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1.
J Acoust Soc Am ; 153(3): 1791, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37002076

RESUMO

This paper presents new experimental and numerical evidence that perforations in a pipe wall result in a low-frequency bandgap within which sound waves rapidly attenuate. These perforations are modelled as an acoustically soft boundary condition on the pipe wall and show that a low frequency bandgap is created from 0 Hz. The upper bound of this bandgap is determined by the dimensions and separation of the perforations. An analytical model based on the transfer matrix method is proposed. This model is validated against numerical predictions for the pipe with varying perforation geometries. A numerical study is undertaken to model the effect of perforations with ideal acoustically soft boundary conditions and surrounded with an air gap. Close agreement is found between the numerical and analytical models. Experimental evidence shows that the width of the bandgap is accurately predicted with the numerical and analytical models.

2.
Proc Biol Sci ; 288(1945): 20202966, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33622122

RESUMO

Research on the 'ecology of fear' posits that defensive prey responses to avoid predation can cause non-lethal effects across ecological scales. Parasites also elicit defensive responses in hosts with associated non-lethal effects, which raises the longstanding, yet unresolved question of how non-lethal effects of parasites compare with those of predators. We developed a framework for systematically answering this question for all types of predator-prey and host-parasite systems. Our framework reveals likely differences in non-lethal effects not only between predators and parasites, but also between different types of predators and parasites. Trait responses should be strongest towards predators, parasitoids and parasitic castrators, but more numerous and perhaps more frequent for parasites than for predators. In a case study of larval amphibians, whose trait responses to both predators and parasites have been relatively well studied, existing data indicate that individuals generally respond more strongly and proactively to short-term predation risks than to parasitism. Apart from studies using amphibians, there have been few direct comparisons of responses to predation and parasitism, and none have incorporated responses to micropredators, parasitoids or parasitic castrators, or examined their long-term consequences. Addressing these and other data gaps highlighted by our framework can advance the field towards understanding how non-lethal effects impact prey/host population dynamics and shape food webs that contain multiple predator and parasite species.


Assuntos
Parasitos , Comportamento Predatório , Animais , Medo , Cadeia Alimentar , Humanos , Dinâmica Populacional
3.
S Afr Med J ; 110(2): 123-125, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32657682

RESUMO

BACKGROUND: Hospital-acquired infections (HAIs) are a major cause of morbidity and mortality. Surgical site infection (SSI) rates are reported to range from 2.5% to 41%. HAI increases the risk of death by 2 - 11%, and three-quarters of these deaths are directly attributable to SSIs. OBJECTIVES: To determine the incidence of HAI and to identify risk factors amenable to modification with a resultant reduction in infection rates. METHODS: An analysis of HAIs was performed between January and April 2018 in the trauma centre surgical wards at Groote Schuur Hospital, Cape Town, South Africa. RESULTS: There were 769 admissions during the study period. Twenty-two patients (0.03%) developed an HAI. The majority were men, and the mean age was 32 years (range 18 - 57). The mean length of hospital stay (LoS) was 9 days, higher than the mean LoS for the hospital of 6 days. Fourteen patients underwent emergency surgery, 3 patients underwent abbreviated damage control surgery, and 9 patients were admitted to the critical care unit. Most patients with nosocomial sepsis were treated with appropriate culture-based antibiotics (82%). Four patients were treated with amoxicillin/clavulanic acid presumptively prior to culture and sensitivity results, after which antibiotic therapy was tailored. All but 1 patient received antibiotics. CONCLUSIONS: A combination of measures is required to prevent trauma-related infections. By determining the incidence of nosocomial infections in our trauma patients, uniform policies to reduce infection rates further could be determined. Our low incidence of infection may be explained by established preventive care bundles already in place.


Assuntos
Antibacterianos/administração & dosagem , Infecção Hospitalar/epidemiologia , Sepse/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Adolescente , Adulto , Infecção Hospitalar/prevenção & controle , Feminino , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Sepse/tratamento farmacológico , África do Sul/epidemiologia , Centros de Traumatologia , Serviços Urbanos de Saúde , Adulto Jovem
4.
Ann Anat ; 232: 151563, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32585296

RESUMO

PURPOSE: Today, ultrasound-guided peripheral endovascular interventions have the potential to be an alternative to conventional interventions that are still X-ray and contrast agent based. For the further development of this approach, a research environment is needed that represents the individual patient-specific endovascular properties as realistically as possible. Aim of the project was the construction of a phantom that combines ultrasound capabilities and the possibility to simulate peripheral endovascular interventions. MATERIAL AND METHODS: We designed a modular ultrasound-capable phantom with exchangeable patient specific vascular anatomy. For the manufacturing of the vascular pathologies, we used 3D printing technology. Subsequently, we evaluated the constructed simulator with regards to its application for endovascular development projects. RESULTS: We developed an ultrasound-capable phantom with an exchangeable 3D-printed segment of the femoral artery. This modality allows the study of several patient-specific 3D-printed pathologies. Compared to the flow properties of a human artery (male; age 28) the phantom shows realistic flow properties in the duplex ultrasound image. We proved the feasibility of the simulator by performing an ultrasound-guided endovascular procedure. Overall, the simulator showed realistic intervention conditions. CONCLUSIONS: With the help of the constructed simulator, new endovascular procedures and navigation systems, such as ultrasound-guided peripheral vascular interventions, can be further developed. Additionally, in our opinion, the use of such simulators can also reduce the need for animal experiments.


Assuntos
Procedimentos Endovasculares/métodos , Artéria Femoral/anatomia & histologia , Imagens de Fantasmas/classificação , Impressão Tridimensional , Adulto , Alternativas ao Uso de Animais , Simulação por Computador , Estudos de Viabilidade , Humanos , Masculino , Ultrassonografia de Intervenção
5.
S Afr J Surg ; 56(3): 2-8, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30264935

RESUMO

BACKGROUND: Surgery has previously been neglected as a development initiative, despite the obvious effect of surgical illnesses on morbidity and mortality. Recently, greater attention has been given to surgical services, as there is growing evidence of cost-effectiveness of surgical interventions. Operating theatre numbers have been used as a measure of surgical capacity, despite there being limitations associated with this use of this metric. This study aims to analyse part of the surgical resources in South Africa. METHODS: A descriptive analysis of surgical infrastructure in all nine provinces was performed. The total number of functional operating theatres was documented for all public and private hospitals in South Africa. Hospitals were contacted during the period from 1 October 2014 until 31 December 2014. RESULTS: The results showed 3.59 operating theatres per 100 000 population. This fell below the global average of 6.2 operating theatres per 100 000 as well as other developed countries. Theatres were concentrated in metropolitan areas, and there were a greater number of private operating theatres per insured population than in the uninsured public sector. CONCLUSION: Strengthening surgical systems will reduce the surgical burden of disease and improve health outcomes globally. Little is known about the available surgical resources such as operating theatre density, although using this metric to evaluate surgical capacity has its limitations.


Assuntos
Recursos em Saúde/economia , Salas Cirúrgicas/economia , Salas Cirúrgicas/estatística & dados numéricos , Países em Desenvolvimento , Pesquisas sobre Atenção à Saúde , Necessidades e Demandas de Serviços de Saúde , Hospitais Privados/estatística & dados numéricos , Hospitais Públicos/estatística & dados numéricos , Humanos , África do Sul
6.
Nat Commun ; 9(1): 3287, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-30120234

RESUMO

Leukocytes are coated with a layer of heterogeneous carbohydrates (glycans) that modulate immune function, in part by governing specific interactions with glycan-binding proteins (lectins). Although nearly all membrane proteins bear glycans, the identity and function of most of these sugars on leukocytes remain unexplored. Here, we characterize the N-glycan repertoire (N-glycome) of human tonsillar B cells. We observe that naive and memory B cells express an N-glycan repertoire conferring strong binding to the immunoregulatory lectin galectin-9 (Gal-9). Germinal center B cells, by contrast, show sharply diminished binding to Gal-9 due to upregulation of I-branched N-glycans, catalyzed by the ß1,6-N-acetylglucosaminyltransferase GCNT2. Functionally, we find that Gal-9 is autologously produced by naive B cells, binds CD45, suppresses calcium signaling via a Lyn-CD22-SHP-1 dependent mechanism, and blunts B cell activation. Thus, our findings suggest Gal-9 intrinsically regulates B cell activation and may differentially modulate BCR signaling at steady state and within germinal centers.


Assuntos
Linfócitos B/metabolismo , Galectinas/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Transdução de Sinais , Amino Açúcares/química , Sinalização do Cálcio , Linhagem Celular , Núcleo Celular/metabolismo , Proliferação de Células , Endocitose , Galectinas/sangue , Centro Germinativo/metabolismo , Humanos , Fatores Imunológicos/metabolismo , Memória Imunológica , Antígenos Comuns de Leucócito/metabolismo , Ativação Linfocitária/imunologia , Tecido Linfoide/metabolismo , Modelos Biológicos , N-Acetilexosaminiltransferases/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Fosforilação , Ligação Proteica , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Quinases da Família src/metabolismo
7.
S Afr J Surg ; 56(2): 16-20, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30010259

RESUMO

BACKGROUND: The full extent of the global burden of surgical disease is largely unknown, however, the scope of the problem is thought to be large. Despite the substantial burden of surgical disease, surgical services are inaccessible to many of those who need them most. There are disparities between public and private sectors in South Africa, which compound inequitable access to surgical care. This study forms part of a series analysing surgical resources in South Africa. METHOD: This study involved a descriptive analysis of surgical resources and included the total number of hospitals, of hospital beds, the number of surgical beds, the number of general surgeons (specialist and non-specialist), and the number of functional operating theatres in South Africa. A comparison was performed between the public and private sectors. Hospitals were contacted during the period from 1 October 2014 until 31 December 2014. RESULTS: Surgical resources were concentrated in metropolitan areas of urban provinces. There were striking differences between the public and private sectors, where private resources were comparable to those available in high income countries (HICs). CONCLUSION: Improving access to surgical services in lower middle income countries (LMICs) requires addressing gaps between the public and private sector regarding infrastructure, personnel, as well as equipment. These data identified disparities between geographic regions which may be contributing to ongoing inequity in South Africa, and by doing so allows for evidence-based planning towards improving surgical infrastructure and workforce.


Assuntos
Recursos em Saúde/economia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde , Setor Privado/economia , Setor Público/economia , Países em Desenvolvimento , Estudos de Avaliação como Assunto , Cirurgia Geral/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , África do Sul
8.
World J Surg ; 42(12): 3849-3855, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29947987

RESUMO

BACKGROUND: In the era of global surgery, there are limited data regarding the available surgical workforce in South Africa. METHODS: This aim of this study was to determine the orthopaedic surgeon density in South Africa. This involved a quantitative descriptive analysis of all registered specialist orthopaedic surgeons in South Africa, using data collected from various professional societal national databases. RESULTS: The results showed 1.63 orthopaedic surgeons per 100,000 population. The vast majority were male (95%) with under two-thirds (65%) being under the age of 55 years. The majority of the orthopaedic surgeons were found in Gauteng, followed by the Western Cape and Kwa-Zulu Natal. The majority of specialists reportedly worked either full time or part time in the private sector (95%), and the orthopaedic surgeon density per uninsured population (0.36) was far below that of the private sector (8.3). CONCLUSION: Interprovincial differences as well as intersectoral differences were marked indicating geographic and socio-economic maldistribution of orthopaedic surgeons. This parallels previous studies which looked at other surgical sub-disciplines in South Africa. Addressing this maldistribution requires concerted efforts to expand public sector specialist posts as well as quantifying the burden of orthopaedic disease in both private and public sectors before recommendations can be made regarding workforce allocation in the future. LEVEL OF EVIDENCE: IV.


Assuntos
Cirurgiões Ortopédicos/provisão & distribuição , Setor Privado/estatística & dados numéricos , Setor Público/estatística & dados numéricos , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Área Carente de Assistência Médica , Pessoa de Meia-Idade , Setor Privado/organização & administração , Setor Público/organização & administração , África do Sul
9.
S Afr J Surg ; 56(1): 12-18, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29638087

RESUMO

BACKGROUND: Human resources are the backbone of health-care delivery systems and the lack of surgical workforce in developing countries is often the greatest challenge to providing surgical care. The workforce availability and composition is an important indicator of the strength of the health system. This study aimed to analyse the distribution of general surgeons within South Africa. METHOD: A descriptive analysis of the general surgical workforce in South Africa was performed. The total number of specialist and non-specialist general surgeons working in the public sector in South Africa was documented between the periods from the 1 October 2014 until 31 December 2014. RESULTS: There were significant disparities in the number and distribution of general surgeons in South Africa. There were 1.78 specialist general surgeons per 100 000, of which 0.69 per 100 000 specialist general surgeons were working in the public sector. There were 2.90 non-specialist general surgeons per 100 000. There were 6 specialist general surgeons per 100 000 insured population working in the private sector, which is comparable with the United States (US). Urban provinces such as Gauteng, the Western Cape and KwaZulu-Natal had the largest number of specialist general surgeons per 100 000. These areas had the largest number of medical aid beneficiaries and nearly 60% of specialist general surgeons were estimated to work exclusively in the private sector. CONCLUSION: There was a major shortage of surgical providers in South Africa, and in particular the public sector.


Assuntos
Países em Desenvolvimento , Cirurgia Geral/organização & administração , Setor Público , Cirurgiões/provisão & distribuição , Humanos , África do Sul
10.
World J Surg ; 42(2): 541-548, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28799008

RESUMO

BACKGROUND: Surgical conditions lead to premature death and disability resulting in a massive economic burden. Contributing to this global crisis is the lack of data on the limited surgical infrastructure and workforce in many low- and middle-income countries. METHODS: This study involved a descriptive analysis of surgical resources in South Africa and included the total number of hospitals, number of hospital beds, number of surgical beds, number of general surgeons, and the number of functional operating theatres. All hospitals in South Africa were contacted between the 1 October 2014 and the 31 December 2014. An international comparison of South Africa's surgical resources was then made with several countries. RESULTS: The results showed one hospital per 100,000 population. There were 186.64 hospital beds, 41.55 surgical beds, 1.78 specialist general surgeons, 2.90 non-specialist general surgeons, and 3.59 operating theatres per 100,000 people in South Africa. These numbers fell far below international recommendations, as well as for developed countries such as the UK and USA. CONCLUSION: Strengthening surgical systems will reduce the surgical burden of disease and improve health outcomes globally. This description of surgical infrastructure and workforce provided insight into the surgical capacity of South Africa. Furthermore, this research provided a comparison of surgical resources between South Africa and the rest of the world.


Assuntos
Recursos em Saúde/provisão & distribuição , Hospitais/estatística & dados numéricos , Cirurgiões/provisão & distribuição , Países em Desenvolvimento , Número de Leitos em Hospital/estatística & dados numéricos , Humanos , Renda , Salas Cirúrgicas/estatística & dados numéricos , África do Sul
11.
S. Afr. j. surg. (Online) ; 56(1): 12-20, 2018. ilus
Artigo em Inglês | AIM (África) | ID: biblio-1271004

RESUMO

Background:Human resources are the backbone of health-care delivery systems and the lack of surgical workforce in developing countries is often the greatest challenge to providing surgical care. The workforce availability and composition is an important indicator of the strength of the health system. This study aimed to analyse the distribution of general surgeons within South Africa. Methods: A descriptive analysis of the general surgical workforce in South Africa was performed. The total number of specialist and non-specialist general surgeons working in the public sector in South Africa was documented between the periods from the 1 October 2014 until 31 December 2014. Results: There were significant disparities in the number and distribution of general surgeons in South Africa. There were 1.78 specialist general surgeons per 100 000, of which 0.69 per 100 000 specialist general surgeons were working in the public sector. There were 2.90 non-specialist general surgeons per 100 000. There were 6 specialist general surgeons per 100 000 insured population working in the private sector, which is comparable with the United States (US). Urban provinces such as Gauteng, the Western Cape and KwaZulu-Natal had the largest number of specialist general surgeons per 100 000. These areas had the largest number of medical aid beneficiaries and nearly 60% of specialist general surgeons were estimated to work exclusively in the private sector. Conclusion: There was a major shortage of surgical providers in South Africa, and in particular the public sector


Assuntos
Cirurgia Geral , África do Sul , Cirurgia Plástica
12.
S. Afr. j. surg. (Online) ; 56(2): 16-20, 2018. ilus
Artigo em Inglês | AIM (África) | ID: biblio-1271010

RESUMO

Background:The full extent of the global burden of surgical disease is largely unknown, however, the scope of the problem is thought to be large. Despite the substantial burden of surgical disease, surgical services are inaccessible to many of those who need them most. There are disparities between public and private sectors in South Africa, which compound inequitable access to surgical care. This study forms part of a series analysing surgical resources in South Africa. Methods:This study involved a descriptive analysis of surgical resources and included the total number of hospitals, of hospital beds, the number of surgical beds, the number of general surgeons (specialist and non-specialist), and the number of functional operating theatres in South Africa. A comparison was performed between the public and private sectors. Hospitals were contacted during the period from 1 October 2014 until 31 December 2014.Results: Surgical resources were concentrated in metropolitan areas of urban provinces. There were striking differences between the public and private sectors, where private resources were comparable to those available in high income countries (HICs).Conclusion: Improving access to surgical services in lower middle income countries (LMICs) requires addressing gaps between the public and private sector regarding infrastructure, personnel, as well as equipment. These data identified disparities between geographic regions which may be contributing to ongoing inequity in South Africa, and by doing so allows for evidence-based planning towards improving surgical infrastructure and workforce


Assuntos
Doença , Cirurgia Geral , África do Sul , Procedimentos Cirúrgicos Operatórios
13.
S. Afr. j. surg. (Online) ; 56(3): 2-8, 2018. ilus
Artigo em Inglês | AIM (África) | ID: biblio-1271020

RESUMO

Background:Surgery has previously been neglected as a development initiative, despite the obvious effect of surgical illnesses on morbidity and mortality. Recently, greater attention has been given to surgical services, as there is growing evidence of cost-effectiveness of surgical interventions. Operating theatre numbers have been used as a measure of surgical capacity, despite there being limitations associated with this use of this metric. This study aims to analyse part of the surgical resources in South Africa. Methods: A descriptive analysis of surgical infrastructure in all nine provinces was performed. The total number of functional operating theatres was documented for all public and private hospitals in South Africa. Hospitals were contacted during the period from 1 October 2014 until 31 December 2014.Results:The results showed 3.59 operating theatres per 100 000 population. This fell below the global average of 6.2 operating theatres per 100 000 as well as other developed countries. Theatres were concentrated in metropolitan areas, and there were a greater number of private operating theatres per insured population than in the uninsured public sector. Conclusion: Strengthening surgical systems will reduce the surgical burden of disease and improve health outcomes globally. Little is known about the available surgical resources such as operating theatre density, although using this metric to evaluate surgical capacity has its limitations


Assuntos
Cirurgia Geral , Cirurgia Geral/mortalidade , África do Sul
14.
S Afr Med J ; 107(12): 1099-1105, 2017 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-29262964

RESUMO

BACKGROUND: The global burden of surgical disease has been studied to a limited extent. Despite the proven benefits of surgery, surgical services remain poorly resourced. Contributing to this global crisis is the critical lack of data regarding available resources. OBJECTIVE: To analyse the distribution of some resources necessary for the provision of surgical care. The distribution and number of surgical resources (number of surgical beds) relative to the general resources (number of hospitals and total number of beds) in South Africa were analysed. METHODS: All hospitals in the country, including those in the public and private sectors, were contacted, and the total number of hospitals, the level of care (district v. regional v. tertiary), the total number of hospital beds, and the number of surgical beds were determined. The data were analysed according to the provincial distribution and the public v. private sector distribution relative to the size of the population. RESULTS: A total of 544 hospitals were included in the study - 327 in the public sector and 217 in the private sector. The public sector hospitals included 257 district-, 49 regional- and 21 tertiary-level hospitals. Nationally, there were 1 hospital, 187 hospital beds and 42 surgical beds per 100 000 population. Gauteng Province (GP), the Eastern Cape, KwaZulu-Natal (KZN) and the Western Cape had the most hospitals and GP had the largest number of private hospitals. GP and KZN had the largest total number of beds (n=29 181 and n=22 889, respectively) and number of surgical beds (n=7 289 and n=4 651, respectively). GP had the largest number of private surgical beds (n=4 837). There was a marked variation in the number of hospitals, total number of beds, and number of surgical beds among provinces. CONCLUSION: This study provided an estimation of the number of hospitals, total number of beds, and number of surgical beds, and showed a marked variation among provinces and between the public and private sectors.

15.
Proc Biol Sci ; 284(1869)2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29263283

RESUMO

Animal movement impacts the spread of human and wildlife diseases, and there is significant interest in understanding the role of migrations, biological invasions and other wildlife movements in spatial infection dynamics. However, the influence of processes acting on infections during transient phases of host movement is poorly understood. We propose a conceptual framework that explicitly considers infection dynamics during transient phases of host movement to better predict infection spread through spatial host networks. Accounting for host transient movement captures key processes that occur while hosts move between locations, which together determine the rate at which hosts spread infections through networks. We review theoretical and empirical studies of host movement and infection spread, highlighting the multiple factors that impact the infection status of hosts. We then outline characteristics of hosts, parasites and the environment that influence these dynamics. Recent technological advances provide disease ecologists unprecedented ability to track the fine-scale movement of organisms. These, in conjunction with experimental testing of the factors driving infection dynamics during host movement, can inform models of infection spread based on constituent biological processes.


Assuntos
Doenças dos Animais/transmissão , Distribuição Animal , Animais Selvagens/fisiologia , Interações Hospedeiro-Parasita , Doenças dos Animais/parasitologia , Animais , Modelos Biológicos
16.
S Afr J Surg ; 54(3): 18-22, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28240463

RESUMO

BACKGROUND: Bile leaks from the parenchymal transection margin are a major cause of morbidity following major liver resections. The aim of this study was to benchmark the incidence and identify the risk factors for postoperative bile leakage after hepatic resection. PATIENTS AND METHODS: A prospective database of 467 consecutive liver resections performed by the University of Cape Town HPB surgical unit between January 1990 and January 2016 was analysed. The relationship of demographic, clinical and perioperative factors to the development of bile leakage was determined. Bile leak and postoperative complications severity were graded using the International Study Group of Liver Surgery and Accordion classifications. RESULTS: Overall morbidity was 24% (n = 112), with bile leaks occurring in 25 (5.4%) patients. Significantly more bile leaks occurred in patients who had major resections (≥ 3 segments) and longer total operative times (p < 0.05). There were 5 Grade A bile leaks which stopped spontaneously. Seventeen Grade B leaks required a combination of percutaneous drainage (n = 15), endoscopic biliary stenting (n = 8) and percutaneous transhepatic biliary drainage (n = 3). All 3 Grade C leaks required laparotomy for definitive drainage. Median hospital stay in the 442 patients without a bile leak was 8 days (IQR 1-98) compared with 12 days (IQR 6-30) for the 25 with bile leaks (p < 0.05) with no mortality. Major resections (≥ 3 segments) and total operative time (> 180mins) were significantly associated with bile leaks. CONCLUSION: The incidence of bile leakage was 5.4% and occurred after major liver resections with longer operative times and resulted in significantly extended hospitalisation. Most were effectively treated nonoperatively by percutaneous drainage of the collection and/or endoscopic or percutaneous biliary drainage without mortality.

17.
Leukemia ; 24(4): 821-32, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20147977

RESUMO

SHIP-1 (SH2 (Src homology 2)-containing inositol 5'-phosphatase-1) functions as a negative regulator of immune responses by hydrolyzing phosphatidylinositol-3,4,5-triphosphate generated by phosphoinositide-3 (PI 3)-kinase activity. As a result, SHIP-1 deficiency in mice results in myeloproliferation and B-cell lymphoma. On the other hand, SHIP-1-deficient mice have a reduced T-cell population, but the underlying mechanisms are unknown. In this work, we hypothesized that SHIP-1 plays anti-apoptotic functions in T cells upon stimulation of the death receptor CD95/APO-1/Fas. Using primary T cells from SHIP-1(-/-) mice and T leukemic cell lines, we report that SHIP-1 is a potent inhibitor of CD95-induced death. We observed that a small fraction of the SHIP-1 pool is localized to the endoplasmic reticulum (ER), in which it promotes CD95 glycosylation. This post-translational modification requires an intact SH2 domain of SHIP-1, but is independent of its phosphatase activity. The glycosylated CD95 fails to oligomerize upon stimulation, resulting in impaired death-inducing signaling complex (DISC) formation and downstream apoptotic cascade. These results uncover an unanticipated inhibitory function for SHIP-1 and emphasize the role of glycosylation in the regulation of CD95 signaling in T cells. This work may also provide a new basis for therapeutic strategies using compounds inducing apoptosis through the CD95 pathway on SHIP-1-negative leukemic T cells.


Assuntos
Apoptose , Linfoma de Células T/patologia , Monoéster Fosfórico Hidrolases/fisiologia , Linfócitos T/patologia , Receptor fas/antagonistas & inibidores , Animais , Western Blotting , Células Cultivadas , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/metabolismo , Retículo Endoplasmático , Citometria de Fluxo , Glicosilação , Humanos , Inositol Polifosfato 5-Fosfatases , Linfoma de Células T/metabolismo , Camundongos , Camundongos Knockout , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases , Fosforilação , Processamento de Proteína Pós-Traducional , RNA Interferente Pequeno/farmacologia , Transdução de Sinais , Linfócitos T/metabolismo , Receptor fas/metabolismo
18.
J Thromb Haemost ; 8(1): 137-45, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19874459

RESUMO

BACKGROUND: von Willebrand factor (VWF) is a key component for maintenance of normal hemostasis. Its glycan moieties, accounting for about 20% of its molecular weight, have been shown to affect many of its properties. Previous studies reported correlations between VWF secretion, half-life and the nature or presence of its N-glycans, and more importantly between VWF plasma level and the type of N-linked ABH antigens. Despite the presence of 10 predicted O-glycosylation sites, the O-glycome remains poorly characterized, impairing the complete elucidation of its influence on VWF functions. So far only a single glycan structure, a disialyl core 1 glycan, has been identified. OBJECTIVES: To define an exhaustive profile of the VWF O-glycan structures to help the understanding of their role in VWF regulation and properties. METHODS: Plasma-derived VWF O-linked sugars were isolated and analyzed using state-of-the-art mass spectrometry methodologies. RESULTS AND CONCLUSIONS: We provide here a detailed analysis of the human plasma-derived VWF O-glycome. Eighteen O-glycan structures including both core 1 and core 2 structures are now demonstrated to be present on VWF. Amongst the newly determined structures are unusual tetra-sialylated core 1 O-glycans and ABH antigen-containing core 2 O-glycans. In conjunction with current models explaining VWF activity, knowledge of the complete O-glycome will facilitate research aimed at providing a better understanding of the influence of glycosylation on VWF functions.


Assuntos
Sistema ABO de Grupos Sanguíneos/metabolismo , Glicômica , Processamento de Proteína Pós-Traducional , Fator de von Willebrand/metabolismo , Motivos de Aminoácidos , Configuração de Carboidratos , Cromatografia Gasosa-Espectrometria de Massas , Glicômica/métodos , Glicosilação , Humanos , Conformação Proteica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem , Fator de von Willebrand/química
19.
Mol Microbiol ; 71(2): 421-33, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19017269

RESUMO

Previously mutations in a putative protein O-mannosyltransferase (SCO3154, Pmt) and a polyprenol phosphate mannose synthase (SCO1423, Ppm1) were found to cause resistance to phage, phiC31, in the antibiotic producing bacteria Streptomyces coelicolor A3(2). It was proposed that these two enzymes were part of a protein O-glycosylation pathway that was necessary for synthesis of the phage receptor. Here we provide the evidence that Pmt and Ppm1 are indeed both required for protein O-glycosylation. The phosphate binding protein PstS was found to be glycosylated with a trihexose in the S. coelicolor parent strain, J1929, but not in the pmt(-) derivative, DT1025. Ppm1 was necessary for the transfer of mannose to endogenous polyprenol phosphate in membrane preparations of S. coelicolor. A mutation in ppm1 that conferred an E218V substitution in Ppm1 abolished mannose transfer and glycosylation of PstS. Mass spectrometry analysis of extracted lipids showed the presence of a glycosylated polyprenol phosphate (PP) containing nine repeated isoprenyl units (C(45)-PP). S. coelicolor membranes were also able to catalyse the transfer of mannose to peptides derived from PstS, indicating that these could be targets for Pmt in vivo.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas Periplásmicas/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Streptomyces coelicolor/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Glicosilação , Manose/metabolismo , Dados de Sequência Molecular , Proteínas Periplásmicas/genética , Proteínas de Ligação a Fosfato/genética , Análise de Sequência de Proteína , Streptomyces coelicolor/genética
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