"Functional food" for acceleration of growth in short children born small for gestational age.

OBJECTIVE: To assess the effect of nutritional supplementation on growth in short children born small for gestational age (SGA). PATIENTS: Fifty four short but otherwise healthy children (26 boys), 6.4 +/- 1.8 years of age, were referred for growth retardation. METHODS: Following a 6 month observation period the participants were randomly allocated to receive growth hormone therapy (GH) 1.26 IU/kg/day (0.042 mg/kg/day) or nutritional program (NUT) or passive observation (OBS). Patients in the nutritional program received 10 mg/day iron, 11 mg zinc-three times a week and 10000 IU/week of vitamin A. The following parameters were obtained 3 monthly: height, weight, dietary intake and serum IGF-1. RESULTS: Six months of nutritional supplement induced growth acceleration somewhat lower than that seen in the growth hormone treated children, but significantly greater than noted in the observation group (OBS 4.6 +/- 1.3, NUT 7.9 +/- 1.7, GH 9.1 +/- 1.8 cm/yr, P<0.001). CONCLUSIONS: Six months of vitamin A, iron and zinc supplementation induces growth acceleration in short children born SGA with subnormal nutrients intake similar to growth hormone therapy.

Effects of inhaled corticosteroids and inhaled cromolyn sodium on urinary growth hormone excretion in asthmatic children.

Over the past few years there has been an increasing awareness that asthma is a chronic inflammatory airways disease. The current therapeutic strategies for treating asthma focus on suppressing the inflammatory process by using cromones or inhaled corticosteroids (ICS). The beneficial effects of ICS in asthma are now well known, but its detrimental effect on linear growth remains a controversial issue. The aim of this open label, nonrandomized, cross-sectional, one-time study was to determine the influence of these drugs on urinary growth hormone (U-GH) levels in prepubertal asthmatic children. U-GH levels were measured in 47 prepubertal asthmatic children who had been treated for at least 6 months with either ICS (beclomethasone or budesonide at a mean daily dose of 360 microg) or with 80 mg daily dose of cromolyn sodium (CrS). There were also nine healthy children who served as a control. These three groups of children were matched for age and gender ratio. The mean level of U-GH in the CrS-treated group was 2.94 +/- 0.96 ng/night; this was significantly higher compared to the mean level of the ICS-treated group (1.99 +/- 0.83 ng/night; P < 0.001) and to the mean level of the control group (1.98 +/- 0.39 ng/night; P < 0.006). There was no significant difference between the mean level of U-GH in the group treated by ICS and the controls (P < 0.9). These results show that the mean levels of U-GH secretion of the children who were treated by CrS for 6 months was significantly increased, compared to the mean U-GH level of the ICS-treated group and the controls. The mean U-GH levels in the last two groups showed no statistically significant difference.

Establishment of an in vitro bioassay and radio receptor assay for LH/CG in human sera using immortalized granulosa cells transfected with LH/CG receptor.

Levels of gonadotropic hormones in human sera or urine are routinely measured by radioimmunoassay or by enzyme-linked immunoassay (ELISA), which determine the immunoactivity of the hormone, but not its biological activity. We have utilized immortalized stable steroidogenic granulosa cells, which express 5-10 times more of the luteinizing hormone/chorionic gonadotropin (LH/CG) receptors than the primary cells, to develop a biological assay and radioreceptor assay for this hormone. We found that stimulation of cells expressing LH/CG receptor with increasing doses of human LH or human CG resulted in a dose-dependent increase of cAMP and progesterone with an ED(50) of 30 and 57 mlU/mL, respectively. These dose-response data served as calibration curves for measuring the gonadotropin bioactivity in human serum samples at concentrations as low as 1-5 mlU/mL. We found a close correlation between LH levels measured by enzyme immunoassay (EIA) and the in vitro bioassay in normal cycling and menopausal women, as well as in normal adult men. Also, a close correlation was found between the EIA and the in vitro biological assay of hCG in pregnant women. In addition, we have developed a radioreceptor assay (RRA) for this hormone using enriched cell membranes of the appropriate cell line, which corresponds well to both the EIA and the bioassay in human sera. Deglycosylated hCG was fully active in RRA, but failed to activated cAMP response in these cells, demonstrating the importance of the bioassay in the biologically inactive form of gonadotropins. We believe this novel in vitro bioassay of gonadotropic hormones will serve as a useful tool for a more comprehensive set of assays that will determine not only the amount, but also the possible modulation in bioactivity of the gonadotropin associated with gonadal failure and miscarriage.

Amniotic fluid and plasma levels of parathyroid hormone-related protein and hormonal modulation of its secretion by amniotic fluid cells.

Parathyroid hormone-related (PTHrP), the major mediator of humoral hypercalcemia of malignancy, may also regulate placental calcium flux, uterine contraction and fetal tissue development. In the present study, we demonstrated that the mean immunoreactive PTHrP concentrations in amniotic fluid at mid-gestation (21.2 +/- 3.7 pmol/l) and at term (19.0 +/- 2.7 pmol/l) were 13-16-fold higher than levels measured in either fetal (1.6 +/- 0.1 pmol/l) or maternal plasma (1.4 +/- 0.3 pmol/l) at term and equal to levels found in plasma of patients with humoral hypercalcemia of malignancy. In vitro studies pointed to three possible sources of PTHrP in amniotic fluid: cultured amniotic fluid cells, cells derived from the amniotic membrane overlying the placenta and placental villous core mesenchymal cells. Treatment of cultured amniotic fluid cells with human prolactin, human placental lactogen (hPL) or human growth hormone (100 micrograms/l) increased PTHrP secretion after 24 h by 43%, 109% and 90%, respectively. Insulin-like growth factors I and II (100 micrograms/l), insulin (100 micrograms/l) and epidermal growth factor (EGF) (10 micrograms/l) increased PTHrP secretion by 53%, 46%, 68% and 118%, respectively. The stimulation of PTHrP secretion by EGF or by hPL was both time- and dose-dependent. In contrast, calcitriol and dexamethasone (10 nmol/l) decreased PTHrP secretion by 32% and 75%, respectively. Estradiol, progesterone, dihydrotestosterone and human chorionic gonadotropin had no effect on PTHrP secretion. These findings support the notion that PTHrP may play a physiological role in the uteroplacental unit and demonstrate that human amniotic fluid cells could be a useful model for studying the regulation of PTHrP production and secretion by hormones and growth factors.

Low-dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids.

The aim of the present study was to examine the use of low-dose ACTH-(1-24) stimulation for assessment of adrenal function and the detection of mild adrenal insufficiency. The criteria for normal response to ACTH-(1-24) are a peak cortisol level of more than 500 nmol/L (18.1 micrograms/dL) and an increment of the cortisol level above the basal one of more than 200 nmol/L (7.2 micrograms/dL). These criteria were satisfied by 32 of 33 healthy children and adults subjected to an ACTH-(1-24) dose 500 times lower (0.5 micrograms/1.73 m2) than the dose of 250 micrograms in the standard test. At 20 min, the peak cortisol level was the same in the low-dose test [(621 +/- 28 nmol/L) (22.5 +/- 1.0 microgram/dL)] as in the standard ACTH test [(654 +/- 31 nmol/L) (23.7 +/- 1.1 microgram/dL)]. Of 46 asthmatic patients who had been treated with inhaled beclomethasone dipropionate (482 +/- 42 micrograms/m2 daily; n = 32) or budesonide (507 +/- 62 micrograms/m2 daily; n = 14) for over 6 months, 16 (35%) failed to reach a cortisol peak of more than 500 nmol/L (18.1 micrograms/dL) following stimulation with 0.5 micrograms ACTH-(1-24)/1.73 m2. Of these, 11 (24%) showed a cortisol increment of less than 200 nmol/L (7.2 micrograms/dL). These 16 patients, showing insufficient response to low-dose ACTH-(1-24), also had a significantly lower (P < 0.01) mean 24-h urinary free cortisol excretion [(71 +/- 10 nmol/m2.24 h) (25.7 +/- 3.6 micrograms/m2.24 h)] than patients who responded normally [(118 +/- 11 nmol/m2.24 h) (42.8 +/- 4.0 micrograms/m2.24 h). Nonetheless, all but one of the poor responders to a 0.5 microgram ACTH showed normal stimulation with the standard 250 micrograms ACTH test. Therefore, it appears that a low-dose ACTH test is capable of revealing mild adrenal insufficiency, which is not detected by the standard high-dose ACTH test.

[Decreased interleukin-1 and interleukin-2 production after splenectomy].

Production of interleukin-1 and of interleukin-2 was measured in 57 splenectomized patients. 11 of them were after elective operations (aged 14-37 years, mean 24) and 46 posttraumatic (aged 20-36, mean 23) and in 20 appropriate controls. There was significant reduction of both interleukins in the splenectomized group, more evident in the elective group. The deficiency was not related to age of patient or time since splenectomy. These results support the view that a consequence of splenectomy is immunoregulatory deficit.

Prolactin release from perifused human decidual explants; effects of decidual prolactin-releasing factor (PRL-RF) and prolactin release-inhibitory factor (PRL-IF).

The dynamics of prolactin release from human decidual explants were studied under basal conditions, in response to decidual prolactin-releasing factor (PRL-RF), and in response to PRL-RF in the presence of decidual prolactin release-inhibitory factor (PRL-IF) or other factors known to inhibit prolactin release in static cultures. Explants were perifused with medium at a rate of 6 ml/h, and the medium was collected at 5 min intervals. The explants released prolactin for up to 20 h without evidence of cell necrosis, with the rate of prolactin decreasing gradually from 3.9 +/- 0.1 ng/5 min during the first 2 h to 2.2 +/- 0.1 ng/5 min during the last 2 h of exposure. PRL-RF, a 23.5 KMr protein released by the placenta, stimulated a dose-dependent increase in prolactin release from the perifused explants that occurred within the first 5 min of exposure and persisted until the exposure to the releasing factor was discontinued. PRL-IF, a 35-45 K Mr protein released by the decidua, caused a dose-dependent inhibition of PRL-RF-mediated prolactin release. Dibutyryl cAMP, cholera toxin, sn-1, 2-dioctonylglycerol, PMA, and arachidonic acid, which inhibit basal prolactin release from static decidual cultures, also caused a dose-dependent inhibition of prolactin release in response to PRL-RF. In each instance, the maximal dose of the agents tested inhibited PRL-RF-mediated prolactin release by greater than 84 per cent. These results indicate that the stimulation of prolactin by PRL-RF is inhibited by PRL-IF and pharmacologic agents that inhibit basal prolactin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin stimulates the synthesis and release of prolactin from human decidual cells.

Insulin-like growth factor I (IGF-I) and insulin have been implicated in the regulation of differentiated functions in many cells. We have reported that IGF-I stimulates the release of decidual PRL, acting through the type I IGF receptor (1). To determine whether insulin regulates the synthesis and secretion of decidual PRL, monolayer cultures of human decidual cells were exposed to insulin at concentrations ranging from 10 ng to 10 micrograms/ml for up to 5 days. Insulin stimulated a dose-dependent increase in PRL release (half-maximal concentration, 50 ng/ml), beginning 48 h after initial exposure. Insulin-exposed cells released 62 +/- 2% (mean +/- SEM), 97 +/- 3% and 82 +/- 6% more PRL than control cultures on days 3, 4, and 5, respectively. Insulin also stimulated de novo PRL synthesis. During the final 24-h culture period, insulin-exposed cells released 73 +/- 7% more immunoprecipitable [35S]-methionyl PRL than control cells, comparable to the 60 +/- 7% increase in PRL (by RIA) during the same period. Insulin effects were relatively specific to PRL, since insulin had a much smaller effect on the synthesis of total trichloroacetic acid-precipitable proteins. Additionally, insulin had no significant effect on cell number, total DNA, or total cellular protein. Specific and saturable insulin-binding sites were observed in decidual cells, and polyclonal antibodies to the insulin receptor acted as insulin agonists, stimulating an increase in PRL release comparable to that produced by insulin alone. These observations suggest that the responses to insulin are mediated through the insulin receptor. Furthermore, our studies suggest that insulin may have a role in the regulation of PRL synthesis and release from human decidua.

Superoxide dismutase activity in the erythrocyte of the term newborn and premature.

Superoxide dismutase (SOD) activity was determined in the erythrocytes of 16 full-term and 12 preterm neonates and the mothers of these babies. Blood samples were obtained from the umbilical cord (or within the first 12 h and samples were again obtained 48 h after delivery. The results of the study show that SOD activity in the erythrocytes of the full-term newborn is identical to the SOD activity in the erythrocytes of their mothers. Exposing the newborn to atmospheric oxygen for 48 h caused no change in the activity of SOD. The activity of SOD in the erythrocytes of the preterm was not different from that of the full-term neonate.

Tuftsin stimulates IL-1 production by human mononuclear cells, human spleen cells and mouse spleen cells in vitro.

Human peripheral adherent cells from splenectomized subjects, human spleen cells and mouse spleen cells were tested for IL-1 production in vitro in presence or absence of synthetic tuftsin (Thr-Lys-Pro-Arg). Application of synthetic tuftsin to peripheral blood adherent cells from normal donors as well as from splenectomized subjects induces IL-1 production. In splenectomized subjects the extent of induction was more evident than in controls. In human splenic cells tuftsin stimulates IL-1 production without KLH or LPS. In mouse spleen cells tuftsin alone did not stimulate the IL-1 secretion. However, addition of tuftsin to mouse spleen cells incubated with KLH augmented significantly the IL-1 secretion. As removal of the spleen leads to tuftsin deficiency, our present findings may perhaps explain the fulminant nature of the postplenectomy sepsis and some immune disturbances described in the postplenectomy state.

Insulin-like growth factor I stimulates the synthesis and release of prolactin from human decidual cells.

Recent studies suggest a role for insulin-like growth factor I (IGF-I) in the regulation of hormone release from placental, gonadal, and pituitary tissues. To examine whether IGF-I may also regulate the release of PRL from human decidual tissue, we have investigated the effect of recombinant human IGF-I on PRL release from monolayer cultures of human decidual cells exposed to IGF-I for up to 4 days. IGF-I (10-1000 ng/ml) stimulated a sustained dose-dependent increase in PRL release (half-maximal concentration, 25 ng/ml) beginning 48 h after initial exposure, but had no effect on the intracellular PRL content. The amounts of PRL released from maximally stimulated cultures on days 3 and 4 were 168 +/- 3% (mean +/- SEM) and 258 +/- 8% of control values, respectively. IGF-I-mediated effects were inhibited by cycloheximide (3.6 microM), suggesting that the increase in PRL was the result of newly synthesized hormone. The increase in PRL release was not due to a generalized effect on protein release, since IGF-I had no effect on the release of trichloroacetic acid-precipitable [35S]methionyl proteins. Radioligand competition studies indicate that the biological actions of IGF-I are mediated through interaction with the IGF-I receptor. Binding of radiolabeled IGF-I to decidual cells in suspension was specific, saturable, and displacable by unlabeled IGF-I, with a potency nearly 10 times greater than that of insulin. Furthermore, exposure of decidual cells to a monoclonal antibody to the IGF-I receptor (alpha-IR3) completely inhibited both IGF-I-mediated PRL release and specific binding of [125I]IGF-I to decidual cells. Since the actions of IGF-I occurred at physiological concentrations, these findings strongly support a role for IGF-I in the regulation of PRL secretion by human decidua.

Prolactin stimulates creatine kinase activity and DNA synthesis in explants of human amnion.

To characterize the action of hPRL and human placental lactogen on the amnion, decidua and placenta, we examined the effects of these hormones on the brain type isozyme of creatine kinase in cultured explants of these tissues from normal deliveries. In the amnion, hPRL (1 mg/l) caused a 1.8-fold increase in creatine kinase specific activity in 24 h, whereas hGH (1 mg/l) or human placental lactogen (1 mg/l) had no effect; oPRL (1 mg/l) also caused a 2.5-fold increase in creatine kinase activity. Neither hPRL, human placental lactogen nor hGH had a significant effect on creatine kinase activity in the placenta or decidua. [3H]thymidine incorporation into DNA increased in parallel to the stimulation of creatine kinase activity. The predominant isozyme of creatine kinase in both the unstimulated and stimulated explants was the brain type isozyme. Creatine kinase activity in the amniotic tissue increased significantly 2 h after hPRL treatment and reached its highest value at 4 h. The enzyme activity in the amnion rose with increasing hPRL dose and showed a significant increase at physiologic concentrations as low as 0.01 mg/l. This study, therefore, provides evidence for biological action of prolactin in amniotic tissue, suggesting that the amnion is physiologically responsive to prolactin.

Decidual prolactin (PRL)-releasing factor stimulates the synthesis of PRL from human decidual cells.

Previous studies from our laboratory demonstrated that the acute release of PRL from human decidual tissue is stimulated by a 23.5 kilodalton placental protein which we designated decidual PRL-releasing factor (PRL-RF). To determine whether PRL-RF may also affect the synthesis of PRL and/or cause a secondary increase in PRL release, we have examined the effects of purified PRL-RF on the synthesis and release of PRL over a 96-h period. Exposure of dispersed decidual cells to PRL-RF (0.5 microgram/ml) stimulated a biphasic increase in PRL release with acute transient stimulation during the first 0.5 h and a delayed and sustained stimulation beginning about 8 h after exposure which persisted for the duration of the 96 h. The amounts of PRL released from PRL-RF-exposed cells after 0.5, 8, 12, 24, and 96 h were 321.2 +/- 36.2 (mean +/- SEM, n = 3), 110.2 +/- 5.3, 138.2 +/- 7.2, 194.5 +/- 11.2, and 201.5 +/- 14.2% that of control cells. Studies of the de novo synthesis of [35S]methionyl PRL indicated that the increase in PRL release after the first few hours of exposure to PRL-RF was secondary to an increase in PRL synthesis. Somatostatin (100 nM) inhibited the acute stimulatory effect of PRL-RF, but had no effect on the delayed stimulation of PRL release. On the other hand, cycloheximide (20 microM) completely inhibited the secondary increase in PRL release in response to PRL-RF but had no effect on the acute release. These results demonstrate that PRL-RF stimulates both the synthesis and release of decidual PRL.

Antibodies to insulin receptor followed by anti-idiotype. Antibodies to insulin in child with hypoglycemia.

A child presenting severe hypoglycemia despite low or normal secretion of insulin was found to have IgM antibodies to the insulin receptor. These antibodies stimulated lipogenesis in fat cells in vitro and competed with insulin for binding to insulin receptors. After treatment with glucocorticoids, the anti-receptor antibodies and the hypoglycemia both disappeared, and antibodies to insulin appeared in the patient's serum. The anti-insulin antibodies were isolated by affinity chromatography and were found to inhibit the anti-insulin-receptor antibodies that were present earlier. The interaction between the patient's anti-insulin antibodies and his anti-receptor antibodies suggests that these two species of antibodies are related as idiotypes and anti-idiotypes. We also studied the interaction of the hypoglycemic patient's anti-receptor antibodies with anti-insulin antibodies of a diabetic patient and with anti-insulin antibodies of mice immunized to insulin. The hypoglycemic patient's anti-receptor antibodies were neutralized by the diabetic patient's anti-insulin antibodies, indicating that anti-insulin antibodies with a common idiotype may arise in both diabetes and hypoglycemia. Moreover, mouse anti-insulin antibodies that interacted with mouse anti-receptor antibodies neutralized the hypoglycemic patient's anti-receptor antibodies. In contrast, mouse anti-insulin antibodies that did not interact with the mouse anti-receptor antibodies did not neutralize the hypoglycemic patient's anti-receptor antibodies. Thus, the human anti-insulin antibodies share an idiotype with a specific class of mouse anti-insulin antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of creatine kinase activity by calcium-regulating hormones in explants of human amnion, decidua, and placenta.

We have used stimulation of the activity of the brain type creatine kinase (CK) isoenzyme as a response marker to examine the effects of vitamin D metabolites, PTH, and calcitonin in cultured explants of placenta, decidua, and amnion from normal human deliveries. We found a biological response to PTH in placenta and amnion and to vitamin D metabolites in all three tissues. In the amnion, CK activity increased 2.3-fold after 24 h of incubation in 2.5 nM 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], 3.8-fold when incubated with 12.5 nM 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] and 2.7-fold when incubated with 10 U/ml bovine PTH. In the decidua, 24,25-(OH)2D3, but not 1,25-(OH)2D3 or bPTH caused a 1.7-fold increase in CK activity. In contrast, the placenta responded to 1,25-(OH)2D3 with a 1.6-fold increase in CK activity and to bPTH, with a 1.7-fold increase but did not respond to 24,25-(OH)2D3. Bovine calcitonin (100 ng/ml) had no effect on CK activity in any of the three tissues. Nearly all CK in both the unstimulated and stimulated explants was the brain type isoenzyme. CK activity increased significantly between 1 and 4 h after hormonal treatment in all experiments. The enzyme activity rose steeply with dose and reached a significant increase, and usually a plateau, at hormone concentrations considered to be physiological in vivo. [3H]Thymidine incorporation into DNA increased in parallel to stimulation of CK activity in all experiments, except that PTH did not increase DNA synthesis in the placenta. PTH did cause an increase in cAMP production in explants of amnion (1.5-fold) and placenta (2.6-fold).

Characterization and partial purification of a serum protein which stimulates the release of human placental lactogen in vitro.

The factors that regulate the release of human placental lactogen (hPL) are poorly understood. To determine whether hPL is regulated by a factor(s) in pregnancy serum, placental explants were exposed for up to 9 h to a pool of serum samples from 50 women in the third trimester. In static explant cultures, the addition of the serum (0.6-10.8 mg protein/ml) caused a dose-dependent and reversible increase in hPL release during a 6-h period. The maximum release by the explants exposed to pregnancy serum was 200-250% greater than that of control explants, and the half-maximal dose was 2-3 mg/ml. Perifusion of placental explants with 15% pregnancy serum (final concentration, 10.5 mg protein/ml) also caused a significant release in hPL within 15 min, which reached a maximum of 200-225% above control levels. Two other pools of pregnancy serum samples as well as individual samples from four pregnant women also stimulated hPL release. Although pregnancy serum significantly stimulated hPL release, there was no increase in either the release of hCG or trichloroacetic acid-precipitable 35S-labeled proteins. Serum from nonpregnant women and men, as well as bovine serum, also stimulated hPL release, but their potencies were only 20-25% that of pregnancy serum. Chicken and porcine serum (10.8 mg/ml each) caused only small (less than 10%) increases in hPL release, and purified human albumin and ovalbumin had no effect. Dialysis or ultrafiltration of pregnancy serum using membranes with mol wt exclusions of 10K daltons caused no loss of activity. Delipidation of pregnancy serum with acetone-ethanol or acid-charcoal also caused no loss of activity, but treatment with trypsin caused greater than 95% loss of activity. Purification of the stimulatory activity by successive chromatographies on Sephadex G-150, Cibacron blue, and Sephadex G-75 resulted in an approximately 800-fold increase in specific activity. Approximately 90% of the total activity eluted from Sephadex G-75 with an apparent mol wt of 31,000, the remainder eluted in the void volume. Although partially purified pregnancy serum stimulated hPL release, the active fractions did not affect the release of rat LH, FSH, or GH from rat pituitary cells or the release of PRL from human decidual explants. Incubation of placental explants in calcium-deficient medium blocked the stimulatory effect of the partially purified pregnancy serum by greater than 90%. These studies indicate that human serum contains a protein(s) that causes a specific, rapid, dose-dependent, and reversible increase in hPL release.(ABSTRACT TRUNCATED AT 400 WORDS)

Stimulation of creatine kinase activity in rat organs by human growth hormone in vivo and in vitro.

Intraperitoneal injection of human GH (hGH) (4 micrograms/g BW) into 21-day-old rats causes, 24 h later, an increase in creatine kinase (CK) specific activity in kidney (1.7-fold), liver (1.6-fold), and in epiphyseal cartilage (1.8-fold). Similar stimulation was obtained when tissue explants were incubated for 24 h with hGH (1 microgram/ml); CK activity rose 1.8-fold in kidney, 1.9-fold in the liver, and 2.6-fold in epiphyseal cartilage. Highly significant stimulation of CK specific activity was obtained in these same organs in hypophysectomized rats. The increase in CK specific activity in the kidney, to some extent in the liver, but not in the epiphyseal cartilage, was also obtained on in vivo treatment with either human placental lactogen or ovine PRL. Stimulation of CK in these three organs by hGH is followed by a parallel increase in DNA synthesis. Dexamethasone, which was also found to increase CK activity in rat kidney and liver, did not affect the increase of CK by hGH in the kidney, stimulated the effect of hGH in the liver, and partially inhibited the effect of hGH in the epiphyseal cartilage. Diethylaminoethyl cellulose chromatography revealed that the basal and induced activity of CK in all cases was due to the brain type isozyme. On the basis of this evidence for a direct effect of hGH on CK brain type activity, we suggest that its stimulation is potentially a convenient and sensitive assay for biological activity of GH.

Pseudohypoaldosteronism in a female infant and her family: diversity of clinical expression and mode of inheritance.

Pseudohypoaldosteronism was diagnosed in an infant that clinically presented severe failure to thrive and vomiting. Evaluation of her extended family revealed many other affected family members with a vast range of clinical expression. The mode of inheritance is most likely autosomal dominant. Salt supplementation during infancy was effective in restoring normal growth, weight gain and serum electrolytes.

Decreased prolactin secretion by decidual tissue of pre-eclampsia in vitro.

In vitro prolactin (hPrl) secretion by explants of decidual tissue was studied in pre-eclampsia and normal controls. Our results indicate diminished hPrl production by decidua of pre-eclampsia as compared to the normal controls. Incubation of normal decidual tissue in the presence of serum obtained from pre-eclamptic patients did not induce an inhibitory effect on hPrl production.