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1.
Gene ; 792: 145735, 2021 Aug 05.
Article in English | MEDLINE | ID: mdl-34048875

ABSTRACT

Human immunodeficiency virus (HIV) infection causes acquired immunodeficiency syndrome (AIDS), one of the most devastating diseases affecting humankind. Here, we have proposed a framework to examine the differences among microarray gene expression data of uninfected and three different HIV-1 infection stages using module preservation statistics. We leverage the advantage of gene co-expression networks (GCN) constructed for each infection stages to detect the topological and structural changes of a group of differentially expressed genes. We examine the relationship among a set of co-expression modules by constructing a module eigengene network considering the overall similarity/dissimilarity among the genes within the modules. We have utilized different module preservation statistics with two composite statistics: "Zsummary" and "MedianRank" to examine the changes in co-expression patterns between modules. We have found several interesting results on the preservation characteristics of gene modules across different stages. Some genes are identified to be preserved in a pair of stages while altering their characteristics across other stages. We further validated the obtained results using permutation test and classification techniques. The biological significances of the obtained modules have also been examined using gene ontology and pathway-based analysis. Additionally, we have identified a set of key immune regulatory hub genes in the associated protein-protein interaction networks (PPINs) of the differentially expressed (DE) genes, which interacts with HIV-1 proteins and are likely to act as potential biomarkers in HIV-1 progression.


Subject(s)
Antigens, CD/genetics , Chemokines/genetics , HIV Infections/genetics , HIV-1/pathogenicity , Host-Pathogen Interactions/genetics , Human Immunodeficiency Virus Proteins/genetics , Acute Disease , Antigens, CD/classification , Antigens, CD/immunology , Chemokines/classification , Chemokines/immunology , Chronic Disease , Datasets as Topic , Disease Progression , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , Gene Regulatory Networks , HIV Infections/immunology , HIV Infections/pathology , HIV Infections/virology , HIV-1/growth & development , Host-Pathogen Interactions/immunology , Human Immunodeficiency Virus Proteins/classification , Human Immunodeficiency Virus Proteins/immunology , Humans , Microarray Analysis , Molecular Sequence Annotation , Protein Binding , Signal Transduction
2.
PLoS One ; 15(7): e0235449, 2020.
Article in English | MEDLINE | ID: mdl-32716916

ABSTRACT

BACKGROUND: Several disease modifying drugs (DMDs) have been approved for the treatment of multiple sclerosis (MS), however, little is known about their differential impact on peripheral blood (PB) B cell subsets. METHODS: We performed a cross sectional study on PB B cells in MS patients treated with interferon-ß (n = 25), glatiramer acetate (n = 19), dimethyl fumarate (n = 15), fingolimod (n = 16) or natalizumab (n = 22), untreated MS patients (n = 20), and in patients with non-inflammatory neurological diseases (n = 12). Besides analyzing routine laboratory data, flow cytometry was performed to analyze naïve B cells (CD19+CD20+CD27-IgD+), non-class switched (CD19+CD20+CD27+IgD+) and class-switched memory B cells (CD19+CD20+CD27+IgD-), double negative B cells (CD19+CD20lowCD27-IgD-) and plasmablasts (CD19+CD20lowCD27+CD38++). RESULTS: Treatment associated changes were found for the overall B cell pool as well as for all B cell subsets. Natalizumab increased absolute numbers and percentage of all B cells mainly by expanding the memory B cell pool. Fingolimod decreased absolute numbers of all B cell subsets and the percentage of total B cells. Fingolimod, dimethyl fumarate and interferon-ß treatments were associated with an increase in the fraction of naïve B cells while class switched and non-class switched memory B cells showed decreased percentages. CONCLUSION: Our results highlight differential effects of DMDs on the PB B cell compartment. Across the examined treatments, a decreased percentage of memory B cells was found in dimethyl fumarate, interferon-ß and fingolimod treated patients which might contribute to the drugs' mode of action in MS. Further studies are necessary to decipher the exact role of B cell subsets during MS pathogenesis.


Subject(s)
B-Lymphocyte Subsets/drug effects , B-Lymphocytes/drug effects , Immunologic Memory/drug effects , Multiple Sclerosis/drug therapy , Adult , Aged , Aged, 80 and over , Antigens, CD/classification , Antigens, CD/immunology , Antigens, CD19 , B-Lymphocyte Subsets/classification , B-Lymphocyte Subsets/immunology , B-Lymphocytes/immunology , Cross-Sectional Studies , Dimethyl Fumarate/administration & dosage , Female , Fingolimod Hydrochloride/administration & dosage , Flow Cytometry , Glatiramer Acetate/administration & dosage , Humans , Immunologic Memory/immunology , Immunophenotyping , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/immunology , Interferon-beta/administration & dosage , Male , Middle Aged , Multiple Sclerosis/blood , Multiple Sclerosis/immunology , Multiple Sclerosis/pathology , Natalizumab/administration & dosage , Young Adult
3.
J Cancer Res Ther ; 16(1): 120-126, 2020.
Article in English | MEDLINE | ID: mdl-32362621

ABSTRACT

OBJECTIVE: The presence of specific chemotherapeutic protocols for hairy cell leukemia (HCL) makes it essential to discriminate this entity from other lymphoproliferative disorders. Hence, awareness of the variations in clinical presentations and immunophenotypic aberrancies is requisite to ensure diagnostic accuracy. MATERIALS AND METHODS: A retrospective study was carried out to analyze the clinical-pathological profile of patients with HCL diagnosed over a period of 81 months (2010-September 2017) in our institute. Flow cytometry was performed in all the patients, and further, BRAFV600E mutation analysis was performed by real-time polymerase chain reaction in a limited number of samples. RESULT: A total of 353 lymphoproliferative disorders were assessed during the period, of which 16 (4.5%) were diagnosed as HCL, which included 15 cases of classical HCL and single case of HCL-v. Striking male predominance was noted with a median age of 52 (range 22-90 years). 47% patients presented with pancytopenia, while 20% cases had leukocytosis. Three patients presented with bleeding diathesis in the form of melena and purpuric spots. The absence of splenomegaly was observed in 20% patients (4/15) while 2 (13.3%) cases had lymphadenopathy. Hypocellular marrow was observed in 13% cases. Bright expression of CD20/CD22 along with CD25/CD103/CD123/CD11c was noted in all the patients of classical HCL. Aberrant expression of CD23 and CD5 was seen in 33% ( n =5) and 6.7% ( n =1) cases respectively. CD200 was positive in all the 5/15 cases tested. The case of HCL-v presented with very high leukocyte count and exhibited a CD103/CD11c+ and CD123/CD25- profile. BRAFV600E, mutation was present in all the four patients tested who included patients with a hypocellular marrow and absent splenomegaly. CONCLUSION: HCL has characteristic profiles, yet it may exhibit unusual clinical and immunophenotypic presentations. Perspicacious use of flow cytometry and BRAFV600E mutation analysis will aid in the diagnosis in unprecedented cases.


Subject(s)
Antigens, CD/metabolism , Immunophenotyping/methods , Leukemia, Hairy Cell/pathology , Mutation , Proto-Oncogene Proteins B-raf/genetics , Adult , Aged , Aged, 80 and over , Antigens, CD/classification , Female , Flow Cytometry/methods , Humans , India , Leukemia, Hairy Cell/drug therapy , Leukemia, Hairy Cell/genetics , Male , Middle Aged , Retrospective Studies , Young Adult
4.
Biogerontology ; 20(4): 545-569, 2019 08.
Article in English | MEDLINE | ID: mdl-31119497

ABSTRACT

The study investigated mechanisms underlying sex differences in thymic involution in Dark Agouti rats. Adverse effects of aging on thymus were more pronounced in males than in females. Thymi from old males exhibited more prominent: (i) fibro-adipose degeneration which correlated with greater intensity of thymic oxidative stress and enhanced thymic TGF-ß and IL-6 expression and (ii) decline in thymopoiesis, as suggested by the number of the most mature CD4+CD8-/CD4-CD8+ single positive (SP) TCRαßhigh thymocytes. The greater accumulation of adipose tissue in old male thymus was linked with greater age-related increase in thymic expression of PPARγ and STAT3, a transcription factor regulating the expression of PPARγ downstream genes, in male than in female rats. In aged thymi of both sexes the early CD4-CD8- double negative (DN) stage of thymocyte development was affected, so relative accumulation of the least mature CD45RC+CD2- cells followed by decreased frequency of their DN and CD4+CD8+ double positive (DP) TCRαß- descendants was observed. Additionally, in old males, because of the increased thymic expression of Nur77, a nuclear receptor involved in negative selection, and decreased CD90 (a negative regulator of thymocyte selection threshold) MFI on DP TCRαßint thymocytes, less efficient positive/more efficient negative selection was found. Moreover, in male rats, thymocyte post-selection differentiation/maturation was skewed towards CD4-CD8+ SP TCRαßhigh cells compared with age-matched females, reflecting, at least partly, greater IL-15 expression in their thymi. The study indicated mechanisms underlying sex-based differences in age-related thymic changes and consequently necessity of sex-specific approaches in designing strategies to rejuvenate thymus.


Subject(s)
Cellular Senescence/physiology , Thymus Gland , Animals , Antigens, CD/classification , Correlation of Data , Fibrosis , Inflammation , Interleukin-6/metabolism , Oxidative Stress , PPAR gamma/metabolism , Rats , Sex Characteristics , Thymocytes/immunology , Thymocytes/metabolism , Thymus Gland/immunology , Thymus Gland/metabolism , Thymus Gland/pathology , Transforming Growth Factor beta/metabolism
5.
J Immunol Methods ; 470: 1-5, 2019 07.
Article in English | MEDLINE | ID: mdl-31022389

ABSTRACT

BACKGROUND: Flow cytometric analysis of the lymphocyte subsets has become one of the most commonly used techniques in the routine clinical laboratory. It is frequently used in monitoring lymphocyte recovery after hematopoietic stem cell transplantation (HSCT), as well as diagnosis and treatment of acquired immunodeficiency syndrome (AIDS). Reliable biological variation (BV) data is needed for safe clinical application of these tests. In this study, similar preanalytical and analytical protocols to the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) checklist were followed and a stringent statistical approach was applied to define BV of T-lymphocytes. METHODS: During the 10 weeks study period, weekly blood samples were obtained from 30 healthy individuals (20 females, 10 males) and analyzed with Facs Canto (BD Biosciences, San Jose, CA, USA) analyzer using 4-colour BD Multitest CD3/CD8/CD45/CD4 reagents. Data were assessed in terms of normality, tendencies, outliers and variance homogeneity prior to applying coefficient of variance (CV)- analysis of variance (ANOVA) test. Sex-stratified within-individual (CVI) and between-individual (CVG) BV estimates of CD3+, CD3 + CD4+, CD3 + CD8+, and CD3 + CD4 + CD8+ T lymphocytes were calculated. RESULTS: No difference was found between males and females. Except for the CD3 + CD4 + CD8+ subset, stable BV was found for CD3+, CD3 + CD4+, and CD3 + CD8+ subsets. CONCLUSSION: Instead of using the conventional reference ranges of CD3+, CD3 + CD4+ and CD3 + CD8+ counts for monitoring HIV positive or post-HSCT patients, RCV should be used. Because individualityis characteristic of lymphocytes subsets RCVs should be used instead of RIs for patient monitoring.


Subject(s)
Antigens, CD/genetics , Flow Cytometry/standards , Immunophenotyping/standards , Lymphocyte Subsets/classification , Adult , Antigens, CD/classification , Antigens, CD/immunology , Biomarkers/analysis , Female , Gene Expression , Genetic Variation , Healthy Volunteers , Humans , Lymphocyte Count , Lymphocyte Subsets/cytology , Lymphocyte Subsets/metabolism , Male , Middle Aged , Reference Values
6.
Clin Interv Aging ; 14: 253-263, 2019.
Article in English | MEDLINE | ID: mdl-30787601

ABSTRACT

PURPOSE: The aim of this study was to evaluate the effects of a proanthocyanidin-rich extract of sea buckthorn berry (SBB-PE) on the numbers of various types of adult stem cells in the blood circulation of healthy human subjects. STUDY DESIGN AND METHODS: A randomized, double-blind, placebo-controlled, cross-over trial was conducted in 12 healthy subjects. Blood samples were taken immediately before and at 1 and 2 hours after consuming either placebo or 500 mg SBB-PE. Whole blood was used for immunophenotyping and flow cytometry to quantify the numbers of CD45dim CD34+ CD309+ and CD45dim CD34+ CD309- stem cells, CD45- CD31+ CD309+ endothelial stem cells, and CD45- CD90+ mesenchymal stem cells. RESULTS: Consumption of SBB-PE was associated with a rapid and highly selective mobilization of CD45dim CD34+ CD309- progenitor stem cells, CD45- CD31+ CD309+ endothelial stem cells, and CD45- CD90+ lymphocytoid mesenchymal stem cells. In contrast, only minor effects were seen for CD45dim CD34+ CD309+ pluripotential stem cells. CONCLUSION: Consumption of SBB-PE resulted in selective mobilization of stem cell types involved in regenerative and reparative functions. These data may contribute to the understanding of the traditional uses of SBB for preventive health, regenerative health, and postponing the aging process.


Subject(s)
Antigens, CD , Hippophae/chemistry , Plant Extracts , Proanthocyanidins/pharmacology , Stem Cells , Adult , Aged , Antigens, CD/analysis , Antigens, CD/classification , Antioxidants/pharmacology , Cell Movement/drug effects , Double-Blind Method , Female , Flow Cytometry/methods , Fruit , Healthy Volunteers , Humans , Male , Middle Aged , Plant Extracts/chemistry , Plant Extracts/pharmacology , Regeneration/drug effects , Regeneration/physiology , Rejuvenation/physiology , Stem Cells/classification , Stem Cells/immunology , Treatment Outcome
7.
Am J Med Sci ; 357(3): 242-246, 2019 03.
Article in English | MEDLINE | ID: mdl-30797505

ABSTRACT

BACKGROUND: The prognostic role of peripheral lymphocyte subsets in early stage of acute pancreatitis (AP) is unknown. METHODS: After enrollment, blood samples were collected in the first 24 hours of the onset of AP in 164 patients. The lymphocyte count and the percentage of CD3+, CD3+CD4+, CD3+CD8+, CD3-CD19+and CD3-CD (16 + 56)+ cells were assessed. RESULTS: Reduction of the lymphocyte count and the percentage of CD3+CD8+ and CD3-CD (16 + 56)+ cells within 24 hours of the onset of AP as well as an increase in the percentage of CD3+ and CD3+CD4+ cells were observed. The percentage of CD3-CD (16 + 56)+ cells had the highest accuracy in prediction of AP severity. CONCLUSIONS: Marked changes of the percentages of lymphocyte subset were found in peripheral blood in the early stage of AP. The percentage of CD3-CD (16 + 56)+ cells in peripheral blood could be a potent prognostic predictor.


Subject(s)
Antigens, CD/classification , Lymphocyte Subsets/immunology , Pancreatitis , Acute Disease , Adult , Aged , Female , Flow Cytometry/methods , Humans , Male , Middle Aged , Pancreatitis/blood , Pancreatitis/diagnosis , Predictive Value of Tests , Prognosis , Reproducibility of Results , Severity of Illness Index , Time Factors
8.
Immunol Lett ; 205: 51-58, 2019 01.
Article in English | MEDLINE | ID: mdl-29958894

ABSTRACT

The leukocyte ectonucleotidases are a recently defined family included in the last Human Leukocyte Differentiation Antigens Workshop, giving prominence to these membrane proteins whose catalytic activity is expressed outside the cell. Among the most important substrates of the leukocyte ectonucleotidases are extracellular ATP and NAD+ whose transient increases are not immunologically silent but rather perceived as danger signals by the host. Among the host responses to the release of ATP, NAD+ and related small molecules is their breakdown on behalf of a panel of leukocyte ectonucleotidases - CD38, CD39, CD73, CD157, CD203a and CD203c -, whose activities are concatenated to form two nucleotide-catabolizing channels defined as the canonical and non-canonical adenosinergic pathways. Here, after briefly reviewing the structure and function of the proteins involved in these pathwys, we focus on the genes encoding the ectoenzymes of these adenosinergic pathways. The chromosomal localizations of the enzyme-encoding genes yield a first level of information concerning their origins by duplication and modes of regulation. Further information was obtained from phylogenetic analyses that show ectoenzyme orthologs are conserved in major tetrapod species whereas examination of synteny conservation revealed that the chromosomal regions harboring the ADP-ribosyl cyclases on human chromosome 4 and the ENTPDase CD39 on chromosome 10 show striking similarities in gene content consistent with their being paralogous chromosomal regions derived from a vertebrate whole genome duplication. Thus the connections between some of the leukocyte ectoenzymes run deeper than previously imagined.


Subject(s)
Antigens, CD/classification , Antigens, CD/genetics , Leukocytes/enzymology , Phylogeny , Adenosine/metabolism , Animals , Antigens, CD/chemistry , Antigens, CD/metabolism , Evolution, Molecular , Gene Expression Regulation/immunology , Humans , Leukocytes/metabolism , Nucleotidases/genetics , Protein Domains , Signal Transduction
9.
Haematologica ; 104(9): 1853-1865, 2019 09.
Article in English | MEDLINE | ID: mdl-30573502

ABSTRACT

Embryonic megakaryopoiesis starts in the yolk sac on gestational day 7.5 as part of the primitive wave of hematopoiesis, and it continues in the fetal liver when this organ is colonized by hematopoietic progenitors between day 9.5 and 10.5, as the definitive hematopoiesis wave. We characterized the precise phenotype of embryo megakaryocytes in the liver at gestational day 11.5, identifying them as CD41++CD45-CD9++CD61+MPL+CD42c+ tetraploid cells that express megakaryocyte-specific transcripts and display differential traits when compared to those present in the yolk sac at the same age. In contrast to megakaryocytes from adult bone marrow, embryo megakaryocytes are CD45- until day 13.5 of gestation, as are both the megakaryocyte progenitors and megakaryocyte/erythroid-committed progenitors. At gestational day 11.5, liver and yolk sac also contain CD41+CD45+ and CD41+CD45- cells. These populations, and that of CD41++CD45-CD42c+ cells, isolated from liver, differentiate in culture into CD41++CD45-CD42c+ proplatelet-bearing megakaryocytes. Also present at this time are CD41-CD45++CD11b+ cells, which produce low numbers of CD41++CD45-CD42c+ megakaryocytes in vitro, as do fetal liver cells expressing the macrophage-specific Csf receptor-1 (Csf1r/CD115) from MaFIA transgenic mice, which give rise poorly to CD41++CD45-CD42c+ embryo megakaryocytes both in vivo and in vitro In contrast, around 30% of adult megakaryocytes (CD41++CD45++CD9++CD42c+) from C57BL/6 and MaFIA mice express CD115. We propose that differential pathways operating in the mouse embryo liver at gestational day 11.5 beget CD41++CD45-CD42c+ embryo megakaryocytes that can be produced from CD41+CD45- or from CD41+CD45+ cells, at difference from those from bone marrow.


Subject(s)
Cell Lineage/genetics , Embryo, Mammalian/metabolism , Leukocyte Common Antigens/genetics , Megakaryocyte Progenitor Cells/metabolism , Megakaryocytes/metabolism , Animals , Antigens, CD/classification , Antigens, CD/genetics , Antigens, CD/metabolism , Biomarkers/metabolism , Cell Differentiation , Embryo, Mammalian/cytology , Flow Cytometry , Gene Expression , Hematopoiesis/genetics , Immunophenotyping/methods , Leukocyte Common Antigens/metabolism , Liver/cytology , Liver/metabolism , Megakaryocyte Progenitor Cells/classification , Megakaryocyte Progenitor Cells/cytology , Megakaryocytes/classification , Megakaryocytes/cytology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Primary Cell Culture , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Tetraploidy
10.
Sci Rep ; 8(1): 16022, 2018 10 30.
Article in English | MEDLINE | ID: mdl-30375429

ABSTRACT

Although there have been a plethora of radiogenomics studies related to glioblastoma (GBM), most of them only used genomic information from tumor cells. In this study, we used radiogenomics profiling to identify MRI-associated immune cell markers in GBM, which was also correlated with prognosis. Expression levels of immune cell markers were correlated with quantitative MRI parameters in a total of 60 GBM patients. Fourteen immune cell markers (i.e., CD11b, CD68, CSF1R, CD163, CD33, CD123, CD83, CD63, CD49d and CD117 for myeloid cells, and CD4, CD3e, CD25 and CD8 for lymphoid cells) were selected for RNA-level analysis using quantitative RT-PCR. For MRI analysis, quantitative MRI parameters from FLAIR, contrast-enhanced (CE) T1WI, dynamic susceptibility contrast perfusion MRI and diffusion-weighted images were used. In addition, PFS associated with interesting mRNA data was performed by Kaplan-Meier survival analysis. CD163, which marks tumor associated microglia/macrophages (TAMs), showed the highest expression level in GBM patients. CD68 (TAMs), CSF1R (TAMs), CD33 (myeloid-derived suppressor cell) and CD4 (helper T cell, regulatory T cell) levels were highly positively correlated with nCBV values, while CD3e (helper T cell, cytotoxic T cell) and CD49d showed a significantly negative correlation with apparent diffusion coefficient (ADC) values. Moreover, regardless of any other molecular characteristics, CD49d was revealed as one independent factor for PFS of GBM patients by Cox proportional-hazards regression analysis (P = 0.0002). CD49d expression level CD49d correlated with ADC can be considered as a candidate biomarker to predict progression of GBM patients.


Subject(s)
Glioblastoma/diagnostic imaging , Glioblastoma/genetics , Image Interpretation, Computer-Assisted , Integrin alpha4/genetics , Adult , Antigens, CD/classification , Antigens, CD/genetics , Cell Lineage/genetics , Cell Proliferation , Diffusion Magnetic Resonance Imaging , Female , Gene Expression Regulation, Neoplastic/genetics , Genome, Human/genetics , Genomics/methods , Glioblastoma/pathology , Humans , Image Interpretation, Computer-Assisted/methods , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Progression-Free Survival
11.
J Immunol ; 195(10): 4555-63, 2015 Nov 15.
Article in English | MEDLINE | ID: mdl-26546687

ABSTRACT

CD (cluster of differentiation) Ags are cell surface molecules expressed on leukocytes and other cells relevant for the immune system. CD nomenclature has been universally adopted by the scientific community and is officially approved by the International Union of Immunological Societies and sanctioned by the World Health Organization. It provides a unified designation system for mAbs, as well as for the cell surface molecules that they recognize. This nomenclature was established by the Human Leukocyte Differentiation Antigens Workshops. In addition to defining the CD nomenclature, these workshops have been instrumental in identifying and determining the expression and function of cell surface molecules. Over the past 30 y, the data generated by the 10 Human Leukocyte Differentiation Antigens Workshops have led to the characterization and formal designation of more than 400 molecules. CD molecules are commonly used as cell markers, allowing the identification and isolation of leukocyte populations, subsets, and differentiation stages. mAbs against these molecules have proven to be essential for biomedical research and diagnosis, as well as in biotechnology. More recently, they have been recognized as invaluable tools for the treatment of several malignancies and autoimmune diseases. In this article, we describe how the CD nomenclature was established, present the official updated list of CD molecules, and provide a rationale for their usefulness in the 21st century.


Subject(s)
Antibodies, Monoclonal/immunology , Antigens, CD/classification , Terminology as Topic , Antigens, CD/immunology , Biomarkers , Humans
12.
Front Biosci (Landmark Ed) ; 19(6): 986-1002, 2014 06 01.
Article in English | MEDLINE | ID: mdl-24896331

ABSTRACT

The major ADP-ribosylating enzyme families are the focus of this special issue of Frontiers in Bioscience . However, there is room for another family of enzymes with the capacity to utilize nicotinamide adenine dinucleotide (NAD): the ADP-ribosyl cyclases (ARCs). These unique enzymes catalyse the cyclization of NAD to cyclic ADP ribose (cADPR), a widely distributed second messenger. However, the ARCs are versatile enzymes that can manipulate NAD, NAD phosphate (NADP) and other substrates to generate various bioactive molecules including nicotinic acid adenine dinucleotide diphosphate (NAADP) and ADP ribose (ADPR). This review will focus on the group of well-characterized invertebrate and vertebrate ARCs whose common gene structure allows us to trace their origin to the ancestor of bilaterian animals. Behind a facade of gene and protein homology lies a family with a disparate functional repertoire dictated by the animal model and the physical trait under investigation. Here we present a phylogenetic view of the ARCs to better understand the evolution of function in this family.


Subject(s)
ADP-ribosyl Cyclase 1/genetics , ADP-ribosyl Cyclase/genetics , Antigens, CD/genetics , Evolution, Molecular , Phylogeny , ADP-ribosyl Cyclase/classification , ADP-ribosyl Cyclase/metabolism , ADP-ribosyl Cyclase 1/classification , ADP-ribosyl Cyclase 1/metabolism , Animals , Antigens, CD/classification , Antigens, CD/metabolism , GPI-Linked Proteins/classification , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolism , Humans , NAD/metabolism , Species Specificity
13.
Protein J ; 32(2): 143-54, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23344551

ABSTRACT

Cluster of differentiation (CD) is a group of proteins with highly immunological and medical importance, and some are established therapeutics. These membrane proteins are used to investigate of cell surface molecules of blood cells especially WBC. We selected a population of fifteen members with most medical importance, which includes CD2, CD4, CD5, CD6, CD7, CD9, CD14, CD16, CD19, CD22, CD28, CD33, CD36, CD38, and CD44 and performed in silico analysis using algorithm analysis and mathematical models. The results suggest that LEU (L) is well aligned. CD16 is rooted with CD22 and likewise, CD4 is closely related to CD44. Notably, highest number of highly conserved amino acids is recorded in CD22. WebLogo were formed up to 350 amino acid position and Met (M) is found to be tallest logo. Our results would be useful for upcoming researchers to obtain fundamental idea about the particular regions CD proteins which is having the structural and functional significance related to the evolutionary biology.


Subject(s)
Antigens, CD/chemistry , Antigens, CD/genetics , Evolution, Molecular , Multigene Family , Phylogeny , Amino Acid Sequence , Antigens, CD/classification , Antigens, CD/metabolism , Computational Biology , Humans , Molecular Sequence Data , Sequence Alignment
14.
Exp Neurol ; 241: 56-66, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23261766

ABSTRACT

Vorinostat, a histone deacetylase inhibitor, has been used clinically as an anticancer drug and also has immunosuppressive properties. However, the underlying mechanisms of effects of vorinostat on central nervous system (CNS) inflammatory diseases remain incomplete. Here, this study investigates the effects of vorinostat on human CD14(+) monocyte-derived dendritic cells (DCs) and mouse immature DC in vitro. Furthermore, we explore the therapeutic effects and cellular mechanisms of vorinostat on animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) in vivo. Our findings demonstrate that vorinostat inhibited human CD14(+) monocyte-derived DCs differentiation, maturation, endocytosis, and further inhibited mDCs' stimulation of allogeneic T-cell proliferation. In addition, vorinostat inhibited DC-directed Th1- (Type 1T helper) and Th17-polarizing cytokine production. Furthermore, vorinostat ameliorated Th1- and Th17-mediated EAE by reducing CNS inflammation and demyelination. What's more, Th1 and Th17 cell functions were suppressed in vorinostat-treated EAE mice. Finally, vorinostat suppressed expression of costimulatory molecules of DC in EAE mice. These suggest therapeutic effects of vorinostat on EAE which may by suppress DCs and DCs-mediated Th1 and Th17 cell functions. Our findings warrant further investigation in the potential of vorinostat for the treatment of human multiple sclerosis.


Subject(s)
Dendritic Cells/drug effects , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/pathology , Histone Deacetylase Inhibitors/therapeutic use , Hydroxamic Acids/therapeutic use , Animals , Antigens, CD/classification , Antigens, CD/metabolism , Cell Count , Cell Differentiation/drug effects , Cell Polarity/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Cytokines/genetics , Cytokines/metabolism , Dendritic Cells/cytology , Dendritic Cells/pathology , Disease Models, Animal , Dose-Response Relationship, Drug , Encephalomyelitis, Autoimmune, Experimental/chemically induced , Female , Humans , Lipopolysaccharides/toxicity , Lymphocyte Activation/drug effects , Lymphocytes/drug effects , Mice , Mice, Inbred C57BL , Myelin-Oligodendrocyte Glycoprotein/toxicity , Peptide Fragments/toxicity , RNA, Messenger/metabolism , Vorinostat
15.
J Clin Lab Anal ; 26(6): 431-40, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23143625

ABSTRACT

The authors conducted a flow cytometry immunophenotyping study in patients with acute lymphoblastic leukemia (ALL) from Natal, Rio Grande do Norte, Brazil. The patients (n = 126) were newly diagnosed using a panel of monoclonal antibodies: CD1a, CD2, CD3, CD4, CD7, CD8, CD10, CD13, CD33, CD14, CD19, CD22, CD79a, CD117, CD34, anti-IgM, anti-TdT, anti-HLA-Dr, and anti-human kappa and lambda light chains. Additional data, such as patients' age and gender, clinical and laboratory findings such as presence of tumor masses, lymphadenopathy, hepatomegaly, splenomegaly, leukemic infiltration in the central nervous system (CNS) were also investigated. Results showed that 56.7% of the cases were B-lineage ALL and 55% were T-cell ALL. Also, we found that males were more affected by the disease, regardless of immunological classification. The correlation between age and immunological subtypes showed that the B-lineage ALL occurred more frequently in patients aged under 15 while the T-cell ALL subtype was more frequent in adults. Immunophenotypic profiles and morphological subtypes showed a direct correlation between L3 subtype and B-lineage ALL, while L1 and L2 subtypes correlated more often with B-cell lineage and T-cell ALL, respectively. Correlation analysis between immunophenotypic and clinical profiles showed that T-cell ALL was more associated with a higher incidence of lymphadenopathy, hepatomegaly, splenomegaly and CNS leukemic infiltration, also showing a greater blast cell count in peripheral blood than the other subgroups. The presented data suggest that immunophenotyping is an important method in the diagnosis, monitoring and prognostic assessment in determining the pathological mechanisms of evolution of ALL.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/classification , Adolescent , Adult , Antigens, CD/blood , Antigens, CD/chemistry , Antigens, CD/classification , Child , Child, Preschool , Flow Cytometry/methods , Humans , Immunophenotyping/methods , Infant , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Prognosis , Treatment Outcome
17.
Lab Chip ; 12(1): 167-73, 2012 Jan 07.
Article in English | MEDLINE | ID: mdl-22048158

ABSTRACT

We present a simple system for CD4 and CD8 counting for point-of-care HIV staging in low-resource settings. Automatic sample preparation is achieved through a dried reagent coating inside a thin (26 µm) counting chamber, allowing the delayed release of fluorochrome conjugated monoclonal antibodies after the filling of the chamber with whole blood by capillary flow. A custom-built image cytometer is used to capture fluorescence images representing more than 1 µl of blood. The thin layer of blood in combination with the large image area allows the use of whole blood from a finger prick without the need for dilution, lysis or cell enrichment. Automatic cell counting of CD4(+) and CD8(+) T-lymphocytes correlates well with results obtained by flow cytometry.


Subject(s)
Antibodies, Monoclonal , CD4 Lymphocyte Count/instrumentation , CD4 Lymphocyte Count/methods , Flow Cytometry/instrumentation , Fluorescent Antibody Technique/instrumentation , Microfluidic Analytical Techniques/instrumentation , Antibodies, Monoclonal/metabolism , Antigens, CD/chemistry , Antigens, CD/classification , Antigens, CD/metabolism , Blood Specimen Collection , CD4-Positive T-Lymphocytes/chemistry , CD4-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/chemistry , CD8-Positive T-Lymphocytes/cytology , Fluorescent Dyes/chemistry , Humans , Protein Stability
18.
Neurol Med Chir (Tokyo) ; 51(11): 767-73, 2011.
Article in English | MEDLINE | ID: mdl-22123479

ABSTRACT

The mechanisms through which moyamoya disease occurs and progresses remain unknown. Recent studies have indicated the involvement of circulating endothelial progenitor cells (EPCs) in the development of moyamoya disease. This study directly investigated the participation of EPCs in moyamoya disease, using specimens of the supraclinoid internal carotid artery collected from two adult patients. The specimens were stained with primary antibodies against CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR2) to localize the circulating EPCs in the thickened intima of occlusive arterial lesion. The CD34- and VEGFR2-positive cells were densely found in the thickened intima of occlusive arterial lesion, particularly clustered in the superficial layer of thickened intima. However, the number of CD34- and CD133-positive cells was very small. The CD34-positive cells also expressed von Willebrand factor on the surface of thickened intima and were also positive for α-smooth muscle actin in the deeper layer. These findings suggest that circulating EPCs may be involved in the development of occlusive arterial lesion in moyamoya disease.


Subject(s)
Carotid Artery, Internal/pathology , Endothelial Cells/cytology , Moyamoya Disease/pathology , Stem Cells/cytology , Tunica Intima/pathology , Antigens, CD/classification , Antigens, CD/metabolism , Bone Marrow Cells/cytology , Carotid Artery, Internal/metabolism , Endothelial Cells/metabolism , Female , Humans , Immunohistochemistry , Middle Aged , Moyamoya Disease/metabolism , Stem Cells/metabolism , Tunica Intima/metabolism , Young Adult
19.
Immunogenetics ; 63(10): 679-89, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21667045

ABSTRACT

We studied the evolution of the CD2 family in tetrapods by extracting and analyzing CD2-like genes from the genome of the amphibian species Silurana (Xenopus) tropicalis. An exhaustive analysis of the genomic and cDNA databases resulted in the identification of at least 70 CD2-like genes. The predicted receptors mostly maintain the typical VC2 ectodomains, but are highly diverse in their C-termini, which suggests a broad range of signaling capacities. Apart from the presumed monomeric receptors with ITSM and/or ITIM motifs, the Silurana family includes secreted proteins. Furthermore, a fraction of the receptors contain a conserved TM subtype with the NxxR motif that is known to promote an association with the FcRγ subunit and that was previously found in the members of the FcR- and KIR-related receptors. The expression analysis of a sample of the genes showed broad tissue distribution and gene-specific expression patterns. Phylogenetic analysis predicted that the CD58, CD150/SLAM, and SLAMF8 genes were maintained as single-copy genes in both mammals and amphibians, while others expanded/contracted in a lineage-specific manner.


Subject(s)
Antigens, CD/genetics , CD2 Antigens/genetics , Receptors, Cell Surface/genetics , Xenopus/immunology , Amino Acid Sequence , Animals , Antigens, CD/classification , CD2 Antigens/classification , Evolution, Molecular , Molecular Sequence Data , Phylogeny , Receptors, Cell Surface/classification , Sequence Alignment , Signal Transduction , Signaling Lymphocytic Activation Molecule Family Member 1 , Xenopus/genetics
20.
Article in English | MEDLINE | ID: mdl-21237436

ABSTRACT

OBJECTIVE: Oral lichen planus (OLP) is a chronic disease with bandlike lymphocyte infiltration. STUDY DESIGN: To elucidate the immunologic phenotype of OLP, we analyzed the presence of CD5(+), CD20(+), CD27(+) and/or CD38(+) lymphocytes in a series of 70 atrophic OLP biopsy samples. RESULTS: CD27(+) and CD38(+) cells were present in 84% and 54% of the lesions, respectively. The lesions were graded as T-cell dominant, B-cell dominant, or a mixed lesion based on CD5(+) and CD20(+) cells in the inflammatory infiltration with the following results: 26%, 7%, and 67%, respectively. CD27 expression was found in 67% of the T-cell dominant, in 80% of the B-cell dominant, and in 91% of mixed lesions. The corresponding figures for CD38 were 72%, 80%, and 62%. CONCLUSIONS: CD27(+) and CD38(+) lymphocytes represent abnormal mononuclear cell populations in atrophic OLP lesions indicating 2 forms of OLP might exist with different pathogenesis, despite similar histology and clinical behavior.


Subject(s)
ADP-ribosyl Cyclase 1/metabolism , B-Lymphocyte Subsets/metabolism , Lichen Planus, Oral/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 7/metabolism , ADP-ribosyl Cyclase 1/immunology , Adult , Aged , Antigens, CD/classification , Antigens, CD/immunology , Antigens, CD/metabolism , B-Lymphocyte Subsets/classification , B-Lymphocyte Subsets/immunology , Female , Follow-Up Studies , Humans , Lichen Planus, Oral/pathology , Male , Middle Aged , T-Lymphocyte Subsets/classification , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Tumor Necrosis Factor Receptor Superfamily, Member 7/immunology
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