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H pylori infection causes chronic pancreatitis in Mongolian gerbils

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World Journal of Gastroenterology 2007年第29期13卷 3939-3947页

作者： Gabriele Rieder Arno Karnholz Mechthild Stoeckelhuber juanita l merchant Rainer Haas Max von Pettenkofer-Institute for Hygiene and Medical Microbiology Ludwig-Maximilians-University 80336 Munich Germany Institute of Anatomy Ludwig- Maximilians-University 80336 Munich Germany University of Michigan Departments of Internal Medicine and Molecular and Integrative Physiology Ann Arbor Michigan United States

AIM: To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system. METHODS: Mongolian gerbils were infected with wild type (WT) H pylori typeⅠstrain B128 or its isogenic mutant B128 ?cagY (defective type Ⅳ secretion). After seven months of infection, H pylori was reisolated from antrum and corpus and H pylori DNA was analyzed by semi- nested polymerase chain reaction (PCR). Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry. Cytokine mRNA, gastric pH, plasma gastrin, amylase, lipase, and glucose levels were determined. RESUlTS: The H pylori infection rate was 95%. Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immuno- histochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals and those developing transmural inflammation and pancreatitis were significantly increased. levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas. CONClUSION: H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.

关键词：慢性胰腺炎幽门胃炎穿透性溃疡蒙古沙鼠

Histamine 3 receptor activation mediates inhibition of acid secretion during Helicobacter-induced gastritis

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World Journal of Gastrointestinal Pathophysiology 2010年第5期1卷 154-165页

作者： Yana Zavros Nisreen Mesiwala Meghna Waghray Andrea Todisco Arthur Shulkes juanita l merchant Departments of Internal Medicine-Gastroenterology University of Michigan Department of Molecular and Cellular Physiology University of Cincinnati Department of Surgery Austin and Repatriation Medical CenterUniversity of Melbourne Departments of Internal Medicine and Molecular and Integrative Physiology University of Michigan

AIM:To test the hypothesis that histamine 3 receptor (H3R)activation during Helicobacter infection inhibits gastric acid secretion in vivo and in vitro.METHODS:Helicobacter felis(H.felis)infected and uninfected C57Bl/6 mice were infused with either PBS or the H3 receptor antagonist thioperamide(THIO)for 12 wk.After treatment,mice were analyzed for morphological changes and gastric acid content.Total RNA was prepared from the stomachs of each group and analyzed for changes in somatostatin and gastrin mRNA abundance by real time-polymerase chain reaction(RTPCR).location of H3 receptors in the stomach was analyzed by co-localization using antibodies specific for the H3 receptor and parietal cell marker H + ,K + -ATPase βsubunit. RESUlTS:Inflammation and parietal cell atrophy was observed after 12 wk of H.felis infection.Interestingly, treatment with the H3R antagonist thioperamide(THIO) prior to and during infection prevented H.felis-induced inflammation and atrophy.Compared to the uninfected controls,infected mice also had significantly decreased gastric acid.After eradication of H.felis with THIO treatment,gastric acidity was restored.Compared to the control mice,somatostatin mRNA abundance was decreased while gastrin gene expression was elevated during infection.Despite elevated gastric acid levels, after eradication of H.felis with THIO,somatostatin mRNA was elevated whereas gastrin mRNA was suppressed.Immunofluorescence revealed the presence of H3 receptors on the parietal cells,somatostatin-secreting D-cells as well as the inflammatory cells. CONClUSION:This study shows that during H.felis infection,gastric acidity is suppressed as a consequence of an inhibitory effect on the parietal cell by H3R activation.The stimulation of gastric mucosal H3Rs increases gastrin expression and release by inhibiting release of somatostatin.

关键词： Gastrin Somatostatin Histamine Parietal

land use and dingo baiting are correlated with the density of kangaroos in rangeland systems

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Integrative Zoology 2023年第2期18卷 299-315页

作者： Stuart J.DAWSON Tracey l.KREPlINS Malcolm S.KENNEDY juanita RENWICK Mark A.COWAN Patricia A.FlEMING Terrestrial Ecosystem Science and Sustainability Harry Butler InstituteMurdoch UniversityMurdochAustralia Department of Primary Industries and Regional Development(present address) South PerthAustralia Department of Primary Industries and Regional Development NorthamAustralia Queensland Department of Environment and Science Australia Queensland Department of Environment and Science MoggillAustralia Department of Biodiversity Conservation and AttractionsWoodvaleAustralia

Rangelands worldwide have been subject to broadscale modiﬁcation,such as widespread predator control,intro-duction of permanent livestock water and altered vegetation to improve grazing.In Australia,these landscape changes have resulted in kangaroos(i.***.large macropods)populations increasing over the past 200 years.Kan-garoos are a key contributor to total grazing pressure and in conjunction with livestock and feral herbivores have been linked to land degradation.We used 22 years of aerial survey data to investigate whether the density of 3 macropod species in the southern rangelands of Western Australia was associated with:(i)land use,including type of livestock,total livestock,density of feral goats,type of land tenure,and kangaroo commercial harvest effort;(ii)predator management,including permitted dingo control effort,estimated dingo abundance,and presence of the State Barrier Fence(a dingo exclusion fence);and(iii)environmental variables:ruggedness,rainfall,fractional cover,and total standing dry matter.Red kangaroos(Osphranter rufus)were most abundant inﬂat,open vegetation,on pastoral land,where area permitted for dingo control was high,and numbers were positively associated with antecedent rainfall with a 12-month delay.Western grey kangaroos(Macropus fuliginosus)were most abundant onﬂat,agricultural land,but less abundant in areas with high permitted dingo control.Euros(Osphranter robustus)were most abundant in rugged pastoral land with open vegetation,where permitted dingo control was high.While environmental variables are key drivers of landscape productivity and kangaroo populations,anthropogenic factors such as land use and permitted dingo control are strongly associated with kangaroo abundance.

关键词： herbivores livestock macropods overgrazing rangelands total grazing pressure

Immuno-oncology combinations： raising the tail of the survival curve

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Cancer Biology & Medicine 2016年第2期13卷 171-193页

作者： Samuel J. Harris Jessica Brown juanita lopez Timothy A. Yap Drug Development Unit Royal Marsden Hospital and The Institute of Cancer Research London SM2 5PT UK lung Unit Royal Marsden Hospital and The Institute of Cancer Research London SM2 5PT UK

There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small cell lung cancer,immune checkpoint inhibitors also appears to have significant antitumor activity in multiple other tumor types. An exciting component of immunotherapy is the durability of antitumor responses observed, with some patients achieving disease control for many years. Nevertheless, not all patients benefit, and efforts should thus now focus on improving the efficacy of immunotherapy through the use of combination approaches and predictive biomarkers of response and resistance. There are multiple potential rational combinations using an immunotherapy backbone, including existing treatments such as radiotherapy, chemotherapy or molecularly targeted agents, as well as other immunotherapeutics. The aim of such antitumor strategies will be to raise the tail on the survival curve by increasing the number of long term survivors, while managing any additive or synergistic toxicities that may arise with immunotherapy combinations. Rational trial designs based on a clear understanding of tumor biology and drug pharmacology remain paramount. This article reviews the biology underpinning immuno-oncology, discusses existing and novel immunotherapeutic combinations currently in development, the challenges of predictive biomarkers of response and resistance and the impact of immuno-oncology on early phase clinical trial design.

关键词：免疫疗法生存曲线肿瘤学尾部抗肿瘤活性免疫治疗生物标志物非小细胞肺癌

Phenoloxidase and Melanization Innate Immune Activities in Green Darner Dragonfly Nymphs (Anax junius)

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Advances in Biological Chemistry 2022年第4期12卷 130-141页

作者： Mark merchant Matthew R. McClure Department of Chemistry McNeese State University Lake Charles USA Department of Biology Lamar State College Orange Orange USA

Insects in the Order Odonata are highly subject to infection by gregarine parasites. However, despite the important ecological roles that insects play in every ecosystem in which they exist, little research has been devoted to the description of insect immunity. Insects rely heavily on the rapid actions of innate immune mechanisms to prevent infection. We characterized the melanization response in the hemolymph of green darner dragonfly (Anax junius) nymphs. Incubation of chymotrypsin-activated hemolymph with l-DOPA resulted in volume- and time-dependent production of dopaquinone via the phenoloxidase (PO) enzyme, with biphasic accumulation of product. The PO activity was temperature-dependent, with a stepwise increase from 20℃ - 35℃ and maximum activity measured at 35℃ - 40℃. The formation of product was also inhibited in a concentration-dependent manner by diethylcarbonate, a specific inhibitor of PO activity, which indicated that the observed activity was due to the presence of PO enzyme. The rate of formation and quantity of melanin was dependent on exposure to different titers of bacteria. This is the first characterization of both PO activity and melanization response in green darner dragonflies.

关键词： Aquatic Insects Arthropod Dragonfly Hemolymph Innate Immunity Insect

Introduction of new techniques and technologies in surgery: Where is transanal total mesorectal excision today?

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World Journal of Gastrointestinal Surgery 2020年第5期12卷 203-207页

作者： Antonio Caycedo-Marulanda Sunil Patel Shaila merchant Carl Brown Department of surgery Queen’s University and Kingston General HospitalKingston K7L 2V7OntarioCanada Department of Surgery University of British Columbia and St.Paul HospitalVancouver V6Z 1Y6British ColumbiaCanada

The introduction of new surgical techniques and technologies has traditionally been unregulated.In many settings surgeons frequently adopt novel procedures without following a structured program of implementation or supervision.The appearance of innovative technology played a pivotal role in the advancement of new surgical techniques during the industrial revolution.Innovation has been an essential component of surgical development,which led to contemporary surgical techniques such as minimally invasive surgery.Different initiatives have been developed to guide the safe introduction of new surgical techniques and other procedures.Those include comprehensive concepts such as the Idea,Development,Exploration,Assessment,long-term study framework,which could be particularly relevant when reflecting on the novel transanal total mesorectal excision(taTME),introduced a decade ago.This relatively novel and complex procedure promised to overcome some of the major limitations of traditional surgical approaches for rectal cancer.According to the Idea,Development,Exploration,Assessment,long-term study framework,taTME is in the phase of exploration,where there is an existing and increasing number of reports being published as the experience grows.The current management of rectal cancer is in a state of radical evolution,with multiple options that were not previously available.Ta TME is only one technique amongst many which could be part of a rectal cancer surgeon’s armamentarium;however,it requires further rigorous study and evaluation.

关键词： Rectal cancer New technology Safety Innovation Transanal surgery

Proteomics and metabolic phenotyping define principal roles for the aryl hydrocarbon receptor in mouse liver

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3806-3819页

作者： Jian Jin Banrida Wahlang Monika Thapa Kimberly Z.Head Josiah E.Hardesty Sudhir Srivastava Michael l.merchant Shesh N.Rai Russell A.Prough Matthew C.Cave Department of Pharmacology&Toxicology theUniversity of Louisville School ofMedicineLouisvilleKY 40202USA Department of Endocrinology the Second Affiliated Hospital&Yuying Children’s HospitalWenzhou Medical UniversityWenzhou 325027China Division of Gastroenterology Hepatology&NutritionDepartment of Medicinethe University of Louisville School of MedicineLouisvilleKY 40202USA Superfund Research Center the University of LouisvilleLouisvilleKY 40202USA eDepartment of Biochemistry and Molecular Geneticsthe University of Louisville School of MedicineLouisvilleKY 40202USA Department of Bioinformatics and Biostatistics the School of Public Health and Information Sciencesthe University of LouisvilleLouisvilleKY 40202USA Centre for Agricultural Bioinformatics ICAR-Indian Agricultural Statistics Research InstituteNew Delhi 110012India The Center for Integrative Environmental Health Sciences University of LouisvilleLouisvilleKY 40202USA Division of Nephrology&Hypertension Department of Medicinethe University of Louisville School of MedicineLouisvilleKY 40202USA The Hepatobiology and Toxicology Center University of LouisvilleLouisvilleKY 40202USA Alcohol Research Center University of LouisvilleLouisvilleKY 40202USA Biostatistics and Bioinformatics Facility James Graham Brown Cancer CenterLouisvilleKY 40202USA

Dioxin-like molecules have been associated with endocrine disruption and liver disease.To better understand aryl hydrocarbon receptor(AHR)biology,metabolic phenotyping and liver proteomics were performed in mice following ligand-activation or whole-body genetic ablation of this receptor.Male wild type(WT)and Ahr^(-/-) mice(Taconic)were fed a control diet and exposed to 3,3',4,4',5-pentachlorobiphenyl(PCB126)(61 nmol/kg by gavage)or vehicle for two weeks.PCB126 increased expression of canonical AHR targets(Cyp1 a1 and Cyp1 a2)in WT but not Ahr^(-/-).Knockouts had increased adiposity with decreased glucose tolerance;smaller livers with increased steatosis and perilipin-2;and paradoxically decreased blood lipids.PCB126 was associated with increased hepatic triglycerides in Ahr^(-/-).The liver proteome was impacted more so by Ahr^(-/-) genotype than ligandactivation,but top gene ontology(GO)processes were similar.The PCB126-associated liver proteome was Ahr-dependent.Ahr principally regulated liver metabolism(e.g.,lipids,xenobiotics,organic acids)and bioenergetics,but it also impacted liver endocrine response(e.g.,the insulin receptor)and function,including the production of steroids,hepatokines,and pheromone binding proteins.These effects could have been indirectly mediated by interacting transcription factors or microRNAs.The biologic roles of the AHR and its ligands warrant more research in liver metabolic health and disease.

关键词： AHR Endocrine disruption Environmental liver disease Nonalcoholic fatty liver disease Perilipin-2 Pheromones PCB126

low skeletal muscle mass is associated with non-alcoholic fatty liver disease in Korean adults： the Fifth Korea National Health and Nutrition Examination Survey

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Hepatobiliary & Pancreatic Diseases International 2016年第1期15卷 39-47页

作者： hee yeon kim chang wook kim chung-hwa park jong young choi kyungdo han anwar t merchant yong-moon park division of hepatology department of internal medicinecollege of medicinethe catholic university of korea222Banpo-daeroSeocho-guSeou1 06591Republic of Korea department of biostatistics college of medicinethe catholic university of korea222Banpo-daeroSeocho-guSeou1 06591Republic of Korea department of epidemiology and biostatistics arnold school of public healthuniversity of south carolinaColumbiaSC 29208USA epidemiology branch national institute of environmental health sciencesnational institutes of healthdepartment of health and human servicesResearch Triangle ParkNC 27709USA

BACKGROUND： Sarcopenia and non-alcoholic fatty liver dis- ease （NAFlD） share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFlD has been recently investigated. The study investigated whether low skel- etal muscle mass is differentially associated with NAFlD by gender in Korean adults. METHODS： We conducted a cross-sectional analysis of the data from the Fifth Korea National Health and Nutrition Examination Survey. The skeletal muscle index （SMI） was obtained by the appendicular skeletal muscle mass divided by the weight. NAFlD was defined as a fatty liver index （FlI）〉60 in the absence of other chronic liver disease. RESUlTS： Among the included subjects, 18.3% （SE： 1.4%） in men and 7.0% （SE： 0.7%） in women were classified as having FlI-defined NAFlD. Most of the risk factors for FlI-defined NAFlD showed a significant negative correlation with the SMI in both genders. Multiple logistic regression analysis showed that low SMI was associated with FlI-defined NAFlD, inde- pendent of other metabolic and lifestyle parameters in both genders [males： odds ratio （OR）=1.35; 95% confidence inter- val （CI）： 1.17-1.54; females： OR=1.36; 95% CI： 1.18-1.55]. The magnitude of the association between FlI-defined NAFlD and low SMI was higher in middle aged to elderly males （OR-1.50; 95% CI： 1.22-1.84） than in males less than 45 years of age （OR=1.25; 95% CI： 1.02-1.52） and in premenopausal females （OR=l.50; 95% CI： 1.12-2.03） than in postmenopausal females （OR-1.36; 95% CI： 1.20-1.54）.CONClUSIONS： low SMI is associated with the risk of FlI- defined NAFlD independent of other well-known metabolic risk factors in both genders. This association may differ ac- cording to age group or menopausal status. Further studies are warranted to confirm this relationship.

关键词： Korea National Health and Nutrition Examination Survey non-alcoholic fatty liver disease sarcopenia skeletal muscle

Usefulness of supraclavicular flap in reconstruction following resection of oral cancer

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2018年第2期4卷 148-152页

作者： B. Vageesh Padiyar S.M. Azeem Mohiyuddin A. Sagayaraj Shuaib merchant Department of Otorhinolaryngology Head and Neck Surgery Sri Devaraj Urs Medical College and Research Centre Tamaka Kolar Karnataka 563101 India

Objective: To evaluate the usefulness of supraclavicular artery flap in reconstruc-tion of defects following resection of buccal mucosa cancer. Methods: Twenty-five patients who presented to R.l Jalappa Hospital and Research centre and diagnosed as squamous cell carcinoma of buccal mucosa staged T2 and above were included in our study. All patients underwent wide excision of tumour and neck dissection. Six patients un-derwent hemi-mandibulectomy while 4 patients underwent marginal mandibulectomy depend-ing on extent of the tumour along with neck dissection. The defect following surgery was reconstructed using the supraclavicular artery flap and were followed up for minimum 6 months during which they were assessed for the functional and aesthetic outcome using a scoring system. The details of the scoring system comprised of 7 attributes. Each attribute was given a score of 10 if the patients experienced that attribute, while a score of 0 was given if the patient did not experience that particular attribute. Results: Seven (28％) patients had complete necrosis of the flap. One patient had a local recur-rence 2 months following surgery and was lost to follow up. The remaining 17 patients were followed up for a minimum of 6 months and a scoring system was adopted to evaluate the func-tional and aesthetic outcome of the supraclavicular flap. We observed that 14 patients had an excellent outcome score (58％), 3 patients had a good outcome score (13％), while 7 patients (28％) had flap necrosis.Conclusions: We find the supraclavicular flap to be safe, technically simple, sensate, thin, pliable and reliable regional fasciocutaneous flap in reconstructing intra oral defects. Preser-ving the external jugular vein and sacrificing supraclavicular nerves give good outcome.

关键词： Squamous cell carcinoma Buccal mucosa cancer External jugular vein Supraclavicular artery flap