bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary Follicle-Stimulating Hormone for Normogonadotropic Clomiphene-Resistant Anovulatory Infertility: Prospective, Randomized Comparison between Low Dose Step-Up and Step-Down Dose Regimens1
Authors: van Santbrink Evert J. P. , Fauser Bart C. J. M. 
Published: January 2014

A low dose step-up and step-down regimen for induction of ovulation using urinary FSH was compared in a prospective randomized fashion in 37 normogonadotropic clomiphene-resistant oligo- or amenorrheic infertile women. The objectives was to assess potential differences in duration of treatment, ovarian stimulation (serum FSH levels), and response [serum estradiol (E2) levels and number and size of follicles]. Monitoring (blood sampling and transvaginal sonography) took place on the day of initiation of treatment, the first day of ovarian response as assessed by ultrasound (i.e. the first day a follicle ≥10 mm could be recognized), the day of hCG administration to induce ovulation, and 3 days thereafter.
The median duration of treatment in the low dose step-up group was 18 (range, 7–41) days compared to 9 (range, 4–16) days in the step-down group (P = 0.003), and the total numbers of ampules administered were 20 (range, 7–69) and 14 (range, 7–33), respectively (P = NS). Serum FSH levels from the first day of sonographic ovarian response until the administration of hCG were constant (median increase, 2%/day) in patients receiving the low dose step-up protocol, but showed a decrease (median, 5%/day) in step-down cycles (P &lt; 0.001). Monofollicular growth, defined as not more than one follicle 16 mm or larger on the day of hCG administration, was observed in 56% of low dose step-up and 88% of step-down cycles (P = 0.04). The percentage of patients with normal range periovulatory E2 serum levels (500–1500 pmol/L) was 33% in the low dose step-up group vs. 71% in the step-down group (P = 0.03).
We conclude that a step-down protocol for gonadotropin induction of ovulation exhibits a more physiological, late follicular phase FSH serum profile than a low dose step-up protocol. This results in a shorter duration of treatment, a greater number of monofollicular cycles, and more cycles with periovulatory E2 levels within the normal range in the step-down protocol.
Somatostatin and Growth Hormone-Releasing Hormone in Normal and Tumoral Human Breast Tissue: Endogenous Content, in Vitro Pulsatile Release, and Regulation
Authors: Benlot Caroline , Lévy Laurence , Fontanaud Pierre , Roche Annick , Rouannet Philippe , Joubert Dominique 
Published: January 2014

AbstractEndogenous production of SRIH and GHRH was analyzed in human breast tissue. SRIH precursor (pro-SRIH) was identified after Sephadex G-50 filtration of acetic acid extracts of normal and tumoral human breast samples. SRIH-(1–14) or -(1–28) could not be detected in breast tissue, whereas the immunoreactive SRIH released in vitro was characterized as SRIH-(1–28). Endogenous production of GHRH was assessed by identification of GHRH messenger ribonucleic acid by PCR followed by sequencing of the amplified complementary DNA and by high performance liquid chromatographic characterization of immunoreactive GHRH contained in the tissue and released in vitro. There were no differences in pro-SRIH or GHRH-(1–44) tissue contents between normal and tumoral samples. The release of both peptides was evidenced in perifusion and static incubation. Perifusion of normal breast tissue (n = 3) showed pulsatile release of SRIH and GHRH. Perifusion of tumors (n = 4) showed SRIH release in 50% of the cases. SRIH release was pulsatile in one case. GHRH release was observed in the four tumoral samples analyzed, but was pulsatile in only one case. In static incubation, tumors (n = 6) secreted 13 times more GHRH than did normal samples (n = 3; 383 ± 92 vs. 29.6 ± 4.6 fmol/mg protein; P &lt; 0.05). Stimulation of GHRH release by exogenous SRIH was observed only with the normal tissue.Together these data provide evidence for the existence of local production of SRIH and GHRH by human breast. Hypersecretion of GHRH by breast tumors indicates that this peptide could play a role in maintaining epithelial cell proliferation as is the case for other peptides produced locally.
The Pituitary-Adrenal Responses to Exogenous Human Corticotropin-Releasing Hormone in Preterm, Very Low Birth Weight Infants
Authors: Ng P. C. , Wong G. W. K. , Lam C. W. K. , Lee C. H. , Wong M. Y. , Fok T. F. , Wong W. , Chan D. C. F. 
Published: January 2014

Abstract
To evaluate the pituitary-adrenal reserve and to standardize the methodology of performing the human CRH (hCRH) stimulation test, we performed the hCRH test on 14 preterm (&lt;32 gestational weeks), very low birth weight infants, who did not receive antenatal or postnatal corticosteroid treatment, on days 7 and 14 of life. Blood samples were obtained 0 (baseline), 15, 30, and 60 min after an iv dose of hCRH (1μ g/kg). The plasma ACTH concentration rose from a basal value of 5.7 ± 0.6 pmol/L (mean ± sem) to 11.9 ± 2.1 pmol/L (P &lt; 0.005), 9.2 ± 1.2 pmol/L (P &lt; 0.005), and 7.7 ± 0.8 pmol/L (P &lt; 0.005) at 15, 30, and 60 min, respectively. The corresponding rises in serum cortisol from a basal concentration of 396 ± 67 nmol/L were 509 ± 71 nmol/L (P&lt; 0.0001), 647 ± 62 nmol/L (P &lt; 0.0001), and 578 ± 60 nmol/L (P &lt; 0.0001). The plasma ACTH concentration consistently peaked early at 15 min, whereas the maximum cortisol response occurred 30 min post-hCRH stimulation. No significant differences were detected between the hCRH tests performed on days 7 and 14 (P &gt; 0.15). Mechanical ventilation, infant gender, and mode of delivery did not significantly influence the hormonal responses (P &gt; 0.25).
We have defined in this study the pattern, the magnitude of the pituitary-adrenal response, and the timing of the peak concentrations of plasma ACTH and serum cortisol in relation to a standard iv dose of hCRH. The hCRH test in very low birth weight infants appears to be safe and reproducible, and produces a pituitary-adrenal response comparable to that seen in older children and adults, indicating that pituitary-adrenal function is mature at these early stages of gestation.
Characterization of a New Case of Autoimmune Type I Hyperlipidemia: Long-Term Remission under Immunosuppressive Therapy1
Authors: Pruneta Valerie , Moulin Philippe , Labrousse Florence , Bondon Pierre-Jean , Ponsin Gabriel , Berthezene Francois 
Published: January 2014

AbstractOnly a few cases of type I hyperlipidemia occurring in patients with autoimmune disease have been reported. We describe the case of a 35-yr-old woman suffering from severe type I hyperchylomicronemia. A combination of various hypolipidemic treatments, including strict hypolipidemic dietary therapy and administration of fibrates or n-3 fatty acids, was inefficient. Because of a history of familial autoimmunity, we introduced an immunosuppressive therapy that resulted in consistent long term and stable remission. Two attempts to reduce the immunosuppressor dose resulted in major relapses. To explain the defect of chylomicron hydrolysis, we investigated the postheparin plasma lipase activities. Hepatic triglyceride lipase activity was normal, whereas that of lipoprotein lipase (LPL) was reduced to about 30% of normal. Immunosuppressive therapy resulted in a complete and durable normalization of LPL activity. Using Western blot analysis, we found in the plasma of the patient a circulating IgG specifically directed against LPL, which became undetectable during immunosuppressive therapy. Western blot analysis revealed that the whole circulating anti-LPL autoantibody was bound to chylomicrons. Proteins extracted from patient’s chylomicrons were able to induce a dose-related inhibition of LPL activity in vitro, whereas that of hepatic triglyceride lipase remained unchanged.These data constitute the first description of autoimmune hyperchylomicronemia due to an exclusive defect of LPL activity, and they show that a complete remission has been obtained after immunosuppressive therapy. Finally, our finding that the anti-LPL autoantibody is bound to chylomicrons emphasizes their previously unrecognized ability to transport LPL, already described for other lipoprotein fractions.
Effect of Plasma Osmolality on Pituitary-Adrenal Responses to Corticotropin-Releasing Hormone and Atrial Natriuretic Peptide Changes in Central Diabetes Insipidus*
Authors: Elias Lucila L. K. , Antunes-Rodrigues José , Elias Paula C. L. , Moreira Ayrton C. 
Published: January 2014

Abstract
The objective of the present study was to examine the effect of changes in plasma osmolality (pOsm) on the responses of the pituitary-adrenal axis to CRH and atrial natriuretic peptide (ANP) release in patients with central diabetes insipidus (DI). Eight normal subjects and six DI patients were subjected to human CRH (hCRH) (1 μg/kg) stimulation alone or associated with isotonic volume loading (0.9% NaCl, 12 mL·kg·60 min) or an osmotic stimulus (5% NaCl, 0.06 mL·kg/min·120 min). The DI group showed significantly increased pOsm and undetectable or low plasma arginine vasopressin (AVP) during all tests. In the control group, pOsm and plasma AVP increased only during the osmotic stimulus. The DI group presented lower plasma ANP levels than controls during osmotic stimulus and isotonic volume loading. The lower ANP secretion in DI patients corroborates the importance of neurohypophyseal hormones in ANP regulation. Basal plasma ACTH and cortisol levels did not differ between controls and DI. The latter group presented a higher ACTH response than controls during stimulation with hCRH alone [area under the curve (AUC) 1138 ± 99 vs. 709 ± 62 pmol·L/min] and hCRH/5% NaCl (AUC 1602 ± 209 vs. 1158 ± 187 pmol·L·min). The DI cortisol AUC were higher than controls during stimulation with hCRH alone (65,471 ± 6,070 vs. 48,062 ± 3,476 nmol·L·min) and hCRH/5% NaCl (89,005 ± 10,043 vs. 62,105 ± 5,600 nmol·L·min). The highest ACTH and cortisol responses to hCRH in both groups were obtained with hCRH/5% NaCl. There was a significant correlation between mean pOsm and ACTH response to hCRH (r = 0.62). The increased responses to hCRH with increasing pOsm were present in control subjects and in patients with DI. However, at any given level of pOsm, there was no difference in ACTH response between controls and DI. These data indicate that the acute increases in pOsm augmented the ACTH and cortisol responses to hCRH that involve other factors besides magnocellular AVP.
A Novel Point Mutation in the Insulin Gene Giving Rise to Hyperproinsulinemia*
Authors: Warren-Perry Margaret G. , Manley Susan E. , Ostrega Diane , Polonsky Ken , Mussett Sandra , Brown Phil , Turner Robert C. 
Published: January 2014

Abstract
A 58-yr-old obese white Caucasian male type 2 diabetic, entered into the UK Prospective Diabetes Study, was found to have raised fasting total proinsulin levels 708 pmol/L−1 (normal range, 3–16 pmol/L−1) and normal specific plasma insulin level 29 pmol/L−1 (normal range, 21–75 pmol/L−1). Immunoreactive plasma insulin, measured by RIA, was 503 pmol/L−1. DNA was extracted, the insulin gene amplified by the PCR, and by direct sequencing, a novel point mutation, G1552C, was identified, which resulted in the substitution of proline (CCT) for arginine (CGT) at position 65. This prevented cleavage of the C-peptide A-chain dibasic cleavage site (lys-arg) by the processing protease in the pancreatic β-cells. The plasma proinsulin and insulin levels were in accord with expression of both the wild-type and the mutant alleles. The G1552C mutation was not linked with diabetes, because it was present in a 37-yr-old nondiabetic daughter and not in a 35-yr-old daughter who had had gestational diabetes.
Proteolysis of Insulin-Like Growth Factor-Binding Protein-3 by Human Skin Keratinocytes in Culture in Comparison to that in Skin Interstitial Fluid: The Role and Regulation of Components of the Plasmin System1
Authors: Xu Su , Savage Paul , Burton John L. , Sansom Jane , Holly Jeffrey M. P. 
Published: January 2014

AbstractProteolysis of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is an important determinant of IGF action on cells. We have investigated this in a human skin keratinocyte cell line HaCaT. Although these cells did not normally produce an active IGFBP-3 protease, addition of plasminogen resulted in a dose-dependent proteolysis of endogenous and exogenous IGFBP-3, producing fragments similar to those cleaved by skin interstitial fluid, but different from those generated by plasmin. Protease inhibitor profiles suggested the enzyme in the conditioned medium to be a calcium-dependent serine protease.Exogenous IGFBP-3 either inhibited or slightly stimulated IGF-I-induced cell proliferation when it was coincubated or preincubated with the cells, respectively. Both effects were attenuated in the presence of plasminogen.Preincubation of cells with IGF-I or long R3 IGF-I divergently changed plasminogen activator inhibitor-1 and -2 secretion, but only IGF-I blocked IGFBP-3 proteolysis. Such inhibition was also observed in a cell-free protease assay. IGF-I, however, had no effect on plasmin-induced IGFBP-3 degradation.Together, these data indicate that an IGFBP-3 protease similar to that in skin interstitial fluid is generated in plasminogen-treated HaCaT cells, and it attenuates the effects of IGFBP-3 on IGF action. IGF-I, probably by coupling with IGFBP-3, can protect it from the action of this protease.
Long-Term Testosterone Administration Increases Visceral Fat in Female to Male Transsexuals1
Authors: Elbers Jolanda M. H. , Asscheman Henk , Seidell Jacob C. , Megens Jos A. J. , Gooren Louis J. G. 
Published: January 2014

The amount of intraabdominal (visceral) fat is an important determinant of disturbances in lipid and glucose metabolism. Cross-sectional studies in women have found associations between high androgen levels and visceral fat accumulation. The causal relation between these phenomena is unknown. We, therefore, studied prospectively the effect of testosterone administration on body fat distribution in 10 young, nonobese, female to male transsexuals undergoing sex reassignment. Before, after 1 yr, and after 3 yr of testosterone administration, magnetic resonance images were obtained at the level of the abdomen, hip, and thigh to quantify both sc and visceral fat depots. After 1 yr of testosterone administration, sc fat depots at all levels showed significant reductions compared to baseline measurements. The mean visceral fat area did not change significantly, but subjects who gained weight in the first year after testosterone administration showed an increase in visceral fat. After 3 yr of testosterone administration, sc fat depots were no longer significantly lower compared to pretreatment measurements, but the mean visceral fat depot had increased significantly by 13 cm2 (95% confidence interval, 4–22 cm2), a relative increase of 47% (95% confidence interval, 8–91%) from baseline. The increase in visceral fat was most pronounced in those subjects who had gained weight.
We conclude that long term testosterone administration in young, nonobese, female subjects increases the amount of visceral fat. In addition, an increase in weight in this hyperandrogenic state leads to a preferential storage of fat in the visceral depot.
Dehydroepiandrosterone Treatment Is Not Beneficial to the Immune Response to Influenza in Elderly Subjects*
Authors: Danenberg H. D. , Ben-Yehuda A. , Zakay-Rones Z. , Gross D. J. , Friedman G. 
Published: January 2014

AbstractBackground. Dehydroepiandrosterone (DHEA) is a native steroid with an immunomodulating activity that was suggested to counterregulate some phenomena of immunosenescence. Recently, it was shown to reverse the age-associated decline of immune response against influenza vaccine in aged mice. The present study was designed to evaluate the effect of DHEA on the immunization of elderly volunteers against influenza.Methods. Seventy-one elderly volunteers age 61–89 yr were enrolled in a prospective randomized, double-blind study to receive either DHEA (50 mg qd p.o. for four consecutive days starting two days before immunization) or placebo. Antibody response to the vaccine was measured before and 28 days after vaccination.Results. DHEA treatment significantly increased serum DHEA-sulfate (DHEA-S). No enhancement in established immunity was observed. A significant decrease in attainment of protective antibody titer (1:40 or higher) against the A/Texas strain in subjects with nonprotective baseline antibody titer was recorded following DHEA treatment compared with placebo (52% vs. 84%, P &lt; 0.05). Baseline DHEA-S serum levels were inversely related to attainment of immunization in DHEA-treated subjects. Influenza-like morbidity during the winter was low in the study group with no difference between the DHEA and placebo groups.Conclusions. Although highly effective in aged rodents, a short course of DHEA treatment did not improve the age-related declined response to immunization against influenza in human subjects. Higher baseline DHEA-S levels are not predictive of better immunization against influenza in the elderly.
The Effect of Oral Glucose on Serum Free Insulin-Like Growth Factor-I and -II in Healthy Adults*
Authors: Frystyk Jan , Grøfte Thorbjørn , Skjærbæk Christian , Ørskov Hans 
Published: January 2014

Abstract
Insulin-like growth factor (IGF) binding protein-I (IGFBP-1) has been suggested to regulate the availability of free IGF and the glucose lowering activity of the IGF-system in relation to fuel supply. Our recent observations of significant inverse correlations between free IGF-I and IGFBP-1 in cross-sectionally collected fasting serum samples support a possible physiological association between the peptides. To further study the impact of IGFBP-1 on free IGF levels and the possible participation of the IGF-system in glucose homeostasis, we studied the time course of changes in IGFBP-1 and free IGFs in 13 healthy subjects undergoing an oral glucose tolerance test (OGTT). Serum was collected every 30 min for 330 min.
Glucose, insulin, and GH followed the expected patterns and had regained baseline levels at 270 min. Total IGF-I and free and total IGF-II remained unaltered. IGFBP-1 decreased significantly by 37–52% (P &lt; 0.05) from 150 to 210 min, whereafter the concentration gradually increased by 75% to a level that tended to be above baseline (P = 0.052). Free IGF-I decreased by 29–38% (P &lt; 0.05) at the end of the study (270–330 min). IGFBP-1 was inversely correlated to free IGF-I at baseline (r = −0.57; P &lt; 0.05), as well as during the OGTT (r = 0.66; P &lt; 0.0001). In contrast, free IGF-II was not correlated to IGFBP-1. Insulin, but not free IGF-I, correlated significantly with serum glucose (P &lt; 0.05).
These results extend our previous findings of an inverse correlation between free IGF-I and IGFBP-1 in cross-sectional studies to include longitudinal observations, and thus further substantiates the hypothesis that IGFBP-1 is an important determinant of free IGF-I in vivo. Significant changes in free IGF-I were observed only in the late postprandial phase, when glucose and insulin were fully normalized, demonstrating that free IGFs probably do not participate in glucoregulation to any significant degree during an oral glucose load in healthy subjects.
Corticotropin-Releasing Hormone Receptor Subtype 1 Is Significantly Up-Regulated at the Time of Labor in the Human Myometrium1
Authors: Stevens M. Yvette , Challis John R. G. , Lye Stephen J. 
Published: January 2014

Circulating concentrations of CRH rise late in human pregnancy, reaching a peak at labor. The presence of functional CRH receptors, CRH-R1 and CRH-R2, in the human myometrium suggests that CRH may modulate uterine activity. We hypothesized that the number of CRH receptors would be higher in myometrium than fetal membranes (FM) and would change during labor.
Myometrial samples were collected from the lower segment (LS) in nonpregnant, preterm (32 ± 2 weeks), and term (39 ± 1.6 weeks) pregnant patients before and at labor. Fundus and LS samples were also collected from nonpregnant, pregnant, laboring, and postpartum women. FM were collected at term and at labor. We identified CRH receptors in myometrium and FM by semiquantitative RT-PCR and immunohistochemistry.
CRH-R1 messenger ribonucleic acid (mRNA) in the LS was decreased in pregnancy and increased significantly in both preterm and term labor (P &lt; 0.05), but remained unchanged in the fundus. CRH-R2 mRNA was present in 28% of LS myometrium with no change at labor. CRH-R1 and CRH-R2 protein was localized to myometrial smooth muscle in nonpregnant and laboring patients, with lower levels at term. CRH-R1 mRNA was present in chorion and decidua, but CRH-R2 was undetectable in these tissues. We conclude that CRH-R1 is expressed preferentially in myometrium and FM. Changes in CRH receptors during labor are consistent with CRH mediating effects on myometrial activity.
Cortisol Secretion Is Related to Electroencephalographic Alertness in Human Subjects during Daytime Wakefulness1
Authors: Chapotot Florian , Gronfier Claude , Jouny Christophe , Muzet Alain , Brandenberger Gabrielle 
Published: January 2014

To determine whether human hypothalamo-pituitary-adrenal axis activity is related to the alertness level during wakefulness, 10 healthy young men were studied under resting conditions in the daytime (0900–1800 h) after an 8-h nighttime sleep (2300–0700 h). A serial 70-sec gaze fixation task was required every 10 min throughout the daytime experimental session. The corresponding waking electroencephalographic (EEG) segments were submitted to quantitative spectral analysis, from which EEG β activity (absolute power density in the 13–35 Hz frequency band), an index of central alertness, was computed. Blood was collected continuously through an indwelling venous catheter and sampled at 10-min intervals. Plasma cortisol concentrations were measured by RIA, and the corresponding secretory rates were determined by a deconvolution procedure.
Analysis of individual profiles demonstrated a declining tendency for EEG β activity and cortisol secretory rate, with an overall temporal relationship indicated by positive and significant cross-correlation coefficients between the two variables in all subjects (average r= 0.565, P &lt; 0.001). Changes in cortisol secretion lagged behind fluctuations in EEG β activity, with an average delay of 10 min for all the subjects. On the average, 4.6 ± 0.4 cortisol secretory pulses and 4.9 ± 0.5 peaks in EEG β activity were identified by a detection algorithm. A significant, although not systematic, association between the episodes in the two variables was found: 44% of the peaks in EEG β activity (relative amplitude, near 125%; P &lt; 0.001) occurred during an ascending phase of cortisol secretion, cortisol secretory rates increasing by 40% (P &lt; 0.01) 10-min after peaks in EEG β activity. However, no significant change in EEG β activity was observed during the period from 50 min before to 50 min after pulses in cortisol secretion.
In conclusion, the present study describes a temporal coupling between cortisol release and central alertness, as reflected in the waking EEGβ activity. These findings suggest the existence of connections between the mechanisms involved in the control of hypothalamo-pituitary-adrenal activity and the activation processes of the brain, which undergoes varying degrees of alertness throughout daytime wakefulness.