bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial DNA sequence variation and phylogenetic relationships among Iberian pigs and other domestic and wild pig populations
Authors: Alves E. , Óvilo C. , Rodríguez M. C. , Silió L.
Published: September 2003

Nucleotide sequences of mitochondrial DNA (mtDNA) cytochrome B gene (1140 bp) and control region (707 bp) were used to determine the phylogenetic relationships among 51 pig samples representing ancient and current varieties of Iberian pigs (26), Spanish wild boars (seven) and other domestic pigs (18) of cosmopolitan (Duroc, Large White, Landrace, Pietrain and Meishan) and local (Spotted Black Jabugo, Basque and Mangalitza) breeds. A neighbour‐joining tree constructed from pairwise distances provide evidence of the European origin of both Iberian pigs and Spanish wild boars. The introgression of Asian mtDNA haplotypes in the genetic pool of the Iberian breed seems unlikely. Four estimates of sequence divergence between European and Asian clades were calculated from the two main domains of the D‐loop region and the synonymous and nonsynonymous nucleotide substitutions in the cytochrome B gene. The time since the divergence of pig ancestors was estimated at about 600 000 years before present.
DGAT1, a new positional and functional candidate gene for intramuscular fat deposition in cattle
Authors: Thaller G. , Kühn C. , Winter A. , Ewald G. , Bellmann O. , Wegner J. , Zühlke H. , Fries R.
Published: September 2003

Intramuscular fat content, also assessed as marbling of meat, represents an important beef quality trait. Recent work has mapped a quantitative trait locus (QTL) with an effect on marbling to the centromeric region of bovine chromosome 14, with the gene encoding thyroglobulin (TG) being proposed as a positional and functional candidate gene for this QTL. Recently, the gene encoding diacylglycerol O‐acyltransferase (DGAT1), which also has been mapped within the region of the marbling QTL, has been demonstrated to affect the fat content of milk. In the present study, the effects of a 5′‐polymorphism of TG and of a lysine/alanine polymorphism of DGAT1 on the fat content of musculus (m.) semitendinosus and m. longissimus dorsi in 55 bovine animals (28 German Holstein and 27 Charolais) has been investigated. Significant effects were found for both candidate genes in both the breeds. These effects seem to be independent of one another because the alleles of the two polymorphisms showed no statistically significant disequilibrium. The DGAT1 effect is mainly on the m. semitendinosus. The TG polymorphism only affects m. longissimus dorsi. However, both intramuscular fat enhancing effects seem to be recessive. The possibility of two linked loci, acting recessively on intramuscular fat content, will require special strategies when selecting for higher marbling scores.
No disease‐associated mutations found in the coding sequence of the canine polycystic kidney disease gene 1 in Bull Terriers with polycystic kidney disease
Authors: O'Leary C. A. , Atwell R. B. , Laing N. G.
Published: September 2003

The aim of this study was to identify possible disease‐associated mutations in the canine homologue of the polycystic kidney disease gene 1 (PKD1) in Bull Terriers with autosomal dominant polycystic kidney disease. Messenger RNA was obtained from the blood or renal tissue of five Bull Terriers with the disease and four close relatives without the disease. Reverse transcription, PCR and 3′ rapid amplification of cDNA ends were used to amplify the coding and 3′ untranslated regions of this transcript. Comparison of PKD1 sequence between the affected and unaffected Bull Terriers, revealed six polymorphisms, but no disease‐associated mutations.
Mapping of 1400 expressed sequence tags in the bovine genome using a somatic cell hybrid panel
Authors: Itoh T. , Takasuga A. , Watanabe T. , Sugimoto Y.
Published: September 2003

A bovine/hamster hybrid cell panel consisting of 30 independent hybrids was developed to locate genes. Polymerase chain reaction analysis of 279 microsatellites on the cattle linkage map in this panel revealed the presence of all chromosomes in either entire or fragmented form. Among primer pairs prepared from bovine 3′‐expressed sequence tags (ESTs), 1400 ESTs were assigned to specific chromosomes, of which 1303 were newly assigned in this study, and mapped 854 (61%) to 1 of 192 chromosomal segments using this panel. The regional mapping of new genes to cattle chromosomes can be rapidly achieved using this panel.
Experimental population design for estimation of dominant molecular marker effect on egg‐production traits
Authors: Kaiser M. G. , Lakshmanan N. , Arthur J. A. , O'Sullivan N. P. , Lamont S. J.
Published: September 2003

A potential limitation of the use of a dominant molecular marker system such as DNA fingerprinting (DFP) is the inability to distinguish homozygous from heterozygous allele state in an individual, and a resulting inaccuracy in estimating effects of the marker alleles. The objective of this study was to accurately estimate the effect of DFP markers on egg‐production traits. A BC1 population was produced from two distinct layer lines. Four DFP bands, each originating predominantly in one of the two parental lines, were evaluated for linkage with egg‐production quantitative trait loci in the BC1 population. The egg‐production traits consisted of eight early period and seven late period measurements. Eight marker‐trait linkages were identified out of 60 total statistical tests. By utilizing information on frequency of DFP bands in two parental lines, selecting F1 sires with DFP bands present, and backcrossing to the line lacking these bands, the population design allowed definitive identification of the DFP zygosity in the BC1 resource population hens. In this manner, accurate estimates of marker allele effects on egg‐production traits were obtained from the dominant marker system of DNA fingerprinting.
Association of twelve candidate gene polymorphisms and response to challenge with Salmonella enteritidis in poultry
Authors: Kramer J. , Malek M. , Lamont S. J.
Published: September 2003

Breeding for disease resistance to Salmonella enteritidis (SE) could be an effective approach to control Salmonella in poultry. The candidate gene approach is a useful method to investigate genes that are involved in genetic resistance. In this study, 12 candidate genes that are involved in the pathogenesis of Salmonella infection were investigated using five different genetic groups of meat‐type chicken. The genes were natural resistance associated macrophage protein 1 (SLC11A1, previously known as NRAMP1), inhibitor of apoptosis protein 1 (IAP1), prosaposin (PSAP), Caspase‐1 (CASP1), inducible nitric oxide production (iNOS), interferon‐gamma (IFNG), interleukin‐2 (IL2), immunoglobulin light chain (IGL), ZOV3, and transforming growth factors B2, B3 and B4 (TGFB2, B3 and B4). In total, 117 birds of all groups were challenged with SE at the age of 3 weeks. In all birds at 7‐day post‐infection SE load in caecum content, spleen and liver were quantified. Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) assays were used to genotype all animals for each gene. Overall we found the most significant associations with caecum content, nine of 12 genes showed a significant association (SLC11A1, IAP1, PSAP, CASP1, iNOS, IL2, IGL, TGFB2 and TGFB4). For liver, five genes (SLC11A1, CASP1, IL2, IGL, and TGFB4) and for spleen, only one gene (TGFB3) showed a significant association with SE load. By showing associations of 12 PCR‐RFLP assays with SE load after a pathogen challenge, this study confirmed the polygenic nature of disease resistance to SE.
A new mutation in the coding region of the bovine leptin gene associated with feed intake
Authors: Lagonigro R. , Wiener P. , Pilla F. , Woolliams J. A. , Williams J. L.
Published: September 2003

An experimental cattle population was screened for polymorphisms in the leptin gene and five SNPs were found in the regions containing the coding sequences. The association of these polymorphisms with feed intake and fat‐related traits was evaluated. The results suggest an association between a polymorphism in exon 2, described here for the first time, and feed intake. Individuals with genotype A/T at this position had 19% greater mean feed intake than individuals with genotype A/A. There was also evidence for a link between leptin haplotypes and some fat‐related traits.
Identification of a sex‐determining region in Nile tilapia (Oreochromis niloticus) using bulked segregant analysis
Authors: Lee B.‐Y. , Penman D. J. , Kocher T. D.
Published: September 2003

Sex determination in the Nile tilapia (Oreochromis niloticus) is thought to be an XX‐XY (male heterogametic) system controlled by a major gene. We searched for DNA markers linked to this major locus using bulked segregant analysis. Ten microsatellite markers belonging to linkage group 8 were found to be linked to phenotypic sex. The putative Y‐chromosome alleles correctly predict the sex of 95% of male and female individuals in two families. Our results suggest a major sex‐determining locus within a few centimorgans of markers UNH995 and UNH104. A third family from the same population showed no evidence for linkage of this region with phenotypic sex, indicating that additional genetic and/or environmental factors regulate sex determination in some families. These markers have immediate utility for studying the strength of different Y chromosome alleles, and for identifying broodstock carrying one or more copies of the Y haplotype.
Progressive decline of vasopressin secretion in familial autosomal dominant neurohypophyseal diabetes insipidus presenting a novel mutation in the vasopressin‐neurophysin II gene
Authors: Elias Paula C. L. , Elias Lucila L. K. , Torres Natalia , Moreira Ayrton C. , Antunes‐Rodrigues Jose , Castro Margaret
Published: September 2003

objective  Familial autosomal dominant neurohypophyseal diabetes insipidus (FNDI) is a rare form of central diabetes insipidus (DI), which is caused by mutations in the vasopressin‐neurophysin II (AVP‐NPII) gene. The present study evaluated the AVP secretion over time and analysed the structure of the AVP‐NPII gene in a Brazilian family with FNDI.

subjects and design  Four affected members and one nonaffected member from one Brazilian family with FNDI were studied. The diagnosis of central DI was established by fluid deprivation test and hypertonic saline infusion. Two affected members were assessed twice within a 6‐year interval. For molecular analysis, genomic DNA was extracted and the AVP‐NPII gene was amplified by polymerase chain reaction.

results  The functional assessment of patients with FNDI over time confirmed a progressive loss in AVP secretion. Two patients were first diagnosed as partial central DI and, several years later, they developed severe central DI. Sequencing analysis revealed a heterozygous new point mutation in the nucleotide 1892 in the coding sequence for neurophysin‐II of the AVP‐NPII gene (1892G > C) predicting an amino acid substitution (A68P) in all affected members.

conclusion  Our data demonstrate a gradual vasopressinergic deficiency due to a novel mutation in the AVP‐NPII gene in a Brazilian family with FNDI. The accumulation of A68P mutated precursor might have a cytotoxicity effect, leading to a gradual death of magnocellular neurones, and a progressive decline in AVP secretion.
Effect of acute reduction of free fatty acids by acipimox on growth hormone‐releasing hormone‐induced GH secretion in type 1 diabetic patients
Authors: Alvarez Paula , Isidro Luisa , Peinó Roberto , Leal‐Cerro Alfonso , Casanueva Felipe F. , Dieguez Carlos , Cordido Fernando
Published: September 2003

background  In type 1 diabetes mellitus (DM1), high GH basal levels and exaggerated responses to several stimuli have been described. Acipimox is an antilipolytic drug that produces an acute reduction of free fatty acids (FFA). The aim of this study was to evaluate the effect of the reduction of plasma FFA with acipimox, alone or in combination with GHRH, on GH secretion in DM1.

methods  Six type 1 diabetic patients were studied (three women, three men), mean age of 30 ± 2·1 years, body mass index (BMI) 23·1 ± 1·5 kg/m2. As a control group, six normal healthy subjects of similar age, sex and weight were studied. Each patient and control received GHRH [1 µg/kg intravenously (i.v.) at min 180], acipimox (250 mg orally at min 0 and 120) and GHRH plus acipimox on three separated days. Subjects served as their own control. Blood samples were taken at appropriate intervals for determination of GH, FFA and glucose.

result  In control subjects, the GH area under the curve (AUC; µg/l × 120 min) was for acipimox‐treated 1339 ± 292 and 1528 ± 330 for GHRH‐induced secretion. The GH AUC after the administration of GHRH plus acipimox was 3031 ± 669, significantly greater than the response after acipimox alone (P < 0·05) or GHRH alone (P < 0·05). In diabetic patients, the GH AUC was for acipimox‐treated 2516 ± 606 and 1821 ± 311 for GHRH‐induced secretion. The GH AUC after the administration of GHRH plus acipimox was 7311 ± 1154, significantly greater than the response after acipimox alone (P < 0·05) or GHRH alone (P < 0·05). The GH response after acipimox was increased in diabetic when compared with normal (P < 0·05), with a GH AUC of 1339 ± 292 and 2515 ± 606 for normal subjects and diabetic patients, respectively. The GH response after acipimox plus GHRH was increased in diabetic when compared with normal (P < 0·05), with a GH AUC of 3031 ± 669 and 7311 ± 1154 for normal subjects and diabetic patients, respectively. The administration of acipimox induced a FFA reduction during the entire test.

conclusions  Reduction of free fatty acids with acipimox is a stimulus for GH secretion in DM1. The combined administration of GHRH plus acipimox induces a markedly increased GH secretion in type 1 diabetic patients when compared with normal subjects. These data suggest that patients with DM1 exhibit a greater GH secretory capacity than control subjects, despite the fact that endogenous FFA levels seems to exert a greater inhibitory effect on GH secretion in these patients.
A functional site on the human TSH receptor: a potential therapeutic target in Graves’ disease
Authors: Johnstone Alan P. , Cridland Jeremy C. , Da Costa Clive R. , Nussey Stephen S. , Shepherd Philip S.
Published: September 2003

objective  Identifying sites on the TSH‐receptor that are involved in the pathological stimulation of the thyroid by autoantibodies in Graves’ disease would aid the development of new therapies. We tested a series of monoclonal antibodies that recognize the native receptor for their ability to inhibit stimulation of the receptor in vitro.

patients and methods  Heterologous cells expressing the recombinant human TSH‐receptor were stimulated with TSH or serum samples from 13 Graves’ disease patients or the MRC Long‐Acting Thyroid Stimulator standard B (LATS‐B) and their cAMP responses measured. The effect on this stimulation of various doses of purified monoclonal antibodies with defined epitopes was determined.

results  Antibodies against one epitope (residues 381–384) inhibited TSH‐stimulated cyclic adenosine monophosphate (cAMP) production (1 µg/ml causing 50% inhibition of the response to 100 µU/ml TSH) and also inhibited cAMP production induced by sera from approximately 40% (6/14) of Graves’ disease patients, including the MRC LATS‐B standard.

conclusions  Residues 381–384 of the human TSH‐receptor are important in the physiological and pathological stimulation of the thyroid. This opens the possibility of more specific therapy of some Graves’ disease patients by agents directed against this epitope.
Association of two apolipoprotein A‐I gene MspI polymorphisms with high density lipoprotein (HDL)‐cholesterol levels and indices of obesity in selected healthy Chinese subjects and in patients with early‐onset type 2 diabetes
Authors: Ma Yan Qing , Thomas G Neil , Ng Maggie C. Y. , Critchley Julian A. J. H. , Cockram Clive S. , Chan Juliana C. N. , Tomlinson Brian
Published: September 2003

objective  Previous studies have reported associations between two apolipoprotein A‐I (apoA‐I) gene MspI polymorphisms (G‐75A and C83T) and high density lipoprotein (HDL)‐cholesterol and/or apoA‐I levels, but have not investigated the relationship with obesity.

methods  We determined the distribution of these polymorphisms in 482 early‐onset (≤ 40 years) Type 2 Chinese diabetics and 167 Chinese selected healthy controls.

results  The −75A and 83T allele frequencies were similar in the diabetic and healthy subjects. In the healthy control subjects, HDL‐cholesterol levels were significantly higher in the AA homozygotes than in the GG/GA carriers (1·74 ± 0·58 vs. 1·45 ± 0·58 mmol/l, P < 0·001). Furthermore, analyses showed a significant relationship between increasing HDL‐cholesterol tertiles and the AA genotype frequency in the selected healthy subjects (3·6, 8·9 and 16·1%, P = 0·026). For the C83T polymorphism, healthy male CT carriers had higher HDL‐cholesterol levels than CC homozygotes (1·71 ± 0·57 vs. 1·25 ± 0·30 mmol/l, P = 0·001), but this was not found in females. No relationship between these polymorphisms and lipid levels was found in the diabetics, who had a more adverse lipid profile than the selected controls. In the diabetics, but not the controls, in CT carriers compared to CC homozygotes there were lower levels of body mass index (BMI; 23·8 ± 3·9 vs. 25·4 ± 4·7 kg/m2, P = 0·048) and waist‐to‐height ratio (0·49 ± 0·06 vs. 0·52 ± 0·07, P = 0·023), and this relationship was supported by tertile analysis.

conclusions  The −75AA genotype was associated with higher HDL‐cholesterol levels in the selected healthy, but not diabetic, subjects. The 83T allele was associated with greater indices of obesity in the diabetic patients, and with higher HDL‐cholesterol in heterozygous healthy male subjects.
Neuromuscular dysfunction in adult growth hormone deficiency
Authors: Webb Susan M. , De Andrés‐Aguayo Irene , Rojas‐García Ricard , Ortega Emilio , Gallardo Eduard , Mestrón Antonio , Serrano‐Munuera Carmen , Casamitjana Roser , Illa Isabel
Published: September 2003

background  Adult growth hormone deficiency (AGHD) is associated with fatigue, tiredness and myalgias, which improve after initiating recombinant human GH (rhGH) therapy.

aim  To conduct an extensive neuromuscular investigation of patients with AGHD in an attempt to explain their neuromuscular symptoms.

patients and methods  Twenty adult patients (11 males) with untreated GHD of whom 10 were childhood‐onset (CO) underwent a prospective neurological protocol, including physical examination and a neurophysiological study that comprised sensory and motor neurography, repetitive stimulation, electromyogram (EMG) and interference pattern analysis (IPA). In the first seven patients (four CO), a biceps muscle biopsy was also performed for histochemical analysis and Western blot, and investigation of signal transducers and activators of transcription (STATs)‐1 and ‐3 and the two isoforms STAT‐5a and ‐5b.

results  Neuromuscular examination, sensory and motor neurography and repetitive stimulation were normal in 20/20 patients. Fourteen [seven CO and seven adult‐onset (AO)] of the 20 patients had abnormal EMG and/or IPA suggestive of a neurogenic involvement. In those seven patients with initially abnormal results, who also remained on regular rhGH for at least 1 year, repeated IPA was normal in six and improved in the remaining patient (P = 0·004). The biceps muscle biopsy disclosed abnormal groupings in the seven cases tested, indicative of a neurogenic pattern. No changes in skeletal muscle STAT‐1 and ‐3 were seen compared to controls, but a marked increase in both STAT‐5 isoforms was observed in all seven patients.

conclusion  Skeletal muscle of patients with both adult‐onset and childhood‐onset adult GH deficiency shows a neuromuscular dysfunction, indicated by the muscle biopsy and the neurophysiological study, which in the subgroup of treated patients responds positively to rhGH therapy. The results obtained suggest that the STAT‐5 signal transduction pathway in muscle is abnormal in adult GH deficiency.
Effect of dehydroepiandrosterone supplementation on fatty acid and hormone levels in patients with X‐linked adrenoleucodystrophy
Authors: Assies J. , Haverkort E. B. , Lieverse R. , Vreken P.
Published: September 2003

objective  In X‐linked adrenoleucodystrophy (X‐ALD) the peroxisomal β‐oxidation of saturated very long‐chain fatty acids (VLCFAs; carbon length > 22 atoms) is impaired. These fatty acids accumulate in blood and tissues, in particular in the nervous system, adrenal cortex and testis. Most patients have a primary adrenocortical insufficiency with low levels of cortisol and dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA‐S), collectively called DHEA(S). Surprisingly, very low plasma levels of DHEA(S) may be found when plasma cortisol and ACTH levels are normal. In animal studies DHEA administration had a peroxisome proliferating effect and induced the expression of peroxisomal enzymes involved in the β‐oxidation of fatty acids.

patients and design  To study the effect of DHEA on fatty acids in X‐ALD patients, we conducted a randomized double‐blind study in which 14 men (age range 21–63 years) and one boy (12 years) received 50 mg of DHEA or placebo for 3 months, followed by a 1‐month wash‐out period, then 3 months of placebo or vice versa.

results  A significant rise was seen in the plasma levels of DHEA‐S, Δ4‐androstenedione and IGF‐I. The elevated saturated VLCFAs in plasma and erythrocytes did not change. However, in erythrocytes significant decreases were found in the total amount of fatty acids, in C16:0, C18:0 and in C20:4ω‐6, C22:5ω‐6, C18:1ω‐9, C20:1ω‐9 and C20:3ω‐9. In plasma, decreases were found for C18:1ω‐9 and increases for C20:1ω‐9.

conclusions  Dehydroepiandrosterone supplementation for 3 months did not lower the elevated plasma levels of saturated very long‐chain fatty acids in patients with X‐linked adrenoleucodystrophy. Instead, a decrease in saturated and mono‐ and polyunsaturated fatty acids in erythrocytes and plasma was found. An increase of C20:1ω‐9 was found in plasma only.
Psychological effects of withdrawal of growth hormone therapy from adults with growth hormone deficiency
Authors: McMillan C. V. , Bradley C. , Gibney J. , Healy M. L. , Russell‐Jones D. L. , Sönksen P. H.
Published: September 2003

objective  Growth hormone (GH) is known to be required for physical well‐being. Although it is also widely believed to be important for quality of life (QoL) and psychological health, there is less supportive evidence. The objective of this study was to investigate the psychological effects of discontinuation of GH replacement from adults with severe GH deficiency (GHD).

design  A double‐blind, placebo‐controlled trial in which GH replacement therapy was discontinued for 3 months from 12 of 21 GH‐deficient adults, where nine continued with GH replacement.

patients  GH‐treated adults (10 men, 11 women), all with severe GHD (peak GH < 7·7 mU/l on provocative testing), mean age 44·9 years (range 25–68 years).

measurements  Semi‐structured interviews were given at baseline and end‐point plus questionnaires that included a new hormone‐deficiency specific, individualized, QoL questionnaire (HDQoL), the General Well‐being Index (GWBI), the Well‐being Questionnaire (W‐BQ12), the Short‐Form 36 health status questionnaire (SF‐36), the Nottingham Health Profile (NHP) and the General Health Questionnaire (GHQ).

results  Three months after baseline the serum total IGF‐I of placebo‐treated patients fell from normal, age‐related levels (mean 26·6 ± 13·2 nmol/l) to levels indicative of severe GHD (11·6 ± 6·6 nmol/l) (P < 0·001). Psychological symptoms of GH withdrawal, reported in interviews at end‐point by placebo‐treated patients, included decreased energy, and increased tiredness, pain, irritability and depression. Patients who believed they knew which treatment they had received correctly identified the treatment (GH or placebo) at end‐point (χ2 = 11·25, P < 0·01). Significant between‐treatment‐group differences in change scores were found for SF‐36 General Health (P < 0·01), W‐BQ12 Energy (P < 0·01) and HDQoL do physically (P < 0·05), indicating reduced general health, reduced energy and greater perceived impact of hormone deficiency on physical capabilities in the placebo‐treated group at end‐point relative to GH‐treated patients.

conclusion  Withdrawal of GH treatment from adults with severe GH deficiency has detrimental psychological effects.
The glutamine 27 glutamic acid polymorphism of the β2‐adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population‐based study in Spain
Authors: González Sánchez J. L. , Proenza A. M. , Martínez Larrad M. T. , Ramis J. M. , Fernández Pérez C. , Palou A. , Serrano Ríos M.
Published: September 2003

objetive  Given the important role of the β2‐adrenoceptor (β2‐AR) in lipid mobilization and the lack of studies in Southern European countries, the aim of this study was to investigate the role of the glutamine 27 glutamic acid (Gln27Glu) β2‐AR polymorphism in the susceptibility to obesity and its metabolic complications in a population‐based nationwide multicentre study in Spain, especially focusing on the hypothetical influence of gender.

design  Cross‐sectional population‐based study.

patients  We studied 666 nonrelated adults (47·9% men and 52·1% women), aged 35–64 years, chosen randomly from a nationwide population‐based survey of obesity, and related conditions including insulin resistance and cardiovascular risk factors.

measurements  Body mass index (BMI), waist‐to‐hip ratio (WHR), sagittal abdominal diameter (SAD), systolic and diastolic blood pressure, fasting and 2‐h post‐glucose load glycaemic levels, total cholesterol, high density lipoprotein (HDL)‐ and low density lipoprotein (LDL)‐cholesterol, triglycerides, insulin, proinsulin and leptin plasma levels were measured. β2‐AR Gln27Glu genotypes were determined by restriction fragment length polymorphism (RFLP)‐polymerase chain reaction (PCR).

results  Glu27 homozygous obese men had significantly higher BMI and SAD mean values than both heterozygous and Gln27 homozygous obese men. Two‐hour post‐load plasma glucose concentration was higher in Glu27 homozygous than in Gln27 homozygous in the whole population and only in men when stratified by gender. No differences according to the genotype were found for the rest of the parameters studied, including homeostasis model assessment (HOMA), insulin, proinsulin and leptin levels, but for total and LDL‐cholesterol these increased in men. We did not find differences in the anthropometrical and biochemical parameters according to the genotype in women. Multivariate logistic regression analysis showed that Glu27 homozygosity after adjustment for SAD was associated with type 2 diabetes mellitus.

conclusions  Our results suggest that the glutamic acid 27 allele of the β2‐adrenoceptor may be a risk factor in men but not in women for the accumulation of visceral fat and for its association with the development of type 2 diabetes mellitus.
The gender differences in growth hormone‐binding protein and leptin persist in 80‐year‐old men and women and is not caused by sex hormones
Authors: Bülow B. , Ahrén B. , Fisker S. , Dehlin O. , Hagberg B. , Jensen E. , Svensson T. , Samuelsson G. , Erfurth E. M.
Published: September 2003

objective  Leptin and growth hormone‐binding protein (GHBP) both show gender differences that might be explained by sex hormones. To study the potential relevance of oestradiol and testosterone, we have examined 80‐year‐old subjects in whom oestradiol is higher in men than in women. The interrelationships between leptin, insulin, GHBP and fat mass in this age group were also investigated.

design and subjects  Ninety‐four subjects (55 females and 39 males), all 80 years old, were investigated in a community‐based study. None of the investigated subjects was being treated for diabetes mellitus and none of the women had oestrogen replacement.

methods  Levels of testosterone, oestradiol, SHBG, IGF‐I, GHBP, glucose, insulin and leptin were analysed. Body composition was measured with bioimpedance analysis (BIA).

results  As in younger age groups, serum leptin, the ratio leptin/kilogram fat mass and serum GHBP were higher in the women (all, P ≤ 0·007), although serum oestradiol was higher in the men (P < 0·001). There were no significant associations between sex hormones and leptin or GHBP either in women or in men (all, r < 0·13, P > 0·1). Leptin correlated to kilogram fat mass in both women (r = 0·55, P < 0·001) and men (r = 0·47, P = 0·003), but in contrast, there were no significant correlations between GHBP and fat mass and GHBP and IGF‐I, either in women or in men (all, r < 0·24, P > 0·2). Insulin and leptin were significantly associated with GHBP, both in women (r = 0·48, P < 0·001 and r = 0·43, P = 0·001, respectively) and in men (r = 0·40, P = 0·01 and r = 0·34, P = 0·03, respectively).

conclusions  Although the 80‐year‐old men had higher oestradiol levels than the women, the women had higher levels of leptin and GHBP. There were no correlations between sex hormones and leptin and GHBP, which indicates that the gender differences are not caused by sex hormones in old age. In contrast to studies in younger subjects, GHBP did not correlate to fat mass in the investigated 80‐year‐old men and women. In the older subjects investigated, as in younger subjects, GHBP was significantly correlated with leptin and insulin.
Bone density and body composition in children with growth hormone insensitivity syndrome receiving recombinant IGF‐I
Authors: Shaw N. J. , Fraser N. C. , Rose S. , Crabtree N. J. , Boivin C. M.
Published: September 2003

objective  There are few reports of the metabolic action of insulin‐like growth factor 1 (IGF‐I) in vivo. Growth hormone insensitivity syndrome is a good model to examine the effects of IGF‐I deficiency. This study was designed to assess body composition and bone density in children with growth hormone insensitivity syndrome before and after receiving treatment with recombinant IGF‐I.

design  A prospective longitudinal study.

patients  Four prepubertal boys age 6·1–9·8 years with short stature due to growth hormone insensitivity syndrome.

measurements  Assessment of body fat by skinfold thickness measurements and dual energy X‐ray absorptiometry (DXA) was made during the first 6 months of recombinant IGF‐I treatment. Assessment of lumbar spine bone density by DXA was performed prior to IGF‐I treatment and during the subsequent five years.

results  Each child showed a significant reduction in fat mass (0·26–1·22 kg) after 6 weeks of IGF‐I treatment. Bone density prior to treatment was reduced in comparison to age‐matched controls but calculated volumetric bone density was within the normal range. Volumetric bone density progressively improved over the 5‐year treatment period.

conclusions  Children with growth hormone insensitivity syndrome exhibit a metabolic response to IGF‐I within 6 weeks analogous to that seen in GH‐deficient children receiving GH. Bone density when corrected for body size is within normal limits and demonstrates a response to IGF‐I, confirming the anabolic action on bone.
Glucose homeostasis in acromegaly: effects of long‐acting somatostatin analogues treatment
Authors: Baldelli Roberto , Battista Claudia , Leonetti Frida , Ghiggi Maria‐Rosaria , Ribaudo Maria‐Cristina , Paoloni Antonella , D’Amico Eugenio , Ferretti Elisabetta , Baratta Roberto , Liuzzi Antonio , Trischitta Vincenzo , Tamburrano Guido
Published: September 2003

objective  Acromegaly is a syndrome with a high risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Somatostatin analogues, which are used for medical treatment of acromegaly, may exert different hormonal effects on glucose homeostasis. Twenty‐four active acromegalic patients were studied in order to determine the long‐term effects of octreotide‐LAR and SR‐lanreotide on insulin sensitivity and carbohydrate metabolism.

design  Prospective study.

patients  We studied 24 patients with active acromegaly, 11 males and 13 females, aged 50·7 ± 12·7 years, body mass index (BMI) 30·1 ± 4·8 (kg/m2).

measurements  All patients underwent an oral glucose tolerance test (OGTT) and 12 also had an euglycaemic hyperinsulinaemic clamp. All patients were evaluated at baseline and after 6 months of somatostatin analogues therapy.

results  Acromegalic patients showed low M‐values in respect to the control group at baseline (P < 0·05), followed by a significant improvement after 6 months of therapy (P < 0·005 vs. baseline). Serum glucose levels at 120 min during OGTT worsened (P < 0·05) during somatostatin analogs therapy in patients with normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This was associated with a reduced (P < 0·05) and 30 min delayed insulin secretion during OGTT. Also, HbA1c significantly deteriorated in all subjects after treatment (4·7 ± 0·6% and 5·1 ± 0·5%, basal and after six months, respectively, P < 0·005).

conclusion  In acromegalic patients, somatostatin analogues treatment reduces insulin resistance, and also impairs insulin secretion. This may suggest that the use of oral secretagogue hypoglycaemic agents and/or insulin therapy should be considered rather than insulin sensitizers, as the treatment of choice in acromegalic patients who develop frank hyperglycaemia during somatostatin analogues therapy.
Congenital hypothyroidism due to a new deletion in the sodium/iodide symporter protein
Authors: Tonacchera Massimo , Agretti Patrizia , De Marco Giuseppina , Elisei Rossella , Perri Anna , Ambrogini Elena , De Servi Melissa , Ceccarelli Claudia , Viacava Paolo , Refetoff Samuel , Panunzi Claudio , Bitti Maria Luisa Manca , Vitti Paolo , Chiovato Luca , Pinchera Aldo
Published: September 2003

objective  Iodide transport defect (ITD) is a rare disorder characterised by an inability of the thyroid to maintain an iodide gradient across the basolateral membrane of thyroid follicular cells, that often results in congenital hypothyroidism. When present the defect is also found in the salivary glands and gastric mucosa and it has been shown to arise from abnormalities of the sodium/iodide symporter (NIS).

patient  We describe a woman with hypothyroidism identified at the 3rd month of life. The diagnosis of ITD was suspected because of nodular goitre, and little if any iodide uptake by the thyroid and salivary glands. Treatment with iodide partially corrected the hypothyroidism; however, long‐term substitution therapy with l‐thyroxine was started.

measurements  Thyroid radioiodide uptake was only 1·4% and 0·3% at 1 and 24 h after the administration of recombinant human TSH. The saliva to plasma I− ratio was 1·1 indicating that the inability of the thyroid gland to concentrate I− was also present in the salivary glands.

results  Analysis of the patient's NIS gene revealed a 15 nucleotide (nt) deletion of the coding sequence (nt 1314 through nt 1328) and the insertion of 15 nt duplicating the first 15 nt of the adjacent intron. The patient was homozygous for this insertion/deletion, while both consanguineous parents were heterozygous. This deletion predicts the production of a protein lacking the five terminal amino acids of exon XI (439–443) which are located in the 6th intracellular loop.

 COS‐7 cells transfected with a vector expressing the mutant del‐(439–443) NIS failed to concentrate iodide, suggesting that the mutation was the direct cause of the ITD in this patient.

conclusion  In conclusion we describe the first Italian case of congenital hypothyroidism due to a new deletion in the NIS gene.
Circulating resistin levels in essential hypertension
Authors: Furuhashi Masato , Ura Nobuyuki , Higashiura Katsuhiro , Murakami Hideyuki , Shimamoto Kazuaki
Published: September 2003

objective  Resistin, a novel cysteine‐rich protein secreted by adipocytes, has been proposed to serve as a link between obesity and insulin resistance in rodents, but this has remained controversial. Most of the data obtained in previous studies are restricted to mRNA levels in tissues.

design and patients  We examined the association between insulin resistance and circulating protein levels of resistin in 33 essential hypertensive patients (EHT) and 18 normotensive subjects (NT). insulin sensitivity (M‐value) was evaluated by the euglycaemic hyperinsulinaemic glucose clamp technique.

results  Using a cutoff point of mean – 1 SD of the M‐value in the NT, the EHT were divided into two groups: one group of 12 insulin‐resistant patients (EHT‐R) and one group of 21 noninsulin‐resistant patients (EHT‐N). There were no intergroup differences in age, gender, body mass index (BMI; range: 20·1–30·4 kg/m2), fasting glucose and total cholesterol. The EHT‐R had significantly higher levels of fasting insulin and triglyceride than did the NT and the EHT‐N. The EHT‐R had higher levels of free fatty acid and lower levels of high‐density lipoprotein cholesterol than did the EHT‐N. The M‐value was negatively correlated with fasting insulin, free fatty acid, and triglyceride. Circulating resistin levels were not significantly different among the three groups and were not correlated with the M‐value, BMI, blood pressure, or lipid variables.

conclusions  Our results suggest that circulating resistin levels are not related to insulin resistance, at least in patients with essential hypertension, although disturbance of lipid metabolism may be associated with insulin resistance.
Interleukin‐13 gene polymorphisms in patients with Graves’ disease
Authors: Bednarczuk Tomasz , Placha Grzegorz , Jazdzewski Krystian , Kurylowicz Alina , Kloza Marta , Makowska Urszula , Hiromatsu Yuji , Nauman Janusz
Published: September 2003

objective  In patients with Graves’ disease (GD), an elevation of serum immunoglobulin E (IgE) has been recently reported to be associated with the severity of hyperthyroidism and ophthalmopathy. Interleukin 13 (IL‐13) is a major cytokine involved in IgE synthesis and therefore may be a potential candidate gene contributing to the development of GD or influencing the clinical course of the disease.

design  In a case–control study, we examined IL‐13 gene single‐nucleotide polymorphisms in the 5′ promoter region at position −1112 (C to T change, termed as C−1112T) and in exon 4 at position 2044 (G to A change, G2044A, which results in an amino acid exchange Arg130Gln) in 261 patients with GD. The control groups consisted of healthy young subjects (n = 168) and subjects over 100 years old with no history of autoimmune or allergic diseases recruited from the Polish Centenarians Project (n = 50).

measurements  C−1112T and G2044A polymorphisms were defined by fluorescent single‐strand conformational polymorphism and by restriction fragment length polymorphism analysis, respectively.

results  In patients with GD, the distribution of IL‐13 alleles (−1112T 31%; 2044A 25%) and genotypes (−1112T/T 10%; 2044A/A 7%) did not differ significantly compared to control groups. Subdividing GD patients according to clinically evident ophthalmopathy (NOSPECS class III or higher, n = 93) revealed no significant differences in the frequencies of −1112T allele (33%vs. 29%; P = 0·4), −1112T/T genotype (13%vs. 8%; P = 0·3), 2044A allele (27%vs. 24%; P = 0·5) and 2044A/A genotype (9%vs. 7%; P = 0·7) between GD patients with and without eye involvement. In order to analyse the association with the severity of hyperthyroidism, we examined patients with a first onset of GD treated with antithyroid drugs (n = 32). IL‐13 genotypes were not associated with the laboratory findings at diagnosis (thyroid volume, serum levels of FT4, TRAb, TPOAb, TGAb) and with the outcome of antithyroid drug treatment.

conclusions  Our results suggest that IL‐13 gene polymorphisms at positions −1112 (C → T) and 2044 (G → A): (1) do not confer genetic susceptibility to Graves’ disease; (2) do not contribute to the development of clinically evident ophthalmopathy; (3) are not associated with severity of hyperthyroidism.
Suppression and recovery of LH secretion by a potent and selective GnRH‐receptor antagonist peptide in healthy early follicular‐phase women are mediated via selective control of LH secretory burst mass
Authors: Gianotti L. , Veldhuis J. D. , Destefanis S. , Lanfranco F. , Ramunni J. , Arvat E. , Marzetto M. , Boutignon F. , Deghenghi R. , Ghigo E.
Published: September 2003

aim  GnRH antagonists are competitive inhibitors of GnRH receptors. Their administration induces prompt suppression of the gonadal axis. In animals, GnRH antagonists upregulate the activity of GnRH‐secreting neurones, which could cause gonadotrophin rebound following inhibition. The aim of this study was to evaluate the effects of a potent GnRH antagonist, Teverelix (TEV), on the gonadal axis in healthy young women.

subjects and measurements  In nine women [20–35 years old, body mass index (BMI) 19–25 kg/m2] in the early follicular phase, serum LH and FSH levels were evaluated every 10 min from 08·00 to 12·00 h before, and 24 h and 96 h after TEV injection (2·5 mg in 1 ml subcutaneusly on day 0). Serum gonadotrophin and oestradiol levels were also evaluated at baseline and at 6, 8, 12, 48, 72 h after TEV.

results  The antagonist reduced both serum LH and FSH concentrations; LH levels were significantly and promptly reduced at +6 h (nadir at +8 h) until +48 h and recovered at +72 h, while FSH levels were reduced (P < 0·05) 24 h after the antagonist and normalized at +48 h. LH (but not FSH) concentrations at +96 h exceeded baseline (P < 0·05). TEV suppressed oestradiol concentrations (P < 0·05) with a nadir at +24 h, comparable reduction at +48 h and recovery to baseline at +72 h. Deconvolution analysis showed that the antagonist peptide suppressed (P < 0·02) the pulsatile production rate, burst mass and amplitude of LH on day 1. Pulsatile FSH secretion also fell at this time (P < 0·05). LH and FSH pulse frequency were not modified by TEV. At +96 h, LH pulsatility did not significantly differ from that at baseline. Suppression of mean LH or FSH concentrations did not affect the relative pattern regularity (approximate entropy) of LH and FSH secretion.

conclusions  This study demonstrates that the acute administration of a potent GnRH antagonist induces prompt inhibition of the gonadal axis lasting for 2 days in women due to mechanistically specific suppression of LH secretory burst mass and the mean FSH secretion rate. The trend toward rebound release of LH following the end of the pharmacological effect of the antagonist could reflect a rise in endogenous GnRH activity.
The effect of parasitoid host‐size preference on host population growth rates: an example of Aphidius colemani and Aphis glycines
Authors: Lin Li A. , Ives Anthony R.
Published: September 2003

Abstract.  1. Direct observations of Aphidius colemani foraging for Aphis glycines demonstrated that A. colemani attacks large aphid size classes selectively, in contrast to other Aphidiinae (Hymenoptera: Braconidae) species that generally prefer small or medium‐sized nymphs of different host species.

2. To determine the effect of this size preference on the potential ability of A. colemani to control A. glycines outbreaks, the stage‐dependent survival and fecundity of A. glycines were measured to parameterise a stage‐structured demographic model for the density‐independent population growth rate of the aphid.

3. Compared with hypothetical parasitoids that show either no size preference or preference for medium‐sized host nymphs, the preference of A. colemani for large hosts caused a greater reduction in the population growth rate of A. glycines. This occurs in the model because, by attacking reproductive adults, A. colemani kills those aphids that have the greatest immediate effect on the population growth rate.

4. The strong effect of size preference by A. colemani is diminished somewhat by the continued reproduction of A. glycines adults, which can reproduce for up to 3 days following parasitism. Nonetheless, reproduction by parasitised aphids is not enough to compensate for the stronger, negative effect of the preference of A. colemani for large aphids, which removes individuals with the greatest reproductive value from the A. glycines population.
Adaptive significance of facultative infanticide in the semi‐solitary parasitoid Echthrodelphax fairchildii
Authors: Yamada Yoshihiro Y. , Ikawa Kenji
Published: September 2003

Abstract.  1. This is the first work to show how imperfect kin recognition influences the behavioural strategy of parasitoids.

2. The female of Echthrodelphax fairchildii lays an egg on the right or left side of the host thorax. When superparasitising on the side without the first offspring, it often probed the opposite side with its sting and killed the first offspring more than 50% of the time. The frequency of probing increased with increasing inter‐oviposition interval, and was higher in conspecific superparasitism than in self superparasitism.

3. The adaptiveness of probing was assessed by the difference in fitness returns between superparasitism with probing and superparasitism without probing. Fitness returns from self‐superparasitism and those from conspecific superparasitism were assessed by the fitness performance of both first and second comers, and that of second comers respectively.

4. In terms of the survival rate of immatures (one fitness component), probing under conspecific superparasitism guaranteed higher fitness returns than not probing for longer oviposition intervals, but under self‐superparasitism not probing guaranteed higher fitness returns for shorter intervals because superparasitism for such intervals often resulted in two‐adult emergence.

5. In terms of head width (another fitness component), probing produced higher fitness returns for shorter oviposition intervals for both self and conspecific superparasitism.

6. Assuming that offspring quantity contributes more to fitness returns than does offspring quality, the observed frequencies of probing were considered adaptive for parasitoids whose abilities to distinguish between self and conspecifically parasitised hosts and to estimate inter‐oviposition intervals are imperfect.
Effects of specialist parasitoids on oviposition preference of phytophagous insects: encounter–dilution effects in a tritrophic interaction
Authors: Shiojiri Kaori , Takabayashi Junji
Published: September 2003

Abstract.  1. Host plant preferences of the female diamondback moth Plutella xylostella were studied.

2. Female moths preferred conspecific‐damaged cabbage plants over undamaged cabbage plants. The performance of P. xylostella larvae on conspecific‐infested plants did not differ significantly from that of larvae on undamaged plants.

3. Cotesia plutellae, the specialist parasitoid wasp of P. xylostella larvae, displayed equal preference for plants with differing levels of host‐larvae damage, and the wasp attacked only one or two hosts on average before leaving an infested plant, irrespective of the number of hosts on the plant. It is hypothesised that the oviposition preferences of P. xylostella females for host plants already damaged by conspecific larvae demonstrate an encounter–dilution effect against C. plutellae.