Effects of uteroplacental restriction on the relaxin-family receptors, Lgr7 and Lgr8, in the uterus of late pregnant rats.

The peptide hormone relaxin stimulates uterine growth and endometrial angiogenesis and inhibits myometrial contractions in a variety of species. The receptor for relaxin is a leucine-rich repeat containing G-protein-coupled receptor Lgr7 (RXFP1) that is highly expressed in the myometrium of late pregnant mice, with a significant decrease in receptor density observed at term. The present study first compared the expression of Lgr7 with another relaxin-family receptor Lgr8 (RXFP2) in the uterus and placenta of late pregnant rats.

TRB3 inhibits the transcriptional activation of stress-regulated genes by a negative feedback on the ATF4 pathway.

The integrated stress response (ISR) is defined as a highly conserved response to several stresses that converge to the induction of the activating transcription factor 4 (ATF4). Because an uncontrolled response may have deleterious effects, cells have elaborated several negative feedback loops that attenuate the ISR. In the present study, we describe how induction of the human homolog of Drosophila tribbles (TRB3) attenuates the ISR by a negative feedback mechanism.

ATF2 is required for amino acid-regulated transcription by orchestrating specific histone acetylation.

The transcriptional activation of CHOP (a CCAAT/enhancer-binding protein-related gene) by amino acid deprivation involves the activating transcription factor 2 (ATF2) and the activating transcription factor 4 (ATF4) binding the amino acid response element (AARE) within the promoter. Using a chromatin immunoprecipitation approach, we report that in vivo binding of phospho-ATF2 and ATF4 to CHOP AARE are associated with acetylation of histones H4 and H2B in response to amino acid starvation. A time course analysis reveals that ATF2 phosphorylation precedes histone acetylation, ATF4 binding and the increase in CHOP mRNA.

Evidence for local relaxin ligand-receptor expression and function in arteries.

Relaxin is a 6 kDa protein hormone produced by the corpus luteum and secreted into the blood during pregnancy in rodents and humans. Growing evidence indicates that circulating relaxin causes vasodilatation and increases in arterial compliance, which may be among its most important actions during pregnancy. Here we investigated whether there is local expression and function of relaxin and relaxin receptor in arteries of nonpregnant females and males.

Relaxin and the extracellular matrix: molecular mechanisms of action and implications for cardiovascular disease.

Myocardial fibrosis is a common endpoint in a variety of cardiac pathologies. It results from excessive accumulation of collagen and other materials that together comprise the extracellular matrix (ECM). In the past decade, the peptide hormone relaxin has emerged as an important regulator of the ECM within several organs, including the heart, and has been suggested as a novel therapeutic agent for the treatment of fibrotic disorders.

The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores.

To insure an adequate supply of nutrients, omnivores choose among available food sources. This process is exemplified by the well-characterized innate aversion of omnivores to otherwise nutritious foods of imbalanced amino acid content. We report that brain-specific inactivation of GCN2, a ubiquitously expressed protein kinase that phosphorylates translation initiation factor 2 alpha (eIF2alpha) in response to intracellular amino acid deficiency, impairs this aversive response.

Increased expression of the relaxin receptor (LGR7) in human endometrium during the secretory phase of the menstrual cycle.

This study investigated localization and expression of relaxin and its receptor, LGR7, in the human endometrium during the proliferative and secretory phases of the menstrual cycle. H2 relaxin binding was identified in endometrium, but not myometrium, and particularly in the epithelium of the endometrial glands and uterine lumen. Binding sites increased in the early secretory phase of the menstrual cycle and were paralleled by similar increases in LGR7 mRNA measured by Q-PCR.

Effects of the sucking stimulus on relaxin receptor (LGR7) expression in the mammary apparatus of the tammar wallaby (Macropus eugenii).

Macropodid marsupials suckle young of different ages simultaneously, a phenomenon known as asynchronous lactation. The growth of the mammary glands supporting young of different ages varies considerably. This study investigates relaxin receptor (LGR7) expression in different mammary glands and nipples during early lactation in the wallaby.

Oxytocin and estrogen receptor expression in the myometrium of pregnant relaxin-deficient (Rlx-/-) mice.

Relaxin decreases oxytocin-stimulated rat myometrial contractions in vitro. This study used pregnant relaxin-deficient (Rlx-/-) mice to investigate the interaction between relaxin, oxytocin receptor (OTR), and estrogen receptor (ER) expression in the myometrium. Myometrial OTRs were significantly decreased on gestation day 18.

Mechanisms of relaxin action in the reproductive tract: studies in the relaxin-deficient (Rlx-/-) mouse.

The major functions of relaxin (RLX) are associated with female reproductive tract physiology, namely, the regulation of biochemical processes involved in remodeling of extracellular matrix components in the cervix and vagina at term. Studies in RLX-deficient mice (Rlx-/-) demonstrate that although females give birth to live young without apparent dystocia, the pubic symphysis is not elongated, and they have abnormal cervical and vaginal morphology. The current study examined phenotypic differences in collagen, matrix metalloproteinases (MMP), and estrogen receptors (ERs) in the cervix and vagina of pregnant Rlx+/+ and Rlx-/- mice.

A randomised trial of early warning signs relapse prevention training in the treatment of alcohol dependence.

A pragmatic randomised trial examined the effects of Early Warning Signs Relapse Prevention Training (EWSRPT) on drinking in alcohol dependent persons with history of relapse. Participants were 124 abstinent alcohol dependent patients with a history of relapse (median five relapses) who entered the trial as they completed a 6-week day treatment programme. They were randomly allocated to receive either (1) Aftercare as Usual (AU) or (2) AU plus 15 individual sessions of EWSRPT using Gorski's protocol.

A mouse model of tuberous sclerosis 1 showing background specific early post-natal mortality and metastatic renal cell carcinoma.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in either the TSC1 or the TSC2 genes and characterized by the development of benign hamartomatous growths in multiple organ systems. We have inactivated Tsc1 in the mouse germ line by gene targeting in ES cells and confirmed that the mutant allele (Tsc1-) has a recessive embryonic lethal phenotype. We found that a significant number (approximately 27%) of heterozygous (Tsc1+/-) mice on the C57BL/6 background died before weaning (P = 0.

Differential expression of mesotocin receptors in the uterus and ovary of the pregnant tammar wallaby.

Mesotocin, an oxytocin-like peptide, is released in highest concentrations during parturition in macropodid marsupials. In late pregnant wallabies, uterine sensitivity to mesotocin increases markedly in the myometrium of the gravid uterus. This coincides with a significant increase in myometrial mesotocin receptor concentrations 3-4 days before term.

An investigation of neuronal integrity in severe paediatric traumatic brain injury.

Magnetic Resonance Spectroscopy (MRS) and its association with neuropsychological functioning was examined in the chronic injury phase of paediatric traumatic brain injury (TBI). Fifteen children, aged 10-16 years, with severe TBIs were compared with 15 controls, matched for age and gender. The TBI group was found to have significantly lower levels of -acetyl aspartate (NAA) and Choline (Cho) in the right frontal lobe and generally displayed reduced performances on neuropsychological tests.

Seasonal changes in mesotocin and localization of its receptor in the prostate of the brushtail possum (Trichosurus vulpecula).

The prostate gland in the brushtail possum grows and regresses seasonally. It has similarities to the human prostate and may therefore provide a unique model for investigating prostatic hyperplasia. Oxytocin has been implicated in the regulation of prostate growth in eutherian mammals, and the initial aim of this study was to identify and localize the marsupial equivalent, mesotocin, and its receptor in the prostate of the brushtail possum.

NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency.

complex I deficiency, the most common respiratory chain defect, is genetically heterogeneous: mutations in 8 nuclear and 7 mitochondrial DNA genes encoding complex I subunits have been described. However, these genes account for disease in only a minority of complex I-deficient patients. We investigated whether there may be an unknown common gene by performing functional complementation analysis of cell lines from 10 unrelated patients.

Increased expression of the relaxin receptor (LGR7) in human endometrium during the secretory phase of the menstrual cycle.

Relaxin (RLX) is a structural homolog of insulin that is the ligand for the LGR7 receptor. Although the 6k peptide is produced by the ovaries to cause connective tissue remodeling of the rodent and pig reproductive tracts to facilitate parturition, in human reproduction, the role of RLX is less well understood. Binding of human gene 2 (H2) [(33)P]-RLX, expression of RLX peptides and the LGR7 receptor was examined in the human uterus at different stages of the menstrual cycle.

Steroid-independent regulation of uterine oxytocin receptors.

The oxytocin receptor is an important contractile-associated protein, up-regulated at term in the myometrium in many mammalian species. We conducted studies in a novel animal model to challenge the general view that gonadal steroids are a major regulatory factor of uterine oxytocin receptors. Female marsupials have separate uteri and, in monovular species such as the tammar wallaby, the conceptus is present in one uterus whereas the contralateral uterus is empty.

Anal function following third degree tears.

Objective: To assess the anal function of women who have suffered a third degree perineal tear during parturition.

Patients: Fifty-three consecutive women who sustained a third degree tear, between January 1998 and March 2000, at the Princess Anne Maternity Unit, Royal Bolton Hospital were assessed.

Methods: Women were assessed at 3 months post partum using the Cleveland Clinic Incontinence Score, digital assessment of anal sphincter and endo-anal ultrasound scan.

Relaxin down-regulates renal fibroblast function and promotes matrix remodelling in vitro.

Background: Renal fibroblasts are important effector cells in tubulointerstitial fibrosis, with experimental antifibrotic strategies focusing on the functional down-regulation of these cells. Several experimental models of fibrosis have provided evidence for the effectiveness of the polypeptide hormone relaxin as a potential antifibrotic agent. This study was conducted to further elucidate the antifibrotic mechanisms of relaxin on renal fibroblasts in vitro.

Inhibition of oxytocin receptor and estrogen receptor-alpha expression, but not relaxin receptors (LGR7), in the myometrium of late pregnant relaxin gene knockout mice.

This study used relaxin (RLX) gene knockout mice (Rlx-/-) to investigate the effects of RLX on myometrial oxytocin receptor (OTR) and estrogen receptor (ER)-alpha gene expression in late gestation. We also characterized the temporal expression of the RLX receptor (LGR7) and demonstrated gene transcripts in the myometrium of Rlx+/+ and Rlx-/- mice. There was a significant (P < 0.

Cognitive outcome of long-term survivors of multisystem langerhans cell histiocytosis: a single-institution, cross-sectional study.

Purpose: Damage to the CNS, including the cerebellum, and to the hypothalamopituitary axis, is documented in Langerhans cell histiocytosis (LCH). Neuropsychologic deficits have been recognized, but this is the first study in which cognitive function has been systematically assessed in a cohort of patients.

Patients And Methods: Twenty-eight long-term survivors of multisystem LCH (mean age, 15.

Four years of monitoring for viral haemorrhagic septicaemia virus in marine waters around the United Kingdom.

Between 1995 and 1998, marine fish from around the coast of the UK were collected and samples analysed for viral haemorrhagic septicaemia virus (VHSV) using cell culture isolation methods. In 1997 and 1998 the samples were also analysed for VHSV by reverse transcription PCR (RT-PCR). A total of 1867 fish of 11 species were tested, but VHSV was isolated on only 1 occasion, from herring Clupea harengus, in 1996.

Physiological or pathological--a role for relaxin in the cardiovascular system?

The omnipresent 6kDa polypeptide relaxin (RLX) is emerging as a multi-functional endocrine and paracrine factor, with a broad range of target tissues that includes the cardiovascular system. Humans and other higher primates have three RLX genes, designated H1, H2 and H3, of which H2 RLX is the major stored and circulating form. Rodents have only two RLX genes: relaxin-1 (equivalent to H2 RLX) and relaxin-3 (equivalent to H3 RLX).