bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annexin 1-deficient neutrophils exhibit enhanced transmigration in vivo and increased responsiveness in vitro
Authors: Chatterjee Bristi E , Yona Simon , Rosignoli Guglielmo , Young Rebecca E , Nourshargh Sussan , Flower Roderick J , Perretti Mauro 
Published: July 2005

AbstractThe role of the endogenous anti-inflammatory mediator annexin 1 (AnxA1) in controlling polymorphonuclear leukocyte (PMN) trafficking and activation was addressed using the recently generated AnxA1 null mouse. In the zymosan peritonitis model, AnxA1 null mice displayed a higher degree (50–70%) of PMN recruitment compared with wild-type littermate mice, and this was associated with reduced numbers of F4/80+ cells. Intravital microscopy analysis of the cremaster microcirculation inflamed by zymosan (6 h time-point) indicated a greater extent of leukocyte emigration, but not rolling or adhesion, in AnxA1 null mice. Real-time analysis of the cremaster microcirculation did not show spontaneous activation in the absence of AnxA1; however, superfusion with a direct-acting PMN activator (1 nM platelet-activating factor) revealed a subtle yet significant increase in leukocyte emigration, but not rolling or adhesion, in this genotype. Changes in the microcirculation were not secondary to alterations in hemodynamic parameters. The phenotype of the AnxA1 null PMN was investigated in two in vitro assays of cell activation (CD11b membrane expression and chemotaxis): the data obtained indicated a higher degree of cellular responses irrespective of the stimulus used. In conclusion, we have used a combination of inflammatory protocols and in vitro assays to address the specific counter-regulatory role of endogenous AnxA1, demonstrating its inhibitory control on PMN activation and the consequent impact on the inflamed microcirculation.
Circulating Leptin Correlates with Left Ventricular Mass in Morbid (Grade III) Obesity before and after Weight Loss Induced by Bariatric Surgery: A Potential Role for Leptin in Mediating Human Left Ventricular Hypertrophy
Authors: Perego Lucia , Pizzocri Pierluigi , Corradi Domenico , Maisano Francesco , Paganelli Michele , Fiorina Paolo , Barbieri Michelangela , Morabito Alberto , Paolisso Giuseppe , Folli Franco , Pontiroli Antonio E. 
Published: July 2005

Abstract
Context: Obesity is frequently associated with left ventricular hypertrophy, even when uncomplicated by hypertension or diabetes mellitus. Left ventricular hypertrophy is an important risk factor for congestive heart failure.
Objective: The objective of this study was to evaluate the relationship between leptin and left ventricular mass in uncomplicated, morbid (grade 3) obesity and the existence of leptin receptors and intracellular signaling proteins in the human heart.
Design: Left ventricular mass (LVM) was calculated through electrocardiogram reading in normotensive grade III obese patients (World Health Organization classification) undergoing bariatric surgery [laparoscopic adjustable gastric banding (LAGB)] at baseline and 1 yr later. The control group was composed of healthy lean normotensive subjects. Leptin receptors were detected by PCR and immunocytochemistry in human heart biopsies.
Setting: This study was performed at university hospitals.
Patients: Thirty-one grade 3 obese patients and 30 healthy nonobese normotensive, age- and sex-matched control subjects were studied.
Intervention: Obese subjects underwent LAGB to induce weight loss and were evaluated at baseline and after 1 yr.
Results: LVM, plasma leptin, glucose, insulin levels, and homeostasis model assessment index were higher in obese than in lean controls (P &lt; 0.01); at univariate regression analysis, LVM correlated with body mass index, leptin, and homeostasis model assessment index; at multiple regression analysis, LVM only correlated with leptin levels (P = 0.001). Obese subjects were reevaluated 1 yr after LAGB, when their body mass index changed from 46.2 ± 1.24 to 36.6 ± 1.05 kg/m2 (P &lt; 0.01); the decrease in LVM correlated only with the decrease in leptin levels (P &lt; 0.01). We demonstrated that long and short isoforms of the leptin receptor and intracellular proteins mediating leptin signaling were expressed in human heart by RT-PCR, immunocytochemistry, or both methods.
Conclusions: These data suggest that leptin could contribute to the left ventricular hypertrophy in humans.
Cutoff Levels of 17-α-Hydroxyprogesterone in Neonatal Screening for Congenital Adrenal Hyperplasia Should Be Based on Gestational Age Rather Than on Birth Weight
Authors: van der Kamp Hetty J. , Oudshoorn Caren G. M. , Elvers Bert H. , van Baarle Maja , Otten Barto J. , Wit Jan M. , Verkerk Paul H. 
Published: July 2005

AbstractObjective: In newborn screening programs for congenital adrenal hyperplasia, 17-α-hydroxyprogesterone (17OHP) cutoff levels are based on birth weight (BW) or on gestational age (GA). We investigated which approach would result in the greatest specificity and sensitivity.Study design: For the determination of 17OHP, a neonatal 17OHP assay was used in filter paper blood of 9492 newborns. The relationships between 17OHP and BW and between 17OHP and GA were studied by regression analysis. Reference curves with a specificity of 99.95% were constructed with the method that summarizes the distribution by three smoothed curves representing the skewness (L curve), the median (M curve), and the coefficient of variation (S curve). Median cutoff levels for BW and for GA according to the 99.95% reference curves were calculated.Results: Regression analysis showed that GA is a better predictor of 17OHP than BW (R2 was 50.6 vs. 35.8%, respectively). At a specificity of 99.95%, the calculated median 17OHP cutoff level was lower for GA [12.6 μg/liter (38 nmol/liter)] than for BW [17.6 μg/liter (54 nmol/liter)], thus leading to a greater sensitivity.Conclusion: This study demonstrates that GA is a better predictor of 17OHP in newborns and will result in greater specificity than BW despite the fact that the determination of GA might be less reliable than BW.
Obesity and Type 2 Diabetes Do Not Alter Splanchnic Cortisol Production in Humans
Authors: Basu Rita , Singh Ravinder J. , Basu Ananda , Chittilapilly Elizabeth G. , Johnson Michael C. , Toffolo Gianna , Cobelli Claudio , Rizza Robert A. 
Published: July 2005

Abstract
Context: Cortisol is a potent regulator of carbohydrate, fat, and protein metabolism.
Objective: The objective of the study was to determine whether obesity alone or in combination with type 2 diabetes increases splanchnic and/or leg cortisol production.
Design: Splanchnic and leg cortisol production were measured using the hepatic and leg catheterization technique combined with infusion of D4-cortisol.
Setting: The study was conducted in a General Clinical Research Center.
Participants: Nine lean nondiabetic, 10 obese nondiabetic, and 11 obese diabetic subjects were studied.
Interventions: Diabetic volunteers were withdrawn from their glucose-lowering medications before study.
Main Outcome Measures: Rates of total body, splanchnic and leg cortisol, and D3-cortisol production were measured.
Results: Rates of splanchnic cortisol production equaled or exceeded those occurring in extrasplanchnic tissues (e.g. the adrenals) in all three groups. However, because concurrent splanchnic cortisol uptake also occurred, net splanchnic cortisol release was minimal. Splanchnic cortisol production and splanchnic D3-cortisol production (an index of splanchnic 11β-hydroxysteroid dehydrogenase type 1 activity) did not differ among the three groups. In addition, splanchnic cortisol production did not correlate with either visceral fat or endogenous glucose production. On the other hand, splanchnic cortisol uptake was greater in the obese diabetic than lean nondiabetic subjects (25 ± 2.9 vs. 15.3 ± 2.5 μg/min; P &lt; 0.05). Splanchnic, but not leg, D3-cortisol production was correlated with total body D3-cortisol production (r = 0.70; P &lt; 0.001).
Conclusions: Although large amounts of cortisol are produced within the splanchnic bed, implying high intrahepatic glucocorticoid concentrations, rates do not differ in lean and obese nondiabetic humans and are not influenced by the presence of type 2 diabetes mellitus. On the other hand, obesity but not diabetes increases splanchnic cortisol uptake.
A Critical Analysis of Pituitary Tumor Shrinkage during Primary Medical Therapy in Acromegaly
Authors: Melmed Shlomo , Sternberg Richard , Cook David , Klibanski Anne , Chanson Philippe , Bonert Vivien , Vance Mary Lee , Rhew David , Kleinberg David , Barkan Ariel 
Published: July 2005

Abstract
Context: Somatostatin analogs have been successfully used to treat patients with GH-secreting pituitary adenomas because they are safe, effective, and usually well tolerated. The results of studies evaluating acromegaly treatment with the somatostatin receptor ligands (SRLs), octreotide and lanreotide, have supported the use of these agents for primary medical therapy before or as an alternative to traditional interventions of surgery and radiotherapy in selected cases.
Evidence Acquisition: We therefore undertook a systematic literature overview to characterize the results of studies involving primary therapy with somatostatin analogs and their effects on pituitary tumor size. Because most studies in which pituitary tumor shrinkage has been assessed involve uncontrolled, open-label, prospective trials or retrospective case series, the lack of a control arm does not permit pooling of data in a metaanalytic fashion to determine tumor size reduction. Therefore, this systematic review was designed to document and stratify data by study design, summarize therapeutic regimens and patient characteristics, assess the percentage of patients showing changes in tumor size, and calculate the weighted average effect on size reduction.
Evidence Synthesis: Overall, for patients who experience significant shrinkage, an approximately 50% decrease in pituitary mass is achieved when a somatostatin analog is used exclusively or before surgery or radiotherapy. Fourteen studies (n = 424) provided a definition of significant tumor shrinkage, and the results showed that 36.6% (weighted mean percentage) of patients receiving primary SRL therapy for acromegaly experienced a significant reduction in tumor size. The weighted mean percent reduction in tumor size was 19.4% for those studies in which all patients received SRLs and change in tumor size was reported for all patients.
Conclusions: Clinical implications are discussed for patients in whom tumor size control with SRLs is an important objective, typically those who have failed surgery or are being treated with primary medical therapy with large tumors.
Efficacy of Octreotide-LAR in Dieting Women with Abdominal Obesity and Polycystic Ovary Syndrome
Authors: Gambineri Alessandra , Patton Laura , De Iasio Rosaria , Cantelli Barbara , Cognini Graciela Estela , Filicori Marco , Barreca Antonina , Diamanti-Kandarakis Evanthia , Pagotto Uberto , Pasquali Renato 
Published: July 2005

AbstractContext: Somatostatin reduces LH, GH, and insulin, and somatostatin receptors are present at the ovarian level; somatostatin analogs are thus potential candidates for treatment of the polycystic ovary syndrome (PCOS).Objective: The purpose of this study was to evaluate the effect of octreotide-LAR, a long-acting somatostatin analog, in anovulatory abdominal obese women with PCOS.Design: A single-blind, placebo-controlled study was performed, lasting for 7 months.Setting: The patients were ambulatory throughout the study.Patients: Twenty PCOS subjects were enrolled. Eighteen completed the study.Interventions: A low-calorie diet was given during the first month, a low-calorie diet plus octreotide-LAR (10 mg; n = 10 subjects) or placebo (n = 10 subjects) was then given, with one im injection every 28 d (for 6 months).Main Outcome Measures: The main outcome measures were clinical features, computerized tomography measurement of fat distribution, androgens, GH, IGF-I, IGF-binding proteins (IGFBPs), fasting and glucose-stimulated insulin, and ovulation.Results: Octreotide had no additional effect in reducing body fat or improving fat distribution than placebo. Conversely, octreotide produced an additional decrease in fasting (P = 0.018) and glucose-stimulated (P = 0.038) insulin levels, an increase in IGFBP-2 (P = 0.042) and IGFBP-3 (P = 0.047), and an improvement in hirsutism (P = 0.004). Moreover, a trend toward greater reductions in testosterone (P = 0.061) and androstenedione (P = 0.069) was observed in women treated with octreotide-LAR compared with those given placebo. All women treated with octreotide ovulated at the end of the study compared with only one of those receiving placebo (P &lt; 0.001).Conclusions: Octreotide-LAR may be usefully applied to hypocalorically dieting, abdominal obese PCOS women to improve hyperandrogenism and the insulin-IGF-I system. Restoration of ovulatory menstrual cycles appears to be another advantage of this treatment.
Identification of 9α,11β-Prostaglandin F2 in Human Amniotic Fluid and Characterization of Its Production by Human Gestational Tissues
Authors: Mitchell Murray D. , Chang Maxwell C. , Chaiworapongsa Tinnakorn , Lan Hao-Yi , Helliwell Rachel J. A. , Romero Roberto , Sato Timothy A. 
Published: July 2005

AbstractContext: 9α,11β-Prostaglandin F2 (9α,11β-PGF2) can contract uterine smooth muscle with a potency equal to PGF2α. Its presence in the human uterus and production by human gestational tissues is unknown.Objective: These studies were performed to determine whether the PGD2-derived 9α,11β-PGF2 is both present in human amniotic fluid and synthesized by human gestational tissues and if so, whether labor-related substances could regulate its production.Results: Detectable concentrations of 9α,11β-PGF2 were found in amniotic fluid samples and appeared to increase in late gestation. All gestational tissues studied synthesized 9α,11β-PGF2, with the placenta having the highest basal production rate, followed by the amnion and then the choriodecidua. IL-1β and TNFα caused concentration-dependent increases in 9α,11β-PGF2 production in human amnion and choriodecidual explants. Moreover, treatment of choriodecidual and placental explants with lipopolysaccharide resulted in a significant increase in 9α,11β-PGF2 production rates, reaching a maximum of 13-fold in the choriodecidua. Studies examining the effects of the addition of exogenous PGD2 strongly indicated that the choriodecidua has significant ability to convert PGD2 to 9α,11β-PGF2, whereas the amnion has little.Conclusions: These results demonstrate for the first time that 9α,11β-PGF2 is present in human amniotic fluid and that it is produced by human gestational tissues and up-regulated by bacterial cell wall components and proinflammatory cytokines. We suggest that this prostaglandin may play a part in the mechanisms of human labor at term and preterm.
Fibroblast Growth Factor-23 in Patients with Graves’ Disease before and after Antithyroid Therapy: Its Important Role in Serum Phosphate Regulation
Authors: Yamashita Hiroyuki , Yamazaki Yuji , Hasegawa Hisashi , Yamashita Takeyoshi , Fukumoto Seiji , Shigematsu Takashi , Kazama Junichiro James , Fukagawa Masafumi , Noguchi Shiro 
Published: July 2005

Abstract
Objective: Hyperthyroidism is a well-described cause of hyperphosphatemia. We aimed to clarify the physiological role of fibroblast growth factor (FGF)-23 in serum phosphate homeostasis in patients with Graves’ disease during the course of treatment for hyperthyroidism.
Context: The study group comprised 56 patients (45 for a cross-sectional study and 11 for a longitudinal study) with Graves’ disease. For the cross-sectional study, patients were assigned, on the basis of their serum phosphate level, to a hypophosphatemia group (n = 14), a normophosphatemia group (n = 16), or a hyperphosphatemia group (n = 15). Serum FGF-23, calcium, phosphate, PTH, and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were compared between the three groups. For the longitudinal study, we assessed changes in these biochemical indices before and after antithyroid treatment.
Results: In the cross-sectional study, the serum FGF-23 level was significantly higher (P &lt; 0.05) in the hyperphosphatemia group than in the other groups (61 ± 36 ng/liter vs. 31 ± 22 ng/liter and 30 ± 9 ng/liter). In the longitudinal study, serum levels of FGF-23 decreased significantly (P &lt; 0.05) from a high of 54 ± 12 ng/liter before treatment to 29 ± 14 ng/liter after treatment. In contrast, the serum 1,25(OH)2D level increased significantly (P &lt; 0.005) from 55 ± 22 pmol/liter before treatment to 185 ± 76 pmol/liter 3 months after treatment. Serum FGF-23 levels were positively correlated with serum phosphate levels (P &lt; 0.0001) and negatively correlated with serum 1,25(OH)2D levels (P &lt; 0.0001).
Conclusions: The significant positive correlation between serum levels of phosphate and FGF-23 indicates that FGF-23 may play an important role in serum phosphate homeostasis by its up-regulation in the hyperphosphatemic condition.
Limited Efficacy of Growth Hormone (GH) during Transition of GH-Deficient Patients from Adolescence to Adulthood: A Phase III Multicenter, Double-Blind, Randomized Two-Year Trial
Authors: Mauras Nelly , Pescovitz Ora Hirsch , Allada Vivek , Messig Michael , Wajnrajch Michael P. , Lippe Barbara 
Published: July 2005

Abstract
Context: Treatment of GH-deficient adolescents in transition to adulthood remains challenging.
Objective: The objective was to assess the safety and efficacy of GH in GH-deficient adolescents in transition.
Patients: Fifty-eight GH-deficient adolescents (mean age, 15.8 ± 1.8 yr; 33 males) at near completion of their linear growth participated in the study.
Intervention: Baseline studies were done while subjects were on GH. Subjects were retested (insulin-induced hypoglycemia) 4 wk after GH discontinuation and reclassified as persistently GH-deficient or controls (n = 18). GH-deficient subjects were randomized to GH (n = 25, ∼20 μg/kg·d) or placebo (n = 15).
Setting: The multicenter study was conducted over a 2-yr period.
Main Outcomes: Changes in body composition, bone mineral density (BMD), quality of life (QOL), cardiovascular and metabolic markers were measured.
Results: All groups had normal measures of lipid and carbohydrate metabolism, body composition, BMD, cardiac function, muscle strength, and QOL at baseline and after 2 yr. IGF-I concentrations decreased in all, but less so in the GH-group (P = 0.013). There was a greater increase in lean body mass (lesser adiposity) in the GH group than placebo at 12 months, but not at 24 months.
Conclusions: 1) GH-deficient patients properly treated in childhood can have normal BMD, body composition, cardiac function, muscle strength, carbohydrate and lipid metabolism, and QOL when reaching adult height; and 2) continuation of GH therapy for 2 yr did not change these measures as compared to placebo-treated or control subjects. GH-deficient adolescents in good metabolic status at the time of epiphyseal fusion may safely discontinue GH for at least 2 yr. Follow-up is needed to determine whether GH therapy is eventually warranted in subjects treated with GH during childhood.
Androgen Levels in Adult Females: Changes with Age, Menopause, and Oophorectomy
Authors: Davison S. L. , Bell R. , Donath S. , Montalto J. G. , Davis S. R. 
Published: July 2005

Abstract
Context: Changes in androgen levels across the adult female life span and the effects of natural menopause and oophorectomy have not been clearly established.
Objective: The objective of this study was to document the effects of age on androgen levels in healthy women and to explore the effects of natural and surgical menopause.
Design, Setting, and Participants: A cross-sectional study was conducted of 1423 non-healthcare-seeking women, aged 18–75 yr, randomly recruited from the community over 15 months.
Main Outcome Measures: Serum levels by age of total testosterone (T), calculated free T, dehydroepiandrosterone sulfate, and androstenedione in a reference group of women free of confounding factors. Women in the reference group had no usage of exogenous steroid therapy; no history of tubal ligation, hysterectomy, or bilateral oophorectomy; and no hyperprolactinemia or polycystic ovarian syndrome. The effects of natural and surgical menopause on sex steroid levels were also examined.
Results: In the reference population (n = 595), total T, calculated free T, dehydroepiandrosterone sulfate, and androstenedione declined steeply with age (P &lt; 0.001), with the decline of each being greater in the earlier than the later decades. Examination of serum androgen levels by year in women aged 45–54 yr showed no independent effect of menopausal status on androgen levels. In women aged 55 yr or older, those who reported bilateral oophorectomy and were not on exogenous steroids had significantly lower total T and free T levels than women 55 yr or older in the reference group.
Conclusions: We report that serum androgen levels decline steeply in the early reproductive years and do not vary because a consequence of natural menopause and that the postmenopausal ovary appears to be an ongoing site of testosterone production. These significant variations in androgens with age must be taken into account when normal ranges are reported and in studies of the role of androgens in women.
Immunoquantitative PCR for Prion Protein Detection in Sporadic Creutzfeldt–Jakob Disease
Authors: Gofflot Stéphanie , Deprez Manuel , el Moualij Benaïssa , Osman Awad , Thonnart Jean-François , Hougrand Olivier , Heinen Ernst , Zorzi Willy 
Published: July 2005

Abstract
Background: The most common human prion disorder is Creutzfeldt–Jakob disease (CJD); it includes sporadic, familial, iatrogenic, and variant subtypes. Diagnostic tests aim at detection with the highest specificity of very small deposits of abnormal prion protein (PrP).
Methods: We used immunoquantitative PCR (iqPCR) to detect proteinase K–resistant PrP (PrPRes) in tissue from the middle frontal gyrus of 7 patients with sporadic CJD and 7 non-CJD cases. We compared iqPCR with routine optimized ELISA, Western blotting, and immunohistochemical analyses.
Results: The 4 methods showed similar 100% sensitivity and specificity for the diagnosis of CJD. Along with high specificity, however, iqPCR had a threshold for PrPRes detection at least 10-fold lower than that of the classic ELISA.
Conclusions: iqPCR is a new method for PrPRes detection that combines 100% specificity with a detection threshold at least 10-fold lower than classic techniques. This method may improve the detection of minute PrPRes deposits in tissues and body fluids and thus be useful for diagnostic and sterilization applications.