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1. A high incidence of serum IgG antibodies to the Epstein-Barr virus replication activator protein in nasopharyngeal carcinoma

   Mathew A, Cheng HM, Sam CK, Joab I, Prasad U, Cochet C

   Cancer Immunol Immunother, 1994 Jan;38(1):68-70.

   PMID: 8299121

   Abstract

   The BamHI Z EBV replication activator (ZEBRA) protein is involved in the switch from latency to productive cycle of Epstein-Barr virus. A recombinant ZEBRA protein was synthesized and assessed in enzyme-linked immunosorbent assay (ELISA) for serum IgG response in nasopharyngeal carcinoma (NPC) patients. In 100 NPC serum samples that were positive for IgA to the EBV viral capsid antigen (VCA), 75% had IgG anti-ZEBRA antibodies. In contrast, only 3/83 (3.6%) serum samples from healthy donors and 2/50 (4%) from other cancers were positive for IgG to ZEBRA. Interestingly, in a selected group of 100 NPC sera negative for IgA to VCA, 25% contained IgG anti-ZEBRA antibodies. This suggests that the ELISA for IgG anti-ZEBRA may also identify earlier cases of NPC not detected by the conventional immunofluorescence test for IgA to VCA.

   MeSH terms: Antibodies, Viral/blood*; Antigens, Viral/immunology; Breast Neoplasms/immunology; Carcinoma/immunology*; Uterine Cervical Neoplasms/immunology; DNA-Binding Proteins/immunology*; Enzyme-Linked Immunosorbent Assay; Herpesvirus 4, Human/immunology; Female; Gastrointestinal Neoplasms/immunology; Humans; Immunoglobulin A/blood; Immunoglobulin G/blood*; Kidney Neoplasms/immunology; Nasopharyngeal Neoplasms/immunology*; Recombinant Proteins/immunology; Sensitivity and Specificity; Tumor Virus Infections/immunology; Viral Proteins/immunology; Trans-Activators/immunology*; Capsid Proteins*
2. Linear epitopes of the replication-activator protein of Epstein-Barr virus recognised by specific serum IgG in nasopharyngeal carcinoma

   Cheng HM, Foong YT, AbuSamah AJ, Dillner J, Sam CK, Prasad U

   Cancer Immunol Immunother, 1995 Apr;40(4):251-6.

   PMID: 7750123

   Abstract

   The linear antigenic epitopes of the Epstein-Barr virus replication activator protein (ZEBRA), recognised by specific serum IgG in nasopharyngeal carcinoma (NPC), were determined. This was achieved by synthesizing the entire amino acid sequence of ZEBRA as a set of 29, 22-residue peptides with an overlap of 14 amino acids. The ZEBRA peptides were tested in enzyme-linked immunosorbent assay (ELISA) for IgG binding in sera from 37 selected NPC patients who had IgG antibodies to the native ZEBRA protein. The most immunogenic epitope was peptide 1 at the amino-terminal end with 36 of the sera reactive against it. Further analysis of peptide 1, using the multipin peptide-scanning technique, defined a 10-amino-acid sequence FTPDPYQVPF, which was strongly bound by IgG. Two other regions of ZEBRA were also identified as immunodominant IgG epitopes, namely peptide 11 (amino acids 82-103) and peptide 19/20 (amino acids 146-175) with 8-13 of the NPC sera reactive against the peptides. The number of peptides reactive with individual NPC serum varies from 1 to 6 or more and there is some correlation between a greater number of peptide (at least 4) bound and a higher (at least 1:40) titre of serum IgA to viral capsid antigen. The immunodominant ZEBRA peptide 1 could be utilised in IgG ELISA for the detection of NPC.

   MeSH terms: Amino Acid Sequence; Antibody Specificity; DNA-Binding Proteins/blood; DNA-Binding Proteins/immunology*; Enzyme-Linked Immunosorbent Assay; Herpesvirus 4, Human/immunology*; Humans; Immunoglobulin G/blood*; Molecular Sequence Data; Nasopharyngeal Neoplasms/immunology*; Nasopharyngeal Neoplasms/virology; Peptide Fragments/immunology; Viral Proteins/immunology*; Trans-Activators/blood; Trans-Activators/immunology*; Immunodominant Epitopes/analysis*
3. Ossification of caroticoclinoid ligament and its clinical importance in skull-based surgery

   Das S, Suri R, Kapur V

   Sao Paulo Med J, 2007 Nov 01;125(6):351-3.

   PMID: 18317606

   Abstract

   CONTEXT: The medial end of the posterior border of the sphenoid bone presents the anterior clinoid process (ACP), which is usually accessed for operations involving the clinoid space and the cavernous sinus. The ACP is often connected to the middle clinoid process (MCP) by a ligament known as the caroticoclinoid ligament (CCL), which may be ossified, forming the caroticoclinoid foramen (CCF). Variations in the ACP other than ossification are rare. The ossified CCL may have compressive effects on the internal carotid artery. Thus, anatomical and radiological knowledge of the ACP and the clinoid space is also important when operating on the internal carotid artery. Excision of the ACP may be required for many skull-based surgical procedures, and the presence of any anomalies such as ossified CCL may pose a problem for neurosurgeons.

   CASE REPORT: We observed the presence of ossified CCL in a skull bone. A detailed radiological study of the CCL and the CCF was conducted. Morphometric measurements were recorded and photographs were taken. The ACP was connected to the MCP and was converted into a CCF. Considering the fact that standard anatomy textbooks do not provide morphological descriptions and radiological evaluations of the CCL, the present study may be important for neurosurgeons operating in the region of the ACP.

   MeSH terms: Carotid Artery Diseases/etiology; Carotid Artery Diseases/pathology; Carotid Artery, Internal/pathology*; Humans; Ligaments/abnormalities; Ligaments/anatomy & histology*; Ossification, Heterotopic/pathology*; Radiography; Skull/pathology*; Sphenoid Bone/abnormalities; Sphenoid Bone/pathology
4. Fulltext Importance of hypertension and social isolation in causing sleep disruption in dementia

   Eshkoor SA, Hamid TA, Nudin SS, Mun CY

   Am J Alzheimers Dis Other Demen, 2014 Feb;29(1):61-6.

   PMID: 24085252 DOI: 10.1177/1533317513505136

   Abstract

   This study aimed to determine the effects of diabetes mellitus (DM), hypertension (HT), heart disease, social isolation, and sociodemographic factors on sleep in the elderly patients with dementia. Samples included 1210 noninstitutionalized, Malaysian elderly patients with dementia. The multiple logistic regression analysis was applied to estimate the risk of sleep disturbances among respondents. Approximately 41% of the patients experienced sleep problems. The results showed that age (odds ratio [OR] = 1.02), social isolation (OR = 1.33), and HT (OR = 1.53) significantly increased sleep disruption in respondents (P .05). It was concluded that age, social isolation, and HT increased sleep disruption but education and ethnic non-Malay reduced the risk of sleep problems. Moreover, HT was the most important variable to increase sleep disturbances in the elderly patients with dementia.

   MeSH terms: Aged; Dementia/epidemiology*; Diabetes Mellitus/epidemiology*; Educational Status; Female; Heart Diseases/epidemiology*; Humans; Hypertension/epidemiology*; Malaysia/epidemiology; Male; Middle Aged; Risk Factors; Sex Factors; Sleep Wake Disorders/ethnology; Sleep Wake Disorders/epidemiology*; Social Isolation*; Social Support; Causality; Prevalence; Multivariate Analysis; Logistic Models
5. Sleep Quality and Nocturnal Sleep Duration in Pregnancy and Risk of Gestational Diabetes Mellitus

   Cai S, Tan S, Gluckman PD, Godfrey KM, Saw SM, Teoh OH, et al.

   Sleep, 2017 Feb 01;40(2).

   PMID: 28364489 DOI: 10.1093/sleep/zsw058

   Abstract

   STUDY OBJECTIVES: To examine the influence of maternal sleep quality and nocturnal sleep duration on risk of gestational diabetes mellitus (GDM) in a multiethnic Asian population.

   METHODS: A cohort of 686 women (376 Chinese, 186 Malay, and 124 Indian) with a singleton pregnancy attended a clinic visit at 26-28 weeks of gestation as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI). GDM was diagnosed based on a 75-g oral glucose tolerance test administered after an overnight fast (1999 WHO criteria). Multiple logistic regression was used to model separately the associations of poor sleep quality (PSQI score > 5) and short nocturnal sleep duration (<6 h) with GDM, adjusting for age, ethnicity, maternal education, body mass index, previous history of GDM, and anxiety (State-Trait Anxiety Inventory score).

   RESULTS: In the cohort 296 women (43.1%) had poor sleep quality and 77 women (11.2%) were categorized as short sleepers; 131 women (19.1%) were diagnosed with GDM. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of GDM (poor sleep, adjusted odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.11 to 2.76; short sleep, adjusted OR = 1.96, 95% CI 1.05 to 3.66).

   CONCLUSIONS: During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibited abnormal glucose regulation. Treating sleep problems and improving sleep behavior in pregnancy could potentially reduce the risk and burden of GDM.

   MeSH terms: Adult; China/ethnology; Darkness; Ethnic Groups; Female; Glucose/metabolism; Glucose Tolerance Test; Humans; India/ethnology; Malaysia/ethnology; Maternal Age; Pregnancy; Risk Factors; Singapore; Sleep/physiology*; Time Factors; Cohort Studies; Logistic Models; Odds Ratio; Diabetes, Gestational/diagnosis; Diabetes, Gestational/etiology*; Asian Continental Ancestry Group
6. Fulltext Expression of full-length Plasmodium falciparum P48/45 in P. berghei blood stages: A method to express and evaluate vaccine antigens

   Othman AS, Lin JW, Franke-Fayard BM, Kroeze H, van Pul FJA, Chevalley-Maurel S, et al.

   Mol Biochem Parasitol, 2018 Sep;224:44-49.

   PMID: 30053393 DOI: 10.1016/j.molbiopara.2018.07.009

   Abstract

   The transmission-blocking vaccine candidate Pfs48/45 from the human malaria parasite Plasmodium falciparum is known to be difficult to express in heterologous systems, either as full-length protein or as correctly folded protein fragments that retain conformational epitopes. In this study we express full-length Pfs48/45 in the rodent parasite P. berghei. Pfs48/45 is expressed as a transgene under control of the strong P. berghei schizont-specific msp1 gene promoter (Pfs48/45@PbMSP1). Pfs48/45@PbMSP1 schizont-infected red blood cells produced full-length Pfs48/45 and the structural integrity of Pfs48/45 was confirmed using a panel of conformation-specific monoclonal antibodies that bind to different Pfs48/45 epitopes. Sera from mice immunized with transgenic Pfs48/45@PbMSP1 schizonts showed strong transmission-reducing activity in mosquitoes infected with P. falciparum using standard membrane feeding. These results demonstrate that transgenic rodent malaria parasites expressing human malaria antigens may be used as means to evaluate immunogenicity and functionality of difficult to express malaria vaccine candidate antigens.

   MeSH terms: Animals; Antigens, Protozoan/biosynthesis; Antigens, Protozoan/genetics; Antigens, Protozoan/immunology*; Disease Models, Animal; Malaria/prevention & control; Membrane Proteins/biosynthesis; Membrane Proteins/genetics; Membrane Proteins/immunology*; Plasmodium berghei/genetics*; Plasmodium falciparum/genetics*; Promoter Regions, Genetic; Recombinant Proteins/biosynthesis; Recombinant Proteins/genetics; Recombinant Proteins/immunology*; Gene Expression; Malaria Vaccines/immunology*; Disease Transmission, Infectious/prevention & control; Transgenes; Mice
7. Fulltext CRISPR/Cas9-Mediated Foxp1 Silencing Restores Immune Surveillance in an Immunocompetent A20 Lymphoma Model

   Felce SL, Anderson AP, Maguire S, Gascoyne DM, Armstrong RN, Wong KK, et al.

   Front Oncol, 2020;10:448.

   PMID: 32309216 DOI: 10.3389/fonc.2020.00448

   Abstract

   The interaction of lymphoma cells with their microenvironment has an important role in disease pathogenesis and is being actively pursued therapeutically using immunomodulatory drugs, including immune checkpoint inhibitors. Diffuse large B-cell lymphoma (DLBCL) is an aggressive high-grade disease that remains incurable in ~40% of patients treated with R-CHOP immunochemotherapy. The FOXP1 transcription factor is abundantly expressed in such high-risk DLBCL and we recently identified its regulation of immune response signatures, in particular, its suppression of the cell surface expression of major histocompatibility class II (MHC-II), which has a critical role in antigen presentation to T cells. Using CRISPR/Cas9 genome editing we have depleted Foxp1 expression in the aggressive murine A20 lymphoma cell line. When grown in BALB/c mice, this cell line provides a high-fidelity immunocompetent disseminated lymphoma model that displays many characteristics of human DLBCL. Transient Foxp1-depletion using siRNA, and stable depletion using CRISPR (generated by independently targeting Foxp1 exon six or seven) upregulated cell surface I-Ab (MHC-II) expression without impairing cell viability in vitro. RNA sequencing of Foxp1-depleted A20 clones identified commonly deregulated genes, such as the B-cell marker Cd19, and hallmark DLBCL signatures such as MYC-targets and oxidative phosphorylation. Immunocompetent animals bearing Foxp1-depleted A20 lymphomas showed significantly-improved survival, and 20% did not develop tumors; consistent with modulating immune surveillance, this was not observed in immunodeficient NOD SCIDγ mice. The A20 Foxp1 CRISPR model will help to further characterize the contribution of Foxp1 to lymphoma immune evasion and the potential for Foxp1 targeting to synergize with other immunotherapies.
8. Fulltext Sandwich dot-immunogold filtration assay (DIGFA) for specific immunodiagnosis of active neuroangiostrongyliasis

   Eamsobhana P, Tungtrongchitr A, Yong HS, Prasartvit A, Wanachiwanawin D, Gan XX

   Parasitology, 2021 Feb;148(2):234-239.

   PMID: 33004092 DOI: 10.1017/S0031182020001894

   Abstract

   Serological tests may yield false-negative results for specific antibodies detection before or at the early seroconversion phase. Tests that detect circulating antigens of Angiostrongylus cantonensis would therefore be of value in diagnosis to distinguish current or past infection. Here, a quick, easy to perform, portable and inexpensive diagnostic device for detection of 31-kDa A. cantonensis specific antigens had been developed. This sandwich dot-immunogold filtration assay (AcDIGFAAg), for detecting active angiostrongyliasis was produced using anti-A. cantonensis polyclonal antibody dotted on the nitrocellulose membrane as a capture agent and colloidal gold-labelled anti-31 kDa A. cantonensis antibody as a detection agent. A well-defined pink dot, indicating positivity, was seen readily by naked eye within 10-15 min. The AcDIGFAAg detected A. cantonensis-specific antigens in cerebrospinal fluid samples from 4 out of 10 serologically confirmed angiostrongyliasis cases and 2 out of 5 suspected cases with negative anti-A. cantonensis antibodies. Among the 19 patient sera with A. cantonensis infection, 2 showed positive reaction by AcDIGFAAg. No positive AcDIGFAAg reaction was observed in all the serum samples with other parasitic diseases, and the healthy controls. The present 'AcDIGFAAg' enables rapid qualitative detection of the specific 31-kDa antigens of A. cantonensis in clinical samples with potential for application even under resource-limited settings.

   MeSH terms: Animals; Humans; Immunohistochemistry/methods*; Parasitology/methods; Angiostrongylus cantonensis/isolation & purification; Strongylida Infections/diagnosis*; Strongylida Infections/parasitology
9. Fulltext Amoebicidal activity of Cassia angustifolia extract and its effect on Acanthamoeba triangularis autophagy-related gene expression at the transcriptional level

   Boonhok R, Sangkanu S, Norouzi R, Siyadatpanah A, Mirzaei F, Mitsuwan W, et al.

   Parasitology, 2021 Aug;148(9):1074-1082.

   PMID: 33966667 DOI: 10.1017/S0031182021000718

   Abstract

   Cassia angustifolia Vahl. plant is used for many therapeutic purposes, for example, in people with constipation, skin diseases, including helminthic and parasitic infections. In our study, we demonstrated an amoebicidal activity of C. angustifolia extract against Acanthamoeba triangularis trophozoite at a micromolar level. Scanning electron microscopy (SEM) images displayed morphological changes in the Acanthamoeba trophozoite, which included the formation of pores in cell membrane and the membrane rupture. In addition to the amoebicidal activity, effects of the extract on surviving trophozoites were observed, which included cyst formation and vacuolization by a microscope and transcriptional expression of Acanthamoeba autophagy in response to the stress by quantitative polymerase chain reaction. Our data showed that the surviving trophozoites were not transformed into cysts and the trophozoite number with enlarged vacuole was not significantly different from that of untreated control. Molecular analysis data demonstrated that the mRNA expression of AcATG genes was slightly changed. Interestingly, AcATG16 decreased significantly at 12 h post treatment, which may indicate a transcriptional regulation by the extract or a balance of intracellular signalling pathways in response to the stress, whereas AcATG3 and AcATG8b remained unchanged. Altogether, these data reveal the anti-Acanthamoeba activity of C. angustifolia extract and the autophagic response in the surviving trophozoites under the plant extract pressure, along with data on the formation of cysts. These represent a promising plant for future drug development. However, further isolation and purification of an active compound and cytotoxicity against human cells are needed, including a study on the autophagic response at the protein level.

   MeSH terms: Amebicides/pharmacology*; Plant Extracts/pharmacology*; Plant Extracts/chemistry; Transcription, Genetic/drug effects*; Genes, Protozoan/drug effects*; Senna Plant/chemistry*; Acanthamoeba castellanii/drug effects*; Acanthamoeba castellanii/genetics
10. Fulltext HSV-1 ICP22 Is a Selective Viral Repressor of Cellular RNA Polymerase II-Mediated Transcription Elongation

    Isa NF, Bensaude O, Aziz NC, Murphy S

    Vaccines (Basel), 2021 Sep 22;9(10).

    PMID: 34696162 DOI: 10.3390/vaccines9101054

    Abstract

    The Herpes Simplex Virus (HSV-1) immediate-early protein ICP22 interacts with cellular proteins to inhibit host cell gene expression and promote viral gene expression. ICP22 inhibits phosphorylation of Ser2 of the RNA polymerase II (pol II) carboxyl-terminal domain (CTD) and productive elongation of pol II. Here we show that ICP22 affects elongation of pol II through both the early-elongation checkpoint and the poly(A)-associated elongation checkpoint of a protein-coding gene model. Coimmunoprecipitation assays using tagged ICP22 expressed in human cells and pulldown assays with recombinant ICP22 in vitro coupled with mass spectrometry identify transcription elongation factors, including P-TEFb, additional CTD kinases and the FACT complex as interacting cellular factors. Using a photoreactive amino acid incorporated into ICP22, we found that L191, Y230 and C225 crosslink to both subunits of the FACT complex in cells. Our findings indicate that ICP22 interacts with critical elongation regulators to inhibit transcription elongation of cellular genes, which may be vital for HSV-1 pathogenesis. We also show that the HSV viral activator, VP16, has a region of structural similarity to the ICP22 region that interacts with elongation factors, suggesting a model where VP16 competes with ICP22 to deliver elongation factors to viral genes.