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Cytoplasmic expression of p27^(kip1) is associated with a favourable prognosis in colorectal cancer patients

World Journal of Gastroenterology 2006年第39期12卷 6299-6304页

作者： nicholas FS Watson Lindy G Durrant John H Scholefield Zahra Madjd Duncan Scrimgeour Ian Spendlove Ian O Ellis poulam M patel Section of Gastrointestinal Surgery University of Nottingham Queens' Medical Centre Nottingham United Kingdom Academic Department of Clinical Oncology University of Nottingham Institute of Infections Immunity and Inflammation City Hospital Nottingham United Kingdom Academic Department of Clinical Oncology (with LGD ZM DS and PMP) University of Nottingham Institute of Infections Immunity and Inflammation City Hospital Nottingham United Kingdom Department of Histopathology Nottingham City Hospital and University of Nottingham Nottingham United Kingdom

AIM: To evaluate the prognostic significance of p27kip1 in colorectal cancer patients. METHODS: Cytoplasmic and nuclear p27kip1 expression was evaluated in 418 colorectal cancers using tissue microarrays. Data were associated with known patient and tumor variables and long-term patient outcomes, providing further insight into the mechanisms by which p27kip1 may influence tumor development. RESULTS: Nuclear and cytoplasmic p27Kip1 expressions were detected in 59% and 19% of tumors respectively. Cytoplasmic p27Kip1 was almost invariably associated with positive nuclear p27Kip1 expression. Neither case correlat- ed with known clinical or pathological variables, includ- ing tumor stage, grade or extramural vascular invasion. Furthermore, nuclear p27kip1 expression had no impact on survival. However, we identified a significant correla- tion between expression of cytoplasmic p27kip1 and longer disease-specific survival times. On multivariate analysis, TNM stage and extramural vascular invasion were highly significant independent prognostic factors, with positive cytoplasmic p27 expression showing a trend towards im- proved patient survival (p = 0.059).CONCLUSION: These findings support the recent evi- dence that cytoplasmic p27kip1 has a distinct and impor- tant biological role that can influence tumor outcome.

关键词： Colorectal cancer Tissue microarray p27^Kip1 prognostic factor

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Effect of preoperative biliary drainage on outcome of classical pancreaticoduodenectomy

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World Journal of Gastroenterology 2007年第8期13卷 1240-1242页

作者： Chandra Shekhar Bhati Chandrashekhar Kubal pankaj Kumar Sihag Ankur Atal Gupta Raj Kamal Jenav nicholas G Inston Jagdish M Mehta Upgraded Department of Surgery SMS Medical CollegeJaipurIndia Liver UnitQueen Elizabeth Hospital Birmingham United Kingdom Liver Unit Queen Elizabeth Hospital Birmingham United Kingdom Upgraded Department of Surgery SMS Medical CollegeJaipurIndia

AIM: To investigate the role of preoperative biliary drainage (pBD) in the outcome of classical pancreaticodu odenectomy. METHODS: A 10-year retrospective data analysis was performed on patients (n = 48) undergoing pancreaticoduodenectomy from March 1994 to March 2004 in department of surgery at SMS medical college, Jaipur, India. Demographic variables, details of preoperative stenting, operative procedure and post operative complications were noted. RESULTS: preoperative biliary drainage was performed in 21 patients (43.5%). The incidence of septic complications was significantly higher in patients with biliary stent placement (p p of patients also had a significantly higher minor biliary leak rate. Mortality and hospital stay in each group was comparable. CONCLUSION: Within this study population the use of pBD by endoscopic stenting was associated with a high incidence of infective complications. These findings do not support the routine use of biliary stenting in patients prior to pancreatico-duodenectomy.

关键词： Whipple's operation preoperative stenting Sepsis preoperative biliary drainage

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Experimental models to study cholangiocyte biology

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World Journal of Gastroenterology 2002年第1期8卷 1-4页

作者： pamela S.Tietz Robert C.Huebert Anatoliy Masyuk Tatyana Masyuk patrick L.Splinter nicholas F.LaRusso Center for Basic Research in Digestive Diseases Department of Internal Medicine and Biochemistry and Molecular BiologyMayo Medical SchoolClinic and FoundationRochesterMN 55905

Cholangiocytes-the epithelial cells which line the bileducts-are increasingly recognized as importanttransporting epithelia actively involved in the absorptionand secretion of water,ions,and *** is due in part to the recent development ofnew experimental *** biologic concepts haveemerged including the identification and topography ofreceptors and flux proteins on the apical and/orbasolateral membrane which are involved in the molecularmechanisms of ductal bile *** isolatedand/or perfused bile duct units from livers of rats andmice serve as new,physiologically relevant in vitromodels to study cholangiocyte *** treedimensions and novel insights into anatomic remodeling ofproliferating bile ducts have emerged from three-dimensional reconstruction using CT scanning andsophisticated ***,new pathologicconcepts have arisen regarding the interaction ofcholangiocytes with pathogens such as *** concepts and associated methodologiesmay provide the framework to develop new therapies forthe cholangiopathies,a group of important hepatobiliarydiseases in which cholangiocytes are the target cell.

关键词： Animals Bile Ducts Biological Transport Epithelial Cells Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, p.H.S.

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Multimode vibrational strong coupling in direct laser written mid-IR plasmonic MIM nano-patch antennas

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photonics Research 2023年第12期11卷 2136-2148页

作者： nicholas V.pROSCIA MICHAEL A.MEEKER nicholas SHARAC FRANK K.pERKINS CHASE T.ELLIS pAUL D.CUNNINGHAM JOSEpH G.TISCHLER NRC postdoc residing at U.S.Naval Research Laboratory WashingtonD.C.20375USA U.S.Naval Research Laboratory WashingtonD.C.20375USA Current address:Rigetti Computing FreemontCalifornia 94538USA Current address:Homer L.Dodge Department of physics and Astronomy The University of OklahomaNormanOklahoma 73019USA

Strong coupling of mid-infrared(mid-IR)vibrational transitions to optical cavities provides a means to modify and control a material’s chemical reactivity and offers a foundation for novel chemical detection ***,the relatively large volumes of the mid-IR photonic cavities and weak oscillator strengths of vibrational transitions restrict vibrational strong coupling(VSC)studies and devices to large ensembles of molecules,thus representing a potential limitation of this nascent ***,we experimentally and theoretically investigate the mid-IR optical properties of 3D-printed multimode metal-insulator-metal(MIM)plasmonic nanoscale cavities for enabling strong light-matter interactions at a deep subwavelength *** observe strong vibration-plasmon coupling between the two dipolar modes of the L-shaped cavity and the carbonyl stretch vibrational transition of the polymer *** cavity mode volume is half the size of a typical square-shaped MIM geometry,thus enabling a reduction in the number of vibrational oscillators to achieve strong *** resulting three polariton modes are well described by a fully coupled multimode oscillator model where all coupling potentials are *** 3D printing technique of the cavities is a highly accessible and versatile means of printing arbitrarily shaped submicron-sized mid-IR plasmonic cavities capable of producing strong light–matter interactions for a variety of photonic or photochemical ***,similar MIM structures fabricated with nanoscopic voids within the insulator region could constitute a promising microfluidic plasmonic cavity device platform for applications in chemical sensing or photochemistry.

关键词： coupling vibrational shaped

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Orofacial Clefts in High prevalence Area of Birth Defects—Five Counties,Shanxi province,China,2000–2020

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China CDC weekly 2021年第37期3卷 773-777页

作者： Jufen Liu Yali Zhang Le Zhang Linlin Wang Lei Jin nicholas D E Greene Zhiwen Li Aiguo Ren Institute of Reproductive and Child Health/Key Laboratory of Reproductive Health National Health Commission of the People’s Republic of ChinaPeking UniversityBeijingChina Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijingChina UCL Great Ormond Street Institute of Child Health University College LondonLondonUK.

Summary What is already known on this topic?The prevalence of structural birth defects,especially neural tube defects,decreased after national folic acid(FA)supplementation *** is added by this report?The prevalence of orofacial clefts(OFCs)in five counties of Shanxi province in northern China,including most subtypes except cleft palate,showed a downward trend in the past two *** this study,pre-perinatal prevalence increased due to earlier detection.

关键词： Shanxi defects downward

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Evaluation of HemogloBind<sup>TM</sup>treatment for preparation of samples for cholinesterase analysis

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Advances in Bioscience and Biotechnology 2013年第12期4卷 1020-1023页

作者： Kevin G. McGarry ryan A. Bartlett nicholas J. Machesky Thomas H. Snider Robert A. Moyer David T. Yeung Matthew K. Brittain Battelle Biomedical Research Center Battelle Memorial Institute Columbus USA National Institutes of Health/National Institute of Neurological Disorders and Stroke Bethesda USA

Acetylcholine is an essential neurotransmitter found throughout the nervous system. Its action on postsynaptic receptors is regulated through hydrolysis by various carboxylesterases, especially cholinesterases (ChEs). The acute toxicity of organophosphate (Op) compounds is directly linked to their action as inhibitors of ChE. One widely used assay for evaluating ChE activity is a spectrophotometric method developed by Ellman et al. When the enzyme source is from tissues or, in particular, blood, hemoglobin displays a spectrophotometric peak at the same wave-length used to analyze cholinergic activity. This creates a substantial background that interferes with the Ellman’s assay and must be overcome in order to accurately monitor cholinesterase activity. Herein, we directly compare blood processing methods: classical method (1.67 ± 0.30 U/mL) and HemogloBindTM treatment (1.51 ± 0.17 U/mL), and clearly demonstrate that pretreatment of blood samples with HemoglobindTM is both a sufficient and rapid sample preparation method for the assessment of ChE activity using the Ellman’s method.

关键词： Acetylcholinesterase Cholinesterase HemogloBindTM Sample preparation Hemoglobin

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Lipopolysaccharide Modified Liposomes for Amyotropic Lateral Sclerosis Therapy: Efficacy in SOD1 Mouse Model

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Advances in Nanoparticles 2012年第3期1卷 44-53页

作者： nicholas J. Wiley A. B. Madhankumar ryan M. Mitchell Elizabeth B. Neely Elias Rizk Gregory L. Douds Zachary Simmons James R. Connor Department of Neurology Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center Hershey USA George M. Leader Family Laboratory Department of Neurosurgery Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center Hershey USA

Activation of microglia is a histological feature observed in neurodegenerative diseases like ALS. The oral administration of minocycline has been demonstrated to have minimal neuroprotection ability in the animal models and is also associated with inadvertent toxicity due to non-specific oral absorption of the drug. Nonetheless, the drug itself shows promise in a number of disease models suggesting it could be effective if delivered optimally. Thus, we utilized LpS modified liposomes to target TLR4 receptor on the microglia in SOD1G93A mice and compared its efficacy with non- targeted nanoliposomes. The in vitro results indicate that targeting the TLR4 receptor on microglia significantly increases (p G93A mouse model of ALS, targeted and non-targeted minocycline treatment significantly increased (p G93A mice, the non- targeted nanovesicles significantly increased the latency to rotarod failure and both targeted and non-targeted nanovesicles significantly delayed disease endpoints.

关键词： Amyotrophic Lateral Sclerosis Minocycline Liposomes Microglia TLR4 Lipopolysaccharides

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Maternal helminth infection protects offspring from high-fat-diet-induced obesity through altered microbiota and SCFAs

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Cellular & Molecular Immunology 2023年第4期20卷 389-403页

作者： Chien-Wen Su Chih-Yu Chen Tangyou Mao Ning Chen nicholas Steudel Lefei Jiao Jinggang Lan Alessio Fasano WAllan Walker Hai Ning Shi Mucosal Immunology and Biology Research Center Massachusetts General Hospital and Harvard Medical SchoolCharlestownMAUSA Laboratory for Lipid Medicine and Technology Department of MedicineMassachusetts General Hospital and Harvard Medical SchoolCharlestownMAUSA Department of Gastroenterology Dongfang HospitalBeijing University of Chinese MedicineBeijingChina Shenzhen Institute for Drug Control ShenzhenChina.

Helminth-induced Th2 immunity and gut microbiota have been recently shown to be highly effective in modulating metabolic syndromes in animal *** study aimed to determine whether maternal immunity and microbial factors affect the induction and development of obesity in ***,Heligomosomoides polygyrus(Hp)-infected or control female C57BL/6J mice mated with normal males and their offspring were fed a high-fat diet(HFD)for 9 weeks after *** results showed that Hp-induced maternal outcomes during gestation and lactation significantly impacted offspring metabolic *** was evidenced by results showing that offspring from helminth-infected mothers on an HFD(Hp-offspring+HFD)gained significantly less body weight than those from uninfected mothers(Cont-offspring+HFD).Hp-offspring+HFD exhibited no Th2 phenotype but displayed a pattern of gut microbiota composition similar to that of Hp-infected ***-fostering experiments confirmed that the helminth-induced maternal attenuation of offspring obesity was mediated through both prenatal and postnatal *** results further showed that helminth-infected dams and their offspring had a markedly altered gut microbiome composition,with increased production of short-chain fatty acids(SCFAs).Intriguingly,Hp-infected mothers and Hp-offspring+HFD showed increased SCFA receptor(GpR)expression in adipose and colonic tissues compared to noninfected mothers and Cont-offspring+HFD,***,SCFA supplementation to the pups of uninfected control mothers during lactation protected against HFD-induced weight gain,which corresponded with changes in gut bacterial ***,our findings provide new insights into the complex interaction of maternal immune status and gut microbiome,Hp infection,and the immunity and gut microbiome in obese-prone offspring in infant life.

关键词： Helminth Maternal Th2 immunity Microbiota Offspring Obesity SCFAs

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Alcoholic vs. Nonalcoholic Steatohepatitis: Vascular Branching Heterogeneity on Magnetic Resonance Imaging as a Diagnostic Marker

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 534-539页

作者： Daniel Garrido nicholas Noverati Justin Robbins Jaydev K.Dave Haresh Naringrekar Donald G.Mitchell Dina Halegoua-De Marzio Department of Medicine Division of Gastroenterology and HepatologyThomas Jefferson University HospitalPhiladelphiaPAUSA Department of Medicine Thomas Jefferson University HospitalPhiladelphiaPAUSA Department of Radiology Thomas Jefferson University HospitalPhiladelphiaPAUSA

Background and Aims: Distinguishing alcoholic steato-hepatitis (ASH) and nonalcoholic steatohepatitis (NASH) with biopsy alone is often difficult without a reliable clinical con-text. A novel finding on liver imaging, perivascular branching heterogeneity, has shown promise in distinguishing between these chronic liver diseases. Our study investigated the role of this finding on imaging to differentiate between ASH and NASH. The aim of this study was to determine the utility and reproducibility of this novel radiographic marker to help dis-tinguish ASH from NASH. Methods: This was a retrospective cohort study conducted between 2016 and 2020 in patients with both liver biopsy-confirmed steatohepatitis/chronic hep-atitis and abdominal magnetic resonance imaging within 13 months of each other. Two radiologists, blinded to patient clinical history and diagnosis, categorized the appearance of the liver as: 1- homogeneity, 2- mild heterogeneity, 3- mod-erate heterogeneity, 4- possible perivascular branching, 5- definite perivascular branching. Results: Of the 90 patients in the study, 60 were identified as NASH and 30 as ASH. The area under the curve (AUC) for both reader 1 and 2 when us-ing the 5-point scale was 0.69 (CI: 0.56-0.82, p=0.006) and 0.72 (CI: 0.60-0.85, p=0.001), respectively. The positive predictive value (ppV) for identification of ASH when scoring 5 was 64.7% and 66.7% for reader 1 and 2, respectively. In-terclass correlation coefficient was 0.74 in patients with ASH, indicating moderate reliability among both readers. Conclu-sions: Identification of this perivascular branching pattern on imaging is a promising novel diagnostic marker that can be used with other methods to help distinguish between ASH and NASH.

关键词： Alcoholic liver diseases Steatohepatitis Magnetic resonance imag-ing Nonalcoholic fatty liver disease

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Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation

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World Journal of Clinical Cases 2019年第3期7卷 270-290页

作者： Evaldo Favi Carmelo puliatti Rajesh Sivaprakasam Mariano Ferraresso Federico Ambrogi Serena Delbue Federico Gervasi Ilaria Salzillo nicholas Raison Roberto Cacciola Renal Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico Renal Transplantation Barts Health NHS Trust Royal London Hospital Department of Clinical Sciences and Community Health University of Milan Department of Biomedical Surgical and Dental Sciences University of Milan MRC Centre for Transplantation King’s College London

BACKGROUND polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless,long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also *** To investigate incidence, risk factors, and outcome of BK-virus infection after kidney *** This single-centre observational study with a median follow up of 57(31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasmaquantitative polymerized chain reaction. patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment,rejection, renal function, urologic complications, opportunistic infections, newonset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and *** BK-viremia was detected in 9.5% recipients. Initial viral load was high(≥ 10000 copies/mL) in 66.7% and low(pies/mL) in 33.3% of these ***-associated nephropathy was diagnosed in 6.5% of the study population. patients with high initial viral load were more likely to experience sustained viremia(95% vs 25%, p phropathy(92.

关键词： polyomavirus BK virus Kidney transplantation Outcome Risk factors Immunosuppression Human leukocyte antigen Rejection Cytomegalovirus Ethnicity

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