N,N’-bis(2-chloroethyl)-N-nitrosourea
(BCNU) is one of the major drugs used in chemotherapy against malignant
gliomas due to its effects, such as induction of bifunctional alkylation of
DNA and formation of interstrand DNA cross-linkages, and induces cortical
malformations in the fetal and neonatal rat brain. In this study, pregnant
rats were treated with 7.5 mg/kg of BCNU on gestational day 13 (GD 13), and
their fetuses were collected from 12 to 72 hours after BCNU treatment in
order to examine the timecourses of morphological and immunohistochemical
changes in neural progenitor cells in the developing brain. The number of
pyknotic cells in the telencephalon peaked at 24 h and then gradually
decreased until 72 h. The majority of these pyknotic cells were positive
for cleaved caspase-3, a key executioner of apoptosis. The pyknotic cells
showed the ultrastructural characteristics of apoptosis. The number of
p53-positive cells began to increase prior to the appearance of apoptotic
cells and p21-positive cells. The number of phosphorylated-histone
H3-positive cells (mitotic cells) decreased from 24 to 36 h. The number of
Iba1-positive cells (microglial cells) in the telencephalon increased from
12 to 48 h. These results suggest that BCNU induces p53-dependent apoptosis
and reduces proliferative activity, resulting in reduction of the weight of
the telencephalon and the thickness of the telencephalic wall in the fetal
brain. This study will help to clarify the mechanisms of BCNU-induced fetal
brain toxicity.
We conducted a study to assess the precise incidence of anaerobic infections among patients with pulmonary diseases in Japan. To avoid false-negative results of anaerobic cultures, we used percutaneous transtracheal aspiration and subsequent immediate bedside anaerobic inoculation onto a set of plates with appropriately selected culture media. Fifty-six episodes of pulmonary disease occurred in 50 patients; anaerobes were isolated in 20 (36%) of these episodes. Bacteria were recovered in 30 (94%) of 32 episodes not associated with prior antimicrobial therapy, and anaerobes were isolated in 15 (47%) of these 32 episodes. Rates of anaerobic isolation in episodes of pneumonia (7 of 14), lung abscess (3 of 3), and acute exacerbation of chronic lower respiratory tract infection (5 of 15) that were not associated with prior antimicrobial therapy were 50%, 100%, and 33%, respectively.
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