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Abstract
Receptor-selective effects of endogenous RGS3 and RGS5 to regulate mitogen-activated protein kinase activation in rat vascular smooth muscle cells.
AuthorsWang Qin; Liu Min; Mullah Bashar; Siderovski David P; Neubig Richard R;
JournalJ Biol Chem
PubMed ID12006602
Regulators of G protein signaling (RGS) proteins compose a highly diverse protein family best known for inhibition of G protein signaling by enhancing GTP hydrolysis by Galpha subunits. Little is known about the function of endogenous RGS proteins. In this study, we used synthetic ribozymes targeted to RGS2, RGS3, RGS5, ... More
Silencing of Transcription of the Human Luteinizing Hormone Receptor Gene by Histone Deacetylase-mSin3A Complex.
Authors Zhang Ying; Dufau Maria L;
JournalJ Biol Chem
PubMed ID12091390
'Modification of chromatin structure by histone acetylases and deacetylases is an important mechanism in modulation of eukaryotic gene transcription. The present study investigated regulation of the human luteinizing hormone receptor (hLHR) gene by histone deacetylases. Inhibition of histone deacetylases (HDACs) by trichostatin A (TSA) increased hLHR promoter activity by 40-fold ... More
Distinct Intracellular Signaling in Tumor Necrosis Factor-related Apoptosis-inducing Ligand- and CD95 Ligand-mediated Apoptosis.
Authors Velthuis Jurjen H L; Rouschop Kasper M A; De Bont Hans J G M; Mulder Gerard J; Nagelkerke J Fred;
JournalJ Biol Chem
PubMed ID11980895
'Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in tumor cells but not in healthy cells. Similar to CD95 ligand (CD95L), TRAIL signaling requires ligand-receptor interaction; the downstream signaling molecules, such as Fas-associated death domain and caspase-8, also seem similar. Using cells stably expressing TRAIL and ... More
Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors.
Authors Jørgensen Niklas R; Henriksen Zanne; Sørensen Ole H; Eriksen Erik F; Civitelli Roberto; Steinberg Thomas H;
JournalJ Biol Chem
PubMed ID11756404
'Signaling between osteoblasts and osteoclasts is important in bone homeostasis. We previously showed that human osteoblasts propagate intercellular calcium signals via two mechanisms: autocrine activation of P2Y receptors, and gap junctional communication. In the current work we identified mechanically induced intercellular calcium signaling between osteoblasts and osteoclasts and among osteoclasts. ... More
Single-cell fluorescence resonance energy transfer analysis demonstrates that caspase activation during apoptosis is a rapid process. Role of caspase-3.
Authors Rehm Markus; Dussmann Heiko; Janicke Reiner U; Tavare Jeremy M; Kogel Donat; Prehn Jochen H M;
JournalJ Biol Chem
PubMed ID11964393
'Activation of effector caspases is considered to be the final step in many apoptosis pathways. We transfected HeLa cells with a recombinant caspase substrate composed of cyan and yellow fluorescent protein and a linker peptide containing the caspase cleavage sequence DEVD, and we examined the cleavage kinetics at the single-cell ... More
Galpha 12 and galpha 13 negatively regulate the adhesive functions of cadherin.
Authors Meigs Thomas E; Fedor-Chaiken Mary; Kaplan Daniel D; Brackenbury Robert; Casey Patrick J;
JournalJ Biol Chem
PubMed ID11976333
'Cadherins function to promote adhesion between adjacent cells and play critical roles in such cellular processes as development, tissue maintenance, and tumor suppression. We previously demonstrated that heterotrimeric G proteins of the G(12) subfamily comprised of Galpha(12) and Galpha(13) interact with the cytoplasmic domain of cadherins and cause the release ... More
Cooperativity between the Ras-ERK and Rho-Rho Kinase Pathways in Urokinase-type Plasminogen Activator-stimulated Cell Migration.
Authors Jo Minji; Thomas Keena S; Somlyo Avril V; Somlyo Andrew P; Gonias Steven L;
JournalJ Biol Chem
PubMed ID11805108
'Binding of the urokinase-type plasminogen activator (uPA) to its receptor activates diverse cell signaling pathways. How these signals are integrated so that cell physiology is altered remains unclear. In this study, we demonstrated that migration of MCF-7 breast cancer cells and HT-1080 fibrosarcoma cells on serum-coated surfaces is stimulated by ... More
Identification of a minimum enhancer sequence for the type II collagen gene reveals several core sequence motifs in common with the link protein gene.
Authors Krebsbach P H; Nakata K; Bernier S M; Hatano O; Miyashita T; Rhodes C S; Yamada Y;
JournalJ Biol Chem
PubMed ID8626777
'The type II collagen gene (Col2a1) is expressed primarily in chondrocytes. Transcription of Col2a1 is mediated by cell-specific regulatory elements located within the promoter and first intron. Here, we map a minimal enhancer and identify elements that determine cartilage-specific Col2a1 expression by analyzing the activity of a series of chimeric ... More
Tissue-specific expression of the nonneuronal promoter of the aromatic L-amino acid decarboxylase gene is regulated by hepatocyte nuclear factor 1.
Authors Aguanno A; Afar R; Albert V R;
JournalJ Biol Chem
PubMed ID8626808
'The rat aromatic l-amino acid decarboxylase (AADC) gene contains alternative promoters which direct expression of neuronal and nonneuronal mRNAs that differ only in their 5''-untranslated regions (UTRs). We have analyzed the expression of the nonneuronal promoter of the rat AADC gene in the kidney epithelial cell line LLC-PK1 and in ... More
Doxorubicin induces apoptosis and CD95 gene expression in human primary endothelial cells through a p53-dependent mechanism.
Authors Lorenzo Elisa; Ruiz-Ruiz Carmen; Quesada Antonio Jesús; Hernández Gabriela; RodrÃguez Antonio; López-Rivas Abelardo; Redondo Juan Miguel;
JournalJ Biol Chem
PubMed ID11779855
'Regulation of the homeostasis of vascular endothelium is critical for the processes of vascular remodeling and angiogenesis under physiological and pathological conditions. Here we show that doxorubicin (Dox), a drug used in antitumor therapy, triggered a marked accumulation of p53 and induced CD95 gene expression and apoptosis in proliferating human ... More
Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo.
'A major concern in cancer therapy is resistance of tumors such as glioblastoma to current treatment protocols. Here, we report that transfer of the gene encoding second mitochondria-derived activator of caspase (Smac) or Smac peptides sensitized various tumor cells in vitro and malignant glioma cells in vivo for apoptosis induced ... More
CCAAT/Enhancer Binding Protein alpha Binds to the Epstein-Barr Virus (EBV) ZTA Protein through Oligomeric Interactions and Contributes to Cooperative Transcriptional Activation of the ZTA Promoter through Direct Binding to the ZII and ZIIIB Motifs during Induction of the EBV Lytic Cycle.
AuthorsWu FY, Wang SE, Chen H, Wang L, Hayward SD, Hayward GS,
JournalJ Virol
PubMed ID15078966
'The Epstein-Barr virus (EBV)-encoded ZTA protein interacts strongly with and stabilizes the cellular CCAAT/enhancer binding protein alpha (C/EBPalpha), leading to the induction of p21-mediated G(1) cell cycle arrest. Despite the strong interaction between these two basic leucine zipper (bZIP) family proteins, the ZTA and C/EBPalpha subunits do not heterodimerize, as ... More
Molecular cloning and characterization of a novel UDP-Gal:GalNAc(alpha) peptide beta 1,3-galactosyltransferase (C1Gal-T2), an enzyme synthesizing a core 1 structure of O-glycan.
AuthorsKudo T, Iwai T, Kubota T, Iwasaki H, Takayma Y, Hiruma T, Inaba N, Zhang Y, Gotoh M, Togayachi A, Narimatsu H,
JournalJ Biol Chem
PubMed ID12361956
'Recently, a UDP-Gal:GalNAc(alpha) peptide beta1,3-galactosyltransferase (core 1 synthase 1; C1Gal-T1) has been purified from rat liver and its complementary DNA cloned from several species. We isolated a second candidate for core 1 synthase from a Colo205 cDNA library and named it C1Gal-T2. The deduced amino acid sequence of C1Gal-T2, having ... More
Regulation of mRNA expression in macrophages after Yersinia enterocolitica infection. Role of different Yop effectors.
'The Yop virulon, which comprises a complete type III secretion system and secreted proteins, allows bacteria from the genus Yersinia to resist the nonspecific immune response of the host. This virulon, which is encoded by a plasmid called pYV in Yersinia enterocolitica, enables extracellular bacteria to inject six Yop effectors ... More
Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study.
'BACKGROUND: Allogeneic haemopoietic stem-cell transplantation (HSCT) is the treatment of choice for many haematological malignancies and inherited disorders. When stem cells for transplantation come from a human leucocyte antigen matched unrelated donor, or from a partly mismatched related donor, ex-vivo T-cell depletion of the graft can prevent development of graft-versus-host ... More
Retroviral delivery of connexin genes to human breast tumor cells inhibits in vivo tumor growth by a mechanism that is independent of significant gap junctional intercellular communication.
Authors Qin Hong; Shao Qing; Curtis Heather; Galipeau Jacques; Belliveau Daniel J; Wang Taiqi; Alaoui-Jamali Moulay A; Laird Dale W;
JournalJ Biol Chem
PubMed ID12042301
'The mechanism by which gap junction proteins, connexins, act as potent tumor suppressors remains poorly understood. In this study human breast tumor cells were found to exhibit diverse gap junction phenotypes including (a) undetectable Cx43 and no intercellular communication (HBL100); (b) low levels of Cx43 and sparse intercellular communication (MDA-MB-231); ... More
Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota.
'Somatic hypermutation of immunoglobulin genes is a unique, targeted, adaptive process. While B cells are engaged in germinal centres in T-dependent responses, single base substitutions are introduced in the expressed Vh/Vl genes to allow the selection of mutants with a higher affinity for the immunizing antigen. Almost every possible DNA ... More
Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc.
'beta-Amyloid precursor protein (APP) is a widely expressed transmembrane protein of unknown function that is involved in the pathogenesis of Alzheimer''s disease. The cytoplasmic tail of APP interacts with phosphotyrosine binding (PTB) domain containing proteins (Fe65, X11, mDab-1, and JIP-1) and may modulate gene expression and apoptosis. We now identify ... More
Modulation of basic helix-loop-helix transcription complex formation by Id proteins during neuronal differentiation.
'It is assumed that the Id helix-loop-helix (HLH) proteins act by associating with ubiquitously expressed basic HLH (bHLH) transcription factors, such as E47 and E2-2, which prevents these factors from forming functional hetero- or homodimeric DNA binding complexes. Several tissue-specific bHLH proteins, including HASH-1, dHAND, and HES-1, are important for ... More
Expression of functional receptor-coupled TRPC3 channels in DT40 triple receptor InsP3 knockout cells.
Authors Venkatachalam K; Ma H T; Ford D L; Gill D L;
JournalJ Biol Chem
PubMed ID11466302
'The TRPC3 channel, an intensively studied member of the widely expressed transient receptor potential (TRP) family, is a Ca(2+)-conducting channel activated in response to phospholipase C-coupled receptors. Despite scrutiny, the receptor-induced mechanism to activate TRPC3 channels remains unclear. Evidence indicates TRPC3 channels interact directly with intracellular inositol 1,4,5-trisphosphate receptors (InsP(3)Rs) ... More
Tat acetyl-acceptor lysines are important for human immunodeficiency virus type-1 replication.
The human immunodeficiency virus type-1 trans-activator Tat is a transcription factor that activates the HIV-1 promoter through binding to the trans-activation-responsive region (TAR) localized at the 5'-end of all viral transcripts. We and others have recently shown that Tat is directly acetylated at lysine 28, within the activation domain, and ... More
Caspase-11 gene expression in response to lipopolysaccharide and interferon-gamma requires nuclear factor-kappa B and signal transducer and activator of transcription (STAT) 1.
Murine caspase-11, together with caspase-1, is essential for the production of IL-1beta in response to lipopolysaccharide (LPS). In most cells, caspase-11 is only expressed upon induction with pro-inflammatory stimuli. To understand how caspase-11 expression is transcriptionally regulated, we isolated the caspase-11 gene promoter by genome walking and investigated the mechanisms ... More
Delay between fusion pore opening and peptide release from large dense-core vesicles in neuroendocrine cells.
Peptidergic neurotransmission is slow compared to that mediated by classical neurotransmitters. We have studied exocytotic membrane fusion and cargo release by simultaneous capacitance measurements and confocal imaging of single secretory vesicles in neuroendocrine cells. Depletion of the readily releasable pool (RRP) correlated with exocytosis of 10%-20% of the docked vesicles. ... More
Human macrophage-derived chemokine (MDC), a novel chemoattractant for monocytes, monocyte-derived dendritic cells, and natural killer cells.
A cDNA encoding a novel human chemokine was isolated by random sequencing of cDNA clones from human monocyte-derived macrophages. This protein has been termed macrophage-derived chemokine (MDC) because it appears to be synthesized specifically by cells of the macrophage lineage. MDC has the four-cysteine motif and other highly conserved residues ... More
The p85 regulatory subunit controls sequential activation of phosphoinositide 3-kinase by Tyr kinases and Ras.
AuthorsJimenez C, Hernandez C, Pimentel B, Carrera AC,
JournalJ Biol Chem
PubMed ID12196526
Class IA phosphoinositide 3-kinase (PI3K) is a heterodimer composed of a p85 regulatory and a p110 catalytic subunit that regulates a variety of cell responses, including cell division and survival. PI3K is activated following Tyr kinase stimulation and by Ras. We found that the C-terminal region of p85, including the ... More
Human MutY homolog, a DNA glycosylase involved in base excision repair, physically and functionally interacts with mismatch repair proteins human MutS homolog 2/human MutS homolog 6.
Authors Gu Yesong; Parker Antony; Wilson Teresa M; Bai Haibo; Chang Dau-Yin; Lu A-Lien;
JournalJ Biol Chem
PubMed ID11801590
Adenines mismatched with guanines or 7,8-dihydro-8-oxo-deoxyguanines that arise through DNA replication errors can be repaired by either base excision repair or mismatch repair. The human MutY homolog (hMYH), a DNA glycosylase, removes adenines from these mismatches. Human MutS homologs, hMSH2/hMSH6 (hMutSalpha), bind to the mismatches and initiate the repair on ... More
Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice.
Authors Lee Tzong-Shyuan; Chau Lee-Young;
JournalNat Med
PubMed ID11875494
The mechanisms underlying the action of the potent anti-inflammatory interleukin-10 (IL-10) are poorly understood. Here we show that, in murine macrophages, IL-10 induces expression of heme oxygenase-1 (HO-1), a stress-inducible protein with potential anti-inflammatory effect, via a p38 mitogen-activated protein kinase-dependent pathway. Inhibition of HO-1 protein synthesis or activity significantly ... More
Analysis of a truncated form of cathepsin H in human prostate tumor cells.
Increased expression of proteases has been correlated with the malignant progression of a variety of tumors. We found a significant increase in cathepsin H expression in high-grade prostatic intraepithelial neoplasia and carcinoma of the prostate. Two forms of cathepsin H, the full-length form (CTSH) and a truncated form with a ... More
Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivo.
The gastric pathogen Helicobacter pylori uses a type IV secretion system to inject the bacterial CagA protein into gastric epithelial cells. Within the host cell, CagA becomes phosphorylated on tyrosine residues and initiates cytoskeletal rearrangements. We demonstrate here that Src-like protein-tyrosine kinases mediate CagA phosphorylation in vitro and in vivo. ... More
Transcriptional regulation of the membrane-associated prostaglandin E2 synthase gene. Essential role of the transcription factor Egr-1.
Membrane-associated prostaglandin (PG) E2 synthase (mPGES) is an inducible terminal enzyme in the biosynthetic pathway for prostaglandin E2, which participates in many biological processes. In this study, we investigated the molecular mechanism controlling the inducible expression of mPGES. The mouse mPGES gene consisted of three exons, and its 5'-proximal promoter ... More
Differential association of HLA-B*2705 and B*2709 to ankylosing spondylitis correlates with limited peptide subsets but not with altered cell surface stability.
Authors Ramos Manuel; Paradela Alberto; Vazquez Miriam; Marina Anabel; Vazquez Jesus; Lopez de Castro Jose A;
JournalJ Biol Chem
PubMed ID12042320
In contrast to HLA-B*2705, B*2709 is weakly or not associated to ankylosing spondylitis. Both allotypes differ by a single D116H change. We compared the B*2705- and B*2709-bound peptide repertoires by mass spectrometry to quantify the effect of B*2709 polymorphism on peptide specificity. In addition, shared and differentially bound ligands were ... More
Human class I histone deacetylase complexes show enhanced catalytic activity in the presence of ATP and co-immunoprecipitate with the ATP-dependent chaperone protein Hsp70.
Authors Johnson Colin A; White Darren A; Lavender Jayne S; O'Neill Laura P; Turner Bryan M;
JournalJ Biol Chem
PubMed ID11777905
Antibodies to histone deacetylases (HDACs) have been used to immuno-isolate deacetylase complexes from HeLa cell extracts. Complexes shown to contain HDAC1, HDAC3, HDAC6, and HDAC1+2 as their catalytic subunits have been used in an antibody-based assay that detects deacetylation of whole histones at defined lysines. The class II deacetylase HDAC6 ... More
Tissue-specific enhancer-promoter interactions regulate high level constitutive expression of matrix metalloproteinase 2 by glomerular mesangial cells.
Authors Harendza S; Pollock A S; Mertens P R; Lovett D H;
JournalJ Biol Chem
PubMed ID7642529
The 72-kDa gelatinase A (MMP-2) is a central mediator of the response of the intrinsic glomerular mesangial cell to inflammatory stimuli and is regulated in a unique, cell-specific manner. We isolated a 6-kilobase pair genomic fragment of the rat MMP-2 gene and sequenced and characterized 1686-base pair of the 5'-flanking ... More
Vav1 Couples T Cell Receptor to Serum Response Factor-dependent Transcription via a MEK-dependent Pathway.
The Vav family of guanine nucleotide exchange factors for Rho family GTPases plays a critical role in lymphocyte proliferation, gene transcription, and cytoskeleton reorganization following immunoreceptor stimulation. However, its role in immediate early gene activation is unclear. In this study, we have investigated the mechanisms by which Vav1 can regulate ... More
HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells.
Authors Deregibus Maria Chiara; Cantaluppi Vincenzo; Doublier Sophie; Brizzi Maria Felice; Deambrosis Ilaria; Albini Adriana; Camussi Giovanni;
JournalJ Biol Chem
PubMed ID11994280
In this study we found that Tat protected vincristine-treated Kaposi's sarcoma cells from apoptosis and from down-regulation of several anti-apoptotic genes such as AKT-1, AKT-2, BCL2, BCL-XL, and insulin-like growth factor I and induced the de novo expression of the interleukin-3 gene. Moreover, we found that Tat enhanced phosphorylation of ... More
Cell docking and on-chip monitoring of cellular reactions with a controlled concentration gradient on a microfluidic device.
Authors Yang Mengsu; Li Cheuk-Wing; Yang Jun;
JournalAnal Chem
PubMed ID12199565
We have developed a microfluidic device for on-chip monitoring of cellular reactions. The device consists of two primary analytical functions: control of cell transport and immobilization, and dilution of an analyte solution to generate a concentration gradient. In this device, a dam structure in parallel to the fluid flow was ... More
Peroxisome Proliferator-activated Receptor gamma Agonists Inhibit HIV-1 Replication in Macrophages by Transcriptional and Post-transcriptional Effects.
Authors Hayes Michael M; Lane Brian R; King Steven R; Markovitz David M; Coffey Michael J;
JournalJ Biol Chem
PubMed ID11847231
Previous studies have demonstrated that cyclopentenone prostaglandins (cyPG) inhibit human immunodeficiency virus type 1 (HIV-1) replication in various cell types. We investigated the role of PG in the replication of HIV-1 in primary macrophages. The cyPG, PGA(1) and PGA(2), inhibited HIV-1 replication in acutely infected human monocyte-derived macrophages (MDM). Because ... More
C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity.
C75, a known inhibitor of fatty acid synthase is postulated to cause significant weight loss through decreased hypothalamic neuropeptide Y (NPY) production. Peripherally, C75, an alpha-methylene-gamma-butyrolactone, reduces adipose tissue and fatty liver, despite high levels of malonyl-CoA. To investigate this paradox, we studied the effect of C75 on fatty acid ... More
Identification of amino acid residues critical for biological activity in human interleukin-18.
Authors Kim Soo-Hyun; Azam Tania; Novick Daniela; Yoon Do-Young; Reznikov Leonid L; Bufler Philip; Rubinstein Menachem; Dinarello Charles A;
JournalJ Biol Chem
PubMed ID11790772
Interleukin-18 (IL-18) is a pro-inflammatory cytokine, and IL-18-binding protein (IL-18BP) is a naturally occurring protein that binds IL-18 and neutralizes its biological activities. Computer modeling of human IL-18 identified two charged residues, Glu-42 and Lys-89, which interact with oppositely charged amino acid residues buried in a large hydrophobic pocket of ... More
Uncoupling protein 2 plays an important role in nitric oxide production of lipopolysaccharide-stimulated macrophages.
The expression of uncoupling protein 2 (UCP2) was reduced in macrophages after stimulation with lipopolysaccharide (LPS). The physiological consequence and the regulatory mechanisms of the UCP2 down-regulation by LPS were investigated in a macrophage cell line, RAW264 cells. UCP2 overexpression in RAW264 cells transfected with eukaryotic expression vector containing ucp2 ... More
EMR4, a Novel Epidermal Growth Factor (EGF)-TM7 Molecule Up-regulated in Activated Mouse Macrophages, Binds to a Putative Cellular Ligand on B Lymphoma Cell Line A20.
Authors Stacey Martin; Chang Gin-Wen; Sanos Stephanie L; Chittenden Laura R; Stubbs Lisa; Gordon Siamon; Lin Hsi-Hsien;
JournalJ Biol Chem
PubMed ID12023293
A novel member of the EGF-TM7 family, mEMR4, was identified and characterized. The full-length mouse EMR4 cDNA encodes a predicted 689-amino acid protein containing two epidermal growth factor (EGF)-like modules, a mucin-like spacer domain, and a seven-transmembrane domain with a cytoplasmic tail. Genetic mapping established that mEMR4 is localized in ... More
Malignant effusions and immunogenic tumour-derived exosomes.
BACKGROUND: Exosomes derived from tumours are small vesicles released in vitro by tumour cell lines in culture supernatants. To assess the role of these exosomes in vivo, we examined malignant effusions for their presence. We also investigated whether these exosomes could induce production of tumour-specific T cells when pulsed with ... More
Identification of human male germ cell-associated kinase, a kinase transcriptionally activated by androgen in prostate cancer cells.
Authors Xia Liang; Robinson Dan; Ma Ai-Hong; Chen Hua-Chien; Wu Frederick; Qiu Yun; Kung Hsing-Jien;
JournalJ Biol Chem
PubMed ID12084720
Androgen is involved in both normal development and malignant transformation of prostate cells. The signal transduction pathways associated with these processes are not well understood. Using a novel kinase display approach, we have identified a protein kinase, human male germ cell-associated kinase (hMAK), which is transcriptionally induced by the androgenic ... More
BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies.
Authors Black Gillian F; Weir Rosemary E; Floyd Sian; Bliss Lyn; Warndorff David K; Crampin Amelia C; Ngwira Bagrey; Sichali Lifted; Nazareth Bernadette; Blackwell Jenefer M; Branson Keith; Chaguluka Steven D; Donovan Linda; Jarman Elizabeth; King Elizabeth; Fine Paul E M; Dockrell Hazel M;
JournalLancet
PubMed ID11978337
BACKGROUND: The efficacy of BCG vaccines against pulmonary tuberculosis varies between populations, showing no protection in Malawi but 50-80% protection in the UK. To investigate the mechanism underlying these differences, randomised controlled studies were set up to measure vaccine-induced immune responsiveness to mycobacterial antigens in both populations. METHODS: 483 adolescents ... More