Browsing by Author "SERONFERRE, M"
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- ItemADRENAL REST TUMOR OF THE LIVER CAUSING CUSHINGS-SYNDROME - TREATMENT WITH KETOCONAZOLE PRECEDING AN APPARENT SURGICAL CURE(1985) CONTRERAS, P; ALTIERI, E; LIBERMAN, C; GAC, A; ROJAS, A; IBARRA, A; RAVANAL, M; SERONFERRE, MKetoconazole, an imidazole derivative which inhibits cytochrome P450-dependent adrenal enzymes, was given to a patient with a functioning adrenal rest tumor of the liver in preparation for surgery. The drug was administered in a stepwise manner for 42 days starting with 400 mg and reaching 1 g the last 4 wk of the trial. Clear clinical improvement was evident early in the trial and was associated with evidence of amelioration of her hypercortisolism and striking changes in serum and urinary levels of steroid hormones and metabolites. Sex steroids in serum and urine fell dramatically from the 1st day to the end of the trial. Urinary 17-ketosteroid excretion fell from a basal average of 139 mg/24 h to near normal levels within 1 wk of therapy; serum testosterone fell from a basal level of 2.4 to 0.18 ng/ml; serum 17.beta.-estradiol fell likewise from 1096 to 156 pg/ml. Cortisol levels in serum and urine increased in the first 2 wk of the trial and subsequently fell to values below the basal levels. Serum 17.alpha.-OH-progesterone levels increased 63% above the basal levels by day 6 of the trial and declined afterwards. At 9 mo. after successful tumor resection the patient is apparently cured as judged by steroid hormone levels and physical appearance. Ketoconazole was evidently effective in blocking tumoral steroidogenesis, which resulted in clinical benefit.
- ItemCERTAIN LARGE FORMS OF CIRCULATING IMMUNOREACTIVE HUMAN GROWTH-HORMONE ARE IN FACT IMMUNOGLOBULINS(1990) CAMPINO, C; SZECOWKA, J; MICHELSEN, H; SERONFERRE, MTo explain frequent discordances between serum GH levels and clinical manifestation of acromegaly, we investigated the possibility that certain immunoglobulins G (IgGs) might be responsible for the displacement of [125I]human (h) GH in the hGH RIA. We incubated dilute sera from seven active acromegalics (basal immunoreactive hGH, 22-313 .mu.g/L) with rat adipocyte plasma membranes adsorbed on polystyrene plates. IgGs that bound to GH receptor sites in the absence and presence of 250 nM hGH (for nonspecific binding) were detected using anti-hIgG (Fc-specific) antibody conjugated with alkaline phosphatase. In this system two of the seven sera studied tested positive for IgGs against GH-binding sites (serum 4 in1:400 dilution, and serum 7 in 1:10 dilution). We studied further the serum with the highest titer. On Sephadex G-100, most of the GH-like immunoreactivity (assayed by RIA) present in serum 4 coeluted with IgGs (assayed by immunodiffussion) as a high mol wt (.gtoreq.150 kDa) component. To confirm its IgG nature, this material was then adsorbed on protein-A-Sepharose and eluted with 0.1 M sodium citrate, pH 3.0. The protein-A-purified IgGs from serum 4 bound specificially to GH receptor sites in adipocyte membranes and displaced [125I]hGH in the hGH RIA. In contrast, IgGs purified from another acromegalic patient (313 .mu.g/L hGH) repeatedly tested negative in the membrane binding assay and hGH RIA. We conclude that some active acromegalics have circulating IgGs that bind both to hGH-specific antibodies in the RIA and to GH receptor sites; certain forms of the socalled big GH may correspond to these IgGs; and possible metabolic effects of these GH-like IgGs should be taken into consideration.
- ItemCIRCADIAN VARIATION OF BASAL PLASMA PROLACTIN, PROLACTIN RESPONSE TO SUCKLING, AND LENGTH OF AMENORRHEA IN NURSING WOMEN(1989) DIAZ, S; SERONFERRE, M; CARDENAS, H; SCHIAPPACASSE, V; BRANDEIS, A; CROXATTO, HBThe circadian pattern of plasma PRL levels and the PRL response to suckling were examined at various times during the first postpartum year and related to the length of lactational amenorrhea. Ten healthy women whose infants were breast-fed exclusively and who were amenorrheic 3 months postpartum were studied 3, 6, and 9-11 months postpartum. The women and their babies were admitted to a metabolic unit for 48 h. On the second day, blood samples were drawn at 2-h intervals for 26 h starting at 0800 h and also 10 and 30 min after the initiation of six of the nursing episodes. During the three postpartum periods, there was a circadian rhythm of basal plasma PRL concentrations; the peak concentrations occurred between 2400-0600 h. Suckling induced a significant rise in plasma PRL levels at all hours except 0800 h. There was a positive correlation between the duration of the nursing episode and the suckling-induced PRL increase at 30 min. Both the basal plasma PRL levels and the PRL responses to suckling diminished with time after delivery. This trend was less evident at 0400 h and was not fully explained by changes in the nursing pattern. The five women in whom menstrual cycles resumed before day 180 postpartum had lower basal and suckling-induced plasma PRL levels than in the women who had amenorrhea for a longer period. This difference was present in the third month, when all women were amenorrheic and fully nursing and when the frequency and duration of nursing episodes and infant growth rates were similar. The results indicate that comparable nursing patterns may be associated with different plasma PRL levels, which are associated with different lengths of lactational amenorrhea. An early difference in the sensitivity of the breast-hypothalamus-pituitary system to suckling may explain the differences in the duration of lactational amenorrhea, which are not dependent on the breastfeeding pattern. The magnitude of the PRL response to suckling may predict the likelihood of recovering ovarian function during lactation.
- ItemCIRCADIAN VARIATION OF RECTAL TEMPERATURE IN NEWBORN SHEEP(1987) RECABARREN, SE; VERGARA, M; LLANOS, AJ; SERONFERRE, MIn adult animals, body temperature shows a 24 h rhythm that is endogenously generated. We examined the existence of 24 h rhythms of temperature in 10 newborn sheep. Four newborns, aged 5 to 28 days were kept with their mothers under nycthemeral conditions, and the remaining 6 lambs, aged 21 to 43 days, were kept with their mothers in constant light from day 3 after birth. Experiments were performed with both groups of lambs in the laboratory. Additional experiments were performed with the 6 lambs kept under constant light while they were in the pen with their mothers to rule out artifacts due to manipulation or artificial feeding. During the experiments done in the laboratory, the lambs were kept blindfolded in a canvas sling and were fed baby formula approximately every four hours (lambs kept under nycthemeral conditions) or every hour (constant light lambs). Lights were on in the room during the whole experiment. Temperature in the room was maintained at 18 .+-. 0.1.degree. C (mean .+-. SEM). In the experiments done in the pen, animals remained with the mother and room temperature was not controlled. In all experiments, rectal temperature was hourly measured for 24 h with a thermocouple inserted in the lamb''s rectum and connected to a Philipp Schenk digital recorder. Lambs kept under nycthemeral conditions show a variation of mean rectal temperature (t.degree.) with a period of 24 h, that fits a cosine function (P < 0.001): Rectal t.degree. (.degree.C)=40.6 + 0.4 cos [15 (t-16.22)]. The mesor is 40.6, the amplitude 0.4, and the acrophase expressed in h is 16.22 (n=4). Lambs kept under constant light show a variation of rectal temperature with a period of 24 h, independently of whether the measurements were done in the laboratory or in the pens. The acrophases varied widely in these animals, when the acrophase were synchronized so .theta.=2400, mean rectal temperature showed a variation with a period of 24 h that fits the equation (P < 0.001): Rectal t.degree. (.degree.C)=39.5 + 0.18 cos [15 (t-0.23)]. The presence of a 24 h rhythm of rectal t.degree. in lambs kept under nycthemeral conditions, and its persistence in lambs kept under constant light suggests that the rhythm of rectal temperature observed in the newborn lamb is a true circadian rhythm. From these data it can be inferred therefore, that the part of the circadian system controlling core body temperature is functional in the newborn lamb.
- ItemDEVELOPMENT OF A CIRCADIAN VARIATION OF PLASMA OXYTOCIN CONCENTRATION IN THE LATE GESTATION RHESUS-MONKEY(1991) SERONFERRE, M; TAYLOR, NF; MARTIN, MC; LEAKE, RDThe 24-h pattern of oxytocin (OT) concentrations in maternal plasma was investigated serially from 112-168 days gestation in four chair-restrained pregnant rhesus monkeys. No change in the mean daily plasma OT concentration was observed with advancing gestational age; there was a change in the pattern of plasma OT secretion throughout the period, however. About 21 days from delivery (150.8 +/- 1.8 days gestational age), plasma OT levels showed occasional fluctuations, distributed throughout the day. About 8 days from delivery (163.2 +/- 2.4 days gestational age), a clear circadian pattern of OT was detected, with an acrophase at 2200 h. These results suggest that there is a relationship between the pattern of OT secretion and advancing pregnancy. This may account partially for the increase in uterin activity known to occur in term rhesus monkeys.
- ItemGROWTH-HORMONE (GH) RECEPTOR ANTIBODIES WITH GH-LIKE ACTIVITY OCCUR SPONTANEOUSLY IN ACROMEGALY(1992) CAMPINO, C; SZECOWKA, J; LOPEZ, JM; MULCHAHEY, J; SERONFERRE, MPrevious studies in our laboratory have identified a portion of big-big GH as actually being anti-GH receptor immunoglobulins. We now report the isolation of two types of anti-GH receptor antibodies from the serum of active acromegalic patients. One of them (patient A) interferes with the human GH RIA, thus overestimating the real plasma GH values. The other type of immunoglobulin G (IgG; patient B) was detected in an acromegalic patient with almost normal immunoreactive GH level. The main aim of the present study was to explore whether these anti-GH receptor IgGs possess GH-like biological activity. The IgGs of both patients were isolated by chromatography on Sephadex G-100 and then on protein-A-Sepharose. In the bioassay, cultured Nb2 lymphoma cells were incubated with hGH standards and serial dilutions of the purified IgGs, and cell proliferation was used as a measure of biological activity. The IgGs of both patients showed GH-like bioactivities, which, when calculated as equivalents of human GH, correspond to approximately 260 and 120-mu-g/L, respectively. The results suggest that biologically active anti-GH receptor antibodies may contribute in the pathology of some cases of acromegaly.
- ItemLUTEINIZING-HORMONE PULSATILE RELEASE AND THE LENGTH OF LACTATIONAL AMENORRHEA(1995) DIAZ, S; CARDENAS, H; ZEPEDA, A; BRANDEIS, A; SCHIAPPACASSE, V; MIRANDA, P; SERONFERRE, M; CROXATTO, HBThe pattern of luteinizing hormone (LH) pulsatile release and the mean concentrations of follicle-stimulating hormone, oestradiol and progesterone were studied in nursing and non-nursing women. Blood samples were drawn at 5 min intervals between 10:00 and 14:00 h and between 22:00 and 02:00 h at months 3-4, 5-6, 7-8 and 9-10 post-partum in nursing women and in the follicular phase in non-nursing women. In nursing women, mean LH concentrations at months 3-4 were significantly lower than in non-nursing cycling women only in the subgroup which subsequently experienced >6 months of lactational amenorrhoea, although all were fully nursing with a similar suckling frequency. LH pulses in plasma were found at all times in nursing women. There were no significant differences in the frequency (about four pulses every 4 h), amplitude or duration of LH pulses related to the duration of amenorrhoea, nor did these parameters vary significantly between amenorrhoeic or cycling nursing women and nonnursing women. Nursing amenorrhoeic women exhibited a normal frequency of LH pulse well in advance of the resumption of the first post-partum menses, suggesting that mechanisms other than the suppression of the gonadotrophin-releasing hormone pulse generator intervened in the inhibition of ovarian function during lactation.
- ItemONTOGENY OF THE CIRCADIAN VARIATION OF PLASMA PROLACTIN IN SHEEP(1989) VERGARA, M; PARRAGUEZ, VH; RIQUELME, R; FIGUEROA, JP; LLANOS, AJ; SERONFERRE, MThe ontogeny of circadian rhythms is unknown. The newborn sheep has a circadian rhythm of temperature; to study the ontogeny of other rhythms, we examined the 24-h variation of plasma prolactin concentration in fetal and newborn sheep. To this effect, we measured plasma prolactin concentration in chronically catheterized fetuses (n = 7) and in newborn lambs raised under short day nycthemeral (12 light:12 dark n = 13) or constant light conditions (n = 5). Indwelling catheters were implanted into the jugular vein and carotid artery of late gestation fetuses (0.9 gestation) and newborns (5-29 days old). Experiments were performed 4 or more days after surgery. Lambs were kept in a canvas sling and were fed cow''s milk either by mouth or through a nasogastric catheter at established time intervals. Haematocrit, pH, and blood gases were measured before and after the experiments in all cases and remained within normal values. Lights were on and room temperature was maintained constant during the whole experiment. Samples were obtained every 1-2 h for 24 h in fetuses and newborn lambs under nycthemeral conditions and every hour for 48 h in newborn lambs kept under constant light. Plasma prolactin was measured by radioimmunoassay. The presence of a 24 h rhythm was determined by Cosinor analysis. Fetuses, aged 129 .+-. 6 days (SD) n = 7, showed a variation in plasma prolactin concentration with a period of 24 h that fits the equation: plasma prolactin (ng ml-1) = 97.0 + 15.4 cos 15 (t-23.0), P = 0.035. Newborn lambs, aged 7.9 .+-. 2.3 days old (n = 11), kept under nycthemeral conditions showed a variation of plasma prolactin with a period of 24 h that fits the equation: plasma prolactin (ng ml-1) = 75.3 + 12.9 cos 15 (t-12.0), P = 0.036. This rhythm disappeared in newborns of 23.4 .+-. 3.8 days of age (n = 7). Newborn lambs, aged 22.0 .+-. 2.7 days (n = 5), raised under constant light, showed a 24 h variation of plasma prolactin in the individual data. These newborns showed a tendency to higher prolactin values and a wider dispersion of plasma prolactin concentration than the two other groups. To normalize the variance the group mean was calculated after log transformation. When log values were synchronized considering the acrophase of the theoretical function as 24 h a rhythm that fits the equation: log plasma prolactin (ng ml-1) = 1.8 + 0.29 cos 15 (t-0.5), P = 0.031, was observed. This indicates that the rhythm of prolactin in the newborn sheep free-runs under constant light. The presence of a rhythm in plasma prolactin with a period of 24 h in fetuses and in the newborn, and the existence of this free running rhythm in newborns kept under constant light, suggest that the prolactin rhythm observed is a circadian rhythm endogenously generated. In addition, the disappearance of the rhythm in older newborns raised under short nycthemeral conditions, and its maintenance in newborns of similar age kept under constant light, suggests that the newborn sheep is sensitive to photoperiod.
- ItemONTOGENY OF THE CIRCADIAN-RHYTHM OF CORTISOL IN SHEEP(1989) PARRAGUEZ, VH; VERGARA, M; RIQUELME, R; RAIMANN, R; LLANOS, AJ; SERONFERRE, MIn this work we investigated the ontogeny of the rhythm of plasma cortisol in sheep. Plasma cortisol was measured by radioimmunoassay in blood samples obtained every 1 or 2 h, for periods of 24 or 48 h, in 13 fetal sheep (124-140 days of gestation; 130.6 .+-. 1.5, mean .+-. SE) and in 23 newborn (5-39 days of age). To this end, indwelling polyvinyl catheters were implanted into the femoral artery and vein in all animals. The presence of rhythm was determined by Cosinor Analysis. Newborns were separated into four groups. Group 1, newborns younger than 15 days of age (7.9 .+-. 0.7 days), and Group 2, newborns older than 15 days of age (25.4 .+-. 2.3), were raised under nyctohemeral conditions (12L:12D). Group 3, newborns younger than 15 days of age (11.4 .+-. 0.9 days), and Group 4, newborns older than 15 days of age (22.0 .+-. 1.2 days), were raised under constant light conditions. A 24-h rhythm of plasma cortisol (F) was observed in newborns over 15 days of age under both nyctohemeral: F (ng/ml) = 16.1 .+-. 7.6 cos [15 (t-12.9)], (p = 0.01, n = 8) and constant llight conditions: F (ng/mL) = 17.1 + 3.9 cos [15 (t-7.9)], (p = 0.02, n = 5). No rhythm was observed in fetal sheep or in newborn sheep younger than 15 days of age under nyctohemeral or constant light conditions.
- ItemRELATIONSHIP OF CIRCADIAN-RHYTHMS OF UTERINE ACTIVITY WITH TERM AND PRETERM DELIVERY(1993) GERMAIN, AM; VALENZUELA, GJ; IVANKOVIC, M; DUCSAY, CA; GABELLA, C; SERONFERRE, MOBJECTIVE: Our aim was to document the presence or significance of circadian uterine activity rhythms in pregnant women who delivered at term and preterm.
- ItemTIME OF DAY OF BIRTH AND ABSENCE OF ENDOCRINE AND UTERINE CONTRACTILE ACTIVITY RHYTHMS IN SHEEP(1993) APOSTOLAKIS, EM; RICE, KE; LONGO, LD; SERONFERRE, M; YELLON, SMTo determine whether 24-h rhythms characterize hormone secretion and uterine activity in the pregnant sheep, blood samples were drawn every 1-4 h for 48 h from ewes and fetuses from day 120 of gestation to term. Repetitive 24-h rhythms were absent for cortisol, progesterone, and prolactin in maternal and fetal circulation and for hourly mean uterine contraction rate and amplitude. To test whether photoperiod or pineal melatonin contributes to the absence of rhythms, pineal-intact and pinealectomized ewes and their fetuses were studied in reverse photoperiod. Again, there was little evidence to suggest 24-h endocrine rhythms except for prolactin in two fetuses by cosinor analyses. Prolactin concentrations were increased in pinealectomized ewes and their fetuses. In the apparent absence of rhythms, 20 of 21 pineal-intact ewes gave birth at night; however, 6 out of 7 pinealectomized ewes gave birth during the day. Thus photoperiod and the maternal pineal gland profoundly influenced the time of day of birth in the absence of circadian endocrine or uterine activity rhythms.