Stability of the replicative Mcm3 protein in proliferating and differentiating human cells

Mcm proteins are abundant nuclear proteins involved in the regulation of genome replication. Previous experiments had shown that levels of Mcm-specific mRNAs increase at the G1/S phase transition of the cell cycle, but that the amounts of Mcm proteins do not change much during the cell cycle. To learn more about the stability of an Mcm protein we performed experiments which showed that: (i) more than 60% of [35S]methionine pulse-labeled Mcm3 protein appears to be degraded during a 24-h chase in HeLa cells; (ii) the amount of Mcm3 protein significantly decreases during the differentiation of HL60 cells in vitro (whereas another replication-initiation protein, hOrc2, remains fairly constant); and (iii) according to immunohistochemical staining, Mcm3 protein is present in nuclei of cells in the proliferating zone of human epidermal tissue, but in decreasing amounts in nuclei of differentiating cells of the upper cell layers. Our interpretation is that Mcm3 protein is no longer synthesized after initiation of differentiation and slowly disappears at a half-life of approximately 24 h.     

Causes and consequences of natal dispersal in root voles, Microtus oeconomus

To test the causes and consequences of variation in natal dispersal in root voles we released 53 matrilines (mothers with newly weaned litters) separately in field enclosures, during nine consecutive periods. The matrilines could disperse and distribute themselves among three pre-emptied habitat patches. Two dispersal measures were recorded: short-distance dispersal defined as individuals immigrating to a neighbouring patch, and long-distance dispersal defined as unsettled individuals captured along the fence of the enclosures. We analysed the role of social factors (i.e. maternal and litter characteristics), habitat quality (i.e. seasonal effect) and experimentally manipulated shape of the natal patch in dispersal. The consequences of dispersal were analysed with respect to the spatial distribution of kin, and to pregnancy in females and sexual maturation in males. Dispersal was unrelated to patch shape. In agreement with the inbreeding avoidance hypothesis, long-distance dispersal was male biased and philopatric males were most frequently reproductively inactive. Whilst young males avoided their mother, they seemed to disperse, settle and mature sexually independently of their sisters. In agreement with the resource competition hypothesis, young females avoided their mother and were most frequently reproductively inactive when residing in their mother's patch. We conclude that inbreeding avoidance was underlying the male dispersal pattern. For females, long-distance dispersal was most in agreement with the inbreeding avoidance hypothesis while short-distance dispersal could be explained by the resource competition hypothesis. (c) 1998 The Association for the Study of Animal Behaviour.     

Is Kaposi's sarcoma--associated herpesvirus ubiquitous in urogenital and prostate tissues?

Controversy exists as to whether Kaposi's sarcoma-associated herpesvirus (KSHV) is more widespread than originally reported. Recently, Monini et al reported that KSHV is ubiquitous in urogenital and prostate tissues and sperm of healthy Italian adults using nested polymerase chain reaction (PCR). We have examined for the presence of KSHV in 10 normal prostates from Italian men and 10 from men from the United States, as well as 32 prostatic, 30 vulvar, 24 ovarian, 20 cervical, and 30 testicular cancer specimens from patients from the United States. None of the patients had a history of human immunodeficiency virus infection. The samples were tested by nested PCR. The sensitivity of this assay was determined by a dilution study performed by diluting KSHV DNA from the KS-1 cells (a primary effusion lymphoma cell line which is estimated to have 16 copies of KSHV per cell) in DNA from a K562 myeloid cell line. The nested PCR that we used can detect 2.4 copies of KSHV sequences on a background of K562 DNA. All the samples were negative for KSHV sequences. Therefore, we cannot confirm the finding that KSHV sequences are ubiquitous in urogenital and prostate tissues. Furthermore, because our samples were from both the United States and Italy, the discrepancy between results is unlikely to be explained by either ethnic or environmental factors. False-positive results easily occur using nested primer PCR because of contamination. Our data argue that KSHV is not widely disseminated in urogenital tissues from nonimmunosuppressed individuals.     

A logistic regression model when some events precede treatment: the effect of thrombolytic therapy for acute myocardial infarction on the risk of cardiac arrest

When outcomes occur in clinical trials before treatment can be given, neither intent-to-treat nor according-to-protocol analyses give optimal estimates of the treatment effect. A better approach employs a time-dependent variable for treatment. Intent-to-treat analyses are conservative, biasing against treatment; according-to-protocol analyses bias in favor of treatment. We show how to measure the effect of a time-dependent variable in a logistic regression using person-time intervals as units of measurement and describe appropriate methods for reporting model performance. The method is applied to develop a model to predict the probability that a patient with a myocardial infarction will have a sudden cardiac arrest within 48 hours of presentation to emergency medical services both when treated with thrombolysis and when not treated. We use a time-dependent treatment variable because many patients went into cardiac arrest while awaiting treatment. This technique has been programmed into an electrocardiograph for real-time use in an emergency department.     

T-cell large granular lymphocytic leukemia associated with pure red cell aplasia, successfully treated with cyclophosphamide

Authors report effective treatment of T-cell large granular lymphocyte (LGL) leukaemia and secondary pure cell aplasia with cyclophosphamide. The current classification of LGL proliferations is presented, with emphasis on the issues of diagnosis, clinical course and treatment. LGL proliferations are not so rare that previously thought and should be involved in the differential diagnosis of neutropenia, pure red cell aplasia, Felty's syndrome and vasculitis of unknown origin.