WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues

The adhesive interactions of cells with other cells and with the extracellular matrix are crucial to all developmental processes, but have a central role in the functions of the immune system throughout life Three families of cell-surface molecules regulate the migration of lymphocytes and the interactions of activated cells during immune responses

Adhesion receptors of the immune system.

Mitogen-dependent progression through the first gap phase (G1) and initiation of DNA synthesis (S phase) during the mammalian cell division cycle are cooperatively regulated by several classes of cyclin-dependent kinases (CDKs) whose activities are in turn constrained by CDK inhibitors (CKIs). CKIs that govern these events have been assigned to one of two families based on their structures and CDK targets. The first class includes the INK4 proteins (inhibitors of CDK4), so named for their ability to specifically inhibit the catalytic subunits of CDK4 and CDK6. Four such proteins [p16 (Serrano et al. 1993), p15 (Hannon and Beach 1994), p18 (Guan et al. 1994; Hirai et al. 1995), and p19 (Chan et al. 1995; Hirai et al. 1995)] are composed of multiple ankyrin repeats and bind only to CDK4 and CDK6 but not to other CDKs or to D-type cyclins. The INK4 proteins can be contrasted with more broadly acting inhibitors of the Cip/Kip family whose actions affect the activities of cyclin D-, E-, and A-dependent kinases. The latter class includes p21 (Gu et al. 1993; Harper et al. 1993; El-Deiry et al. 1993; Xiong et al. 1993a; Dulic et al. 1994; Noda et al. 1994), p27 (Polyak et al. 1994a,b; Toyoshima and Hunter 1994), and p57 (Lee et al. 1995; Matsuoka et al. 1995), all of which contain characteristic motifs within their amino-terminal moieties that enable them to bind both to cyclin and CDK subunits (Chen et al. 1995, 1996; Nakanishi et al. 1995; Warbrick et al. 1995; Lin et al. 1996; Russo et al. 1996). Based largely on in vitro experiments and in vivo overexpression studies, CKIs of the Cip/Kip family were initially thought to interfere with the activities of cyclin D-, E-, and A-dependent kinases. More recent work has altered this view and revealed that although the Cip/Kip proteins are potent inhibitors of cyclin Eand A-dependent CDK2, they act as positive regulators of cyclin Ddependent kinases. This challenges previous assumptions about how the G1/S transition of the mammalian cell cycle is governed, helps explain some enigmatic features of cell cycle control that also involve the functions of the retinoblastoma protein (Rb) and the INK4 proteins, and changes our thinking about how either p16 loss or overexpression of cyclin D-dependent kinases contribute to cancer. Here we focus on the biochemical interactions that occur between CKIs and cyclin Dand E-dependent kinases in cultured mammalian cells, emphasizing the manner by which different positive and negative regulators of the cell division cycle cooperate to govern the G1-to-S transition. To gain a more comprehensive understanding of the biology of CDK inhibitors, readers are encouraged to refer to a rapidly emerging but already extensive literature (for review, see Elledge and Harper 1994; Sherr and Roberts 1995; Chellappan et al. 1998; Hengst and Reed 1998a; Kiyokawa and Koff 1998; Nakayama 1998; Ruas and Peters 1998).

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CDK inhibitors: positive and negative regulators of G1-phase progression

Emerging infectious diseases (EIDs) are a significant burden on global economies and public health. Their emergence is thought to be driven largely by socio-economic, environmental and ecological factors, but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of EIDs. Here we analyse a database of 335 EID 'events' (origins of EIDs) between 1940 and 2004, and demonstrate non-random global patterns. EID events have risen significantly over time after controlling for reporting bias, with their peak incidence (in the 1980s) concomitant with the HIV pandemic. EID events are dominated by zoonoses (60.3% of EIDs): the majority of these (71.8%) originate in wildlife (for example, severe acute respiratory virus, Ebola virus), and are increasing significantly over time. We find that 54.3% of EID events are caused by bacteria or rickettsia, reflecting a large number of drug-resistant microbes in our database. Our results confirm that EID origins are significantly correlated with socio-economic, environmental and ecological factors, and provide a basis for identifying regions where new EIDs are most likely to originate (emerging disease 'hotspots'). They also reveal a substantial risk of wildlife zoonotic and vector-borne EIDs originating at lower latitudes where reporting effort is low. We conclude that global resources to counter disease emergence are poorly allocated, with the majority of the scientific and surveillance effort focused on countries from where the next important EID is least likely to originate.

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Global trends in emerging infectious diseases

Natural selection acts on phenotypes, regardless of their genetic basis, and produces immediate phenotypic effects within a generation that can be measured without recourse to principles of heredity or evolution. In contrast, evolutionary response to selection, the genetic change that occurs from one generation to the next, does depend on genetic variation. Animal and plant breeders routinely distinguish phenotypic selection from evolutionary response to selection (Mayo, 1980; Falconer, 1981). Upon making this critical distinction, emphasized by Haldane (1954), precise methods can be formulated for the measurement of phenotypic natural selection. Correlations between characters seriously complicate the measurement of phenotypic selection, because selection on a particular trait produces not only a direct effect on the distribution of that trait in a population, but also produces indirect effects on the distribution of correlated characters. The problem of character correlations has been largely ignored in current methods for measuring natural selection on quantitative traits. Selection has usually been treated as if it acted only on single characters (e.g., Haldane, 1954; Van Valen, 1965a; O'Donald, 1968, 1970; reviewed by Johnson, 1976 Ch. 7). This is obviously a tremendous oversimplification, since natural selection acts on many characters simultaneously and phenotypic correlations between traits are ubiquitous. In an important but neglected paper, Pearson (1903) showed that multivariate statistics could be used to disentangle the direct and indirect effects of selection to determine which traits in a correlated ensemble are the focus of direct selection. Here we extend and generalize Pearson's major results. The purpose of this paper is to derive measures of directional and stabilizing (or disruptive) selection on each of a set of phenotypically correlated characters. The analysis is retrospective, based on observed changes in the multivariate distribution of characters within a generation, not on the evolutionary response to selection. Nevertheless, the measures we propose have a close connection with equations for evolutionary change. Many other commonly used measures of the intensity of selection (such as selective mortality, change in mean fitness, variance in fitness, or estimates of particular forms of fitness functions) have little predictive value in relation to evolutionary change in quantitative traits. To demonstrate the utility of our approach, we analyze selection on four morphological characters in a population of pentatomid bugs during a brief period of high mortality. We also summarize a multivariate selection analysis on nine morphological characters of house sparrows caught in a severe winter storm, using the classic data of Bumpus (1899). Direct observations and measurements of natural selection serve to clarify one of the major factors of evolution. Critiques of the "adaptationist program" (Lewontin, 1978; Gould and Lewontin, 1979) stress that adaptation and selection are often invoked without strong supporting evidence. We suggest quantitative measurements of selection as the best alternative to the fabrication of adaptive scenarios. Our optimism that measurement can replace rhetorical claims for adaptation and selection is founded in the growing success of field workers in their efforts to measure major components of fitness in natural populations (e.g., Thornhill, 1976; Howard, 1979; Downhower and Brown, 1980; Boag and Grant, 1981; Clutton-Brock et

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1558-5646.1983.tb00236.x

The measurement of selection on correlated characters

The CD4 (or T4) surface antigen of human T lymphocytes is an important part of the receptor for the human immunodeficiency virus (HIV) After binding to the receptor, the HIV may enter the T cell and induce the formation of syncytia In an attempt to identify the receptor site more closely, monoclonal antibodies (Mab's) to CD4 were tested for their ability to block HIV infection in a syncytium formation assay, and the CD4 epitopes so identified were mapped by antibody cross-blocking The antibodies that showed strong inhibition of HIV fell into two main families while a third group of Mab's blocked syncytia formation weakly or not at all Several different isolates of HIV as well as the laboratory strain CBL1 grown in CEM cells were used to induce the syncytia The data indicate that only some epitopes of CD4 are important for virus binding and imply that the virus-binding site for CD4 is conserved in different isolates of HIV with substantially divergent env gene sequences Preliminary studies of patients suggest that polymorphism of these epitopes does not play a role in determining susceptibility to infection

https://science.sciencemag.org/content/sci/234/4780/1120.full.pdf

Epitopes of the CD4 antigen and HIV infection.

HIV testing on all pregnant women.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus linked to the development of Kaposi's sarcoma and a rare B cell lymphoma, primary effusion lymphoma. The KSHV gene ORF K9 encodes vIRF which is a protein with low but significant homology to members of the interferon (IFN) regulatory factor (IRF) family responsible for regulating intracellular interferon signal transduction (Moore PS, Boshoff C, Weiss RA and Chang Y. (1996). Science, 274, 1739-1744). vIRF inhibits IFN-beta signal transduction as measured using an IFN-responsive ISG54 reporter construct co-transfected with ORF K9 into HeLa and 293 cells. vIRF also suppresses genes under IFN regulatory control as shown by inhibition of the IFN-beta inducibility of p21WAF1/CIP1, however, no direct DNA-binding or protein-protein interactions characteristic for IRF repressor proteins were identified. Stable transfectant NIH3T3 clones expressing vIRF grew in soft agar and at low serum concentrations, lost contact inhibition and formed tumors after injection into nude mice indicating that vIRF has the properties of a viral oncogene. Since vIRF is primarily expressed in KSHV-infected B cells, not KS spindle cells, this study suggests that vIRF is a transforming oncogene active in B cell neoplasias that may provide a unique immune escape mechanism for infected cells. This data is consistent with tumor suppressor pathways serving a dual function as host cell antiviral pathways.

KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway

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Cyclin encoded by KS herpesvirus

When endogenous retroviruses (ERV) were discovered in the late 1960s, the Mendelian inheritance of retroviral genomes by their hosts was an entirely new concept. Indeed Howard M Temin's DNA provirus hypothesis enunciated in 1964 was not generally accepted, and reverse transcriptase was yet to be discovered. Nonetheless, the evidence that we accrued in the pre-molecular era has stood the test of time, and our hypothesis on ERV, which one reviewer described as 'impossible', proved to be correct. Here I recount some of the key observations in birds and mammals that led to the discovery of ERV, and comment on their evolution, cross-species dispersion, and what remains to be elucidated.

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Robin A. Weiss

Papers

Epitopes of the CD4 antigen and HIV infection.

HIV testing on all pregnant women.

KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway

Cyclin encoded by KS herpesvirus

The discovery of endogenous retroviruses