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“Autoinflammatory psoriasis”-genetics and biology of pustular psoriasis

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Cellular & Molecular Immunology 2021年第2期18卷 307-317页

作者： Ranjitha Uppala lam C.Tsoi paul W.Harms Bo Wang Allison C.Billi Emanual Maverakis J.Michelle Kahlenberg Nicole L.Ward Johann E.Gudjonsson Graduate Program in Immunology University of MichiganAnn ArborMIUSA Department of Dermatology University of MichiganAnn ArborMIUSA Department of Pathology University of MichiganAnn ArborMIUSA Department of Dermatology University of CaliforniaDavisSacramentoCAUSA Division of Rheumatology Department of Internal MedicineUniversity of MichiganAnn ArborMIUSA A.Alfred Taubman Medical Research Institute Ann ArborMIUSA Departments of Nutrition and Dermatology Case Western Reserve UniversityClevelandOHUSA

Psoriasis is a chronic inflammatory skin condition that has a fairly wide range of clinical *** psoriasis,which is the most common manifestation of psoriasis,is located on one end of the spectrum,dominated by adaptive immune responses,whereas the rarer pustular psoriasis lies on the opposite end,dominated by innate and autoinflammatory immune *** recent years,genetic studies have identified six genetic variants that predispose to pustular psoriasis,and these have highlighted the role of IL-36 cytokines as central to pustular psoriasis *** this review,we discuss the presentation and clinical subtypes of pustular psoriasis,contribution of genetic predisposing variants,critical role of the IL-36 family of cytokines in disease pathophysiology,and treatment perspectives for pustular *** further outline the application of appropriate mouse models for the study of pustular psoriasis and address the outstanding questions and issues related to our understanding of the mechanisms involved in pustular psoriasis.

关键词： Pustular psoriasis Genetics IL-36 Autoinflammation Clinical features Histology

Atmospheric polychlorinated biphenyls measured during the 2008 Chinese National Arctic Research Expedition

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Advances in Polar Science 2015年第3期26卷 239-248页

作者： WU Xiaoguo James C W lam XIA Chonghuan KANG Hui XIE Zhouqing paul K S lam Institute of Polar Environment School of Earth and Space Sciences University of Science and Technology of China Advanced Lab for Environmental Research and Technology (ALERT) University of Science and Technology of ChinaCity University of Hong Kong (USTC-City U) Joint Advanced Research CenterDushu Lake Higher Education Town SIP State Key Laboratory in Marine Pollution and Department of Biology and Chemistry City University of Hong Kong

From July to September 2008, air samples were collected aboard the R/V XUE LONG icebreaker （Snow Dragon） as part of the 2008 Chinese National Arctic Research Expedition program. ∑20PCBs in the atmosphere ranged from 6.20 to 365 pg.m^-3 with average concentration 117±107 pg.m^- 3. Congener profiles in all samples showed a prevalence of tri- and tetrachlorobiphenyls, dominated by PCB-18, PCB-28, PCB-44 and PCB-52. Along the cruise, the highest concentration was observed over the Sea of Japan and the lowest over the high-latitude Arctic Ocean. Air mass backward trajectories indicated that samples with relatively high levels of PCBs might have been influenced by atmospheric transport of these chemicals from primary and/ or secondary sources. PCB-18 displayed a significant correlation between vapor pressure and ambient temperature along the cruise, but there was no such correlation between gas-phase concentration and latitude. This suggests that atmospheric PCB-18 was related to volatilization from the earth surface during summer 2008, during which temperatures were relatively high. PCB-52 presented a significant correlation between gas-phase concentration and latitude, but no such correlation was found between vapor pressure and ambient temperature, indicating that atmospheric PCB-52 detected during the cruise might be attributed directly to atmospheric transport from source regions. In the Arctic, levels of PCB-52 in the floating sea ice region were higher than those measured in the open sea area and pack ice region. Intense ice retreat during summer 2008 might have enhanced the volatilization of previously accumulated PCBs from sea ice, especially those with heavier molecular weight and lower vapor pressure such as PCB-52.

关键词： PCBs North Pacific Ocean Arctic Ocean air sea ice

Crystal structure of acetylcholinesterase catalytic subunits of the malaria vector Anopheles gambiae

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Insect Science 2018年第4期25卷 721-724页

作者： Qian Han Dawn M. Wong Howard Robinson Haizhen Ding Polo C. H. lam Maxim M. Totrov paul R. Carlier Jianyong Li Laboratory of Tropical Veterinary Medicine and Vector Biology and Hainan Key Laboratory of Sustainable Utilization of Tropical Bioresources College of Agriculture Hainan University Haikou China Department of Biochemistry Virginia Tech Blacksburg Virginia USA Department of Chemistry Virginia Tech Blacksburg Virginia USA Biology Department Brookhaven National Laboratory Upton New York USA Molsoft LLC San Diego California USA

Dear Editor, Acetylcholinesterase （ACHE） hydrolyzes the neurotransmitter acetylcholine at cholinergic synapses in the central nervous system （Toutant, 1989）. Inhibition of the enzyme in insects could lead to the d... 详细信息

关键词： ACETYLCHOLINESTERASE ANOPHELES gambiae CRYSTAL structure

Analysis of inborn errors of metabolism： disease spectrum for expanded newborn screening in Hong Kong

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Chinese Medical Journal 2011年第7期124卷 983-989页

作者： Han-Chih Hencher Lee Chloe Miu Mak Ching-Wan lam Yuet-Ping Yuen, Angel On-Kei Chan Chi-Chung Shek Tak-Shing Siu Chi-Kong Lai Chor-kwan Ching Wai-kwan Siu Sammy Pak-lam Chen Chun-Yiu Law Morris Hok-Leung Tai Sidney Tam Albert Yan-Wo Chan Chemical Pathology Laboratory Department of Pathology Princess Margaret Hospital Hong Kong SAR China Division of Clinical Biochemistry Queen Mary Hospital Hong Kong SAR China Department of Pathology Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China Chemical Pathology Laboratory Department of Pathology Queen Elizabeth Hospital Hong Kong SAR China

Background Data of classical inborn errors of metabolism （IEM） of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence, spectrum and other characteristics of classical IEM in Hong Kong, which would be important in developing an expanded newborn screening program for the local area.

关键词： biochemical genetics chemical pathology expanded newborn screening Hong Kong," inborn errorsof metabolism tandem mass spectrometry

Phenylketonuria in Hong Kong Chinese： a call for hyperphenylalaninemia newborn screening in the Special Administrative Region, China

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Chinese Medical Journal 2011年第16期124卷 2556-2558页

作者： Chloe Miu Mak Chun-hung Ko Ching-wan lam Wai-ling Lau Wai-kwan Siu Sammy Pak-lam Chen Chun-yiu Law Chi-kong Lai Chak-man Yu Albert Yan-wo Chan Kowloon West Cluster Laboratory Genetic Service ChemicalPathology Laboratory Department of Pathology Princess MargaretHospital Hong Kong China Department of Paediatrics and Adolescent Medicine CaritasMedical Centre Hong Kong China Department of Pathology Li Ka Shing Faculty of Medicine TheUniversity of Hong Kong Hong Kong China

Hyperphenylalaninemia is one of the commonest inborn errors of metabolism affecting approximately 1 in 15 000 live births. Among Chinese, BH4 deficiency leading to hyperphenylalaninemia is much commoner than in Caucasians. Exact diagnosis is important for the treatment and genetic counseling. In 2000, newborn screening for phenylketonuria is mandatory by law in China throughout the whole country. However, it is not yet included in the newborn screening program of the Hong Kong Special Administrative Region, China. Published data on hyperphenylalaninemia among Hong Kong Chinese are largely lacking. We report a 1-year-old Hong Kong Chinese girl with severe 6-pyruvoyl-tetrahydropterin synthase （PTPS） deficiency. The patient presented with infantile hypotonia and was misdiagnosed as cerebral palsy. She had very mild hyperphenylalaninemia （95 IJmol/L）, significantly high phenylalnine-to-tyrosine ratio （3.1）, and ele~,ated prolactin of 1109 m lU/L. Genetic analysis confirmed a homozygous known disease-causing mutation PTS NM_000317.1： c.259C〉T; NP_000308.1： p.P87S in the proband. In our local experience, while the estimated prevalence of hyperphenylalaninemia due to PTPS deficiency was reported to be 1 in 29 542 live births, not a single case of phenylalanine hydroxylase deficiency has been reported. Furthermore, there is a general lack of awareness of inherited metabolic diseases in the community as well as among the medical professionals. Very often, a low index of clinical suspicion will lead to delay in diagnosis, multiple unnecessary and costly investigations, prolonged morbidity and anxiety to the family affected. We strongly recommend that expanded newborn screening for hyperphenylalaninemia should be implemented for every baby born in the Hong Kong Special Administrative Region, China.

关键词： Hong Kong Chinese hyperphenylalaninemia newborn screening phenylketonuria 6-pyruvoyl-tetrahydropterin synthase deficiency

Anti-inflammatory mechanisms of the novel cytokine interleukin-38 in allergic asthma

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Cellular & Molecular Immunology 2020年第6期17卷 631-646页

作者： Xiaoyu Sun Tianheng Hou Edwin Cheung Tiffany Nga-Teng Iu Victor Wai-Hou Tam Ida Miu-Ting Chu Miranda Sin-Man Tsang paul Kay-Sheung Chan Christopher Wai-Kei lam Chun-Kwok Wong Department of Chemical Pathology The Chinese University of Hong KongHong KongChina Cancer Centre/Centre of Precision Medicine Research and Training Faculty of Health SciencesUniversity of MacaoMacaoChina Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Microbiology The Chinese University of Hong KongHong KongChina Faculty of Medicine and State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong KongHong KongChina

We elucidated the anti-inflammatory mechanisms of IL-38 in allergic *** bronchial epithelial cells and eosinophils were cocultured upon stimulation with the viral RLR ligand poly(I:C)/LyoVec or infection-related cytokine TNF-αto induce expression of cytokines/chemokines/adhesion *** dust mite(HDM)-induced allergic asthma and humanized allergic asthma NOD/SCID murine models were established to assess anti-inflammatory mechanisms in ***-38 significantly inhibited induced proinflammatory IL-6,IL-1β,CCL5,and CXCL10 production,and antiviral interferon-βand intercellular adhesion molecule-1 expression in the coculture *** cytometry and RNA-sequencing analysis revealed that IL-38 could antagonize the activation of the intracellular STAT1,STAT3,p38 MAPK,ERK1/2,and NF-κB pathways,and upregulate the expression of the host defense-related gene POU2AF1 and anti-allergic response gene *** injection of IL-38 into HDM-induced allergic asthma mice could ameliorate airway hyperreactivity by decreasing the accumulation of eosinophils in the lungs and inhibiting the expression of the Th2-related cytokines IL-4,IL-5,and IL-13 in the bronchoalveolar lavage fluid(BALF)and lung *** examination indicated lung inflammation was alleviated by reductions in cell infiltration and goblet cell hyperplasia,together with reduced Th2,Th17,and innate lymphoid type 2 cell numbers but increased proportions of regulatory T cells in the lungs,spleen,and lymph ***-38 administration suppressed airway hyperreactivity and asthma-related IL-4 and IL-5 expression in humanized mice,together with significantly decreased CCR3^(+) eosinophil numbers in the BALF and lungs,and a reduced percentage of human CD4^(+)CRTH2^(+)Th2 cells in the lungs and mediastinal lymph ***,our results demonstrated the anti-inflammatory mechanisms of IL-38 and provided a basis for the development of a regulatory cytokine-based treatment for allergic

关键词： allergic asthma eosinophils IL-38 ILC2s Tregs

HM30181A,a potent P-glycoprotein inhibitor,potentiates the absorption and in vivo antitumor efficacy of paclitaxel in an orthotopic brain tumor model

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Cancer Biology & Medicine 2020年第4期17卷 986-1001页

作者： Wu Zeng Betty Yuen kwan Law Vincent Kam Wai Wong Denise So Bik Chan Simon Wing Fai Mok Joyce Jia Ying Gao Rebecca Ka Yan Ho Xu Liang Jia Hao Li Ming Tsung Lee Weng Li Yoon Michael P Smolinski Johnson Yiu Nam Lau Christopher Wai Kei lam Manson Fok State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina At he nex Hong Kong Irmo vative Limited Hong Kong China Faculty of Medici ne Macao Un iversity of Science and TechnologyMacaoChina Athenex Inc. New York 14203USA

Objective:Delivery of chemotherapeutic drugs to the brain has remained a major obstacle in the treatment of glioma,owing to the presence of the blood-brain barrier and the activity of P-gp,which pumps its substrate back into the systemic *** aim of the present study was to develop an intravenous formulation of HM30181 A(HM)to inhibit P-gp in the brain to effectively deliver paclitaxel(PTX)for the treatment of malignant ***:Two formulations of solubilized HM were designed on the basis of different solid dispersion strategies:i)spray-drying[polyvinlypyrrolidone(PVP)-HM]and ii)solvent evaporation[HP-β-cyclodextrin(cyclodextrin)-HM].The P-gp inhibition of these 2 formulations was assessed on the basis of rhodamine 123 uptake in cancer *** and brain pharmacokinetic parameters were also determined,and the antitumor effect of cyclodextrin-HM with PTX was evaluated in an orthotopic glioma xenograft mouse ***:Although both PVP-HM and cyclodextrin-HM formulations showed promising P-gp inhibition activity in vitro,cyclodextrin-HM had a higher maximum tolerated dose in mice than did *** study of cyclodextrin-HM revealed a plasma concentration plateau at 20 mg/kg,and the mice began to lose weight at doses above this ***-HM(10 mg/kg)administered with PTX at 10 mg/kg showed optimal antitumor activity in a mouse model,according to both tumor volume measurement and survival time(P<0.05).Conclusions:In a mouse orthotopic brain tumor model,the intravenous co-administration of cyclodextrin-HM with PTX showed potent antitumor effects and therefore may have potential for glioma therapy in humans.

关键词： HM30181A glioma pharmacokinetics paclitaxel P-glycoprotein

An automated multiwell plate reading flim microscope for live cell autofluorescence lifetime assays

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Journal of Innovative Optical Health Sciences 2014年第5期7卷 99-113页

作者： Douglas J.Kelly Sean C.Warren Sunil Kumar Joao L.Lagarto Benjamin T.Dyer Anca Margineanu Eric W.-F.lam Chris Dunsby paul M.W.French Photonics Group Department of PhysicsImperial College London South Kensington CampusLondonSW72AZUK Institute of Chemical Biology Department of Chemistry Imperial College LondonSouth Kensington Campus LondonSWT 2AZUK National Heart&Lung Institute Imperial Centre for Eaperimental&Translational Medicine Du Cane Road LondonW12 ONNUK Department of Surgery and Cancer Imperial Cllege London Du Cane RoadLondonW12 ONNUK Centre for Histopathology Imperial College London Du Cane RoadLondonW120NNUK

Fluorescence lifetime imaging(FLIM)is increasingly used to read out cellular autofluorescenceoriginating from the coenzyme NADH in the context of investigating cell metabolic *** here an automated multiwell plate reading FLIM microscope optimized for UV illumi-nation with the goal of extending high content fluorescence lifetime asays to readouts ofmetabolism,We demonstrate its application to automated cellular autofluorescence lifetime imaging and discuss the key practical issues associated with its *** particular,weillustrate its capability to read out the NADH-lifetime response of cells to metabolic modulators,thereby illustrating the potential of the instrument for cytotoxicity studies,assays for drugdiscovery and stratified medicine.

关键词： High content analysis FLIM NADH metabolism cisplatin.

Statistical analyses for NANOGrav 5-year timing residuals

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Research in Astronomy and Astrophysics 2017年第2期17卷 63-76页

作者： Yan Wang James M. Cordes Fredrick A. Jenet Shami Chatterjee paul B. Demorest Timothy Dolch Justin A. Ellis Michael T. lam Dustin R. Madison Maura A. McLaughlin Delphine Perrodin Joanna Rankin Xavier Siemens Michele Vallisneri MOE Key Laboratory of Fundamental Physical Quantities Measurements School of Physics Huazhong University of Science and Technology Wuhan 430074 China Center for Advanced Radio Astronomy University of Texas at Brownsville 1 West University Boulevard Brownsville TX 78520 USA Department of Physics and Astronomy University of Texas at Brownsville 1 West University Boulevard Brownsville TX 78520 USA Department of Astronomy Cornell University Ithaca NY 14853 USA National Radio Astronomy Observatory 520 Edgemont Road Charlottesville VA 22903 USA Department of Physics Hillsdale College 33 E. College Street Hillsdale M149242 USA Jet Propulsion Laboratory California Institute of Technology 4800 Oak Grove Drive Pasadena CA 91106 USA Department of Physics West Virginia University EO. Box 6315 Morgantown WV 26505 USA INAF-Osservatorio Astronomico di Cagliari Via della Scienza 5 09047 Selargius (CA) Italy Department of Physics University of Vermont Burlington VT 05405 USA Center for Gravitation Cosmology and Astrophysics Department of Physics University of Wisconsin-Milwaukee P.O. Box 413 Milwaukee WI 53201 USA

In pulsar timing, timing residuals are the differences between the observed times of arrival and predictions from the timing model. A comprehensive timing model will produce featureless resid- uals, which are presumably composed of dominating noise and weak physical effects excluded from the timing model （e.g. gravitational waves）. In order to apply optimal statistical methods for detecting weak gravitational wave signals, we need to know the statistical properties of noise components in the residuals. In this paper we utilize a variety of non-parametric statistical tests to analyze the whiteness and Gaussianity of the North American Nanohertz Observatory for Gravitational Waves （NANOGrav） 5- year timing data, which are obtained from Arecibo Observatory and Green Bank Telescope from 2005 to 2010. We find that most of the data are consistent with white noise; many data deviate from Gaussianity at different levels, nevertheless, removing outliers in some pulsars will mitigate the deviations.

关键词： pulsar timing array general -- statistical tests