bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adiponectin levels in adolescent girls with polycystic ovary syndrome (PCOS)
Authors: Pinhas‐Hamiel Orit , Singer Sigal , Pilpel Nurit , Koren Ilana , Boyko Valentina , Hemi Rina , Pariente Clara , Kanety Hannah 
Published: April 2009

SummaryObjective  To determine serum adiponectin concentrations in adolescent girls with and without polycystic ovary syndrome (PCOS) and to assess possible correlations of adiponectin levels with insulin and androgen levels.Design  Prospective case–control study.Setting  Endocrine clinics in the community.Patients  Forty‐four adolescent girls were grouped as follows: 14 were overweight [body mass index (BMI) standard deviation score >1·645] with PCOS; 16 were lean (BMI SDS <1·036) with PCOS; and 14 were lean (BMI SDS <1·036) without PCOS.Intervention  Blood samples were collected from all girls between 8 and 11 am, after an overnight fast.Main outcome measures  Serum levels of adiponectin, leptin, insulin, Müllerian‐inhibiting substance, luteinizing hormone, follicle‐stimulating hormone, testosterone, 17‐alpha‐hydroxyprogesterone, androstendione, dehydroepiandrosterone sulphate (DHEAS) and 17β‐oestradiol.Results  Adiponectin concentrations were significantly decreased in obese adolescents with PCOS (10·5 ± 5·5 μg/ml) compared with that in lean girls with or without PCOS (16·9 ± 8·64 and 18·0 ± 7·4 μg/ml respectively). Leptin levels were significantly elevated in obese adolescents with PCOS compared with the levels in normal weight adolescents with PCOS, and compared with that in normal weight controls. Insulin levels were markedly higher in obese adolescents with PCOS compared with that in normal weight adolescents (12·3 ± 12·2 vs. 4·5 ± 2·9, P < 0·05), and compared with that in normal weight PCOS adolescents (7·4 ± 4·9); however, this difference was not statistically significant. Insulin levels did not differ between normal weight adolescents with PCOS and normal controls. Adiponectin concentrations correlated inversely with BMI, leptin and insulin.Conclusions  Hypoadiponectinaemia is evident only in obese adolescents with PCOS and therefore does not seem to be involved in the pathogenesis of PCOS in this age group.
Increase in frequency of myeloid‐derived suppressor cells in mice with spontaneous pancreatic carcinoma
Authors: Zhao Fei , Obermann Sonja , Von Wasielewski Reinhard , Haile Lydia , Manns Michael P. , Korangy Firouzeh , Greten Tim F. 
Published: April 2009

SummaryPancreatic adenocarcinoma is one of the deadliest cancers with poor survival and limited treatment options. Immunotherapy is an attractive option for this cancer that needs to be further developed. Tumours have evolved a variety of mechanisms to suppress host immune responses. Understanding these responses is central in developing immunotherapy protocols. The aim of this study was to investigate potential immune suppressor mechanisms that might occur during development of pancreatic tumours. Myeloid‐derived suppressor cells (MDSC) from mice with spontaneous pancreatic tumours, mice with premalignant lesions as well as wild‐type mice were analysed. An increase in the frequency of MDSC early in tumour development was detected in lymph nodes, blood and pancreas of mice with premalignant lesions and increased further upon tumour progression. The MDSC from mice with pancreatic tumours have arginase activity and suppress T‐cell responses, which represent the hallmark functions of these cells. Our study suggests that immune suppressor mechanisms generated by tumours exist as early as premalignant lesions and increase with tumour progression. These results highlight the importance of blocking these suppressor mechanisms early in the disease in developing immunotherapy protocols.
Chimeric IgG4 PR3‐ANCA induces selective inflammatory responses from neutrophils through engagement of Fcγ receptors
Authors: Hussain Abdullah , Pankhurst Tanya , Goodall Margaret , Colman Rachel , Jefferis Royston , Savage Caroline O. S. , Williams Julie M. 
Published: April 2009

SummaryAnti‐proteinase 3 antibodies are implicated in the pathogenesis of small vessel vasculitis. These are primarily immunoglobulin G (IgG), with different subclasses predominating at different stages of disease. However, little is known of their respective roles in pathogenesis. We have previously shown that patient IgG4 was able to induce superoxide release from human neutrophils. To circumvent difficulties in separating the subclasses and additional differences in polyclonal patient antibodies we have generated monoclonal mouse/human IgG1 and IgG4 anti‐proteinase 3 antibodies. Using these antibodies we have compared effects of IgG1 and IgG4 on human neutrophils in terms of superoxide release, cytokine production, degranulation and adhesion. Additionally we have investigated the interaction of the subclasses with Fc receptors expressed by the neutrophil. Chimeric antibodies were generated using human constant regions of each subclass and a variable region taken from a monoclonal antibody directed against proteinase 3. Superoxide release from neutrophils was measured by the reduction of ferricytochrome C, degranulation by the conversion of a synthetic colour substrate, cytokine release by interleukin‐8 enzyme‐linked immunosorbent assay, and adhesion by a flow‐based adhesion assay. Fc receptor binding was assessed using blocking antibodies. The IgG4 anti‐proteinase 3 was able to induce a dose‐dependent release of superoxide, degranulation and adhesion. The antibody was not able to stimulate the secretion of interleukin‐8. Fc receptors were essential for neutrophil stimulation and the constitutive Fc receptors were necessary for different stimulatory pathways. The IgG4 anti‐proteinase 3 antibodies are able to stimulate neutrophils to undergo a pro‐inflammatory response and may play a role in the pathogenesis of small vessel vasculitis.
A tolerogenic peptide down‐regulates mature B cells in bone marrow of lupus‐afflicted mice by inhibition of interleukin‐7, leading to apoptosis
Authors: Ben‐David Hava , Sharabi Amir , Parameswaran Reshmi , Zinger Heidy , Mozes Edna 
Published: April 2009

SummarySystemic lupus erythematosus (SLE) is an autoimmune disease mediated by T and B cells. It is characterized by a variety of autoantibodies and systemic clinical manifestations. A tolerogenic peptide, designated hCDR1, ameliorated the serological and clinical manifestations of SLE in both spontaneous and induced models of lupus. In the present study, we evaluated the status of mature B cells in the bone marrow (BM) of SLE‐afflicted mice, and determined the effect of treatment with the tolerogenic peptide hCDR1 on these cells. We demonstrate herein that mature B cells of the BM of SLE‐afflicted (New Zealand Black × New Zealand White)F1 mice were largely expanded, and that treatment with hCDR1 down‐regulated this population. Moreover, treatment with hCDR1 inhibited the expression of the pathogenic cytokines [interferon‐γ and interleukin (IL)‐10], whereas it up‐regulated the expression of transforming growth factor‐β in the BM. Treatment with hCDR1 up‐regulated the rates of apoptosis of mature B cells. The latter was associated with inhibited expression of the survival Bcl‐xL gene and of IL‐7 by BM cells. Furthermore, the addition of recombinant IL‐7 abrogated the suppressive effects of hCDR1 on Bcl‐xL in the BM cells and resulted in elevated levels of apoptosis. Hence, the down‐regulated production of IL‐7 contributes to the hCDR1‐mediated apoptosis of mature B cells in the BM of SLE‐afflicted mice.
Impaired macrophage function following bacterial stimulation in chronic granulomatous disease
Authors: Rahman Farooq Z. , Hayee Bu’Hussain , Chee Ronnie , Segal Anthony W. , Smith Andrew M. 
Published: April 2009

SummaryNicotinamide adenine dinucleotide phosphate (NADPH) oxidase is critical for phagocyte anti‐microbial activity and plays a major role in innate immunity. Defects in genes coding for components of the NADPH oxidase enzyme system are responsible for chronic granulomatous disease (CGD), a rare primary neutrophil immunodeficiency associated with recurrent, life‐threatening bacterial and fungal infections. Microbial killing and digestion within the neutrophil phagosomal compartment are defective in these patients. NADPH oxidase activity is also crucial for optimal macrophage and dendritic cell function and has recently been implicated in both cross‐presentation and T‐cell priming. We present evidence of impaired macrophage function in CGD, with attenuated pro‐inflammatory cytokine and increased interleukin‐10 secretion following bacterial stimulation. These results highlight additional abnormalities in macrophage function associated with CGD and the importance of NADPH oxidase activity in immunity.
Oral colonization by Lactobacillus reuteri ATCC 55730 after exposure to probiotics
Authors: ÇAGLAR ESBER , TOPCUOGLU NURSEN , ÇILDIR SULE KAVALOGLU , SANDALLI NUKET , KULEKCI GUVEN 
Published: April 2009

Objective.  The aim of this study was to investigate whether Lactobacillus reuteri ATCC 55730 can be detected in the oral cavity after discontinuation of administration of a product prepared with this bacterium.Materials and Methods.  The study consisted of three 2‐week periods: clearance period, intervention period, and post‐treatment period. Twenty‐five volunteers consumed a chewable tablet of L. reuteri ATCC 55730 (108 cfu/tablet) during a 14‐day trial period. Saliva samples were collected and cultured onto MRS agar after a clearance period of 2 weeks and then daily after a 2‐week intervention period for as long as L. reuteri was found. Lactobacillus reuteri colonies were analysed in saliva samples. The analysis was performed using selective media for L. reuteri followed by confirmation using the specific detection of reuterin produced by L. reuteri.Results.  The number of L. reuteri carriers decreased gradually, and after 1 week only 8% of the subjects harboured the bacterium. After 5 weeks, L. reuteri was not detected in any of the subjects.Conclusion.  Consuming L. reuteri for 2 weeks does not seem to be sufficient for permanent colonization of L. reuteri in the oral cavity.
Emergency department nurses’ understanding and experiences of implementing discharge planning
Authors: Han Chin‐Yen , Barnard Alan , Chapman Helen 
Published: April 2009

AbstractTitle.  Emergency department nurses’ understanding and experiences of implementing discharge planning. Aim.  This paper is a report of a study conducted to describe emergency department nurses’ understanding and experiences of implementing discharge planning.Background.  Discharge planning in the emergency department is an important issue because of increased healthcare costs and greater emphasis on continuity of care. When executed as a collaborative process involving a multi‐disciplinary team with the patient and family, discharge planning provides continuity of care for patients, less demand on hospitals, improvement in community services and in the services of other healthcare organizations.Method.  The qualitative approach of phenomenography was used in this study. Thirty‐two emergency department nurses were recruited between July and September 2005. Semi‐structured interviews were conducted.Findings.  From interviewees’ descriptions of implementing discharge planning, six categories were established: implementing discharge planning as ‘getting rid of my patients’, completing routines, being involved in patient education, professionally accountable practice, autonomous practice and demonstrating professional emergency department nursing care. The referential meaning of implementing discharge planning ‘in the outcome space’ was the professional commitment to emergency department provision of effective discharge services.Conclusion.  The results of this research contribute to knowledge of emergency department nurses’ experience in the implementation of the discharge planning process. Key requirements for the provision of manageable discharge services both in Taiwan and worldwide highlighted by this study include adequate workloads, sufficient time, clear policies and standards of discharge planning and enhancement of professional commitment.
The Internet as a research site: establishment of a web‐based longitudinal study of the nursing and midwifery workforce in three countries
Authors: Huntington Annette , Gilmour Jean , Schluter Philip , Tuckett Anthony , Bogossian Fiona , Turner Catherine 
Published: April 2009

AbstractTitle.  The Internet as a research site: establishment of a web‐based longitudinal study of the nursing and midwifery workforce in three countries. Aim.  The aim of this paper is to describe the development of a web‐based longitudinal research project, The Nurses and Midwives e‐cohort Study.Background.  The Internet has only recently been used for health research. However, web‐based methodologies are increasingly discussed as significant and inevitable developments in research as Internet access and use rapidly increases worldwide.Method.  In 2006, a longitudinal web‐based study of nurses and midwives workforce participation patterns, health and wellbeing, and lifestyle choices was established. Participating countries are Australia, New Zealand and the United Kingdom. Data collection is handled through a dedicated website using a range of standardized tools combined into one comprehensive questionnaire. Internet‐specific data collection and a range of recruitment and retention strategies have been developed for this study.Discussion.  Internet‐based technology can support the maintenance of cohorts across multiple countries and jurisdictions to explore factors influencing workforce participation. However, barriers to widespread adoption of web‐based approaches include website development costs, the need for fast broadband connection for large data collection instruments, and varying degrees of Internet and computer literacy in the nursing and midwifery workforce.Conclusion.  Many of the issues reported in this paper are transitional in nature at a time of rapid technological development. The development of on‐line methods and tools is a major and exciting development in the world of research. Research via the world‐wide web can support international collaborations across borders and cultures.
DNA‐based test: when and why to apply it to primary hyperparathyroidism clinical phenotypes
Authors: Falchetti A. , Marini F. , Giusti F. , Cavalli L. , Cavalli T. , Brandi M. L. 
Published: April 2009

Abstract.Several cancer‐related genes have been discovered and molecular test for the cancer genetic risk assessment has been widely increasing. Disorders such as Multiple Endocrine Neoplasia syndromes have received benefits from the identification of the responsible genes whose mutations account for the genetic susceptibility to develop endocrine tumours. Primary hyperparathyroidism (PHPT)is a clinical phenotype frequently associated to Multiple Endocrine Neoplasia syndromes, but it can also represent the unique endocrinopathy recurring as a familial cluster. In recent years, care options have been made available to patients and families with hereditary PHPT, and the process of systematically assessing the genetic risk has been becoming increasingly important. This review aims to help health providers not frequently dealing with genetic testing use and it will introduce some general concepts concerning genetic diagnosis issues. As an example the role and the practical usefulness of DNA‐based diagnosis in patients affected by different forms of congenital PHPT is described, with a close look on why, when and how genetic testing should be performed in these subjects and their relatives. Some practical recommendations and suggestions concerning on how to deal when a suspect or known case of familial PHPT has to be faced conclude this manuscript.
Medullary thyroid carcinoma and biomarkers: past, present and future
Authors: Van Veelen W. , De Groot J. W. B. , Acton D. S. , Hofstra R. M. W. , Höppener J. W. M. , Links T. P. , Lips C. J. M. 
Published: April 2009

Abstract.The clinical management of patients with persistent or recurrent medullary thyroid carcinoma (MTC) is still under debate, because these patients either have a long‐term survival, due to an indolent course of the disease, or develop rapidly progressing disease leading to death from distant metastases. At this moment, it cannot be predicted what will happen within most individual cases. Biomarkers, indicators which can be measured objectively, can be helpful in MTC diagnosis, molecular imaging and treatment, and/or identification of MTC progression. Several MTC biomarkers are already implemented in the daily management of MTC patients. More research is being aimed at the improvement of molecular imaging techniques and the development of molecular systemic therapies. Recent discoveries, like the prognostic value of plasma calcitonin and carcino‐embryonic antigen doubling‐time and the presence of somatic RET mutations in MTC tissue, may be useful tools in clinical decision making in the future. In this review, we provide an overview of different MTC biomarkers and their applications in the clinical management of MTC patients.
Parafibromin – functional insights
Authors: Newey P. J. , Bowl M. R. , Thakker R. V. 
Published: April 2009

Abstract.Parafibromin is a predominantly nuclear protein with a tumour suppressor role in the development of hereditary and nonhereditary parathyroid carcinomas, and the hyperparathyroidism‐jaw tumour syndrome, which is associated with renal and uterine tumours. Parafibromin is a component of the highly conserved PAF1 complex, which regulates transcriptional events and histone modifications. The parafibromin/PAF1 complex regulates genes involved in cell growth and survival, and via these, parafibromin plays a pivotal role in embryonic development and survival of adults.
Multiple endocrine neoplasias: advances and challenges for the future
Authors: Alevizaki M. , Stratakis C. A. 
Published: April 2009

Abstract.Several important advances have been made over the last 2 years, since the last international workshop on multiple endocrine neoplasias (MENs) that was held in Marseilles, France (MEN2006). The series of articles that are included in this issue summarize the most important of these advances as they were presented in Delphi, Greece, during the 11th International Workshop on MENs, September 25–27, 2008 (MEN2008). This editorial summarizes some of these advances: the identification of the AIP, and the PDE11A and PDE8B genes by genome‐wide association (GWA) studies as predisposing genes for pituitary and adrenal tumours, respectively, the discovery of p27 mutations in a new form of MEN similar to MEN type 1 (MEN 1) that is now known as MEN 4, the molecular investigations of Carney triad (CT), a disorder that associates paragangliomas (PGLs), gastrointestinal stromal tumour (GISTs), and pulmonary chondromas (PCH) with pheochromocytomas and adrenocortical adenomas and other lesions, and the molecular elucidation of the association of GISTs with paragangliomas (Carney–Stratakis syndrome) that is now known to be because of SDHB, SDHC, and SDHD mutations. Molecular investigations in Carney complex (another MEN also described by Dr. Carney, who during the meeting, along with Dr. Charles E. (‘Gene’) Jackson was honoured for his life‐long and many contributions to the field) have also revealed the role of cyclic AMP signalling in tumorigenesis. As our knowledge of the molecular causes of MENs increases, the challenge is to translate these discoveries in better treatments for our patients. Indeed, new advances in the preventive diagnosis and molecular treatment of MEN 1 and MEN 2, respectively, continued unabated, and an update on this front was also presented at MEN2008 and is included in this issue.
SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma–paraganglioma syndromes
Authors: Pasini B. , Stratakis C. A. 
Published: April 2009

Abstract.A genetic predisposition for paragangliomas and adrenal or extra‐adrenal phaeochromocytomas was recognized years ago. Beside the well‐known syndromes associated with an increased risk of adrenal phaeochromocytoma, Von Hippel Lindau disease, multiple endocrine neoplasia type 2 and neurofibromatosis type 1, the study of inherited predisposition to head and neck paragangliomas led to the discovery of the novel ‘paraganglioma–phaeochromocytoma syndrome’ caused by germline mutations in three genes encoding subunits of the succinate dehydrogenase (SDH) enzyme (SDHB, SDHC and SDHD) thus opening an unexpected connection between mitochondrial tumour suppressor genes and neural crest‐derived cancers. Germline mutations in SDH genes are responsible for 6% and 9% of sporadic paragangliomas and phaeochromocytomas, respectively, 29% of paediatric cases, 38% of malignant tumours and more than 80% of familial aggregations of paraganglioma and phaeochromocytoma. The disease is characterized by autosomal dominant inheritance with a peculiar parent‐of‐origin effect for SDHD mutations. Life‐time tumour risk seems higher than 70% with variable clinical manifestantions depending on the mutated gene. In this review we summarize the most recent knowledge about the role of SDH deficiency in tumorigenesis, the spectrum and prevalence of SDH mutations derived from several series of cases, the related clinical manifestantions including rare phenotypes, such as the association of paragangliomas with gastrointestinal stromal tumours and kidney cancers, and the biological hypotheses attempting to explain genotype to phenotype correlation.
Beyond RET: potential therapeutic approaches for advanced and metastatic medullary thyroid carcinoma
Authors: Santarpia L. , Ye L. , Gagel R. F. 
Published: April 2009

Abstract.Medullary thyroid carcinoma (MTC) is a rare calcitonin‐producing neuroendocrine tumour that originates from the parafollicular C‐cells of the thyroid gland. The RET proto‐oncogene encodes the RET receptor tyrosine kinase, which has essential roles in cell survival, differentiation and proliferation. Activating mutations of RET are associated with the pathogenesis of MTC and have been demonstrated in nearly all hereditary and in 30–50% of sporadic MTC cases, making this receptor an excellent target for small‐molecule inhibitors for this tumour. Clinical trials of small organic inhibitors of tyrosine kinase receptors (TKIs) targeting the RET receptor have shown efficacy for treatment of metastatic MTC with 30–50% of patients responding to these agents. Despite the importance of the RET receptor in MTC, it is clear that other signal transduction pathways, tyrosine kinase receptors, and tumour suppressor genes are involved in MTC tumourigenesis and progression. A better understanding of molecular cross‐talk between these signal pathways and the RET receptor may lead to combinatorial therapy that will improve outcomes beyond what is currently possible with RET‐directed TKIs. Finally, there is evidence that immunological‐based therapy using dendritic cell vaccination strategies have been effective for reducing tumour mass in a small number of patients. The identification of additional MTC‐specific tumour antigens and a better understanding of specific epitopes in these tumour antigens may lead to improvement of response rates.