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1.
J Dent Res ; : 220345221128226, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36314491

RESUMO

Patients with persistent orofacial pain (POFP) can go through complex care pathways to receive a diagnosis and management, which can negatively affect their pain. This study aimed to describe 44-y trends in attendances at Welsh medical practices for POFP and establish the number of attendances per patient and referrals associated with orofacial pain and factors that may predict whether a patient is referred. A retrospective observational study was completed using the nationwide Secure Anonymised Information Linkage Databank of visits to general medical practices in Wales (UK). Data were extracted using diagnostic codes ("Read codes"). Orofacial and migraine Read codes were extracted between 1974 and 2017. Data were analyzed using descriptive statistics and univariate and multivariable logistic regression. Over the 44-y period, there were 468,827 POFP and migraine diagnostic codes, accounting for 468,137 patient attendances, or 301,832 patients. The overall attendance rate was 4.22 attendances per 1,000 patient-years (95% confidence interval [CI], 4.21-4.23). The attendance rate increased over the study period. Almost one-third of patients (n = 92,192, 30.54%) attended more than once over the study period, and 15.83% attended more than once within a 12-mo period. There were 20,103 referral codes that were associated with 8,183 patients, with over half these patients being referred more than once. Odds of receiving a referral were highest in females (odds ratio [OR], 1.23; 95% CI, 1.17-1.29), in those living in rural locations (OR, 1.17; 95% CI, 1.12-1.22), and in the least deprived quintile (OR, 1.39; 95% CI, 1.29-1.48). Odds also increased with increasing age (OR, 1.03; 95% CI, 1.03-1.03). The increasing attendance may be explained by the increasing incidence of POFP within the population. These patients can attend on a repeated basis, and very few are referred, but when they are, this may occur multiple times; therefore, current care pathways could be improved.

2.
J Dent Res ; 101(4): 407-413, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34582311

RESUMO

One-third of the UK population is composed of problem-oriented dental attenders, seeking dental care only when they have acute dental pain or problems. Patients seek urgent dental care from a range of health care professionals, including general medical practitioners. This study aimed to identify trends in dental attendance at Welsh medical practices over a 44-y period, specifically in relation to dental policy change and factors associated with repeat attendance. A retrospective observational study was completed via the nationwide Secure Anonymised Information Linkage (SAIL) Databank of visits to general medical practice in Wales. Read codes associated with dental diagnoses were extracted for patients attending their general medical practitioner between 1974 and 2017. Data were analyzed with descriptive statistics and univariate and multivariable logistic regression. Over the 44-y period, there were 439,361 dental Read codes, accounting for 288,147 patient attendances. The overall attendance rate was 2.60 attendances per 1,000 patient-years (95% CI, 2.59 to 2.61). The attendance rate was negligible through 1987 but increased sharply to 5.0 per 1,000 patient-years in 2006 (95% CI, 4.94 to 5.09) before almost halving to 2.6 per 1,000 in 2017 (95% CI, 2.53 to 2.63) to a pattern that coincided with changes to National Health Service policies. Overall 26,312 patients were repeat attenders and were associated with living in an area classified as urban and deprived (odds ratio [OR], 1.22; 95% CI, 1.19 to 1.25; P < 0.0001) or rural (OR, 0.84; 95% CI, 0.83 to 0.85; P < 0.0001). Repeat attendance was associated with greater odds of having received an antibiotic prescription (OR, 2.53; 95% CI, 2.50 to 2.56; P < 0.0001) but lower odds of having been referred to another service (OR, 0.75; 95% CI, 0.70 to 0.81; P < 0.0001). Welsh patients' reliance on medical care for dental problems was influenced by social deprivation and health policy. This indicates that future interventions to discourage dental attendance at medical practitioners should be targeted at those in the most deprived urban areas or rural areas. In addition, health policy may influence attendance rates positively and negatively and should be considered in the future when decisions related to policy change are made.


Assuntos
Encaminhamento e Consulta , Medicina Estatal , Pessoal de Saúde , Humanos , Estudos Retrospectivos , País de Gales/epidemiologia
3.
Int Endod J ; 52(3): 279-287, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30229950

RESUMO

AIM: To develop and preliminarily evaluate a new screening instrument for atypical odontalgia (AO) or persistent dentoalveolar pain disorder (PDAP). To evaluate the instrument's performance in detecting AO/PDAP amongst a heterogeneous group of orofacial pain conditions and pain-free controls and empirically compare its performance with an established neuropathic screening instrument (S-LANSS), which is the best available standard. METHODS: The study design was cross-sectional; subjects recruited included a convenience sample of pain-free controls (n = 21) and four groups of orofacial pain conditions: AO/PDAP (n = 22); trigeminal neuralgia (n = 21); temporomandibular disorder (n = 41); and acute dental pain (n = 41). The instrument's internal reliability and factor structure were examined alongside its sensitivity and specificity and ROC-determined threshold score. RESULTS: The 9 AO/PDAP-specific items were found to moderately correlate with the S-LANSS (r = 0.58; P < 0.01). The 14-items of the full instrument were examined using exploratory factor analysis and reduced to ten items in a two-factor structure that explained 96% of the variance. This 10-item final instrument had a ROC area of 0.77 (95% CI: 0.67; 0.88), sensitivity of 77% (95% CI: 55; 92%), and specificity of 69% (95% CI: 60; 77%) with an intentionally higher false-positive rate than false-negative rate. In contrast, the S-LANSS exhibited sensitivity of 32% (95% CI: 14;55%) and specificity of 78% (95% CI: 70;85%) with less optimal false-positive versus false-negative rates. CONCLUSION: This preliminary study confirms the new screening instrument for AO/PDAP merits progression to field testing.


Assuntos
Medição da Dor/métodos , Transtornos da Articulação Temporomandibular/diagnóstico , Odontalgia/diagnóstico , Neuralgia do Trigêmeo/diagnóstico , Estudos Transversais , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Minnesota , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
4.
J Oral Rehabil ; 44(2): 105-111, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27896841

RESUMO

The aim of this study was to examine the number of patients attending a medical emergency department (MED) with dental problems over a three-year period. This cross-sectional study was carried out as part of a service evaluation. Data were collected via a database search of patient attendances at the MED using free text and the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) for oral and dental diagnoses. Data were analysed using descriptive statistics, t-test and chi-squared tests. Over the three-year period, there were 2504 visits to the MED for dental-related complaints, accounting for 0·7% of all attendances. The majority of patients were male (53·9%), with a mean age of 29 (s.d. 19·4) years for men, and 32 (s.d. 19·7) years for females. The mean index of multiple deprivation per cent rank was 35·0%. The most common diagnosis was unspecified dental disorder. Ten per cent of dental attendances to MED were repeat attendances by the same patients. In conclusion, patient attendances at MED for dental problems account for 0.7% of all attendances. MED may not be the most appropriate place for these patients to attend, in terms of care pathways, and also for economic reasons. The reasons why patients attend MED for dental problems clearly warrant further research.


Assuntos
Doença Aguda/epidemiologia , Assistência Odontológica/estatística & dados numéricos , Emergências , Serviço Hospitalar de Emergência/estatística & dados numéricos , Odontalgia/diagnóstico , Doença Aguda/economia , Adulto , Estudos Transversais , Assistência Odontológica/economia , Emergências/economia , Emergências/epidemiologia , Serviço Hospitalar de Emergência/economia , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Fatores Socioeconômicos , Odontalgia/economia , Odontalgia/epidemiologia
5.
J Oral Rehabil ; 42(12): 883-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26174692

RESUMO

One-third of the population will only attend the dentist for an acute problem, often waiting a period of time before presenting. The objective of this study was to investigate the levels of pain in patients presenting for a dental emergency and the impact this had on their quality of life. Questionnaires were provided to adult patients attending dental emergency services over 1 week. Demographic and clinical details were collected. Quality of life was measured using EQ-5D-5L. Pain and the interference it caused were examined using the graded chronic pain scale. Data were analysed in STATA using descriptive statistics, Mann-Whitney and chi-squared tests. Results showed that majority of patients (64%) seen were male; the mean age was 36 (±14) years. Forty six per cent of patients reported having a general dental practitioner. One-third of the patients had attended this service previously for emergency care, and 13% consulted for the same problem. The mean duration of pain was 17·7 (±52·3) days prior to seeking care. The mean characteristic pain intensity was 53·6 (±23·6). The mean disability score was 43·4 (±33·6). The mean EQ-5D-5L score was 0·57 (±0·27). In conclusion, a large number of patients attend the emergency dental services despite being 'registered' with a general dental practitioner. A proportion of these individuals will re-attend for the same condition. Patients will often be in pain for over 2 weeks before attending, which may have a significant impact on their quality of life. Further research is warranted to investigate these care-seeking behaviours and patterns.


Assuntos
Assistência Odontológica , Emergências , Doença Aguda , Adulto , Estudos Transversais , Inglaterra , Feminino , Humanos , Masculino , Medição da Dor , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários
6.
Br Dent J ; 216(11): E23, 2014 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-24923961

RESUMO

OBJECTIVES: To explore general dental practitioners' opinions about continuing professional development (CPD) and potential barriers to translating research findings into clinical dental practice. DESIGN: Qualitative focus group and interviews. SUBJECTS, SETTING AND METHODS: Four semi-structured interviews and a single focus group were conducted with 11 general dental practitioners in North East England. OUTCOME MEASURE: Transcripts were analysed using the constant comparative method to identify emergent themes. RESULTS: The key theme for practitioners was a need to interact with colleagues in order to make informed decisions on a range of clinical issues. For some forms of continuing professional development the value for money and subsequent impact upon clinical practice was limited. There were significant practice pressures that constrained the ability of practitioners to participate in certain educational activities. The relevance of some research findings and the formats used for their dissemination were often identified as barriers to their implementation in general dental practice. CONCLUSIONS: There are a number of potential barriers that exist in general dental practice to the uptake and implementation of translational research. CPD plays a pivotal role in this process and if new methods of CPD are to be developed consideration should be given to include elements of structured content and peer review that engages practitioners in a way that promotes implementation of contemporary research findings.


Assuntos
Odontólogos/psicologia , Educação Continuada em Odontologia/organização & administração , Odontologia Geral/organização & administração , Atitude do Pessoal de Saúde , Pesquisa em Odontologia , Inglaterra , Grupos Focais , Humanos
7.
J Laryngol Otol ; 126(8): 851-3, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22642940

RESUMO

OBJECTIVES: We report a case of an internal carotid artery aneurysm presenting as orofacial pain. METHOD: Case report and discussion. RESULTS: A 59-year-old patient presented with a four-year history of chronic oral pain accompanied by a right-sided occipital headache. No local organic pathology was detected, and a provisional diagnosis of persistent idiopathic facial pain was made. A neurosurgery referral was made to exclude neurovascular pathology, which resulted in the detection of an aneurysm originating from the right posterior communicating artery. This was successfully treated by coil embolisation, with subsequent resolution of symptoms. CONCLUSION: In this patient, an atypical history of pain with no other neurological signs or symptoms, other than accompanying occipital headache, led to the discovery of an intracranial aneurysm. This case highlights the need for appropriate referral and imaging in cases in which the clinical history and findings are not classical, and also emphasises the need for interdisciplinary management.


Assuntos
Doenças das Artérias Carótidas/diagnóstico , Artéria Carótida Interna/diagnóstico por imagem , Dor Facial/etiologia , Cefaleia/etiologia , Aneurisma Intracraniano/diagnóstico , Doenças das Artérias Carótidas/complicações , Diagnóstico por Imagem , Feminino , Humanos , Aneurisma Intracraniano/complicações , Pessoa de Meia-Idade , Radiografia , Nervo Trigêmeo/patologia
8.
J Biol Chem ; 276(42): 38870-6, 2001 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-11481335

RESUMO

Studies involving the cloning and disruption of the gene for acyl-CoA:diacylglycerol acyltransferase (DGAT) have shown that alternative mechanisms exist for triglyceride synthesis. In this study, we cloned and characterized a second mammalian DGAT, DGAT2, which was identified by its homology to a DGAT in the fungus Mortierella rammaniana. DGAT2 is a member of a gene family that has no homology with DGAT1 and includes several mouse and human homologues that are candidates for additional DGAT genes. The expression of DGAT2 in insect cells stimulated triglyceride synthesis 6-fold in assays with cellular membranes, and DGAT2 activity was dependent on the presence of fatty acyl-CoA and diacylglycerol, indicating that this protein is a DGAT. Activity was not observed for acyl acceptors other than diacylglycerol. DGAT2 activity was inhibited by a high concentration (100 mm) of MgCl(2) in an in vitro assay, a characteristic that distinguishes DGAT2 from DGAT1. DGAT2 is expressed in many tissues with high expression levels in the liver and white adipose tissue, suggesting that it may play a significant role in mammalian triglyceride metabolism.


Assuntos
Aciltransferases/classificação , Aciltransferases/genética , Células 3T3 , Aciltransferases/química , Tecido Adiposo/metabolismo , Sequência de Aminoácidos , Animais , Northern Blotting , Diferenciação Celular , Linhagem Celular , Células Cultivadas , Clonagem Molecular , DNA Complementar/metabolismo , Bases de Dados como Assunto , Diacilglicerol O-Aciltransferase , Relação Dose-Resposta a Droga , Eletroforese em Gel de Poliacrilamida , Insetos , Cinética , Fígado/metabolismo , Cloreto de Magnésio/farmacologia , Camundongos , Dados de Sequência Molecular , Mortierella/enzimologia , Família Multigênica , Filogenia , Ligação Proteica , Homologia de Sequência de Aminoácidos , Fatores de Tempo , Distribuição Tecidual , Triglicerídeos/biossíntese
9.
J Biol Chem ; 276(11): 8205-12, 2001 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-11084049

RESUMO

In mammalian cells, phosphatidylserine is synthesized by two different enzymes, phosphatidylserine synthase (PSS)-1 and -2, via a base exchange reaction in which the head group of a phospholipid (phosphatidylcholine or phosphatidylethanolamine) is replaced by l-serine. Since the amino acid sequences of PSS1 and PSS2 are only approximately 30% identical, it is likely that they are encoded by different genes. We have screened a murine liver genomic DNA library, included in bacterial artificial chromosomes, with full-length murine PSS1 cDNA and isolated a clone containing the majority of the PSS1 gene. This gene spans approximately 35 kilobases and contains 13 exons and 12 introns. The sizes of the exons range from 44 to 1035 base pairs. The gene was localized to chromosome 13 in region B-C1. According to reverse transcriptase-mediated polymerase chain reaction, PSS1 and PSS2 mRNAs were expressed in all murine tissues examined. The mRNA encoding PSS1 was most abundant in kidney, brain, and liver, whereas PSS2 mRNA was most highly expressed in testis. In general agreement with the levels of mRNA expression, the choline exchange activity (contributed by PSS1, but not PSS2) was highest in brain, whereas serine and ethanolamine exchange activities were highest in testis and kidney. The transcriptional initiation site for PSS1 was identified 111 base pairs upstream of the ATG specifying the start of translation. The putative 5'-proximal promoter region of the gene contained no TATA or CAAT box, but did have a high GC content. Isolation of the murine PSS1 gene is a step toward generation of genetically modified mouse models that will help to understand the functions of PSS1 and PSS2 in animal biology.


Assuntos
Transferases de Grupos Nitrogenados/genética , Animais , Sequência de Bases , Mapeamento Cromossômico , Clonagem Molecular , DNA Complementar/química , Éxons , Íntrons , Camundongos , Dados de Sequência Molecular , Transferases de Grupos Nitrogenados/análise , Transferases de Grupos Nitrogenados/química , Regiões Promotoras Genéticas , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Genética
10.
J Biol Chem ; 275(44): 34534-40, 2000 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-10938271

RESUMO

We report the subcellular localization of enzymes involved in phosphatidylserine biosynthesis in mammalian cells. Several lines of evidence suggest that phosphatidylserine synthase-1 (PSS1) is highly enriched in mitochondria-associated membranes (MAM) and is largely excluded from the bulk of the endoplasmic reticulum (ER). Taking advantage of the substrate specificity of PSS1, we showed that (i) MAM contain choline exchange activity, whereas this activity is very low in the bulk of the ER, (ii) serine exchange activity is inhibited by choline to a much greater extent in MAM than in ER, and (iii) MAM use phosphatidylcholine and phosphatidylethanolamine as substrates for phosphatidylserine biosynthesis, whereas the ER utilizes only phosphatidylethanolamine. According to immunoblotting of proteins from both CHO-K1 cells and murine liver, PSS1 is localized to MAM, and in hepatoma cells stably expressing PSS1 this protein is highly enriched in MAM. Since the ER contains serine and ethanolamine exchange activities, we had predicted that PSS2 would account for the serine exchange activity in the ER. Unexpectedly, using immunoblotting experiments, we found that (i) PSS2 of CHO-K1 cells is present only in MAM and (ii) PSS2 is restricted to MAM of McArdle cells expressing recombinant PSS2. These data leave open the question of which enzyme imparts PSS activity to the ER and suggest that a third isoform of PSS might be located in the ER.


Assuntos
Membranas Intracelulares/enzimologia , Mitocôndrias/enzimologia , Transferases de Grupos Nitrogenados/metabolismo , Sequência de Aminoácidos , Animais , Western Blotting , Células CHO , Cricetinae , Retículo Endoplasmático/enzimologia , Camundongos , Microscopia de Fluorescência , Tripsina/metabolismo , Células Tumorais Cultivadas
11.
AACN Clin Issues ; 11(4): 517-30, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11288416

RESUMO

Postpyloric placement of feeding tubes into the duodenum or jejunum is often recommended to support early feeding, improve tolerance of enteral nutrition, and decrease the risk of aspiration pneumonia. Achieving small bowel feeding tube placement can be a difficult, time-consuming, and costly process that may delay the initiation of enteral nutrition. Various bedside techniques, including air insufflation, pH assisted, and spontaneous passage with or without motility agents are available to facilitate transpyloric feeding tube passage. A discussion of these methods is presented in this article, including a hospital-based quality initiative project designed to facilitate early enteral nutrition.


Assuntos
Cuidados Críticos/métodos , Nutrição Enteral/métodos , Nutrição Enteral/enfermagem , Doença Aguda/enfermagem , Duodeno , Humanos , Piloro
12.
Biochem J ; 342 ( Pt 1): 57-64, 1999 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-10432300

RESUMO

Phosphatidylserine (PtdSer) is synthesized in mammalian cells by two base-exchange enzymes: PtdSer synthase (PSS)-1 primarily uses phosphatidylcholine as a substrate for exchange with serine, whereas PSS2 uses phosphatidylethanolamine (PtdEtn). We previously expressed murine PSS1 in McArdle hepatoma cells. The activity of PSS1 in vitro and the synthesis of PtdSer and PtdSer-derived PtdEtn were increased, whereas PtdEtn synthesis from the CDP-ethanolamine pathway was inhibited [Stone, Cui and Vance (1998) J. Biol. Chem. 273, 7293-7302]. We have now cloned and stably expressed a murine PSS2 cDNA in McArdle cells and M.9.1.1 cells [which are ethanolamine-requiring mutant Chinese hamster ovary (CHO) cells defective in PSS1]. Expression of the PSS2 in M.9.1.1 cells reversed the ethanolamine auxotrophy. However, the PtdEtn content was not normalized unless the culture medium was supplemented with ethanolamine. In both M.9.1.1 and hepatoma cells transfected with PSS2 cDNA the rate of synthesis of PtdSer and PtdSer-derived PtdEtn did not exceed that in parental CHO cells or control McArdle cells respectively, in contrast to cells expressing similar levels of murine PSS1. These observations suggest that PtdSer synthesis via murine PSS2, but not PSS1, is regulated by end-product inhibition. Moreover, expression of murine PSS2 in McArdle cells did not inhibit PtdEtn synthesis via the CDP-ethanolamine pathway, whereas expression of similar levels of PSS1 activity inhibited this pathway by approx. 50%. We conclude that murine PSS1 and PSS2, which are apparently derived from different genes, independently modulate phospholipid metabolism. In addition, mRNAs encoding the two synthases are differentially expressed in several murine tissues, supporting the idea that PSS1 and PSS2 might perform unique functions.


Assuntos
CDPdiacilglicerol-Serina O-Fosfatidiltransferase/genética , CDPdiacilglicerol-Serina O-Fosfatidiltransferase/metabolismo , Regulação Enzimológica da Expressão Gênica , Fígado/enzimologia , Fosfolipídeos/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , CDPdiacilglicerol-Serina O-Fosfatidiltransferase/química , Células CHO , Divisão Celular , Clonagem Molecular , Cricetinae , Cistina Difosfato/análogos & derivados , Cistina Difosfato/metabolismo , Etanolaminas/metabolismo , Cinética , Fígado/citologia , Fígado/metabolismo , Camundongos , Dados de Sequência Molecular , Mutação , Fosfatidiletanolaminas/metabolismo , Fosfatidilserinas/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/genética , Ratos , Serina/metabolismo , Células Tumorais Cultivadas
13.
J Biol Chem ; 273(13): 7293-302, 1998 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-9516423

RESUMO

In eukaryotic cells, phosphatidylserine (PtdSer) is synthesized by two distinct synthases on the endoplasmic reticulum by a base-exchange reaction in which the polar head-group of an existing phospholipid is replaced with serine. We report the cloning and expression of a cDNA for mouse liver PtdSer synthase-1. The deduced protein sequence is >90% identical to that of PtdSer synthase-1 from Chinese hamster ovary cells and a sequence from a human myeloblast cell line. PtdSer synthase-1 cDNA was stably expressed in M.9.1.1 cells which are mutant Chinese hamster ovary cells defective in PtdSer synthase-1 activity, are ethanolamine auxotrophs, and have a reduced content of PtdSer and phosphatidylethanolamine (PtdEtn). The growth defect of M.9.1.1 cells was eliminated, and a normal phospholipid composition was restored in the absence of exogenous ethanolamine, implying that the cloned cDNA encoded PtdSer synthase. Mouse liver PtdSer synthase-1 was also expressed in McArdle 7777 rat hepatoma cells. In addition to a 3-fold higher in vitro serine-exchange activity, these cells also exhibited enhanced choline- and ethanolamine-exchange activities and incorporated more [3H]serine into PtdSer than did control cells. However, the levels of PtdSer and PtdEtn in cells overexpressing PtdSer synthase-1 activity were not increased. Excess PtdSer produced by the transfected cells was rapidly decarboxylated to PtdEtn and the degradation of PtdSer, and/or PtdEtn derived from PtdSer, was increased. Moreover, the CDP-ethanolamine pathway for PtdEtn biosynthesis was inhibited. These data suggest that (i) cellular levels of PtdSer and PtdEtn are tightly controlled, and (ii) the metabolism of PtdSer and PtdEtn is coordinately regulated to maintain phospholipid homeostasis.


Assuntos
Cistina Difosfato/análogos & derivados , Etanolaminas/metabolismo , Fígado/enzimologia , Proteínas de Membrana/genética , Transferases de Grupos Nitrogenados/genética , Fosfatidiletanolaminas/biossíntese , Fosfatidilserinas/biossíntese , Sequência de Aminoácidos , Animais , Sequência de Bases , Células CHO , Carcinoma Hepatocelular , Clonagem Molecular , Cricetinae , Cistina Difosfato/metabolismo , DNA Complementar/química , DNA Complementar/isolamento & purificação , Regulação Enzimológica da Expressão Gênica , Humanos , Camundongos , Dados de Sequência Molecular , Ratos , Serina/metabolismo , Células Tumorais Cultivadas
14.
Biochim Biophys Acta ; 1344(3): 286-99, 1997 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-9059519

RESUMO

Endoplasmic reticulum-like membranes (MAM) that are associated with mitochondria have been implicated as intermediates in the import of lipids, particularly phosphatidylserine, from the endoplasmic reticulum to mitochondria (Vance, J.E. (1990) J. Biol. Chem. 265, 7248-7256; Shiao, Y.-J. et al. (1995) J. Biol. Chem. 270, 11190-11198). We have now examined further the role of MAM in lipid metabolism using the mnd/mnd mouse, a model for the human degenerative disease neuronal ceroid lipofuscinosis. The biochemical phenotype of the mnd/mnd mutant mouse (in which lipids and proteins accumulate abnormally in storage bodies in cells of affected tissues) suggested that the mutation might lead to impaired mitochondrial import of lipids and proteins as a result of a defective linkage between MAM and mitochondria. We, therefore, investigated the status of MAM and phospholipid metabolism in mnd/mnd mice livers. Separation of MAM from livers of older, but not younger, mnd/mnd mice was aberrant. In addition, the amount of the MAM-specific protein, phosphatidylethanolamine N-methyltransferase-2 (PEMT2), was greatly reduced in homogenates and MAM from livers of mnd/mnd mice of all ages, although PEMT2 mRNA abundance was normal. Moreover, PEMT activity in MAM from mnd/mnd mice was 60% less than in control mice. Activities of two additional phospholipid biosynthetic enzymes-CTP:phosphocholine cytidylyltransferase and phosphatidylserine synthase-were also reduced by > 50% in mnd/mnd microsomes. Radiolabeling experiments in hepatocytes indicated that neither the mitochondrial import nor the subsequent metabolism of phosphatidylserine was grossly affected in mnd/mnd mice. However, 3 proteins (cytochrome b5, NADH:cytochrome b5 reductase and mitochondrial F1Fzero-ATP synthase c subunit) which are normally present in mitochondria were partially redistributed to microsomes in mnd/mnd mouse liver. These studies indicate that MAM are defective in the mnd/mnd mutant mouse in which the biochemical phenotype includes an abnormal accumulation of lipids and proteins in storage bodies.


Assuntos
Membranas Intracelulares/enzimologia , Mitocôndrias Hepáticas/enzimologia , Lipofuscinoses Ceroides Neuronais/enzimologia , Lipofuscinoses Ceroides Neuronais/patologia , Transferases de Grupos Nitrogenados , Fosfolipídeos/biossíntese , Animais , Fracionamento Celular , Diacilglicerol Colinofosfotransferase/metabolismo , Modelos Animais de Doenças , Etanolaminofosfotransferase/metabolismo , Humanos , Membranas Intracelulares/ultraestrutura , Lipídeos/biossíntese , Fígado/enzimologia , Metiltransferases/metabolismo , Camundongos , Camundongos Mutantes , Mitocôndrias Hepáticas/ultraestrutura , Fosfatidiletanolamina N-Metiltransferase , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Frações Subcelulares/enzimologia , Transferases/metabolismo
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