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Childhood Langerhans cell histiocytosis:a disease with many faces

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World Journal of Pediatrics 2019年第6期15卷 536-545页

作者： Alexander K.C.Leung joseph m.Lam Kin Fon Leong Department of Pediatrics The University of Calgaryand The Alberta Children's Hospital#20023316th Avenue NWCalgaryAB T2M 0H5Canada Department of Pediatrics University of British ColumbiaVancouverBCCanada Department of Dermatology and Skin Sciences University of British ColumbiaVancouverBCCanada Pediatric Institute Kuala Lumpur General HospitalKuala LumpurMalaysia

Background Langerhans cell histiocytosis(LCH)is a group of diseases characterized by the proliferation and accumulation of Langerhans *** presentations of LCH vary *** sources A Pubmed search was conducted using Clinical Queries with the key term "Langerhans cell histiocytosis".The search strategy included meta-analyses,randomized controlled trials,clinical trials,observational studies,and *** paper is based on,but not limited to,the search *** Generally,patients with LCH can be divided into two groups based on the extent of involvement at diagnosis,namely,single-system LCH and multisystem *** involvement may be unifocal or *** with isolated bone lesions typically present between 5 and 15 years of age,whereas those with multisystem LCH tend to present before 5 years of *** clinical spectrum is broad,ranging from an asymptomatic isolated skin or bone lesion to a life-threatening multisystem *** manifestations include,among others,"punched out" lytic bone lesion,seborrheic dermatitis-like erup-tion,erythematous/reddish-brown crusted/scaly papules/maculopapules/plaques/patches,and eczematous lesions,diabetes insipidus,hepatosplenomegaly,cytopenias,lymphadenopathy,and an acute fulminant disseminated multisystem condition presenting with fever,skin rash,anemia,thrombocytopenia,lymphadenopathy,and *** diagnosis is clinicopathologic,based on typical clinical findings and histologic/immunohistochemical examination of a biopsy of lesional *** CD1a,S100,and/or CD207(Langerin)immunohistochemical staining of lesional cells is required for a definitive *** waiting is recommended for patients with skin-only *** with symptomatic or refractory skin-only LCH may be treated with topical tacrolimus/corticosteroids,topical nitrogen mustard,oral methotrexate,or oral *** current recommended first-line therapy for patients with multisystem LCH i

关键词： Cytopenia Diabetes insipidus Eczematous lesions Hepatosplenomegaly Lymphadenopathy Seborrheic dermatitis-like eruption

The emerging role and targetability of the TCA cycle in cancer metabolism

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Protein & Cell 2018年第2期9卷 216-237页

作者： Nicole m. Anderson Patrick mucka joseph G. Kern Hui Feng Abramson Family Cancer Research Institute University of Pennsylvania Philadelphia PA 19104-6160 USA Perelman School of medicine at the University of Pennsylvania Philadelphia PA 19104 USA Departments of Pharmacology and medicine The Center for Cancer Research Section of Hematology and Medical Oncology Boston University School of Medicine Boston MA 02118 USA Program in Biomedical Sciences Boston University School of Medicine Boston MA 02118 USA

The tricarboxylic acid （TCA） cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance require- ments. Despite early dogma that cancer cells bypass the TCA cycle and primarily utilize aerobic glycolysis, emerging evidence demonstrates that certain cancer cells, especially those with deregulated oncogene and tumor suppressor expression, rely heavily on the TCA cycle for energy production and macromolecule synthesis. As the field progresses, the importance of aberrant TCA cycle function in tumorigenesis and the potentials of applying small molecule inhibitors to perturb the enhanced cycle function for cancer treatment start to evolve. In this review, we summarize current knowledge about the fuels feeding the cycle, effects of oncogenes and tumor suppressors on fuel and cycle usage, common genetic alterations and deregulation of cycle enzymes, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo model organism studies, it is our hope that studies of this previously overlooked biochemical hub will provide fresh insights into cancer metabolism and tumorigenesis, subsequently revealing vulnerabilities for thera- peutic interventions in various cancer types.

关键词： glutaminolysis the TCA cycle cancer metabolism glycolysis

A cost-effective method to enhance adenoviral transduction of primary murine osteoblasts and bone marrow stromal cells

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Bone Research 2016年第2期4卷 91-100页

作者： Atum m Buo mark S Williams Jaclyn P Kerr joseph P Stains Department of Orthopaedics University of Maryland School of Medicine Department of microbiology and Immunology University of Maryland School of Medicine

We report here a method for the use of poly-L-lysine （PLL） to markedly improve the adenoviral transduction efficiency of primary murine osteoblasts and bone marrow stromal cells （BmSCs） in culture and in situ, which are typically difficult to transduce. We show by fluorescence microscopy and flow cytometry that the addition of PLL to the viral-containing medium significantly increases the number of green fluorescence protein （GFP）-positive osteoblasts and BmSCs transduced with an enhanced GFP-expressing adenovirus. We also demonstrate that PLL can greatly enhance the adenoviral transduction of osteoblasts and osteocytes in situ in ex vivo tibia and calvaria, as well as in long bone fragments. In addition, we validate that PLL can improve routine adenoviral transduction studies by permitting the use of low multiplicities of infection to obtain the desired biologic effect. Ultimately, the use of PLL to facilitate adenoviral gene transfer in osteogenic cells can provide a cost-effective means of performing efficient gene transfer studies in the context of bone research.

关键词： A cost-effective method to enhance adenoviral transduction of primary murine osteoblasts and bone marrow stromal cells PLL bone

Clinical implications of COVID-19 in patients with metabolicassociated fatty liver disease

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World Journal of Gastroenterology 2023年第3期29卷 487-502页

作者： mohammad Sadiq Jeeyavudeen Rahul Chaudhari joseph m Pappachan Sherouk Fouda Department of Endocrinology and metabolism University Hospitals of EdinburghEdinburgh EH42XUUnited Kingdom Department of Gastroenterology Hepatology and NutritionVirginia Commonwealth UniversityRichmondVA 23298United States Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom School of Health and Biomedical Sciences RMIT UniversityMelbourne VICAustralia

People across the world are affected by the"coronavirus disease 2019(COVID-19)",brought on by the"SARS-CoV type-2 coronavirus".Due to its high incidence in individuals with diabetes,metabolic syndrome,and metabolic-associated fatty liver disease(mAFLD),COVID-19 has gained much *** metabolic syndrome's hepatic manifestation,mAFLD,carries a significant risk of *** link between the above two conditions has also drawn increasing consideration since mAFLD is intricately linked to the obesity *** of the metabolic syndrome,mAFLD may impact the severity of the viral infections,including COVID-19 or may even be a risk *** important question is whether the present COVID-19 pandemic has been fueled by the obesity and mAFLD *** liver markers are seen elevated in *** patients with associated comorbid conditions like obesity,cardiovascular disease,renal disease,malignancy,hypertension,and old age are prone to develop severe *** is an urgent need for more studies to determine the link between the two conditions and whether it might account for racial differences in the mortality and morbidity rates linked to *** role of innate and adaptive immunity alterations in mAFLD patients may influence the severity of *** review investigates the implications of COVID-19 on liver injury and disease severity and *** also addressed the severity of COVID-19 in patients with prior mAFLD and its potential implications and therapeutic administration in the clinical setting.

关键词： metabolic-associated fatty liver disease COVID-19 metabolic syndrome Non-alcoholic steatohepatitis Angiotensin converting enzyme 2

Advances in immuno-oncology biomarkers for gastroesophageal cancer:programmed death ligand 1,microsatellite instability,and beyond

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World Journal of Gastroenterology 2018年第25期24卷 2686-2697页

作者： Emily m Lin Jun Gong Samuel J Klempner joseph Chao Department of Internal medicine Harbor-UCLA Medical CenterTorranceCA 90509United States Department of medical Oncology and Developmental Therapeutics City of Hope Comprehensive Cancer CenterDuarteCA 91010United States The Angeles Clinic and Research Institute Los AngelesCA 90404United States Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical CenterLos AngelesCA 90048United States

Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. microsatellite instability(mSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with mSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer.

关键词： Immunotherapy programmed cell death 1 programmed death ligand 1 microsatellite instablility Gastric cancer

Epidemiological, Clinical and Paraclinical Profile of Osteoarthritis of the Lower Limbs in Obese Patients at the Cocody University Teaching Hospital

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Open Journal of Rheumatology and Autoimmune Diseases 2024年第2期14卷 69-76页

作者： Nzima Brice Kollo Aboubakar Bamba¹ Aboubacar Sidiki Condé Nzima Hilary Ngon Kanbaye medom Ada Nina Kpami Yaya Coulibaly Kan joseph Enoch Koffi Ehaulier Soh Christian Louis Kouakou mohamed Diomandé¹ Edmond Eti Rheumatology Department Cocody University Hospital Abidjan C&#244te d&#8217Ivoire Internal medicine Department Yaounde University Hospital Yaounde Cameroon Rheumatology Department Bouake University Hospital Bouake C&#244te d&#8217Ivoire

Objective: To describe the epidemiological, clinical and paraclinical characteristics of osteoarthritis of the lower limbs in obese patients at the Cocody University Teaching Hospital. methodology: This was an analytical cross-sectional study carried out in the rheumatology department of the Cocody UTH in Abidjan (Ivory Coast) from march 1 to April 30 2023. Patients who came for rheumatology consultation presenting with mechanical arthralgia of the lower limbs, who were obese, had radiographic images were included. All patients without radiographic images were excluded. Obesity was defined as a body mass index (BmI) greater than or equal to 30 kg/m. The Chi2 test was used to compare proportions and determine the existence of associations between osteoarthristis and obesity, obesity severity and radiographic stage of osteoarthritis as well as the functional impact. A p-value below a predefined threshold (p = 0,05) indicates a significant relationship between the variables. Result: Out of 185 patients received for osteoarthritis of the lower limbs during the study period, 136 were obese (74%). There were 115 women (84.6%) with an average age of 56.03 with a standard deviation of 12.72 years (extremes: 22 and 84 years). The main socio-professional category was the informal sector (30%). The majority of patients had a low socio-economic level (80.2%) and lived in urban areas (92.6%). The most common past medical history was hypertension (33.08%) followed by peptic ulcer disease (16.91%). Patients had a body mass index class 1 (81.6%), class 2 (15.40%) and class 3 (2.90%). The average duration of symptom progression until diagnosis was 11 months. Genu varum was the main static disorder (56.10%) and the knee joint was the dominant topography (90.4%) with a bilateral localization (80%). The average Lequesne index was greater than 8 (59.5%). The Kellgren and Lawrence radiographic stages were stage 1 (9.20%), stage 2 (46.90%), stage 3 (29.20%) and stage 4 (6.90%).

关键词： Osteoarthritis Lower Limbs Obesity Abidjan

Visceral Leishmaniasis at the National Reference University Hospital Center of N’Djamena (Chad): Epidemiological, Clinical, Diagnostic, Therapeutic and Prognostic Aspects

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Advances in Infectious Diseases 2024年第2期14卷 478-486页

作者： joseph mad-Toïngué mahamat Ali Ahmat Oumaïma mahamat Djarma Alifa Adjibera Philippe Ali mahamat moussa Ngakoutou Rangar Choua Ouchemi mahamat Ali Bolti Djiddi Ali Sougoudi mamissou Didi mahamat Doungous Atim Service des maladies Infectieuses CHU de Référence Nationale N’Djamena Chad Service de Gastroentérologie et médecine Interne CHU de Référence Nationale N’Djamena Chad Service de Pneumologie et Phtisiologie CHU de Référence Nationale N’Djamena Chad Service de Chirurgie viscérale CHU de Référence Nationale N’Djamena Chad Service de médecine CHU de la Renaissance N’Djamena Chad

Introduction: leishmaniasis is a group of parasitic diseases caused by a parasite of the genus Leishmania transmitted by the bite of an infected vector called a sandfly. There are four forms. Visceral leishmaniasis is the most severe form. The aim of our work is to study the epidemiological, clinical, diagnostic, therapeutic and prognostic aspects of the disease in the Infectious Diseases Department of the Centre Hospitalier Universitaire de Référence Nationale in N'Djaména. methodology: Patients were recruited on the basis of clinical signs suggestive of visceral leishmaniasis, i.e. prolonged fever, splenomegaly and altered general condition. Biological confirmation was performed with a rapid diagnostic test using recombinant K39 parasite antigen, which is known to have good specificity and sensitivity. Epidata version 3.1 software was used to process patient data. Results: From 05/04/21 to 15/12/23, 153 positive cases were managed. The mean age of patients was 18 years, with a sex ratio of 9.2. Of these patients, 103 (67.3%) had recently stayed at gold mining sites. Patients testing positive were treated with sodium stibogluconate combined with paromomycin for 17 days. The mortality rate was 13.2%. Conclusion: Leishmaniasis is a serious and little-known disease in Chad. In order to respond to the disease, it is necessary to reinforce the capacities of health structures and to carry out appropriate actions in the outbreaks.

关键词： Visceral Leishmaniasis Gold mining Sites Chad

Generating a CRISPR knockout mouse through a strong premature termination codon:a cautionary tale

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The Journal of Biomedical Research 2021年第2期35卷 174-178,1-4页

作者： Lyu Qing Rex Yao Peng miano joseph m Aab Cardiovascular Research Institute University of Rochester School of Medicine & Dentistry USA Rochester NY14642 Vascular Biology Center Medical College of Georgia at Augusta University USA Augusta GA30912 Institute of Biomedicine and Health Chongqing Institute of Green and Intelligent Tec Chongqing 400714

Dear Editor,Genetic inactivation or gene knockout(KO)has been a powerful method of elucidating gene function in *** traditional method of generating KO mice via targeting mouse embryonic stem cells through homologous ... 详细信息

关键词： knockout inactivation termination

management of metabolic-associated fatty liver disease: The diabetology perspective

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World Journal of Gastroenterology 2023年第1期29卷 126-143页

作者： mohammad Sadiq Jeeyavudeen Shahanas K A Khan Sherouk Fouda joseph m Pappachan Department of Endocrinology and metabolism University Hospitals of EdinburghEdinburgh EH42XUUnited Kingdom Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom School of Health and Biomedical Sciences RMIT UniversityMelbourneVIC 3046Australia Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology University of ManchesterManchester M139PLUnited Kingdom

The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease(mAFLD)and type 2 diabetes mellitus(T2Dm).Because of the similarity in pathobiology shared between T2Dm and mAFLD,both disorders coexist in many patients and may potentiate the disease-related outcomes with rapid progression and increased complications of the individual *** fact,awareness about this coexistence and the risk of complications are often overlooked by both hepatologists and *** of these individual disorders in a patient should be addressed wholistically using an appropriate multidisciplinary team approach involving both the specialists and,when necessary,liaising with dieticians and *** comprehensive review is to compile the current evidence from a diabetologist's perspective on mAFLD and T2Dm and to suggest optimal management strategies.

关键词： metabolic syndrome metabolic-associated fatty liver disease Type 2 diabetes mellitus Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Diabetology perspective Obesity