Increase of CCR7- CD45RA+ CD8 T cells (T(EMRA)) in chronic graft-versus-host disease.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
A Salerno
Publications and source records attributed to A Salerno.
Magnetically driven growth of anthracene thin films by organic molecular beam deposition.
The possible use of a static magnetic field during organic molecular beam deposition of thin molecular films for inducing some preferential growth is discussed and the magnetic properties of diamagnetic molecules and molecular crystals are recalled. Considering prototypical materials, namely anthracene molecules and potassium phthalate substrates, which interact and may give rise to polycrystalline films with specific orientations, we show that in the presence of a magnetic field the films display a macroscopic preferential orientation as a result of minimization of the magnetic energy contribution. A very good agreement between the results of optical spectroscopy, atomic force microscopy, and predictions made on the basis of the anisotropic magnetic susceptibility of anthracene is found.
Journal Article↗
Cytokine profile, HLA restriction and TCR sequence analysis of human CD4+ T clones specific for an immunodominant epitope of Mycobacterium tuberculosis 16-kDa protein.
The identification of immunodominant and universal mycobacterial peptides could be applied to vaccine design and have an employment as diagnostic reagents. In this paper we have investigated the fine specificity, clonal composition and HLA class II restriction of CD4+ T cell clones specific for an immunodominant epitope spanning amino acids 91-110 of the 16-kDa protein of Mycobacterium tuberculosis. Twenty-one of the tested 28 clones had a Th1 profile, while seven clones had a Th0 profile. None of the clones had a Th2 profile. While the TCR AV gene usage of the clones was heterogeneous, a dominant TCR BV2 gene family was used by 18 of the 28 clones. The CDR3 regions of BV2+ T cell clones showed variation in lengths, but a putative common motif R-L/V-G/S-Y/W-E/D was detected in 13 of the 18 clones. Moreover, the last two to three residues of the putative CDR3 loops, encoded by conserved BJ sequences, could also play a role in peptide recognition. Antibody blockade and fine restriction analysis using HLA-DR homozygous antigen-presenting cells established that 16 of 18 BV2+ peptide-specific clones were DR restricted and two clones were DR-DQ and DR-DP restricted. Additionally, five of the 18 TCRBV2+ clones recognized peptide 91-110 in association with both parental and diverse HLA-DR molecules, indicating their promiscuous recognition pattern. The ability of peptide 91-110 to bind a wide range of HLA-DR molecules, and to stimulate a Th1-type interferon (IFN)-gamma response more readily, encourage the use of this peptide as a subunit vaccine component.
Antigens, Bacterial↗
A human leucocyte antigen-DR1 transgene confers susceptibility to experimental allergic encephalomyelitis elicited by an epitope of myelin basic protein.
Much evidence now indicates that human leucocyte antigen (HLA) class I and class II transgenic (Tg) mice can be of value in analysing HLA-restricted presentation of T-cell epitopes relevant to experimental models of autoimmune diseases. One area where this has been applied is the characterization of myelin epitopes presented by HLA class II molecules in experimental model of multiple sclerosis (experimental allergic encephalomyelitis (EAE)). As a first step towards humanized disease models in HLA Tg mice, we have analysed immune response of lymph node cells of HLA-DR1 Tg mice immunized with the human myelin basic protein (MBP) peptides 13-33, 87-106 and 139-154 bound by HLA-DR1. We report here that HLA-DR1 Tg mice display a hierarchy of response in vivo and in vitro to MBP epitopes depending on the binding affinity to DRB*0101 molecule. In fact, the 13-33 epitope induced a strong T helper 1 (Th1) response accompanied by high T-cell precursor frequency and caused mild EAE, while the two other epitopes gave poor (139-154) or no disease (87-106), and these data correlate with in vitro Th1 response. These data could prove a useful tool in understanding the role played by different MBP epitopes in EAE.
Amino Acid Sequence↗
Autosomal microsatellite and mtDNA genetic analysis in Sicily (Italy).
DNA samples from 465 blood donors living in 7 towns of Sicily, the largest island of Italy, have been collected according to well defined criteria, and their genetic heterogeneity tested on the basis of 9 autosomal microsatellite and mitochondrial DNA polymorphisms for a total of 85 microsatellite allele and 10 mtDNA haplogroup frequencies. A preliminary account of the results shows that: a) the samples are genetically heterogeneous; b) the first principal coordinates of the samples are correlated more with their longitude than with their latitude, and this result is even more remarkable when one outlier sample (Butera) is not considered; c) distances among samples calculated from allele and haplogroup frequencies and from the isonymy matrix are weakly correlated (r = 0.43, P = 0.06) but such correlation disappears (r = 0.16) if the mtDNA haplogroups alone are taken into account; d) mtDNA haplogroups and microsatellite distances suggest settlements of people occurred at different times: divergence times inferred from microsatellite data seem to describe a genetic composition of the town of Sciacca mainly derived from settlements after the Roman conquest of Sicily (First Punic war, 246 BC), while all other divergence times take root from the second to the first millennium BC, and therefore seem to backdate to the pre-Hellenistic period. A more reliable association of these diachronic genetic strata to different historical populations (e.g. Sicani, Elymi, Siculi), if possible, must be postponed to the analysis of more samples and hopefully more informative uniparental DNA markers such as the recently available DHPLC-SNP polymorphisms of the Y chromosome.
Alleles↗
Granulysin-dependent killing of intracellular and extracellular Mycobacterium tuberculosis by Vgamma9/Vdelta2 T lymphocytes.
Contribution of Vgamma9/Vdelta2 T lymphocytes to immune protection against Mycobacterium tuberculosis is still a matter of debate. It was reported earlier that Vgamma9/Vdelta2 T lymphocytes kill macrophages harboring live M. tuberculosis through a granule-dependent mechanism that results in killing of intracellular bacilli. This study found that Vgamma9/Vdelta2 T lymphocytes reduce the viability of both extracellular and intracellular M. tuberculosis. Granulysin and perforin, both detected in Vgamma9/Vdelta2 T lymphocytes, play a major role, which indicates that Vgamma9/Vdelta2 T lymphocytes directly contribute to a protective host response against M. tuberculosis infection.
Antigens, Differentiation, T-Lymphocyte↗
Differential activation of human gammadelta cells by nonpeptide phosphoantigens.
Human T cells expressing Vgamma9Ndelta2-encoded TCR recognize several nonpeptide phosphoantigens in the absence of major histocompatibility complex restriction. As these cells respond differentially to increasing concentrations of structurally related phosphoantigens, such ligands constitute agonists of different strengths. By analyzing early cellular events and late effector responses of gammadelta T cells, we compared their patterns of stimulation by weak, medium and strong phosphoantigen agonists. We found that, although the early metabolic activation as assessed by cytosensor microphysiometry directly reflects the intensity of subsequent effector response by gammadelta cells, TCR down-modulation is dissociated from the latter. Weak and mid-range phosphoantigen agonists induce a time- and dose-dependent down-modulation of the gammadelta TCR, whereas strong phosphoantigen agonists induce little or no TCR down-regulation. This indicates that gammadelta TCR down-modulation does not match the extent of TCR signaling as assessed by microphysiometry or conventional effector responses (TNF-alpha production and cytotoxicity). This differential pattern of gammadelta cell activation by phosphoantigens could explain the stronger potencies of some of these agonists.
Acids↗
Short latency facilitation between pairs of threshold magnetic stimuli studied in amyotrophic lateral sclerosis.
The aim of the present study was to investigate the effects of short latency facilitation between pairs of threshold magnetic stimuli on the motor cortex of amyotrophic lateral sclerosis (ALS) patients, at an interstimulus interval (ISI) of 1-5 ms. As compared to controls, the facilitatory effects normally recorded at ISI 1 and 3 ms were considerably reduced. This suggested that the neuronal circuitry responsible for these effects, which is supposed to be the same as those generating I-waves, is impaired in ALS.
Differential Threshold↗
Idiosyncratic reaction after oxaliplatin infusion.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis.
Immunohistochemistry provides an important indicator for differential diagnosis between pleural malignant mesothelioma and lung adenocarcinoma, which have complex therapeutic and medicolegal implications. To pinpoint a reliable, restricted panel of markers, the authors evaluated the efficacy of select commercial antibodies in a series of patients with confirmed clinicopathologic diagnosis of mesothelioma or lung adenocarcinoma with the aid of multiple logistic classification tables. Specimens of 46 mesotheliomas and 20 lung adenocarcinomas were examined with calretinin, thrombomodulin, cytokeratins (CKs) 5/6, and high-molecular weight CKs (indicators of mesothelioma), alongside MOC 31, Ber-EP4, and carcinoembryonic antigen (CEA; indicators of lung adenocarcinoma). Of the mesotheliomas, 40 of 46 (87%) were positive with calretinin, 29 of 46 (63%) with thrombomodulin, 40 of 46 (87%) with CKs 5/6, and 41 of 46 (89%) with high-weight CKs; five of 46 mesotheliomas (11%) were focally reactive with MOC 31, four of 46 (9%) with Ber-EP4, and two of 46 (4%) with CEA. Of the lung adenocarcinomas, 18 of 20 (90%) were positive with MOC 31, 20 of 20 (100%) with Ber-EP4, and 17 of 20 (85%) with CEA; and two of 20 (10%) were focally reactive with calretinin, one of 20 (5%) with thrombomodulin, none of 20 (0%) with CKs 5/6, and five of 20 (25%) with high-weight CKs. Multiple logistic modeling indicated two batteries of three antibodies permitting more than 98% overall accuracy: Ber-EP4 plus CKs 5/6 plus calretinin, and Ber-EP4 plus CKs 5/6 plus CEA.
Adenocarcinoma↗
Role of gamma-delta T cells in cutaneous hypersensitivity reactions.
Explore the source record for details and available documents.
Animals↗
Biology of gammadelta T cells in tuberculosis and malaria.
Tuberculosis and malaria remain the leading causes of mortality among human infectious diseases in the world. It is estimated that 3 to 5 million people die from tuberculosis and malaria each year. Although it is traditionally believed that CD4 and CD8 alphabeta T lymphocytes are mandatory for protective immune responses against Mycobacterium tuberculosis and Plasmodium falciparum (the ethiologic agents of tuberculosis and the most severe form of malaria, respectively), there is still incomplete understanding of the mechanisms of immune protection and of the causes of its failure in the affected patients. Several studies in humans and animal models have suggested that Vgamma9/Vdelta2 T cells may play an important role in the immune responses against Mycobacterium tuberculosis and Plasmodium falciparum. Vgamma9/Vdelta2 T cells represent about 75% of all circulating gammadelta T cells while they can be greatly expanded during the acute phase of Mycobacterium tuberculosis and Plasmodium falciparum malaria. Vgamma9/Vdelta2 T recognize a new class of antigenic molecules which are nonpeptidic in nature and contain critical phosphate moieties (phosphoantigens). Interestingly, phosphoantigens isolated from Mycobacterium tuberculosis and Plasmodium falciparum share strong structural homology and are probably identical. However, despite a large body of data reported in the literature, it is not yet clear whether Vgamma9/Vdelta2 T cells play a protective or pathogenic role in immune responses against Mycobacterium tuberculosis and Plasmodium falciparum. In this review we summarize our current knowledge of the biology of Vgamma9/Vdelta2 T cells in response to the two pathogens, Mycobacterium tuberculosis and Plasmodium falciparum, and provide evidence suggesting definition of a novel and important protective role through which Vgamma9/Vdelta2 T cells can contribute to the killing of microorganisms residing in intracellular compartments.
Animals↗
Resistance of natural killer T cell-deficient mice to systemic Shwartzman reaction.
The generalized Shwartzman reaction in mice which had been primed and challenged with lipopolysaccharide (LPS) depends on interleukin (IL)-12-induced interferon (IFN)-gamma production at the priming stage. We examined the involvement in the priming mechanism of the unique population of Valpha14 natural killer T (NKT) cells because they promptly produce IFN-gamma after IL-12 stimulation. We report here that LPS- or IL-12-primed NKT cell genetically deficient mice were found to be resistant to LPS-elicited mortality. This outcome can be attributed to the reduction of IFN-gamma production, because injection of recombinant mouse IFN-gamma, but not injection of IL-12, effectively primed the NKT cell-deficient mice. However, priming with high doses of LPS caused mortality of severe combined immunodeficiency, NKT cell-deficient, and CD1-deficient mice, indicating a major contribution of NKT cells to the Shwartzman reaction elicited by low doses of LPS, whereas at higher doses of LPS NK cells play a prominent role. These results suggest that the numerically small NKT cell population of normal mice apparently plays a mandatory role in the priming stage of the generalized Shwartzman reaction.
Animals↗
In utero fetal liver hematopoietic stem cell transplantation: is there a role for alloreactive T lymphocytes.
Explore the source record for details and available documents.
Blood Transfusion, Intrauterine↗
Vgamma9/Vdelta2 T lymphocytes reduce the viability of intracellular Mycobacterium tuberculosis.
An effective immune response against the intracellular pathogen Mycobacterium tuberculosis is strictly dependent on T cell activation. Although this protective response mainly depends on local release of pro-inflammatory cytokines by Th1 CD4(+) T cells, contribution of Vgamma9 / Vdelta2 T lymphocytes to immune protection against this pathogen is suggested by the antimycobacterial reactivity of this subset and its ability to produce large amounts of Th1 cytokines. Here we show that Vgamma9 / Vdelta2 T lymphocytes kill macrophages harboring live M. tuberculosis. The cytotoxic activity of Vgamma9 / Vdelta2 T lymphocytes was not MHC class I or class II restricted but was blocked by anti-TCR monoclonal antibodies, thus indicating that it involved specific interaction between the TCR and the target cell. The cytotoxicity of Vgamma9 / Vdelta2 T lymphocytes was not mediated by TNF-alpha or Fas-Fas ligand, but was shown to occur through a granule-dependent mechanism that resulted in reduction of the viability of intracellular bacilli. Perforin was shown to play an important role in killing of both infected macrophages and intracellular mycobacteria. These data strongly suggest that Vgamma9 / Vdelta2 T lymphocytes contribute to the host defense against M. tuberculosis infection.
Cells, Cultured↗
Whole body irradiation induces IFN-gamma production in BALB/c mice by preventing the appearance of a V alpha 14(+)NK T downregulatory population.
Lymph node cells from TNCB-immune BALB/c mice fail to produce IFN-gamma when exposed to antigen in vitro. Conversely, lymph node cells of irradiated (550 rads) BALB/c mice produce IFN-gamma. Transfer experiments show that normal BALB/c mice contain cells which suppress IFN-gamma production. These downregulatory cells are CD4(+)alpha beta(+)and rearrange the invariant V alpha 14-J alpha 281 T cell receptor alpha chain, thus belonging to the NK T cell subset. Downregulatory cells probably act by producing IL-4 as their effect is blocked by mAb to IL-4.
Animals↗
Townes-Brocks syndrome and renal dysplasia: a novel mutation in the SALL1 gene.
A 14-year-old African-American boy had chronic renal failure and Townes-Brocks syndrome (TBS). There were no affected family members. Features were imperforate anus, rectoperineal fistula, triphalangeal thumb, bifid thumb, rocker bottom feet, bilateral ear tags, satyr ear, sensorineural hearing loss, hypospadias, bilateral renal hypoplasia, and progressive chronic renal failure. Renal and urological anomalies in TBS include renal hypoplasia, renal dysplasia, unilateral renal agenesis, horseshoe kidney, posterior urethral valves, uretero-vesical reflux, and meatal stenosis. TBS is caused by a dominantly inherited defect in the gene encoding the SALL1 putative transcription factor, a protein possibly required for urological, renal, limb, ear, brain, and liver development. This patient had a novel mutation in this gene. The extent of renal involvement in patients with TBS should be evaluated for optimum treatment and prediction of prognosis.
Abnormalities, Multiple↗
[Spontaneous electromyographic activity. Practical importance].
Spontaneous activities are a major semeiologic sign in electromyography. The present article deals with the different aspects recorded in practice in normal and pathological cases. There are two types of spontaneous activities, those related to motor unit hyperactivity (fasciculations and myokymia) and those related to the hyperactivity of one or more muscle fibers: fibrillations, positive sharp waves, myotonic discharges and complex repetitive discharges. In the first case the lesion is located in the axone and in the second in the membrane of the muscle fibers; All theories related to the cells' abnormalities share a common feature: spontaneous activities result from abnormal firing of the membrane action potential of muscular fibers. This functional abnormality may results from different types of lesions within the cells' membrane and determines the aspects of spontaneous activities. Impaired function of muscular cells' membranes can be produced by denervation or lesion of the membrane structure itself. The latter can be multiple and linked with the membrane proteins (such as laminine or dystrophin as in AIDS diseases) or with ion channel disturbances. Multiple membrane cell alterations may produce the same kind of spontaneous activity; for instance, myotonic discharges have the same morphology in Thomsen and Steinert's disease despite their different mechanisms and fibrillations seen in denervations and myopathies. The practical consequences are discussed and a new classification of these spontaneous activities is proposed.
Action Potentials↗