The link between short sleep duration and obesity: we should recommend more sleep to prevent obesity.
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Adolescent↗
Biomedical subjects
S Taheri
Publications and source records attributed to S Taheri.
Streptococcus A in paediatric accident and emergency: are rapid streptococcal tests and clinical examination of any help?
BACKGROUND: Rapid streptococcal tests (RSTs) for streptococcal pharyngitis have made diagnosis at once simpler and more complicated. The American Academy of Pediatrics recommends that all RSTs be confirmed by a follow up throat culture unless local validation has proved the RST to be equally sensitive. AIMS: To evaluate (a) RST as a single diagnostic tool, compared with RST with or without throat culture; (b) clinical diagnosis and the relative contribution of different symptoms. METHODS: The study included 213 patients with clinical signs of pharyngitis. Throat swabs were analysed using Quickvue+ Strep A Test; negative RSTs were backed up by throat culture. Thirteen clinical features commonly associated with strep throat were analysed using backward stepwise logistic regression. RESULTS: Positive results (RST or throat culture) were obtained in 33 patients; RST correctly identified 21. Eleven samples were false negative on RST. At a strep throat prevalence of 15.9%, sensitivity of RST was 65.6% (95% CI 46.8% to 81.4%) and specificity 99.4% (96.7% to 99.9%). Sensitivity of clinical diagnosis alone was 57% (34% to 78%) and specificity 71% (61% to 80%). Clinically, only history of sore throat, rash, and pyrexia contributed to the diagnosis of strep throat (p<0.05). CONCLUSION: The high specificity of RST facilitates early diagnosis of strep throat. However, the low sensitivity of RST does not support its use as a single diagnostic tool. The sensitivity in the present study is markedly different from that reported by the manufacturer. Clinical examination is of limited value in the diagnosis of strep throat. It is important to audit the performance of new diagnostic tests, previously validated in different settings.
Antigens, Bacterial↗
5,10-Methylenetetrahydrofolate reductase C677T gene polymorphism in Behcet's patients with or without ocular involvement.
BACKGROUND: Increased serum levels of homocysteine (Hcy) have been reported in patients with Behçet's disease (BD) with an established risk factor for vascular involvement. Recently, the authors demonstrated that elevated Hcy levels are associated with ocular involvement in such patients. On the other hand, elevated levels of Hcy can result from genetic errors. Indeed, a mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR C677T) gene influences Hcy metabolism and, therefore, MTHFR C677T polymorphism provokes hyperhomocysteinaemia. AIM: To investigate the possible genetic factor for the elevation of plasma Hcy level in patients with BD by examining gene interaction with the MTHFR C677T polymorphism, a crucial factor of the Hcy metabolism. In addition, the authors aimed to evaluate if there is an association between the C677T polymorphism and the presence of ocular involvement in such patients. METHOD: A total of 59 patients with BD (25 men, 34 women) with a mean age of 34.9 years and 42 age and sex matched healthy control subjects (19 men, 23 women; mean age 32.2) were included in this investigation. MTHFR gene polymorphism was investigated by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) of a genomic DNA fragment at nucleotide 677 in all subjects in both groups. The genetic equilibrium is assumed for the gene frequencies of the MTHFR polymorphism in both samples. RESULTS: The genotype of the MTHFR gene differed between the Behçet's patients and control subjects (TT: 11.9 v 2.4%; CT: 55.9 v 61.9%; CC: 32.2 v 35.7 %). TT homozygous genotype was more frequently in BD patients than the controls, though the difference was not significant (p = 0.063). In BD patients with ocular involvement, however, the frequencies of MTHFR TT homogenetic type (27.8%) were significantly and statistically higher than those in BD patients without ocular involvement (4.9%, p = 0.022, odds ratio = 7.5), or the controls (2.4%, p = 0.003, odds ratio = 20.0). TT homozygous genotype was associated with an increased risk for ocular involvement. CONCLUSION: Elevated serum levels of Hcy seem to be a result of C677T polymorphism of the MTHFR gene, with increased TT individuals over CC and CT genotype BD patients. Although no association was shown between the MTHFR reductase C677T polymorphism and the increased risk of oral aphtahe or genital ulcers, a mutation in this gene was associated with an increased risk of ocular involvement, suggesting genetic instability with a potential initiation of Hcy lowering therapy in this patient group.
Adult↗
The genetics of sleep disorders.
Most sleep disorders result from complex interactions between genes and the environment. Modern molecular techniques are increasingly applied to determine the contribution of genes to sleep and its disorders. The genetic basis of circadian rhythms has been explored using Drosophila and rodent models. This culminated in the identification of the molecular basis of one autosomal dominant form of familial advanced sleep phase syndrome: mutations in the human period 2 gene. Genetic studies in an autosomal recessive canine model of narcolepsy and in gene-targeted mice have identified the hypothalamic hypocretin (orexin) neuropeptide system as a key target for human narcolepsy. In this case, animal models have provided important clues to a human disorder with complex genetics. The study of the role of genes in the obstructive sleep apnoea syndrome is likely to provide important clues to a phenotype associated with respiratory, cardiovascular, and metabolic dysfunction. This brief review will present the role of genetic factors in the obstructive sleep apnoea syndrome, restless leg syndrome, narcolepsy, and circadian rhythm disorders.
Age Factors↗
CSF hypocretin levels in Guillain-Barré syndrome and other inflammatory neuropathies.
CSF hypocretin-1 was measured in 28 Guillain-Barré syndrome (GBS), 12 Miller-Fisher syndrome, 12 chronic inflammatory demyelinating polyneuropathy (CIDP), and 48 control subjects. Seven GBS subjects had undetectably low hypocretin-1 levels (<100 pg/mL). Hypocretin-1 levels were moderately reduced in an additional 11 GBS, 5 Miller-Fisher syndrome, and 1 CIDP subject. Low levels in GBS occurred early in the disease and were associated with upper CNS level abnormalities.
Adolescent↗
Do macrophages and monocytes impede regeneration of transplanted cardiomyocytes?
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Animals↗
Measurement of hypocretin/orexin content in the mouse brain using an enzyme immunoassay: the effect of circadian time, age and genetic background.
The hypocretins (1 and 2) have emerged as key regulators of sleep and wakefulness. We developed a high-throughput enzyme immunoassay (EIA) to measure total brain hypocretin levels from large numbers of mice. Hypocretin levels were not altered by circadian time or age. However, significant differences in one or both hypocretin peptides were observed between different mouse strains. We studied hypocretin levels in knockout and transgenic mouse models with obesity, circadian gene mutations or monoaminergic defects. Compared to controls, only histamine receptor knockouts had lower hypocretin levels. This was most pronounced in H1 receptor knockouts suggesting the existence of a positive feedback loop between hypocretin and histaminergic neurons.
Aging↗
Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency.
Holocarboxylase synthetase (HLCS) is an enzyme that catalyzes the incorporation of biotin into apo-carboxylases, and its deficiency causes biotin-responsive multiple carboxylase deficiency. The reported sequences of cDNA for human HLCS from liver, lymphocyte, and KG-1 myeloid cell lines differ at their 5' regions. To elucidate variations of the human HLCS mRNA and longer 5' cDNA ends, we performed screening of the human liver cDNA library and rapid amplification of the cDNA ends (RACE). Our results suggest the existence of three types of HLCS mRNA that start at different exons. The first type starts at exon 1, and the second type starts at exon 3, and both are found in various human tissues. The third type, corresponding to the cDNA from the KG-1 cell, starts at exon 2 of the HLCS gene. Various splicing patterns from exons 3-6 were also observed. None of the variations of cDNA found created a new initiation codon. Mutation screening from exons 6-14, therefore, was sufficient to detect amino acid changes in HLCS in patients. Our direct sequencing strategy for screening mutations in the HLCS gene revealed mutations in five Japanese patients and seven non-Japanese patients. Our analyses involving 12 Japanese and 13 non-Japanese patients and studies by others indicate that (1) there is no panethnically prevalent mutation; (2) the Arg508Trp, Gly581Ser, and Val550Met mutations are found in both Japanese and non-Japanese populations; (3) the IVS10+5G-->A mutation is predominant and probably a founder mutation in European patients; (4) the 655-656insA, Leu237Pro, and 780delG mutations are unique in Japanese patients; (5) the spectrum of the mutations in the HLCS gene may vary substantially among different ethnic groups.
Base Sequence↗
Orexins: effects on behavior and localisation of orexin receptor 2 messenger ribonucleic acid in the rat brainstem.
The orexins are neuropeptides originally reported to be involved in the stimulation of food intake. However, analysis of orexin immunoreactive fibres have revealed the densest innervation in brain sites involved in arousal and sleep-wake control, notably the noradrenergic locus coeruleus, an area that also expresses orexin receptor 1 (OX1R) messenger RNA (mRNA). We report here that, in the rat, a single intracerebroventricular injection of orexin A (1 and 3 nmol) or orexin B (3 nmol), during the early light phase, did not increase food intake over the first 4 h postinjection. However, the frequency of active behaviors such as grooming, rearing, burrowing and locomotion increased. Feeding behavior and food intake subsequently decreased over the following 20 h (4-24 h postinjection period) in the orexin A 3 nmol injected group whilst the frequency of inactive behavior (still or asleep) in this group increased. Using riboprobes, we performed in situ hybridization histochemistry to map the distribution of orexin receptor 2 (OX2R) mRNA within the rat brainstem. We report here, for the first time, the presence of OX2R mRNA in the nucleus of the solitary tract and the lateral reticular field (LRt). The LRt is a brainstem site that, amongst other functions, is implicated in attention and wakefulness. This distribution of OX2R and the effects on behavior support recent reports that the orexins might modulate central nervous system arousal and sleep-wake mechanisms rather than exclusively being involved in the control of food intake.
Animals↗
Orexin A immunoreactivity and preproorexin mRNA in the brain of Zucker and WKY rats.
The primary role of the orexins was originally believed to be appetite regulation, but is now believed to be the regulation of sleep, arousal and locomotor activity. Orexin A immunoreactivity (orexin A-IR) and prepro-orexin mRNA were measured in the CNS of obese and lean Zucker rats. There were no differences in orexin A-IR or prepro-orexin mRNA levels between obese and lean Zucker rats. The orexins are therefore unlikely to be important in this model of obesity. Levels of orexin A-IR and prepro-orexin mRNA were measured in the CNS of Wistar-Kyoto (WKY) rats, which are hypoactive and have abnormal sleep architecture. Compared to Wistar rats, WKY rats had significantly lower orexin A-IR (with differences of up to 100% in some brain regions) and prepro-orexin mRNA levels. These observations suggest that the sleep and activity phenotype of the WKY strain may be related to orexin deficiency and that this strain may be a useful model of partial orexin deficiency.
Animals↗
Proglucagon-derived peptides in intestinal epithelial proliferation: glucagon-like peptide-2 is a major mediator of intestinal epithelial proliferation in rats.
Proglucagon-derived peptides have been implicated in the control of intestinal mucosal cell division. To investigate the actions of these peptides on intestinal cell proliferation, different doses of enteroglucagon, oxyntomodulin, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) were tested in male Wistar rats maintained on total parenteral nutrition. Crypt cell proliferation was assessed by the analysis of arrested metaphases in microdissected crypts. Enteroglucagon and oxyntomodulin had no effect on intestinal weight or cell proliferation. GLP-1 had a slight effect on stomach and small intestinal weights and on epithelial cell proliferation in the small and large intestines. GLP-2 infusion dose-dependently increased the weights of the stomach, small intestine, colon, and cecum and increased crypt cell proliferation in the small and large intestines of parenterally fed rats. In orally fed animals, GLP-2 increased intestinal weight but had little effect on proliferation. Therefore, of the proglucagon-derived peptides, GLP-2 appears to be a major mediator of intestinal epithelial proliferation.
Animals↗
Orexins/hypocretins: waking up the scientific world.
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Amino Acid Sequence↗
Orexin A interactions in the hypothalamo-pituitary gonadal axis.
The distribution of orexin A-immunoreactive neurons and orexin type I receptors in the CNS suggests important roles in regulating the hypothalamo-pituitary gonadal (HPG) axis and sexual behaviors. We examined orexin A interactions in the HPG axis in vivo and in vitro. Orexin A stimulated LH-releasing hormone (LHRH) release in hypothalamic explants harvested from male rats (+133%) and from females at proestrus (+233%), with no effect at estrus or metestrus. Orexin A dose dependently inhibited LHRH-stimulated LH release in dispersed pituitaries from proestrous females only. A selective NPY1-receptor antagonist abolished in vitro release of LHRH by orexin A. Hyperestrogenization in female rats reduced orexin A content in hypothalamus (-28%), midbrain (-26%), medulla (-40%), thalamus (-36%), olfactory tubercles (-25%), and cortex (-35%), brain regions that are important in HPG control and sex-cycle specific behaviors. Orexin A content was lower in hypothalamus (-20%) and higher in midbrain (+40%), medulla (+31%), and thalamus (+33%) at late proestrus vs. other cycle stages. Orexin A release after administration of 56 mM KCl was significantly greater in hypothalamic explants harvested on the morning of proestrus than at estrus or metestrus, and orexin A release was stimulated by estradiol (E2) in explants from males. These results reveal important interactions for orexin A in the HPG axis.
Animals↗
Ghrelin causes hyperphagia and obesity in rats.
Ghrelin, a circulating growth hormone-releasing peptide derived from the stomach, stimulates food intake. The lowest systemically effective orexigenic dose of ghrelin was investigated and the resulting plasma ghrelin concentration was compared with that during fasting. The lowest dose of ghrelin that produced a significant stimulation of feeding after intraperitoneal injection was 1 nmol. The plasma ghrelin concentration after intraperitoneal injection of 1 nmol of ghrelin (2.83 +/- 0.13 pmol/ml at 60 min postinjection) was not significantly different from that occurring after a 24-h fast (2.79 +/- 0.32 pmol/ml). After microinjection into defined hypothalamic sites, ghrelin (30 pmol) stimulated food intake most markedly in the arcuate nucleus (Arc) (0-1 h food intake, 427 +/- 43% of control; P < 0.001 vs. control, P < 0.01 vs. all other nuclei), which is potentially accessible to the circulation. After chronic systemic or intracerebroventricular (ICV) administration of ghrelin for 7 days, cumulative food intake was increased (intraperitoneal ghrelin 13.6 +/- 3.4 g greater than saline-treated, P < 0.01; ICV ghrelin 19.6 +/- 5.5 g greater than saline-treated, P < 0.05). This was associated with excess weight gain (intraperitoneal ghrelin 21.7 +/- 1.4 g vs. saline 10.6 +/- 1.9 g, P < 0.001; ICV ghrelin 15.3 +/- 4.3 g vs. saline 2.2 +/- 3.8 g, P < 0.05) and adiposity. These data provide evidence that ghrelin is important in long-term control of food intake and body weight and that circulating ghrelin at fasting concentrations may stimulate food intake.
Animals↗
Cocaine- and amphetamine-regulated transcript, glucagon-like peptide-1 and corticotrophin releasing factor inhibit feeding via agouti-related protein independent pathways in the rat.
The melanocortin-4 receptor (MC4-R) appears to be an important downstream mediator of the action of leptin. We examined to what extent the anorectic effects of cocaine- and amphetamine-regulated transcript (CART), glucagon-like peptide-1 (GLP-1) and corticotrophin releasing factor (CRF) might be mediated via MC4-R. alpha-Melanocyte stimulating hormone (alpha-MSH), the MC4-R agonist, administered intracerebroventricularly (ICV) at a dose of 1 nmol reduced food intake by approximately half. Agouti-related protein (Agrp) (83-132), a biologically active fragment of the endogenous MC4-R antagonist, administered ICV at a dose of 1 nmol completely blocked the anorectic effect of 1 nmol alpha-MSH. CART (55-102) (0.2 nmol), GLP-1 (3 nmol) and CRF (0.3 nmol) produced a reduction in feeding of approximately the same magnitude as 1 nmol alpha-MSH. Agrp (83-132) (1 nmol) administered ICV did not block the anorectic effects of CART (55-102) (1 h food intake, 0.2 nmol CART (55-102), 2.7+/-0.8 g vs. CART (55-102)+Agrp (83-132), 2.6+/-0.6 g, P=0.87; saline control 5.4+/-0.3 g, P<0.001 vs. both groups). Agrp (83-132) also did not block the anorectic effects of GLP-1 or CRF (1 h food intake, 0.3 nmol CRF, 0.7+/-0.3 g vs. CRF+Agrp (83-132), 0.7+/-0.3 g, P=0.91; 3 nmol GLP-1, 1.9+/-0.4 g vs. GLP-1+Agrp (83-132), 1.1+/-0. 5 g, P=0.23; saline control 5.0+/-0.6 g, P<0.001 vs. all four groups). Thus, as previous data suggests, GLP-1 and CRF do not appear to reduce food intake predominantly via MC4-R, we here demonstrate for the first time that CART, in addition to GLP-1 and CRF primarily acts via Agrp independent pathways.
Agouti-Related Protein↗
Role of orexins in sleep and arousal mechanisms.
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Animals↗
Diurnal variation in orexin A immunoreactivity and prepro-orexin mRNA in the rat central nervous system.
Orexins are a family of neuropeptides originally believed to be important mediators of food intake. The wide distribution of orexins and their receptors, however, has suggested other regulatory functions for these peptides including involvement in sleep and arousal mechanisms. In this study, we have demonstrated diurnal variation in orexin A immunoreactivity in the pons, from where locus coeruleus noradrenergic neurones innervate other brain areas to stimulate arousal, and in the preoptic/anterior hypothalamic region, an area implicated in the regulation of sleep and circadian rhythms. Orexin A immunoreactivity decreased by 50% in the preoptic/anterior hypothalamus from 09:00 to 21:00 h (P < 0.0001), whilst in the pons, it increased by over 30% from 09:00 to 01:00 h (P = 0.02). Prepro-orexin mRNA also displayed diurnal variation. This further suggests that orexins are involved in the regulation of the sleep/wake cycle.
Animals↗
The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion.
Ghrelin, a novel 28 amino acid peptide found in hypothalamus and stomach, was recently identified as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). We have now found that both intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of ghrelin in freely feeding rats stimulated food intake. The onset of increased feeding was rapid and after i.c.v. administration was sustained for 24 hours. Following i.c.v. administration of 3 nmol ghrelin, the duration and magnitude of the feeding stimulation was similar to that following 5 nmol neuropeptide Y (NPY). Plasma growth hormone (GH) concentration increased following both i.c.v. and i.p. administration of ghrelin. Release of adrenocorticotrophic hormone (ACTH) was stimulated and thyroid stimulating hormone (TSH) inhibited following i.c.v. administration of ghrelin. These data suggest a possible role for the newly identified endogenous hypothalamic peptide, ghrelin, in stimulation of feeding and growth hormone secretion.
Adrenocorticotropic Hormone↗