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1.
Pediatr Obes ; 12(1): e1-e5, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-26843446

RESUMO

BACKGROUND: Investigations on sugar-sweetened beverage (SSB) intake and cardiometabolic risks among Asians are scant. OBJECTIVES: This study aimed to examine associations between SSB intake and cardiometabolic risks among Malaysian adolescents. METHODS: Anthropometric data, blood pressure (BP), fasting blood glucose (FBG), lipid profiles and insulin levels measured involved 873 adolescents (aged 13 years). SSB intake, dietary patterns and physical activity level (PAL) were self-reported. RESULTS: Mean SSB consumption was 177.5 mL day-1 with significant differences among ethnicities (Malay, Chinese, Indians and Others) (p < 0.05). SSB intake was deleteriously associated with increased waist circumference, elevated triglycerides, FBG, insulin, insulin resistance and low HDL-cholesterol, independent of PAL, body mass index and dietary patterns. Significant U-shaped and inverse trends were noted between SSB intake and LDL-cholesterol and BP, respectively. CONCLUSION: Sugar-sweetened beverage intake was unfavourably associated with cardiometabolic health outcomes among young adolescents. Concerted efforts towards healthy hydration are imperative to mitigate risk of cardiometabolic events.


Assuntos
Bebidas/efeitos adversos , Sacarose Alimentar/efeitos adversos , Comportamento Alimentar , Síndrome Metabólica/etiologia , Adolescente , Antropometria , Glicemia/análise , Pressão Sanguínea , Estudos Transversais , Exercício Físico , Feminino , Humanos , Insulina/sangue , Lipídeos/sangue , Malásia , Masculino , Síndrome Metabólica/epidemiologia , Fatores de Risco
2.
Child Care Health Dev ; 41(6): 1216-26, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25873448

RESUMO

BACKGROUND: Physical functioning and psychological resilience in adulthood is shaped during adolescence. Self-reported health-related quality of life (HRQoL) assessments during this life phase are important first-hand accounts of their well-being. This study aimed, firstly, to identify differences in HRQoL according to gender, ethnicity, socio-economic status and weight status; and secondly, to examine associations between weight status and HRQoL among an urban sample of multi-ethnic adolescents in Kuala Lumpur, Malaysia. METHODS: A cross-sectional study involving 652 adolescents (aged 13 years) was conducted in Kuala Lumpur. Weight and height were measured. Body mass index z-scores were categorized according to the International Obesity Task Force criteria. HRQoL was assessed using the Malay version of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales. Univariate analyses of differences in HRQoL according to gender, ethnicity (Malays, Chinese and Indians), maternal education level and weight status were performed. Complex samples general linear model was used to examine the associations between HRQoL and weight status, adjusted for confounders. RESULTS: Female adolescents reported significantly lower emotional functioning scores (mean, 95% confidence interval: 59.25, 57.33-61.17). When the three main ethnic groups were studied, Malay adolescents scored significantly lower emotional functioning scores (59.00, 57.13-60.87) compared with their Chinese peers. Adolescents with tertiary-educated mothers reported lower emotional functioning scores (57.45, 53.85-61.06) compared with those with primary-educated mothers. Obese adolescents reported poorer HRQoL scores with significantly impaired physical and social functioning after controlling for confounders. CONCLUSIONS: These findings detected disparities in HRQoL among the adolescents when gender, ethnicity, maternal education level and weight status were considered. Further studies should address these health inequalities by implementing gender-specific and culturally appropriate measures to attain optimal well-being and avoid potential burden of disease.


Assuntos
Disparidades nos Níveis de Saúde , Qualidade de Vida , Adolescente , Peso Corporal , Estudos Transversais , Países em Desenvolvimento , Etnicidade , Feminino , Humanos , Malásia , Masculino , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos , População Urbana
3.
J Biol Rhythms ; 29(5): 355-69, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25252712

RESUMO

The female reproductive cycle is gated by the circadian timing system and may be vulnerable to disruptions in the circadian system. Prior work suggests that vasoactive intestinal peptide (VIP)-expressing neurons in the suprachiasmatic nucleus (SCN) are one pathway by which the circadian clock can influence the estrous cycle, but the impact of the loss of this peptide on reproduction has not been assessed. In the present study, we first examine the impact of the genetic loss of the neuropeptide VIP on the reproductive success of female mice. Significantly, mutant females produce about half the offspring of their wild-type sisters even when mated to the same males. We also find that VIP-deficient females exhibit a disrupted estrous cycle; that is, ovulation occurs less frequently and results in the release of fewer oocytes compared with controls. Circadian rhythms of wheel-running activity are disrupted in the female mutant mice, as is the spontaneous electrical activity of dorsal SCN neurons. On a molecular level, the VIP-deficient SCN tissue exhibits lower amplitude oscillations with altered phase relationships between the SCN and peripheral oscillators as measured by PER2-driven bioluminescence. The simplest explanation of our data is that the loss of VIP results in a weakened SCN oscillator, which reduces the synchronization of the female circadian system. These results clarify one of the mechanisms by which disruption of the circadian system reduces female reproductive success.


Assuntos
Ritmo Circadiano/fisiologia , Ciclo Estral/fisiologia , Reprodução/fisiologia , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Neuropeptídeos/metabolismo , Proteínas Circadianas Period/metabolismo , Núcleo Supraquiasmático/metabolismo , Núcleo Supraquiasmático/fisiologia
4.
Transplant Proc ; 46(5): 1371-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24836837

RESUMO

There are few reports about the quality of life (QOL) and morbidities of pediatric living donor liver transplantation (LDLT) donors. We evaluated the potential morbidities and identified the predictive factors regarding the QOL of living donors after pediatric LDLT. This cross-sectional study was a single-center analysis of 100 donors for pediatric LDLT. The severity of morbidities was assessed with the Clavien classification, the QOL was investigated with the short form-36 (SF-36), and the decision-making process regarding donation was analyzed with questionnaires. The median follow-up period was 3.8 years (range, 2.2-6.0 years). A total of 13% of the donors developed postoperative complications of Clavien grades I (7%), II (3%), and IIIA (3%). There was no grade IV morbidity or mortality. Eighty-one donors responded to the questionnaire and SF-36. The analysis of the questionnaires revealed that the donors had difficulty in the decision-making process, and suggested that it may be necessary to administer multistep informed consent. We identified unique predictive risk factors for lower SF-36 scores in the donors, which were the time to donation (more than 4 weeks) and the predonation self-oriented perception. The donors who have risk factors require enhanced pre- and post-donation psychological care.


Assuntos
Transplante de Fígado , Doadores Vivos , Qualidade de Vida , Adulto , Criança , Estudos Transversais , Humanos , Resultado do Tratamento
5.
Artigo em Inglês | MEDLINE | ID: mdl-25571430

RESUMO

Orientation of human body segments is an important quantity in many biomechanical analyses. To get robust and drift-free 3-D orientation, raw data from miniature body worn MEMS-based inertial measurement units (IMU) should be blended in a Kalman filter. Aiming at less computational cost, this work presents a novel cascaded two-step Kalman filter orientation estimation algorithm. Tilt angles are estimated in the first step of the proposed cascaded Kalman filter. The estimated tilt angles are passed to the second step of the filter for yaw angle calculation. The orientation results are benchmarked against the ones from a highly accurate tactical grade IMU. Experimental results reveal that the proposed algorithm provides robust orientation estimation in both kinematically and magnetically disturbed conditions.


Assuntos
Algoritmos , Corpo Humano , Sistemas Microeletromecânicos/métodos , Orientação , Aceleração , Fenômenos Biomecânicos , Humanos , Locomoção
7.
Transplant Proc ; 44(5): 1373-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22664018

RESUMO

AIM: Vascular complications (VC) are a major cause of significant morbidity and mortality in pediatric liver transplantation (LT). We reviewed our series to study the evolution of vascular reconstructions and its effect on the incidence of VC after LT, particularly with regard to the portal vein (PV). METHODS: The medical records of 81 pediatric LT performed in 76 children (38 boys) from 1991 to 2010 in the National University Hospital, Singapore, were reviewed to identify VC pertaining to PV, hepatic artery (HA), and hepatic veins (HV) and to analyse the data for the entire series and in 2 consecutive cohorts: initial 40 LT (group 1) and subsequent 41 LT (group 2). Specific interventions in group 2 were characterized by surgical innovations for reconstruction of the difficult PV and routine use of Doppler ultrasound intraoperatively and postoperatively. RESULTS: The overall incidence of VC was 19.7% (n = 16) and individually HA thrombosis 4.9% (n = 4), HA stenosis 1.2% (n = 1), PV thrombosis 12.3% (n = 9), PV stenosis 1.2% (n = 1), and HV thrombosis 1.2% (n = 1). The overall 1- and 5-year survival rates in our series were 89% and 85%, respectively. The 1- and 5-year survival rates in patients with and without VC were 81.25% and 68.75% and 90.8% and 89.2%, respectively. The incidence of VC decreased from 27.5% in group 1 to 12.1% in group 2 (p = .08). The major contribution to this appears to be a decrease in PV complications from 17.5% in group 1 to 7.3% in group 2 (P = .1). The incidence of HA (3 vs 2) and HV (1 vs 0) complications was similar between the 2 groups. CONCLUSIONS: Vascular reconstructions in small recipients are technically challenging and associated with a learning curve. Application of meticulous techniques in general, surgical innovations to the difficult PV in particular and attention to postoperative monitoring contribute toward a major reduction in VC.


Assuntos
Arteriopatias Oclusivas/etiologia , Artéria Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Veia Porta/cirurgia , Trombose/etiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Trombose Venosa/etiologia , Adolescente , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/mortalidade , Pré-Escolar , Competência Clínica , Constrição Patológica , Feminino , Humanos , Lactente , Curva de Aprendizado , Transplante de Fígado/mortalidade , Masculino , Singapura , Trombose/diagnóstico , Trombose/mortalidade , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler , Procedimentos Cirúrgicos Vasculares/mortalidade , Trombose Venosa/diagnóstico , Trombose Venosa/mortalidade
8.
Pediatr Transplant ; 16(4): E120-4, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21834802

RESUMO

PV thrombosis is not an uncommon occurrence following pediatric LT. Symptomatic PHT following PV thrombosis is treated medically, surgical portosystemic shunting (mesorex, splenorenal, and mesocaval) being reserved for refractory cases. A 10-yr-old boy suffered recurrent malena and hemorrhagic shock because of chronic PV thrombosis following LT nine yr ago (1999). Extensive work-up failed to localize the bleeding source. The liver function remained normal. Initial attempts at surgical shunts failed owing to thrombosis (mesocaval 2001, splenorenal, inferior mesenteric-left renal vein, splenic-left external iliac vein 2008). In this situation, we performed a Clatworthy shunt by anastomosing the divided lower end of the LCIV to the side of SMV. There was a single, large caliber anastomosis. Post-operatively, the malena stopped completely, and clinically, there was no lower limb edema or encephalopathy. Doppler USG revealed persistence of hepatopetal flow within the portal collaterals. Follow-up at two yr reveals stable hepatic function with a patent shunt. To the best of our knowledge, we are not aware of a Clatworthy shunt being performed in a transplant setting. We reviewed the literature pertaining to this shunt in non-transplant patients with PHT.


Assuntos
Transplante de Fígado , Veia Porta/patologia , Derivação Portossistêmica Cirúrgica/métodos , Complicações Pós-Operatórias/cirurgia , Trombose/cirurgia , Criança , Humanos , Masculino , Trombose/etiologia
9.
Eur J Neurosci ; 27(7): 1771-9, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18380671

RESUMO

Light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that utilize glutamate as a neurotransmitter. A variety of evidence suggests that the release of glutamate then activates N-methyl-D-aspartate (NMDA) receptors within the SCN and triggers a signaling cascade that ultimately leads to phase shifts in the circadian system. In this study, we first sought to explore the role of the NR2B subunit in mediating the effects of light on the circadian system of hamsters and mice. We found that localized microinjection of the NR2B subunit antagonist ifenprodil into the SCN region reduces the magnitude of light-induced phase shifts of the circadian rhythm in wheel-running activity. Next, we found that the NR2B message and levels of phospho-NR2B vary with time of day in SCN tissue using semiquantitative real-time polymerase chain reaction and western blot analysis, respectively. Functionally, we found that blocking the NR2B subunit with ifenprodil significantly reduced the magnitude of NMDA currents recorded in SCN neurons. Ifenprodil also significantly reduced the magnitude of NMDA-induced Ca2+ changes in SCN cells. Together, these results demonstrate that the NR2B subunit is an important component of NMDA receptor-mediated responses within SCN neurons and that this subunit contributes to light-induced phase shifts of the mammalian circadian system.


Assuntos
Ritmo Circadiano/fisiologia , Estimulação Luminosa/métodos , Subunidades Proteicas/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Animais , Ritmo Circadiano/efeitos dos fármacos , Cricetinae , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Piperidinas/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Núcleo Supraquiasmático/citologia , Núcleo Supraquiasmático/efeitos dos fármacos , Núcleo Supraquiasmático/metabolismo , Núcleo Supraquiasmático/fisiologia
10.
Singapore Med J ; 48(10): e265-7, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17909661

RESUMO

Mesenteric cystic lymphangioma is a rare lesion that is not often described in the literature. A four-year-old boy, who presented with abdominal distension and pain, is reported. At surgery, a huge mesenteric cyst was found to be the cause of the intestinal obstruction and was completely excised. Histology was consistent with a cystic lymphangioma. Abdominal lymphangioma is a rare cause of bowel obstruction. Clinical presentation varies and may be misleading due to a lack of awareness of the clinical condition. Occasionally, the diagnosis is made during surgery. General awareness of this entity with a high index of suspicion is needed to avoid complications.


Assuntos
Obstrução Intestinal/etiologia , Linfangioma Cístico/complicações , Cisto Mesentérico/complicações , Pré-Escolar , Humanos , Obstrução Intestinal/diagnóstico por imagem , Linfangioma Cístico/diagnóstico , Linfangioma Cístico/cirurgia , Masculino , Cisto Mesentérico/diagnóstico , Radiografia
11.
J Biol Chem ; 282(39): 28951-28959, 2007 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-17640869

RESUMO

Translation elongation factor eEF1A, formerly known as EF-1 alpha, exists as two variant forms; eEF1A1, which is almost ubiquitously expressed, and eEF1A2, whose expression is restricted to muscle and brain at the level of whole tissues. Expression analysis of these genes has been complicated by a general lack of availability of antibodies that specifically recognize each variant form. Wasted mice (wst/wst) have a 15.8-kilobase deletion that abolishes activity of eEF1A2, but before this study it was unknown whether the deletion also affected neighboring genes. We have generated a panel of anti-peptide antibodies and used them to show that eEF1A2 is expressed at high levels in specific cell types in tissues previously thought not to express this variant, such as pancreatic islet cells and enteroendocrine cells in colon crypts. Expression of eEF1A1 and eEF1A2 is shown to be generally mutually exclusive, and we relate the expression pattern of eEF1A2 to the phenotype seen in wasted mice. We then carried out a series of transgenic experiments to establish whether the expression of other genes is affected by the deletion in wasted mice. We show that aspects of the phenotype such as motor neuron degeneration relate precisely to the relative expression of eEF1A1 and eEF1A2, whereas the immune system abnormalities are likely to result from a stress response. We conclude that loss of eEF1A2 function is solely responsible for the abnormalities seen in these mice.


Assuntos
Regulação da Expressão Gênica , Sistema Imunitário/metabolismo , Fator 1 de Elongação de Peptídeos/biossíntese , Síndrome de Emaciação/metabolismo , Animais , Sequência de Bases/genética , Colo/imunologia , Colo/metabolismo , Colo/patologia , Regulação da Expressão Gênica/imunologia , Humanos , Sistema Imunitário/anormalidades , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , Doença dos Neurônios Motores/genética , Doença dos Neurônios Motores/imunologia , Doença dos Neurônios Motores/metabolismo , Doença dos Neurônios Motores/patologia , Especificidade de Órgãos/genética , Especificidade de Órgãos/imunologia , Fator 1 de Elongação de Peptídeos/genética , Fator 1 de Elongação de Peptídeos/imunologia , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Deleção de Sequência , Síndrome de Emaciação/genética , Síndrome de Emaciação/imunologia , Síndrome de Emaciação/patologia , Desmame
12.
Singapore Med J ; 47(7): 595-8, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16810431

RESUMO

INTRODUCTION: The advent of liver transplantation has revolutionised the outcome of children with both acute liver failure and chronic end-stage liver disease. The aim of this study was to review the outcome of all paediatric liver transplants performed since the National Liver Transplant Programme began in 1990. METHODS: A retrospective review of all paediatric liver transplants from 1990 to December 2004 was performed. RESULTS: 46 liver transplants were performed in 43 children, of whom 23 (53.3 percent) were female. Median age at transplant was 21 months (range 11 months to 14 years). The most common indication for liver transplant was biliary atresia (71.7 percent). Living-related transplants accounted for 63 percent (29). Re-transplant rate was 6.5 percent with allograft loss as a result of hepatic artery thrombosis (two) and hepatic vein thrombosis (one). Tacrolimus was the primary immunosuppressive agent used in 89 percent of patients, with a 19.6 percent incidence of acute allograft rejection within the first six months. There were nine deaths. They were related to portal vein thrombosis (three), chronic rejection (one), sepsis (two), post-transplant lymphoproliferative disease (two) and primary graft non-function (one). Overall actuarial one- and five-year survival rate was 85.7 percent and 81.8 percent, respectively. CONCLUSION: Liver transplantation is an established form of intervention for end-stage liver disease and a variety of liver-related metabolic disease. Our results are comparable to those of well-established liver transplant centres.


Assuntos
Transplante de Fígado/mortalidade , Transplante de Fígado/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Hepatopatias/cirurgia , Transplante de Fígado/efeitos adversos , Doadores Vivos/estatística & dados numéricos , Masculino , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Análise de Sobrevida
13.
Ann Acad Med Singap ; 34(10): 632-5, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16382249

RESUMO

INTRODUCTION: Neoplastic growths of myofibroblasts occurring on a background of plasma cell and lymphocytic proliferation have been designated as inflammatory myofibroblastic tumours (IMTs). These unusual tumours were first described in pulmonary location in adults. Though extrapulmonary masses have been reported in children; retroperitoneal growths are exceedingly rare. We report a case of retroperitoneal IMT that presented with constitutional symptoms without any palpable abdominal mass. CLINICAL PICTURE: A previously well 12-year-old boy presented with fever, right-sided flank pain and weight loss of 1-month duration. There were no foci of infection. The erythrocyte sedimentation rate (ESR) was raised; the white cell count was normal. An abdominal computed tomography (CT) scan revealed a right suprarenal tumour measuring 3.5 cm without any calcification. The urinary catecholamines and vanilmandelic acid were normal. TREATMENT: A laparotomy with complete excision of the tumour was performed. Final histology revealed an inflammatory myofibroblastic tumour without any correlates of aggressive behaviour. OUTCOME: Postoperatively, the constitutional symptoms of fever, weight loss and raised ESR normalised. Follow-up CT was normal and further treatment was not necessary. CONCLUSION: Although rare, IMTs should be considered in any abdominal solid tumour with associated constitutional and laboratory features of an inflammatory response. Complete surgical excision is effective treatment for biologically benign tumours.


Assuntos
Granuloma de Células Plasmáticas/diagnóstico , Espaço Retroperitoneal , Criança , Diagnóstico Diferencial , Seguimentos , Granuloma de Células Plasmáticas/cirurgia , Humanos , Laparotomia , Masculino , Tomografia Computadorizada por Raios X
14.
Singapore Med J ; 46(1): 28-30, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15633006

RESUMO

Since the routine use of antenatal ultrasonography, congenital pelviureteric junction (PUJ) obstruction rarely presents as an incidental diagnosis following renal trauma. Gross haematuria following seemingly trivial trauma should arouse the suspicion of a pre-existing abnormality. We report a 14-year-old girl with previously asymptomatic and undetected PUJ obstruction who first presented with gross haematuria following a trivial fall. The diagnosis was established by an abdominal computed tomography that showed left chronic hydronephrosis, and was subsequently confirmed on a renal isotope scan. Since the pre-existing hydronephrosis has little impact on the recovery from the injury itself, the initial management was non-operative with an aim to conserve the kidney. As standard surgery has a good outcome, once the renal scan confirmed good renal function, a delayed Anderson-Hynes' pyeloplasty was performed following healing of the kidney laceration as seen on ultrasonography.


Assuntos
Hidronefrose/congênito , Rim/lesões , Ferimentos não Penetrantes/complicações , Adolescente , Feminino , Hematúria/etiologia , Humanos , Rim/diagnóstico por imagem , Rim/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
15.
Ann Acad Med Singap ; 33(4): 530-1, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15329771

RESUMO

INTRODUCTION: Serosal inflammation of the appendix in association with a significant peritoneal exudate can be mistaken for early acute appendicitis. We highlight the importance of looking for other sources of intra-abdominal sepsis in this clinical setting. CLINICAL PICTURE: We present 3 cases of so-called "mild" appendicitis with serosal inflammation that was ultimately shown to be caused by Meckel's diverticulitis. TREATMENT: All 3 patients initially underwent an appendicectomy. In 2 of these cases, a further laparotomy and excision of a Meckel's diverticulum was carried out. All 3 made an uneventful recovery. CONCLUSION: Meckel's diverticulitis can mimic acute appendicitis in clinical history, physical findings and operative findings. It is important to always consider this as a possible cause for an acute abdomen.


Assuntos
Dor Abdominal/etiologia , Apendicite/diagnóstico , Divertículo Ileal/complicações , Divertículo Ileal/diagnóstico , Criança , Pré-Escolar , Humanos , Masculino
16.
Pediatr Surg Int ; 19(4): 266-7, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12721709

RESUMO

This report describes three cases of significant lower gastro-intestinal haemorrhage caused by a bleeding Meckel's diverticulum. In the first two cases a pre-operative technetium-pertechnetate or Meckel's scan was negative or inconclusive, and in the third case no Meckel's scan was carried out. The diagnosis was established at laparoscopy in all three cases and in each case the diverticulum was excised extracorporeally.


Assuntos
Hemorragia Gastrointestinal/cirurgia , Laparoscopia , Divertículo Ileal/diagnóstico , Adolescente , Criança , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Lactente , Masculino , Divertículo Ileal/complicações , Divertículo Ileal/cirurgia
17.
Mol Psychiatry ; 6(2): 173-8, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11317219

RESUMO

Two overlapping and antiparallel genes on chromosome 1, Disrupted In Schizophrenia 1 and 2 (DISC1 and DISC2), are disrupted by a (1;11)(q42.1;q14.3) translocation which segregates with schizophrenia through at least four generations of a large Scottish family. Consequently, these genes are worthy of further investigation as candidate genes potentially involved in the aetiology of major psychiatric illness. We have constructed a contiguous clone map of PACs and cosmids extending across at least 400 kb of the chromosome 1 translocation breakpoint region and this has provided the basis for examination of the genomic structure of DISC1. The gene consists of thirteen exons, estimated to extend across at least 300 kb of DNA. The antisense gene DISC2 overlaps with exon 9. Exon 11 contains an alternative splice site that removes 66 nucleotides from the open reading frame. The final intron of DISC1 belongs to the rare AT-AC class of introns. We have also mapped marker DIS251 in close proximity to DISC1, localising the gene within a critical region identified by several independent studies. Information regarding the structure of the DISC1 gene will facilitate assessment of its involvement in the aetiology of major mental illness in psychotic individuals unrelated to carriers of the translocation.


Assuntos
Ligação Genética , Proteínas do Tecido Nervoso/genética , Esquizofrenia/genética , Translocação Genética , Linhagem Celular , Marcadores Genéticos , Genoma Humano , Humanos , Hibridização in Situ Fluorescente , Íntrons , Dados de Sequência Molecular , Sítios de Splice de RNA/genética
18.
Genes Dev ; 14(5): 521-35, 2000 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10716941

RESUMO

SATB1 is expressed primarily in thymocytes and can act as a transcriptional repressor. SATB1 binds in vivo to the matrix attachment regions (MARs) of DNA, which are implicated in the loop domain organization of chromatin. The role of MAR-binding proteins in specific cell lineages is unknown. We generated SATB1-null mice to determine how SATB1 functions in the T-cell lineage. SATB1-null mice are small in size, have disproportionately small thymi and spleens, and die at 3 weeks of age. At the cellular level, multiple defects in T-cell development were observed. Immature CD3(-)CD4(-)CD8(-) triple negative (TN) thymocytes were greatly reduced in number, and thymocyte development was blocked mainly at the DP stage. The few peripheral CD4(+) single positive (SP) cells underwent apoptosis and failed to proliferate in response to activating stimuli. At the molecular level, among 589 genes examined, at least 2% of genes including a proto-oncogene, cytokine receptor genes, and apoptosis-related genes were derepressed at inappropriate stages of T-cell development in SATB1-null mice. For example, IL-2Ralpha and IL-7Ralpha genes were ectopically transcribed in CD4(+)CD8(+) double positive (DP) thymocytes. SATB1 appears to orchestrate the temporal and spatial expression of genes during T-cell development, thereby ensuring the proper development of this lineage. Our data provide the first evidence that MAR-binding proteins can act as global regulators of cell function in specific cell lineages.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Ligação à Região de Interação com a Matriz , Matriz Nuclear/fisiologia , Linfócitos T/fisiologia , Envelhecimento , Animais , Linfócitos B/fisiologia , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Humanos , Masculino , Camundongos , Camundongos Knockout , Proto-Oncogene Mas , Receptores de Interleucina-2/genética , Receptores de Interleucina-7/genética , Proteínas Recombinantes de Fusão/biossíntese , Subpopulações de Linfócitos T/fisiologia , Linfócitos T/ultraestrutura , Testículo/metabolismo , Timo/imunologia
19.
Mol Cell Biol ; 19(6): 4200-8, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10330160

RESUMO

Mice deficient in the transmembrane protein tyrosine phosphatase CD45 exhibit a block in thymocyte development. To determine whether the block in thymocyte development was due to the inability to dephosphorylate the inhibitory phosphorylation site (Y505) in p56(lck) (Lck), we generated CD45-deficient mice that express transgenes for the Lck Y505F mutation and the DO11.10 T-cell antigen receptor (TCR). CD4 single-positive T cells developed and accumulated in the periphery. Treatment with antigen resulted in thymocyte apoptosis and the loss of transgenic-TCR-bearing cells. Peripheral CD45-deficient T cells from the mice expressing both transgenes responded to antigen by increasing CD69 expression, interleukin-2 production, and proliferation. These results indicate that thymocyte development requires the dephosphorylation of the inhibitory site in Lck by CD45.


Assuntos
Antígenos Comuns de Leucócito/fisiologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Timo/crescimento & desenvolvimento , Animais , Apoptose , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Cruzamentos Genéticos , Eletroforese em Gel de Poliacrilamida , Citometria de Fluxo , Regulação da Expressão Gênica , Immunoblotting , Camundongos , Camundongos Transgênicos , Fosfotransferases/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Proteínas Recombinantes de Fusão , Baço/metabolismo , Fatores de Tempo
20.
Percept Mot Skills ; 86(3 Pt 1): 1051-60, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9656307

RESUMO

Three questionnaire studies involving 101, 270, and 144 college students examined the relationship between affectionate behaviors and aggressive behaviors in the family environment as rated by the college students. Measures of affection and aggression were significantly negatively associated in nearly all analyses. Participants' ratings of parental alcohol abuse were positively associated with measures of parental aggression and negatively correlated with measures of parental affection.


Assuntos
Agressão/psicologia , Alcoolismo/psicologia , Emoções , Relações Familiares , Adulto , Alcoolismo/diagnóstico , Saúde da Família , Feminino , Humanos , Amor , Masculino , Núcleo Familiar/psicologia , Relações Pais-Filho , Cônjuges/psicologia , Inquéritos e Questionários
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