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1.
Tech Coloproctol ; 27(11): 1091-1098, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37133735

RESUMO

PURPOSE: To assess whether preoperative radiologically defined lean muscle measures are associated with adverse clinical outcomes in patients undergoing elective surgery for colorectal cancer. METHODS: This retrospective UK-based multicentre data collection study identified patients having had colorectal cancer resection with curative intent between January 2013 to December 2016. Preoperative computed-tomography (CT) scans were used to measure psoas muscle characteristics. Clinical records provided postoperative morbidity and mortality data. RESULTS: This study included 1122 patients. The cohort was separated into a combined group (patients with both sarcopenia and myosteatosis) and others group (either sarcopenia or myosteatosis, or neither). For the combined group, anastomotic leak was predicted on univariate (OR 4.1, 95% CI 1.43-11.79; p = 0.009) and multivariate analysis (OR 4.37, 95% CI 1.41-13.53; p = 0.01). Also for the combined group, mortality (up to 5 years postoperatively) was predicted on univariate (HR 2.41, 95% CI 1.64-3.52; p < 0.001) and multivariate analysis (HR 1.93, 95% CI 1.28-2.89; p = 0.002). A strong correlation exists between freehand-drawn region of interest-derived psoas density measurement and using the ellipse tool (R2 = 81%; p < 0.001). CONCLUSION: Measures of lean muscle quality and quantity, which predict important clinical outcomes, can be quickly and easily taken from routine preoperative imaging in patients being considered for colorectal cancer surgery. As poor muscle mass and quality are again shown to predict poorer clinical outcomes, these should be proactively targeted within prehabilitation, perioperative and rehabilitation phases to minimise negative impact of these pathological states.


Assuntos
Neoplasias Colorretais , Cirurgia Colorretal , Sarcopenia , Humanos , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/cirurgia , Músculos Psoas/diagnóstico por imagem , Músculos Psoas/patologia , Tomografia Computadorizada por Raios X/métodos , Reino Unido , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia
2.
Colorectal Dis ; 15(7): 848-57, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23451900

RESUMO

AIM: Many women undergoing sacral neuromodulation for faecal incontinence have coexisting pelvic floor dysfunction. We used a global pelvic-floor assessment questionnaire to evaluate the effect of sacral neuromodulation on non-bowel related symptomatology. METHOD: The electronic Personnel Assessment Questionnaire - Pelvic Floor (ePAQ-PF) is a validated Web-based electronic pelvic floor questionnaire. Women with faecal incontinence underwent assessment using the ePAQ. Pre- and poststimulator data were analysed over a 4.5-year period. RESULTS: Forty-three women (mean age 56.5 years; median follow up 6.8 months) were included. All (100%) had urinary symptoms, 81.4% had vaginal symptoms and 85.7% described some sexual dysfunction. There was a significant improvement in faecal incontinence and in bowel-related quality of life (P < 0.005) as well as in irritable bowel syndrome (IBS)-related symptoms (P < 0.01) and in bowel-related sexual heath (P < 0.01). Symptoms of vaginal prolapse significantly improved (P = 0.05). There was also improvement in symptoms of overactive bladder (P = 0.005) and in urinary-related quality of life (P < 0.05). A global health improvement was reported in 58.1%, mainly in bowel evacuation (P < 0.01) and in vaginal pain and sensation (P < 0.05). In sexually active female patients, significant improvements in vaginal and bowel-related sexual health were seen (P < 0.005). Improvement in general sex life following stimulation was reported in 53.3%. CONCLUSION: A Web-based electronic pelvic-floor assessment questionnaire has demonstrated global improvement in pelvic floor function in bowel, urinary, vaginal and sexual dimensions in women following sacral neuromodulation for faecal incontinence.


Assuntos
Terapia por Estimulação Elétrica/métodos , Incontinência Fecal/terapia , Distúrbios do Assoalho Pélvico/terapia , Prolapso de Órgão Pélvico/terapia , Nervos Espinhais , Incontinência Urinária/terapia , Incontinência Fecal/complicações , Feminino , Humanos , Neuroestimuladores Implantáveis , Pessoa de Meia-Idade , Distúrbios do Assoalho Pélvico/complicações , Prolapso de Órgão Pélvico/complicações , Qualidade de Vida , Região Sacrococcígea , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/terapia , Inquéritos e Questionários , Resultado do Tratamento , Incontinência Urinária/complicações
3.
Biochem Soc Trans ; 31(Pt 6): 1445-6, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14641085

RESUMO

Sprouty was first identified in Drosophila as a novel antagonist of the fibroblast growth factor signalling pathway. Sprouty proteins comprise a big family, members of which are characterized by a cysteine-rich domain which confers inhibitory activity, whereas differences in the N-terminal region may be responsible for functional divergence. The role of Sprouty in RTK (receptor tyrosine kinase) signalling pathways is still controversial. Sprouty may negatively or positively regulate RTK signalling via differential interaction with different signalling molecules, and hence exert different mechanism of action.


Assuntos
Proteínas de Drosophila/fisiologia , Proteínas de Membrana/fisiologia , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais/fisiologia , Animais , Proteínas de Drosophila/metabolismo , Proteínas de Membrana/metabolismo
4.
Cell Calcium ; 30(2): 95-106, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11440467

RESUMO

In adherent SH-SY5Y human neuroblastoma cells, activation of G-protein-coupled muscarinic M3 receptors evoked a biphasic elevation of both intracellular [Ca(2+)] ([Ca(2+)]i) and inositol-1,4,5-trisphosphate (D-Ins(1,4,5)P3) mass. In both cases, temporal profiles consisted of rapid transient elevations followed by a decline to a lower, yet sustained level. In contrast, platelet-derived growth factor (PDGF), a receptor tyrosine kinase agonist acting via PDGF receptor b chains in these cells, elicited a slow and transient elevation of [Ca(2+)]i that returned to basal levels within 5 to 10 min with no evidence of inositol phosphate generation. Full responses for either receptor type required intracellular and extracellular Ca(2+) and mobilization of a shared thapsigargin-sensitive intracellular Ca(2+) store. Strategies that affected the ability of D-Ins(1,4,5)P3 to interact with the Ins(1,4,5)P3-receptor demonstrated an Ins(1,4,5)P3-dependency of the muscarinic receptor-mediated elevation of [Ca(2+)]i but showed that PDGF-mediated elevations of [Ca(2+)]i are Ins(1,4,5)P3-independent in these cells.


Assuntos
Cálcio/metabolismo , Inositol 1,4,5-Trifosfato/metabolismo , Neuroblastoma/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais , Adesão Celular , Regulação para Baixo , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Humanos , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Receptores Muscarínicos/metabolismo , Tapsigargina/farmacologia , Timerosal/farmacologia , Fatores de Tempo , Células Tumorais Cultivadas
5.
J Gen Virol ; 72 ( Pt 4): 923-31, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1707948

RESUMO

Hamsters were immunized with either an affinity-purified preparation of equid herpesvirus 1 (EHV-1) glycoprotein 13 (gp13) or synthetic peptides representing three sequences within the homologous glycoprotein of EHV-4, resulting in the production of anti-peptide (in the case of peptide-immunized animals) or antivirus antibodies. The sera from gp13-immunized hamsters contained antibodies which showed virus-neutralizing activity and complement-mediated antibody lysis of EHV-1-infected target cells. These hamsters were protected from EHV-1 challenge. The characteristics of a panel of anti-gp13 monoclonal antibodies (P28, P17, 14H7, 16E4 and 16H9) were assessed both in vivo and in vitro. 16E4 and P28 showed high levels of complement-mediated neutralization of virus, complement-mediated lysis of virus-infected target cells and passive protection of hamsters. Furthermore, epitope mapping studies demonstrated that this glycoprotein contains a neutralizing epitope recognized by EHV-1-immune horse serum. The data imply that gp13 has potential as a candidate antigen for a molecular vaccine.


Assuntos
Herpesvirus Equídeo 1/imunologia , Proteínas do Envelope Viral/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais , Formação de Anticorpos , Cromatografia de Afinidade , Proteínas do Sistema Complemento , Cricetinae , Ensaio de Imunoadsorção Enzimática , Epitopos/análise , Herpesvirus Equídeo 1/isolamento & purificação , Imunização Passiva , Fígado/microbiologia , Pulmão/microbiologia , Mesocricetus , Dados de Sequência Molecular , Testes de Neutralização , Peptídeos/síntese química , Proteínas do Envelope Viral/isolamento & purificação
6.
J Gen Virol ; 71 ( Pt 10): 2407-16, 1990 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2172454

RESUMO

The high Mr glycoprotein (gp300) of equine herpesvirus type 1 was found to have an Mr, estimated by SDS-PAGE, of over 400,000 and was confirmed as being a surface glycoprotein by 125I-labelling. In contrast to [3H]glucosamine, gp300 showed very low levels of [3H]glucosamine, gp300 showed very low levels of [3H]mannose incorporation. The Mr of gp300 showed no detectable change upon treatment of purified virus with N-glycanase, and showed only a small change in virus-infected cells treated with tunicamycin. In addition, gp300 failed to bind the lectin concanavalin A. Taken together, these results indicate a lack of N-linked carbohydrate on gp300. The major carbohydrate species were found to be composed primarily of O-linked chains, as indicated by the sensitivity of the protein to monensin, to exoglycanase enzymes specific for sugars present in O-linked chains and to mild alkaline borohydride treatment, which revealed three species of carbohydrate of Mr of greater than 10,000, 2400 and 1100, respectively. Neuraminidase treatment and binding of Helix pomatia lectin indicated the presence of alpha-N-acetylglucosamine and sialic acid as terminal sugars. Immunological cross-reactivity of gp300 with a high Mr protein of equine herpesvirus type 4 was shown and it also exhibited a marked Mr variation in the vaccine strain Rhinomune.


Assuntos
Glicoproteínas/química , Herpesvirus Equídeo 1/análise , Proteínas Virais/química , Amidoidrolases/farmacologia , Anticorpos Monoclonais , Western Blotting , Carboidratos/análise , Eletroforese em Gel de Poliacrilamida , Glicoproteínas/imunologia , Glicosilação , Herpesvirus Equídeo 1/classificação , Herpesvirus Equídeo 1/imunologia , Herpesvirus Equídeo 1/ultraestrutura , Lectinas/metabolismo , Peso Molecular , Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase , Testes de Precipitina , Precursores de Proteínas/metabolismo , Proteínas Virais/imunologia
7.
Cryobiology ; 27(2): 164-70, 1990 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2331889

RESUMO

Skin from an inbred strain of hairless mouse was used as a homogeneous model tissue for studies of skin cryopreservation. Tetrazolium reductase enzyme activity was used to assess tissue viability. Hepes-buffered 199 tissue culture medium was confirmed to be a suitable basal medium, to which cryoprotectants were added. Addition of serum to the cryoprotective cocktail had no beneficial effect. Three cryoprotectants, dimethyl sulfoxide, ethanediol, and glycerol were evaluated. There was no evidence of specific toxicity attributable to the cryoprotective agents during the permeation period; however, short permeation times at low temperature were associated with maximum skin viability. Following freezing and thawing, higher viabilities were obtained when using a slow (-1 degree C min-1) or medium (-60 degree C min-1) rather than a fast (immersion in liquid nitrogen) cooling rate. Dimethyl sulfoxide was a marginally better cryoprotectant overall, although this difference was not statistically significant.


Assuntos
Criopreservação/métodos , Pele , Animais , Sobrevivência Celular , Crioprotetores , Dimetil Sulfóxido , Estudos de Avaliação como Assunto , Feminino , Camundongos , Camundongos Pelados , Camundongos Endogâmicos , NADH Tetrazólio Redutase/metabolismo , Pele/citologia , Pele/enzimologia , Transplante de Pele
8.
J Biol Chem ; 265(7): 4020-4, 1990 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-2137460

RESUMO

Eukaryotic cells adhere to at least two different regions of the fibronectin molecule: a central domain present in all fibronectin isoforms, and the type III connecting segment domain (IIICS), the expression of which is controlled by complex alternative splicing of precursor mRNA. Using affinity chromatography on a matrix containing a synthetic peptide ligand (CS1) representing the strongest active site within the IIICS, we have isolated the human melanoma cell receptor recognizing this region of fibronectin. The receptor is a complex of two polypeptides with subunit molecular masses of 145 and 125 kDa. This heterodimeric structure resembles that of receptors for other extracellular matrix proteins. Immunological analysis with specific antibodies identified these polypeptides as the integrin subunits alpha 4 and beta 1. In addition, antifunctional monoclonal antibodies directed against either alpha 4 or beta 1, but not against other integrin subunits, were potent inhibitors of CS1-mediated melanoma cell spreading. Furthermore, when the function of the central cell-binding domain was blocked, anti-alpha 4 and anti-beta 1 antibodies abolished spreading of A375-M cells on fibronectin, indicating that alpha 4 beta 1 is an authentic fibronectin receptor. Taken together, these results identify the human fibronectin IIICS receptor as the integrin heterodimer alpha 4 beta 1.


Assuntos
Fibronectinas/metabolismo , Integrinas/isolamento & purificação , Melanoma/imunologia , Receptores Imunológicos/isolamento & purificação , Sequência de Aminoácidos , Especificidade de Anticorpos , Complexo Antígeno-Anticorpo , Adesão Celular , Linhagem Celular , Cromatografia de Afinidade/métodos , Humanos , Integrinas/metabolismo , Cinética , Dados de Sequência Molecular , Peso Molecular , Peptídeos/síntese química , Receptores de Antígenos/isolamento & purificação , Receptores de Fibronectina , Receptores Imunológicos/metabolismo , Células Tumorais Cultivadas/imunologia
9.
Cryobiology ; 27(1): 24-30, 1990 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2311410

RESUMO

In order to evaluate the many variables that can affect cryopreservation success, a simple, highly reproducible model system is required. We have evaluated the use of tetrazolium reductase activity as a prognostic indicator of skin viability in an inbred murine model. Two inbred hairless mouse strains were characterized in studies on autografting and allografting following different skin-storage protocols. Skin tetrazolium reductase (TR) activity correlated well with oxygen consumption, and with graft success--the ultimate performance criterion--following varying degrees of cryogenic injury. The assay was shown to be highly reproducible. In a series of factorial experiments the only factors affecting TR activity were those concerning the mouse donors, i.e., mouse strain, age, sex, and body area. The effects of these factors on TR activity were fully characterized.


Assuntos
Criopreservação/métodos , Pele , Preservação de Tecido/métodos , Animais , Feminino , Masculino , Camundongos , Camundongos Pelados , Camundongos Endogâmicos C3H , NADH Tetrazólio Redutase/metabolismo , Consumo de Oxigênio , Pele/lesões , Pele/metabolismo , Transplante de Pele
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