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C Pons

Publications and source records attributed to C Pons.

At least 37 records · Page 2Linked to original sources
PubMed1994

Aggressive natural killer cell leukaemia/lymphoma in two patients with lethal midline granuloma.

We report two patients with leukaemic proliferations of large granular lymphocytes. The immunophenotype study showed that the leukaemic cells were positive for CD2, CD38, CD56 and anti-HLA-DR monoclonal antibodies and negative for other T-cell (CD3, CD4, CD8) and B-cell markers (CD19, CD20 and surface immunoglobulins). The clinical course was acute and a diagnosis of aggressive natural killer cell leukaemia/lymphoma was made. No clonal rearrangements of either C beta T-cell receptor or JH immunoglobulin genes were found. Functional studies done in one patient demonstrated non-restricted cytotoxic activity after activation with IL-2. Lethal midline granuloma had been previously diagnosed in both patients. A possible relationship between this entity and the natural killer cell leukaemia is discussed.

Antigens, CD↗
PubMed1993

Mutagenicity of soluble and insoluble nickel compounds at the gpt locus in G12 Chinese hamster cells.

Nickel is an established human and animal carcinogen, but efforts to demonstrate its mutagenicity in a number of cell types have not been successful. In this report we describe the mutational response to nickel compounds in the G12 cell line, an hprt deficient V79 cell line containing a single copy of the E. coli gpt gene. This cell line has a low spontaneous background, making it suitable for assessment of mutagenic responses to environmental contaminants. When G12 cells were treated with insoluble particles of crystalline nickel sulfide < 5 microns in diameter, a strong, dose-dependent mutagenic response was observed up to 80 times the spontaneous background. Of 48 mutant gpt(-) clones isolated that were induced by insoluble nickel, all were capable of DNA amplification of the gpt sequences by polymerase chain reaction (PCR). The ability to produce full-length PCR products is an indication that large deletions of gene sequences have not occurred. When G12 cells were treated with soluble nickel sulfate, the mutational response was not significantly increased over the spontaneous background. This difference in mutagenic response reflects a large difference in the mutagenic potential of soluble and insoluble nickel compounds, which reflects the carcinogenic potential of these forms of nickel.

Animals↗
PubMed1991

Hydroxylation and formation of electrophilic metabolites of tienilic acid and its isomer by human liver microsomes. Catalysis by a cytochrome P450 IIC different from that responsible for mephenytoin hydroxylation.

Tienilic acid (TA) is metabolized by human liver microsomes in the presence of NADPH with the major formation of 5-hydroxytienilic acid (5-OHTA) which is derived from the hydroxylation of the thiophene ring of TA. Besides this hydroxylation, TA is oxidized into reactive metabolites which covalently bind to microsomal proteins. Oxidation of an isomer of tienilic acid (TAI), bearing the aroyl substituent on position 3 (instead of 2) of the thiophene ring, by human liver microsomes, gives a much higher level of covalent binding to proteins. Both covalent binding of TA and TAI metabolites are almost completely suppressed in the presence of glutathione. These three activities of human liver microsomes (TA 5-hydroxylation, covalent binding of TA and TAI metabolites) seem dependent on the same cytochrome P450 of the IIC subfamily, since (i) antibodies against human liver cytochromes P450 IIC strongly inhibit these three activities, (ii) there is a clear correlation between these activities in various human liver microsomes, and (iii) TA acts as a competitive inhibitor for TAI activation into electrophilic metabolites (Ki approximately equal to 25 microM) and TAI inhibits TA 5-hydroxylation. However cross inhibition experiments indicate that tienilic acid hydroxylation and mephenytoin hydroxylation, a typical reaction of some human liver P450 IIC isoenzymes, are not catalysed by the same member of the P450 IIC subfamily.

Biotransformation↗
PubMed1991

Detection of human hepatitis anti-liver kidney microsomes (LKM2) autoantibodies on rat liver sections is predominantly due to reactivity with rat liver P-450 IIC11.

Anti-liver kidney microsomes (anti-LKM2) autoantibodies, appearing in patients treated with tienilic acid and suffering from hepatitis, react with proteins in rat liver sections. The nature of the rat proteins responsible for this recognition and detection of anti-LKM2 has been investigated. Immunoblot testing of the anti-LKM2 with liver microsomes from diversely treated rats and with purified rat liver cytochromes P450 (IA1, IA2, IIB1, IIB2, IIC6, IIC11 and IVA1) showed that these antibodies cross-reacted with cytochrome P450IIC11 and also with phenobarbital-induced cytochromes P450IIB1 and IIB2. Moreover, metabolic activation of tienilic acid and of a tienilic acid isomer by untreated rat liver microsomes was partially inhibited by anti-LKM2. On the other hand, monospecific polyclonal anti-rat P450IIC11 antibodies cross-reacted with human microsomal cytochromes P450 and recognized the same cytochromes P450 as anti-LKM2. This antibody also gave an immunofluorescence pattern on rat and mouse liver and kidney sections very similar to anti-LKM2. The data presented here show that anti-LKM2 recognize epitopes shared by rat P450 IIC11, and a human P450 of the family IIC. All the results indicate rat P450 IIC11, the major isoenzyme present in normal adult male rat liver, as the main antigen recognized by human anti-LKM2 autoantibodies; this is the basis of the immunofluorescence test for detection of these antibodies.

Animals↗
PubMed1990

[Peripheral T-cell lymphoma. Morphologic, immunophenotypic and immunogenotypic studies of 10 cases].

We describe the histopathology, immunophenotype and immunogenotype of 10 cases of peripheral T-cell lymphoma. The majority of patients showed disseminated disease at the time of diagnosis. From a histopathological view point the cases were classified into 5 types: T zone lymphoma (4 cases); Lennert lymphoma (2 cases); pleomorphic lymphoma, small all type (2 cases); pleomorphic lymphoma of medium-sized cell type (1 case); pleomorphic lymphoma of large cell type (1 case). In most of them the neoplastic cells demonstrated a mature T-cell phenotype: CD3+, CD4+, CD8-, CD43+, CD45RO+, CD45RA-, CD20- and surface immunoglobulins. All cases studied displayed gene rearrangements for the T-cell receptor beta chain while the immunoglobulins genes remained in germinal configuration. Antibodies against the human T-cell lymphotropic virus type I were not found in the 9 samples studied.

Adult↗
PubMed1990

Oxidative activation of the thiophene ring by hepatic enzymes. Hydroxylation and formation of electrophilic metabolites during metabolism of tienilic acid and its isomer by rat liver microsomes.

Tienilic acid (TA) is metabolized by liver microsomes from phenobarbital-treated rats in the presence of NADPH with the major formation of 5-hydroxytienilic acid (5-OHTA) which is derived from the regioselective hydroxylation of the thiophene ring of TA. During this in vitro metabolism of TA, reactive electrophilic intermediates which bind irreversibly to microsomal proteins are formed. 5-Hydroxylation of TA and activation of TA to reactive metabolites which covalently bind to proteins both required intact microsomes, NADPH and O2 and are inhibited by metyrapone and SKF 525A, indicating that they are dependent on monooxygenases using cytochromes P-450. Microsomal oxidation of an isomer of tienilic acid (TAI) bearing the aroyl substituent on position 3 (instead of 2) of the thiophene ring also leads to reactive intermediates able to bind covalently to microsomal proteins. Covalent binding of TAI, as that of TA, depends on cytochrome P-450-dependent monooxygenases and is almost completely inhibited in the presence of sulfur containing nucleophiles such as glutathione, cysteine or cyteamine. These results show that 5-OHTA, which has been reported as the major metabolite of TA in vivo in humans, is formed by liver microsomes by a cytochrome P-450-dependent reaction. They also show that two thiophene derivatives, TA and TAI, bind to microsomal proteins after in vitro metabolic activation, TAI giving a much higher level of covalent binding than TA (about 5-fold higher) and a much higher covalent binding: stable metabolites ratio (4 instead of 0.5).

Animals↗
PubMed1986

[Efficacy of hyperselective vagotomy on duodenal ulcer. 284 cases].

Two hundred and eighty-four patients who underwent highly selective vagotomy for duodenal or prepyloric ulcer were followed up for at least 1 year, and 47.9% of them for at least 5 years (mean : 58 months). The actuarial recurrence rates were 4.7% at 3 years, 9.6% at 5 years and 13.1% at 7 years. These results do not agree with the recently published figure of 20%. The authors insist on the necessity to dissect the lower oesophagus on a length of at least 5 cm. In duodenal ulcers, this technical detail should result in a cure rate of about 90% at 5 years.

Actuarial Analysis↗
PubMed1982

Cerebellar nuclear topography of simple and synergistic movements in the alert baboon (Papio papio).

Movements elicited by the stimulation of the cerebellar nuclei were studied in alert baboons chronically prepared. The motor responses were filmed and recorded in eight muscles through chronically implanted electrodes. Two types of motor effects were observed: (1) Simple movements that concerned the unidirectional displacement of a limb segment. (2) Complex movements that involved distinct and frequently noncontiguous muscles were stereotyped and could not be dissociated. These movements are defined as motor synergies. Electromyographic study allowed us to investigate the motor response latencies and the modality of cerebellar control on musculature. Simple movements were due to the activation of muscles within the involved segment in addition to the co-contraction of muscles of a nearby segment. Thus they could be due to a cerebellar control over muscular synergies. Complex movements would correspond to the simultaneous activation of distinct muscular groups and could also be the outcome of a cerebellar control on motor synergies. Thus the effects of the interposed nucleus concern preferably flexor muscles whereas the effects of the dentate nucleus appear to be equally distributed among flexor and extensor muscles. Somatotopic motor localization were evidenced both in the interposed and dentate nuclei: there are somatotopic relations between every region of the interposed nucleus and musculature. As regards the dentate nucleus, two subdivisions were distinguished according to the complexity of elicited motor effects: (A) an antero-medial region from which motor synergies can be elicited. (B) a postero-lateral region giving rise to simple movements, mainly hand movements.

Animals↗
PubMed1981

Contribution of the dentato-thalamo-cortical system to control of motor synergy.

Stimulation of the dentate nucleus in the chronically implanted baboon elicits both movements restricted to a single joint and also complex movements of several body segments. The complex movements correspond to precise but stereotyped coordinating activity. Two types of data reveal that the cerebello-thalamo-cortical system is concerned in the elaboration of complex movements. (1) Examination of cortical, pyramidal and muscle response latencies shows that the message might be transmitted by this pathway. (2) The complex movement which is produced by stimulation of a site in the dentate nucleus is similar to the sum of movements induced by stimulation of each cortical point receiving excitatory projection from this particular dentate focus.

Animals↗
PubMed1981

Long-term effects of a tryptophan-free diet on serotonin metabolism and sleep-waking balance in rats.

1. A long-term (up to 16 weeks) tryptophan (TRP)-free diet was administered to chronically implanted adult rats in order to study the effects of a sustained reduction of endogenous brain serotonin (5-HT) levels on the sleep-waking cycle. Twenty-four hours polygraphic recordings were made either periodically on an EEG apparatus, or uninterruptedly over 50 days by a frequency analyser. Quantitative changes in wakefulness (W), slow wave sleep (SWS) and paradoxical sleep (PS), as well as the number and duration of these episodes, were studied over 24 h, with a dark period (DP) and a light period (LP). Biochemical changes in 5-HT metabolism were measured in both plasma and brain. 2. Under control conditions, the percentage of W was twice as great in DP as in LP, while the quantities of SWS and PS were twice as high in LP as in DP. Surprisingly, in spite of a decrease of about 50% in brain 5-HT under TRP-deprived conditions, no dramatic changes were observed in the qualitative or quantitative aspects of W, SWS or PS. The only electrocorticographic (ECoG) change was a disappearance of sleep spindles, which became total after 14 weeks. During the first month, there was a 7% increase in W accompanied by a 6% decrease in SWS and a 5-9% reduction in PS. Later, W and SWS returned to their control values, while the PS deficit persisted throughout the TRP-deprivation period. Despite the absence of severe quantitative disturbances over 24 h, an internal reorganization of the sleep cycle took place. This new balance, established after 2 months, was characterized by a tendency toward an equal distribution of the stages in DP and LP, resulting in the disappearance of the sleep circadian rhythm. 3. Our results are compared with those of other authors who lowered the endogenous 5-HT levels by various means, including 'acute' or partial TRP-deprivation. The present findings suggest that adaptive cerebral mechanisms are able to compensate for the disturbances in 5-HT metabolism, in structures responsible for W and SWS. They indicate that the neurohumoral processes underlying sleep circadian rhythm in the rat are serotoninergic and/or noradrenergic.

Animals↗
PubMed1980

[Simple and synergistic motor effects, induced by the stimulation of the dentate nucleus, in the awake baboon. Determination of the area of hand control].

In the Baboon, two regions could be distinguished within the dentate nucleus according to the complexity of motor effects induced through localised electrical stimulation. (a) A rostromedial region, from which synergistic effects were elicited. This part mainly controls proximal muscles. (b) A caudolateral region from which simple movements were induced. A separate area for hand control could be identified within this part of the nucleus.

Animals↗