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P Nève

Publications and source records attributed to P Nève.

At least 19 recordsLinked to original sources
PubMed2002

Frequent discordance of the light-chain isotypes expressed by serum monoclonal components and leukaemic B-cells.

In B-cell malignancies, it is generally held that the monoclonal components (MC) are produced by the malignant clones. Genetic relatedness implies the concordant expression of light-chain (LC) isotypes in the MC and at the surface of the malignant lymphocytes. We reviewed a series of 91 B-cell leukaemias, immunophenotyped by flow cytometry in our laboratory. A serum MC had been sought in 75 of these patients, and had been found in 23 (31%). Biclonal serum components were detected in three cases. LC concordance could not be assessed in three cases of surface LC-null lymphocytes. Of the 23 MC studied in 20 patients, light-chains were discordant in 39%, mostly due to kappa MC in lambda leukaemias. The origin of LC discordance remains speculative. It could be due to the emergence of subclones with the same primal VDJ gene rearrangement or, alternatively, to the development of new B-cell clones escaping immune surveillance from deregulated T-cells.

Aged↗
PubMed2000

[Serotonin syndrome secondary to the use of sertraline and metoclopramide].

The authors report the case of a patient who developed a serotonin syndrome after taking sertraline and metoclopramide. The symptoms included malaise, cardiac arrhythmia, sudation, hyperreflexia, sialosis, diarrhea and were improved by cyproheptadine. The authors review the physiological bases of the serotonin syndrome, its incidence, clinical manifestations and treatment.

Adult↗
PubMed1998

Age delays thyroglobulin progression towards dense lysosomes in the cream hamster thyroid.

We have shown that large lysosomes appear in thyroids of aging male cream hamsters. To investigate the role of this lysosomal change in the age-dependent reduction in hormone secretion, thyroids of young (<4 months of age) and old (>22 months of age) male and female hamsters were labeled with 125I at near isotopic equilibrium. Changes in thyroid morphology were analyzed by light- and electron-microscopic morphometry. Changes in thyroglobulin processing were analyzed by subcellular fractionation and identification of 125I-compounds by sucrose gradients and reverse-phase high-pressure liquid chromatography (HPLC). Sexual dimorphism present in thyroids of young animals became more marked upon aging. The parallel increase in thyroid weight and thyroglobulin content was more conspicuous in old females than in old males. Two morphological observations were specific to old females: (1) large follicles with flat epithelium and evenly labeled colloid and (2) deposits of amyloid material (possibly immunoglobulin light chain-related) between follicles. Although lysosomes were enlarged in female and male aged thyroids, they did not accumulate iodine. However, after isopycnic centrifugation of crude lysosomal fractions in Percoll gradients, 125I in old thyroids was not distributed mainly in the dense fraction L1 (lysosomes) as in young thyroids, but partly in particles of lower density (light L2 and buoyant fractions). 125I in the lighter particles was mostly found in intact thyroglobulin and in large iodopeptides. This 125I shift towards less dense particles was more marked in females than in males. These results indicate that age delays thyroglobulin progression towards dense lysosomes and suggest that the slower traffic of thyroglobulin in the endocytic pathway contributes to the reduction in thyroid hormone secretion in the aged cream hamster.

Aging↗
PubMed1995

Effect of dietary high doses of vitamin E on the cell size of T and B lymphocyte subsets in young and old CBA mice.

Using anti-CD5 and anti-SIgM fluorescent monoclonal antibodies, four subsets of lymphocytes can be distinguished in CBA mice, SIgM+ (T2) and SIgM- (T1) T lymphocytes and, CD5+ (B1) and CD5- (B2) B lymphocytes. L3T4 anti-CD4 and Lyt2 anti-CD8 positivities delineate two major T lymphocyte subsets. The cell size of these subsets has been evaluated by their forward light scatter in flow cytometry after cell fixation. The mean cell size of the different subsets differs, according to subset, age and vitamin E treatment. Globally, there is an age-related increase in size for all subsets. In vitamin-E treated young animals, all subsets are smaller, and the percentages of the biggest B1 and B2 cells decrease. In old mice, the vitamin-E effect is far more variable. B2 cells tend to increase in size but the percentage of the biggest cells diminishes. On the contrary, there is a marked expansion of the large B1 cells. No effect is discernible on CD5+ T lymphocytes, but L3T4 and Lyt2 subpopulations increase in size. This study is a retrospective one and the mechanisms affecting cell size are speculative. Since the lymphocyte cell size was measured after fixation in an hypertonic medium devised for human blood processing, we cannot differentiate a real size modification from a differential volume resistance to experimental conditions. Whatever the case, the changes in cell volume argue for age-related changes in cell membrane permeability and volume homeostasis. For some subsets, cell activation and consequent size increase must also be considered. As far as vitamin E has marked anti-oxidant properties, its effect on cell size provides indirect evidence for a role of free radicals in the observed changes and gives support to the oxidant stress theory of ageing in immune senescence.

Aging↗
PubMed1995

T4 accumulation in lysosomes of rat thyroid remnants after subtotal thyroidectomy.

In chronically stimulated rat thyroids after subtotal thyroidectomy, lysosomes increased in number and volume. They contained iodocompounds and did not appear in iodine-deficient animals. In this study, we analyzed the subcellular localization and the nature of these intracellular iodocompounds. Classical subcellular fractions were isolated from homogenates of rat thyroids and remnants 14 weeks after sham-operation or subtotal thyroidectomy. Two lysosome subpopulations of increasing density, a light fraction, lysosomes 2 (L2, density 1.065-1.08 g/ml) and a dense fraction, lysosomes 1 (L1, density > 1.08 g/ml) were separated from crude lysosomal particulate fractions (ML) by centrifugation in Percoll gradients. Results obtained with thyroids of normal rats were used as controls. In TSH-stimulated thyroid remnants, total activities of three lysosomal enzymes and iodine concentration were increased by 1.6-fold compared with thyroids of sham-operated rats. Total iodoprotein-derived T3 and T4 concentrations, measured after pronase hydrolysis, were slightly decreased. Thyroglobulin (Tg) concentration in the supernatant was reduced by 50%. Iodine, T3 and T4 contents of Tg were not modified. After differential centrifugation, the iodine excess of remnants sedimented with subcellular particulate fractions. The concentration of iodine in dense lysosomes (L1) was 6 times that in sham L1. Intact Tg did not accumulate in L1. Two thirds of the iodine in L1 was soluble in methanol, double the normal proportion, with twice as much iodine included in hydrophobic peptides eluted after T4 by reverse-phase HPLC. Although iodoprotein-derived T4 and T3 concentrations were decreased in the remnant homogenate, they were increased in particles, particularly in L1 where they were increased by 8 and 4-fold, respectively. In contrast, specific activities of lysosomal enzymes in ML and L1 remained unchanged. It is concluded that the chronic TSH stimulation of thyroid remnants in subthyroidectomized rats receiving a normal iodine supply induces the endocytosis of a normal Tg with iodine kept in dense lysosomes. The expansion of the lysosomal compartment resulted from a limitation in iodopeptides degradation as though secondary lysosomes would be overloaded with Tg. The accumulation in L1 of hydrophobic iodopeptides and of more iodoprotein-derived T4 than T3 suggests that exopeptidases involved in the liberation of T4 become rate-limiting.

Animals↗
PubMed1994

Effect of dietary high doses of vitamin E on lymphocyte subsets in young and old CBA mice.

Different theories of ageing exist. Oxidative stress by generating neo-antigens and affecting cellular communications may precipitate immune disregulation, and both may concur in the whole ageing process. In the present study, we have analysed the effect of dietary high doses of vitamin E, a free radical scavenger, on blood and spleen leukocytes and lymphocyte subsets, in young (3-month-old) and old (23-month-old) CBA mice. Age per se induced an increase in blood leukocytes, especially phagocytic cells, and a splenic atrophy, affecting both weight and cellularity. A differential effect of age on blood or spleen lymphocyte subsets was observed. In blood, there was a decrease in T cells, particularly CD4+ cells (T helper cells) and CD5+ cells without surface IgM (conventional T cells), along with a corresponding increase in B cells, principally B1 CD5+ cells (polyreactive autoimmunity-prone B cells). In the spleen, the relative percentage of each subset remained unchanged. Vitamin E supplementation for 7 weeks before sacrifice in young animals resulted in a decrease in CD4+ and CD5+ SIgM+ (putative Fc-receptor positive) T cells and B1 cells in blood. Similar changes in the splenic lymphocyte subsets were found, while more leukocytes could be recovered from less weighty spleens. Considering the free radical scavenging properties of vitamin E, it was assumed that oxidative stress might play some role in the ontogenesis of the immune system in young adulthood. Vitamin E for 20 months before sacrifice in old animals did not prevent splenic atrophy and had no effect on splenocytes. In blood, the ratio of SIgM+ (assumed Fc-R+) to SIgM- CD5+ T cells decreased and the B1:B2 B-cell ratio increased. In this setting, oxidative stress seemed to play a lesser role in post-adulthood immune senescence. It must be stressed that no functional test was realized that could have uncovered qualitative changes in immune reactivity. Vitamin E supplementation had complex effects on the weight of our animals, so that influences on physical activity, energy metabolism and hormonal status should be considered in interpreting its impact on the immune system. However, the observed age-related changes in T-cell and B-cell subsets are consistent with diminished immune function and increased autoimmunity in senescence. Vitamin E, by a direct anti-oxidant effect or some other mechanisms, can prevent some changes and seems to decrease the potential for autoimmune reactivity.

Aging↗
PubMed1994

Co-expression of CD2 or CD8 antigens in B-cell chronic lymphocytic leukaemia. A flow cytometry analysis of 3 cases.

Three cases of biphenotypic CD2 or CD8 positive chronic lymphocytic B-cell leukaemias are reported. This represents an incidence of 15% in the authors' series, a frequency never mentioned previously. CD2 expression could be an example of asynchronous expression of an early pre-B antigen. CD8 expression might probe a true mixed lineage phenotype. These aberrant phenotypes were not associated with any peculiar clinical presentation.

Aged↗
PubMed1992

Hyperferritinemia in adult onset Still's disease and the hemophagocytic syndrome.

Increments in serum ferritin levels in adult onset Still's disease (AOSD) were reported to be higher than one could expect for a simple inflammatory state. When we analyzed the scores of 40 patients with various severe inflammatory diseases aside from AOSD, we recorded no serum ferritin values higher than 3,300 ng/ml (N less than 200 ng/ml). In 3 of 10 consecutive patients with AOSD, the ferritin levels were higher than 3,500. Among these 3 patients, one case had a ferritin value of 3,600 ng/ml and bone marrow aspirate showed a marked hyperplasia of mature appearing histiocytes, and the 2 other patients (serum ferritin levels of 65,000 ng/ml and 250,000 ng/ml) displayed the features of a hemophagocytic syndrome. In 2 patients with normal or mildly increased levels of ferritin, the bone marrow examination was normal. We suggest that very high serum ferritin levels encountered in AOSD reflect the presence of histiocytic hyperactivity that sometimes leads to a hemophagocytic syndrome.

Adult↗
PubMed1991

Age-related accumulation of lysosomes and other cytological features in active thyroid follicles of the CBA mouse.

This study attempts to elucidate the mechanism through which lysosomal accumulation occurs with age in the epithelial cells of the thyroid gland and especially in the "active" follicles of the aging mouse thyroid. Thyroid morphology and function in old CBA (at least 24 months of age) male mice were compared with those in young (2 months of age) animals. The effects of different intake of iodine were tested and compared in both cohorts, each of which was divided into three groups: (i) low iodine group, (ii) moderate iodine group, and (iii) high iodine group. As expected, the present work confirmed the well-known accumulation with age of "cold" follicles coexisting with "active" follicles in the old mouse thyroid. Attention has been focused on the active follicles whose follicular cells contained in their cytoplasm a large number of pleomorphic dense bodies. The lysosomal nature of these bodies, referred to as secondary lysosomes, was confirmed by histochemistry; however, they displayed variability in acid phosphatase staining. In old animals, regardless of the type of iodine regimen, the ratio between relative follicular volume and relative colloid volume as determined by morphometry remained unchanged. Ultrastructurally, the relative volume occupied by secondary lysosomes in "active" follicles was always higher than in the young groups. Autoradiographic studies with 125I revealed that a large part of the radioactivity was located in secondary lysosomes of thyroid cells in "active" follicles of old mice when radioiodine was injected 3 weeks before death. Two different types of vacuoles were present in a non-negligible number of thyrocytes of the "active" follicles in aged cohorts. The first type was made up of grossly dilated rough endoplasmic cisternae, the second corresponded to intracytoplasmic microfollicular vacuoles. Both aspects have been described in conditions of chronic stimulation. It is concluded (1) that different intake of iodine for 6 weeks does not modulate the thyroid morphology in old mice; (2) that in the thyrocytes of the "active" follicles in old mice accumulation of secondary lysosomes occurs due to a slowdown of turnover; and (3) that the follicular cells of "active" follicles feature morphological aspects suggesting a hyperactive state compensating the lack of hormone production in the "cold" follicles.

Aging↗
PubMed1991

Neuroendocrine rhythms and sleep in aging men.

To delineate the physiological effects of aging on basal levels and temporal patterns of neuroendocrine secretions, the 24-h profiles of cortisol, thyroid-stimulating hormone (TSH), melatonin, prolactin, and growth hormone (GH) levels were simultaneously obtained at frequent intervals in eight healthy, active elderly men, age 67-84 yr and in eight young male adults, age 20-27 yr. The study was preceded by an extended period of habituation to laboratory conditions, and sleep was polygraphically recorded. Mean cortisol levels in the elderly were normal, but the amplitude of the circadian rhythm was reduced. Circulating levels of daytime and nighttime levels of both TSH and GH were greatly diminished in old age. In contrast, prolactin and melatonin concentrations were decreased during the nighttime only. The circadian rises of cortisol, TSH, and melatonin occurred 1-1.5 h earlier in elderly subjects, and the distribution of rapid-eye-movement stages during sleep was similarly advanced, suggesting that circadian timekeeping is modified during normal senescence. Despite perturbations of sleep, sleep-related release of GH and prolactin occurred in all elderly men. Age-related decreases in hormonal levels were associated with a decrease in the amplitude, but not the frequency, of secretory pulses. These findings demonstrate that the normal process of aging involves alterations in the central mechanisms controlling the temporal organization of endocrine release in addition to a reduction of secretory outputs.

Adult↗
PubMed1991

[Still's disease in adults].

Retrospective case series for the last five years have focussed the attention of the authors on some clinical and biological patterns of adult onset Still's disease. Its diagnosis is made difficult because of the great diversity of clinical and biological signs. Organ failures complicate sometimes the disease, and may be fatal. Major high levels of plasma ferritin associated with an haemophagocytic syndrome occur in 20 percent of the acute cases: this association could eventually respond well to an immunodepressive therapy.

Adult↗
PubMed1991

[Non-neoplastic hypercoagulability states].

Patients with proven recurrent venous or arterial thrombosis should be investigated for a predisposing cause corresponding to a hypercoagulable state. The latter is made up of two broad categories: the first consists of inherited thrombotic disorders; the second of a heterogeneous array of acquired clinical disorders, some of which are illustrated by clinical reports encountered in our department of internal medicine. Although the development and application of specific tests have provided valuable information about the pathogenesis of intravascular thromboses, these assays are currently able to provide aetiological diagnoses in fewer than 20 percent of young patients with recurrent venous thromboembolism.

Adolescent↗
PubMed1991

[Behçet's disease].

The different clinical aspects of Behçet disease are reviewed. This systemic disease is related to vasculitis involving small vessels. New diagnostic criteria have been established and new therapeutic approaches can be applied.

Adrenal Cortex Hormones↗
PubMed1991

[Corticosteroid therapy of various systemic diseases (non-neoplastic, noninfectious)].

The authors evoke how the corticosteroids work (as antiinflammatory and immunosuppressive agents) and how to prescribe them, orally, intravenously, in association with an antimitotic drug. They insist on the suspended and non curative effects of corticotherapy, its side effects and the additive effect of the antimitotic drugs. They suggest different therapeutic programs against rheumatoid arthritis, Still's disease, lupus, dermatomyositis, Behçet's disease, Horton's disease and polymyalgia rheumatica.

Adrenal Cortex Hormones↗
PubMed1988

Ultrastructure of human E-rosettes: a re-examination.

In contrast with previous published studies, it has been found that T-lymphocytes interact through broad-base contacts with sheep erythrocytes (SRBC) in E-rosettes. An electron dense material was spontaneously observed between the lymphocyte and erythrocyte plasma membranes. These findings fit more closely with the known metabolic effects of SRBC upon lymphocytes and the SRBC-capping phenomenon.

Animals↗
PubMed1988

Aztreonam in the treatment of serious gram-negative infections in the elderly.

The efficacy and safety of aztreonam in the treatment of serious gam-negative infections were investigated in 20 patients, 19 of whom were more than 60 years old. There were 13 cases of upper urinary tract infection, 6 of septicemia and one of peritonitis. Half the patients were in a critical clinical condition with significant severe underlying disease. Aztreonam was given i.v. or i.m. in doses ranging from 1.5 to 4 g/day according to the severity of the infection. The duration of treatment ranged from 7 to 20 days. In 5 patients with mixed infections due to gram-positive and anaerobic organisms in addition to gram-negative pathogens, aztreonam was given in combination with clindamycin and metronidazole as appropriate. Clinical and bacteriological cures were observed in all 20 patients. There were two cases of reinfection and 3 of superinfection--all occurred in patients with severe underlying disease. Untoward effects were few and of minor severity. Creatinine clearance remained stable or improved during aztreonam treatment, even in patients with significant renal impairment. In conclusion, aztreonam was shown to be both effective and safe in the treatment of serious gram-negative infections in elderly patients--even those with impaired renal function. In such indications aztreonam appears to be a good alternative to potentially toxic drugs such as the aminoglycosides.

Aged↗