P53 expression, DNA ploidy and S-phase cell fraction in operable locally advanced non-small-cell lung cancer.

The identification of biomarkers to complement pathological stage for a more accurate prognosis and help clinicians decide on treatment is still an open problem for patients with lung cancer. Expression of P53 protein was detected by an immunohistochemical approach using the monoclonal antibody PAb1801 on paraffin-embedded sections of tumours obtained surgically from 102 stage II - IIIa patients with non-small-cell lung cancer (52 squamous cell carcinomas, 50 adenocarcinomas). [3H]Thymidine labelling index, an indicator of the S-phase cell fraction, was evaluated on histological sections of [3H]thymidine-labelled tumour samples. DNA ploidy was defined by flow cytometric analysis on frozen tumour tissue. The biomarkers, histology and pathological stage were analysed in relation to relapse-free survival in univariate and multivariate analyses. Stage and interaction between [3H]thymidine labelling index and histology provided significant prognostic information for the overall series. [3H]thymidine labelling index was an independent prognostic indicator of 3 year relapse-free survival in patients with adenocarcinoma. The results indicate the importance of cell proliferation to complement prognostic information provided by pathological stage in patients with stage II-IIIa adenocarcinomas.     

Effect of melphalan and hyperthermia on p34cdc2 kinase activity in human melanoma cells.

We previously reported that combined treatment with melphalan and mild hyperthermia (1 h at 42 degrees C) caused a synergistic cytotoxic effect in JR8 melanoma cells, paralleled by a stabilisation of a melphalan-induced G2-phase cell block. In this study, we investigated the effect of melphalan and hyperthermia on proteins that regulate G2-M transition. Neither hyperthermia nor melphalan at a concentration of 2.5 micrograms ml-1, which had no antiproliferative effect at 37 degrees C, interfered with cyclin B1 expression or p34cdc2 kinase activity. At a concentration of 8.5 micrograms ml-1, which reduced cell growth by 50% at 37 degrees C, melphalan inhibited p34cdc2 kinase activity as a consequence of an increased tyrosine phosphorylation of the protein. A similar inhibitory effect on p34cdc2 kinase was obtained when the lowest melphalan concentration (2.5 micrograms ml-1) was used under hyperthermic conditions. Our results indicate that thermal enhancement of melphalan cytotoxicity could be mediated at least in part by an inhibition of p34cdc2 kinase activity, which prevents cell progression into mitosis.     

Effect of exogenous surfactant on total respiratory system compliance

We measured total respiratory system compliance (Crs) before and after instilling 25 mg artificial surfactant in 1 ml saline down the endotracheal tube of preterm babies requiring resuscitation at birth, and compared results with data from 6 similar babies receiving saline only. Surfactant did not produce a significant improvement in Crs.     

Inter-hemispheric asymmetry of cerebral flow velocities during generalized spike-wave discharges

The aim of this study was to verify the symmetry of cerebral blood flow changes during the generalized spike-wave discharges of typical absence seizures. A recording of mean flow velocity in the left and right middle cerebral arteries and of electroencephalographic activity was performed simultaneously in two subjects with multiple daily absence seizures. A total of 12 generalized spike-wave discharges were recorded. Mean flow velocities showed a significant increase during the discharges with respect to baseline. The increase of flow velocity started simultaneously or a few seconds before the discharges. In 91.6 % of all recordings, the percentage increase of mean flow velocity was significantly higher in the left than in the right side (7.03 % ± 3.3 vs 5.14 % ± 3.3; p < 0.1). The extent of the following decrease of flow velocity was also significantly greater in the left than in the right side (-16.91 % ± 8.1 vs -14.07 % ± 8.3; p < 0.01). These findings show an inter-hemispheric asymmetry in cerebral blood flow during generalized spike-wave discharges in two patients with absence seizures. Transcranial Doppler ultrasonography promises to be an interesting approach to detect rapid changes in cerebral hemispheric activity not otherwise recognizable. Received: 14 November 2001, Received in revised form: 18 February 2002, Accepted: 5 March 2002     

Evaluation of apoptosis and the glucocorticoid receptor in the cartilage growth plate and metaphyseal bone cells of rats after high-dose treatment with corticosterone

A connection has been suggested between glucocorticoid-induced osteopenia and an increase in the apoptosis of bone cells, and between the dimerization of the glucocorticoid receptor (GR) and the development of apoptosis. On this basis, a study has been carried out on the relationships between the occurrence of apoptotic cells and their detectable GR content, and between apoptosis frequency and changes in histomorphometric variables, in the growth plate and secondary spongiosa of rat long bones after the high-dose (10 mg/day) administration of corticosterone (CORT) and after recovery. The main results of the CORT treatment were: a significant increase in apoptotic osteoblasts, and a concomitant decrease in the histomorphometric variables of bone formation, with a reversal of both values during recovery; a nonsignificant increase in the apoptosis of osteoclasts, without changes in the histomorphometric variables of bone resorption; a significant increase in apoptotic terminal hypertrophic chondrocytes; the presence of GR in all types of skeletal cells in control rats, with different (cytoplasmic and/or nuclear) immunohistochemical detection in the same type of cell; a decrease in GR detection in proliferative chondrocytes and osteocytes in CORT and recovery groups, and in the maturative/hypertrophic chondrocytes of the recovery group; a fall in growth cartilage width, possibly due to the reduced proliferation of proliferative chondrocytes and increased apoptosis in terminal hypertrophic chondrocytes. In conclusion, pharmacological doses of CORT reduce bone formation by increasing osteoblast apoptosis; they reduce growth cartilage width, probably by inhibiting chondrocyte proliferation and increasing the apoptosis of terminal hypertrophic chondrocytes, and they reduce osteocyte GR. Although these effects appear to be mediated by the presence of GR in all skeletal cells, no precise correlation between GR immunohistochemical detection and apoptosis induction has been found.     

Noonan's and DiGeorge syndromes with monosomy 22q11

A boy with the dysmorphic features of Noonan's syndrome and pulmonary valve stenosis who had evidence of hypoparathyroidism and abnormal T lymphocyte numbers in the neonatal period is reported. He had a normal karyotype but molecular analysis revealed a submicroscopic deletion within chromosome 22q11, the region deleted in DiGeorge syndrome. Thus this child has both Noonan's syndrome and DiGeorge syndrome; 22q11 is a candidate region for a gene defective in Noonan's syndrome.     

Malnutrition as a prognostic factor in lymphoblastic leukaemia: a multivariate analysis

One hundred and twenty eight Brazilian children with lymphoblastic leukaemia were intensively treated with a Berlin-Frankfurt-Munich based protocol. More children had a white cell count above 50 x 10(9)/l (31%) then observed in developed countries. After a median follow up of 31 months (11-58 months), the estimated probability of relapse free survival was 41% (7%) for the whole group. After adjustment in the Cox's multivariate model, malnutrition was the most significant adverse factor affecting duration of complete remission. Age above 8 years and high peripheral white cell count were also significant adverse factors. Among the nutritional indices, the height for age and weight for age z scores were both significant, whether the cut off points of z-2 or z = -1.28 were chosen to define malnutrition. A strong statistical association between the two indices was found; the contribution of height for age z score to the prediction of relapse free survival was more significant. Children with height for age z score < -2 had a relapse risk of 8.2 (95% confidence interval 3.1 to 21.9) relative to children with z score > -2. The results of this study suggest that socioeconomic and nutritional factors should be considered in the prognostic evaluation of children with leukaemia in developing countries.