Biomedical subjects

S S Daniel

Publications and source records attributed to S S Daniel.

At least 19 recordsLinked to original sources

PubMed2001

Cognitive risk factors and suicide attempts among formerly hospitalized adolescents: a prospective naturalistic study.

OBJECTIVE: To examine the relationship between cognitive variables and time until suicide attempts among 180 adolescents who were monitored for as much as 6.9 years after discharge from an inpatient psychiatry unit. METHOD: In a prospective naturalistic study, adolescents were assessed at the time of their psychiatric hospitalization and semiannually thereafter. Suicidal behavior at index hospitalization and over the follow-up period was assessed with semistructured psychiatric diagnostic interviews. At hospitalization, cognitive risk factors were assessed with a problem-solving task and with questionnaires assessing hopelessness, expectations for posthospitalization suicidal behavior, reasons for living, and dysfunctional attitudes. RESULTS: Expectations about future suicidal behavior were related to posthospitalization suicide attempts. Among youths with previous suicide attempts, higher levels of hopelessness were associated with increased risk, and greater survival and coping beliefs were associated with decreased risk for posthospitalization suicide attempts. Hopelessness and survival and coping beliefs were not related to posthospitalization attempts among adolescents without prior suicidal behavior, and hopelessness was not predictive after controlling for overall severity of depression. CONCLUSIONS: Expectations for suicidal behavior, hopelessness, and survival and coping beliefs provide important prognostic information about later suicidal behavior and should be targeted in interventions with suicidal youths.

Adolescent↗

PubMed1999

Amniotic fluid composition in the fetal lamb with intrauterine growth restriction.

OBJECTIVE: Our aim was to examine changes from normal in the composition of amniotic fluid in fetal lambs with mild and severe hypoxemia and intrauterine growth restriction. STUDY DESIGN: Pregnant sheep underwent maternal catheterization at 88 to 93 days' gestation and fetal catheterization at 105-112 days' gestation. Twelve pregnancies (group 1) provided control data (fetal PaO 2 18-22 mm Hg), in 12 fetuses (group 2) mild hypoxemia (PaO 2 16-19 mm Hg) was induced by prevention of the normal expansion of maternal blood volume, and in 7 fetuses (group 3) chronic hypoxemia (PaO 2 12-18 mm Hg) developed spontaneously. RESULTS: In group 2 amniotic fluid osmolality and sodium concentrations were lower (approximately 30 mOsm/kg and 10 mEq/L, P <.05) and urea nitrogen level was higher (10 mg/dL, P <.05) than in group 1. In group 3 osmolality and sodium concentrations at approximately 120 days' gestation were similar to those in group 1. Whereas these values decreased with gestation in groups 1 and 2 (P <.05), they remained unchanged or increased in all fetuses in group 3. Mortality rates in groups 1, 2, and 3 were 1 of 12, 4 of 12 (difference not significant), and 5 of 7 (P <.05), respectively. CONCLUSION: Absence of normal decrease in amniotic fluid osmolality with gestation, in association with a high perinatal mortality rate, was found in severely but not in mildly hypoxemic fetuses with intrauterine growth restriction.

Amniotic Fluid↗

PubMed1999

Gestational age related changes in cardiac dynamics of the fetal baboon.

To provide insight into the maturation of neural mechanisms governing fetal heart rate and rate variability, seven chronically instrumented fetal baboons were monitored under steady state conditions between 120 and 165 days gestation (term 175 d). Forty records of 24 h duration (5-7 records/fetus) were evaluated. For each fetus, heart rate decreased with gestational age (mean+/-SD, r = -0.530+/-0.324, P <0.05). In contrast, there were increases with age in markers of various components of autonomic control of fetal R-wave to R-wave interval (RRi) variability as reflected in a positive correlation with age for all fetuses of SD RRi (r = 0.656+/-0.347, P < 0.01), root mean squared differences in RRi (r = 0.686+/-0.223, P <0.05), and power at low frequency in the RRi spectrum (r = 0.800+/-0.161 P < 0.01). In each of the seven fetuses, scatter plots of RRi as a function of the prior RRi (Poincare plots) had increased dispersion around the median with gestational age (0.605+/-0.371, P<0.05). Additional measures of variability evaluated changes in RRi from one interval to the next (deltaRRi). The incidence of sustained deltaRRi changes, either decelerations or accelerations, rose with gestation (r = 0.920+/-0.057, P < 0.001) while the incidence of no detected deltaRRi changes (<+/-1 ms) diminished (r = - 0.649+/-0.364, P <0.05). Sequential decreases in fetal heart rate, increases in RRi variability and increases in changes in RRi and deltaRRi with age imply an overall maturation in autonomic cardio-regulatory control processes. Increases with gestation in measures of high frequency components of variability are compatible with enhanced parasympathetic modulation of fetal heart rate.

Animals↗

PubMed1999

Diurnal rhythms of fetal and maternal heart rate in the baboon.

To investigate the organization of diurnal rhythmicity during gestation, the relationship between daily cycles of maternal and fetal heart rate were measured in long-term studies of healthy chronically instrumented pregnant baboons. In each of six pregnancies, hourly mean values over a 168 h time series were obtained during a 7 to 10 day interval between 135 and 160 days of gestation. Data were modeled by a least squares fit to a cosine function with a period of 24 h. Hourly mean heart rate in the fetus ranged from 161 to 172 bpm (167.9+/-0.6 bpm), and the mother from 105 to 125 bpm (107.9+/-1.4 bpm). The amplitude of the daily fluctuations were 15 to 25 bpm for the fetuses and 25 to 60 bpm for the mothers. The relation between time series data and model estimates were significant (P < 0.001) in all cases with aggregate r2 = 0.747 for fetuses and 0.737 for the mothers. On average the time of day of the peak in fetal heart rate (15:05+/-0.3 h) was about 45 min after the maternal peak (14:21+/-0.4 h). This phase delay was significant (t = 2.63, P < 0.05). There was significant (P < 0.01) diurnal periodicity for each of six parameters used to assess different aspects of fetal heart rate variability with peak variability at night (23:00 to 2:00). Thus, during the latter third of pregnancy in both the maternal and fetal baboon 24 h periodicities of heart rate are present with peak rates in the midafternoon. The daily rhythms in fetal heart rate are linked with periodicities in maternal heart rate with a phase delay in the majority of cases. The synchrony of 24 h fluctuations in rate with parameters of rate variability is consistent with diurnal input into the fetal autonomic nervous system.

Amniotic Fluid↗

PubMed1999

Suicide attempts among formerly hospitalized adolescents: a prospective naturalistic study of risk during the first 5 years after discharge.

OBJECTIVE: To examine risk for suicide attempts among 180 consecutively referred adolescents during the first 5 years after discharge from an inpatient psychiatry unit. METHOD: In a prospective naturalistic study, adolescents were assessed at psychiatric hospitalization and semiannually thereafter for up to 5 years with semistructured psychiatric diagnostic interviews and self-report questionnaires. RESULTS: Approximately 25% of the adolescents attempted suicide and no adolescents completed suicide within the first 5 years after discharge. The first 6 months to 1 year after discharge represented the period of highest risk. The number of prior attempts was the strongest predictor of posthospitalization attempts. Affective disorders by themselves did not predict later suicide attempts but were related to posthospitalization attempts when accompanied by a history of past suicide attempts. Independent of psychiatric diagnoses, severity of depressive symptoms and trait anxiety also predicted suicide attempts. Similar to the effect with affective disorders, depressive symptoms were most strongly related to posthospitalization suicidality among adolescents with a prior history of suicide attempts. CONCLUSIONS: Particularly among youths with prior suicidal behavior, clinicians should be alert to the above constellation of psychiatric predictors of posthospitalization suicidal behavior.

Adolescent↗

PubMed1998

Implications of the kinetics of zidovudine in the pregnant baboon following oral administration.

Zidovudine (ZDV) therapy in pregnancy reduces mother-to-child transmission of HIV. The action of ZDV in the fetus is thought to be an important contributor to efficacy. Previous research in primates has demonstrated that continuous infusion of ZDV to the mother leads to sustained plasma concentrations in the fetus; however, it has not been determined what concentrations of ZDV are achieved in the fetus following oral administration. The pharmacokinetics of drug distribution to the fetus following oral administration of a 100-mg dose of ZDV to the mother are reported from 6 chronically catheterized baboons. The first order elimination half-life of ZDV from both the mother and fetus was approximately 1.2 hours. The area under the concentration-time curve for the fetus was 77% (r2 = 0.98; p < .001) that of the mother and the estimated peak drug levels in the fetus were 52% (r2 = 0.83; p < .01) those in the mother. The rapid transfer and short half-life of ZDV leads to a drug concentration-time profile that would not sustain levels in the fetus with dosing every 4 hours. After comparing these findings with existing data from pregnant and nonpregnant humans, it seems likely that current dose recommendations for ZDV in pregnancy would not maintain levels of the active intracellular metabolite of ZDV in all fetuses. This may explain in part the 8% failure rate of ZDV prophylaxis. The correlation between fetal and maternal plasma concentrations of ZDV would allow titration of dose based on maternal drug levels to achieve fetal levels within the therapeutic range.

Administration, Oral↗

PubMed1998

Psychiatric diagnoses of previous suicide attempters, first-time attempters, and repeat attempters on an adolescent inpatient psychiatry unit.

OBJECTIVE: To compare psychiatric diagnoses of hospitalized adolescents who (a) have made previous but no recent suicide attempts, (b) have recently made their first suicide attempt, (c) have recently made a second or subsequent attempt, or (d) have never made an attempt. METHOD: Semistructured psychiatric diagnostic interviews were used to determine psychiatric diagnoses and history of recent and previous suicidal behavior of 269 consecutively admitted adolescents to an inpatient psychiatric facility. Forty-nine previously suicidal youths, 28 first-time attempters, and 33 repeat attempters were compared with 159 nonsuicidal youths in prevalence of Axis I psychiatric disorders and psychiatric comorbidity with affective disorder. RESULTS: Previous attempters and repeat attempters both reported more affective disorders, whereas first-time attempters reported more adjustment disorders than nonsuicidal youths. Previous attempters and nonsuicidal youths reported the most externalizing disorders. CONCLUSIONS: Previous attempters on an inpatient unit have multiple psychiatric problems. Like repeat attempters, they often are depressed, but like nonsuicidal youths, they also exhibit significant externalizing behaviors. Interventions with these adolescents should focus not only on immediate presenting problems, but also on ameliorating their long-term risk of posthospitalization suicidal behavior.

Adolescent↗

PubMed1998

Placental transfer and fetal metabolism of zidovudine in the baboon.

Zidovudine (azidothymidine, AZT) is used in pregnancy to reduce mother to infant transmission of HIV. Understanding the disposition of AZT in the fetus is necessary to optimize therapeutic regimens directed toward the fetus. Recent studies in primates found similar steady-state levels of the glucuronide metabolite of AZT (AZT-glu) in the fetus to those in the mother, raising the question of whether the metabolite was of fetal or maternal origin. The objective of this study was to determine whether glucuronidation occurred in the fetal compartment and to quantify the placental and fetal clearances of AZT using the two-compartment model at steady state. Steady-state concentrations were obtained after paired maternal and fetal infusions of AZT in chronically catheterized pregnant baboons. During maternal infusion, the mean (+/-SE) fetal to maternal ratio of AZT was < 1 (0.84 +/- 0.06, p < 0.02), suggesting clearance of AZT in the fetus. Mean total maternal clearance of AZT was 725 +/- 49 mL/min and placental clearance was 36 +/- 4 mL/min, or approximately 5% of maternal clearance. Fetal clearance of AZT was estimated at approximately 15% of placental clearance. This suggests fetal nonplacental clearance is minimal compared with that in the mother, but does not preclude the fetus from actively contributing to the metabolite in the fetal circulation. During infusion of AZT to the fetus, the concentration of AZT-glu in the fetus was 7.0 +/- 0.8 times that in the mother. This is compelling evidence that glucuronide can be formed in the fetal compartment. Thus, fetal metabolism has an impact on the concentration of both AZT and AZT-glu in the fetal circulation.

Amniotic Fluid↗

PubMed1997

Effect of zidovudine on blood composition of the pregnant and fetal baboon.

OBJECTIVE: Our purpose was to assess the effect of intravenous zidovudine on placental function and fetal well-being. STUDY DESIGN: Eighteen chronically instrumented third-trimester pregnant baboons and their fetuses were studied after 4- to 48-hour infusions of zidovudine to 14 mothers (0.8 to 2.0 mg/kg/hr) and 6 fetuses (0.2 to 0.22 mg/kg/hr of maternal weight). Fetal and maternal pH and blood gases, hematocrit, blood cell counts, clinical chemistries, electrolytes, and hormones were measured before and after the infusions. RESULTS: In both mother and fetus no significant differences were found between values in the control periods and those after infusions of zidovudine in any of the index values measured. CONCLUSION: Administration of zidovudine from 4 to 48 hours in the baboon was associated with no significant change in any biochemical index values in the mother or fetus. Thus comparable exposure of the human fetus to zidovudine during labor is not expected to affect these index values of placental function and fetal well-being.

Acid-Base Equilibrium↗

PubMed1997

Suicidal ideation and behavior and noncompliance with the medical regimen among diabetic adolescents.

OBJECTIVE: To examine (1) the 1-year and lifetime prevalence of suicidal thoughts and behavior among adolescents with insulin-dependent diabetes mellitus (IDDM), (2) the relationship between suicidal thoughts and serious noncompliance with the medical regimen, and (3) factors including psychiatric disorder, self-efficacy expectations, and hopelessness that might mediate the relationship between suicidal thoughts and noncompliance. METHOD: Semistructured and structured interview instruments and self-report questionnaires were used to determine history of suicidal thoughts and behavior, serious noncompliance with the medical regimen, current psychiatric disorder, hopelessness, and self-efficacy expectations among 91 adolescents attending outpatient clinic appointments. RESULTS: The rate of suicidal ideation among the diabetic adolescents was higher than expected, but the rate of suicide attempts was comparable with that reported for the general population. Suicidal thoughts were strongly associated with serious noncompliance with the medical regimen. Duration of IDDM and psychiatric diagnosis were related to both suicidal ideation within the previous year and lifetime suicidal ideation. Diagnosable psychiatric disorder and not living in a two-parent home were related to noncompliance with medical treatment. CONCLUSIONS: Suicidal thoughts and serious noncompliance with the medical regimen are strongly associated among diabetic teenagers, and psychiatric disorder is a common correlate of both.

Adolescent↗

PubMed1996

Zidovudine kinetics in the pregnant baboon.

The devastating impact of human immunodeficiency virus (HIV) infection during pregnancy has made the pharmacologic evaluation of potentially therapeutic agents of high priority. The results presented here are the maternal pharmacokinetics from a series of experiments to delineate more clearly the complex maternal-fetal pharmacokinetics and the effects of AZT in the chronically instrumented maternal and fetal baboon during both steady state intravenous infusion and oral bolus dosage regimens. Two results of major clinical importance were found. First, during pregnancy, both the clearance and volume of distribution of AZT were increased. Plasma clearance in the pregnant animals was 51 +/- 10 ml/min/kg compared with 37 +/- 2 ml/min/kg in the nonpregnant animals, and steady state volume of distribution was 3.7 +/- 1.21/kg compared with 2.2 +/- 0.61/kg. Second, with continuous intravenous infusion plasma drug concentrations were easily maintained in the therapeutic range, whereas with oral administration plasma concentration fell below therapeutic levels within 2 h of the dose being given. Because maternal plasma concentrations are a major determinant of drug concentration achieved in the fetus, an understanding of drug kinetics in pregnancy is of vital importance when making recommendations regarding optimal drug therapy during pregnancy to maximize the beneficial effect--the prevention of HIV infection in children.

Absorption↗

PubMed1996

Blood pressure and HR in the fetal lamb: relationship to hypoglycemia, hypoxemia, and growth restriction.

We examined blood pressure and heart rate (HR) in relation to glucose and arterial PO2 (PaO2) at approximately 121 days (early) and at approximately 140 days (late) gestation in 12 growth-restricted and 10 control fetal lambs. Mild growth restriction (relative to maternal weight) was produced by withdrawal of 25 ml/day of maternal blood during the second half of pregnancy (P < 0.05). Fetuses from this model are hypoglycemic during early and late gestation but hypoxemic only during late study. Mean systolic and diastolic pressures in the experimental group were approximately 8.0 mmHg lower than the corresponding values in controls at both studies (P < 0.05). Fetal HR (FHR) was 15.4 beats/min lower (P < 0.05) in 10 but was higher than control in 2 experimental fetuses that were also not growth restricted. There were significant correlations between late systolic pressure and HR and PaO2 (r = 0.54, P = 0.046 and r = 0.50, P = 0.049, respectively) and between FHR and blood pressure and birth weight/maternal weight (P < 0.05). We conclude that, in this model, fetal blood pressure and HR may serve as good indicators of hypoxemia and growth restriction.

Animals↗

PubMed1994

Patterns of fetal breathing in the baboon vary with EEG sleep state.

This report examines the hypothesis that the characteristics of breathing activity of the fetal baboon are modulated with respect to sleep state in a fashion similar to that observed in the human fetus. The pattern of fetal breathing activity was examined in relationship to electroencephalographic (EEG) sleep state in studies of six fetuses of chronically monitored pregnant baboons at 143-148 days of gestation (term, 175-180 days). Fetal breaths were defined by fluctuations of tracheal fluid pressure. EEG sleep states were defined with an automated method for discrimination of EEG patterns that are standard indices of quiet and active sleep in immature primates. During more than 250 h of recorded data, the fetuses spent on average 33.3 +/- 3.9% of time in EEG quiet sleep. In comparisons across state the fetuses spent significantly (P = 0.001) less time breathing during quiet than active sleep (49.5 +/- 6.8 vs. 69.0 +/- 3.8%). The inspiratory and expiratory time intervals of fetal breaths were not differentiated by EEG state but, the mean breath to breath interval was significantly (P < 0.001) longer in EEG quiet sleep. In addition to these differences in incidence and time interval of breaths, during epochs of breathing, there was a significantly slower rate, lower amplitude, and lower variability of rate of breathing in quiet sleep (all P-values < 0.02). Thus, periodic breathing activity in the fetal baboon is present in both quiet and active EEG sleep states. Sleep states have a powerful influence on patterns of fetal breathing in the non-human primate, directly comparable to the human fetus.

Animals↗

PubMed1994

Fetal hiccups in the baboon.

Bouts of hiccuping are recognized by pregnant women as distinct episodic movements of their fetuses. Ultrasound imaging of these fetuses has documented the occurrence of hiccups from early gestation through parturition. This study provides a systematic characterization of prenatal hiccuping in the fetal baboon (Papio species). Tracheal fluid pressure was recorded from 11 chronically instrumented fetal baboons for 21.5 +/- 7.3 consecutive days (mean +/- SD) over a range in gestation from 124 to 164 days (term 175 days). In an initial review of pressure recordings by visual inspection, hiccups were recognized as distinctive high-amplitude fluctuations in tracheal pressure that were readily discriminated from fetal breaths. Automated techniques were then developed and validated to detect hiccups and summarize their features. The mean hiccup amplitude was 23.0 +/- 3.1 mmHg, inspiratory time was 0.26 +/- 0.03 s, and expiratory time was 0.27 +/- 0.02 s. Each of these features discriminated hiccups from breaths (P < 0.001). Hiccuping incidence (1.8 +/- 0.4% of time), rate (26.2 +/- 6.2 min-1), bout duration (4.3 +/- 0.8 min), and the interval between bouts (3.35 +/- 0.60 h) were also different (P < 0.01) from breathing. These features of hiccups remained relatively constant over the latter third of gestation with the exception of an increase in duration of the expiratory time interval (r = 0.54, P < 0.01). Despite their vigorous nature, bouts of hiccuping were not associated with transitions in behavioral state. Moreover, the features of hiccups were not differentiated by state. Bouts of hiccuping recurred in a cyclic fashion, on average every 3-4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Patterns of development in fetal breathing activity in the latter third of gestation of the baboon.

Patterns of fetal breathing activity were examined in a longitudinal study of the fetal baboon over the latter third of gestation. More than 1400 h of recorded tracheal fluid pressure in 16 or 24 h records from seven fetuses over a range in gestation from 121 to 172 days (term, 175-180 days) were analyzed. In these 81 records, there was a high degree of variability in the percent of time spent breathing by the fetuses (range, 14-83%) with no apparent influence of gestational age (mean +/- S.D., 45.6 +/- 17.6%). Nonetheless, the mean amplitude of fetal breaths increased with gestation from absolute values of about 5-10 mmHg (r = 0.73, P < 0.001) and the mean inspiratory time interval increased from about 0.45-0.55 s (r = 0.40, P < 0.001). During epochs of breathing, the mean rate decreased from about 42-36 breaths per min (r = -0.54, P < 0.001) and the indices of both short term (r = -0.54, P < 0.001) and long term (r = -0.73, P < 0.001) variability in rate decreased. These results demonstrate a clearly defined pattern of development in the breathing activity of the fetal baboon which is comparable to the pattern described for the human fetus in the third trimester of gestation. These similarities suggest that the progressive functional maturation of the mechanisms generating respiratory patterns are comparable among primate species.

Amniotic Fluid↗

PubMed1992

Long-term acid-base measurements in the fetal and maternal baboon.

OBJECTIVE: The purpose of the study was to examine the relationship between maternal and fetal acid-base indexes in the baboon. STUDY DESIGN: Eight animals maintained in a tether system were studied during the third trimester. Results were analyzed using analysis of variance. RESULTS: After recovery from surgery, pH in carotid artery blood of the fetus was 7.40 +/- 0.027 (mean +/- SD), PO2, 27.5 +/- 3.45 mm Hg; PCO2, 34.0 +/- 2.37 mm Hg; base deficit, 3.0 +/- 2.15 mEq/L; Hot, 33.4% +/- 2.69% and HbO2, 61.3% +/- 8.65%. The corresponding values in the mother were 7.48 +/- 0.035, 100.7 +/- 9.44 mm Hg, 26.4 +/- 2.95 mm Hg, 3.6 +/- 1.71 mEq/L, 32.6% +/- 4.0% and 97.9% +/- 1.28%, respectively. All indexes remained essentially the same until the onset of active labor, at which time the fetus became slightly acidotic and hypoxemic (pH less than 7.35, HbO2 less than 50%). CONCLUSION: The baboon fetus has slightly higher pH2 and lower PaCO2 than the human fetus and PaO2, base deficit, and maternal-fetal gradients across the placenta in these two primate species are comparable.

Acid-Base Equilibrium↗

PubMed1991

Effects of Ro 15-4513 on ethanol discrimination in C57BL/6 mice.

Ro 15-4513, a partial benzodiazepine receptor inverse agonist, counteracts many of the effects of ethanol, however, its effects on ethanol discrimination in operant paradigms remains unclear. The present study examined the effects of Ro 15-4513 on ethanol discrimination by female C57BL/6 mice in a food-reinforced behavior-operant paradigm. Under the time and dosing conditions used in previous reports, Ro 15-4513 did not alter ethanol discrimination whether given prior to or after ethanol exposure. The drug did, however, attenuate ethanol discrimination for brief periods (less than 8 min) when injected after ethanol and at doses and postinjection times which also disrupted responding. The present study confirmed that Ro 15-4513 attenuated ethanol discrimination, but not to the extent as previously reported. The results indicate that postinjection time is a very critical factor in whether Ro 15-4513 attenuates ethanol discrimination.

Animals↗

PubMed1989

The insulin-like growth factor II/mannose-6-phosphate receptor is present in fetal and maternal sheep serum.

A large mol wt binding protein for insulin-like growth factor II (IGF-II) has been described in fetal sheep serum. We now provide evidence to demonstrate that this binding protein is the IGF-II/mannose-6-phosphate (Man-6-P) receptor. Serum and plasma were gel filtered on Sephadex G-200, and the column fractions were assayed for binding of radiolabeled IGF-II. There was significant binding of [125I]IGF-II to the void volume fractions in addition to binding to the 150K and 40K carrier proteins. Binding to the void volume fractions was increased in fetal serum as well as maternal serum and dramatically decreased in the nonpregnant adult. Competitive binding studies with [125I]IGF-II and the void volume pools from fetal and maternal sheep serum demonstrated that IGF-I competed less potently than IGF-II, and insulin did not compete. There was no specific binding of [125I]IGF-I to the void volume pools of either fetal or maternal samples. Chemical cross-linking of [125I]IGF-II to aliquots of the void volume pools from fetal and maternal sheep serum samples and analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of dithiothreitol demonstrated a specific band at about 240K. Western blotting using a specific antiserum (no. 3637) against rat IGF-II/Man-6-P receptor was performed on aliquots of the Sephadex G-200 void volume pools of fetal, maternal, uterine vein, and adult sheep serum; a band of approximately 210K (without dithiothreitol) was seen. The IGF-II/Man-6-P receptor band was more intense in fetal serum than in either maternal or adult nonpregnant sheep serum. There was also increased binding of [125I]IGF-II in the 40K region of the Sephadex G-200 column fractions in the maternal serum compared to that in serum from nonpregnant adult ewes. When fetal, maternal, and adult nonpregnant sheep serum Sephadex G-200 pools were gel filtered on Sephadex G-50 in 1 mol/liter acetic acid to separate bound from free IGF, and IGF-II was measured by RRA, approximately 50% of the circulating IGF-II was associated with this IGF-II/Man-6-P receptor in fetal serum compared to 7% in maternal serum and 3% in adult nonpregnant serum. These data demonstrate that the IGF-II/Man-6-P receptor circulates in fetal sheep serum as well as maternal serum and appears to be a significant carrier for IGF-II in fetal sheep.

Animals↗