A regulatory role for recombinase activating genes, RAG-1 and RAG-2, in T cell development

Effects of etoposide (VP-16) and cytosine arabinoside (Ara-C) on the cell cycle of HL-60 and THP-1 cells were studied by flow cytometry using the bromodeoxyuridine (BrdU)/DNA assay technique to investigate the efficacy of VP-16 for monocytic leukemia cells. VP-16 inhibited the proliferation of THP-1 cells more strongly than that of HL-60 cells at any concentrations used at 24 and 48 hr. VP-16 arrested HL-60 and THP-1 cells in the G2/M phase and reduced them in the G0/G1 and early S phase at higher concentrations. There was no significant difference in the percentage of G2/M phase cells at the same concentration between both cells. However, reduction in the G0/G1 and early S phase cells was more marked in THP-1 than HL-60 cells significantly. On the other hand, Ara-C perturbed the cell cycle of HL-60 cells more than that of THP-1 cells at 24 and 48 hr. These results suggest that the effects of VP-16 on the cell cycle may be more intense in THP-1 than HL-60 cells, and support the efficacy of VP-16 for treating monocytic leukemia in vivo.     

A long term epidemiological study of bovine viral diarrhoea infections in a large herd of dairy cattle

Epidemiological aspects of bovine viral diarrhoea virus (BVDV) infections were studied longitudinally in a large dairy herd for three years. At the start of the study, practically all the cows more than four years old had BVDV antibody titres, whereas the younger stock were almost all seronegative. The spread of the virus was monitored in a part of the population that contained only transiently viraemic cattle and in another part that contained persistently viraemic calves. Among the lactating cows the virus circulated for two-and-a-half years, although they had no direct contact with persistently viraemic cattle during this period. The highest transmission rate occurred when a large number of susceptible heifers was added to the population of cows that contained transiently viraemic cattle. The circulation of BVDV among the lactating cows ceased while 27 seronegative cows were still present. Both findings are in accordance with predictions from simple epidemic models. The susceptibility of the cows that remained seronegative was confirmed experimentally. In contrast with the limited circulation of BVDV caused by transiently viraemic cattle, virtually all susceptible cattle that came into contact with a persistently viraemic calf became seropositive within three months. Transplacental BVDV infections were not detected in the calves born to cows that had antibodies against the virus due to an infection that had occurred at least four years earlier. Transplacental transmission of BVDV did not occur in most of the pregnant cows that were infected before approximately the 60th day of gestation, but when cows became infected later in gestation the virus virtually always invaded the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)     

A novel receptor-mediated nuclear protein import pathway

Targeting of most nuclear proteins to the cell nucleus is initiated by interaction between the classical nuclear localization signals (NLSs) contained within them and the importin NLS receptor complex. We have recently delineated a novel 38 amino acid transport signal in the hnRNP A1 protein, termed M9, which confers bidirectional transport across the nuclear envelope. We show here that M9-mediated nuclear import occurs by a novel pathway that is independent of the well-characterized, importin-mediated classical NLS pathway. Additionally, we have identified a specific M9-interacting protein, termed transportin, which binds to wild-type M9 but not to transport-defective M9 mutants. Transportin is a 90 kDa protein, distantly related to importin beta, and we show that it mediates the nuclear import of M9-containing proteins. These findings demonstrate that there are at least two receptor-mediated nuclear protein import pathways. Furthermore, as hnRNP A1 likely participates in mRNA export, it raises the possibility that transportin is a mediator of this process as well.     

Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice

The bcl-2 proto-oncogene can prevent the death of many cell types. Mice were generated that were chimeric for the homozygous inactivation of bcl-2. Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. In contrast, stimulation of CD3 inhibited the death of these cells. T and B cells with no Bcl-2 disappeared from the bone marrow, thymus, and periphery by 4 weeks of age. Thus, Bcl-2 was dispensable for lymphocyte maturation, but was required for a stable immune system after birth.     

Review of patients with infective endocarditis of native valves over a five-year period

The clinical characteristics, echocardiographic features, bacteriologic data, morbidity and mortality of patients who were admitted to our hospital with infective endocarditis of their native valves over a five-year period were reviewed. There were 32 patients with a mean age of 38.2 +/- 16.2 years (range: 17 to 71 years) in our study population; 24 patients had underlying valvular abnormalities, six patients had congenital heart disease and two patients had no structural cardiac abnormality. Echocardiography was performed for all patients. Vegetations were absent in three (9.4%) patients, single in 19 (59.4%) patients and multiple in ten (31.3%) patients. Of the 24 (75%) patients who had left-sided endocarditis, mitral valve disease was the commonest valvular abnormality (16 patients). Ventricular septal defect was the commonest underlying abnormality in patients with right-sided endocarditis. Blood cultures were positive in 26 (81.3%) patients; the commonest organism was streptococcal (16 or 50% patients). Complications were present in 13 (40.6%) patients, of which eight patients had evidence of embolism, four patients had cardiac failure and one patient had a paravalvular abscess. Four (12.5%) patients died, two as a result of refractory heart failure and two as a consequence of septic embolism. Advances in medicine have resulted in a better outcome for patients with infective endocarditis, however, it remains an important disease with significant morbidity and mortality.