bluuebunny/crossref_metadata_2025_split huggingface dataset:
The advantage of measuring spontaneous growth hormone (GH) secretion compared with the insulin tolerance test in the diagnosis of GH deficiency in young adults
Authors: Radetti Giorgio , Di Iorgi Natascia , Paganini Claudio , Gastaldi Roberto , Napoli Flavia , Lorini Renata , Maghnie Mohamad 
Published: May 2007

SummaryObjective  Reassessment of GH status after the attainment of adult height has important clinical implications in the diagnosis and prognosis of GH deficiency (GHD) in adulthood. The current GH threshold for biochemical definition of GHD in young adults is still a subject of debate.Design  To investigate the role of pharmacological stimulation tests compared with spontaneous 12‐h nocturnal GH secretion in the diagnosis of permanent GHD in young adults with childhood‐onset GHD.Patients  Forty‐five young adults (25 males, 20 females) with childhood‐onset GHD, height standard deviation score (SDS) –1·1 ± 1·3 and body mass index (BMI) SDS 1·0 ± 1·6, were re‐evaluated at the age of 19·8 ± 2·7 years. Sixteen subjects showed a normal pituitary gland on magnetic resonance imaging (MRI), while in 29, consistent structural hypothalamic–pituitary abnormalities were found. GH secretion was assessed by means of an insulin tolerance test (ITT) and a 12‐h spontaneous nocturnal profile as well as by IGF‐I assessment. The results were compared with those of 43 healthy controls.Results  Mean 12‐h spontaneous nocturnal GH secretion was < 3·1 µg/l (the lowest limit of the normal range) in 36 (80%) of the subjects and > 3·1 µg/l in nine (20%). Of these 36 patients, 29 (80%) had abnormal MRI findings and 20 (55%) had multiple pituitary hormone deficiencies (MPHD). All nine subjects with mean spontaneous GH secretion > 3·1 µg/l had a normal pituitary MRI, isolated GHD and a peak GH response to ITT > 5 µg/l. There was a discordance in 14 patients (31%), who showed a peak GH response to ITT > 5 µg/l but a reduced spontaneous GH secretory capacity; 10 had structural hypothalamic–pituitary abnormalities on MRI.Conclusions  Although the ITT provides valuable information and proves to be a sensitive index of permanent GHD, the results of this study emphasize the potential diagnostic value of assessment of 12‐h spontaneous GH secretion in young adults with childhood‐onset GHD.
Maternal serum adiponectin and infant birthweight: the role of adiponectin isoform distribution
Authors: Ong Gabie K. B. , Hamilton Jill K. , Sermer Mathew , Connelly Philip W. , Maguire Graham , Zinman Bernard , Hanley Anthony J. G. , Retnakaran Ravi 
Published: May 2007

SummaryObjective  Adiponectin is an insulin‐sensitizing protein that circulates in oligomeric complexes, including trimers, hexamers and high‐molecular‐weight (HMW) multimers. In pregnant women, conflicting associations have been reported between maternal serum levels of total adiponectin (i.e. reflecting all isoforms) and infant birthweight. As the HMW complex has recently been proposed as the primary mediator of metabolic bioactivity, we hypothesized that differences in isoform distribution may underlie these conflicting reports. Therefore, we evaluated the relationship between maternal adiponectin isoforms and infant birthweight.Design/patients/measurements  HMW and total adiponectin, as well as the ratio of HMW to total adiponectin (ratio known as SA), were measured in healthy pregnant Caucasian women (n = 58) undergoing an oral glucose tolerance test (OGTT), following an abnormal glucose challenge test.Results  On univariate analysis adjusted for neonate gender and length of gestation, birthweight was positively correlated with weight gain in pregnancy (r = 0·29, P = 0·031) and inversely associated with the ISOGTT index of insulin sensitivity (r = –0·27, P = 0·041), total adiponectin (r = –0·31, P = 0·021), HMW adiponectin (r = –0·34, P = 0·0093) and SA (r = –0·34, P = 0·011). On multiple linear regression analyses, however, total adiponectin was not related to birthweight. By contrast, HMW adiponectin was related at borderline significance (t = –1·87, P = 0·068), while SA emerged as an independent negative determinant of infant birthweight (t = –2·46, P = 0·0175). Adjusted mean neonatal birthweight was significantly higher in the infants of women comprising the lowest tertile of SA compared to women in the highest tertile of SA (3684 vs. 3424 g, P = 0·0375).Conclusions  The proportion of maternal serum adiponectin in HMW form (SA) is independently and inversely associated with infant birthweight. Thus, adiponectin isoform distribution, rather than total adiponectin concentration, may be a correlate of foetal size.
Focal uptake of 18F‐fluorodeoxyglucose by thyroid in patients with nonthyroidal head and neck cancers
Authors: Nam Soon Yuhl , Roh Jong‐Lyel , Kim Jae Seung , Lee Jeong Hyun , Choi Seung‐Ho , Kim Sang Yoon 
Published: May 2007

SummaryObjective  To evaluate the prevalence and significance of focal thyroid lesions identified by 18F‐fluorodeoxyglucose (FDG)‐positron emission tomography (PET) in patients with nonthyroidal head and neck cancers (HNC).Patients and measurements  Patients with histologically identified HNC who underwent FDG‐PET and computed tomography (CT) were reviewed retrospectively. We evaluated the prevalence of patients with focal thyroid FDG uptake and the risk of malignancy and proper management in these patients.Results  Of 689 HNC patients, 19 (2·8%) had focal thyroid FDG uptake. Of the 12 patients with a histological diagnosis by surgery or needle biopsy, 5 (41·7%) had carcinomas, 4 papillary and 1 follicular, whereas the others had benign thyroid lesions. The maximum standardized uptake value on PET was not sufficient to discriminate between malignant and benign thyroid lesions (8·4 ± 13·2 vs. 4·2 ± 4·0; P > 0·4). The identification of incidental thyroid diseases helped guide patient counselling and combined surgery with HNC and thyroidectomy.Conclusion  Focal thyroid lesions incidentally found on FDG‐PET in patents with nonthyroidal HNC have a high probability of malignancy. These lesions deserve further diagnostic examination before HNC treatment to ensure adequate therapy for incidental thyroid cancers.
Relationship between serum hsCRP concentration and biochemical bone turnover markers in healthy pre‐ and postmenopausal women
Authors: Kim Beom‐Jun , Yu Yong Mi , Kim Euy Nyong , Chung Yun‐Ey , Koh Jung‐Min , Kim Ghi Su 
Published: May 2007

SummaryObjective   Although osteoporosis and atherosclerosis seem to be related, the mechanisms are not yet understood. We previously observed that women with higher serum concentrations of high sensitivity C‐reactive protein (hsCRP), a strong risk factor for atherosclerosis, had lower bone mineral density (BMD). However, the relationship of hsCRP level with bone turnover rate, an independent risk factor for osteoporotic fracture, is not known.Design   Cross‐sectional hospital‐based survey.Patients   Apparently healthy pre‐ and postmenopausal women (n = 39 and 150, respectively).Measurements   Urinary N‐terminal telopeptide of type I collagen (NTx) and serum bone specific alkaline phosphatase (BALP) were measured using commercially available immunoassay kits. Serum hsCRP concentrations were measured by a particle‐enhanced immunoturbidometric method.Results   Both urinary NTx (γ = 0·288, P < 0·001) and serum BALP (γ = 0·260, P < 0·001) were positively correlated with serum hsCRP levels. Significance remained even after adjustment for age, body mass index and years since menopause (γ = 0·257, P < 0·001, and γ = 0·163, P = 0·027, respectively). Compared with subjects in the lowest hsCRP quartile (≤ 0·6 mg/l), those in the highest hsCRP quartile (≥ 1·6 mg/l) had significantly higher urinary NTx concentrations (P = 0·001) after adjustment for confounding variables. There was an increasing trend of serum BALP concentrations in the higher hsCRP quartile groups (P = 0·073).Conclusion   These findings suggest that low grade systemic inflammation may be a common linking factor between development of atherosclerosis and increased bone turnover rate.
Novel polymorphisms and lack of mutations in the ACD gene in patients with ACTH resistance syndromes
Authors: Keegan Catherine E. , Hutz Janna E. , Krause Andrea S. , Koehler Katrin , Metherell Louise A. , Boikos Sosipatros , Stergiopoulos Sotirios , Clark Adrian J. L. , Stratakis Constantine A. , Huebner Angela , Hammer Gary D. 
Published: May 2007

SummaryObjective  ACTH resistance is a feature of several human syndromes with known genetic causes, including familial glucocorticoid deficiency (types 1 and 2) and triple A syndrome. However, many patients with ACTH resistance lack an identifiable genetic aetiology. The human homolog of the Acd gene, mutated in a mouse model of adrenal insufficiency, was sequenced in 25 patients with a clinical diagnosis of familial glucocorticoid deficiency or triple A syndrome.Design  A 3·4 kilobase genomic fragment containing the entire ACD gene was analysed for mutations in all 25 patients.Setting  Samples were obtained by three investigators from different institutions.Patients  The primary cohort consisted of 25 unrelated patients, primarily of European or Middle Eastern descent, with a clinical diagnosis of either familial glucocorticoid deficiency (FGD) or triple A syndrome. Patients lacked mutations in other genes known to cause ACTH resistance, including AAAS for patients diagnosed with triple A syndrome and MC2R and MRAP for patients diagnosed with familial glucocorticoid deficiency. Thirty‐five additional patients with adrenal disease phenotypes were added to form an expanded cohort of 60 patients.Measurements  Identification of DNA sequence changes in the ACD gene in the primary cohort and analysis of putative ACD haplotypes in the expanded cohort.Results  No disease‐causing mutations were found, but several novel single nucleotide polymorphisms (SNPs) and two putative haplotypes were identified. The overall frequency of SNPs in ACD is low compared to other gene families.Conclusions  No mutations were identified in ACD in this collection of patients with ACTH resistance phenotypes. However, the newly identified SNPs in ACD should be more closely examined for possible links to disease.
The dynamics of western North America: stress magnitudes and the relative role of gravitational potential energy, plate interaction at the boundary and basal tractions
Authors: Flesch Lucy M. , Holt William E. , Haines A. John , Wen Lianxing , Shen-Tu Bingming 
Published: May 2007

Summary
We investigate the forces involved in driving long-term large-scale continental deformation in western North America, and quantify the vertically averaged deviatoric stress field arising from internal buoyancy forces and the accommodation of relative plate motions. In addition, we investigate the ability of regional models to resolve the level of tractions acting at the base of the lithosphere. We directly solve force-balance equations for vertically averaged deviatoric stresses associated with differences in values of 1/(lithospheric thickness) times the gravitational potential energy per unit area (GPE). The GPE values are inferred using both the ETOPO5 topographic data set and the CRUST2.0 crustal thickness model. Deviatoric stresses associated with basal tractions are calculated globally, with inputs determined from an isoviscous upper mantle (η = 1021 Pa s) 3-D large-scale convection model in which mantle density variations were inferred from tomographic data and the history of subduction. In a 211-parameter iterative inversion we then solve for a stress field boundary condition by fitting stress field indicators (i.e. the directions and relative magnitudes of the principal axes of kinematic strain rates). Magnitudes of the total vertically averaged deviatoric stress field (sum of GPE solution with the boundary condition solution) range from 5 to 10 MPa within a 100-km thick lithosphere. These magnitudes are calibrated by the GPE differences, along with the spatial variation in deformation style. There is a trade-off between the scaling of the basal traction deviatoric stress field and the boundary condition solution. However, the combined boundary conditions plus basal traction solution is robust (in both magnitude and style), and when added to the contribution from GPE differences provides a global minimum of misfit between the total deviatoric stress solution and the stress field indicators. GPE variations account for ∼50 per cent of the deviatoric stress magnitudes driving deformation, while boundary condition stresses account for the remaining ∼50 per cent of deviatoric stress magnitude. By comparing possible end-member strength profiles with our vertically averaged deviatoric stresses we infer that the bulk of the strength within the lithosphere in western North America lies within the brittle seismogenic layer.
Evolution of stress in Southern California for the past 200 years from coseismic, postseismic and interseismic stress changes
Authors: Freed Andrew M. , Ali Syed Tabrez , Bürgmann Roland 
Published: May 2007

SummaryThe seismicity of southern California results from stresses that arise from the relative motion of the Pacific and North American Plates being accommodated along the San Andreas Fault (SAF) system and the Eastern California Shear Zone (ECSZ). Here we calculate how the stress field in southern California has evolved over the past two centuries due to interseismic loading, as inferred from current GPS observations of surface velocities, from redistributions of static stress induced by large (Mw ≥ 6.5) earthquakes since the 1812 Wrightwood quake, and postseismic viscoelastic relaxation associated with these events that serves to transfer coseismic stresses from the deep, warm, lower crust and upper mantle to the overlying seismogenic upper crust. We calculate Coulomb stress changes on vertical strike-slip faults striking parallel to the SAF and at the hypocenters on the rupture planes of all Mw ≥ 6 events over the past two centuries. Our results suggest that the 1857 Mw = 8.2 Fort Tejon earthquake, by far the largest event to have occurred in the region over the past two centuries, had a profound influence on the state of stress in Southern California during the 19th century, inducing significant stress increases to the north (Parkfield region and adjoining creeping SAF) and south (southern SAF and San Jacinto fault), and stress relief across the southern ECSZ. These stress changes were then greatly magnified by postseismic relaxation through the early part of the 20th century. Slow interseismic build-up of stress further loads all major strike-slip faults and works to reload the areas of the ECSZ where stress was relieved by the 1857 quake. Our calculations suggest that only 56% of hypocenters were pushed closer to failure by preceding coseismic stress changes, suggesting that the occurrence of large earthquakes is not strongly determined by coseismic Coulomb stress changes. This percentage rises to 70% when postseismic stress changes are also considered. Our calculations demonstrate the importance of postseismic viscoelastic relaxation in the redistribution of stress following large earthquakes. We find, however, that postseismic processes associated with events more than about a decade old are near completion and thus do not significantly influence the regional velocity field presently observed in southern California.
Cytotoxic molecule expression is predictive of prognosis in Hodgkin's‐like anaplastic large cell lymphoma
Authors: Asano N , Suzuki R , Matsuo K , Kagami Y , Ishida F , Tamaru J‐I , Jin G‐S , Sato Y , Shimoyama Y , Yoshino T , Morishima Y , Nakamura S 
Published: May 2007

Aims:  The Revised European American Lymphoma classification uses the term Hodgkin's‐like anaplastic large cell lymphoma (HD‐like ALCL) for borderline cases with features of both anaplastic large cell lymphoma (ALCL) and classical Hodgkin's lymphoma (HL). The aim of this study was to clarify the association between cytotoxic molecule (CM) expression and clinical outcome in HD‐like ALCL.Methods and results:  Subjects were 59 patients with HD‐like ALCL, defined by nodal presentation without mediastinal bulky lesions, T‐ or null‐cell phenotype, CD30+ anaplastic lymphoma kinase (ALK)– phenotype and by confluent sheets or nodules of large cells mimicking classic Hodgkin and Reed–Sternberg cells. We evaluated the presenting features and prognosis of subjects on categorization into two defined groups, namely CM (TIA1 and/or granzyme B)‐positive (n = 21) and CM‐negative (n = 38). The series consisted of 18 women and 41 men ranging from 16 to 88 years of age (median 59 years). The CM+ group had poorer disease‐specific survival than the CM– group (P = 0.02) despite the absence of differences in other clinical characteristics. Multivariate analysis confirmed that CM expression was an independent prognostic factor, in contrast to phenotypic categorization (T‐cell vs. null‐cell group), which had no prognostic impact on disease‐specific survival.Conclusion:  CM expression is predictive of prognosis in HD‐like ALCL.
Osteopontin is linked to p65 and MMP‐9 expression in pulmonary adenocarcinoma but not in malignant pleural mesothelioma
Authors: Frey A B , Wali A , Pass H , Lonardo F 
Published: May 2007

Aims:  Osteopontin (OPN) is a matricellular protein involved in tissue remodelling, cell‐mediated immunity and malignant transformation. High OPN serum levels predict poor prognosis in non‐small cell carcinoma and set patients with malignant pleural mesothelioma (MM) apart from disease‐free asbestos‐exposed individuals. Yet neither the spectrum of tissue expression nor the signalling pathways of OPN in MM and pulmonary adenocarcinoma have been characterized, although in vitro evidence links OPN to the epidermal growth factor receptor (EGFR) pathway. The aim of this study was to address these deficiencies.Methods and results:  OPN expression was investigated immunohistochemically in 104 adenocarcinomas and 38 MM and correlated with histological features, including tumour type, grade and proliferation and with expression of activated intermediary EGFR signalling pathway molecules p65, p‐AKT, p‐ERK, p‐STAT‐3, and of metalloproteinase (MMP)‐1, MMP‐2 and MMP‐9. In MM, OPN expression was widespread (36/38) and independent of the molecular parameters studied. In adenocarcinoma, high OPN expression was correlated with expression of p65, p‐ERK and MMP‐9.Conclusions:  Frequent OPN expression is typical of, but not specific for MM, whereas it appears to select adenocarcinoma cases with p65 and MMP‐9 expression, suggesting a link with EGFR signalling pathways.
C4d immunopositivity is uncommon in ABO‐compatible liver allografts, but correlates partially with lymphocytotoxic antibody status
Authors: Bellamy C O C , Herriot M M , Harrison D J , Bathgate A J 
Published: May 2007

Aims:  To determine whether C4d immunopositivity helps recognition of humoral rejection in dysfunctional liver allografts.Methods and results:  C4d immunopositivity was retrospectively evaluated in liver allografts. There were three staining patterns: portal venular plexus, sinusoidal and hepatocellular. The latter was related to ischaemic necrosis and not scored as positive. C4d immunopositivity was not encountered in 10 preperfusion or 15 consecutive early protocol biopsies. However, three of 12 early protocol biopsy specimens from crossmatch‐positive patients were C4d+, two showing repeated positivity on at least one further biopsy specimen, while others remained negative. C4d was also positive in 2/16 early moderate acute cellular rejections, 3/14 cases of centrilobular necroinflammation, 3/11 biliary obstructions, 3/13 chronic rejections and 1/10 primary non‐functional allografts.Conclusion:  C4d immunopositivity is uncommon in liver allografts. There is a weak positive correlation with a positive lymphocytotoxic crossmatch and some patterns of allograft dysfunction. The morphological associations resemble those reported in lymphocytotoxic crossmatch‐positive patients, plus occasional sinusoidal and hepatocellular injury. Although the practical utility of C4d immunohistochemistry seems limited, it may identify a small subgroup of individuals in whom chronic humoral microvascular injury contributes to allograft dysfunction.
High‐grade ovarian serous carcinoma exhibits significantly higher p16 expression than low‐grade serous carcinoma and serous borderline tumour
Authors: O'Neill C J , McBride H A , Connolly L E , Deavers M T , Malpica A , McCluggage W G 
Published: May 2007

Aims:  A dualistic pathway of ovarian serous carcinogenesis is now well established whereby high‐grade serous carcinoma and low‐grade serous carcinoma represent two distinct tumour types with a different underlying pathogenesis. The aim of this study was to compare expression of p16 INK4A (p16) in these two tumour types. We also included cases of serous borderline tumour, since these are considered to represent a precursor lesion of low‐grade serous carcinoma.Methods and results:  Cases of serous borderline tumour (n = 18), low‐grade ovarian serous carcinoma (n = 22) and high‐grade ovarian serous carcinoma (n = 24) were stained with a monoclonal antibody against p16. Cases were scored both with respect to intensity of immunoreactivity (weak, 1+; moderate, 2+; or strong, 3+) and distribution (0, negative or occasional positive cells; 1+, < 10% cells positive; 2+, 10–25% cells positive; 3+, 26–50% cells positive; 4+, 51–75% cells positive; or 5+, 76–100% cells positive). An immunohistochemical composite score was also calculated (0–15) by multiplying the intensity and distribution scores. There was a statistically significant difference in p16 immunoreactivity with respect to intensity, distribution and composite score between high‐grade serous carcinoma and each of the other two groups, with the high‐grade neoplasms exhibiting stronger and more diffuse positivity. Most high‐grade serous carcinomas exhibited positivity of close to 100% of tumour cells. There was no significant difference in p16 expression between the borderline tumours and low‐grade serous carcinomas.Conclusions:  The increased expression of p16 in high‐grade serous carcinoma compared with low‐grade serous carcinoma and serous borderline tumour is in keeping with a different underlying pathogenesis. p16 may be implicated in the development of high‐grade serous neoplasia within the ovary and elsewhere within the female genital tract.
B‐lymphocyte depletion ameliorates Sjögren's syndrome in Id3 knockout mice
Authors: Hayakawa Ikuko , Tedder Thomas F. , Zhuang Yuan 
Published: May 2007

SummarySjögren's syndrome is an autoimmune disease in which immune cells chronically attack the lachrymal and salivary glands. The Id3 knockout mouse is a newly established animal model for primary Sjögren's syndrome. To address the role of B cells in Sjögren's syndrome and autoimmune disease, we studied the effect of CD20 monoclonal antibody treatment on the disease in Id3 knockout mice. Antibody treatment at 2‐month intervals led to efficient and sustained B‐cell depletion in Id3 knockout mice. A significant improvement of histopathology was observed accompanied by the recovery of saliva secretory function after CD20 antibody treatment. We further show that serum immunoglobulin G3, which is abnormally high in untreated Id3 knockout mice, was reduced after CD20 antibody treatment. This study establishes a new animal model for immunotherapy of Sjögren's symptoms and suggests a possible link between immunoglobulin G3 and disease pathology in Id3 knockout mice.