bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flk2+ common lymphoid progenitors possess equivalent differentiation potential for the B and T lineages
Authors: Karsunky Holger , Inlay Matthew A. , Serwold Thomas , Bhattacharya Deepta , Weissman Irving L. 
Published: April 2008

Abstract
Mature blood cells develop from multipotent hematopoietic stem cells through a series of sequential intermediates in which the developmental potential for particular blood lineages is progressively extinguished. We previously reported the identification of one of these developmental intermediates, the common lymphoid progenitor (CLP), which can give rise to T cells, B cells, dendritic cells (DCs), and natural killer cells (NKs), but lacks myeloid and erythroid potential. Recently, several studies have suggested that the T-cell and DC potential of CLP is limited or absent, and/or that CLP contains significant myeloid potential. Here, we show that the originally identified CLP population can be divided into functionally distinct subsets based on the expression of the tyrosine kinase receptor, Flk2. The Flk2+ subset contains robust in vivo and in vitro T-cell, B-cell, DC, and NK potential, but lacks myeloid potential and, therefore, represents an oligopotent, lymphoid-restricted progenitor. This population of cells does not appear to be B cell–biased and robustly reconstitutes both B and T lineages in vivo, consistent with its being a physiologic progenitor of both of these subsets. Thus, Flk2 expression defines a homogeneous, readily obtainable subset of bone marrow CLP that is completely lymphoid-committed and can differentiate equivalently well into both B and T lineages.
Explorative data analysis of MCL reveals gene expression networks implicated in survival and prognosis supported by explorative CGH analysis
Authors: Blenk Steffen , Engelmann Julia C , Pinkert Stefan , Weniger Markus , Schultz Jörg , Rosenwald Andreas , Müller-Hermelink Hans K , Müller Tobias , Dandekar Thomas 
Published: April 2008

AbstractBackgroundMantle cell lymphoma (MCL) is an incurable B cell lymphoma and accounts for 6% of all non-Hodgkin's lymphomas. On the genetic level, MCL is characterized by the hallmark translocation t(11;14) that is present in most cases with few exceptions. Both gene expression and comparative genomic hybridization (CGH) data vary considerably between patients with implications for their prognosis.MethodsWe compare patients over and below the median of survival. Exploratory principal component analysis of gene expression data showed that the second principal component correlates well with patient survival. Explorative analysis of CGH data shows the same correlation.ResultsOn chromosome 7 and 9 specific genes and bands are delineated which improve prognosis prediction independent of the previously described proliferation signature. We identify a compact survival predictor of seven genes for MCL patients. After extensive re-annotation using GEPAT, we established protein networks correlating with prognosis. Well known genes (CDC2, CCND1) and further proliferation markers (WEE1, CDC25, aurora kinases, BUB1, PCNA, E2F1) form a tight interaction network, but also non-proliferative genes (SOCS1, TUBA1B CEBPB) are shown to be associated with prognosis. Furthermore we show that aggressive MCL implicates a gene network shift to higher expressed genes in late cell cycle states and refine the set of non-proliferative genes implicated with bad prognosis in MCL.ConclusionThe results from explorative data analysis of gene expression and CGH data are complementary to each other. Including further tests such as Wilcoxon rank test we point both to proliferative and non-proliferative gene networks implicated in inferior prognosis of MCL and identify suitable markers both in gene expression and CGH data.
GM-CSF/IL-3/IL-5 receptor common β chain (CD131) expression as a biomarker of antigen-stimulated CD8+ T cells
Authors: Selleri Silvia , Deola Sara , Pos Zoltan , Jin Ping , Worschech Andrea , Slezak Stefanie L , Rumio Cristiano , Panelli Monica C , Maric Dragan , Stroncek David F , Wang Ena , Marincola Francesco M 
Published: April 2008

AbstractBackgroundUpon Ag-activation cytotoxic T cells (CTLs) produce IFN-γ GM-CSF and TNF-α, which deliver simultaneously pro-apoptotic and pro-inflammatory signals to the surrounding microenvironment. Whether this secretion affects in an autocrine loop the CTLs themselves is unknown.MethodsHere, we compared the transcriptional profile of Ag-activated, Flu-specific CTL stimulated with the FLU M1:58-66 peptide to that of convivial CTLs expandedin vitroin the same culture. PBMCs from 6 HLA-A*0201 expressing donors were expanded for 7 days in culture following Flu M1:58-66 stimulation in the presence of 300 IU/ml of interleukin-2 and than sorted by high speed sorting to high purity CD8+ expressing T cells gated according to FluM1:58-66 tetrameric human leukocyte antigen complexes expression.ResultsAg-activated CTLs displayed higher levels of IFN-γ, GM-CSF (CSF2) and GM-CSF/IL-3/IL-5 receptor common β- chain (CD131) but lacked completely expression of IFN-γ receptor-II and IFN-stimulated genes (ISGs). This observation suggested that Ag-activated CTLs in preparation for the release of IFN-γ and GM-CSF shield themselves from the potentially apoptotic effects of the former entrusting their survival to GM-SCF.In vitrophenotyping confirmed the selective surface expression of CD131 by Ag-activated CTLs and their increased proliferation upon exogenous administration of GM-CSF.ConclusionThe selective responsiveness of Ag-activated CTLs to GM-CSF may provide an alternative explanation to the usefulness of this chemokine as an adjuvant for T cell aimed vaccines. Moreover, the selective expression of CD131 by Ag-activated CTLs proposes CD131 as a novel biomarker of Ag-dependent CTL activation.
Non-systemic metamorphosis in male millipede appendages: long delayed, reversible effect of an early localized positional marker?
Authors: Drago Leandro , Fusco Giuseppe , Minelli Alessandro 
Published: April 2008

AbstractBackgroundThe development of specialized appendages involved in sperm transfer in the males of julid millipedes is an extreme case of specialized, complex structures differentiating in a very advanced phase of post-embryonic development. Here, a non-systemic metamorphosis affects the external morphology and the internal anatomy of a trunk double segment only.Presentation of the hypothesisWe hypothesize that during early (possibly embryonic) development a segmental marker is produced that remains unexploited throughout late embryonic and early post-embryonic development, until, activated by a systemic signal, it finally determines the release of a segmentally localized but anatomically major change.Testing the hypothesisKey to testing the hypothesis are (1) the identification of both the putative segmental marker involved in the localization of the legs to be eventually metamorphosed into gonopods and the systemic signal activating it, (2) the identification of the cell population from which the gonopods are built, and (3) a longitudinal study of the marker's expression throughout late embryonic and, possibly, post-embryonic development.Implications of the hypothesisProving the validity of this hypothesis would demonstrate the existence of a cryptic developmental module that will be activated only months, or years, after it has been first laid down during early development. This study also opens a window onto the very poorly explored domain of late expression of developmental genes and molecular control of late developmental events.
Low Circulating Insulin-Like Growth Factor I Bioactivity in Elderly Men Is Associated with Increased Mortality
Authors: Brugts M. P. , van den Beld A. W. , Hofland L. J. , van der Wansem K. , van Koetsveld P. M. , Frystyk J. , Lamberts S. W. J. , Janssen J. A. M. J. L. 
Published: April 2008

Abstract
Context: Low IGF-I signaling activity prolongs lifespan in certain animal models, but the precise role of IGF-I in human survival remains controversial. The IGF-I kinase receptor activation assay is a novel method for measuring IGF-I bioactivity in human serum. We speculated that determination of circulating IGF-I bioactivity is more informative than levels of immunoreactive IGF-I.
Objective: Our objective was to study IGF-I bioactivity in relation to human survival.
Design, Setting, and Study Participants: We conducted a prospective observational study at a clinical research center at a university hospital of 376 healthy elderly men (aged 73–94 yr).
Main Outcome Measures: IGF-I bioactivity was determined by the IGF-I kinase receptor activation assay. Total and free IGF-I were determined by IGF-I immunoassays. Mortality was registered during follow-up (mean 82 months).
Results: During the follow-up period of 8.6 yr, 170 men (45%) died. Survival of subjects in the highest quartile of IGF-I bioactivity was significantly better than in the lowest quartile, both in the total study group [hazard ratio (HR) = 1.8; 95% confidence interval (95% CI) = 1.2–2.8; P = 0.01] as well as in subgroups having a medical history of cardiovascular disease (HR = 2.4; 95% CI = 1.3–4.3; P = 0.003) or a high inflammatory risk profile (HR = 2.3; 95% CI = 1.2–4.5; P = 0.01). Significant relationships were not observed for total or free IGF-I.
Conclusion: Our study suggests that a relatively high circulating IGF-I bioactivity in elderly men is associated with extended survival and with reduced cardiovascular risk.
Treatment of Adrenocorticotropin-Dependent Cushing’s Syndrome: A Consensus Statement
Authors: Biller B. M. K. , Grossman A. B. , Stewart P. M. , Melmed S. , Bertagna X. , Bertherat J. , Buchfelder M. , Colao A. , Hermus A. R. , Hofland L. J. , Klibanski A. , Lacroix A. , Lindsay J. R. , Newell-Price J. , Nieman L. K. , Petersenn S. , Sonino N. , Stalla G. K. , Swearingen B. , Vance M. L. , Wass J. A. H. , Boscaro M. 
Published: April 2008

Abstract
Objective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing’s syndrome, because there is no recent consensus on the management of this rare disorder.
Participants: Thirty-two leading endocrinologists, clinicians, and neurosurgeons with specific expertise in the management of ACTH-dependent Cushing’s syndrome representing nine countries were chosen to address 1) criteria for cure and remission of this disorder, 2) surgical treatment of Cushing’s disease, 3) therapeutic options in the event of persistent disease after transsphenoidal surgery, 4) medical therapy of Cushing’s disease, and 5) management of ectopic ACTH syndrome, Nelson’s syndrome, and special patient populations.
Evidence: Participants presented published scientific data, which formed the basis of the recommendations. Opinion shared by a majority of experts was used where strong evidence was lacking.
Consensus Process: Participants met for 2 d, during which there were four chaired sessions of presentations, followed by general discussion where a consensus was reached. The consensus statement was prepared by a steering committee and was then reviewed by all authors, with suggestions incorporated if agreed upon by the majority.
Conclusions: ACTH-dependent Cushing’s syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. Generally, the treatment of choice for ACTH-dependent Cushing’s syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing’s disease), medical therapy, and bilateral adrenalectomy. Because of the significant morbidity of Cushing’s syndrome, early diagnosis and prompt therapy are warranted.
The Effect of Sports Injury on Insulin-Like Growth Factor-I and Type 3 Procollagen: Implications for Detection of Growth Hormone Abuse in Athletes
Authors: Erotokritou-Mulligan Ioulietta , Bassett E. Eryl , Bartlett Christiaan , Cowan David , McHugh Cathy , Seah Rick , Curtis Benjamin , Wells Victoria , Harrison Kate , Sönksen Peter H. , Holt Richard I. G. ,   The GH-2004 Group
Published: April 2008

Abstract
Context: A method to detect exogenously administered growth hormone (GH) based on the measurement of two GH-dependent markers, IGF-I and type 3 procollagen (P-III-P) has been proposed. Skeletal or soft tissue injury may alter these markers. Elevations in either of these proteins after injury might lead to a false accusation of doping with GH.
Objective: The objective of the study was to assess the effect of musculoskeletal or soft tissue injury on IGF-I and P-III-P concentrations in amateur and elite athletes and assess the effect of injury on the proposed GH detection method.
Design: This was a longitudinal observational study after sporting injury.
Setting: The study was conducted at Southampton General Hospital and British Olympic Medical Centre.
Subjects: Subjects included elite and amateur athletes after an injury.
Intervention: Interventions included measurement of IGF-I and P-III-P and application of the GH-2000 discriminant function score up to 84 d after an injury as well as classification of injury by type and severity.
Outcome Measures: IGF-I and P-III-P concentration and ability to detect GH abuse in athletes without the risk of false accusation because of an injury were measured.
Results: There was no change in IGF-I concentration after an injury. By contrast, P-III-P concentrations rose by 41.1 ± 16.6%, reaching a peak around 14 d after an injury. The rise in P-III-P varied according to injury type and severity. This rise had a trivial effect on the GH-2000 discriminant function score, and no subject reached the threshold needed for a doping offense.
Conclusions: Although there was a rise in P-III-P after injury, this was insufficient to invalidate the GH-2000 detection method based on IGF-I and P-III-P concentrations.
Iodine Prophylaxis Using Iodized Salt and Risk of Maternal Thyroid Failure in Conditions of Mild Iodine Deficiency
Authors: Moleti Mariacarla , Lo Presti Vincenzo Pio , Campolo Maria Cristina , Mattina Filiberto , Galletti Marina , Mandolfino Mattia , Violi Maria Antonia , Giorgianni Grazia , De Domenico Demetrio , Trimarchi Francesco , Vermiglio Francesco 
Published: April 2008

Abstract
Context: Mild to moderate iodine deficiency during pregnancy can cause transient maternal hypothyroidism and impaired mental development of the progeny. These unfavorable effects are preventable by iodine supplementation. In Europe, however, less than 50% pregnant women receive iodine-containing supplements, thus representing dietary iodized salt the only carrier of iodine for most women in this life stage.
Objective/Design: This longitudinal study is aimed to investigate the effects of long-term iodized salt consumption on maternal thyroid function during gestation.
Participants/Outcome Measures: We prospectively evaluated thyroid function in 100 consecutive thyroperoxidase antibody-negative pregnant women from a mildly iodine-deficient area. Sixty-two women who had regularly used iodized salt for at least 2 yr prior to becoming pregnant and 38 who commenced iodized salt consumption upon becoming pregnant were classified as long-term (LT) and short-term (ST) iodine supplemented, respectively.
Results: Long-term iodized salt consumption resulted in a very low prevalence of maternal thyroid failure (MTF) in LT women. Conversely, short-term iodine prophylaxis does not seem to protect against the risk of MTF, the prevalence of which was almost 6-fold higher in ST than LT women (36.8% vs. 6.4%; χ2 14.7, P &lt; 0.0005; relative risk 5.7, 95% confidence interval 2.03–16.08, P &lt; 0.001). The relative risk reduction amounted to 82.5%, this measure indicating the extent to which long-term iodine prophylaxis using iodized salt would reduce the risk of MTF in ST women.
Conclusions: Prolonged iodized salt significantly improves maternal thyroid economy and reduces the risk of maternal thyroid insufficiency during gestation, probably because of a nearly restoring intrathyroidal iodine stores.
Aerobic Capacity and Growth Hormone Deficiency after Traumatic Brain Injury
Authors: Mossberg Kurt A. , Masel Brent E. , Gilkison Charles R. , Urban Randall J. 
Published: April 2008

Abstract
Context: GH deficiency occurs in approximately 20% of all individuals who suffer from a moderate to severe traumatic brain injury.
Objective: This study determined whether GH deficiency secondary to traumatic brain injury had an effect on aerobic capacity.
Design: Subjects were screened for GH deficiency by the glucagon stimulation test and performed a maximal treadmill exercise test.
Setting: Patients were studied in the postacute recovery phase after traumatic brain injury.
Participants: Thirty-five individuals were studied. Groups were formed as follows: normal GH axis, greater than 8 ng/ml response (n = 12); insufficient, GH 3–8 ng/ml response (n = 11); and deficient, less than 3 ng/ml response (n = 12).
Intervention: There was no intervention.
Main Outcome Measure: Aerobic capacity was assessed by measuring expired gases during a graded treadmill exercise test. One-way and two-way ANOVAs were carried out on all peak and submaximal cardiorespiratory variables, respectively. Appropriate post hoc comparisons followed as necessary.
Results: Significantly higher peak oxygen consumption was found in traumatic brain injury subjects with GH normal vs. GH insufficient and deficient [26.4 ± 6.9, 20.8 ± 4.6, and 19.7 ± 5.0, respectively (P &lt; 0.05)]. Submaximal oxygen consumption was significantly higher in the GH normal group. All other variables were statistically similar.
Conclusions: This study shows that individuals with traumatic brain injury with normal GH secretion have below normal aerobic capacity and those patients who have GH insufficiency/deficiency are further deconditioned. Studies of GH replacement in these subjects should be conducted to assess whether GH therapy can improve cardiorespiratory fitness and prevent secondary disability.
Feasibility of a telemedicine ‘booth’ for supporting remote care in Scotland
Authors: Mair Fiona , Peterkin Gordon , Laing Angus , Ferguson James , Fraser Susan 
Published: April 2008

Summary Access to health care in remote settings is becoming increasingly difficult in Scotland. We have investigated the feasibility of a telemedicine ‘booth’. Two telemedicine booths were constructed for display at the Royal Highland Show in Edinburgh. One was equipped for patient use and one for the doctor. The booths contained videoconferencing and physiological monitoring equipment connected via an IP link at a bandwidth of 1.1 Mbit/s. The picture resolution was 4CIF (704 x 576 pixels). A total of 238 members of the public used the booth for a teleconsultation with a doctor. Ninety-three percent completed questionnaires. Of the 221 respondents, 75% saw the booth as an opportunity to access specialist advice; 84% felt that the booth would save them attending a hospital or clinic; 60% felt that it would improve the way they looked after their own health. The concept of a telemedicine booth appears both feasible and acceptable to the public.
Telemedicine via satellite to support offshore oil platforms
Authors: Mair Fiona , Fraser Susan , Ferguson James , Webster Karyn 
Published: April 2008

Summary On any one day, approximately 15,000–28,000 oil industry personnel are employed in the North Sea oil and gas industry. First aid in this remote environment is provided by non-medical staff on the rigs. Remote specialist advice via videoconferencing should improve the quality of offshore health care and reduce avoidable medical evacuations. Satellite communications and videoconferencing equipment was installed on the ‘Alwyn North’ oil platform, with medical advice provided via a call centre in Milan. Over a nine-month period, trial telemedicine links were conducted approximately twice per week. The three onshore physicians were very satisfied on each occasion with communications and diagnostic data image quality, including the ultrasound screening carried out by the rig provider. Remote specialist advice via videoconferencing should reduce unnecessary and/or untimely patient evacuation to hospital or onshore for medical assessment.
A five-year review of ground-to-air emergency medical advice
Authors: Urwin Alastair , Ferguson James , McDonald Roderick , Fraser Susan 
Published: April 2008

Summary We reviewed five years' experience of providing ground-to-air medical advice for commercial passenger aircraft. A total of 273 events occurred in-flight where further advice was sought. The most common age group resulting in calls were from those aged 21–30 years, who generated 38 calls (16%). The 273 cases included gastrointestinal conditions (26%), neurological (22%) and cardiovascular events (14%). Most incidents were managed conservatively in-flight with oxygen and/or other medications. Aircraft diversion occurred on 9% of occasions; cardiovascular and neurological emergencies were the major cause of this. Collaboration between aviation providers should be considered to develop a common database of in-flight emergencies so that contents of medical kits can be standardized in order to improve the quality of care in the air.
Valid Treatment Options for Osteoporosis and Osteopenia in HIV-Infected Persons
Authors: Clay Patrick G , Voss Laura E , Williams Charlott , Daume Eric C 
Published: April 2008

Objective: To review clinical data on bone ossification agents that may be considered for use in the treatment of osteoporosis and osteopenia in HIV-infected patients. Data Sources: A literature search was performed using MEDLINE (1950-January 2008), EMBASE, PubMed, and abstracts from major HIV conferences (February 2001-October 2007). These searches were limited to human data published in English and used the key words bisphosphonates, calcitonin, raloxifene. teriparatide, HAART, osteopenia, osteoporosis, and HIV/AIDS. Additional articles were retrieved from citations of selected references. Study Selection and Data Extraction: Relevant information on the pharmacology, pharmacokinetics, safety, and efficacy of available treatment with hormonal and nonhormonal agents was selected. Greater emphasis was placed on randomized clinical trials than on retrospective studies. Data Synthesis: Osteoporosis in HIV-infected persons is at least as prevalent as in postmenopausal women, yet this population is not listed in primary care guidelines as one that should be considered for screening. In addition to bisphosphonates, calcitonin, raloxifene, and teriparatide are used to treat bone disorders. Three clinical trials to date have evaluated the use of a bisphosphonate in HIV-infected persons. The trials showed a marked increase in bone mineral density in patients taking alendronate versus those in the control groups (with/without calcium, exercise, and/or vitamin D in 1 or both arms). Dosing restrictions complicate the use of these agents; diet, exercise, and calcium supplementation remain the foremost recommended strategies to prevent bone loss. The use of estrogen, testosterone, calcitonin, and teriparatide is less studied in HIV-positive patients, but may be considered in select cases. There are some investigational drugs and agents not available in the US; however, there are not enough data to support their use. Conclusions: Alendronate appears to be a promising treatment option for HIV-infected patients with osteoporosis and osteopenia. Further research is required to determine the safety and efficacy of other available drugs. Until additional information is provided, and with available knowledge on the metabolism profiles of antiretroviral and bone ossification agents, alendronate appears to be the preferred agent to use in this population.