cut‐off of 2·0 µg/l on day 4 provides 100% accuracy, whereas a cut‐off of 1·0 µg/l seems more appropriate. Therefore, in this subset of patients, if any detectable Tg level ≥ 1·0 µg/l is found after rhTSH, re‐evaluation after THST should be advised.
Low cholesteryl ester transfer protein (CETP) concentration but normal CETP activity in serum from patients with short‐term hypothyroidism Lack of relationship to lipoprotein abnormalities
Authors: Dedecjus Marek , Masson David , Gautier Thomas , De Barros Jean‐Paul Pais , Gambert Philippe , Lewinski Andrzej , Adamczewski Zbigniew , Moulin Philippe , Lagrost Laurent 
Published: December 2004

Summaryobjectives Hypothyroidism is associated with a number of abnormalities in lipoprotein metabolism. Although alterations in neutral lipid exchanges among plasma lipoproteins might be one characteristic feature of hypothyroidism, a few human studies of cholesteryl ester transfer protein (CETP) activity have led to heterogeneous and fragmentary observations. The aim of the present study was to analyse the influence of short‐term hypothyroidism on CETP activity, as well as on the structure and composition of lipoproteins.patients, design and measurements Sixty‐six thyroidectomized patients were withdrawn from L‐thyroxine (L‐T4) treatment for 5 weeks. Subsequently, L‐T4 therapy was reinstated for 2 months and patients were compared to 61 matched normolipidaemic controls. Serum CETP activity and mass concentration, serum lipids, apolipoproteins and lipoprotein size distribution were determined in the three groups.results Serum CETP mass concentration was significantly decreased in short‐term hypothyroid patients, as compared to control subjects (3·22 ± 0·98 vs. 3·79 ± 1·2 mg/l, respectively; P < 0·001), and the values were normalized during L‐T4 therapy. The ability of endogenous serum lipoproteins to interact with CETP was normal in short‐term hypothyroid patients. Concordant observations were made regardless of whether neutral lipid transfers were measured from high‐density lipoproteins (HDL) toward apo B‐containing lipoproteins or from liposomes toward HDL. The size distribution of HDL was significantly different in short‐term hypothyroid patients, compared to either the control or treated subgroups, with significant higher proportions of large‐sized HDL2b and HDL2a (HDL2b: 13·6 ± 6·5% before vs. 8·5 ± 4·2% during L‐T4 therapy, P < 0·05; HDL2a, 33·0 ± 7·0% before vs. 29·3 ± 6·9% during L‐T4 therapy, P < 0·05). Although serum CETP mass concentration correlated negatively with the HDL2 to HDL3 ratio in control subjects (r = −0·588; P < 0·0001), no significant correlations were observed in hypothyroid patients, regardless of whether they were treated or not. Similarly, whereas the previously recognized positive correlation of CETP mass concentration with serum LDL cholesterol levels was found in control subjects (r = 0·264; P < 0·05), no significant correlations appeared in treated and untreated patients.conclusions Short‐term hypothyroidism may constitute an unique situation in which concomitant alterations in serum cholesteryl ester transfer protein concentration and lipoprotein parameters are disconnected.
Blood pressure in children and adolescents with congenital adrenal hyperplasia (21‐hydroxylase deficiency): a preliminary report
Authors: Roche Edna F. , Charmandari Evangelia , Dattani Mehul T. , Hindmarsh Peter C. 
Published: December 2004

Summarybackground Classical congenital adrenal hyperplasia (CAH) is characterized by a defect in cortisol and aldosterone secretion, adrenal hyperandrogenism, impaired adrenal medullary function and insulin insensitivity. The latter along with the increased tendency towards obesity raises questions whether other cardiovascular risk factors are altered in CAH.objective To evaluate 24‐h ambulatory blood pressure and obesity in patients with salt‐wasting 21‐hydroxylase deficiency diagnosed in the neonatal period and treated with hydrocortisone and 9α‐fludrocortisone thereafter.methods Thirty‐eight children (15 males) aged 11·2 years (range 6·1–18·2 years) underwent 24‐h ambulatory blood pressure monitoring in the hospital setting. Standard anthropometric measures of height, weight and skinfold thickness were undertaken and body mass index (BMI) derived. All data were expressed as standard deviation scores (SDS) using the UK Growth Reference data.results Mean daytime systolic blood pressure SDS (1·8, SD 1·1) was significantly higher than the reference population (P < 0·001), and 58% of patients (67% males; 52% females) had systolic hypertension. Mean daytime diastolic blood pressure SDS (0·8, SD 0·8) was also elevated and 24% (13% males; 37% females) had diastolic hypertension. Eighty‐four per cent had absence of the physiological nocturnal dip in systolic blood pressure. Height SDS was similar to the reference population but BMI SDS was higher (P < 0·001). BMI SDS was related to systolic blood pressure SDS (r = 0·34; P = 0·03) and the effect was most marked in females where it was related to measures of truncal fat (r = 0·82; P = 0·002).conclusions Children with salt‐wasting 21‐hydroxylase deficiency have elevated 24‐h ambulatory blood pressure and absence of the physiological nocturnal dip in blood pressure. These abnormalities are associated with a raised BMI, particularly in females. Regular measurement and plotting of blood pressure should be part of the management of children with classical CAH.
Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism
Authors: Pannett A. A. J. , Kennedy A. M. , Turner J. J. O. , Forbes S. A. , Cavaco B. M. , Bassett J. H. D. , Cianferotti L. , Harding B. , Shine B. , Flinter F. , Maidment C. G. H. , Trembath R. , Thakker R. V. 
Published: December 2004

Summarybackground Familial isolated hyperparathyroidism (FIHP) is an autosomal dominant disorder characterized by uniglandular or multiglandular parathyroid tumours that occur in the absence of other endocrine tumours. The disorder may represent either an early stage of multiple endocrine neoplasia type 1 (MEN1), or an allelic variant of MEN1, or a distinct entity involving another locus. We have explored these possibilities in seven families in whom primary hyperparathyroidism occurred as the sole endocrinopathy.methods Seven FIHP families were ascertained and venous blood samples obtained from 35 members (17 affected and 18 unaffected) for DNA sequence analysis of the MEN1 gene. The mean (± SD) follow‐up period in the 17 affected members was 15·06 (± 8·83) years.results Four heterozygous germline mutations of the MEN1 gene were identified. These consisted of two 4‐bp intragenic deletions that would result in prematurely truncated proteins, and two missense (Asp153Val and Ala411Pro) mutations. Furthermore, analysis of parathyroid tumour DNA from one individual revealed a loss of the wild‐type allele and retention of the mutant allele, consistent with Knudson's ‘two‐hit’ model of hereditary cancer and a tumour suppressor role for MEN1 in FIHP.conclusions Our results provide further support for FIHP being a distinct allelic variant of MEN1, and an analysis of the 16 mutations reported to date indicate that FIHP is associated with a higher frequency of missense MEN1 mutations.
Evaluation of the reproducibility of the GHRH plus GHRP‐6 test of growth hormone reserve in adults
Authors: Popovic Vera , Pekic Sandra , Micic Dragan , Damjanovic Svetozar , Marikovic Jelena , Simic Mirjana , Dieguez Carlos , Casanueva Felipe F. 
Published: December 2004

Summarybackground  The diagnosis of GH deficiency (GHD) is controversial, relying on GH secretion elicited by the provocative tests of GH reserve. However, the performance of most of the tests in use have not been evaluated rigorously. The repeatability of a test is a prerequisite before evaluating its diagnostic capability.objective  The combined administration of GH‐releasing hormone (GHRH) and GH‐releasing hexapeptide (GHRP‐6) is an efficacious test of GH reserve in adults, and the target of this work was to evaluate its reproducibility.methods  Seventeen healthy subjects were challenged with GHRH plus GHRP‐6 (1 µg/kg i.v.). All subjects underwent four tests on different days separated by at least 2 months. GH peaks were evaluated by several mathematical analyses of reproducibility.results  As a group, the subjects showed high reproducibility after the four tests, with GH peaks of 46·0 ± 5·1; 48·4 ± 6·4; 50·1 ± 5·4 and 52·9 ± 5·8 µg/l, respectively (1 µg/l = 3 mU/l). Individually analysed, the reproducibility was good, and the regression analysis showed a correlation between tests 1 and 2 of R = 0·729, P < 0·0009, between tests 1 and 3 of R = 0·710, P < 0·001, and between tests 1 and 4 of R = 0·683, P < 0·002. Under mathematical analysis, the multiple correlation coefficient analysis, analysis of variance (anova) with repeated measurements, repeatability index, the simplest coefficient of variation and the intraclass correlation coefficient (ICC) all unambiguously showed that the GHRH + GHRP‐6 test was reproducible. Furthermore, the repeated tests did not alter the biochemical diagnosis of the subjects, with absence of false‐positive values.conclusions  The GHRH + GHRP‐6 test of GH reserve is reproducible in adult subjects.
Oestrogen receptor α genotype, and interactions between vitamin D receptor and transforming growth factor‐β1 genotypes are associated with quantitative calcaneal ultrasound in postmenopausal women
Authors: Koh Jung‐Min , Nam‐Goong Il Seong , Hong Jeong Soo , Kim Hong‐Kyu , Kim Jae Seung , Kim Shin‐Yoon , Kim Ghi Su 
Published: December 2004

Summaryobjective  Quantitative ultrasound (QUS) of bone is a new radiation‐free, low‐cost method that measures both bone mass and quality. We investigated associations between QUS parameters and polymorphisms of vitamin D receptor (VDR), oestrogen receptor α (ERα) and transforming growth factor‐β1 (TGF‐β1) genes in postmenopausal women residing in a community.design  QUS and anthropometric characteristics were measured in postmenopausal women, and compared with regard to the VDR, ERα and TGF‐β1 genotypes.patients  Among the 552 women who participated in the population‐based Chung‐Up osteoporosis prevalence study, 206 postmenopausal women, aged 60–69 years, were included.measurements  Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the left calcaneus using QUS measurement of bone, and a stiffness index (SI) was calculated. We determined the BsmI and FokI polymorphisms of VDR gene and the XbaI and PvuII polymorphisms of ERα gene using the polymerase chain reaction‐restriction fragment length polymorphism method, and Τ29 → C polymorphism of TGF‐β1 gene using an allele‐specific polymerase chain reaction assay.results  The XbaI polymorphism of ERα gene was significantly associated with SI (T‐score) and BUA (P = 0·040 and P = 0·024, respectively). There were no significant differences in any QUS parameters among the genotypes of VDR and TGF‐β1. However, significant genetic interactions between the VDR and TGF‐β1 genotypes, were noted (P = 0·017 for SI and P = 0·028 for BUA between the BsmI and Τ29 → C polymorphisms; P = 0·038 for SI and P = 0·035 for BUA between the FokI and T29 → C polymorphisms). The combined genotypes between the BsmI and T29 → C polymorphisms or between the FokI and T29 → C polymorphisms, were significantly associated with the QUS parameters.conclusions  This study indicates that the XbaI polymorphism of ERα gene may influence the Quantitative ultrasound parameters in postmenopausal women, and suggests the need for further investigations about the interactions between the VDR and TGF‐β1 genes.