Nucleolar Organiser Regions

Crocker, J

doi:10.1007/978-3-642-74668-0_3

Cited by 116 publications

(40 citation statements)

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“…These modifications are assessed by computerized image analysis of silver stained nuclei, which show patterns of nucleolar AgNOR segregation and aggregation that characterize each phase of the cell cycle. 47 Here we report results of a further analysis of the cell-cycle dysregulation, which occurs during HIV infection, focusing on (1) intracellular turnover of cyclin B1, p34 cdc2, and cdc25, (2) AgNOR number and area of distribution, and (3) expression and cellular localization of C23/nucleolin. …”

mentioning

confidence: 99%

Abnormal intracellular kinetics of cell-cycle-dependent proteins in lymphocytes from patients infected with human immunodeficiency virus: a novel biologic link between immune activation, accelerated T-cell turnover, and high levels of apoptosis

Cannavò

Paiardini

Galati

et al. 2001

Blood

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Human immunodeficiency virus (HIV)-infection is characterized by loss of CD4؉ T cells associated with high levels of immune activation, T-cell proliferation, and lymphocyte apoptosis. To investigate the role of intrinsic perturbations of cellcycle control in the immunopathogenesis of acquired immunodeficiency syndrome (AIDS), we studied the expression of cellcycle-dependent proteins in lymphocytes from HIV-infected patients. Cyclin B1 expression, Nucleolar Organizer Regions (NORs) number, and NORs area of distribution were all consistently increased in HIV-infected patients, but returned to normal after effective antiretroviral therapy, suggesting that viral replication is directly implicated in the genesis of the observed changes. Analysis of cyclin B1 intracellular turnover showed that the increased cyclin B1 expression is (1) caused by defective degradation in the presence of normal rates of synthesis, and (2) is temporally associated with decreased levels of ubiquitination. After in vitro activation of lymphocytes from healthy individuals, cyclin B1 and cdc25 expression and ubiquitination, p34 cdc2 activity, NORs morphology, and C23/nucleolin localization showed a 72-to 96-hour cyclic pattern that led to a biologic state similar to baseline. On the contrary, complex but consistent changes of the same indices followed activation of T lymphocytes from HIVinfected patients, resulting in a 5-fold increase in apoptosis. Overall, our data indicate that a profound dysregulation of cellcycle control is present in lymphocytes from HIV-infected patients. This finding may provide a novel biologic link between immune activation, accelerated lymphocyte turnover, and increased apoptosis during HIV infection. IntroductionHuman immunodeficiency virus (HIV)-infection induces a progressive depletion of CD4 ϩ T lymphocytes and high susceptibility to opportunistic infections. 1 The mechanisms of HIV-induced CD4 ϩ T-cell loss include the virus-mediated killing of infected cells as well as the death of uninfected bystander cells. 1,2 Among the indirect mechanisms that have been implicated in the lymphocyte depletion of patients with acquired immunodeficiency syndrome (AIDS), increased level of apoptosis may be significant. In HIV-infected patients, increased susceptibility to apoptotic cell death has been shown in CD4 ϩ and CD8 ϩ T lymphocytes and appears to be correlated with the general state of immune activation. [3][4][5][6] Interestingly, both increased propensity to apoptosis and overall levels of immune activation are reversed by the institution of effective anti-HIV therapy. 7,8 It is therefore likely that an abnormal relationship between T-cell activation/proliferation and occurrence of apoptosis may play a significant role in the lymphocyte depletion in the HIV-infected patient. 9,10 Lymphocyte activation in response to extrinsic signals ultimately results in either progression through the cell cycle, or activation of proapoptotic pathway(s). 11,12 Although influenced by many factors, the fate of activated T cells is e...

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mentioning

confidence: 99%

Abnormal intracellular kinetics of cell-cycle-dependent proteins in lymphocytes from patients infected with human immunodeficiency virus: a novel biologic link between immune activation, accelerated T-cell turnover, and high levels of apoptosis

Cannavò

Paiardini

Galati

et al. 2001

Blood

View full text Add to dashboard Cite

show abstract

“…The assessment and grading of non Hodgkin's lymphoma (NHL) is a clinically crucial procedure and accurate evalua- (Crocker & Nar, 1987), and cell imprints and also in the related field of bone marrow aspirate evaluation (Nikicicz & Norback, 1990).…”

Section: Applicationmentioning

confidence: 99%

“…Counts in squamous carcinomas of larynx and bronchus are related inversely to differentiation (Ashworth & Helliwell, 1988;Crocker, 1990); however, squamous tumours of pharynx and larynx cannot be separated on the basis of AgNOR counts (Bryan et al, 1990). It is not yet certain whether AgNORs are related to prognosis for the different histological varieties of lung cancer and investigation are currently underway.…”

Section: Respiratory Tractmentioning

confidence: 99%

“…Gliomas and gliosis can be differentiated using AgNORs (Crocker, 1990) but the diagnosis and prediction of behaviour of occular melanomas is not enhanced by their evaluation (Williams et al, 1988).…”

Section: Cns Tumoursmentioning

confidence: 99%

“…Borderline lesions A continuum of AgNOR numbers is seen in dysplastic laryngeal epithelium (Ashworth & Helliwell, 1988;Crocker, 1990), dysplastic bronchial epithelium and CIN Egan et al, 1990;Rowlands, 1988). In situ transitional carcinoma of the nose can be distinguished from benign and invasive disease .…”

Section: Othermentioning

confidence: 99%

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