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Biomedical subjects

P Neve

Publications and source records attributed to P Neve.

At least 37 records · Page 2Linked to original sources

Effects and interactions of 17 beta-estradiol, T3 and 1,25(OH)2D3 on cultured osteoblasts from mature rats.

Osteoporosis being frequently associated with hyperthyroidism and, mostly after menopause, with deficiency in estrogens, we tried to elucidate the interactions of estrogens and triiodothyronine (T3) with calcitriol by using cultured osteoblast-like cells obtained from mature rat bone. The tested parameters included [3H]thymidine incorporation, evaluation of the alkaline phosphatase activity of the cell layer and osteocalcin production in the culture medium. At physiological concentrations, 17 beta-estradiol and T3 stimulated alkaline phosphatase activity, did not enhance osteocalcin production and slightly inhibited [3H]thymidine incorporation. At higher concentrations, 17 beta-estradiol decreased the alkaline phosphatase and osteocalcin response to calcitriol whereas T3, although decreasing alkaline phosphatase activity, markedly increased the osteocalcin secretion elicited by calcitriol. These observations emphasize the complex physiology of osteoblasts and confirm different behaviors of alkaline phosphatase and of osteocalcin as markers of bone turnover.

Alkaline Phosphatase↗

Leukocyte and lymphocyte subsets after a short pharmacological stress by intravenous epinephrine and hydrocortisone in healthy humans.

Nine healthy volunteers received epinephrine and hydrocortisone intravenously in order to assess the typical acute response to a brief stress, of leukocyte and lymphocyte subsets, acute phase reactants and lymphocyte reactivity to T and B mitogens. At 10 min., all leukocyte subsets were increased, especially mononuclear cells. At 1 hour, moderate lymphopenia and monocytopenia occurred. At 6 hours, neutrophilia and eosinopenia were observed. During the lymphocytic early wave, all the lymphocyte subset counts increased, particularly T-suppressive/cytotoxic and natural killer cells. As a consequence, the percentage of T cells decreased and the CD4/CD8 ratio fell. No changes in acute phase reactants occurred over the 24 hours of the study. All leukocyte and lymphocyte subsets were normalized and mitogen reactivity was unchanged 24 hours after the stress. These typical shifts in leukocyte subsets could probe the adrenocortical and medullary response to an environmental stressor.

Acute-Phase Proteins↗

[Pseudotumor cerebri induced by danazol].

Case report of a 39-year-old woman treated by Danazol for a paroxystic nocturnal hemoglobinuria who developed benign intracranial hypertension and sclerosing cholangitis. Bilateral papilloedema cleared 4 weeks after Danazol was stopped. Twelve similar cases have already been reported in the literature. Danazol should be added to the list of drugs potentially inducing pseudo-tumor cerebri.

Adult↗

Decreased basal and stimulated thyrotropin secretion in healthy elderly men.

To delineate the effects of aging on basal and stimulated TSH secretion, we studied the 24-h profile of plasma TSH levels and the TSH response to TRH stimulation (200 micrograms TRH, iv) in eight healthy elderly men, aged 67-84 yr, and eight normal young men, aged 20-27 yr. Subjects with thyroid antibodies against microsomal or thyroglobulin antigens were excluded. During the 24-h study, blood was sampled at 15-min intervals. TSH levels were measured by an ultrasensitive immunoradiometric assay. Sleep was polygraphically monitored, and circadian and pulsatile TSH variations were quantified using specifically designed computer algorithms. In older men, the 24-h mean TSH concentration was approximately 50% lower than that in young men (0.78 +/- 0.37 vs. 1.43 +/- 0.41 microU/mL; P less than 0.01), but basal T3 levels were only slightly lower (93 +/- 12 vs. 115 +/- 16 ng/dL; P less than 0.02), while basal T4 levels were normal. The normal diurnal variation of TSH levels, with a nocturnal acrophase and an afternoon nadir, as well as the pulsatile nature of TSH release were preserved in elderly men. When expressed in microunits per mL, the amplitude of these temporal variations was reduced in elderly men compared to that in younger subjects. However, when expressed in relation to the mean TSH levels, the amplitudes of diurnal and pulsatile variations were similar in both groups of subjects. TRH-induced TSH secretion was lower in old than in young men (area under the curve, 15.9 +/- 6.3 microU/mL.10 min in elderly men vs. 42.0 +/- 16.6 microU/mL.10 min in young men; P less than 0.002). However, the TRH-induced elevations of T3 and T4 were of similar magnitude in both groups. These results indicate that in healthy elderly men, the overall 24-h TSH secretion is decreased, and the pituitary is less responsive to stimulation by TRH. However, the chronobiological modulation is preserved. These alterations could reflect an adaptative mechanism to the reduced need for thyroid hormones in old age. The thyroid keeps an intact capacity to respond to acute increases in TSH concentrations.

Adult↗

Effects of iodine intake on thyroid secondary lysosomes after subtotal thyroidectomy.

This study tested the effects of different iodine intakes on thyroid ultrastructure and function in thyroid remnants after subtotal thyroidectomy (sub-tx). Removal of most of the thyroid gland causes an elevation of endogenous TSH, which chronically stimulates the residual tissue. Male Sprague-Dawley rats were divided into three groups; Low Iodine Group (LIG), Moderate Iodine Group (MIG), and High Iodine Group (HIG). There was no significant difference among total thyroid weights removed by sub-tx, but thyroid remnant weights and TSH levels were higher at death (6 weeks after sub-tx) in LIG than in MIG and HIG. Total specific activities of cathepsin D and of arylsulfatase A in the sedimentable and nonsedimentable subcellular fractions were at least 38% lower in LIG than in MIG and HIG. The ratio between relative follicular volume and colloid volume determined by morphometry was higher in LIG than in MIG and lower in HIG than in MIG. Ultrastructurally, the relative volume occupied by secondary lysosomes was higher in HIG than in MIG, whereas the number of secondary lysosomes was not higher in LIG than in controls. Autoradiographic studies with 125I revealed that a large part of the radioactivity was in thyroid cell secondary lysosomes in MIG and HIG when radioiodine was injected 3 weeks before death. It is concluded that after sub-tx, iodine 1) regulates the weight of thyroid remnants, perhaps only indirectly through TSH, 2) modulates the number of secondary lysosomes in thyroid cells, and 3) slows down the turnover of secondary lysosomes. An iodine-deficient regimen impedes the secondary lysosomes to increase. Because of these findings, we postulate that chronic TSH stimulation along with a possible toxic role of iodine after sub-tx could induce an accumulation of lysosomal bodies.

Animals↗

Effect of age, sex and health status on human lymphocyte functions: demonstration of a sex-related defect in suppressor cell function.

The mitogenic response of human lymphocytes and the short-lived suppressor cell function on concanavalin A response were studied as dependent variables in 194 patients using multiple regression analysis, with health status and sex as dummy variables, and age as an explicative one. This study confirms a decrease of the lymphocyte functional response to mitogens with aging. A sex-related defect in suppressor cell function is put forward in females independently of age. An inverse linear relationship is found between the functional response to pokeweed mitogen (T and B mitogen) and suppressor cell function in males but not in females. No such relationship is found with the pure T mitogens (Con A and phytohemagglutinin-A). The present study suggests that a defect in short-lived suppressor cells can play some role in the greater incidence and prevalence of autoimmune diseases in women while the depressed lymphocyte response of old people cannot be explained by modifications of the activity of these suppressor cells.

Adult↗

Thyroid, lipid and other biological variables in elderly patients with asymptomatic autoimmune thyroiditis: a statistical analysis.

Asymptomatic autoimmune thyroiditis (AAT), especially prevalent in elderly women and associated with the presence of thyroid antibodies (HT), is recognized as a precursor of hypothyroidism and is an intermediate between euthyroidism and hypothyroidism. This paper is concerned with the possible modifications of biochemical variables - some of which are not directly related to the thyroid - in patients with AAT. Thirty-seven serum factors were investigated in euthyroid, AAT, and HT subjects over 69 years of age. They were thyroglobulin; microsomal, gastric and adrenal antibodies; LE cells, and thyroid, lipid and immunological variables linked to the inflammatory process. In women the only variable, other than those related to the thyroid, which showed any modification in the AAT state was the cholesterol level. Wholly different observations were made in men, stressing the necessity of separate analysis of male and female data: the thyroid-related variables which were modified in the AAT state are not the same as in women, the cholesterol is not increased but triglycerides, HDL, albumin and inflammatory variables are modified. Furthermore, the lipid variables showed an unexpected age dependency in AAT, but not in euthyroid women (between 69-90 years of age).

Aged↗

Formation of intracellular lumina in dispersed pig thyroid cells.

Intracellular cavities characterized by the presence of microvilli have been identified in dispersed thyroid cells. These structures resembling follicular lumina were called intracellular lumina or ICL. Freshly dispersed cells did not contain ICL. At 37 degrees C, ICL formation was a rapid process. After 60 min of incubation, ICL were present in 15 to 20% of the cells; the number of ICL remained rather constant during 3 to 4 h of incubation. In the presence of thyrotropin, the number of ICL increased with time to reach a value ranging from 40 to 60 ICL per 100 cells after 4 h of incubation. ICL formation was also increased in the presence of dibutyryl cyclic AMP (2 mM). Vinblastine (30 microM), a microtubule-disrupting agent and monensin (30 microM), an ionophore inhibiting Golgi functions blocked the formation of ICL in control and thyrotropin-stimulated cells. Cycloheximide (0.5 mM) and puromycin (0.5 mM) did not inhibit ICL formation in either control or thyrotropin stimulated cells. The iodination capacity of ICL was studied by quantitative electron microscopic autoradiography after incubation of thyroid cells with 125 I-iodide for 2 to 60 min. Radioiodinated products appeared first in ICL. After 1 h of labeling autoradiographic grains were found mainly in ICL (60-70%) and over the cytoplasm. The labeling of ICL was heterogeneous; ICL contained either few or numerous overlapping grains. Whatever the labeling time, a high proportion of ICL (70-80%) were labeled. The labeling of ICL as well as the labeling over the cytoplasm was increased in the presence of thyrotropin and almost completely inhibited in the presence of an iodide trapping inhibitor: sodium perchlorate. Pulse-chase experiments revealed that thyrotropin stimulated the discharge of 125 I-labeled material from ICL.

Animals↗

Immune senescence: effect of age, sex and health on human blood mononuclear subpopulations.

The respective influence of age, sex and health states on peripheral blood mononuclear subpopulations has been investigated in 194 institutionalized subjects. The "ill group' includes patients with various diseases and the "reference group' was referred to admission criteria for immuno-gerontological disease. A decline of total mature T-cell (OKT3) and helper T-cell (OKT4) proportions with ageing has been found only in the ill group and remains stable in the reference group. This age-dependent decline should represent either a susceptibility for illness or a consequence of higher incidence of illness with ageing. Suppressor-cytotoxic (OKT8), B- and T-activated (OKIa1), null (OKM1), and early E-rosette forming cells do not vary with ageing in both groups. It has been established previously that women have higher values of the percentages of early E-rosette forming cells.

Aged↗

Reduction due to ageing of TSH-stimulated thyroid hormone release in the cream hamster.

The in vitro secretion by thyroid lobes from young (2-month-old) and from "aged" (more than 21 months old) male cream hamsters was estimated by measuring the butanol-extractable 125I (BE-125I) released into the medium after 2 and 4 h of incubation in the presence or absence of thyroid stimulating hormone (TSH). Lobes were fixed at the end of incubation for examination by both light and electron microscopy. Other lobes from both groups were collected for estimation of cyclic AMP contents. BE-125I release by lobes from aged animals after TSH stimulation was significantly lower than that of young animals. Similarly, pseudopods resorbing colloid, the morphological markers of secretion, were much less prominent in the aged group than in the young group. As this observation and the reduced BE-125I release contrast with an equivalent increase of cyclic AMP in both the young and aged groups, it is suggested that the age-dependent defect resulting in reduced hormone secretion is located at a step beyond the generation of cyclic AMP in the cascade of events occurring between binding of TSH to plasma membrane receptors on the target cell and hormone release.

Aging↗

Effect of vitamin C supplements on cell-mediated immunity in old people.

Both ageing and vitamin C (VC) deficiency result in immune defect. Since low serum and tissue levels of VC are found in the elderly, we have in a placebo-controlled study, tested the effect of VC supplements (500 mg/day i.m. for 1 month) on various immune parameters. Indeed, VC enhances the proliferative response of T lymphocytes in vitro, and the tuberculin skin hypersensitivity in vivo. Neither the serum concentrations of IgA, IgG and IgM, nor the proportion of E-rosette-forming cells were modified. No significant change was observed in the placebo-treated group.

Aged↗

Increased stability of E-rosettes and restricted capping of sheep erythrocytes by lymphocytes of aged humans.

The processes of E-rosette dissociation and sheep red blood cell (SRBC) capping provide simple assays for studying age-related changes in membrane dynamics of T-lymphocytes. After incubation at 4 degrees C, no significant difference is observed between young-adult and elderly subjects, either in the number of rosette-forming-cells (E-RFC) or in the distribution of SRBC at the lymphocyte surface. However, when the E-RFC are incubated at 22 or 37 degrees C after resuspension, the rosettes disintegrate to a larger extent forming fewer morula-like structures and more caps in young donors. An inverse relationship is noted between the number of E-RFC and the percentage of capping cells, suggesting a role for the lateral movement of the SRBC receptors in the dissociation process. In the elderly, rosette disintegration seems to be related only to the random release of SRBC. It is speculated that this increased stability of the E-rosettes represents some locking of the T-lymphocyte membrane receptors, which could alter the transduction of cell-cell signals.

Adult↗

E rosette dissociation: evidence for a role of the cytoskeleton.

When put into 37 degrees C incubation, the E rosettes dissociate spontaneously and the sheep erythrocytes (SRBC) form caps at one pole of the lymphocytes. This process is associated with changes in cell morphology such as uropod formation or membrane budding. The disintegration of E rosettes and the capping of SRBC can be retarded by addition of cytochalasin B plus colchicine, chlorpromazine or sodium azide. These findings suggest a pivotal role of the cytoskeleton in the dissociation process of E rosettes. However, other mechanisms of disintegration are to be considered since none of the drugs can prevent the dissociation of E rosette entirely.

Adolescent↗

Pharmacokinetic study of cefuroxime in the elderly.

1 The pharmacokinetics of cefuroxime have been investigated in 18 patients at least 70 years old. The drug was given either by continuous infusion (7 cases) or by multiple injections (11 cases) for 3 to 11 days (mean duration: 7 days). 2 The unchanged drug was assayed in blood plasma and in the urine by high performance liquid chromatography (h.p.l.c). 3 Cefuroxime was cleared, unchanged, almost exclusively by the kidneys, even when kidney function was impaired. Creatinine clearance ranged from 1.02 to 4.08 1/h (17 to 68 ml/min) in this group of patients and plasma clearance of cefuroxime varied from 1.02 to 8.16 1/h (17 to 136 ml/min) (r = 0.7 P less than 0.001 for linear correlation), but the apparent rate constant for nonrenal elimination remained quite small (average: 0.04 h-1) and independent of creatinine clearance (r = 0.06, n = 17). 4 Since creatinine clearance decreases sharply with age, it might be suggested that cefuroxime dosage be related to creatinine clearance in the elderly, even when no renal impairment is suspected.

Aged↗

Early biochemical events associated with lymphocyte activation in ageing. I. Evidence that Ca2+ dependent processes induced by PHA are impaired.

The requirement for Ca2+, a divalent ion which plays a fundamental role in cell activation, has been analysed in cultures of PHA-stimulated human peripheral blood lymphocytes (PHA-PBL) from adult (range: 20-35 years) and old (over 70 years) subjects. For this purpose, increasing concentrations of Ca2+ chelators (EGTA and EDTA) were added to cultures in order to compare the effect of progressive extracellular Ca2+ (Ca2+EC) depletion on [3H]-Tdr incorporation by PHA-PBL. Kinetic analysis showed that Ca2+EC requirement was restricted to the first 24 h after culture initiation. At optimal doses of PHA, the PHA-PBL from old subjects were more sensitive than those from adult subjects to increasing concentrations of both chelators. They also required larger amounts of Ca2+ supplements to restore their normal response after total inhibition by EGTA. Furthermore, the PHA-PBL from the elderly were hypersensitive to verapamil (Isoptin), a drug which instigates a reversible inhibition of Ca2+-dependent processes associated with lymphocyte transformation, by a quite similar reaction to that induced by chelators. We conclude that the Ca2+-dependent processes in lymphocyte activation are impaired with ageing. Following further experiments and recent work suggesting that lymphocytes need more than one signal to proliferate, the authors speculate on a deficiency of a late activation signal requiring cell-cell interactions in the elderly.

Adult↗