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1.
Eur Phys J C Part Fields ; 82(5): 432, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572035

RESUMO

The electromagnetic form factors of charged and neutral kaons are strongly constrained by their low-energy singularities, in the isovector part from two-pion intermediate states and in the isoscalar contribution in terms of ω and ϕ residues. The former can be predicted using the respective π π → K ¯ K partial-wave amplitude and the pion electromagnetic form factor, while the latter parameters need to be determined from electromagnetic reactions involving kaons. We present a global analysis of time- and spacelike data that implements all of these constraints. The results enable manifold applications: kaon charge radii, elastic contributions to the kaon electromagnetic self energies and corrections to Dashen's theorem, kaon boxes in hadronic light-by-light (HLbL) scattering, and the ϕ region in hadronic vacuum polarization (HVP). Our main results are: ⟨ r 2 ⟩ c = 0.359 ( 3 ) fm 2 , ⟨ r 2 ⟩ n = - 0.060 ( 4 ) fm 2 for the charged and neutral radii, ϵ = 0.63 ( 40 ) for the elastic contribution to the violation of Dashen's theorem, a µ K -box = - 0.48 ( 1 ) × 10 - 11 for the charged kaon box in HLbL scattering, and a µ HVP [ K + K - , ≤ 1.05 GeV ] = 184.5 ( 2.0 ) × 10 - 11 , a µ HVP [ K S K L , ≤ 1.05 GeV ] = 118.3 ( 1.5 ) × 10 - 11 for the HVP integrals around the ϕ resonance. The global fit to K ¯ K gives M ¯ ϕ = 1019.479 ( 5 ) MeV , Γ ¯ ϕ = 4.207 ( 8 ) MeV for the ϕ resonance parameters including vacuum-polarization effects.

2.
Ann Med Surg (Lond) ; 62: 1-9, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33489107

RESUMO

BACKGROUND: Cardiopulmonary exercise-testing (CPET) and the (Portsmouth) Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity ((P)-POSSUM) are used as pre-operative risk stratification and audit tools in general surgery, however, both have been demonstrated to have limitations in major hepatopancreatobiliary (HPB) surgery. MATERIALS AND METHODS: The aim of this review is to determine if CPET and (P)-POSSUM scoring systems accurately predict morbidity and mortality. Eligible articles were identified with an electronic database search. Analysis according to surgery type and tool used was performed. RESULTS: Twenty-five studies were included in the final review. POSSUM predicted morbidity demonstrated weighted O/E ratios of 0.75(95%CI0.57-0.97) in hepatic surgery and 0.85(95%CI0.8-0.9) in pancreatic surgery. P-POSSUM predicted mortality in pancreatic surgery demonstrated an O/E ratio of 0.75(95%CI0.27-2.13) and 0.94(95%CI0.57-1.55) in hepatic surgery. In both pancreatic and hepatic surgery an anaerobic threshold(AT) of between 9 0.5-11.5 ml/kg/min was predictive of post-operative complications, and in pancreatic surgery ventilatory equivalence of carbon dioxide(˙VE/˙VCO2) was predictive of 30-day mortality. CONCLUSION: POSSUM demonstrates an overall lack of predictive fit for morbidity, whilst CPET variables provide some predictive power for post-operative outcomes. Development of a new HPB specific risk prediction tool would be beneficial; the combination of parameters from POSSUM and CPET, alongside HPB specific markers could overcome current limitations.

3.
J Gastrointest Surg ; 24(4): 918-932, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31900738

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are evidence-based, multimodal and patient-centred approach to optimize patient care and experience during their perioperative pathway. It has been shown to be effective in reducing length of hospital stay and improving clinical outcomes. However, evidence on its effective in liver surgery remains weak. The aim of this review is to investigate clinical benefits, cost-effectiveness and compliance to ERAS protocols in liver surgery. METHODS: A systematic literature search was conducted using CINAHL Plus, EMBASE, MEDLINE, PubMed and Cochrane for randomized control trials (RCTs) and cohort studies published between 2008 and 2019, comparing effect of ERAS protocols and standard care on hospital cost, LOS, complications, readmission, mortality and compliance. RESULTS: The search resulted in 6 RCTs and 21 cohort studies of 3739 patients (1777 in ERAS and 1962 in standard care group). LOS was reduced by 2.22 days in ERAS group (MD = -2.22; CI, -2.77 to -1.68; p < 0.00001) compared to the standard care group. Fewer patients in ERAS group experienced complications (RR, 0.71; 95% CI, 0.65-0.77; p = < 0.00001). Hospital cost was significantly lower in the ERAS group (SMD = -0.98; CI, -1.37 to - 0.58; p < 0.0001). CONCLUSION: Our review concluded that the introduction of ERAS protocols is safe and feasible in hepatectomies, without increasing mortality and readmission rates, whilst reducing LOS and risk of complications, and with a significant hospital cost savings. Laparoscopic approach may be necessary to reduce complication rates in liver surgery. However, further studies are needed to investigate overall compliance to ERAS protocols and its impact on clinical outcomes.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Custos Hospitalares , Humanos , Tempo de Internação , Fígado , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Recuperação de Função Fisiológica
4.
J Photochem Photobiol B ; 202: 111636, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31739259

RESUMO

Titanium dioxide (TiO2) nanoparticles (NPs) have been doped with varying amounts (0.005, 0.010 and 0.015 M) of silver nanoparticles (Ag NPs) using hydrothermal method. Further, in this work, a green approach was followed for the formation of Ag@TiO2 NPs using Aloe vera gel as a capping and reducing agent. The structural property confirmed the presence of anatase phase TiO2. Increased peak intensity was observed while increasing the Ag concentration. Further, the morphological and optical properties have been studied, which confirmed the effective photocatalytic behavior of the prepared Ag@TiO2 NPs. The photocatalytic performance of Ag@TiO2 has been considered for the degradation of picric acid in the visible light region. The concentration at 0.010 M of the prepared Ag@TiO2 has achieved higher photocatalytic performance within 50 min, which could be attributed to its morphological behavior. Similarly, anticancer activity against lung cancer cell lines (A549) was also determined. The Ag@TiO2 NPs generated a large quantity of reactive oxygen species (ROS), resulting in complete cancer cell growth suppression after their systemic in vitro administration. Ag@TiO2 NPs was adsorbed visible light that leads to an enhanced anticancer sensitivity by killing and inhibiting cancer cell reproduction through cell viability assay test. It was clear that 0.015 M of Ag@TiO2 NPs were highly effective against human lung cancer cell lines and showed increased production of ROS in cancer cell lines due to the medicinal behavior of the Aloe vera gel.


Assuntos
Antineoplásicos/química , Nanopartículas Metálicas/química , Prata/química , Titânio/química , Células A549 , Aloe/química , Aloe/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Catálise , Sobrevivência Celular/efeitos dos fármacos , Química Verde , Humanos , Luz , Nanopartículas Metálicas/toxicidade , Picratos/química , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Espécies Reativas de Oxigênio/metabolismo
5.
Int J Biol Macromol ; 124: 50-59, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30445094

RESUMO

In this present study, isolation, characterization and protective effect of sulfated polysaccharide (SP) isolated from the brown algae Padina gymnospora was investigated. SP was isolated and characterized through FT-IR, 1H NMR, TGA, GC-MS and CHN analysis. The molecular weight of SP was found to be 16 kDa. The isolated SP contains 29.4 ±â€¯0.35% of sulfate, 27 ±â€¯0.11% of fucose, 0.05 ±â€¯0.12% of protein, respectively. Furthermore, SP exhibits its excellent radical scavenging effects were evaluated by DPPH, ABTS radical scavenging and reducing power assays. Moreover, pretreatment with SP significantly mitigates H2O2 induced cytotoxicity in L-929 cells in a dose dependent manner. Furthermore, SP pretreatment ameliorates oxidative stress induced apoptosis and DNA damage, alleviates the generation of intracellular reactive oxygen species (ROS) and restores mitochondrial membrane potential (MMP) in L-929 cells through its antioxidant potential. Together, these results suggest that SP can be exploited as a natural antioxidant in the food and pharmaceutical industries.


Assuntos
Antioxidantes/química , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/química , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Dano ao DNA/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Sequestradores de Radicais Livres/química , Humanos , Peróxido de Hidrogênio/química , Espectroscopia de Ressonância Magnética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/patologia , Peso Molecular , Phaeophyceae/química , Polissacarídeos/farmacologia , Espécies Reativas de Oxigênio/química , Espectroscopia de Infravermelho com Transformada de Fourier , Sulfatos/química
6.
Ann R Coll Surg Engl ; 99(5): e145-e147, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28462645

RESUMO

A 43-year-old man had a peritoneovenous shunt inserted for the treatment of chylous ascites secondary to myelofibrosis. Despite being on anticoagulation for superior mesenteric vein thrombosis, he developed shunt dysfunction within two weeks of insertion. Superior venacavography showed multiple filling defects in the right axillary vein, no filling of the right brachiocephalic and right subclavian vein, and thrombotic occlusion of the internal jugular veins bilaterally. The shunt was removed 11 days after insertion, and there was extensive thrombosis of the venous end of the shunt and the compressible pump chamber. Shunt thrombosis is known to occur but remains a rare complication, with 87% of such obstructions being due to a thrombus at the tip of the venous end of the shunt. Extensive thrombosis of the shunt (as in the present case) is very rare.


Assuntos
Ascite Quilosa/cirurgia , Derivação Peritoneovenosa/efeitos adversos , Complicações Pós-Operatórias , Trombose Venosa/etiologia , Adulto , Humanos , Masculino , Falha de Prótese
7.
Ann R Coll Surg Engl ; 99(3): e1-e2, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28071951

RESUMO

There have been reports of late discharge of gallstones through operative wounds after spillage into the peritoneal cavity during laparoscopic cholecystectomy and after the development of spontaneous cholecystocutaneous fistulae. However, spontaneous discharge of gallstones from the tract of a percutaneous cholecystostomy or percutaneous drainage of a perforated gall bladder has not, to the best of our knowledge, been reported previously. We report a case in which a patient who had a percutaneous drain inserted for a perforated gall bladder discharged 34 gallstones from the tract after removal of the 7-F pigtail catheter.


Assuntos
Fístula Biliar , Fístula Cutânea , Cálculos Biliares/diagnóstico por imagem , Complicações Pós-Operatórias , Idoso de 80 Anos ou mais , Colecistostomia , Drenagem , Feminino , Doenças da Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/cirurgia , Cálculos Biliares/cirurgia , Humanos , Tomografia Computadorizada por Raios X
9.
Ann R Coll Surg Engl ; 95(2): 87-92, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23484986

RESUMO

INTRODUCTION: Retained sponges and instruments (RSI) due to surgery are a recognised medical 'never event' and have catastrophic implications for patients, healthcare professionals and medical care providers. The aim of this review was to elucidate the extent of the problem of RSI and to identify preventative strategies. METHODS: A comprehensive literature search was performed on MEDLINE(®), Embase™, the Science Citation Index and Google™ Scholar for articles published in English between January 2000 and June 2012. Studies outlining the incidence, risk, management and attempts to prevent RSI following surgical intervention were retrieved. RESULTS: The overall incidence of RSI is low although its incidence is substantially higher in operations performed on open cavities. Sponges are the most commonly retained item when compared with needles and instruments. Clinical presentation is varied, leading to avoidable morbidity, and the error is indefensible medicolegally. Risk factors include emergency operations, operations involving unexpected change in procedure, raised body mass index, and a failure to perform accurate sponge and instrument counts. The existing strategy for prevention is manual counting of sponges and instruments undertaken by surgical personnel. This, however, is fallible. Computer assisted counting of sponges using barcodes and gauze sponges tagged with a radiofrequency identification device aiding manual counting have been trialled recently, with success. CONCLUSIONS: Vigilance among operating theatre personnel is paramount if RSI is to be prevented. Prospective multicentre trials to assess efficacy of new technologies aiding manual counting should be undertaken if this medical error is to be eliminated completely.


Assuntos
Corpos Estranhos/prevenção & controle , Erros Médicos/prevenção & controle , Agulhas , Instrumentos Cirúrgicos , Tampões de Gaze Cirúrgicos , Diagnóstico Precoce , Corpos Estranhos/etiologia , Humanos , Incidência , Fatores de Risco
10.
Eur J Surg Oncol ; 36(10): 941-8, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20547445

RESUMO

BACKGROUND: Staging laparoscopy (SL) may prevent non-therapeutic laparotomy in patients with otherwise resectable pancreatico-biliary cancers, but evidence is inconclusive. This meta-analysis aims to ascertain the true benefit of SL. METHODS: All studies undertaking SL as a diagnostic sieve were included and data homogenised. Standard meta-analytical tools with emphasis on sensitivity testing and meta-regression to detect the cause for heterogeneity between studies were used. RESULTS: 29 studies satisfied the criteria. 3305 patients underwent SL of which 12 were incomplete. Morbidity (n = 15) and mortality (n = 1) was low. True yield of SL for pancreatic/perpancreatic cancers (PPC) was 25% (95% CI 24-27) with a Diagnostic Odds Ratio (DOR) of 104 (95% CI 48-227). Resection rate improved from 61% to 80%. For proximal biliary cancers (PBC), SL increased the curative resection rate from 27% to 50%, with true yield of 47% (95% CI 42-52) and a DOR 61 (95% CI 19-189). Sub-group analysis for detection of liver and peritoneal lesions demonstrated a sensitivity of 88% (95% CI 83-92) and 92% (95% CI 84-96) for PPC; 83% (95% CI 69-92) and 93% (95% CI 81-99) for PBC, respectively. There was no between-study heterogeneity for peritoneal lesions. However for detection of local invasion, sensitivity was low: 58% (95% CI 51-65) for PPC and only 34% (95% CI 22-47) for PBC. Meta-regression did not reveal any cause for the observed heterogeneity between studies. CONCLUSION: SL offers significant benefit to patients with resectable pancreatico-biliary cancers in avoiding non-therapeutic laparotomy and should be adopted in routine clinical practice in a judicious algorithm.


Assuntos
Neoplasias do Sistema Biliar/diagnóstico por imagem , Neoplasias do Sistema Biliar/cirurgia , Estadiamento de Neoplasias/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias do Sistema Biliar/patologia , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Biópsia por Agulha , Feminino , Humanos , Imuno-Histoquímica , Laparoscopia/métodos , Masculino , Invasividade Neoplásica/patologia , Pancreatectomia/métodos , Neoplasias Pancreáticas/patologia , Cuidados Pré-Operatórios/métodos , Sensibilidade e Especificidade , Ultrassonografia
11.
HPB (Oxford) ; 10(5): 327-31, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18982147

RESUMO

AIM: Ethnic background and geographical location are important when measuring the incidence of gallbladder carcinoma leading to variable mortality rates across the world. METHOD: Age standardized mortality rates [ASR(W)] were extracted separately for males and females from a database maintained by the International Agency for Research on Cancer for 50 countries across the world (Europe 32; the Americas 8; and Asia 10) for the period 1992-2002 and log-linear regression was performed to analyse trends in the last decade. RESULT: In the period 1992-2002, declining trends in mortality for both sexes were observed in Germany, Sweden, Japan, USA, and Hungary (p<0.001), and in France, Canada, United Kingdom, The Netherlands, and Hong Kong (p<0.01). Austria, Czechoslovakia, Slovenia, Denmark, Spain, and Israel exhibited decreasing mortality trends more significant in women (p<0.01) than in men (p<0.05). Decreasing female mortality trends were seen in Finland, Italy, and Portugal (p<0.01) and in Georgia, Luxembourg, and Belgium (p<0.05). Iceland, Costa Rica, and Korea were the only countries with an increase in male mortality (p<0.05). CONCLUSIONS: Overall, there was a decline in ASR(W) for gallbladder cancer. Better diagnostic modalities resulting in appropriate staging of gallbladder/biliary cancers, as well as changes in the ICD classification and perhaps increased awareness, may have contributed to these trends.

12.
HPB (Oxford) ; 10(1): 58-62, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18695761

RESUMO

INTRODUCTION: Pancreas cancer is the fourth commonest cause of cancer-related mortality across the world, with incidence equalling mortality. A recent study has suggested that both the incidence and the mortality of pancreatic cancer are falling in the UK. We investigated whether this trend was being seen all over the world. METHODS: Age-standardized mortality (world) rates [ASR(W)] for pancreatic cancer were extracted separately for males and females from a database maintained by the International Agency for Research on Cancer for 51 countries across the world (Europe, 33 countries; Americas, 8 countries; and Asia, 10 countries) for the period 1992-2002; log-linear regression analysis was performed to analyse trends in the past decade. RESULTS: In the period 1992-2002, the ASR(W) remained static across most countries for both sexes. The highest mortality rates (for both sexes) were seen in Central Europe [range: men (8-12), women (4.5-7)] with trends towards increasing mortality in Romania (p<0.001), along with Albania, Spain and Croatia (p<0.01). Korea in the Far East, too, demonstrated increasing mortality trends for both sexes (men p<0.001, women p<0.01). Increasing mortality trends were also observed among women in France (p<0.001). In Canada, there was a decline in mortality [men (7.5-6.4), women (5.9-5); p<0.01], while for men there was a downward trend in Ireland, the UK, Switzerland, Austria, and Poland [p<0.05]. CONCLUSION: The changes perhaps reflect standardization and consolidation of diagnostic tests for pancreatic cancer in the Western world and further in-depth analysis would be required.

13.
Ann R Coll Surg Engl ; 89(5): 504-9, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17688724

RESUMO

INTRODUCTION: The incidence of fragility fractures could double in the next 50 years. Effective treatments for osteoporosis exist and the British Orthopaedic Association (BOA) has guidelines governing how to manage underlying osteoporosis in patients with fragility fractures. This study assessed how well two trauma units treat underlying osteoporosis and whether the BOA guidelines made any impact. PATIENTS AND METHODS: Case notes of patients with a fracture of their proximal femur admitted during January and February in 2003, 2004 and 2005 were reviewed. The results were analysed for differences between site and year. RESULTS: A total of 602 case notes were reviewed. There was a significant difference in the number of patients discharged on osteoporosis medication between the two sites (27% at LRI, 8% at KGH; P < 0.001), but not between 2003 and 2005 (22% and 16%; P = 0.16). Of the patients started on treatment, 83% were started on calcium and/or vitamin D(3) supplements. CONCLUSIONS: The number of patients who had their underlying osteoporosis addressed was low and the type of treatment sub-optimal. This suggests the BOA guidelines have not made an impact and further work is required to improve the management of these patients.


Assuntos
Fraturas do Fêmur/cirurgia , Fraturas Espontâneas/cirurgia , Osteoporose/complicações , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas Espontâneas/etiologia , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Cuidados Pré-Operatórios/estatística & dados numéricos , Prática Profissional , Fatores de Risco , Listas de Espera
14.
J Pediatr Hematol Oncol ; 22(4): 351-4, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10959907

RESUMO

A female, term newborn born to a mother with a history of idiopathic thrombocytopenic purpura and antinuclear antibodies, single-stranded A antibody, and IgM anticardiolipin antibodies presented with immune thrombocytopenia, disseminated intravascular coagulation (DIC), microangiopathic hemolytic anemia, and a characteristic lupus rash in the periorbital areas. She responded to combined treatment with dexamethasone and intravenous immunoglobulin (IVIG). At age 9 months, she was readmitted with severe thrombocytopenia, DIC, and microangiopathic hemolytic anemia. She again responded to IVIG. This suggests that microangiopathic hemolysis can be a presenting symptom in neonatal lupus erythematosus and that reoccurrence of the microangiopathic hemolysis may occur even after the disappearance of lupus antibodies.


Assuntos
Anemia Hemolítica Congênita/terapia , Lúpus Eritematoso Sistêmico/terapia , Anemia Hemolítica Congênita/imunologia , Dexametasona/uso terapêutico , Coagulação Intravascular Disseminada/congênito , Coagulação Intravascular Disseminada/imunologia , Coagulação Intravascular Disseminada/terapia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Recém-Nascido , Lúpus Eritematoso Sistêmico/congênito , Lúpus Eritematoso Sistêmico/imunologia , Plasma , Transfusão de Plaquetas , Trombocitopenia/congênito , Trombocitopenia/imunologia , Trombocitopenia/terapia
15.
Blood ; 95(2): 715-8, 2000 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-10627485

RESUMO

Three C-C chemokines inhibit human immunodeficiency virus (HIV) entry into macrophages: macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and regulated-upon activation, normal T-cell expressed and secreted (RANTES). We studied the ability of placental cord blood mononuclear cells (CBMC) to secrete these C-C chemokines in comparison to adult blood mononuclear cells (ABMC). CBMC had diminished ability to secrete RANTES, as determined by enzyme-linked immunosorbent assay. Secretion of MIP-1alpha and MIP-1beta were similar in CBMC and ABMC. Whereas MIP-1alpha and MIP-1beta secretion were comparable in monocytes and lymphocytes, RANTES was secreted primarily by lymphocytes. Flow cytometric analysis of RANTES expression showed diminished intracellular RANTES expression in cord blood lymphocytes (CBL) compared to adult (peripheral) blood lymphocytes (ABL). A subset analysis of RANTES-producing CBL and ABL demonstrated that RANTES was produced predominantly by CD8+/CD45RO+ cells. CBL had a reduced proportion of CD8+/CD45RO+ cells compared with ABL, which may account for the diminished RANTES secretion by CBMC. These results may be relevant to the pathogenesis of perinatal HIV infection. (Blood. 2000;95:715-718)


Assuntos
Quimiocina CCL5/sangue , Quimiocinas CC/sangue , Sangue Fetal/citologia , Leucócitos Mononucleares/imunologia , Linfócitos T/imunologia , Adulto , Antígenos CD/sangue , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocina CCL5/biossíntese , Quimiocinas CC/biossíntese , Ensaio de Imunoadsorção Enzimática , Humanos , Recém-Nascido , Proteínas Inflamatórias de Macrófagos/sangue , Monócitos/imunologia , Valores de Referência
16.
AIDS Res Hum Retroviruses ; 15(17): 1545-52, 1999 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-10580405

RESUMO

The AC133 is a novel antigen selectively expressed on primitive CD34bright stem cells and is a valuable marker for the selection of long-term culture-initiating cells (LTC-ICs) and severe combined immunodeficiency (SCID)-repopulating cells. Human placental cord blood (HPCB) is a rich source of CD34+AC133+ cells. Since AC133 antibody is likely to be used as an alternative to CD34 for the selection of stem cells in transplant and gene therapy situations, we examined the susceptibility of HPCB-isolated CD34+AC133+ stem cells to infection with free and cell-associated HIV-1 in vitro. Freshly isolated HPCB CD34+AC133+ stem cells were not susceptible to HIV-1 infection as determined by PCR and reverse transcriptase assays. Inoculation with HIV-1 did not affect the viability and clonogenic ability of HPCB CD34+AC133+ cells. Although the highly purified HPCB CD34+AC133+ stem cells contained mRNA for CD4 and CXCR4 receptors, CD4 and CXCR4 proteins were not expressed on these cells. Similarly, CCR5 protein, the major macrophage-tropic HIV-1 coreceptor, was not expressed in freshly isolated HPCB CD34+AC133+ stem cells, although the transcript for CCR5 was identified in these cells. Expression of CD4, CXCR4, and CCR5 receptor proteins on the progeny derived from HPCB CD34+AC133+ stem cells was detected and correlated with susceptibility to HIV-1 infection in vitro. These findings suggest that freshly isolated HPCB CD34+AC133+ stem cells are not susceptible to HIV-1 infection and may not be a viral reservoir. These data have important implications for the use of AC133 antibody as a means of enriching for primitive hematopoietic stem cells from placental cord blood and in the design of stem cell or progenitor cell-based gene therapeutic strategies for perinatal HIV-1 infection.


Assuntos
Antígenos CD34/metabolismo , Sangue Fetal/citologia , Glicoproteínas/metabolismo , HIV-1 , Peptídeos/metabolismo , Provírus/isolamento & purificação , Células-Tronco/imunologia , Células-Tronco/virologia , Antígeno AC133 , Antígenos CD , Antígenos CD4/genética , Antígenos CD4/metabolismo , Ensaio de Unidades Formadoras de Colônias , DNA Viral/análise , Citometria de Fluxo , Transcriptase Reversa do HIV/análise , HIV-1/isolamento & purificação , Humanos , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Receptores CCR5/genética , Receptores CCR5/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo
17.
Blood ; 93(4): 1137-44, 1999 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-9949155

RESUMO

The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of their expression influences infectivity by HIV. We report here that interferon-gamma (IFN-gamma) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5 and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN-gamma showed increased chemotaxis to the CCR5 ligands macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta, confirming the functional relevance of IFN-gamma-induced CCR5 expression. However, IFN-gamma suppressed HIV entry into macrophages. Interestingly, we demonstrated that IFN-gamma inhibited cell surface expression of CD4, the major receptor for HIV. This finding may explain the suppressive effect of IFN-gamma on HIV entry into macrophages, despite its enhancing effect on the expression of CCR5 and CCR3 by these cells. In addition, IFN-gamma-induced secretion of C-C chemokines (RANTES, MIP-1alpha, and MIP-1beta) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are consistent with a novel paradigm in which cytokines regulate HIV infection and leukocyte migration by reciprocal and opposing effects on the expression of CD4 and chemokine receptors.


Assuntos
Antineoplásicos/farmacologia , Interferon gama/farmacologia , Monócitos/metabolismo , Receptores CCR5/biossíntese , Adulto , Quimiocina CCL3 , Quimiocina CCL4 , Quimiotaxia/efeitos dos fármacos , Feminino , Sangue Fetal/citologia , Humanos , Proteínas Inflamatórias de Macrófagos/farmacologia , Monócitos/citologia , Gravidez , Receptores CCR5/agonistas , Regulação para Cima/efeitos dos fármacos
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