bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leptin Replacement Prevents Weight Loss-Induced Metabolic Adaptation in Congenital Leptin-Deficient Patients
Authors: Galgani Jose E. , Greenway Frank L. , Wong Ma-Li , Licinio Julio , Ravussin Eric 
Published: January 2014

ABSTRACT
Context: Leptin regulates energy homeostasis by suppressing food intake; however, its role in energy expenditure and fat oxidation remains uncertain in humans.
Objective: The aim of the study was to assess 24-h energy metabolism before and after weight loss induced by leptin treatment in congenital leptin-deficient subjects or low-calorie diet in controls.
Design and Patients: We measured 24-h energy expenditure, 24-h fat oxidation, and body fat in three null homozygous leptin-deficient obese adults before and after weight loss induced by a 19-wk leptin replacement period (0.02-0.04 mg/kg/d). The same measures were performed in three obese controls pair-matched for sex, age, and weight loss induced by a 10- to 21-wk low-calorie diet. Measurements were preceded for 1 wk of weight stabilization. Energy expenditure was adjusted for fat-free mass, fat mass, sex, and age based on a reference population (n = 842; R2 = 0.85; P &lt; 0.0001). Similarly, fat oxidation was adjusted for fat-free mass, percentage body fat, energy balance, and diet composition during the 24-h respiratory chamber stay (R2 = 0.38; P &lt; 0.0001).
Results: Before weight loss, congenital leptin-deficient and control subjects had similar energy expenditure. However, after weight loss (∼15 kg), controls had energy expenditures lower than expected for their new weight and body composition (−265 ± 76 kcal/d; P = 0.04), whereas leptin-treated subjects had values not different from the reference population (−128 ± 119 kcal/d; P = 0.67). Before weight loss, fat oxidation was similar between groups. However, after weight loss, leptin-treated subjects had higher fat oxidation than controls (P = 0.005) and higher than the reference population (P = 0.0001).
Conclusion: In congenital leptin-deficient subjects, leptin replacement prevented the decrease in energy expenditure and fat oxidation often observed after weight loss.
Materno-Fetal Cardiovascular Complications in Turner Syndrome after Oocyte Donation: Insufficient Prepregnancy Screening and Pregnancy Follow-Up Are Associated with Poor Outcome
Authors: Chevalier Nicolas , Letur Hélène , Lelannou Dominique , Ohl Jeanine , Cornet Dominique , Chalas-Boissonnas Cécile , Frydman René , Catteau-Jonard Sophie , Greck-Chassain Thérèse , Papaxanthos-Roche Aline , Dulucq Marie-Christine , Couet Marie-Laure , Cédrin-Durnerin Isabelle , Pouly Jean-Luc , Fénichel Patrick ,   the French Study Group for Oocyte Donation
Published: January 2014

Context: Recombinant human GH treatment and oocyte donation (OD) have improved the quality of life in women with Turner syndrome (TS). However, life expectancy is reduced, mainly due to cardiovascular complications. Pregnancy may itself increase that risk and be associated with hazardous materno-fetal outcome.
Objective: The objective of this study was to evaluate the materno-fetal outcome of ongoing pregnancies beyond 20 wk of gestation obtained by OD in TS.
Design: This was a multicenter retrospective study including all assisted reproductive technology centers affiliated with the French Study Group for Oocyte Donation.
Results: Among 93 patients, only 37.6% were prescreened with echocardiography or thoracic magnetic resonance imaging. Maternal outcome was dominated by 37.8% of pregnancy-associated hypertensive disorders including preeclampsia in 54.8% and severe eclampsia in four patients. Prematurity occurred in 38.3% and was correlated with PAHD (P = 0.01). The frequency of in utero growth retardation was 27.5%. One fetal demise was linked to eclampsia. Two patients died from aortic rupture after cesarean section in a context of aortic root dilatation. Only 40% of pregnancies were associated with an absolutely normal materno-fetal outcome.
Conclusions: OD pregnancies in TS who have not been managed following recent specific recommendations were at high risk for maternal death by aortic dissection and for preeclampsia and its complications (fetal distress and in utero growth retardation). These recommendations include previous echocardiography, thoracic magnetic resonance imaging, and overnight blood pressure monitoring associated with a tight follow-up during pregnancy. Until future assessment of these recent recommendations, pregnancies obtained in TS after OD must be still considered as very high-risk pregnancies.
Increased Disorderliness of Basal Insulin Release, Attenuated Insulin Secretory Burst Mass, and Reduced Ultradian Rhythmicity of Insulin Secretion in Older Individuals1
Authors: Meneilly Graydon S. , Ryan Alice S. , Veldhuis Johannes D. , Elahi Dariush 
Published: January 2014

Insulin is secreted in a pulsatile fashion. Rapid pulses are considered to be important for inhibiting hepatic glucose output, and ultradian pulses for stimulating peripheral glucose disposal. Aging is characterized by a progressive impairment in carbohydrate tolerance. We undertook the current studies to determine whether alterations in pulsatile insulin release accompany the age-related changes in carbohydrate metabolism. Healthy young (n = 8; body mass index, 21 ± 1 kg/m2; age, 24 ± 1 yr) and old (n = 9; body mass index, 24 ± 1 kg/m2; age, 77 ± 2 yr) volunteers underwent two studies. In the first study, insulin was sampled every 1 min for 150 min, and pulse analysis was conducted using a recently validated multiparameter deconvolution technique. In the second study, insulin was sampled every 10 min for 600 min, and insulin release was evaluated by Cluster analysis. In the 150-min studies, insulin secretory burst mass (P &lt; 0.05) and amplitude (P &lt; 0.01) were reduced in the elderly. In addition, approximate entropy, a measure of irregularity or disorderliness of insulin release, was increased in the aged (P &lt; 0.01). In the 600-min studies, interpulse interval was greater in the aged (P &lt; 0.05), and burst number was less (P &lt; 0.05).
We conclude that normal aging is characterized by more disorderly insulin release, a reduction in the amplitude and mass of rapid insulin pulses, and a decreased frequency of ultradian pulses. Whether these alterations in insulin pulsatility contribute directly to the age-related changes in carbohydrate metabolism will require further study.
Measurement of Human Growth Hormone Receptor Messenger Ribonucleic Acid by a Quantitative Polymerase Chain Reaction-Based Assay: Demonstration of Reduced Expression after Elective Surgery*
Authors: Hermansson Majlis , Wickelgren Ruth B. , Hammarqvist Folke , Bjarnason Ragnar , Wennström Ingmar , Wernerman Jan , Carlsson Björn , Carlsson Lena M. S. 
Published: January 2014

Abstract
Studies of GH receptor (GHR) gene expression in human tissues have been hampered by the limited amount of tissue available for analysis and the low sensitivity of conventional methods. We have developed a quantitative reverse transcriptase-PCR assay for measurement of GHR messenger ribonucleic acid levels in small human tissue biopsies. To compensate for sample to sample variation, an internal RNA standard, which differs from the wild-type GHR transcript by only a few nucleotides, was reverse transcribed and amplified together with the GHR transcripts. PCR was carried out using one biotinylated primer to permit the purification of single stranded PCR products on streptavidin-coated microtiter plates. The ratio between the wild-type and mutated transcripts was determined by two separate minisequence reactions in which a primer, annealed immediately 3′ of a variable nucleotide, was extended by a single 3H-labeled nucleotide, complementary to either the wild-type or mutated sequence. The assay range was 0.125–8 × 105 transcripts/sample, the mean intraassay coefficient of variation was 8.7%, and the lower limit of detection was 0.125 × 105 transcripts/sample. GHR messenger ribonucleic acid levels were detectable in small amounts (10–100 ng) of total RNA extracted from adipose tissue, skeletal muscle, and liver. The GHR gene expression in liver was approximately 10-fold higher than that in skeletal muscle, whereas intermediate levels were found in adipose tissue. In nine patients undergoing elective abdominal surgery, GHR gene expression in skeletal muscle was reduced on day 3 after surgery compared to the baseline level. The decrease in GHR gene expression was accompanied by a decrease in skeletal muscle glutamine. This suggests that the postoperative protein catabolism may be caused at least partly by acquired GH insensitivity due to reduced expression of the GHR gene.
Prolactin Receptor Messenger Ribonucleic Acid in Normal and Neoplastic Human Pituitary Tissues1
Authors: Jin Long , Qian Xiang , Kulig Elzbieta , Scheithauer Bernard W. , Calle-Rodrigue Rocio , Abboud Charles , Davis Dudley H. , Kovacs Kalman , Lloyd Ricardo V. 
Published: January 2014

AbstractWe examined the specific cell types in normal human pituitaries that expressed PRL receptor (PRL-R) messenger ribonucleic acid (mRNA) by combined in situ hybridization and immunohistochemistry. The distribution of PRL-R mRNA in 28 pituitary adenomas was examined by in situ hybridization and reverse transcription-PCR in 12 cases of adenomas. In another set of experiments, 34 PRL adenomas from men, women, and bromocriptine-treated patients were analyzed for PRL-R by in situ hybridization.In the normal pituitary, PRL- and LH-producing cells had significantly more mean grain counts per cell and higher percentages of cells positive for PRL-R than GH and TSH cells. PRL-R mRNA was present in all groups of adenomas by in situ hybridization and reverse transcription-PCR. PRL adenomas had a significantly higher density of labeling compared to other adenoma types. Although there was no difference in the levels of PRL-R mRNA in PRL adenomas from men and premenopausal and postmenopausal women, patients treated with bromocriptine before pituitary surgery had significantly lower levels of PRL-R compared to all other groups. These results indicate that in the normal pituitary, PRL and LH cells have the highest level of PRL-R mRNA, whereas PRL adenomas have significantly higher levels of PRL-R mRNA than other types of adenomas, and bromocriptine treatment decreases the levels of PRL-R mRNA in PRL adenomas.
Cloning and Characterization of the Promoter Regions of the Human Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Gene: Analysis of Deoxyribonucleic Acid from Normal Subjects and Patients with Pseudohypoparathyroidism Type 1b*
Authors: Bettoun J. David , Minagawa Masanori , Kwan Mei Yee , Lee Han S. , Yasuda Toshiyuki , Hendy Geoffrey N. , Goltzman David , White John H. 
Published: January 2014

AbstractExpression of the PTH/PTH-related peptide (PTHrP) receptor (PTHR) in the mouse is controlled by at least two promoters. The downstream promoter (P2) is ubiquitously expressed, whereas expression of the upstream promoter (P1) is largely restricted to kidney. These observations may provide a genetic basis for a human PTH resistance syndrome, pseudohypoparathyroidism type 1b (PHP1b), in which renal, but not osseous, signaling by PTH is defective. We, therefore, cloned and characterized the 5′-end of the human PTHR gene and found that its organization is very similar to that of the mouse. Transcription initiation sites of human P1 and P2 promoters are in similar, but not identical, positions to those of the mouse gene. The identification of a human P2 promoter is significant because no P2-specific human PTHR complementary DNAs have been isolated to date. Southern analysis of genomic DNA from seven PHP1b patients did not reveal any rearrangements in proximal promoter regions or exons encoding 5′-untranslated region sequences. No significant sequence differences were found in clones of normal and patient DNAs encompassing proximal promoter sequences, and untranslated region and signal sequence exons. Thus, in the seven PHP1b patients analyzed, no defects were identified that would influence initiation site selection, stability, or splicing of renal PTHR transcripts. These data indicate that the genetic defect(s) in PHP1b in these patients lies in distal enhancer elements of the gene, in an essential transcriptional regulator, or in some as yet unidentified cofactor required for renal PTH signaling.
The Use of Tolbutamide-Induced Hypoglycemia to Examine the Intraislet Role of Insulin in Mediating Glucagon Release in Normal Humans*
Authors: Peacey Steven R. , Rostami-Hodjegan Amin , George Emad , Tucker Geoffrey T. , Heller Simon R. 
Published: January 2014

Abstract
Disruption of intraislet mechanisms could account for the impaired glucagon response to hypoglycemia in type 1 diabetes. However, in contrast to animals, there is conflicting evidence that such mechanisms operate in humans. We have used iv tolbutamide (T) (1.7 g bolus + 130 mg/h infusion) to create high portal insulin concentrations and compared this with equivalent hypoglycemia using an iv insulin infusion (I) (30 mU/m2·min). Ten normal subjects underwent two hypoglycemic clamps; mean glucose; I (53 ± 1 mg/dL); and T (53 ± 1 mg/dL) (2.9 ± 0.04 mmol/L vs. 2.9 ± 0.05 mmol/L), held for 30 min. During hypoglycemia, mean peripheral insulin levels were greater with I (59 ± 4 mU/L) than T (18 ± 3 mU/L), P &lt; 0.001. Calculated peak portal insulin concentrations were greater during T (282 ± 28 mU/L) than I (78 ± 4 mU/L), P &lt; 0.00005. The demonstration of a reduced glucagon response during T-induced hypoglycemia (111 ± 8 ng/L vs. 135 ± 12 ng/L, P &lt; 0.05) with higher portal insulin concentrations suggests that intraislet mechanisms may contribute to the release of glucagon during hypoglycemia in man.
Inhibin A and Activin A in the First Trimester of Human Pregnancy
Authors: Birdsall Mary , Ledger William , Groome Nigel , Abdalla Hossam , Muttukrishna Shanthi 
Published: January 2014

Abstract
Recent studies show that high concentrations of inhibin A and activin A are present in the maternal serum throughout human pregnancy. The aim of this study was to determine whether the corpus luteum produces significant quantities of inhibin A and activin A during the first trimester of pregnancy. This prospective study examined two groups of women who had blood samples taken from 5–12 weeks gestation. One group consisted of 14 women with donor egg pregnancies (8 singletons and 6 multiples) who did not have corpora lutea, and the other group consisted 5 women with spontaneous pregnancies who had corpora lutea. Inhibin A and activin A were measured at weekly intervals using specific enzyme immunoassays. All pregnancies progressed to term, with healthy babies being delivered.
Maternal serum concentrations of inhibin A significantly increased throughout the study period in the donor egg pregnancies (P &lt; 0.001) and the control pregnancies (P &lt; 0.001). Circulating concentrations of activin A also increased significantly in both the spontaneous and donor egg pregnancies (P &lt; 0.001) during the study period. However, the concentrations of inhibin A and activin A in the first trimester of human pregnancy were not significantly different in the women with or without corpora lutea, suggesting a fetoplacental origin. Multiple donor egg pregnancies were found to have higher concentrations of inhibin A (P &lt; 0.001) and activin A (P &lt; 0.05) compared with singleton donor egg pregnancies, which also supports a placental source.
Biochemical Markers for Puberty in the Monkey Testis: Desmosterol and Docosahexaenoic Acid1
Authors: Connor William E. , Lin Don S. , Neuringer Martha 
Published: January 2014

AbstractWe previously reported that the sperm of rhesus monkeys and humans uniquely contain large amounts of desmosterol not found in other tissues and have a high concentration of the highly polyunsaturated n-3 fatty acid, docosahexaenoic acid (22:6 n-3). However, the lipid composition of the testis, from which sperm originate, is unknown. During puberty, the testis undergoes remarkable morphological changes as testosterone levels rise and sperm production begins. We hypothesized that testicular maturation might also involve dramatic changes in lipid composition. Accordingly, we characterized the sterol and fatty acid composition of the testis of rhesus monkeys throughout the lifespan, from birth to old age.Although the cholesterol content in the testis remained relatively unchanged throughout life, the desmosterol content first decreased from 59 μg/g in infants to 6 μg/g in prepubertal monkeys, increased to 83 μg/g during puberty, and reached a plateau of 248 μg/g in the young adult, where it remained into old age. The polyunsaturated fatty acid composition of the testis also changed markedly. Docosahexaenoic acid (22:6 n-3) increased from 5.1% of total fatty acids in infants and juveniles to 18.1% in postpubertal young adults. Although some n-6 fatty acids, arachidonic (20:4 n-6) and linoleic (18:2 n-6), decreased from 16.0% and 10.0% in prepubertal juveniles, respectively, to 7.1% and 3.3% in young adults; dihomogamma-linolenic acid (20:3 n-6), the precursor of 1 series PGs, increased greatly from 1.8% to 10.3%. Similar changes occurred in both membrane and storage lipids (phospholipids and triglycerides), respectively. After puberty, the testicular fatty acid pattern remained stable into old age.Our data demonstrated that puberty is accompanied by substantial changes in the lipid composition of the primate testis. These changes suggest that desmosterol and both n-3 and n-6 polyunsaturated fatty acids may have important roles in sexual maturation.
Glucose Homeostasis in Children with Falciparum Malaria: Precursor Supply Limits Gluconeogenesis and Glucose Production1
Authors: Dekker Evelien , Hellerstein Marc K. , Romijn Johannes A. , Neese Richard A. , Peshu Norbert , Endert Erik , Marsh Kevin , Sauerwein Hans P. 
Published: January 2014

To evaluate glucose kinetics in children with falciparum malaria, basal glucose production and gluconeogenesis and an estimate of the flux of the gluconeogenic precursors were measured in Kenyan children with uncomplicated falciparum malaria before (n = 11) and during infusion of alanine (1.5 mg/kg·min; n = 6). Glucose production was measured by [6,6-2H2]glucose, gluconeogenesis by mass isotopomer distribution analysis of glucose labeled by [2-13C]glycerol.
Basal plasma glucose concentration ranged from 2.1–5.5 mmol/L, and basal glucose production ranged from 3.3–7.3 mg/kg·min. Glucose production was largely derived from gluconeogenesis (73 ± 4%; range, 52–93%). During alanine infusion, plasma glucose increased by 0.4 mmol/L (P = 0.03), glucose production increased by 0.8 mg/kg·min (P = 0.02), and gluconeogenesis increased by 0.8 mg/kg·min (P = 0.04).
We conclude that glucose production in children with uncomplicated falciparum malaria is largely dependent on gluconeogenesis. However, gluconeogenesis is potentially limited by insufficient precursor supply. These data indicate that in children with falciparum malaria, gluconeogenesis fails to compensate in the presence of decreased glycogen flux to glucose, increasing the risk of hypoglycemia.
Two Years of Growth Hormone (GH) Treatment Increase Isometric and Isokinetic Muscle Strength in GH-Deficient Adults*
Authors: Johannsson Gudmundur , Grimby Gunnar , Sunnerhagen Katharina Stibrant , Bengtsson Bengt-Åke 
Published: January 2014

Abstract
GH deficiency in adults is associated with reduced muscle mass and muscle strength. The objective of this trial was to follow the effect of 2 yr of GH treatment in GH-deficient adults on muscle performance in relation to a reference population. Knee extensor and flexor strengths for isometric and isokinetic concentric muscle strength were measured using a Kin-Com dynamometer. Hand-grip strength was measured in both hands. The fatigue index was calculated as the percent reduction in peak torque at 50 repeated isokinetic knee extensions. Superimposed, single twitch electrical stimulation was performed. The GH-deficient subjects had lower isometric knee extensor, knee flexor, and hand-grip strength than the reference population. Two years of GH treatment increased and normalized the mean isometric knee extensor and flexor strengths. The concentric knee flexor and extensor strength at an angular velocity of π rad/s increased, as did the concentric knee flexor strength at an angular velocity of π/3 rad/s. The increase in muscle strength was more marked in younger patients and in patients with lower initial muscle strength than predicted. Quadriceps endurance decreased, whereas the effect of superimposing single twitches on isometric contraction and hand-grip strength was unaffected by the GH treatment. Two years of GH therapy in GH-deficient adults increased and normalized isokinetic and isometric muscle strength studied in proximal muscle groups. Hand-grip strength and the degree of lack of maximal motor unit activation on voluntary isometric knee extensor force did not change. The dynamic local muscle fatigue index decreased.
Familial Resemblance for Bone Mineral Mass Is Expressed before Puberty1
Authors: Ferrari S. , Rizzoli R. , Slosman D. , Bonjour J.-P. 
Published: January 2014

Genetic factors are known to explain a major proportion of peak bone mineral mass variance. Whether the influence of these genetic factors is expressed before the pubertal bone mineral mass accrual and whether there is tracking of bone mineral mass during pubertal growth, however, are not clearly established. We prospectively investigated correlations for bone mineral content (BMC), density, and bone size between prepubertal daughters and their premenopausal mothers.
Height, weight, lumbar spine (LS), femoral neck (FN) and midfemoral diaphysis BMC, bone area (BA), areal bone mineral density (aBMD), and volumetric bone mineral apparent density (BMAD) were evaluated in 138 mothers (mean age ± sd, 40.0 ± 4.0 yr) and their daughters (8.1 ± 0.7 yr), who were then remeasured at yearly intervals for 2 yr.
Eight-year-old prepubertal daughters had reached 78% and 44% of their mothers’ height and weight, respectively. At the various skeletal sites, they had reached 33–43% of their mothers’ BMC, 47–69% of their BA, 59–78% of their aBMD, and 75–105% of their BMAD. All body size and bone traits (age-adjusted Z-scores) were significantly correlated between prepubertal daughters and their mothers (r: 0.22–0.36, P &lt; 0.01), except midfemoral diaphysis BMAD. Heritability estimates (1/2 h2), after adjustment for body size and dietary calcium intake, showed that 18–37% of bone traits were directly determined by maternal descent. During the next 2 yr, growth was accompanied by a marked increase of BMC, aBMD, and BA, whereas BMAD changed very little. In contrast, during this period, there were only minor changes in body size or bone trait Z-scores (i.e. &lt;0.5 Z-scores), which were thus highly correlated between consecutive measurements (r: 0.75–0.92, P &lt; 0.0001). Accordingly, mother-daughter correlations remained unchanged over that period.
Although more than 60% of peak bone mineral mass is gained during puberty (mostly at the expense of an increase in bone size while volumetric bone density slightly changes), familial resemblance for most bone traits is already present between daughters and their mothers before puberty. In the girls, moreover, yearly measurements were highly correlated, suggesting tracking of bone traits during pubertal growth. These results indicate that genetic susceptibility to osteoporosis may already be detectable in early childhood.