Biomedical subjects

I H Gewolb

Publications and source records attributed to I H Gewolb.

At least 19 recordsLinked to original sources

PubMed1999

Hepatitis B vaccination of premature infants: a reassessment of current recommendations for delayed immunization.

OBJECTIVE: Current American Academy of Pediatrics and United States Public Health Service Immunization Practices Advisory Committee recommendations for hepatitis B immunization in premature infants weighing <2 kg at birth born to hepatitis B surface antigen (HBSAg)-negative mothers are to delay the initiation of vaccination until such infants reach 2 kg or until 2 months of age. This proposal to delay vaccination at birth in these low-risk infants was based on limited studies not conducted in the United States. We sought to reassess current recommendations to delay administration of hepatitis B vaccine in low-risk premature infants by determining the immunogenicity of early hepatitis B vaccination in a US population and identifying variables associated with poor immunogenicity. METHODS: A total of 148 infants <37 weeks' gestation born to mothers negative for HBSAg were recruited at birth and stratified to three birth weight groups: <1000 g, 1000 to 1500 g, and >1500 g. Recombinant hepatitis B vaccine was administered within the first week of life, at 1 to 2 months of age, and at 6 to 7 months of age. Serum obtained at birth and after the second and third doses of vaccine was tested for antibody to HBSAg. Variables associated with poor response were sought prospectively by collecting demographic and clinical data. RESULTS: A total of 118 subjects (83%) completed the study. Postsecond dose sera were available for 117 infants and postthird dose sera were available for 112 infants. The seroprotection rate (attaining >/=10 mIU/mL HBS antibody) after two doses was low (25%) regardless of birth weight; infants weighing <1000 g at birth had the poorest response (11%). The seroprotection response rate after three doses of vaccine increased with birth weight; infants weighing </=1500 g at birth (groups 1 and 2) had lower rates of response (52% and 68%, respectively) than did infants weighing >1500 g at birth (group 3; 84% response rate). The seroprotection response rate of group 3 infants after three doses of vaccine, although low, could not be differentiated from the response rates reported for full-term infants using 95% confidence intervals. Of all infants who did not achieve protective levels of antibody after three doses of vaccine, 96% (26/27) weighed <1700 g at birth. The geometric mean HBS antibody levels in responders were 88 and 386 mIU/mL after two and three doses, respectively. Of 36 children with a birth weight >1500 g, 33 (91%) achieved levels of HBS antibody >100 mIU/mL after three doses of vaccine, compared with 25/35 (71%) of infants with birth weight <1500 g. Using logistic regression analysis, nonresponders were more likely than were responders to have been treated with steroids (26% vs 9%) and to have had a low birth weight (1037 g vs 1455 g). In addition, the seroresponse rate of black infants was more likely than that of white infants to be associated with poor weight gain (falling off 2 percentile ranks in weight) in the first 6 months of life: 22% of black and 60% of white children who failed to gain weight adequately responded to vaccination, compared with 92% of black and 70% of white children who were growing adequately. Of interest, the only infant with a birth weight of >1700 g who did not make protective levels of specific antibody after three doses of vaccine was 2300 g at birth, but had inadequate weight gain in the first 6 months of life. CONCLUSIONS: This study supports current recommendations of the American Academy of Pediatrics and the Centers for Disease Control and Prevention for delaying the initiation of hepatitis B immunization beyond the first week of life for premature infants at low risk for hepatitis B infection, particularly in newborns weighing <1700 g at birth. In addition, we have identified variables other than birth weight that were associated with an inadequate immune response to early hepatitis B vaccination in premature infants, such as poor weight gain in the first 6 months of life

Analysis of Variance↗

PubMed1998

Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology.

The insulin-like growth factor-I receptor (IGF-IR) mediates the biological actions of IGF-I and IGF-II. The IGFs play a critical role in promoting development, stimulating growth and organogenesis via mitogenic, antiapoptotic and chemotactic activity. Recent research has focused on the events that occur intracellularly upon receptor activation. Several pathways have been shown to be important. The insulin-receptor substrate (IRS), SHC, GRB2, CRKII and CRKL adaptor proteins have all been implicated in transmitting signals to the nucleus of the cell. This review outlines some of the signalling pathways believed to be important in converting IGF-IR activation into changes in cell behavior and metabolism.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome.

OBJECTIVES: To examine the safety and pharmacokinetics of multiple intratracheal (IT) doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome who are at risk for developing bronchopulmonary dysplasia (BPD). Methods. Thirty-three infants (700 to 1300 g) were randomized and blindly received saline, 2.5 mg/kg or 5 mg/kg rhSOD IT within 2 hours of surfactant administration. Infants were treated every 48 hours (as long as endotracheal intubation was required) up to 7 doses. Serial blood and urine studies, chest radiographs, neurosonograms, SOD concentration and activity measurements, and tracheal aspirate (TA) inflammatory markers were assessed throughout the 28-day study. RESULTS: SOD concentrations in serum (0.1 [0.05/0.15] microg/mL-geometric mean with lower/upper confidence intervals), tracheal aspirates (TA) (0.2 [0.1/0.3] microg/mL) and urine (0.3 [0.2/0.4] microg/mL) were similar at baseline in all 3 groups and did not change significantly in the placebo group. In the rhSOD treatment groups, SOD concentrations were increased on day 3 and did not change significantly thereafter over the 14-day dosing period (also measured on days 5, 7, and 13). SOD concentrations averaged 0.4 [0.3/0.5] microg/mL in serum, 0.8 [0.6/1.2] microg/mL in TA and 1.1 [1.0/1.3] microg/mL in urine for the low-dose group and 0.6 [0.5/0.7] microg/mL in serum, 1.1 [0.9/1.5] microg/mL in TA, and 2.2 [1.6/2.9] microg/mL in urine for the high-dose group over the 14-day dosing period. Enzyme activity directly correlated with SOD concentration and rhSOD was active even when excreted in urine. TA markers of acute lung injury (neutrophil chemotactic activity, albumin concentration) were lower in the rhSOD agroups compared with placebo. No significant differences in any clinical outcome variable were noted between groups. CONCLUSIONS: These data indicate that multiple IT doses of rhSOD increase the concentration and activity of the enzyme in serum, TA and urine, reduce TA lung injury markers and are well-tolerated. Further clinical trials examining the efficacy of rhSOD in the prevention of BPD are warranted.

Analysis of Variance↗

PubMed1996

Escherichia coli transcytosis in a Caco-2 cell model: implications in neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a serious gastrointestinal disorder of preterm infants. Other than an association with prematurity and gastrointestinal feeding, no single factor or mechanism has been consistently linked to this disease. We have previously demonstrated that Escherichia coli isolates obtained from the stool of infants with NEC caused NEC-like injury in a weanling rabbit ileal loop model; this injury, in turn, could be blocked by coinfection with selected Gram(+) bacteria (Enterococcus faecium) isolated from asymptomatic controls. Using Caco-2 cells in a trans-well system, we now demonstrate that the same E. coli isolates can cross epithelial cell monolayers in the absence of ultrastructural change or damage. These results with E. coli contrast with those seen with Salmonella typhimurium, which passed through the monolayer at a higher rate and were associated with striking ultrastructural damage. Transcytosis of E. coli was reduced 3-5-fold in the presence of E. faecium previously shown to block NEC-like injury in the loop model. There was a mild increase in the rate of E. coli transcytosis when studies were conducted with younger, undifferentiated cells; these immature cells had no brush border, had decreased production of brush border-specific enzymes, but retained well defined tight junctions, as demonstrated by transepithelial electrical resistance and electron microscopy. A further reduction/ complete blockage of E. coli transcytosis was observed when E. faecium was used as the coinfectant in studies with these undifferentiated cells. We hypothesize that the ability of E. coli to cross epithelial cell layer is a critical initial step in the cascade of events which lead ultimately to NEC; blockage or reduction in E. coli transcytosis in the presence of certain Gram(+) organisms may play a significant role in prevention of NEC.

Analysis of Variance↗

PubMed1995

High glucose inhibits maturation of the fetal lung in vitro. Morphometric analysis of lamellar bodies and fibroblast lipid inclusions.

BACKGROUND: High glucose levels inhibit fetal lung maturation in vitro, consistent with the increased incidence of respiratory distress syndrome in diabetic gestation. Lung fibroblast neutral lipid stores may preferentially provide substrate to type II cells for surfactant phospholipid synthesis. EXPERIMENTAL DESIGN: To analyze the impact of high glucose on fetal lung morphology and on fibroblast neutral lipid stores, 20-day fetal rat right upper lobe lung explants were cultured in F-12 medium with final glucose concentrations of 10 mM or 100 mM and were examined by electron microscopy. RESULTS: Decreased numbers of type II pneumocytes/alveolar lining cell (0.19 +/- 0.04 versus 0.34 +/- 0.04; p < 0.05) and lamellar bodies/alveolar lining cell (0.48 +/- 0.13 versus 0.97 +/- 0.14; p < 0.05) were noted in the high glucose-treated explants. Lamellar bodies in potential airspaces were also significantly decreased in the high glucose group. Type II cell glycogen stores were increased in the glucose-treated group. The ratio of lamellar bodies in type II cells to lipid inclusions in adjacent fibroblasts was decreased in glucose-treated explants (0.23 +/- 0.09 versus 0.93 +/- 0.33 in controls; p < 0.01) as was the ratio of the total areal density of lamellar bodies to lipid inclusions in adjacent fibroblasts (2.78 +/- 0.24 versus 4.44 +/- 0.58; p < 0.01). Although the number of lipid inclusions/fibroblast and of fibroblasts/alveolar lining cell did not differ between the two groups, the size of fibroblast lipid inclusions was significantly greater in the high glucose-treated lungs (0.79 +/- 0.12 versus 0.45 +/- 0.04 microM 2; p < 0.02), resulting from a subpopulation of large lipid inclusions measuring > 1 microM 2. CONCLUSIONS: These data confirm our previous biochemical results indicating an adverse effect of high glucose on fetal lung surfactant metabolism in vitro and are suggestive of a block in the trafficking of lipids from fibroblasts to type II cells under these conditions. This block may be involved in the pathogenesis of the delay in fetal lung development observed in the diabetic pregnancy.

Animals↗

PubMed1994

High glucose and insulin decrease fetal lung insulin receptor mRNA and tyrosine kinase activity in vitro.

Specific insulin binding by the fetal lung insulin receptor is reduced in vitro by a combination of high glucose and insulin. Using 19-22 day fetal rat lung, we studied the effect of culture for 48 hours under conditions of low (10mM) and high (100mM) glucose with and without added insulin on insulin receptor tyrosine kinase activity, mRNA abundance, and glucose uptake. Culture in high glucose + insulin reduced tyrosine kinase activity to 77.2 +/- 5.2% of control values (p < .001); high glucose or insulin alone had no effect. Insulin-receptor mRNA abundance was reduced by high glucose + insulin to 37 +/- 6% of control values (p < .05). Again, no significant differences were seen with high glucose or insulin alone. Uptake of 3H-2-deoxy-glucose by explants cultured under high glucose + insulin conditions was also significantly reduced. These data indicate that down-regulation of fetal lung insulin receptors by high glucose + insulin occurs at the pre-translational level and that glucose transport is adversely affected under these conditions. Down-regulation of lung insulin receptors late in fetal life may limit the availability of glucose as substrate for surfactant synthesis in the perinatal period and may partially explain the increased incidence of respiratory distress syndrome in infants of poorly controlled diabetic mothers.

Animals↗

PubMed1994

Occurrence of necrotizing enterocolitis may be dependent on patterns of bacterial adherence and intestinal colonization: studies in Caco-2 tissue culture and weanling rabbit models.

Necrotizing enterocolitis (NEC) is one of the leading causes of death in neonatal intensive care units. The underlying pathophysiology of NEC is poorly defined, although there is a suggestion that bacterial agents play an important role in the process. In this study, we evaluated bacterial isolates from 17 NEC cases and matched asymptomatic control infants. Isolates from NEC patients were no more likely than control isolates to be adherent to enterocytes, as assessed by a Caco-2 cell tissue culture model. Adherent Escherichia coli isolates, from both NEC cases and controls, were able to cause pathologic changes typical of NEC in a weanling rabbit ileal loop model. Adherence of E. coli strains to Caco-2 cells, and subsequent production of disease in weanling rabbits, could be blocked by coinfection with Gram-positive isolates from control children. In contrast, in three of four instances, adherent E. coli from NEC cases retained their adherence and caused illness in rabbits when coinfected with Gram-positive isolates from the homologous child. Our data suggest that patterns of intestinal adherence, as influenced by the underlying intestinal microbial ecology, play a role in the pathophysiology of NEC.

Animals↗

PubMed1994

Endemic necrotizing enterocolitis: lack of association with a specific infectious agent.

We conducted a comprehensive analysis of bacterial, parasitic and viral agents present in stool samples of 23 necrotizing enterocolitis cases and 23 matched and 10 random controls. Enterococcus spp., Staphylococcus epidermidis, and Escherichia coli were the most common aerobic bacterial species isolated. Astrovirus was identified in a stool sample from one control. Eight infants were bacteremic; in 7 of 8 the same organism was also present in the stool. No one bacterial species or strain (as identified by plasmid profile analysis) was associated with occurrence of illness. Plasmid analysis further suggested that each infant was colonized with his or her own distinctive aerobic bacterial flora. With the exception of isolates from two control patients which hybridized with a probe for diffuse adherence, no diarrheagenic E. coli was identified. Five (45%) of 11 case infants were colonized with coagulase-negative staphylococci (all S. epidermidis) that produced delta-hemolysin in vitro, as compared with 13 (87%) of 15 control infants. Necrotizing enterocolitis was not associated with an increased ability to ferment carbohydrate, as measured by in vitro beta-galactosidase activity. Our data do not support the hypothesis that endemic necrotizing enterocolitis in our institution is caused by a single infectious agent, nor was there evidence that previously proposed virulence mechanisms such as production of delta-hemolysin or increased in vitro carbohydrate fermentation play a critical role in disease occurrence.

Bacteriological Techniques↗

PubMed1993

High glucose causes delayed fetal lung maturation as measured by fluorescence anisotropy.

Fluorescence anisotropy has been used to estimate the microviscosity of the surfactant phospholipid bilayer and no predict fetal lung maturity in human amniotic fluid; its usefulness in in vitro systems has been recently demonstrated. To investigate the effect of high glucose on lung development, anisotropy measurements were performed on 20-day fetal rat lung explant homogenates and culture media after culture for 48 hours in medium containing final concentrations of 10, 50, and 100mM glucose. Anisotropy of lung tissue cultured in 100mM glucose was significantly increased when compared to those cultured in 10mM glucose (p < .01). After 48 hours, the media from samples grown in 100mM glucose had significantly higher anisotropy (.2210 +/- .0031) than did media from explants grown in 50mM glucose (.2027 +/- .0079; p < .05), or in 10mM glucose (.1886 +/- .0046; p < .001). Relative fluorescence intensity of explants grown in 100mM glucose was 74.4 +/- 5.7% of those grown in 10mM glucose (p < .01). Fluorescence intensity of media was also decreased by 15-30% under higher glucose considerations (p < .05). These data suggest that surfactant synthesized and secreted under high glucose conditions, such as exist in the infant of the diabetic gestation, may have qualitative as well as quantitative changes.

Animals↗

PubMed1993

Reversal of lung maturational delay in the fetus of the diabetic rat using triiodothyronine or dexamethasone.

Administration of glucocorticoids and thyroid hormone can accelerate fetal lung development. To investigate whether the delayed fetal lung maturation seen in the diabetic rat gestation could be reversed by dexamethasone (DEX) or triiodothyronine (T3), control and streptozotocin-diabetic dams were injected daily from day 18 of gestation with either saline, 0.5 mg/kg DEX, or 1 mg/kg T3 until sacrifice on day 21 or day 22. While DEX did not change glucose levels in diabetic animals, T3 resulted in a slight reduction in both maternal (474 +/- 25 vs. 539 +/- 17 mg%; p < 0.07) and fetal (354 +/- 43 vs. 404 +/- 26 mg%; p < 0.05) serum glucose concentrations. DEX therapy exaggerated the reduction in body and lung weight seen in fetuses of streptozotocin-diabetic dams. Fetal lung phosphatidylcholine and disaturated phosphatidylcholine levels were significantly reduced in saline-treated diabetic animals as compared with controls. However, fetuses of T3- or DEX-treated diabetic rats had significantly increased lung phosphatidylcholine and disaturated phosphatidylcholine levels were significantly reduced in saline-treated diabetic animals as compared with controls. However, fetuses of T3- or DEX-treated diabetic rats had significantly increased lung phosphatidylcholine and disaturated phosphatidylcholine levels as compared with fetuses of untreated diabetic rats; these data suggest that maternal DEX or T3 therapy reverses the delayed fetal lung maturation seen in the diabetic rat gestation. Since glucocorticoids can exacerbate maternal diabetes, treatment with thyroid hormone may be more appropriate, although risks must be weighed against potential benefits.

Animals↗

PubMed1992

The relationship between rhythmic swallowing and breathing during suckle feeding in term neonates.

Little is known of the development of efficient coordination between suckle feeding and breathing in human infants. To establish baseline data, we recorded breathing and swallowing activity during bottle feeds in 23 infants at 14-48 h postnatal age. Most swallows (overall mean 68%) were organized into runs, with intervals starting at 0.6-0.8 s and slowing to 1-1.3 s after 30-40 s. The proportion of run swallows to total swallows increased significantly with age. Swallow intervals were regular (coefficient of variation = 18-38%) compared with breathing (coefficient of variation = 50%). Both breathing rate and tidal volume were significantly reduced by the onset of suckle feeding, and the pattern of respiratory airflow became markedly irregular. Mild transient desaturation was common, but was not accompanied by changes in heart rate. Swallows could occur in all phases of breathing. Overall, equal numbers of swallows were preceded by expiration and inspiration, but twice as many were followed by expiration compared with inspiration. Swallows were classified by the respiratory phases both preceding and following the swallow. Swallows occurred in all possible classifications in each of the infants studied. The incidence of the most frequent classification (inspiration-swallow-expiration), was 24% overall (individual range 5-50%). The phase relation between swallows and breaths changed frequently but showed occasional short periods of stability during which the breathing became regular and tidal volume increased. We conclude that at less than 48 h the normal infant has little coordination between swallowing and breathing rhythms and maintains rhythmic swallowing at the expense of eupnea.

Bottle Feeding↗

PubMed1986

Fetal and maternal corticosterone and corticosteroid binding globulin in the diabetic rat gestation.

Delayed fetal lung development is a feature of the diabetic pregnancy. Since fetal glucocorticoids are important in the regulation of lung maturation, we measured corticosterone and corticosteroid-binding globulin binding capacity in streptozotocin-diabetic pregnant rats and their fetuses. Previous studies have demonstrated delayed fetal lung maturation in this animal model. In control fetuses, total corticosterone concentration increased through day 20 of gestation, then declined until day 22 (term). The unbound steroid, which accounted for 5-10% of the total, increased approximately 3-fold from day 18 to term. Corticosteroid-binding globulin binding capacity peaked on day 19 after which it decreased. Maternal total and unbound corticosterone levels and corticosteroid-binding globulin binding capacity remained relatively constant throughout the final week of normal gestation. When compared to controls, fetuses from diabetic pregnancies had significantly lower total corticosterone from day 19 through 22. Corticosteroid-binding globulin binding capacity was also significantly decreased in these fetuses for the last 4 days of gestation. Similar differences were noted in maternal samples. However, no significant differences in unbound, biologically active, corticosterone were seen when diabetic and control groups were compared. Thus, delayed fetal lung maturation observed in fetuses of streptozotocin-diabetic rats is associated with a decrease in total circulating corticosteroid levels late in gestation. However, since unbound corticosteroid levels were similar in fetuses of control and diabetic animals, it is likely that other mechanisms may be responsible for the observed delay in lung development in fetuses of diabetic pregnancies.

Animals↗

PubMed1986

Fine structural abnormalities of the placenta in diabetic rats.

In the streptozocin-induced diabetic rat, the placenta is larger and the fetus is smaller than normal. To study cellular differences that might contribute to the size and functional disparity between diabetic and control placentas, a light- and electron-microscopic analysis was performed on 14-, 18-, and 22-day (term) control and diabetic placentas. Diabetic placentas, especially later in gestation, were marked by the presence of large numbers of glycogen-distended cells in the basal zone. Within the placental labyrinth, the trophoblastic layers of the interhemal membrane were significantly thicker in the diabetic placentas on days 18 and 22, and large accumulations of liid droplets were present, especially in the inner two trophoblastic layers. In normal placentas there is a marked thinning of the placental barrier in the labyrinth by day 22 of gestation, making the thickness of the labyrinthine layers in age-matched diabetic placentas even more impressive. Finally, the labyrinth of 22-day diabetic placentas contained more glycogen and rough endoplasmic reticulum in the inner trophoblastic layer, a feature that is found in less-mature (18-day) control placentas. Thus, the diabetic placentas have a number of features that are consistent with functional immaturity/dysmaturity. Cytologic evidence confirms the presence of increased glycogen and lipid reserves in both the junctional zone and the cellular area between maternal and fetal blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Delayed pulmonary maturation in the fetus of the streptozotocin-diabetic rat.

Pulmonary maturation was studied in fetuses in streptozotocin-diabetic rats on the final four days of gestation. Diabetes was induced prior to conception by the intravenous injection of streptozotocin. Fetuses were hyperglycemic but did not manifest hyperinsulinemia. Whole lung total phospholipid, phosphatidylcholine, and disaturated phosphatidylcholine were significantly decreased in the diabetic group on day 21 (term = 22 days), but not prior to or after that point in gestation. Morphologic analysis also revealed a decreased number of type II cells and lamellar bodies per alveolar lining cell in the diabetic group only on day 21, coincident with the changes in phospholipid analysis. Activities of enzymes involved in fetal pulmonary phospholipid synthesis were measured to see if differences could account for the observed developmental delay. No significant differences between diabetic and control lungs were noted in any of the enzymes studied from days 20-22, with the exception of an increase in cholinephosphate cytidylyltransferase activity in the diabetic fetuses on day 22. Immaturity in both biochemical and morphologic indices of lung development was present at a specific time late in the diabetic rat gestation. This maturational delay could not be accounted for by changes in the activities of enzymes involved in phospholipid synthesis. The fetus of the streptozotocin-diabetic rat provides a useful model to study the effects of hyperglycemia on fetal lung development.

Animals↗

PubMed1985

Creatine kinase brain isoenzyme: relationship of cerebrospinal fluid concentration to the neurologic condition of newborns and cellular localization in the human brain.

Immunocytochemical study of human brain showed creatine kinase brain isoenzyme (CKBB) present in both neurons and astrocytes. Because creatine kinase brain isoenzyme is an intracellular enzyme that might be released with brain injury, its concentration in the CSF of newborns was measured using a radioimmunoassay. Infants who suffered a documented neurologic insult (a cerebroventricular hemorrhage or a CNS infection) were found to have a greater mean CSF creatine kinase brain isoenzyme concentration than those without a history of neurologic insult. Infants with a high concentration had a poor short-term outcome (death or neurologic abnormality when discharged) more frequently than did those with a lower concentration. Infants with a grade 3 or 4 cerebroventricular hemorrhage had a higher mean concentration than did those with a grade 1 or 2 hemorrhage. These data are consistent with the hypothesis that CSF creatine kinase brain isoenzyme is a metabolic indicator of brain damage in newborns.

Astrocytes↗

PubMed1984

Glucocorticoid-thyroid hormone interactions in fetal rat lung.

Previous studies have shown that triiodothyronine (T3) enhances the effect of dexamethasone on phosphatidylcholine (PC) synthesis in organ cultures of fetal rat lung. The aim of this study was to investigate whether similar interactions occurred in vivo and to explore possible mechanisms for this phenomenon. Injection of 7.0 mg/kg T3 into pregnant rats on d 18 and 19 of gestation resulted in a mean fetal serum T3 level of 2380 ng/dl on d 20 (control, 84 ng/dl) and in maximal (34%) stimulation of choline incorporation into PC. Injection of 1.0 mg/kg betamethasone using the same protocol as for T3 resulted in maximal stimulation of 33% and administration of both hormones together produced a 69% increase, an additive affect. The percentage of PC that was disaturated was increased with betamethasone, but decreased with T3. Betamethasone treatment resulted in an increase in the whole lung disaturated PC content, but treatment with T3 did not. Betamethasone administration also increased fetal serum T3 levels, but T3 injection did not produce elevated fetal serum corticosterone levels. Injection of T3 in vivo, or exposure of explants of 18-d fetal lung to 100 nm T3 for up to 48 h did not result in an increase in cytoplasmic glucocorticoid binding or nuclear translocation of the receptor steroid complex. Exposure of explants to glucocorticoid or T3 in vivo or in culture (dexamethasone, 100 nM and T3, 100 nM; for 48 h) resulted in a significant increase in the activity of cholinephosphate cytidylyltransferase, an enzyme in the choline incorporation pathway of PC synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Placental growth and glycogen metabolism in streptozotocin diabetic rats.

Placental glycogen metabolism was investigated in rat pregnancies complicated by streptozotocin-induced diabetes mellitus. Both diabetic and control placentas had increasing glycogen concentration from day 14 to day 16, after which glycogen concentration declined rapidly. The diabetic placentas had significantly elevated glycogen concentration when compared to controls from day 16 through term (day 22). Near term, when control glycogen content fell close to zero, the diabetic placentas still had appreciable glycogen levels. Total phosphorylase activity in the diabetic placentas was significantly higher than control values from day 16-22. Phosphorylase A activity, however, was lower in the diabetic placentas late in gestation, corresponding to the increased glycogen concentration seen at that time. Diabetic placentas had increased total synthase activity on the final 3 days of gestation, although synthase A activity was lower than corresponding control values. The placentas in this model are markedly increased in size late in gestation. No difference in protein concentration or protein/DNA ratio was noted. Total DNA content per placenta was significantly increased in the diabetic placentas after day 16 when compared to controls. Placental DNA in the diabetics continued to increase until day 18-19 of gestation, whereas DNA content in control placentas remained constant after day 16. Thus, the diabetic placentas apparently continue the process of DNA replication after DNA synthesis is complete in the controls.

Animals↗

PubMed1983

Prenatal diagnosis of a human pseudoacardiac anomaly.

A unique case is presented of dichorionic-diamnionic twins, one of which contained a primitive heart arrested at an early stage of development and which resembled in many other respects a classic case of acardia. Lack of vascular anastomoses, the dichorionic nature of the twins, and ultrasonic evidence of independent heart rates suggest that the primary pathogenesis in acardia may be cardiac dysmorphogenesis rather than reversal of vascular flow. Ultrasonography and fetal echocardiography proved useful in delineating many of the features of the amorphous twin before delivery.

Abnormalities, Multiple↗