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Biomedical subjects

P Olive

Publications and source records attributed to P Olive.

12 recordsLinked to original sources
PubMed2000

Polyploid giant cells provide a survival mechanism for p53 mutant cells after DNA damage.

The relationships between delayed apoptosis, polyploid 'giant' cells and reproductive survivors were studied in p53-mutated lymphoma cells after DNA damage. Following severe genotoxic insult with irradiation or chemotherapy, cells arrest at the G(2)-M cell cycle check-point for up to 5 days before undergoing a few rounds of aberrant mitoses. The cells then enter endoreduplication cycles resulting in the formation of polyploid giant cells. Subsequently the majority of the giant cells die, providing the main source of delayed apoptosis; however, a small proportion survives. Kinetic analyses show a reciprocal relationship between the polyploid cells and the diploid stem line, with the stem line suppressed during polyploid cell formation and restituted after giant cell disintegration. The restituted cell-line behaves with identical kinetics to the parent line, once re-irradiated. When giant cells are isolated and followed in labelling experiments, the clonogenic survivors appear to arise from these cells. These findings imply that an exchange exists between the endocyclic (polyploid) and mitotic (diploid or tetraploid) populations during the restitution period and that giant cells are not always reproductively dead as previously supposed. We propose that the formation of giant cells and their subsequent complex breakdown and subnuclear reorganization may represent an important response of p53-mutated tumours to DNA damaging agents and provide tumours with a mechanism of repair and resistance to such treatments.

Apoptosis↗
PubMed2000

Motor cortical dysfunction disclosed by single and double magnetic stimulation in patients with fibromyalgia.

OBJECTIVE: To investigate the motor cortex by single and double magnetic stimulation, in patients with fibromyalgia. METHODS: Thirteen patients with fibromyalgia and 13 age-matched healthy subjects were examined. We evaluated, in both limbs, motor evoked potential (MEP) latency and amplitude and the MCA/MPA ratio, i.e. MEP cortical amplitude (MCA) /maximal peripheral amplitude of the M response (MPA), the central conduction time (TCC) and the length of the silent period (SP). With double magnetic stimulation, different time intervals between shocks were used: with delays between shocks of 4, 25, 55 and 85 ms, the intensities of the conditioning shock were 80% the relaxed threshold. With delays between shocks of 55, 85, 100, 155, 200, 255 and 355 ms, the intensities of the conditioning shocks were set at 150% the relaxed threshold. In all cases, the intensity of the test shock was 150% the relaxed threshold. The results were also compared with those obtained in 5 women affected by rheumatoid arthritis (RA). RESULTS: As compared to control, the cortical relaxed threshold was enhanced on both sides and limbs (P<0.05). The cortical silent period recorded with single magnetic stimulation was reduced in the upper limbs (P = 2.7x10(-11)) and lower limbs (both sides P = 3.6x10(-5)). The other parameters investigated were normal. With double magnetic stimulation, facilitatory phenomena were absent in fibromyalgic patients and the inhibitory responses recorded with a delay of 155 ms were reduced (P = 0.0052). No significant differences were noted between FM and RA patients. CONCLUSION: This study demonstrated motor cortical dysfunction in patients with fibromyalgia involving excitatory and inhibitory mechanisms. This indicates motor cortical involvement and supports the hypothesis of aberrant central pain mechanisms. The absence of differences between FM and RA suggest that the lesions were not specific and could be related to chronic pain disorders within the central nervous system.

Adult↗
PubMed1999

Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components.

OBJECTIVES: To investigate the potential clinical benefit of a combination therapy. METHODS: 205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying antirheumatoid drugs previously, with an early (< or = 1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68). RESULTS: The mean changes in the DAS during the one year follow up of the study was -1.15, -0.87, -1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007). CONCLUSION: This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

Antirheumatic Agents↗
PubMed1998

Tophaceous gout of the navicular bone as a cause of medial inflammatory tumor of the foot.

A case of tophaceous gout of the navicular bone in a 24-year-old woman is reported. Emphasis is placed on the conditions that might have been precipitating, i.e., anorexia nervosa and alcoholism, and the mechanisms by which increased uric acid level may be explained. The main radiographic patterns of tophaceous gout of the foot are recalled to avoid unnecessary surgery in future cases.

Adult↗
PubMed1998

[Cyst of the conus masquerading as motor neuron disease].

We report on a patient presenting with rapidly progressive painless paraplegia, amyotrophy and fasciculations masquerading as motoneuron disease. There were no bowel or bladder involvement but the patient noted mild paresthesia on the external part of the right foot and hypertrophy of the right calve was present. While lumbar CT Scan was normal, MRI showed a large cyst of the conus. Analysis of the cyst concluded to a benign cyst of the conus. Paraplegia resolved after surgery and after one year, no relapse was observed so that an hidden ependymoma appeared unlikely.

Cauda Equina↗
PubMed1995

Rat mesothelial and tracheal epithelial cells show equal DNA sensitivity to hydrogen peroxide-induced oxidant injury.

To study the relative sensitivity of rat tracheal epithelial and mesothelial cell DNA to oxidant damage, we used the comet assay, a gel microelectrophoresis method that allows visual determination of DNA strand breaks on a cell-by-cell basis, to evaluate damage after hydrogen peroxide exposure. By both a qualitative and a quantitative assay, tracheal epithelial mesothelial cells demonstrated a similar dose-response increase in the number of cells showing strand breaks and the number of breaks per cell after exposure to increasing concentrations of hydrogen peroxide; but even at the highest concentration, some cells failed to show damage. By contrast, 100% of cultured V79 lung fibroblasts showed evidence of damage. Catalase and deferoxamine largely prevented the formation of strand breaks, while superoxide dismutase was not protective. To evaluate DNA repair, cells were exposed to 10 microM hydrogen peroxide for 10 min, washed, and maintained in culture medium; by 2 h the proportion of mesothelial and epithelial cells showing comets had returned to control levels for both cell types. Both cell types also showed a similar pattern of increasing damage after continuous exposure to 10 microM hydrogen peroxide for periods up to 2 h. We conclude that, in this system, 1) mesothelial and tracheobronchial epithelial cells show a similar pattern of DNA injury and repair after hydrogen peroxide exposure; 2) hydrogen peroxide damages DNA of both cell types via a mechanism probably related to the iron-catalyzed formation of hydroxyl radical; and 3) both types of cells appear to be heterogeneous in their sensitivity to oxidant damage, with some cells showing extreme resistance to such damage.

Animals↗
PubMed1993

DNA double-strand break rejoining deficiency in TK6 and other human B-lymphoblast cell lines.

TK6, WI-L2, SB and three other B-lymphoblast lines were deficient in the rejoining of DNA double-strand breaks (DSBs) induced by ionizing radiation. Cells of these cell lines rejoin less than 50% of the breaks in 60 min after exposure, as assayed by filter elution at pH 9.6. The deficiency in TK6 cells was confirmed using the comet assay. IN TK6 cells the percentage of DSB rejoining did not vary markedly with dose and was similar for G1, S, and G2 + M-phase cells. Two B-lymphocyte lines (Raji and GM0606), three T-lymphoblast lines (MOLT-4, Jurkat, and CCRF-HSB-2), HL-60 promyelocytes, and GM3440 human skin fibroblasts rejoined more than 50% of the DSBs in this period after exposure. Radiation sensitivity in terms of cell survival was measured in those cells forming colonies. Of the cell lines tested, those that were deficient in DSB rejoining were radiation-sensitive (TK6 and WI-L2: D0 = 0.64 Gy). However, not all lines that were proficient in DSB rejoining were radiation-resistant, since Jurkat and GM0606 cells were relatively radiation-sensitive (D0 = 0.63-0.73 Gy). TK6 and WI-L2 cells were more sensitive to bleomycin (D0 = 8-9 micrograms/ml) than were HL-60 and Raji cells (D0 = 40-54 micrograms/ml). No relationship of DSB rejoining to V(D)J recombinase activity was observed, since no mRNA hybridizing to the cDNA probes for RAG-1 or RAG-2 was detected in any of the cell lines tested.

B-Lymphocytes↗
PubMed1975

Nitrofurazone-reducing enzymes in E. coli and their role in drug activation in vivo.

Earlier work showed that Escherichia coli contains at least two enzymes which reduce nitrofurazone and other nitrofuran derivatives. One of these enzymes is lacking in some nitrofurazone-resistant mutant strains. We now report that there are three separable nitrofuran reductases in this organism: reductase I (mol. wt. approximately 50 000, insensitive to O2), reductase IIa (mol. wt. approximately 120 000, inhibited by oxygen), reductase IIb (mol. wt. approximately 700 000, inhibited by O2). Unstable metabolites formed during the reduction of nitrofurazone by preparations containing reductases IIa and IIb produce breaks in DNA in vitro. In vivo experiments with nitrofurazone-resistant strains, which lack reductase II but contain reductases IIa and IIb, demonstrated that lethality, mutation, and DNA breakage are all greatly increased when cultures are incubated under anaerobic conditions, i.e., conditions such that reductase II is active. These results provide further evidence for the importance of reductive activation of nitrofurazone.

Aerobiosis↗