bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autologous apoptotic T cells interact with dendritic cells, but do not affect their surface phenotype or their ability to induce recall immune responses
Authors: NEWTON P J , WELLER I V D , KATZ D R , CHAIN B M 
Published: December 2004

SUMMARYDendritic cells (DCs) play an important role in determining immunogenicity and the subsequent immune response. They may also have a role in maintaining peripheral tolerance to self-antigens by initiating an immune response only in the context of danger signals released from cells during stress, damage or death. These signals may originate from surrounding T cells as well as from other cells. Therefore, in this study the effect of autologous T cell injury on DC morphology and function has been investigated. Co-incubation of apoptotic or necrotic T cells with immature DCs altered their morphology towards a more mature appearance, with more cells showing activation as judged by spreading and formation of arborizing long processes. The apoptotic autologous T cells were rarely phagocytosed by immature DCs, compared to macrophages. The DC surface phenotype was not affected by the co-incubation with autologous injured T cells. The ability of DCs to elicit a secondary immune response was not altered by exposure to autologous injured T cells. These findings suggest that DC can continue to function in T cell activation, rather than in tolerogenic mode, even in the presence of large numbers of dying autologous T cells, such as may be present in the aftermath of an acute antiviral response.
Characterization of bronchoalveolar lavage T cell subsets in sarcoidosis on the basis of CD57, CD4 and CD8
Authors: KURUMAGAWA T , SEKI S , KOBAYASHI H , KOIKE Y , KANOH S , HIRAIDE H , MOTOYOSHI K 
Published: December 2004

SUMMARYT cells expressing CD57 (a natural killer cell marker) with interferon-γ (IFN-γ) producing capacity increase under various conditions. CD57+ T cells are also present in the bronchoalveolar lavage fluid (BALF) of sarcoidosis, and several phenotypical and functional analyses of these cells have been reported. In the present study, BALF T cells obtained from 52 patients with sarcoidosis were classified further into CD4+CD57+ T cells, CD4+CD57– T cells, CD8+CD57+ T cells and CD8+CD57– T cells and their phenotypes and functional characteristics were assessed. Substantial proportions of these T cell subsets expressed natural killer cell markers CD161 and CD122. The biased expansion of Vβ2 T cells was observed in both CD4+CD57+ T cells and CD4+CD57– T cells in BALF from most patients, while the expansion of other Vβ T cells was also observed in some patients. Unexpectedly, the biased expansion of certain Vβ T cells was also seen in either CD8+CD57+ T cells or CD8+CD57– T cells, while the expanded Vβ T cells in CD8+ T cells differed substantially among individuals. BALF T cells showed a remarkably lower T cell receptor (TCR) intensity than that of peripheral blood T cells. Both CD8+ T cell subsets in BALF of sarcoidosis expressed the intracellular perforin/granzyme B, while all four subsets expressed intracellular IFN-γ after in vitro activation, and CD4+ T cells, especially CD4+CD57+ T cells, expressed tumour necrosis factor-α. These findings indicate that CD57+ T cells as well as CD57– T cells in the BALF are phenotypically and functionally different from peripheral blood T cells and may play an important role in the Th1 dominant state and inflammation in pulmonary sarcoidosis.
In vitroco-stimulation with anti-CD28 synergizes with IL-12 in the generation of T cell immune responses to leukaemic cells; a strategy forex-vivogeneration of CTL for immunotherapy
Authors: ORLEANS-LINDSAY J K , DERU A , CRAIG J I O , PRENTICE H G , LOWDELL M W 
Published: December 2004

SUMMARYThe existence of an immune based graft-versus-leukaemia (GvL) effect highlighted the prospect of managing relapsed leukaemias with T cell-based adoptive immunotherapy. Thus, various strategies have been explored for the in vitro expansion of acute myeloid leukaemia (AML)-specific T cells. In a popular approach, AML blasts have been genetically modified to express co-stimulatory molecules essential for effective T cell priming. One such tactic has been the modification of AML cells to express the B7/CD80 co-stimulatory molecule that binds to CD28 on T cells initiating events that culminate in enhanced cytokine production, proliferation and development of effector functions by T cells. The success of these strategies has been limited by difficulties in attaining sufficient transduction efficiencies and associated high levels of CD80 expression. We demonstrate that these problems can be circumvented by using anti-CD28 monoclonal antibody. Furthermore, we show that the synergistic relationship between CD80/CD28 pathway and interleukin 12 cytokine (IL-12), documented in the generation of cytotoxic T lymphocytes (CTL) for solid tumours, also applies to AML. CD28/IL-12 synergy facilitated the proliferation of allogeneic T cells in response to stimulation with primary AML blasts. The synergy also favoured generation of a Th1-type immune response, evidenced by gamma interferon (IFN-γ) secretion and facilitated naive and memory T cell proliferation. Unlike some methods of in vitro T cell expansion, use of CD28/IL-12 synergy left T cells in the physiologically appropriate CD45RA–/CCR7– subsets known to be associated with immediate cytotoxic functions.
T cell receptor VB repertoire diversity in patients with immune thrombocytopenia following splenectomy
Authors: FOGARTY P F , RICK M E , ZENG W , RISITANO A M , DUNBAR C E , BUSSEL J B 
Published: December 2004

SUMMARYIn recent years, a pathophysiological role for T cells in immune thrombocytopenia (ITP) has been established. We applied cDNA size distribution analysis of the T cell receptor (TCR) β-variable (VB) complementarity-determining region 3 (CDR3) in order to investigate T cell repertoire diversity among immune thrombocytopenia patients who had either responded or not responded to splenectomy, and compared them to normal controls. ITP patients who had had a durable platelet response to splenectomy showed a mean 2·8 ± 2·1 abnormal CDR3 size patterns per patient, similar to healthy volunteers (2·9 ± 2·0 abnormal CDR3 size patterns). In contrast, patients unresponsive to splenectomy demonstrated evidence of significantly more clonal T cell expansions than patients who had responded to splenectomy or controls (11·3 ± 3·3 abnormal CDR3 size patterns per patient; P &lt; 0·001). Of the VB subfamilies analysed, VB3 and VB15 correlated with response or non-response to splenectomy, each demonstrating oligoclonality in non-responding patients (P &lt; 0·05). These findings suggest that removal of the spleen may lead directly or indirectly to reductions in T cell clonal expansions in responders, or that the extent of T cell clonality impacts responsiveness to splenectomy in patients with ITP.
Influence of human T lymphotrophic virus type I on cryptogenic fibrosing alveolitis − HTLV-I associated fibrosing alveolitis: proposal of a new clinical entity
Authors: MATSUYAMA W , KAWABATA M , MIZOGUCHI A , IWAMI F , WAKIMOTO J , OSAME M 
Published: December 2004

SUMMARYHuman T lymphotrophic virus type-I (HTLV-I), a human retrovirus, infects CD4+ lymphocytes and is thought to modify their function; a possible association with pulmonary diseases has also been suggested. However, little is known about the influence of HTLV-I on cryptogenic fibrosing alveolitis (CFA), a chronic inflammatory interstitial lung disease of unknown aetiology. In order to clarify the influence of HTLV-I infection on CFA, 72 CFA patients with and without HTLV-I infection were examined. HTLV-I positive CFA patients were likely to have larger affected areas and to show traction bronchiectasis with honeycombing change. An imbalance of matrix metalloproteinases and tissue inhibitor of metalloproteinases were also observed in the BALF of HTLV-I positive CFA patients. CD3+/CD25+ lymphocyte percentage was significantly higher in the BALF of HTLV-I positive patients compared to negative patients. MIP-1α, IP-10 and sICAM levels in BALF were also significantly higher in HTLV-I positive patients than in negative patients. The levels of MCP-1 and IL-8 were not significantly different. In HTLV-I positive patients, the MIP-1α and IP-10 levels showed a significant positive correlation with percentage of CD3+/CD25 lymphocytes. HTLV-I positive CFA patients showed a larger lesion than negative patients and exhibited increased levels of certain cytokines that correlated with activated T cells in the BALF. We suggest that HTLV-I infection may contribute to the development of CFA via activation of T cells. We also propose that these features should be taken into consideration in the treatment of CFA in HTLV-I infected individuals.
Plasmodium falciparuminfection of the placenta affects newborn immune responses
Authors: ISMAILI J , VAN DER SANDE M , HOLLAND M J , SAMBOU I , KEITA S , ALLSOPP C , OTA M O , MCADAM K P W J , PINDER M 
Published: December 2004

SUMMARYThe effects of exposure to placental malaria infection on newborn immunological responses, in particular Th1/Th2 cytokines and antigen-presenting cell (APC) function, were compared between cord blood mononuclear cells (CBMC) from parasitized and non-parasitized placentas of Gambian women. Cells were analysed in vitro for their ability to respond to mitogens [phorbol myristate acetate (PMA)/ionomycin, phytohaemagglutinin (PHA)], a malaria-unrelated test antigen [purified protein derivative of Mycobacterium tuberculin[purified protein derivative (PPD)] and Plasmodium falciparum schizont extracts. Mitogens induced strong proliferation and secretion of high concentrations of both IL-13 and sCD30 in CBMC from both groups. Conversely, significantly lower amounts of IFN-γ were induced in the parasitized group in response to low doses of PHA. Protein antigens induced very low amounts of all tested cytokines, in particular IFN-γ. However, a significantly higher release of sCD30 was observed in response to schizont extracts in the parasitized group. Addition of LPS to activate APC to low doses of PHA or schizont extracts increased the IFN-γ production in both groups but levels remained lower in CBMC from the parasitized group. This result correlates with the lower production of IL-12 found following lipopolysaccharide (LPS) stimulation in this group. Taken together, these data show that placental infection with P. falciparum affects Th1 differentiation and sCD30 priming of neonatal lymphocytes and that the probable mode of action is via APC.
Cancer immunotherapy using RNA-loaded dendritic cells
Authors: PONSAERTS P , VAN TENDELOO V F I , BERNEMAN Z N 
Published: December 2004

SUMMARY
Dendritic cells (DC) are the most professional antigen-presenting cells of the immune system and are capable of initiating immune responses in vitro and in vivo. One of the great challenges in immunotherapy protocols is to introduce relevant antigens into DC for stimulation of major histocompatibility complex (MHC) class I- and class II-restricted anti-tumour or anti-viral immunity. This review will focus on the development of mRNA-loaded DC-based immunotherapy vaccines. First, several published results concerning mRNA transfection efficiency in DC are compared. Next, an overview is given for several published studies describing CD8+ and CD4+ T-cell clone activation using RNA-loaded DC. These data show that RNA-loaded DC efficiently process and present antigenic epitopes. Next, published data from in vitro T-cell activation studies using RNA-loaded DC are summarized and provide evidence that RNA-loaded DC can efficiently stimulate in vitro primary and secondary immune responses. Finally, the summarized data provide evidence that RNA-loaded DC are a promising strategy for the development of future cancer vaccination strategies.
Profile of neurokinin B concentrations in maternal and cord blood in normal pregnancy
Authors: Sakamoto Rie , Osada Hisao , Iitsuka Yoshinori , Masuda Kentarou , Kaku Kenshi , Seki Katsuyoshi , Sekiya Souei 
Published: December 2004

Summaryobjective Neurokinin B (NKB) is a neuropeptide with a vasopressor effect belonging to the tachykinin family. This neuropeptide has attracted attention since recent reports indicated that it is also secreted in the placenta and is probably a cause of pre‐eclampsia. To provide a basis for elucidation of the relationship between pre‐eclampsia and NKB, this study aimed to clarify the trend of changes in blood NKB levels during normal pregnancy by measuring NKB concentrations in maternal blood during various gestational periods and in umbilical blood.methods Fifty‐nine normal pregnant women, 12 normal puerperal women and 24 nonpregnant women were studied. The normal pregnant women comprised of 24 at 8–20 weeks’ gestation (early), 11 at 28–34 weeks (middle) and 24 at 35–40 weeks (late). Plasma was separated from peripheral blood samples, umbilical venous blood samples (n = 24) and umbilical arterial blood samples (n = 9). Peptide fractions were extracted from each plasma sample and NKB concentrations were measured by the radioimmunoassay method.results The NKB concentration in early pregnancy was not significantly different from that in the nonpregnant state. During pregnancy, the blood NKB concentration increased with advance in gestational week, and a correlation was demonstrated by a linear regression equation. The concentration during puerperium was significantly lower than that in late pregnancy. The umbilical blood concentration was significantly higher than the maternal blood concentration in late pregnancy. There was no significant difference between umbilical venous and arterial blood.conclusion This study demonstrated that NKB secreted from the placenta during pregnancy enters both the maternal and fetal circulation. These results suggest that NKB may modulate fetoplacental haemodynamics through a paracrine mechanism.
Long‐term follow‐up of bone mineral density in Addison's disease
Authors: Jódar Esteban , Valdepeñas María Pilar Ruiz , Martinez Guillermo , Jara Antonino , Hawkins Federico 
Published: December 2004

Summarybackground and aims There is conflicting evidence regarding the long‐term effects of long‐term glucocorticoid replacement therapy (GRT) on bone mineral density (BMD) in patients with chronic adrenal insufficiency. Our aim was to evaluate bone turnover and changes in BMD in patients on GRT.patients and methods We have studied 25 subjects (six men, 19 women; aged 62·4 ± 11·3 years, duration of disease 21·7 ± 11·7 years, fasting cortisol 63 ± 36 nmol/l) on GRT (hydrocortisone 30 mg/day or prednisone 7·5 mg/day). BMD was assessed at the lumbar spine (LS; L2–L4), proximal femur (PF) and ultra distal radius (UR) by dual energy X‐ray absorptiometry (DXA). The rates of bone loss were calculated using previous DXA measurements at the LS (48 and 60 months earlier). Serum calcium, phosphate alkaline phosphatase (ALP), bone ALP, serum osteocalcin (BGP), intact parathyroid hormone (PTH) and 25(OH) vitamin D were also measured.results BMD [Z‐score; 95% confidence interval (95% CI)] was normal at the LS: (−1·15–+0·07); PF: (−0·90–+0·22) and UDR (−0·77–+0·36). No significant differences were found according to the type of replacement therapy or sex. No significant bone loss (g/cm2; 95% CI) was detected at the LS: (−0·021–+0·023). Fifty‐six per cent of patients met osteoporotic criteria; a greater proportion of patients treated with prednisone had osteoporosis compared with those an hydrocortisone. All bone markers were in their normal ranges.conclusions Patients on long‐term therapy do not show accelerated bone loss at the lumbar spine. Nevertheless, a considerable proportion of patients, mainly those treated with prednisone, showed densitometric osteoporosis.
Ultrasonography‐guided fine‐needle aspiration of thyroid incidentaloma: correlation with pathological findings
Authors: Nam‐Goong Il Seong , Kim Ha Young , Gong Gyungyub , Lee Ho Kyu , Hong Suck Joon , Kim Won Bae , Shong Young Kee 
Published: December 2004

background  There are many reports that diagnostic accuracy of fine‐needle aspiration (FNA) of thyroid is improved with ultrasound guidance, especially for impalpable nodules. Despite its general acceptance, routine use of ultrasound‐guided fine‐needle aspiration (USGFNA) has been the source of much controversy due to the lack of large‐scale studies and lack of data on the natural course of well‐differentiated thyroid cancer of small size.objective  The aim of our study was to define the rate of malignancy in relatively large numbers of patients with incidentally detected impalpable thyroid nodules and to assess the extent of disease in patients with suspicious or malignant cytology on USGFNA of thyroid nodules by surgery.patients  We retrospectively reviewed the medical records of the 267 patients who underwent USGFNA of incidental thyroid nodules from January 2000 to December 2001.results  Three hundred and seventeen nodules from 267 patients were aspirated. The average size of nodules was 0·9 ± 0·3 cm, a range of 0·2 cm to 1·5 cm. All 317 lesions were impalpable. Cytological diagnosis included 101 inadequate specimen (32%), 139 benign (44%), 29 indeterminate (9%), four suspicious of follicular or Hürthle cell neoplasm (1%), 42 papillary carcinoma (13%) and two others. The size of the nodule was not related to the probability of getting an adequate specimen for cytological diagnosis. Forty of 48 patients with suspicious or malignant cytology underwent surgery. All 35 patients with a cytological diagnosis of papillary carcinoma were confirmed to have papillary carcinoma on histological results. One of three patients with a cytological diagnosis of follicular neoplasm had a follicular carcinoma. In 36 patients with well‐differentiated thyroid cancer, extrathyroidal extension was observed in 44% (16/36), regional lymph node metastasis was found in 50% (18/36) and multifocal tumours were found in 39% (14/36).conclusions  The rate of malignancy in incidentally detected impalpable thyroid nodules was 12% in retrospective analysis of our patients. In this subgroup, 69% (25/36) of patients had either extrathyroidal extension or regional node involvement and 39% had multifocal tumours at surgery. This suggests that the small size alone does not guarantee low risk in incidentally found thyroid cancers. USGFNA is a useful diagnostic method in these patients.
Vasopressin responsiveness of subclinical Cushing's syndrome due to ACTH‐independent macronodular adrenocortical hyperplasia
Authors: Tatsuno Ichiro , Uchida Daigaku , Tanaka Tomoaki , Koide Hisashi , Shigeta Azusa , Ichikawa Tomohiko , Sasano Hironobu , Saito Yasushi 
Published: December 2004

Summaryobjective  Vasopressin (AVP) is reported to be an important factor for regulating cortisol secretion in patients with Cushing's syndrome due to ACTH‐independent macronodular adrenocortical hyperplasia (AIMAH). Recently, there have been several case reports of subclinical Cushing's syndrome due to AIMAH, in which the pathophysiological role of AVP has been unknown. The aim was to conduct an extensive investigation of AVP in the autonomous secretion of cortisol in subclinical Cushing's syndrome due to AIMAH.patients and measurements  Five cases of AIMAH with subclinical Cushing's syndrome underwent prospective study including physical examination, imaging (MRI, CT and 131I‐adosterol scintigraphy) and endocrinological evaluation that comprised basal plasma cortisol levels and urinary excretions of steroid metabolites, a dexamethasone suppression test and an AVP stimulation test. In case 1, left adrenalectomy was performed and the pathological diagnosis of AIMAH was established. An in vitro experiment using the cultured AIMAH adrenal cells was conducted to investigate cortisol secretion and expression of the V1‐AVP receptor, mRNA by RT–PCR.results  All five cases were discovered incidentally to have bilateral adrenal nodules. Imaging by MRI and CT revealed large multinodular lesions in both adrenal glands, which showed positive uptake on 131I‐adosterol scintigraphy. Although the basal values of plasma cortisol and urinary excretions of steroid metabolites were within normal limits, autonomous secretion of cortisol was assumed to occur because of lack of suppression during dexamethasone suppression. The five patients had no overt signs of Cushing's syndrome, and they were therefore diagnosed with subclinical Cushing's syndrome due to AIMAH. In all five patients, AVP stimulated cortisol secretion in vivo, whereas desmopressin acetate failed to affect cortisol secretion. In case 1, AVP stimulated cortisol secretion from cultured AIMAH adrenal cells, but this secretion had no relationship with cAMP production. In addition, over‐expression of V1‐AVP receptor mRNA in AIMAH tissue was determined by RT–PCR.conclusion  Patients with subclinical Cushing's syndrome due to AIMAH commonly exhibit cortisol responsiveness to AVP, and this is probably mediated through activation of overexpressed V1‐AVP receptors.
Size at birth, the metabolic syndrome and 24‐h salivary cortisol profile
Authors: Kajantie Eero , Eriksson Johan , Osmond Clive , Wood Peter J. , Forsén Tom , Barker David J. P. , Phillips David I. W. 
Published: December 2004

Summaryobjective  Individual variation in hypothalamic–pituitary–adrenal axis (HPAA) function has been suggested to be important in linking small size at birth with adult cardiovascular disease and its risk factors, in particular the metabolic syndrome. Human studies have, however, so far only been performed in clinic settings, and their results have not been consistent. Our aim was to assess whether HPAA activity in everyday living circumstances is related to the metabolic syndrome and size at birth.design  Clinical birth cohort study.subjects  A total of 151 women born between 1924 and 1933 in Helsinki, Finland, with measurements at birth recorded. The subjects had previously undergone detailed clinical examinations including fasting cortisol measurement and 1 µg ACTH1−24 and overnight 0·25 mg dexamethasone tests.measurements  Salivary cortisol concentration was measured during a normal 24‐h period: at awakening, 15 and 30 min thereafter, at 12·00 h, 17·00 h and 22·00 h and the following morning. In addition, the following summary variables were calculated: awakening response (mean of the three awakening measurements), mean of all individual measurements, and mean, SD and contrast (a measure of blunted diurnal variability, calculated as mean of morning minus mean of 1200, 1700 and 2200) of all individual z scores.results  Salivary cortisol awakening response was correlated with serum fasting (r = 0·17; P = 0·04), ACTH1−24‐stimulated (r = 0·32; P < 0·0001), and dexamethasone‐suppressed (r = 0·29; P = 0·0004) cortisol concentrations. However, no salivary cortisol measurement was associated with any component of the metabolic syndrome (waist circumference, serum triglyceride, HDL cholesterol or glucose concentration, or blood pressure). Moreover, no correlation was observed between salivary cortisol and weight, length, ponderal index, or gestational age at birth.conclusions  In elderly women, cortisol concentrations in an everyday environment do not appear to be associated with the metabolic syndrome or size at birth. We propose that detecting relationships between HPAA function, prenatal events and adult disease might require a test involving HPAA stimulation.