DOCSLIB.ORG

T Anomaly, Cleft Lip and Palate, and Agenesis of the Corpus Callosum, with a Chromosomal Microdeletion Involving 1Q41 to 1Q42.12

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
T Anomaly, Cleft Lip and Palate, and Agenesis of the Corpus Callosum, with a Chromosomal Microdeletion Involving 1Q41 to 1Q42.12 Journal of Perinatology (2012) 32, 238–240 r 2012 Nature America, Inc. All rights reserved. 0743-8346/12 www.nature.com/jp PERINATAL/NEONATAL CASE PRESENTATION A neonate with the Pelger–Hue¨t anomaly, cleft lip and palate, and agenesis of the corpus callosum, with a chromosomal microdeletion involving 1q41 to 1q42.12 RD Christensen1 and HM Yaish2 1Department of Women and Newborns, Intermountain Healthcare, Salt Lake City, UT, USA and 2Primary Children’s Medical Center and the Department of Pediatrics, Division of Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, UT, USA cyanotic and hypotonic with Apgar scores of 1, 5, 6 and 7 (at 1, 5, We observed a neonate with cleft lip and palate, 13 sets of ribs, agenesis of 10 and 15 min). Birth weight was 3177 g (38th percentile), length the corpus callosum, slightly small penis, hypoglycemia, and what initially 48 cm (37th percentile) and occipitofrontal circumference 35 cm appeared to be a marked leukocyte ‘left shift’ on complete blood count, but (67th percentile). The umbilical cord arterial blood had a pH 6.99 which was actually a Pelger–Hue¨t anomaly. A chromosomal microdeletion with a base deficit of À14.4 mmol lÀ1. When the respiratory was identified at1q41-42.12. distress and cyanosis continued despite mask continuous positive Journal of Perinatology (2012) 32, 238–240; doi:10.1038/jp.2011.119 airway pressure application, endotracheal intubation and Keywords: cleft lip and palate; Pelger-Hue¨t; microdeletion mechanical ventilation were provided and umbilical catheters were placed. The CBC showed a neutrophil concentration of 13.2 Â 103 per Introduction ml with 12% segmented neutrophils, 45% band neutrophils, À1 When newborn infants are evaluated for sepsis they generally have hemoglobin 12.6 g dl , hematocrit 40.5%, mean corpuscular volume 95.1 fl, mean corpuscular hemoglobin 29.9 pg, mean a complete blood count (CBC) performed looking for, among À1 1 corpuscular hemoglobin concentration 31.1 g dl , platelets other elements, a leukocyte ‘left shift’. Indeed, the diagnosis of 3 neonatal infection is supported by the finding that the circulating 181 Â 10 per ml and 113 nucleated red blood cells (NRBC)/100 white blood cells. The presentation with flaccidity, acidosis, neutrophils are predominantly band forms and metamyelocytes, 4 with fewer segmented neutrophils.2,3 respiratory failure and elevated NRBC were interpreted as We cared for a term neonate admitted to the NICU because consistent with umbilical cord compression in utero. Intravenous of respiratory distress. A severe cleft lip and palate and a variety antibiotics were administered, with the suspicion of bacterial of minor dysmorphic features were recognized. The initial CBC sepsis and pneumonia. showed a ‘left shift’ as did all subsequent CBCs but evaluation The initial blood glucose concentration measured 120 min following delivery, with no intravenous fluids yet running, was revealed no evidence of infection. Cytogenetic studies showed a 1q4 À1 À1 microdeletion including the genes we propose are responsible for 1mgdl . Dextrose-containing fluids were bolused (2 ml kg the features of this syndrome. intravenous) and the intravenous dextrose infusion rate was increased to 8 and then to 13 mg kgÀ1 per min with an increase in blood glucose to 200 mg dlÀ1. Serum electrolytes were normal and remained so during the hospitalization. Case Over the first 3 days, all cultures of blood, tracheal aspirate The patient was delivered by repeat cesarean section without labor and urine, were sterile. Cultures for cytomegalovirus, herpes, at 39.0 weeks gestation to a married 35 year old G4 P3003 healthy mycoplasma and ureaplasma were also negative. The CBC Caucasian. A cleft lip and palate had been detected by ultrasound continued to have a leukocyte ‘left shift’ despite clinical at 20 weeks gestation. The patient’s mother’s brother was born with improvement, including extubation to room air, weaning and a cleft lip and palate 24 years earlier. At delivery the baby was discontinuation of the intravenous solution and feedings of expressed mother’s milk using a Haberman feeder. Correspondence: Dr RD Christensen, Department of Women and Newborns, Intermountain Cranial ultrasound examination on day of life 2 suggested Healthcare, 4401 Harrison Boulevard, Salt Lake City, UT 84403, USA. E-mail: [email protected] agenesis of the corpus callosum. The initial cardiac echo showed Received 15 July 2011; accepted 25 July 2011 a patent ductus arteriosis and an atrial septal defect. A repeat echo Pelger–Hue¨t anomaly and 1q4 deletion RD Christensen and HM Yaish 239 film, where characteristic findings are observed in neutrophils; unilobed or bilobed (Pince–Nez) nuclei with clumped nuclear chromatin. Similar nuclear changes are sometimes seen in neutrophils of individuals with leukemia, lymphoma, malaria, metastatic disease or Sjogren’s syndrome, and can be induced by drugs such as colchicine.8,9 Disruption of genes near the lamin B receptor gene, at 1q41-44, has been associated with midline craniofacial abnormalities.10 Kalfa et al. recently reported a 10-month old with a constellation of findings and a microdeletion very similar to our case, but the two cases are discordant in some features including 13 sets of ribs in ours and hypoplastic nails and clinodactyly in theirs.11 Figure 1 Photomicrograph of a blood film demonstrating hypolobulation of Mazzeu et al.12 reported two children with deletions encompassing neutrophils with coarse nuclear chromatin and a ‘Pince–Nez’ nucleus 1q41q42.1 with features of Robinow syndrome but with no mention (resembling spectacles). of the Pelger–Hue¨t anomaly or midline craniofacial clefting. We speculate that other children with cleft lip and palate might 2 weeks later showed the ductus arteriosis had closed. have an unrecognized microdeletion involving the 1q4 region. Chest X-rays revealed 13 sets of ribs. Penile length was 2.5 cm Certainly if a child with cleft lip and palate were to have the (2 s.d. below mean5). Pelger–Hue¨t anomaly, a 1q4 deletion would be likely, because of Blood films were consistent with the Pelger–Hue¨t anomaly the proximity of relevant genes. Identifying individuals with cleft (Figure 1) with no nuclear lobulation beyond the bilobed stage, lip and palate who have an associated 1q4 microdeletion could be and with typical Pince–Nez nuclei with highly clumped of value, because the condition would likely be heritable from the chromatin.6 proband in an autosomal dominant fashion. We also speculate that Serum cortisol on day of life 1 was 10.1 mgdlÀ1 (normal) and recognizing the Pelger–Hue¨t anomaly in a neonate can be useful on day 7 was 16.2 mgdlÀ1 (normal). Growth hormone on day of whether or not it is part of the 1q4 syndrome. Recognizing life 8 was 13.2 ng mlÀ1 (normal). Magnetic resonance imaging this anomaly can avoid confusion with a leukocyte ‘left shift’, of the head on day of life 13 showed absence of the middle and supporting the dictum to ‘treat the patientynot the posterior portions of the corpus callosum and a somewhat small laboratory test’. cerebellar vermis. On day of life 4, ARUP Laboratories (Salt Lake City, UT, USA) perfomed whole genome chromosomal microarray analysis using Conflict of interest Affymetrix methodology and software (genotyping Console and The authors declare no conflict of interest. Chromosome Analysis Suite, Affymetrix, Santa Clara, CA, USA). The array includes over 2.1 Â 106 markers across the entire genome. A microdeletion was identified on chromosome 1, involving a References 3.0-Mb segment from 1q41 to 1q42.12, indicating partial monosomy for this region. The deleted region includes the lamin 1 CDC. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR. Centers for Disease Control and Prevention, Atlanta, GA, B receptor gene (causing the Pelger–Hue¨t anomaly). Other deleted 19 November 2010; 59. CDC, 10. genes include LOC440926, FBX028, Clorf65, SUSD4, ENAH, 2 Manroe BL, Rosenfeld CR, Weinberg AG, Browne R. The differential leukocyte count DNAH14, CAPN2, Clorf55, EPHX1, DEGS1, ENAH, CNIH3, in the assessment and outcome of early-onset neonatal group B streptococcal disease. PYCR2, TMEM63A, TLR5, and ACSD3. J Pediatr 1977; 91: 632–637. 3 Christensen RD, Bradley PP, Rothstein G. The leukocyte left shift in clinical and experimental neonatal sepsis. J Pediatr 1981; 98: 101–105. Discussion 4 Christensen RD, Henry E, Andres RL, Bennett ST. Reference ranges for blood concentrations of nucleated red blood cells in neonates. Neonatology 2010; 99: The Pelger–Hue¨t anomaly results from mutations in the lamin B 289–294. receptor gene.6 Most often, the genetic basis for this anomaly is a 5 Feldman KW, Smith DW. Fetal phallic growth and penile standards for newborn missence mutation, resulting in a heterozygous condition heritable male infants. J Pediatr 1975; 86: 395–398. in autosomal dominant fashion. The Pelger–Hue¨t anomaly is a 6 Speeckaert MM, Verhelst C, Koch A, Speeckaert R, Lacquet F. Pelger-Huet anomaly: a critical review of the literature. Acta Haematol 2009; 121: 202–206. benign finding but can be confused with a leukocyte ‘left shift’, 7 Mohamed IS, Wynn RJ, Cominsky K, Reynolds AM, Ryan RM, Kumar VH et al. 1–3,7 which in a neonate suggests the presence of bacterial sepsis. White blood cell left shift in a neonate: a case of mistaken identity. J Perinatol 2006; The anomaly is generally recognized upon examining a blood 26: 378–380. Journal of Perinatology Pelger–Hue¨t anomaly and 1q4 deletion RD Christensen and HM Yaish 240 8 Skubitz KM. Qualitative disorders of leukocytes In: Greer JP, Forester J, Rodgers GM, comparison to the 1q41q42 microdeletion suggests a contiguous 1q4 syndrome. Paraskevas F, Glader B, Arber DA, Means, RT Jr., (eds). Wintrobe’s Clinical Am J Med Genet A 2010; 152: 987–993.
Load more

Recommended publications
  • Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
    Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A.
    [Show full text]
  • The Janus-Like Role of Proline Metabolism in Cancer Lynsey Burke1,Innaguterman1, Raquel Palacios Gallego1, Robert G
    Burke et al. Cell Death Discovery (2020) 6:104 https://doi.org/10.1038/s41420-020-00341-8 Cell Death Discovery REVIEW ARTICLE Open Access The Janus-like role of proline metabolism in cancer Lynsey Burke1,InnaGuterman1, Raquel Palacios Gallego1, Robert G. Britton1, Daniel Burschowsky2, Cristina Tufarelli1 and Alessandro Rufini1 Abstract The metabolism of the non-essential amino acid L-proline is emerging as a key pathway in the metabolic rewiring that sustains cancer cells proliferation, survival and metastatic spread. Pyrroline-5-carboxylate reductase (PYCR) and proline dehydrogenase (PRODH) enzymes, which catalyze the last step in proline biosynthesis and the first step of its catabolism, respectively, have been extensively associated with the progression of several malignancies, and have been exposed as potential targets for anticancer drug development. As investigations into the links between proline metabolism and cancer accumulate, the complexity, and sometimes contradictory nature of this interaction emerge. It is clear that the role of proline metabolism enzymes in cancer depends on tumor type, with different cancers and cancer-related phenotypes displaying different dependencies on these enzymes. Unexpectedly, the outcome of rewiring proline metabolism also differs between conditions of nutrient and oxygen limitation. Here, we provide a comprehensive review of proline metabolism in cancer; we collate the experimental evidence that links proline metabolism with the different aspects of cancer progression and critically discuss the potential mechanisms involved. ● How is the rewiring of proline metabolism regulated Facts depending on cancer type and cancer subtype? 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; ● Is it possible to develop successful pharmacological ● Proline metabolism is widely rewired during cancer inhibitor of proline metabolism enzymes for development.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • 4-6 Weeks Old Female C57BL/6 Mice Obtained from Jackson Labs Were Used for Cell Isolation
    Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4).
    [Show full text]
  • Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters
    pharmaceuticals Review Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters Teresa Iannaccone 1, Carmine Sellitto 1,2,* , Valentina Manzo 1,2 , Francesca Colucci 1, Valentina Giudice 1 , Berenice Stefanelli 1 , Antonio Iuliano 1, Giulio Corrivetti 3 and Amelia Filippelli 1,2 1 Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; [email protected] (T.I.); [email protected] (V.M.); [email protected] (F.C.); [email protected] (V.G.); [email protected] (B.S.); [email protected] (A.I.); afi[email protected] (A.F.) 2 Clinical Pharmacology and Pharmacogenetics Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy 3 European Biomedical Research Institute of Salerno (EBRIS), 84125 Salerno, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-089673848 Abstract: Pharmacogenomics can identify polymorphisms in genes involved in drug pharma- cokinetics and pharmacodynamics determining differences in efficacy and safety and causing inter-individual variability in drug response. Therefore, pharmacogenomics can help clinicians in optimizing therapy based on patient’s genotype, also in psychiatric and neurological settings. Citation: Iannaccone, T.; Sellitto, C.; However, pharmacogenetic screenings for psychotropic drugs are not routinely employed in diagno- Manzo, V.; Colucci, F.; Giudice, V.; Stefanelli, B.; Iuliano, A.; Corrivetti, sis and monitoring of patients treated with mood stabilizers, such as carbamazepine and valproate, G.; Filippelli, A. Pharmacogenetics of because their benefit in clinical practice is still controversial. In this review, we summarize the current Carbamazepine and Valproate: Focus knowledge on pharmacogenetic biomarkers of these anticonvulsant drugs.
    [Show full text]
  • A Pathologic Link Between Wilms Tumor Suppressor Gene, WT1, And
    Volume 10 Number 1 January 2008 pp. 69–78 69 www.neoplasia.com RESEARCH ARTICLE † Marianne K.-H. Kim*, Jacqueline M. Mason , A Pathologic Link between Wilms ‡ § Chi-Ming Li , Windy Berkofsky-Fessler , ∥ WT1 Le Jiang , Divaker Choubey¶, Paul E. Grundy#, Tumor Suppressor Gene, , ∥ and IFI161,2 Benjamin Tycko and Jonathan D. Licht* *Division of Hematology/Oncology, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA; †The Campbell Family Institute for Breast Cancer Research at the Ontario, Cancer Institute, Ontario, Canada; ‡Translational Medicine, Amgen, Thousand Oaks, CA, USA; §Section of Bioinformatics, Genetics and Genomics, Hoffmann-La Roche Inc, Nutley, NJ, USA; ∥Institute for Cancer Genetics and Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY, USA; ¶University of Cincinnati, Cincinnati, OH, USA; #University of Alberta, Alberta, Canada Abstract The Wilms tumor gene (WT1) is mutated or deleted in patients with heredofamilial syndromes associated with the development of Wilms tumors, but is infrequently mutated in sporadic Wilms tumors. By comparing the micro- array profiles of syndromic versus sporadic Wilms tumors and WT1-inducible Saos-2 osteosarcoma cells, we iden- tified interferon-inducible protein 16 (IFI16), a transcriptional modulator, as a differentially expressed gene and a candidate WT1 target gene. WT1 induction in Saos-2 osteosarcoma cells led to strong induction of IFI16 expression and its promoter activity was responsive to the WT1 protein. Immunohistochemical analysis showed that IFI16 and WT1 colocalized in WT1-replete Wilms tumors, but not in normal human midgestation fetal kidneys, suggesting that the ability of WT1 to regulate IFI16 in tumors represented an aberrant pathologic relationship.
    [Show full text]
  • Genetically Lowered Microsomal Epoxide Hydrolase Activity And
    Author Manuscript Published OnlineFirst on June 8, 2011; DOI: 10.1158/1055-9965.EPI-10-1165 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Genetically lowered microsomal epoxide hydrolase activity and tobacco-related cancer in 47,000 individuals Julie Lee1,2, Morten Dahl1,2, Børge G. Nordestgaard1,2,3 1Department of Clinical Biochemistry and 2The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, 3The Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen University Hospital, 1-3Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. Running title: EPHX1 and increased risk of tobacco-related cancer Keywords: Carcinogen-detoxifying enzymes; polymorphisms in carcinogen metabolism and cancer risk; polymorphisms in genes related to androgen and estrogen metabolism in cancer risk; microsomal epoxide hydrolase; EPHX1. 1 Word count Text only: 3330 (max 5000) Abstract: 250 (max 250) References: 38 (max 50) Figures and tables: 3 + 2 (max. 6) Supplementary figures and tables: 1 + 2 Financial support: The following sources supported this work by one grant each: The Danish Lung Foundation; The Danish Heart Association; The Capital Region of Denmark Research Foundation; Chief Physician Johan Boserup and Lise Boserup’s Fund; The Augustinus Foundation; Herlev Hospital, Copenhagen University Hospital; and The European Respiratory Society. Corresponding author: Børge G. Nordestgaard, MD, DMSc., Chief Physician, Professor. Department of Clinical Biochemistry 54M1, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark, Phone: +45 4488 3297. Fax: +45 4488 3311, Email: [email protected] Conflict of interest: All authors declare no conflict of interest. 1 Downloaded from cebp.aacrjournals.org on September 29, 2021.
    [Show full text]
  • Susceptibility to Aflatoxin B1-Related Primary Hepatocellular Carcinoma in Mice and Humans
    [CANCER RESEARCH 63, 4594–4601, August 1, 2003] Susceptibility to Aflatoxin B1-related Primary Hepatocellular Carcinoma in Mice and Humans Katherine A. McGlynn,1, 2 Kent Hunter,2 Thomas LeVoyer, Jessica Roush, Philip Wise, Rita A. Michielli, Fu-Min Shen, Alison A. Evans, W. Thomas London, and Kenneth H. Buetow Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland 20892 [K. A. M.]; Center for Cancer Research, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland 20892 [K. H., J. R., P. W., K. H. B.]; Population Science Division, Fox Chase Cancer Center, Philadelphia, Pennsylvania 70119 [T. L., R. A. M., A. A. E., W. T. L.]; and Fudan Medical University, Shanghai, China [F-M. S.] ABSTRACT exo-8,9-epoxide, which is later detoxified through a variety of meta- bolic processes. The intermediate epoxide has been shown to bind and The genetic basis of disease susceptibility can be studied by several damage DNA, primarily at the N7 position of guanine (3). The means, including research on animal models and epidemiological investi- 3 characteristic genetic change associated with AFB1,aG T transver- gations in humans. The two methods are infrequently used simulta- Ͼ neously, but their joint use may overcome the disadvantages of either sion (4), affects the p53 gene in 50% of the tumors from AFB1- method alone. We used both approaches in an attempt to understand the endemic areas. Despite the high risk conferred by HBV and AFB , not all individ- genetic basis of aflatoxin B1 (AFB1)-related susceptibility to hepatocellular 1 carcinoma (HCC).
    [Show full text]
  • Oncogenic Human Herpesvirus Hijacks Proline Metabolism for Tumorigenesis
    Oncogenic human herpesvirus hijacks proline metabolism for tumorigenesis Un Yung Choia, Jae Jin Leea, Angela Parka, Wei Zhub, Hye-Ra Leec, Youn Jung Choia, Ji-Seung Yood, Claire Yub, Pinghui Fenga,e, Shou-Jiang Gaoa,f,g, Shaochen Chenb, Hyungjin Eoha,1, and Jae U. Junga,1 aDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033; bDepartment of NanoEngineering, University of California San Diego, La Jolla, CA 92093; cDepartment of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, 30019 Sejong, South Korea; dDepartment of Immunology, Faculty of Medicine, Hokkaido University, 060-8638 Sapporo, Japan; eSection of Infection and Immunity, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90089; fUniversity of Pittsburgh Medical Center (UPMC), Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219; and gLaboratory of Human Virology and Oncology, Shantou University Medical College, 515041 Shantou, Guangdong, China Edited by Thomas Shenk, Princeton University, Princeton, NJ, and approved March 2, 2020 (received for review October 24, 2019) Three-dimensional (3D) cell culture is well documented to regain hepatocellular carcinoma (HCC) (9). A recent study has also intrinsic metabolic properties and to better mimic the in vivo situation identified that collagen-derived proline is metabolized to fuel the than two-dimensional (2D) cell culture. Particularly, proline metabo- tricarboxylic acid (TCA) cycle and contribute to cancer cell sur- lism is critical for tumorigenesis since pyrroline-5-carboxylate (P5C) vival under restrictive nutrient conditions (10). This indicates that reductase (PYCR/P5CR) is highly expressed in various tumors and its proline metabolism is critical for 3D tumor formation.
    [Show full text]
  • NRF1) Coordinates Changes in the Transcriptional and Chromatin Landscape Affecting Development and Progression of Invasive Breast Cancer
    Florida International University FIU Digital Commons FIU Electronic Theses and Dissertations University Graduate School 11-7-2018 Decipher Mechanisms by which Nuclear Respiratory Factor One (NRF1) Coordinates Changes in the Transcriptional and Chromatin Landscape Affecting Development and Progression of Invasive Breast Cancer Jairo Ramos [email protected] Follow this and additional works at: https://digitalcommons.fiu.edu/etd Part of the Clinical Epidemiology Commons Recommended Citation Ramos, Jairo, "Decipher Mechanisms by which Nuclear Respiratory Factor One (NRF1) Coordinates Changes in the Transcriptional and Chromatin Landscape Affecting Development and Progression of Invasive Breast Cancer" (2018). FIU Electronic Theses and Dissertations. 3872. https://digitalcommons.fiu.edu/etd/3872 This work is brought to you for free and open access by the University Graduate School at FIU Digital Commons. It has been accepted for inclusion in FIU Electronic Theses and Dissertations by an authorized administrator of FIU Digital Commons. For more information, please contact [email protected]. FLORIDA INTERNATIONAL UNIVERSITY Miami, Florida DECIPHER MECHANISMS BY WHICH NUCLEAR RESPIRATORY FACTOR ONE (NRF1) COORDINATES CHANGES IN THE TRANSCRIPTIONAL AND CHROMATIN LANDSCAPE AFFECTING DEVELOPMENT AND PROGRESSION OF INVASIVE BREAST CANCER A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in PUBLIC HEALTH by Jairo Ramos 2018 To: Dean Tomás R. Guilarte Robert Stempel College of Public Health and Social Work This dissertation, Written by Jairo Ramos, and entitled Decipher Mechanisms by Which Nuclear Respiratory Factor One (NRF1) Coordinates Changes in the Transcriptional and Chromatin Landscape Affecting Development and Progression of Invasive Breast Cancer, having been approved in respect to style and intellectual content, is referred to you for judgment.
    [Show full text]
  • Transmembrane Protein 63A Is a Partner Protein of Haemonchus
    Yuan et al. Parasites & Vectors (2015) 8:211 DOI 10.1186/s13071-015-0816-3 RESEARCH Open Access Transmembrane protein 63A is a partner protein of Haemonchus contortus galectin in the regulation of goat peripheral blood mononuclear cells Cheng Yuan, Hui Zhang, Wang Wang, Yan Li, RuoFeng Yan, LiXin Xu, XiaoKai Song and XiangRui Li* Abstract Background: Hco-gal-m and -f were two isoforms of galectin cloned from male and female Haemonchus contortus, respectively, and it was demonstrated that recombinant Hco-gal-m and -f could act as immune suppressors. However, little is known about the receptors or binding partners of these galectins in the host. The research of the molecular mechanisms that govern the interactions between these galectins and host molecules will fill a gap in our understanding how parasite galectins interact with host cells. Methods: A yeast two-hybrid system was used to identify the binding partners of Hco-gal-m and -f in this research. The interaction between rHco-gal-m and candidate binding protein was validated by co-immunoprecipitation. The localization of transmembrane protein 63A (TMEM63A) in peripheral blood mononuclear cells (PBMCs) was detected by immunofluorescence. The distribution of TMEM63A in T cells, B cells and monocytes in PBMCs was detected by flow cytometry. The immunomodulatory effects of Hco-gal-m and TMEM63A on cell proliferation, migration, apoptosis, nitric oxide production and cytokine secretion were observed by co-incubation of rHco-gal-m and TMEM63A-siRNA with goat PBMCs and monocytes. Results: We found that TMEM63A, a functionally unknown protein, from goat PBMCs could bind to Hco-gal-m and -f.
    [Show full text]
  • Anergic and Regulatory T Lymphocytes Functional and Molecular Comparison Of
    Functional and Molecular Comparison of Anergic and Regulatory T Lymphocytes Birgit Knoechel, Jens Lohr, Shirley Zhu, Lisa Wong, Donglei Hu, Lara Ausubel and Abul K. Abbas This information is current as of September 29, 2021. J Immunol 2006; 176:6473-6483; ; doi: 10.4049/jimmunol.176.11.6473 http://www.jimmunol.org/content/176/11/6473 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2006/05/18/176.11.6473.DC1 Material References This article cites 54 articles, 28 of which you can access for free at: http://www.jimmunol.org/content/176/11/6473.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 29, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Functional and Molecular Comparison of Anergic and Regulatory T Lymphocytes1 Birgit Knoechel,2* Jens Lohr,2* Shirley Zhu,† Lisa Wong,† Donglei Hu,† Lara Ausubel,3* and Abul K.
    [Show full text]