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Biomedical subjects

J Sack

Publications and source records attributed to J Sack.

At least 145 records · Page 8Linked to original sources

Possible mechanisms and significance of the neonatal surge in glucagon secretion: studies in newborn lambs.

Studies were conducted in newborn lambs to gain insight into the significance and mechanism(s) responsible for the rapid rise in plasma immunoreactive glucagon (IRG) which occurs in human and other newborn species immediately after delivery. Three sets of experiments were conducted: group A, control studies (n = 5) in which delivery into room air was followed 1 hr later by cutting of the umbilical cord and periodic blood sampling for a further hour; group B, studies (n = 5) in which somatostatin (SRIF), a known inhibitor of IRG and insulin (IRI) secretion, was infused int othe fetus for 10 min before, and for 1 hr after delivery and immediate cord cutting; group C, studies (n = 5) in which an identical dose regimen of SRIF was infused into fasting newborn lambs aged 24-72 hr. The doses of SRIF used were several fold higher than those proven to suppres pancreatic hormones secretion in other species. In the control studies, plasma IRG levels remained stable until the cord was cut, after which event levels rose 5-6-fold (59 +/- 15 pg/ml to 305 +/- 98 pg/ml, P less than 0.05). Simultaneously, plasma free fatty acid (FFA) concentrations rose significantly (280 +/- 80 to 780 +/- 100 muEq/liter, P less than 0.05) and IRI remained unchanged. Plasma glucose concentrations, however, in contrast to observations in other species, did not fall, and therefore, hypoglycemia was not the stimulus for the glucagon surge. SRIF infusion at birth (group B) did not prevent the rise in IRG. Again blood glucose values did not fall, but in contrast to the control studies plasma IRI levels rose and the rise in FFA did not occur. Later SRIF infusion (group C) resulted a prompt and sustained suppression of IRG and IRI and a significant fall in blood glucose. These results suggest that an adrenergic mechanism rather than curtailment of nutrients is the major stimulus to the neonatal surge in IRG.

Animals↗

The response of newborn sheep to TRH with and without somatostatin.

Hormone responses to a bolus injection of thyrotropin releasing hormone (TRH) were studied in 8 newborn lambs between 6 and 19 hours of age. The effect of a bolus injection and 45 min infusion of somatostatin (SRIF) on these responses was studied in 2 other animals. Serial measurements of serum TSH, prolactin, triiodothyronine (T3) and thyroxine (T4) were conducted for 2 to 6 h in all animals. Mean baseline T4 and T3 concentrations were 12.6 microng/dl and 221 ng/dl, respectively, both significantly higher than values in fetal or adult animals. These high values were due to the events of parturition. In spite of the high baseline T4 and T3 levels, there were rapid and significant increases in both TSH and prolactin concentrations in response to TRH alone. The TSH response evoked further increments in serum T3 and T4 concentrations observed at 30 min and 60 min, respectively, both subsequently increasing progressively through 6 h. During the 45 min period of SRIF infusion, the TSH T4 and T3 responses to the zero time TRH injection were minimal. However, after discontinuing SRIF, late increases in TSH, T4 and T3 were observed. The results indicate that the hyperiodothyroninemia characteristic of the newborn period does not block the response to exogenous TRH, whereas the inhibitory effect of exogenous SRIF is observed in the newborn as in the adult. The increased endogenous TRH secretion presumably responsible for the neonatal TSH surge may be overriding the negative feedback effect of thyroid hormones.

Animals↗

Thyroxine concentration in human milk.

Thyroxine (T4) concentrations were measured by RIA in 37 milk samples from 19 healthy eutryroid mothers, obtained between 3-165 days postpartum. The mean milk T4 concentration in the first week postpartum was 0.38 +/- 0.07 microgram/100 ml (mean +/- SEM). The mean T4 concentrations between 8 and 48 days rose to 4.27 +/- 0.50 microgram/100 ml (mean +/- SEM), and decreased to 1.11 +/- 0.25 microgram/100 ml (mean +/- SEM) after 50 days postpartum. The data suggest that human milk can provide a significant exogenous source of T4 to the infant. In the hypothyroid infant, the amount of T4 in human milk may delay clinical recognition of the disease. Although this exogenous source of T4 may alleviate the disease, it is insufficient to prevent the detrimetal effects of hypothyroidism.

Female↗

Serum thyrotropin, prolactin, and growth hormone levels during the early neonatal period in the human infant.

Normal term newborn infants have been studied during the first four hours after birth. Cord blood and brachial venous blood samples were collected for measurement of serum prolactin (n = 15; 11 vaginal delivery; four cesarean section delivery), thyrotropin (n=8), growth hormone (n=7), tri-iodothyronine (n=7) and thyroxine (n=7). The mean cord serum TSH concentration was 12 +/- 2 muU/ml and peaked in all infants 30 minutes after birth (67 +/- 7 muU/ml). Blood PRL also increased in all of the 15 infants studied; the mean cord blood value of 165 +/- 15 ng/ml increased significantly to a mean of 214 +/- 22 ng/ml at 30 minutes and 204 +/- 17 ng/ml at 60 minutes. The peak blood PRL concentration was observed at 30 minutes in eight newborn infants, at 60 minutes in three, and at 120 minutes in four. Mean serum GH concentrations were statistically similar during the first four hours but there was a tendency for serum levels to fall somewhat during the first hour after birth. The mean cord serum T3 concentration (47 +/- 5 mug/ml) increased significantly to a peak value of 227 +/- 38 ng/dl at 120 minutes. The increase in T4 from a mean of 15.3 +/- 1.2 mug/dl to a mean of 17.9 +/- 2.6 mug/dl at four hours was less dramatic. These data are consistent with the possibility that the same mechanism responsible for the neonatal TSH surge may be responsible for a significant but lesser PRL surge during the early minutes after birth.

Cesarean Section↗

Umbilical cord cutting triggers hypertriiodothyroninemia and nonshivering thermogenesis in the newborn lamb.

The present studies in the newborn sheep were undertaken to further clarify the mechanism or mechanisms for the early increases in serum thyroid hormone concentrations in the newborn as well as the significance of these changes to newborn nonshivering thermogenesis. Six groups of animals were studied to determine the influence of neonatal cooling, cord cutting, and the effects of thyrotropin-releasing hormone (TRH) and triiodothyronine (T3) injections. Group I newborns were delivered into room air with immediate cord cutting. Group II animals were delivered into room air and cord cutting was delayed 60 min. Group II animals were delivered into a 39 degrees water bath and maintained for 60 min with the umbilical cord intact; the cord was cut at the time of removal from the water bath...

Animals↗

The circulating vasopressinase of pregnancy: species comparison with radioimmunoassay.

A vasopressin substrate radioimmunoassay (RIA) system is described for the measurement of the vasopressinase elaborated during pregnancy. Results show that vasopressinase activity increases in the sera of pregnant women throughout gestation. At term, under the in vitro conditions described, pregnancy serum degrades vasopressin (Pitressin) at a rate of 53 mU. per milliliter of serum per minute. Serum obtained from paired umbilical cord samples had an activity of 9.2 muU per milliliter per minute; amniotic fluid obtained at delivery had an activity of 16.6 muU per milliliter per minute. Pregnancy serum obtained from sheep, rabbits, and rats, ovine umbilical cord serum, and ovine amniotic fluid had no detectable vasopressinase activity. Normal human male serum, nonpregnant female serum, and serum from women taking contraceptive agents also exhibited no activity.

Aminopeptidases↗

Thyroxine in human amniotic fluid.

Total and free T3 and T4 concentrations were measured in human amniotic fluid and in fetal and maternal blood. Before 20 weeks, the mean AF-T4 level was 0.24 mug/dl; there is a progressive increase in concentration with gestational age. At term, the mean AF total T4 level was much less (0.64 mug/dl) than in fetal or maternal serum (9.3 and 11.3 mug/dl, respectively). Most of the T4 (99.4%) in AF is protein bound, presumably to TBG as in serum, but the mean FT4 concentration in AF at term (4.13 ng/dl) was significantly greater than the levels in fetal or maternal serum (2.67 or 2.56 ng/dl, respectively). The mean TBG level in AF at term was 0.26 mg/dl. T3 was not measurable in AF (less than 15 ng/dl). There were no significant correlations between the total or free T4 concentrations in maternal or fetal sera and in amniotic fluid. Thus AF thyroid hormone concentrations in the euthyroid fetus do not reliably reflect fetal serum T4 or T3 concentrations.

Amniocentesis↗

Circulating 3,3', 5'-triiodothyronine (reverse T3) in the human newborn.

Serum concentrations of 3,3',5'-triiodothyronine (reverse T3 rT3), 3,3',5-triiodothyronine (T), and thyroxine (T4) were measured in cord blood and invenous blood samples obtained between 2 h and 30 days of postnatal life from healthy full-term newborn infants. The mean serum rT3 concentration of (mean plus or minus SE) 151 plus or minus 12 ng per 100 ml in 18 cord blood samples was significantly higher than the level (41 plus or minus 2 ng per 100 ml) in 27 normal adult sera; the corresponding mean serum T4 of 12.7 plus or minus 0.8 mug per 100 ml in cord blood also was significantly higher than that (8.6 plus or minus 1.9 mug per 100 ml) in 108 normal adults. By contrast, the mean serum T3 concentration in 15 cord blood samples, 24 plus or minus 3 mg per 100 ml, was significantly lower than the value of 126 plus or minus 3.2 ng per 100 ml measured in 108 normal adults. At 4 h of age the mean serum rT3 concentration (165 plus or minus 13 ng per 100 ml) in six newborns was 4ot significantly different from that in paired cord blood samples (194 plus or minus 25 ng per 100 ml); on the other hand, whenever, studied, the mean serum T3 and T4 levels were significantly higher at 4 h than at birth. The failure of serum rT3 concentrations to rise after delivery in response to the early neonatal thyrotropin (TSH) surge and at a time when serum T3 and T4 levels increase significantly prompted a study of the rT3 response to 10 IU of intramuscular TSH in three healthy adult subjects. Just as in the newborns, serum rT3 failed to rise appreciably in these subjects, even though serum T3 and T4 showed the expected increments. Serum rT3 concentrations in 1-4 day-old newborn infants did not differ significantly from values in the cord blood but were significantly lower in older neonates. The mean serum rT3 level in 5-7-day-old infants was higher than that in normal adults, but in 9-11 day and 20-30-day-old infants, mean rT3 values were statistically similar to the adult value. The mean serum T3 concentrations in neonates between 1-30 days old were either higher than or comparable to the values of normal adults. The mean serum T4 concentrations in neonates between birth and 30 days of age were significantly higher than the mean adult level. The mean serum rT3 to T4 ratios (rT3/T4) were elevated in 1-4-day-old neonates; the values in older neonates were similar to those in adults. These results suggest that (a) factors other than TSH are important modulators of serum rT3 in man; (b) high serum rT3 concentration in the newborn becomes comparable to that in the normal adult by 9-11 days of neonatal life.

Adult↗

Thyroid hormone metabolism in amniotic and allantoic fluids of the sheep.

Amniotic and allantoic fluid samples were obtained at the time of uterotomy from healthy pregnant ewes at various time during gestation. In most instances maternal and fetal blood was collected simultaneously. Serum thyroxine (T4) and triiodithyronine (T3) and free T4 were measured in most samples. To determine whether conjugastes of T4 were presented in amniotic and allantoic fluids. T4 was measured before and after 24-hr acid hydrolysis. T4 and T3 turnover from amniotic fluid were measured using kinetic methods after intravenous or intraamniotic fluid injection of radiolabeled hormones. T3 was unmeasurable less than 15 ng/100 ml) in amniotic and allantoic fluids as well as in most fetal serum samples. T4 levels in amniotic fluids were low before 120 days of gestation (0.17 +/- 0.03 mug/100 ml; mean and SEM) concentration between 124 and 152 days was 0.33 +/- 0.03 mug/100 ml. T4 concentrations in allantoic fluid were relatively high before 120 days (0.57 +/- 0.1 mug/100 ml) and did not increase with progression of the pregnancy...

Allantois↗

3,3',5'-Triiodothyronine (reverse T3) and 3,3',5-triiodothyronine (T3) in fetal and adult sheep: studies of metabolic clearance rates, production rates, serum binding, and thyroidal content relative to thyroxine.

To examine the mechanism(s) responsible for high serum concentration of 3,3',5'-triiodothyronine (reverse T3, rT3) and low serum concentration of 3,3',5-triiodothyronine (T3) in the fetus, we studied metabolic clearance rates (MCR) and production rates (PR) of rT3, T3, and thyroxine (T4) in adult nonpregnant sheep and sheep fetuses in utero. The mean fetal MCR-rT3 was significantly lower than that in adult sheep, and the mean fetal PR-rT3 significantly higher. The mean fetal MCR-T3 was higher than, and the mean fetal PR-T3 similar to that in adult sheep. The mean fetal MCR-T4 and PR-T4 were both significantly higher than the corresponding values in adult sheep. The ratios of mean PR-rT3 to PR-T4 (rT3/T4) were similar in fetal and adult sheep. However, the ratio of mean PR-T3 to PR-T4 (T3/T4) in the fetal sheep was much lower than that in the adult sheep. The low fetal MCR-rT3 was not attributable to high serum binding of rT3. On the basis of the thyroidal content and kinetics of iodothyronines, it was estimated that whereas thyroidal secretion may account for nearly all of serum T3 (or PR-T3) in the fetus and about 50% of serum T3 in adults, it accounts for only about 3% of the serum rT3 (or PR-rT3) in both fetal and adult sheep. The results suggest a) that elevated serum rT3 in the fetus is due to its decreased clearance and increased production by mono-deiodination of T4, and b) that low serum T3 in the fetus is due to its increased clearance and decreased production by mono-deiodination of T4. In addition, on the basis of discordant changes in the production of T3 and rT3 from T4, it appears that there may exist two separate, apparently specific, iodothyronine deiodinating activities--one cleaving the iodine atom at the 5'-position and the other acting in the iodine atom at the 5-position of the T4 molecule; 5'-iodothyronine deiodinating activity is apparently reduced in the fetus.

Aging↗

An unusual presentation of pancreatic carcinoma in childhood.

Carcinoma of the pancreas is rare in the pediatric population, with only 58 cases described in subjects under 16 years of age. The clinical presentation generally consists of abdominal pain and mass. We present a case of carcinoma of the pancreas in an 11-year-old girl, with abdominal pain and unusual behavior.

Abdomen↗