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1.
J Community Genet ; 9(4): 387-396, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30218347

ABSTRACT

Congenital anomaly registries have two main surveillance aims: firstly to define baseline epidemiology of important congenital anomalies to facilitate programme, policy and resource planning, and secondly to identify clusters of cases and any other epidemiological changes that could give early warning of environmental or infectious hazards. However, setting up a sustainable registry and surveillance system is resource-intensive requiring national infrastructure for recording all cases and diagnostic facilities to identify those malformations that that are not externally visible. Consequently, not all countries have yet established robust surveillance systems. For these countries, methods are needed to generate estimates of prevalence of these disorders which can act as a starting point for assessing disease burden and service implications. Here, we describe how registry data from high-income settings can be used for generating reference rates that can be used as provisional estimates for countries with little or no observational data on non-syndromic congenital malformations.

2.
J Public Health (Oxf) ; 36(2): 243-50, 2014 Jun.
Article in English | MEDLINE | ID: mdl-23667249

ABSTRACT

BACKGROUND: In 2010 the World Health Assembly called for action to improve the care and prevention of congenital disorders, noting that technical guidance would be required for this task, especially in low- and middle-income countries. Responding to this call, we have developed a freely available web-accessible Toolkit for assessing health needs for congenital disorders. METHODS: Materials for the Toolkit website (http://toolkit.phgfoundation.org) were prepared by an iterative process of writing, discussion and modification by the project team, with advice from external experts. A customized database was developed using epidemiological, demographic, socio-economic and health-services data from a range of validated sources. Document-processing and data integration software combines data from the database with a template to generate topic- and country-specific Calculator documents for quantitative analysis. RESULTS: The Toolkit guides users through selection of topics (including both clinical conditions and relevant health services), assembly and evaluation of qualitative and quantitative information, assessment of the potential effects of selected interventions, and planning and prioritization of actions to reduce the risk or prevalence of congenital disorders. CONCLUSIONS: The Toolkit enables users without epidemiological or public health expertise to undertake health needs assessment as a prerequisite for strategic planning in relation to congenital disorders in their country or region.


Subject(s)
Congenital Abnormalities/epidemiology , Congenital Abnormalities/prevention & control , Global Health , Health Services Needs and Demand , Needs Assessment/standards , Public Health Practice , Congenital Abnormalities/diagnosis , Developing Countries , Humans , Infant, Newborn , Information Services , Internet , Prevalence
3.
Neuropathol Appl Neurobiol ; 38(7): 710-22, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22289121

ABSTRACT

AIMS: This study has investigated how global brain ischaemia/reperfusion (I/R) modifies levels of mRNAs encoding γ-aminobutyric acid type A (GABA(A)) receptor α1, ß2 and γ2 subunits and glutamic acid decarboxylase 65 (GAD65) in an age- and structure-dependent manner. Gene expression in response to treatment with the anti-inflammatory agent meloxicam was also investigated. METHODS: Global ischaemia was induced in 3- and 18-month-old male Sprague-Dawley rats. CA1, CA3, and dentate gyrus (DG) hippocampal areas, cerebral cortex (CC) and caudate putamen (C-Pu) from sham-operated and I/R-injured animals were excised 48 h after the insult and prepared for quantitative polymerase chain reaction assays. Following I/R, meloxicam treatment was also carried out on young animals. RESULTS: Data revealed significant decreases in the levels of all GABA(A) receptor subunit transcripts in the hippocampus of both young and older injured animals compared with sham-operated ones. In contrast, there was either an increase or no change in GAD65 mRNA levels. GABA(A) receptor subunit transcript decreases were also observed in the CC and C-Pu in young injured animals but not in the CC of the older injured ones; interestingly, significant increases were observed in the C-Pu of older injured animals compared with controls. Meloxicam treatment following the insult resulted in a diminution of the previously described I/R response. CONCLUSIONS: The data indicate that I/R results in the modification of the levels of several gene transcripts involved in GABAergic signalling in both the pre- and postsynaptic components, of this neurotransmitter system, in an age- and structure-dependent manner.


Subject(s)
Aging/physiology , Hippocampus/metabolism , Ischemic Attack, Transient/genetics , RNA, Messenger/genetics , Receptors, GABA-A/genetics , Age Factors , Animals , Gene Expression/genetics , Hippocampus/pathology , Male , Meloxicam , Protein Subunits/genetics , Protein Subunits/metabolism , Rats , Rats, Sprague-Dawley , Receptors, GABA-A/metabolism , Thiazines/pharmacology , Thiazoles/pharmacology
4.
Neuroscience ; 157(1): 143-52, 2008 Nov 11.
Article in English | MEDLINE | ID: mdl-18824085

ABSTRACT

The acquisition, production and maintenance of song by oscine birds is a form of audition-dependent learning that, in many ways, resembles the process by which humans learn to speak. In songbirds, the generation of structured song is determined by the activity of two interconnected neuronal pathways (the anterior forebrain pathway and the vocal motor pathway), each of which contains a number of discrete nuclei that together form the song system. It is becoming increasingly evident that inhibitory GABAergic mechanisms are indispensable in counterbalancing the excitatory actions of glutamate and, thus, likely shape the neuronal firing patterns of neurons within this network. Furthermore, there is compelling evidence for the involvement of GABA(A) receptors, although the molecular composition of these has, to date, remained elusive. Here we describe the isolation of a complementary DNA for the zebra finch GABA(A) receptor gamma4 subunit, and map the expression pattern of the corresponding gene within the zebra finch (Taeniopygia guttata) brain. Our findings show, remarkably, that the gamma4-subunit transcript is highly enriched in the major nuclei of the song system, including the lateral magnocellular nucleus of the anterior nidopallium (LMAN), the medial magnocellular nucleus of the anterior nidopallium (MMAN), Area X, the robust nucleus of the arcopallium (RA) and the HVC (used as the proper name), as well as Field L, which innervates the area surrounding HVC. In summary, we have demonstrated the presence of the mRNA for the gamma4 subunit of the GABA(A) receptor, the major inhibitory receptor in brain, in most of the nuclei of the two neural circuits that mediate song production in the zebra finch. This not only marks the beginning of the characterization of the GABA(A) receptor subtype(s) that mediates the actions of GABA in the song system but it also provides a robust molecular marker with which to distinguish song system-specific brain structures.


Subject(s)
Brain Chemistry/genetics , Brain Chemistry/physiology , Finches/physiology , Receptors, GABA-A/biosynthesis , Vocalization, Animal/physiology , Amino Acid Sequence , Animals , Biomarkers , Brain/anatomy & histology , Brain/physiology , Cloning, Molecular , DNA, Complementary/biosynthesis , DNA, Complementary/genetics , In Situ Hybridization , Learning/physiology , Male , Molecular Sequence Data , Neural Pathways/anatomy & histology , Neural Pathways/physiology , RNA/biosynthesis , RNA/isolation & purification , Receptors, GABA-A/genetics
5.
Scand J Clin Lab Invest ; 67(1): 39-69, 2007.
Article in English | MEDLINE | ID: mdl-17365984

ABSTRACT

OBJECTIVE: As a result of global population movements, haemoglobin disorders (thalassaemias and sickle cell disorders) are increasingly common in the formerly non-indigenous countries of Northern and Western Europe and in the indigenous countries of Southern Europe. This article presents an overview of the changing picture and a method for assessing service needs. METHOD: Data on country of birth or ethnic origin of residents are adjusted to obtain the estimated proportions of residents and births in non-indigenous groups at risk for haemoglobin disorders in European countries. The results are combined with prevalence data in each country of origin to obtain country prevalence estimates. Service indicators (annual tests or other interventions required to ensure equitable delivery of treatment and prevention) are then derived by country. RESULTS: Haemoglobin disorders now occur at comparable frequency throughout Northern, Western and Southern Europe. Annually, there are more affected conceptions in Northern and Western than in Southern Europe, and sickle cell disorders are more common than thalassaemias. There is growing need for health policy-makers to support motivated professionals working to develop optimal patient care, carrier diagnosis, genetic counselling and access to prenatal diagnosis throughout the Region. CONCLUSION: There is a strong case for pan-European collaboration on haemoglobin disorders to share policies, standards and the instruments required to support them. These include methods for needs assessment, service standards, education and information strategies and materials, and methods for evaluating service delivery.


Subject(s)
Anemia, Sickle Cell/epidemiology , Health Services Needs and Demand , Hemoglobins, Abnormal , Thalassemia/epidemiology , Anemia, Sickle Cell/prevention & control , Anemia, Sickle Cell/therapy , Delivery of Health Care , Emigration and Immigration , Europe/epidemiology , Health Policy , Humans , Mass Screening , Thalassemia/prevention & control , Thalassemia/therapy
6.
Invert Neurosci ; 5(3-4): 147-55, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16177887

ABSTRACT

The cloning, sequencing and functional expression of Sgbeta1, a novel locust (Schistocerca gregaria) non-alpha nicotinic acetylcholine receptor (nAChR) subunit is described. This subunit shows 80% identity with the Drosophila melanogaster Dbeta1 and 92% identity with the Locusta migratoria beta1, non-alpha subunits but only 38% identity to Sgalpha1 (also referred to as alphaL1), a previously cloned S. gregaria nAChR alpha-subunit. When expressed in Xenopus laevis oocytes, Sgbeta1 does not respond to nicotine. Responses to nicotine are observed, however, in oocytes co-expressing Sgalpha1 and Sgbeta1, but the pharmacology is indistinguishable from that of currents produced by expressing Sgalpha1 alone. We conclude that either Sgbeta1 does not co-assemble with Sgalpha1, or that it is unable to contribute to the functional properties of the receptor, in the Xenopus oocyte expression system.


Subject(s)
Drosophila melanogaster/physiology , Grasshoppers/physiology , Insect Proteins/genetics , Receptors, Nicotinic/genetics , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , Molecular Sequence Data , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid
7.
Neuroscience ; 133(3): 625-33, 2005.
Article in English | MEDLINE | ID: mdl-15908132

ABSTRACT

We have cloned a full-length complementary DNA from the chicken (Gallus gallus domesticus), which encodes a polypeptide that exhibits approximately 75% identity to the product of the mammalian gene Arc (activity-regulated cytoskeleton-associated protein), also known as arg3.1 (activity-regulated gene). Since this gene is an immediate-early gene that has been suggested to play a role in synaptic plasticity and learning and memory processes, its expression has been analyzed in a juvenile form of learning, namely, filial imprinting. Our results demonstrate that Arc/arg3.1 mRNA is detectable in the newborn chick brain, and that at this early age the level of this transcript can be altered by brief sensory/emotional experience. After postnatal exposure to a novel 30-min auditory imprinting stimulus, Arc/arg3.1 mRNA was found to be significantly increased in two higher associative areas, the mesopallium intermediomediale (P = 0.002) and the nidopallium dorso-caudale (P = 0.031), compared with naïve controls. The transcript level was also significantly elevated after imprinting in Area L pallii (P=0.045), which is analogous to the mammalian auditory cortex. In addition, increases were seen in the medio-rostral nidopallium/mesopallium (P = 0.054), which is presumed to be the analog of the mammalian prefrontal cortex, and the hyperpallium intercalatum (P = 0.054), but these did not quite reach significance. We discuss these data in the light of those obtained in an earlier study, in the same paradigm, for the avian immediate-early gene, zenk (an acronym for zif-268, egr-1, ngfi-a and krox-24, which are different names for the orthologous mammalian gene). We conclude that, although both the Arc/arg3.1 and zenk genes are induced by auditory imprinting, they are significantly up-regulated in different learning-relevant brain regions. It is, therefore, evident that they must be activated by different mechanisms.


Subject(s)
Brain/physiology , Cytoskeletal Proteins/genetics , Gene Expression Regulation, Developmental , Imprinting, Psychological/physiology , Nerve Tissue Proteins/genetics , Social Behavior , Acoustic Stimulation , Amino Acid Sequence , Animals , Animals, Newborn , Association Learning/physiology , Brain/growth & development , Chickens , DNA-Binding Proteins/genetics , Early Growth Response Protein 1 , Gene Library , Genes, Immediate-Early/physiology , Immediate-Early Proteins/genetics , Molecular Sequence Data , Neuronal Plasticity/physiology , RNA, Messenger/analysis , Rats , Transcription Factors/genetics
8.
Neuroscience ; 130(3): 611-7, 2005.
Article in English | MEDLINE | ID: mdl-15590145

ABSTRACT

The immediate-early gene zenk (an acronym for the avian orthologue of the mammalian genes zif-268, egr-1, ngfi-a and krox-24) has been extensively employed, in studies on oscine birds, as a marker of neuronal activity to reveal forebrain structures that are involved in the memory processes associated with the acquisition, perception and production of song. Audition-induced expression of this gene, in brain, has also recently been reported for the domestic chicken (Gallus gallus domesticus) and the Japanese quail (Coturnix coturnix japonica). Whilst the anatomical distribution of zenk expression was described for the quail, corresponding data for the chicken were not reported. We have, therefore, used in situ hybridisation to localise the mRNA that encodes the product of the zenk gene (which we call ZENK) within the brain of the 1-day-old chick. We demonstrate that this transcript is present in a number of forebrain structures including the medio-rostral neostriatum/hyperstriatum ventrale (MNH), a region that has been strongly implicated in auditory imprinting (which is a form of recognition memory), and Field L, the avian analog of the mammalian auditory cortex. Because of this pattern of gene expression, we have compared the level of the ZENK mRNA in chicks that have been subjected to a 30-min acoustic imprinting paradigm and in untrained controls. Our results reveal a significant increase (P< or =0.05) in the level of the ZENK mRNA in MNH and Field L, and in the two forebrain hemispheres; no increase was seen in the ectostriatum, which is a visual projection area. The data obtained implicate the immediate-early gene, zenk, in auditory imprinting, which is an established model of juvenile learning. In addition, our results indicate that the ZENK mRNA may be used as a molecular marker for MNH, a region that is difficult to anatomically and histochemically delineate.


Subject(s)
Chickens/physiology , Genes, Immediate-Early/genetics , Imprinting, Psychological/physiology , Neostriatum/metabolism , Acoustic Stimulation , Animals , Animals, Newborn , Densitometry , In Situ Hybridization , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Transcription, Genetic , Up-Regulation/physiology
9.
Bull World Health Organ ; 79(11): 1006-13, 2001.
Article in English | MEDLINE | ID: mdl-11731807

ABSTRACT

OBJECTIVE: To demonstrate the value of a national register for surveillance of services for an inherited disorder. METHODS: Data from the United Kingdom Thalassaemia Register and the United Kingdom Register of Prenatal Diagnosis for Haemoglobin Disorders were combined in a database; these registers include all fetuses known to have been diagnosed with beta thalassaemia major, beta thalassaemia intermedia, or haemoglobin E/beta thalassaemia in the United Kingdom. Data were extracted to show outcomes (selective abortion or live birth) of all fetuses and the status of those born with a disorder (alive, dead, successful bone marrow transplant, or lost to follow-up) by parents' region of residence and ethnicity. FINDINGS: At the end of 1999 the register included 1074 patients, 807 of whom were alive and residing in the United Kingdom. A successful bone marrow transplant has been performed for 117 out of 581 (20%) patients born since 1975. Residents of Pakistani origin are now the main group at risk in the United Kingdom, replacing residents of Cypriot origin. This has led to a marked shift in the need for services from the south-east of England to the Midlands and the north of England. Despite the acceptability of prenatal diagnosis, the proportion of affected births remains 50% higher than would be expected, reflecting a widespread failure to deliver timely screening and counselling to carriers. Even though effective treatment is available the annual number of deaths is rising, indicating that better tolerated treatments are needed. CONCLUSION: A national diagnosis register is a powerful instrument for monitoring the treatment and prevention of inherited disorders and for highlighting correctable shortcomings. In view of the increasing possibilities for genetic screening there is a strong case for central funding for such databases within modern health services.


Subject(s)
Population Surveillance , Registries , beta-Thalassemia/epidemiology , Adolescent , Adult , Bone Marrow Transplantation , Child , Child, Preschool , Female , Genome, Human , Health Services Needs and Demand , Humans , Middle Aged , National Health Programs , Pregnancy , Pregnancy Outcome , Prenatal Diagnosis , Quality of Health Care , United Kingdom/epidemiology , beta-Thalassemia/diagnosis , beta-Thalassemia/genetics , beta-Thalassemia/therapy
10.
Eur J Pharmacol ; 430(2-3): 193-202, 2001 Nov 02.
Article in English | MEDLINE | ID: mdl-11711031

ABSTRACT

Although it is well established that fish possess corticotropin-releasing factor (CRF) and a CRF-like peptide, urotensin I, comparatively little is known about the pharmacology of their cognate receptors. Here we report the isolation and functional expression of two complementary DNAs (cDNAs), from the chum salmon Oncorhynchus keta, which encode orthologues of the mammalian and amphibian CRF type 1 (CRF(1)) and type 2 (CRF(2)) receptors. Radioligand competition binding experiments have revealed that the salmon CRF(1) and CRF(2) receptors bind urotensin I with approximately 8-fold higher affinity than rat/human CRF. These two peptides together with two related CRF-like peptides, namely, sauvagine and urocortin, were also tested in cAMP assays; for cells expressing the salmon CRF(1) receptor, EC(50) values for the stimulation of cAMP production were between 4.5+/-1.8 and 15.3+/-3.1 nM. For the salmon CRF(2) receptor, the corresponding values were: rat/human CRF, 9.4+/-0.4 nM; urotensin I, 21.2+/-2.1 nM; sauvagine, 0.7+/-0.1 nM; and urocortin, 2.2+/-0.7 nM. We have also functionally coupled the O. keta CRF(1) receptor, in Xenopus laevis oocytes, to the endogenous Ca(2+)-activated chloride conductance by co-expression with the G-protein alpha subunit, G(alpha16). The EC(50) value for channel activation by rat/human CRF (11.2+/-2.6 nM) agrees well with that obtained in cAMP assays (15.3+/-3.1 nM). We conclude that although sauvagine is 13- and 30-fold more potent than rat/human CRF and urotensin I, respectively, in activating the salmon CRF(2) receptor, neither receptor appears able to discriminate between the native ligands CRF and urotensin I.


Subject(s)
Oncorhynchus keta/genetics , Receptors, Corticotropin-Releasing Hormone/genetics , Amino Acid Sequence , Animals , Binding, Competitive/drug effects , Cell Line , Cloning, Molecular , Corticotropin-Releasing Hormone/metabolism , Corticotropin-Releasing Hormone/pharmacology , Cyclic AMP/metabolism , DNA, Complementary/chemistry , DNA, Complementary/genetics , Dose-Response Relationship, Drug , Female , Gene Expression , Humans , Male , Membrane Potentials/drug effects , Molecular Sequence Data , Oocytes , Phylogeny , RNA/genetics , RNA/metabolism , Rats , Receptors, Corticotropin-Releasing Hormone/drug effects , Receptors, Corticotropin-Releasing Hormone/metabolism , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Tissue Distribution , Urotensins/metabolism , Urotensins/pharmacology , Xenopus laevis
11.
Eur J Pharmacol ; 419(1): 1-7, 2001 May 04.
Article in English | MEDLINE | ID: mdl-11348623

ABSTRACT

The functional pharmacology of receptors composed of the chicken brain GABA(A) receptor gamma 4 subunit and the mammalian GABA(A) receptor alpha 3 and beta2 subunits was studied by heterologous expression in Xenopus laevis oocytes using the two electrode voltage-clamp technique. GABA-evoked currents had an EC(50) of 180+/-30 microM. Responses were blocked by the competitive and non-competitive GABA(A) receptor antagonists, bicuculline methochloride and picrotoxin. Sodium pentobarbital reversibly potentiated the current several-fold, and Zn(2+) ions blocked the current with high potency (IC50=20 microM). GABA-evoked currents were potentiated by the benzodiazepine site full agonists flunitrazepam and triazolam and less by the partial agonists abecarnil and bretazenil. The inverse agonists methyl-beta-carboline-3-carboxylate (beta-CCM) and methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) reduced the current. However, the imidazobenzodiazepine Ro 15-4513, which acts as an inverse agonist at mammalian alphaxbetaygamma2 GABA(A) receptors (where x=1, 2, 3 or 5, and y=1, 2 or 3), acted as a positive agonist at the gamma 4 subunit-containing receptors.


Subject(s)
GABA Modulators/pharmacology , Receptors, GABA-A/metabolism , Animals , Bicuculline/pharmacology , Brain Chemistry , Chickens , Dose-Response Relationship, Drug , GABA Agonists/pharmacology , GABA Antagonists/pharmacology , Humans , Oocytes/metabolism , Patch-Clamp Techniques , Pentobarbital/pharmacology , Picrotoxin/pharmacology , Protein Subunits , Receptors, GABA-A/chemistry , Receptors, GABA-A/genetics , Recombinant Proteins/metabolism , Xenopus laevis , Zinc/chemistry , Zinc/pharmacology , gamma-Aminobutyric Acid/pharmacology
13.
Lancet ; 355(9220): 2051-2, 2000 Jun 10.
Article in English | MEDLINE | ID: mdl-10885361

ABSTRACT

About 50% of UK patients with beta-thalassaemia major die before the age of 35 years, mainly because conventional iron-chelation therapy is too burdensome for full adherence. Patients require an individually-tailored treatment plan incorporating new, more tolerable approaches.


Subject(s)
Chelating Agents/therapeutic use , Chelation Therapy , Deferoxamine/therapeutic use , beta-Thalassemia/drug therapy , beta-Thalassemia/mortality , Adolescent , Adult , Child , Cohort Studies , Humans , Iron , Patient Compliance , Registries , Survival Analysis , United Kingdom/epidemiology
14.
BMJ ; 320(7231): 337-41, 2000 Feb 05.
Article in English | MEDLINE | ID: mdl-10657326

ABSTRACT

OBJECTIVE: National audit of informed choice in antenatal screening for thalassaemia. DESIGN: Audit from the UK Confidential Enquiry into Counselling for Genetic Disorders. SETTING: Thalassaemia module of the UK Confidential Enquiry into Counselling for Genetic Disorders. SUBJECTS: 138 of 156 couples who had had a pregnancy affected by a major beta thalassaemia from 1990 to 1994. MAIN OUTCOME MEASURES: How and when genetic risk was identified for each couple, and whether and when prenatal diagnosis was offered. RESULTS: Risk was detected by screening before or during the first pregnancy in 49% (68/138) of couples and by diagnosis of an affected child in 28% (38/138) of couples. Prenatal diagnosis was offered in 69% (274/400) of pregnancies, ranging from 94% (122/130) for British Cypriots to 54% (80/149) for British Pakistanis and from 90% in the south east of England to 39% in the West Midlands. Uptake of prenatal diagnosis was 80% (216/274), ranging from 98% (117/120) among British Cypriots in either the first or second trimester to 73% (35/48) among British Pakistanis in the first trimester and 39% (11/28) in the second trimester. A demonstrable service failure occurred in 28% (110/400) of pregnancies, including 110 of 126 where prenatal diagnosis was not offered and 48 of 93 that ended with an affected liveborn infant. CONCLUSION: Although antenatal screening and counselling for haemoglobin disorders are standard practices in the United Kingdom, they are delivered inadequately and inequitably. An explicit national policy is needed, aiming to make prenatal diagnosis in the first trimester available to all couples and including ongoing national audit.


Subject(s)
Genetic Services , Heterozygote , Informed Consent , Pregnancy Complications, Hematologic/diagnosis , Prenatal Diagnosis/methods , Thalassemia/genetics , Choice Behavior , Ethnicity , Female , Genetic Counseling , Genetic Testing/methods , Health Policy , Humans , Medical Audit , Patient Acceptance of Health Care , Pregnancy , Risk Factors , Stereotyping , Thalassemia/prevention & control , United Kingdom
15.
J Adv Nurs ; 31(1): 157-64, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10632804

ABSTRACT

The haemoglobin disorders are among the most common genetically inherited conditions within the United Kingdom. Individuals who are fully affected have severely impaired health while carriers may be faced with difficult reproductive decisions although generally they are well. Policy makers agree that counselling for families at risk should be undertaken in primary care settings and since the early 1980s this service has been undertaken mainly by specialist haemoglobinopathy nurse counsellors. Despite a number of government reports and recommendations for best practice, problems with service provision continue to be highlighted. However, there is little documented information about the work undertaken by the counsellors or how they perceive their role. A descriptive study was therefore conducted to fill this gap. It took the form of a questionnaire survey undertaken with 26 counsellors. The results were analysed by content and used to develop an interview schedule which was employed to obtain more detailed information from staff in four centres. The counsellors suggested that most of their time was spent in client-centred activities and most clients were first seen antenatally. However, there were significant barriers which prevented optimal service provision. These included: problems of communication with other health professionals, obtaining laboratory results crucial to the early identification of couples at risk, late referral from general practitioners and poor facilities for administration, especially maintaining computer databases essential for record keeping. Developing and obtaining written information suitable for families was particularly time-consuming.


Subject(s)
Genetic Counseling , Hemoglobinopathies/nursing , Clinical Competence/statistics & numerical data , Communication Barriers , Genetic Counseling/methods , Genetic Counseling/statistics & numerical data , Hemoglobinopathies/genetics , Heterozygote , Humans , Nurse-Patient Relations , Surveys and Questionnaires , Time Factors , United Kingdom , Workforce
16.
Biochim Biophys Acta ; 1447(2-3): 307-12, 1999 Oct 28.
Article in English | MEDLINE | ID: mdl-10542332

ABSTRACT

GABA(C) receptors mediate rapid inhibitory neurotransmission in retina. We have mapped, in detail, the human genes which encode the three polypeptides that comprise this receptor: rho1 (GABRR1), rho2 (GABRR2) and rho3 (GABRR3). We show that GABRR1 and GABRR2 are located close together, in a region of chromosome 6q that contains loci for inherited disorders of the eye, but that GABRR3 maps to chromosome 3q11-q13.3. Our mapping data suggest that the rho polypeptide genes, which are thought to share a common ancestor with GABA(A) receptor subunit genes, diverged at an early stage in the evolution of this gene family.


Subject(s)
Chromosomes, Human, Pair 3 , Receptors, GABA-B , Receptors, GABA/genetics , Amino Acid Sequence , Base Sequence , Chromosome Mapping , Genetic Linkage , Humans , Molecular Sequence Data , Receptors, GABA-A
19.
Trends Neurosci ; 22(2): 81-8, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10092048

ABSTRACT

It is now well established that neuropeptide receptors, which are present throughout the CNS and in peripheral tissues, frequently exist in a variety of different forms (called subtypes), each of which is encoded by a distinct gene. With the recent identification of new neuropeptide genes, it has become clear that families of neuropeptides also occur, which raises the possibility that specific peptide ligands activate particular receptor subtypes preferentially. This article reviews some of the recent advances in the neuropeptide field and provides evidence in support of three ideas: (1) that different receptor subtypes for a given ligand can be distinguished physiologically; (2) that neuropeptide genes probably arose before the corresponding receptor genes; and (3) that, despite the current wealth of information on neuropeptides and neuropeptide receptors, several new members are likely to be discovered before the beginning of the next millennium.


Subject(s)
Neuropeptides/genetics , Receptors, Neuropeptide/genetics , Animals , Biological Evolution , Isomerism , Neuropeptides/physiology , Receptors, Neuropeptide/physiology
20.
Eur J Pharmacol ; 354(2-3): 253-9, 1998 Aug 07.
Article in English | MEDLINE | ID: mdl-9754927

ABSTRACT

Chicken GABA(A) receptor beta4L and beta4S subunits were expressed in Xenopus oocytes by cRNA injection. Oocytes expressing either beta4 subunit alone or in combination with the chicken alpha1 subunit were studied using the two-electrode voltage-clamp technique. Both the beta4L and beta4S subunits form homomeric GABA-gated Cl- channels with similar efficiencies. In comparison, oocytes expressing either the chicken alpha1 or beta2S polypeptide show no or barely detectable GABA responses, as reported by others for most single-subunit vertebrate GABA(A) receptors. The GABA-gated currents due to the beta4L-subunit homomer were not affected by the presence of actinomycin D during cRNA expression, indicating that nascent oocyte polypeptides are not required for channel formation. The homomeric beta4L-subunit receptors show high affinity for GABA with an EC50 value of 4.3 +/- 0.4 microM and a Hill coefficient of 1.1 +/- 0.1 (n = 6). In response to GABA application at the EC25 value, currents elicited from the beta4L-subunit receptor are enhanced by 50 microM pentobarbital (110 +/- 10%, n = 3) and 10 microM loreclezole (60 +/- 3%, n = 3), inhibited by 10 microM picrotoxinin (93 +/- 3%, n = 3), but not affected by 1 microM diazepam. These properties are similar to those found for oocytes expressing heteromeric chicken alpha1beta4L and alpha1beta2S receptors. Since the beta subunits of GABA(A) receptors provide essential determinants for receptor assembly and subcellular localization, homomeric beta4-subunit receptors are a useful model system for further study of the structure and function of GABA(A) receptors.


Subject(s)
Oocytes/metabolism , Receptors, GABA-A/metabolism , Allosteric Regulation , Animals , Chickens , Dose-Response Relationship, Drug , Ion Channel Gating , Ion Channels/metabolism , Patch-Clamp Techniques , Receptors, GABA-A/biosynthesis , Receptors, GABA-A/genetics , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Xenopus , gamma-Aminobutyric Acid/metabolism
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