bluuebunny/crossref_metadata_2025_split huggingface dataset:
Could associations between breastfeeding and insulin‐like growth factors underlie associations of breastfeeding with adult chronic disease? The Avon Longitudinal Study of Parents and Children
Authors: Martin Richard M. , Holly Jeff M. P. , Smith George Davey , Ness Andrew R. , Emmett Pauline , Rogers Imogen , Gunnell David ,   for the ALSPAC Study Team
Published: June 2005

SummaryObjective  The influence of infant feeding method (breast/formula) on growth factor levels could underlie associations of breastfeeding with childhood growth and risk factors for cardiovascular disease. We investigated associations of having been breastfed with serum IGF‐I and IGFBP‐3 in childhood.Methods  Prospective birth cohort study (subsample of the Avon Longitudinal Study of Parents and Children, UK) based on 871 children born in 1991/1992 who underwent clinical follow‐up and blood tests at age 7–8 years. A total of 488 (56%) children had complete data.Results  In children with complete data, the age‐ and sex‐standardized IGF‐I levels of those who were partially or exclusively breastfed were 6·1 and 13·8 ng/ml higher, respectively, than those who were never breastfed (increase in IGF‐I levels per category of breastfeeding exclusivity: 7·1 ng/ml; 95% CI: 0·3–13·9; P = 0·04). In models also controlling for birthweight, gestational age, mother's age, and socioeconomic and dietary factors, the breastfeeding–IGF‐I association was attenuated (regression coefficient: 3·3 ng/ml; −4·2–10·7; P = 0·4); further adjustment for IGFBP‐3 made little difference (regression coefficient: 4·1 ng/ml; −2·8–10·9; P = 0·2). There was little evidence for an association between breastfeeding and IGFBP‐3 or the molar ratio IGF‐I/IGFBP‐3.Conclusions  The positive association between breastfeeding and IGF‐I could be due to residual confounding or to chance. Nevertheless, the magnitude of the fully adjusted effect estimate and the novelty of the association suggest that larger studies should now be conducted to confirm or refute the hypothesis that variations in IGF‐I by infant feeding mode explain associations of breastfeeding with health in later life.
Relationship between fasting serum glucose, age, body mass index and serum 25 hydroxyvitamin D in postmenopausal women
Authors: Need Allan G. , O'Loughlin Peter D. , Horowitz Michael , Nordin B. E. Christopher 
Published: June 2005

SummaryObjective  Because it has been reported that vitamin D, given to mother or infant, can prevent type I diabetes in children, that diabetes is more common in adults with low serum vitamin D and that insulin secretion and action are related to vitamin D levels in healthy young adults we examined the relationship between serum vitamin D metabolites and fasting serum glucose in patients attending our outpatient clinics.Design  Retrospective examination of convenience sample of postmenopausal women attending our osteoporosis clinics.Patients  A total of 753 postmenopausal women attending a university hospital outpatient clinic and not on any treatment known to affect glucose metabolism.Measurements  Body weight and height, serum 25‐hydroxyvitamin D [25(OH)D], serum 1,25‐dihydroxyvitamin D [1,25(OH)2D], serum PTH and fasting serum glucose.Results  On simple correlation fasting serum glucose was a positive function of age (P < 0·05), weight (P < 0·001) and body mass index (BMI) (P < 0·001) and a negative function of serum 25(OH)D (P < 0·001), but it was not significantly related to either serum 1,25(OH)2D, PTH or creatinine. When fasting serum glucose was regressed simultaneously on age, BMI and 25(OH)D, glucose was still an inverse function of 25(OH)D (P = 0·006).Conclusions  Fasting serum glucose increased as 25(OH)D levels fell throughout the range of serum 25(OH)D measured but the greatest increase was observed in those with 25(OH)D below 40 nmol/l.
Age‐related thymic activity in adults following chemotherapy‐induced lymphopenia
Authors: Sfikakis P. P. , Gourgoulis G. M. , Moulopoulos L. A. , Kouvatseas G. , Theofilopoulos A. N. , Dimopoulos M. A. 
Published: June 2005

AbstractBackground  The potential role of the adult thymus in T‐cell homeostasis subsequent to lymphopenia remains the subject of debate. We examined whether thymic activity contributes to reconstitution of the peripheral T‐cell pool, a critical process for patients recovering from antineoplastic therapy.Methods  In selected patients with various neoplastic diseases we assessed peripheral blood lymphocyte subsets by flow‐cytometry, including thymus‐derived, CD4+ T cells expressing the CD45RA molecule, and thymic size rebound by CT scan before, and 3, 6 and 12 months after completion of cytotoxic therapy.Results  Adult patients (n = 21, mean age of 30 years, range 18–49) had higher baseline numbers of B and lower numbers of NK cells than elderly patients (n = 15, mean age of 79 years, range 70–91), while total T‐cell numbers did not differ. Despite the reduction of lymphocyte counts being comparable in the adult (mean of 45%) and elderly (mean of 49%) groups, occurring at, or near, completion of treatment, an enlargement of the previously atrophic thymus was evident in 63% of the adult, but in none of the elderly, subjects. In 22 patients who remained active disease‐free during the following year, B cells and NK cells recovered to pretreatment levels as soon as at 3 months, whereas overall T‐cell recovery occurred at 6 months post‐treatment. Thymic rebound, observed in 11 of 22 patients who were of younger age, correlated significantly with a faster and more complete recovery of CD45RA+ CD4+ (mainly helper‐naïve) T cells.Conclusion  The adult thymus appears capable of regeneration, at least up to middle age, contributing significantly to the reconstitution of the peripheral T‐cell pool following chemotherapy‐induced lymphopenia. In advanced age, however, although peripheral homeostatic pathways appear intact, regeneration of the naïve repertoire is incomplete.
Five cardiac hormones decrease the number of human small‐cell lung cancer cells
Authors: Vesely B. A. , Song S. , Sanchez‐Ramos J. , Fitz S. R. , Alli A. A. , Solivan S. M. , Gower W. R. , Vesely D. L. 
Published: June 2005

AbstractBackground  Four peptide hormones of a family of six hormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C‐natriuretic peptide (CNP), long acting natriuretic peptide (LANP), vessel dilator and kaliuretic peptide, significantly decrease the number of adenocarcinoma cells in culture. The present investigation was designed to determine whether these peptide hormones’ effects are specific to adenocarcinomas or whether they might decrease the number of cancer cells of a different type of cancer, i.e. small‐cell lung cancer.Methods and materials  These six hormones were evaluated for their ability to decrease the number and/or proliferation of human small‐cell lung cancer cells in culture for 24, 48, 72, and 96 h.Results  Within 24 h, vessel dilator, LANP, kaliuretic peptide, ANP and their intracellular mediator cyclic GMP, each at 1 µM, decreased the number of small‐cell lung cancer cells by 63% (P < 0·001), 21% (P < 0·05), 30% (P < 0·05), 39% (P < 0·05), and 31% (P < 0·05), respectively. There was no proliferation in the 3 days following this decrease in cell number. These same hormones decreased DNA synthesis 68% to 82% (P < 0·001). Brain natriuretic peptide and CNP did not decrease the number of small‐cell lung cancer cells or inhibit their DNA synthesis at 1 µM or 10 µM concentrations. Dose‐response curves revealed that at 100 µM, the vessel dilator decreased 92% of the cancer cells in 24 h while BNP had no effect, but CNP caused a 39% decrease. Western blots revealed that the natriuretic peptide receptors A‐ and C‐ were present in these cancer cells.Conclusions  Five peptide hormones significantly decrease the number of human small‐cell lung cancer cells within 24 h and inhibit their proliferation for at least 96 h. Their mechanism of doing so involves inhibition of DNA synthesis mediated in part by cyclic GMP.
Treatment of osteoporotic ovariectomized rats with 24,25(OH)2D3
Authors: Gal‐Moscovici A. , Gal M. , Popovtzer M. M. 
Published: June 2005

AbstractBackground  Antiresorptive therapeutic regimens are the mainstay of current management of osteoporosis. Treatments that are promoting new bone formation are less available and less affordable. Previous studies have suggested that 24,25(OH)2D3 could enhance bone formation. The effect of 24,25(OH)2D3 on bone formation in ovariectomized osteopenic rats (OVX) was evaluated in this study.Materials and methods  Mature Sabra rats were divided into two groups: sham‐operated and OVX. Three months after surgery the OVX and sham‐operated rats were divided into the following subgroups: (1) sham rats injected with vehicle, (2) sham rats injected with 24,25(OH)2D3, (3) OVX rats injected with vehicle, and (4) OVX rats injected with 24,25(OH)2D3. After 2 weeks’ treatment, histomorphometry of the right tibiae was performed.Results  Ovariectomy resulted in a decrease in total bone volume (TBV/TV) and in bone formation (BFR/BS), P < 0·005 and P < 0·05 respectively, when compared with the sham‐operated rats. Beside the decrease in TBV and BFR, the OVX rats showed an increase in osteoclastic bone resorption (P < 0·001 vs. sham). Administration of 24,25(OH)2D3 was followed by an increase in all static and dynamic bone‐forming parameters. The TBV/BV (P < 0·025), osteoblast surface (Ob.S/BS) (P < 0·001), as well as the BFR/BS (P < 0·005), increased in the OVX‐treated group when compared with the OVX‐untreated and sham‐operated rats. This increment in bone formation was associated with a decrease in bone resorption (P < 0·001 in OVX‐treated vs. OVX‐untreated rats).Conclusions  This study shows that 24,25(OH)2D3 may be of benefit in experimental osteopenia following ovariectomy, both by suppressing osteoclastic hyperactivity and by stimulating bone formation.
WNK4 regulates Na+ transport in airways
Authors: Farfel Z. , Mayan H. , Yaacov Y. , Mouallem M. , Shaharabany M. , Pauzner R. , Kerem E. , Wilschanski M. 
Published: June 2005

AbstractBackground  WNK [With No K (lysine)] kinases are essential for regulation of blood pressure and potassium homeostasis. WNK4 expression was recently found not only in the distal nephron but also in chloride‐transporting epithelia. To establish a physiological role for this distribution we studied patients with familial hyperkalaemia and hypertension (FHH), [pseudohypoaldosteronism type II (PHAII)], which is caused by mutations in WNK4.Design  Measurement of nasal potential difference (NPD) and sweat electrolytes were performed in controls, in six subjects with FHH and ten subjects with cystic fibrosis (CF).Results  Basal NPD was higher in FHH compared with controls (n = 20): 22·8 ± 5·7 vs. 16·2 ± 5·3 mV, respectively (P = 0·014). Maximal response to amiloride was also higher in FHH compared with controls: 14·8 ± 3·5 vs. 10·0 ± 4·8 mV, respectively (P = 0·03). In CF these values were 42·9 ± 9·3 and 29·9 ± 7·4 mV, respectively. The kinetics of the amiloride effect were faster in FHH, and as first reported here also in CF, compared with controls. At 30 s, amiloride‐inhibitable residual PD in FHH was 50 ± 30 vs. 81 ± 9% in controls (P = 0·0003) and 56 ± 7% in CF. The response to chloride‐free and isoproterenol solutions, which determines chloride transport activity, was similar in FHH compared with controls [16·0 ± 8·6 vs. 10·4 ± 5·9 mV (P = 0·08)]. Sweat conductivity in FHH was 49·7 ± 7·3 vs. 38·2 ± 8·1 mmol (NaCl eq) L−1 in 16 controls (P = 0·007) and 94·0 ± 19·3 in CF.Conclusions  Mutant WNK4 increases Na+ transport in airways, and therefore it is regulated by wild‐type WNK4. This may be caused by a regulation of ENaC or a K+ channel.
Heightened levels of circulating 20S proteasome in critically ill patients
Authors: Roth G. A. , Moser B. , Krenn C. , Roth‐Walter F. , Hetz H. , Richter S. , Brunner M. , Jensen‐Jarolim E. , Wolner E. , Hoetzenecker K. , Boltz‐Nitulescu G. , Ankersmit H. J. 
Published: June 2005

AbstractBackground  Recently, circulating proteasome core particles (20S proteasome) have been suggested as a marker of cell damage and immunological activity in autoimmune diseases. Aberrant leucocyte activation and increased lymphocyte apoptosis with consecutive T‐cell unresponsiveness is deemed to play a pivotal role in the sepsis syndrome. Moreover sepsis‐induced muscle proteolysis mainly reflects ubiqutin proteasome‐dependent protein degradation. We therefore sought to investigate serum levels of 20S proteasome in critical ill patients.Material and methods  Case–control‐study at a university hospital intensive care unit; 15 patients recruited within 24–48 h of diagnosis of sepsis, 13 trauma patients recruited within 24 h of admission to the ICU, a control group of 15 patients who underwent abdominal surgery, and 15 healthy volunteers. ELISA was used to measure the concentration of 20S proteasome in the sera of the patients and controls. Data are given as mean ± SEM. Mann–Whitney U‐test was used to calculate significance and a P‐value of 0·05 was considered to be statistically significant.Results  Marked increase of 20S proteasome was detected in the sera of septic patients (33 551 ± 10 034 ng mL−1) as well as in trauma patients (29 669 ± 5750 ng mL−1). In contrast, significantly lower concentrations were found in the abdominal surgery group (4661 ± 1767 ng mL−1) and in the healthy control population (2157 ± 273 ng mL−1).Conclusion  Detection of 20S proteasome may represent a novel marker of immunological activity and muscle degradation in sepsis and trauma patients, and may be useful in monitoring the clinical effect of proteasome‐inhibitors.
Early and late failure of noninvasive ventilation in chronic obstructive pulmonary disease with acute exacerbation
Authors: Carratù P. , Bonfitto P. , Dragonieri S. , Schettini F. , Clemente R. , Di Gioia G. , Loponte L. , Foschino Barbaro M. P. , Resta O. 
Published: June 2005

AbstractBackground  Despite recent encouraging results, the use of noninvasive ventilation (NIV) in the management of acute exacerbations in chronic obstructive pulmonary disease (COPD), complicated by acute respiratory failure (ARF), is not always successful. Failure of NIV may require an immediate intubation after a few hours (usually 1–3) of ventilation (‘early failure’) or may result in clinical deterioration (one or more days later) after an initial improvement of blood gas tension and general conditions (‘late failure’).Materials and methods  We enrolled 122 patients affected by COPD complicated by ARF, and treated with NIV. The schedule of NIV provided sessions of 2–6 h twice daily.Results  Ninety‐nine (81%) patients showed a progressive improvement of the clinical parameters and were discharged. Among the remaining 23 patients, 13 had an early failure and 10 had a late failure. In the ‘success’ group and ‘late failure’ groups we found after an increase of pH 2 h of NIV (from 7·31 ± 0·05 to 7·38 ± 0·04 P < 0·001 and from 7·29 ± 0·03 to 7·36 ± 0·02 P < 0·001, respectively) and a decrease of PaCO2 (from 80·93 ± 9·79 to 66·48 ± 5·95 P < 0·001 and from 85·96 ± 10·77 to 76·41 ± 11·02 P < 0·001, respectively). After 2 h of NIV in the ‘late failure’ group there were no significant changes in terms of pH (from 7·20 ± 0·10 to 7·28 ± 0·06) nor PaCO2 (from 92·86 ± 35·49 to 93·68 ± 23·68). The ‘early failure’ group had different characteristics and, owing to more severe conditions, the value of pH, of Glasgow Coma Score, and Apache II Score were the best predictors of the failure; while, among the complications on admission, metabolic alterations were the only independently significant predictor.Conclusions  Our study confirms that NIV may be useful to avoid intubation in approximately 80% of patients with COPD complicated by moderate‐severe hypercapnic respiratory failure.
Carcinoma ex pleomorphic adenoma (CXPA): immunoprofile of the cells involved in carcinomatous progression
Authors: Altemani A , Martins M T , Freitas L , Soares F , Araújo N S , Araújo V C 
Published: June 2005

Aims : To characterize the cellular component in pleomorphic adenoma (PA) that undergoes malignant transformation in carcinoma ex pleomorphic adenoma (CXPA).Methods and results : A panel of antibodies against cytoskeletal proteins was applied in 16 cases of CXPA: intracapsular carcinoma (five cases), minimally invasive (four cases) and frankly invasive (seven cases). The CXPAs were classified into two main groups according to their predominant cellular component as detected by the panel of antibodies: (i) carcinomas with only epithelial differentiation (75% of the cases), and (ii) carcinomas with a myoepithelial component (25%). CXPA with only epithelial differentiation showed two types of malignant areas in the part of the tumour that was confined by the PA capsule: (i) intraductal carcinoma areas characterized by ductal structures containing both benign myoepithelial cells positive for α‐smooth muscle actin (α‐SMA), vimentin and cytokeratin (CK)14 and proliferating atypical luminal cells reactive for CK7, CK8 and CK19, and (ii) carcinoma areas composed only of epithelial cells reactive for CK7, CK8 and CK19. In the latter, the cells presented morphological and immunohistochemical characteristics similar to those found in areas of invasive carcinoma outside the PA capsule. CXPAs with a myoepithelial component were composed mainly or exclusively of cells that expressed vimentin and α‐SMA. In this group, ductal structures reminiscent of PA filled by malignant cells were not identified.Conclusion : Most CXPAs consist only of epithelial cells that have an immunoprofile comparable to ductal luminal cells of PA. These malignant luminal cells arise in the duct‐like structures as intraductal carcinoma and probably only at this early stage of development should the lesion be considered as a non‐invasive carcinoma.
Up‐regulation of macrophage migration inhibitory factor in infants with acute neonatal necrotizing enterocolitis
Authors: Ren Y , Lin C L , Li Z , Chen X Y , Huang X , Lui V , Nicholls J , Lan H Y , Tam P K H 
Published: June 2005

Aims:  To investigate the role of macrophage migration inhibitory factor (MIF) and its downstream cytokine cascade in necrotizing enterocolitis (NEC).Methods and results:  The expression of MIF mRNA and protein in NEC guts was assayed by in situ hybridization and immunohistochemistry, respectively. Concentrations of MIF, interleukin (IL)‐6 and IL‐8 in the serum and in the supernatant of macrophage cultures were examined by ELISA. Increased expression of MIF mRNA and protein was observed in the NEC guts, mainly in the infiltrating macrophages in the mucosa and submucosal layers. Up‐regulation of MIF was associated with the accumulation of macrophages and T cells. In addition, serum levels of MIF, IL‐6 and IL‐8 in NEC patients during the acute stage of the disease were significantly increased. The expression of MIF decreased both locally and systemically after the disease was resolved. MIF was also found to increase the secretion of IL‐6 and IL‐8 by macrophages isolated from healthy individuals in vitro in NEC.Conclusions:  MIF acts by stimulating macrophage production of IL‐6 and IL‐8. This further aggravates the inflammatory process by increasing the infiltration of neutrophils and activating inflammatory cells. The results of this study suggest that MIF plays an important role in the pathogenesis of NEC and may serve as a target for therapeutic intervention in NEC.
Expression of hypoxia‐inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas
Authors: Couvelard A , O'Toole D , Leek R , Turley H , Sauvanet A , Degott C , Ruszniewski P , Belghiti J , Harris A L , Gatter K , Pezzella F 
Published: June 2005

Aims:  To study the expression of hypoxia‐regulated markers in pancreatic ductal adenocarcinomas (PA) in relationship to the presence of a fibrotic focus, angiogenesis quantification and clinical outcome.Methods and results:  The expression of hypoxia‐inducible factor (HIF)‐1α, HIF‐2α, carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) was immunohistochemically detected in 50 PA and correlated with tumour characteristics, microvascular density (MVD) and survival. HIF‐1α was expressed within tumour cells in 68%, HIF‐2α in 46%, CA9 in 78% and VEGF in 52% of the cases. Stromal expression was also noted for HIF‐2α and CA9 in, respectively, 42% and 48% of the cases. Tumour CA9 expression was associated with that of VEGF (P = 0.004) and that of stromal HIF‐2α (P = 0.013), with the presence of a fibrotic focus (P = 0.046) and with an increased MVD (P = 0.034). Tumour VEGF expression correlated with the presence of a fibrotic focus (P = 0.039) and a greater MVD (P = 0.047). Both the presence of a fibrotic focus (P = 0.0002) and high tumour CA9 expression (P = 0.029) were associated with reduced overall survival.Conclusion:  The strong association of the presence of a fibrotic focus with CA9 expression and lower survival demonstrates that hypoxia‐driven angiogenesis plays an important role in the progression of PA.
The flavonoid luteolin prevents lipopolysaccharide‐induced NF‐κB signalling and gene expression by blocking IκB kinase activity in intestinal epithelial cells and bone‐marrow derived dendritic cells
Authors: Kim Joo Sung , Jobin Christian 
Published: June 2005

SummaryThe nuclear factor (NF)‐κB transcriptional system is a major effector pathway involved in inflammation and innate immune responses. The flavonoid luteolin is found in various herbal extracts and has shown anti‐inflammatory properties. However, the mechanism of action and impact of luteolin on innate immunity is still unknown. We report that luteolin significantly blocks lipopolysaccharide (LPS)‐induced IκB phosphorylation/degradation, NF‐κB transcriptional activity and intercellular adhesion molecule‐1 (ICAM‐1) gene expression in rat IEC‐18 cells. Using chromatin immunoprecipitation, we demonstrate that LPS‐induced RelA recruitment to the ICAM‐1 gene promoter is significantly reduced in luteolin‐treated cells. Moreover, in vitro kinase assays show that luteolin directly inhibits LPS‐induced IκB kinase (IKK) activity in IEC‐18 cells. Using bone‐marrow derived dendritic cells (BMDCs) isolated from interleukin (IL)‐10–/– mice or from recently engineered transgenic mice expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF‐κB cis‐elements (cis‐NF‐κBEGFP), we found that luteolin blocks LPS‐induced IκB phosphorylation and IKK activity, and decreases EGFP, IL‐12 and tumour necrosis factor‐α gene expression. Moreover, intraperitoneal administration of luteolin significantly inhibited LPS‐induced EGFP expression in both peripheral blood mononuclear cells and splenocytes isolated from cis‐NF‐κBEGFP mice. These results indicate that luteolin blocks LPS‐induced NF‐κB signalling and proinflammatory gene expression in intestinal epithelial cells and dendritic cells. Modulation of innate immunity by natural plant products may represent an attractive strategy to prevent intestinal inflammation associated with dysregulated innate immune responses.