Expression of topoisomerase II, bcl-2, and p53 in three human brain tumor cell lines and their possible relationship to intrinsic resistance to etoposide

We characterized three human brain tumor cell lines (D54, HBT-20, and HBT-28) with respect to resistance to etoposide (VP-16), a topoisomerase II-reactive drug. All three cell lines were inherently resistant to VP-16 when compared to other human cell lines, with D54 showing the greatest resistance using colony formation assays. Resistance to VP-16 has been attributed to decreased drug uptake and changes in topoisomerase II; however, drug uptake and topoisomerase II protein levels (immunoblot) were no lower in D54 than in HBT-20 and HBT-28, cell lines relatively more sensitive to VP-16. More to the point, measurement of topoisomerase II-mediated DNA cleavage of cellular DNA after treatment with VP-16 showed that the topoisomerase II in these cells was active. These data indicate mechanisms other than those attributable to decreased drug uptake or altered topoisomerase II exist for clinical resistance to VP-16. VP-16-induced DNA cleavage has been associated with apoptosis in some cell lines; however, neither DNA laddering nor morphological changes characteristic of apoptosis were detected in these cell lines after treatment with VP-16. Bcl-2 and mutant p53 were present in these cells. Either of these conditions can prevent apoptosis and could explain a dissociation between the proximal mediator of VP-16-induced cytotoxicity (topoisomerase II-DNA complex formation) and cellular death.     

The early diagnosis of the severity of blast trauma to the brain and auditory system]

This paper presents the information on the early period of an explosive head trauma and trauma to the auditory system. Different types of hearing impairment, the staging of the pathological process were determined along with various immunological and biochemical changes occurring in this group of patients. The results of the study call for necessity of the early ENT observation of all patients in whom an explosive trauma is suspected.     

Combining beta-core fragment and total oestriol measurements to test for Down syndrome pregnancies

Recent articles by Cuckle et al., Canick et al., and Isozaki et al. have evaluated urine beta-core fragment as a screening test for Down syndrome in second-trimester pregnancies. They found over four-fold elevation of beta-core fragment levels in Down syndrome pregnancies, and between 62 and 88 per cent detection of this trisomy at a 5 per cent false-positive rate. Urine beta-core fragment may be a superior screening test for Down syndrome pregnancies. In the present study, urinary total oestriol has been evaluated as a marker to use in combination with beta-core fragment in screening for Down syndrome pregnancies. The two markers were evaluated separately in relation to the urine creatinine concentration. To amplify screening performance, we evaluated the ratio of beta-core fragment to total oestriol levels (creatinine-independent). beta-core fragment and total oestriol levels were determined (normalized to creatinine, ng/mg creatinine) in urine samples from 480 unaffected and 12 Down syndrome pregnancies, collected consecutively at a single prenatal diagnosis centre. The median beta-core fragment level in Down syndrome cases was 4.5 MOM. Fifty-eight per cent of Down syndrome cases had beta-core fragment levels exceeding the 95th centile of unaffected pregnancies. The median total oestriol level in Down syndrome cases was 0.33 MOM. Forty-two per cent of Down syndrome cases had total oestriol levels exceeding the 95th centile of unaffected pregnancies. We investigated the ratio of the two determinants (beta-core fragment, ng/ml divided by total oestriol, ng/ml) in our sample set. The median beta-core fragment:total oestriol ratio in Down syndrome cases was 13 MOM. Seventy-five per cent of Down syndrome cases had a ratio exceeding the 95th and the 99.5th centile of unaffected pregnancies. Total oestriol complements beta-core fragment in urine screening for Down syndrome pregnancies. A test measuring the ratio of the two urine determinants may be a significant improvement over current serum methods for detecting Down syndrome.     

Effects of size and orientation change on hippocampal activation during episodic recognition: a PET study

To determine whether physical match between studied and tested items influences blood flow increases in the hippocampal formation associated with recognition memory, positron emission tomography (PET) was used to measure changes in regional cerebral blood flow while healthy volunteers made old/new judgements about line drawings of objects. Some objects were tested in the same size and orientation as they had appeared earlier during the study phase of the experiment; other objects were tested in a different size or orientation than when they were studied. Blood flow increases in the vicinity of the hippocampal formation were observed in the same object condition compared with the size change and the orientation change conditions, even though recognition accuracy was affected significantly only by orientation change. Results add to previous findings suggesting that physical similarity between studied items and test cues may contribute to hippocampal activation during episodic retrieval.     

Erythrocyte sodium lithium countertransport in normal and hypertensive pregnancy: relation to haemodynamic changes

OBJECTIVE: To establish the changes in erythrocyte sodium lithium countertransport (SLC) with advancing normal pregnancy and to determine if these changes were different in pregnancy induced hypertension (PIH). The changes in both groups were assessed in relation to haemodynamic changes. DESIGN: SLC, mean arterial pressure (MAP), cardiac output (CO) and total peripheral vascular resistance (TPVR) were determined serially during normal pregnancy and cross-sectionally in PIH. Women were studied again 20 weeks after delivery where possible. SETTING: Routine antenatal clinic and antenatal ward of a regional reference centre. SUBJECTS: Fifty-one normal primigravid women were studied serially and 41 primigravid women with PIH were studied at time of diagnosis. RESULTS: During normal pregnancy SLC (mmol Li/h/l cells) increased from a nonpregnant value of 0.24 +/- 0.02 (mean +/- SEM) to 0.32 +/- 0.02 at 14 weeks, and 0.37 +/- 0.02 at 20 weeks gestation. This was maintained until 38 weeks (0.40 +/- 0.02). The increase until 20 weeks occurred at the time of greatest change in CO (5.10 +/- 0.18 to 6.79 +/- 0.20 l/min) and TPVR (1327 +/- 58 to 969 +/- 33 dyn/s/cm-5). The decrease in TPVR with a rise in SLC is opposite to the relation reported in essential hypertension so that a functional relation is unlikely. However, the changes within pregnancy were positively correlated (r = 0.43, P < 0.01). In hypertensive pregnancies TPVR was elevated compared with normotensive pregnancies (1543 +/- 100 vs 1090 +/- 37) but the SLC was not different from that found in normotensive pregnancies (0.43 +/- 0.02 vs 0.40 +/- 0.02). CONCLUSIONS: The changes in SLC activity suggest dynamic effects on erythrocyte membrane function during pregnancy. However, no differences could be found between normal and hypertensive pregnancy and SLC is unlikely to be of value as a marker of hypertensive risk during pregnancy.