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Biomedical subjects

B Lambert

Publications and source records attributed to B Lambert.

At least 127 records · Page 7Linked to original sources

Solid tumours and chromosome aberrations as late side effects of melphalan therapy in ovarian carcinoma.

Fifty-five ovarian cancer patients treated with melphalan during 1968-1978 were followed during 309 person years and studied with cytogenetic analyses. During the clinical follow-up 7 patients developed a new primary solid tumour. The excess risk of developing new primary solid tumours in patients treated with melphalan was statistically significant (p less than 0.05) and the relative risk corresponded to 3.0. Patients developing a new solid tumour showed a similar pattern of chromosome aberrations in the peripheral lymphocytes to that previously shown for the whole cohort.

Cells, Cultured↗

Karyotypes of human T-lymphocyte clones.

T-Lymphocyte clones from healthy males and females and from melphalan-treated ovarian carcinoma patients were studied with regard to sporadic chromosomal aberrations and clonal karyotype: 85% of the clones showed a normal, diploid karyotype, and sporadic aberrations were found to occur at about the same low frequency as in short-term lymphocyte cultures. An abnormal karyotype was found in 11 of the 72 clones studied. Loss of an X chromosome, which was the most frequent abnormality in female clones, was verified by densitometry of Southern blots of clonal DNA hybridized with a probe for the X-linked hprt locus. Abnormal karyotype due to chromosomal rearrangement was found in nine clones, and, in five of these, chromosome 12 was involved in the aberration. About 33% of the clones from melphalan-treated patients had an abnormal karyotype, in comparison with about 10% of clones from healthy control subjects. This difference indicated that melphalan treatment may induce stable chromosomal rearrangements that are compatible with cellular proliferation and clonal expansion.

Cells, Cultured↗

[Value of magnetic resonance imaging in a lipoma of the left ventricle].

A patient with benign left ventricular lipoma was explored pre- and post-operatively with echocardiography, computerized tomography (CT) and magnetic resonance imaging (MRI). With MRI spin-echo sequences the lipoma emitted a bright signal similar to that of normal fatty tissue on the two echoes of the sequence (28 ms and 65 ms). MRI was not better than CT to demonstrate that the tumour was a lipoma, but it proved to be the best technique to obtain information on tumoral spread to the myocardium and pericardium, and it showed the intracavitary extension without the need for contrast medium injection. After surgery, MRI displayed the remains of a septal lipomatous lesion. This case underlines the usefulness of MRI for the evaluation of cardiac tumours, and particularly lipomas.

Echocardiography↗

Massive ovarian edema in a twin pregnancy.

A case of idiopathic ovarian edema in a 26-year-old woman with a twin pregnancy is reported. The clinical evolution of the condition was benign in spite of acute episodes of left iliac pain. In diagnosis, theca-lutein cysts had to be differentiated from other ovarian enlargements. The authors advise conservative surgery for such a condition.

Adult↗

The effect of gossypol on the frequency of DNA-strand breaks in human leukocytes in vitro.

Gossypol, a human antifertility agent isolated from the cotton plant, was found to induce a dose-dependent increase in the frequency of DNA-strand breaks in human leukocytes exposed to 2-40 micrograms/ml of the drug for 1 h in serum-free medium in vitro. DNA-strand breaks were studied by alkaline elution or alkaline unwinding of DNA followed by hydroxylapatite-chromatography. No decrease of gossypol-induced DNA-strand breaks was observed after post-treatment incubation times up to 24 h, whereas X-ray-induced DNA breaks disappeared within 2 h under the same incubation conditions. Cells exposed to gossypol in the presence of 10% fetal calf serum showed no or little increase of DNA breaks, suggesting that serum proteins inhibit the DNA-damaging activity of the drug. Both optical isomers of gossypol induced DNA-strand breaks. However, the effect of (-)-gossypol was only about half of that of (+)-gossypol and the racemic form. The induction and persistence of DNA-strand breaks by gossypol, as well as the reduction of this effect in the presence of serum should be considered in the evaluation of the potential in vivo genotoxicity of the drug.

Cell Cycle↗

Effects of liquid holding by L-ethionine on the SCE frequency induced by nitrogen mustard in human lymphocyte cultures.

The highest SCE frequency induced by HN2 in PHA-stimulated human lymphocyte cultures is obtained when cells are treated immediately before the S phase, about 27-30 h after PHA stimulation. When HN2 treatment occurs during the G1 phase, the induced SCE frequency is inversely related to the duration between treatment and the onset of the S phase, suggesting that removal of the SCE-inducing lesion occurs during G1. High concentrations of L-ethionine (15-30 mM) inhibit cell-cycle progression in G1. The SCE frequency induced by treatment with HN2 (0.5 muM) during liquid holding is always lower than the SCE frequency induced by treatment with HN2 after release of the cells from liquid holding. This result indicates that SCE-inducing lesions caused by HN2 are removed during the cell-cycle delay. Cultures treated with HN2 after release from 2-12 h of liquid holding in late G1 show a higher SCE frequency than non-arrested, HN2-treated cultures. This effect is likely due to an enrichment of cells in S after release from liquid holding.

Cell Cycle↗

Effects of UV-irradiation on the SCE frequency in human lymphocyte cultures.

UV-irradiation (254 nm) was found to induce a smaller increase of SCE in human lymphocytes than in human fibroblasts and CHO cells. The UV-induced SCE frequency in human lymphocytes was not influenced by the duration between irradiation and the subsequent S-phase. UV-irradiated lymphocytes showed a slightly more than additive response to the SCE-inducing effect of HN2 and acetaldehyde in comparison with non-irradiated cells. The UV-induced SCE frequency was similar in lymphocyte cultures containing 20 and 100 microM of BrdUrd. The results suggest that human lymphocytes are relatively insensitive to the SCE-inducing effect of UV-irradiation, and that SCE-inducing damage caused by UV is not removed during the G1 phase in these cells.

Acetaldehyde↗

Cytotoxicity and SOS-inducing ability of ethidium and photoactivable analogs on E. coli ethidium-bromide-sensitive (Ebs) strains.

In a recently-characterized ethidium-bromide-sensitive E. coli strain, DNA appears to be much more accessible to DNA-binding agents. This strain therefore appears to be of interest for studying the mutagenic properties of chemicals. For this purpose, a series of ethidium-sensitive E. coli strains (Ebs) with normal and defective DNA-repair capacity was constructed and made lysogenic for lambda (sfiA::lacZ). These strains were used to study the cytotoxicity and SOS-inducing ability of ethidium and its two photoactivable analogs 8-azido- and 3,8-diazido-ethidium. When non-covalent DNA complexes are formed, these dyes elicit only a bacteriostatic effect in the Ebs strains, which is almost independent of the strain's DNA-repair capacity. The SOS system is not induced. When covalent DNA adducts are formed after photoactivation of ethidium azido analogs, the effects are quite different. The formation of about 5 DNA monoadducts per cell induces a lethal hit in the Ebs uvrB recA strain and measurable SOS induction in the Ebs uvrB (lambda (sfiA::lacZ) strain. The formation of more than 1000 DNA adducts in the Ebs strain with normal DNA-repair capacity does not induce any measurable cytotoxic effect.

Azides↗

Relationships between the GTP content and the TSH-stimulated adenylate cyclase activity of cultured thyroid cells.

The adenylate cyclase activity of a crude membrane fraction derived from cells cultured for 4 days in the presence of TSH (0.1 mU/ml), when acutely stimulated with 25 mU/ml, is 5-8 times higher than that derived from control cells. It has been suggested that changes in the intracellular content of GTP resulting from TSH chronic treatment were the cause of the modified responsiveness of the cyclase. To investigate this hypothesis, a method for GTP determination was developed. The steady-state concentration of GTP in 4-day TSH-treated cells is 2-3 times higher than in 4-day control cells. The increase in GTP content is concentration dependent between 5 and 500 microU/ml TSH in the culture medium. It presents a maximum on day 4 of culture, but remains elevated up to day 5. Nevertheless the GTP content is not the only factor controlling the cyclase activity, indeed the addition of 0.1 mM GTP to membranes from control cells does not increase the response up to the level reached by membranes from TSH-treated cells. Treatment of the cells with virazole, a drug inhibiting the biosynthesis of guanyl nucleotides, greatly decreases the GTP level, but is unable to suppress the positive effect of the TSH chronic treatment on adenylate cyclase activity. These results show that the increase in GTP level resulting from culture of the cells in the presence of minute amounts of TSH is not exclusively linked to adenylate cyclase responsiveness to TSH.

Adenosine Triphosphate↗

Chromosome damage and second malignancy in patients treated with melphalan.

Cytogenetic studies were carried out on peripheral lymphocytes from cancer patients at different times after therapy with melphalan. The frequency of sister chromatid exchange (SCE) was increased markedly shortly after treatment, and then declined to near pretreatment levels over a four-week period. In-vitro studies showed that the SCE frequency induced by melphalan is reduced slowly in resting G0 lymphocytes and considerably faster in mitogen-stimulated G1 cells. The results demonstrate that measurement of SCE is useful for the study of newly-induced chromosome damage in melphalan-treated cells, but is less suitable for the detection of persistent, cytogenetic alterations long after therapy. The frequency of chromosomal aberrations in a cohort of 50 patients with ovarian carcinoma was increased for up to ten years after melphalan therapy. The predominant aberrations were chromosomal translocations, marker chromosomes and cells with multiple, complex rearrangements. The frequency distribution of chromosomes involved in aberrations was studied in cells from some of the patients. An overrepresentation of chromosomes 8 and 9 was found in these cells, whereas the X chromosome was overrepresented in cells from control subjects. An increased frequency of chromosomal rearrangements was found in long-term cultures of T-lymphocytes from three of the patients, indicating that these aberrations are compatible with cell survival and proliferation. Seven patients in the cohort developed a second, primary tumour during the observation time. The frequencies and types of aberrations in these patients were similar to those of the other patients in the cohort.

Carcinoma↗

Tetradecanoyl phorbol-13-acetate counteracts the responsiveness of cultured thyroid cells to thyrotropin.

We have studied the effects of TPA on the metabolism of porcine thyroid cells cultured for 1-4 days in the absence (control cells) and in the presence of 0.1 mU/ml TSH (TSH cells). The phospholipid turnover, evaluated after a 2 hr incorporation of 32P-phosphate into phospholipids, is markedly modified by the presence of TPA (1.5 microM, 2 hr) in the incubation medium of control and TSH treated cells. The total incorporation is 3-4 times higher than untreated cells, the labelling of phosphatidylinositol (PI) is slightly decreased or unchanged whereas that of phosphatidylcholine (PC) is strongly increased. The increased labelling of PI, promoted by an acute TSH treatment is counteracted by TPA. This TPA effect is not observed when prelabelled cells are challenged for 5 min with the drug. A similar effect is observed when 10 nM TPA is added in the culture medium for 20 hr. The addition of TPA does not affect significantly the protein iodine content in 3 or 4 days control cells incubated for 45 min or 2 hr with 125I-iodine, but dramatically decreases the very high iodination rate of TSH cells. We have tested the TPA effect on the cyclic AMP accumulation for the last 5 min of a 2 hr incubation. TPA inhibits by about 50-80% the stimulation evoked by TSH and only by 10% that evoked by forskolin (0.1 mM). These results suggest a possible link between the PC turnover and the adenylate cyclase responsiveness to TSH and the iodination rate.

Adenylyl Cyclases↗

Comparative effects of cholera and Bordetella pertussis toxins on cyclic AMP and GTP levels and on lipolysis in rat adipocytes incubated in vitro.

The respective effects of cholera and Bordetella pertussis toxins were studied in time and concentration dependent experiments, following glycerol and fatty acid release, GTP and cAMP levels. Cholera toxin, after a lag time of 30 min, stimulated linearly GTP and cAMP accumulation and lipolysis (maximal effect: 2-fold increase at 5 micrograms/ml). Pertussis toxin presented a biphasic effect both in time and concentration dependent studies. Up to a maximum reached after 2 h with 1.4 units LPF/ml the stimulation affected GTP (3 fold) and cAMP (7 fold) levels, glycerol and fatty acid release (15 fold). Beyond this, an inhibition occurred, yielding a decrease towards basal values of GTP and cAMP content whereas the glycerol and fatty acid release was stopped. These results, which are the first reporting the fluctuation of the GTP content of intact cells challenged with bacterial toxins, show a close relationship between GTP and cyclic AMP levels and lipolytic activity.

Adipose Tissue↗