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Biomedical subjects

S E Nelson

Publications and source records attributed to S E Nelson.

At least 19 recordsLinked to original sources

Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood.

CONTEXT: A large body of evidence documents the role of phytoestrogens in influencing hormone-dependent states. Infants fed soy formula receive high levels of phytoestrogens, in the form of soy isoflavones, during a stage of development at which permanent effects are theoretically possible. However, a paucity of data exists on the long-term effects of infant soy formulas. OBJECTIVE: To examine the association between infant exposure to soy formula and health in young adulthood, with an emphasis on reproductive health. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study conducted from March to August 1999 among adults aged 20 to 34 years who, as infants, participated during 1965-1978 in controlled feeding studies conducted at the University of Iowa, Iowa City (248 were fed soy formula and 563 were fed cow milk formula during infancy). MAIN OUTCOME MEASURES: Self-reported pubertal maturation, menstrual and reproductive history, height and usual weight, and current health, compared based on type of formula exposure during infancy. RESULTS: No statistically significant differences were observed between groups in either women or men for more than 30 outcomes. However, women who had been fed soy formula reported slightly longer duration of menstrual bleeding (adjusted mean difference, 0.37 days; 95% confidence interval [CI], 0.06-0.68), with no difference in severity of menstrual flow. They also reported greater discomfort with menstruation (unadjusted relative risk for extreme discomfort vs no or mild pain, 1.77; 95% CI, 1.04-3.00). CONCLUSIONS: Exposure to soy formula does not appear to lead to different general health or reproductive outcomes than exposure to cow milk formula. Although the few positive findings should be explored in future studies, our findings are reassuring about the safety of infant soy formula.

Adult↗

Iron absorption during recovery from malnutrition.

OBJECTIVE: In infants and children recovering from severe malnutrition, iron deficiency is common, and the ability to absorb iron during such recovery is uncertain. The objective of this study was to determine iron absorption during recovery from malnutrition. METHODS: During the later stages of recovery from malnutrition, erythrocyte incorporation of orally administered 58Fe was determined as a surrogate for iron absorption. Based on four indices, subjects were classified as iron-sufficient, iron-deficient or indeterminate. RESULTS: Of the 25 subjects, 9 were classified as iron sufficient, 5 as indeterminate and 11 as iron deficient; all but 5 had evidence of inflammation or infection. Geometric mean erythrocyte incorporation of 58Fe was 32.0% of the dose in the iron-deficient subjects, which was not significantly different (p = 0.073) than the 13.1% in the iron-sufficient subjects. Incorporation of 58Fe by the iron-sufficient subjects did not differ significantly from that by normal subjects in the same age range. Surprisingly, we found no correlation of erythrocyte incorporation of 58Fe and reticulocyte count. CONCLUSIONS: Even in the presence of infection or inflammation, iron absorption by children during a late stage of recovery from malnutrition is not impaired.

Absorption↗

Atrial natriuretic peptide blockade exacerbates high altitude pulmonary edema in endotoxin-primed rats.

High altitude pulmonary edema (HAPE) is associated with increases in pulmonary arterial and hydrostatic pressures and an increase in pulmonary vascular permeability. There is evidence to suggest that inflammatory mediators may cause some forms of HAPE, and Salmonella enteritidis endotoxin (ETX) is known to activate neutrophils and inflammatory mediators, such as TNF-alpha and IL1-beta. Since HAPE has been produced in rats primed with ETX, we hypothesized that ANP release and action may ameliorate HAPE and that ANP blockade may exacerbate HAPE in ETX-primed rats exposed to high altitude (HA). Plasma ANP, right atrial ANP mRNA, and indexes of lung injury were measured in rats primed with endotoxin (ETX) (0.1 mg/kg BW, i.p.) and exposed to simulated HA (4267 m; P(B) = 440 mmHg) for either 12 or 24 h. Catheters were chronically inserted into the right carotid artery, pulmonary artery, and jugular vein for assessment of hemodynamic parameters in response to ETX and/or HA. In addition, some rats were injected with an antibody against ANP (alphaANP) prior to normoxic (NX) or HA exposure. Pulmonary arterial pressure increased in the alphaANP group (50 +/- 20%; p < or = 0.05) and in the HA + alphaANP (51 +/- 15%; p < or = 0.05) group at 12 h compared to NX sham rats injected with normal rabbit serum. In addition, systemic arterial pressure was significantly lower in the HA + ETX rats compared to HA + ETX + alphaANP rats (p < or = 0.001). Plasma ANP levels were significantly higher at 12 and 24 h in ETX, HA, and HA + ETX groups (p <or = 0.05) compared to NX controls. There was an inverse relationship (p <or = 0.001) between plasma ANP levels and lung wet to dry (W/D) weight when data from NX, ETX, HA, and HA + ETX groups were pooled. The HA + alphaANP rats had significantly higher lung W/D ratios (p < 0.001) compared to sham rats. These results support the hypothesis that ANP, at physiological levels, modulates the development of pulmonary edema in HA-exposed ETX-primed rats.

Altitude Sickness↗

Cellular mechanisms by which oxytocin mediates ovine endometrial prostaglandin F2alpha synthesis: role of G(i) proteins and mitogen-activated protein kinases.

Oxytocin stimulates a rapid increase in ovine endometrial prostaglandin (PG) F2alpha synthesis. The overall objective of these experiments was to investigate the cellular mechanisms by which oxytocin induces endometrial PGF2alpha synthesis. The objective of experiment 1 was to determine whether G(i) proteins mediate oxytocin-induced PGF2alpha synthesis. Uteri were collected from four ovary-intact ewes on Day 14 postestrus. Caruncular endometrial explants were dissected and subjected to in vitro incubation. Pertussis toxin, an inhibitor of G(i) proteins, had no effect on the ability of oxytocin to induce PGF2alpha synthesis (P > 0.10). The objective of experiment 2 was to determine whether any of the three mitogen-activated protein kinases (MAPKs), extracellular signal regulated protein kinase (ERK1/2), c-Jun N-terminal/stress-activated protein kinase (JNK/SAPK), or p38 MAPK, mediate oxytocin-induced PGF(2alpha) synthesis. Eleven ovary-intact ewes were given an injection of oxytocin (10 IU; i.v.; n = 5) or physiological saline (i.v.; n = 6) on Day 15 postestrus. Uteri were collected 15 min after injection and caruncular endometrium was dissected. Endometrial homogenates were prepared and subjected to Western blotting. Membranes were probed for both total and phosphorylated forms of all three classes of MAPK. All classes of MAPK were detected in ovine endometrium, but oxytocin treatment had no effect on the expression of these proteins (P > 0.10). ERK1/2 was the only phosphorylated MAPK detected and its concentrations were higher in oxytocin-treated ewes (P < 0.01). The objective of experiment 3 was to further investigate the role of ERK1/2 during oxytocin-induced PGF2alpha synthesis. Uteri were collected from four ovary-intact ewes on Day 14 postestrus. Caruncular endometrial explants were dissected and subjected to in vitro incubation. PD98059, a specific inhibitor of ERK1/2 activity, blocked the ability of oxytocin to stimulate PGF(2alpha synthesis in a dose-dependent manner (P < 0.05). These results indicate that the ovine oxytocin receptor is not coupled to G(i) proteins. These results indicate that oxytocin induces phosphorylation of ERK1/2 and that this MAPK appears to mediate oxytocin-induced PGF2alpha synthesis in ovine endometrium.

Animals↗

Gas production by feces of infants.

BACKGROUND: Intestinal gas is thought to be the cause abdominal discomfort in infants. Little is known about the type and amount of gas produced by the infant's colonic microflora and whether diet influences gas formation. METHODS: Fresh stool specimens were collected from 10 breast-fed infants, 5 infants fed a soy-based formula, and 3 infants fed a milk-based formula at approximately 1, 2, and 3 months of age. Feces were incubated anaerobically for 4 hours at 37 degrees C followed by quantitation of hydrogen (H2), methane (CH4), carbon dioxide (CO2), hydrogen sulfide (H2S), methanethiol (CH3SH), and dimethyl sulfide (CH3SCH3) in the head-space. RESULTS: H2 was produced in greater amounts by breast-fed infants than by infants in either formula group, presumably the consequence of incomplete absorption of breast milk oligosaccharides. CH4 was produced in greater amounts by infants fed soy formula than by infants on other diets. CO2 was produced in similar amounts by infants in all feeding groups. Production of CH3SH was conspicuously low by feces of breast-fed infants and production of H2S was high by soy-formula-fed infants. CH3SCH3 was not detected. Only modest changes with age were observed and there was no relation between gas production and stool consistency, although stools were more likely to be malodorous when concentrations of H2S and/or CH3SH were high. CONCLUSIONS: Gas release by infant feces is strongly influenced by an infant's diet. Of particular interest are differences in production of the highly toxic sulfur gases, H2S and CH3SH, because of the role that these gases may play in certain intestinal disorders of infants.

Carbon Dioxide↗

Binding of agonist but not antagonist leads to fluorescence resonance energy transfer between intrinsically fluorescent gonadotropin-releasing hormone receptors.

We have used spot fluorescence photobleaching recovery methods to measure the lateral diffusion of GnRH receptor (GnRHR) fused at its C terminus to green fluorescent protein (GFP) after binding of either GnRH agonists or antagonist. Before ligand binding, GnRHR-GFP exhibited fast rates of lateral diffusion (D = 18 +/- 2.8 x 10(-10)cm2 x sec(-1)) and high values for fractional fluorescence recovery (%R) after photobleaching (73 +/- 1%). Increasing concentrations of agonists, GnRH or D-Ala6-GnRH, caused a dose-dependent slowing of receptor lateral diffusion as well as a decreased fraction of mobile receptors. Increasing concentrations of the GnRH antagonist Antide slowed the rate of receptor diffusion but had no effect on the fraction of mobile receptors, which remained high. To determine whether the decrease in %R caused by GnRH agonists was due, in part, to increased receptor self-association, we measured the fluorescence resonance energy transfer efficiency between GnRHR-GFP and yellow fluorescent protein-GNRHR: There was no energy transfer between GnRHR on untreated cells. Treatment of cells with GnRH agonists led to a concentration-dependent increase in the energy transfer between GnRH receptors to a maximum value of 16 +/- 1%. There was no significant energy transfer between GnRH receptors on cells treated with Antide, even at a concentration of 100 nM. These data provide direct evidence that, before binding of ligand, GnRHR exists as an isolated receptor and that binding of GnRH agonists, but not antagonist, leads to formation of large complexes that exhibit slow diffusion and contain receptors that are self-associated.

Animals↗

Confirmation of confocal microscopy diagnosis of Acanthamoeba keratitis using polymerase chain reaction analysis.

BACKGROUND: Acanthamoeba keratitis has commonly been identified with in vivo confocal microscopy and confirmed with histologic examination of an epithelial biopsy specimen. OBJECTIVE: To determine if Acanthamoeba keratitis can be verified using polymerase chain reaction (PCR) of epithelial biopsy specimens. METHODS: Epithelial specimens from patients with suspected Acanthamoeba keratitis by confocal microscopy were tested for Acanthamoeba with PCR of Acanthamoeba ribosomal DNA. RESULTS: Twenty-four of 31 patients with evidence of Acanthamoeba keratitis were positive for Acanthamoeba on PCR analysis using 3 sets of primers. In 22 cases, the sequence obtained closely matched Acanthamoeba castellanii. CONCLUSIONS: This study demonstrates that PCR analysis of epithelial biopsy specimens can provide definitive verification of the confocal microscopic and histologic identification of Acanthamoeba organisms associated with keratitis. Acanthamoeba keratitis is probably quite common, especially in contact lens wearers, although more than half of the patients in this study did not wear contact lenses.

Acanthamoeba↗

Intestinal blood loss during cow milk feeding in older infants: quantitative measurements.

OBJECTIVE: To determine the response, in terms of fecal hemoglobin excretion and clinical symptoms, of normal 9 1/2-month-old infants to being fed cow milk. DESIGN: Longitudinal (before-after) trial in which each infant was fed formula for 1 month (baseline) followed by 3 months during which cow milk was fed. SETTING: Healthy infants living in Iowa City, Iowa, a town with a population of about 60,000. MAIN OUTCOME MEASURES: Hemoglobin concentration in spot stools, 96-hour quantitative fecal hemoglobin excretion, stool characteristics, feeding-related behaviors, and iron nutritional status. RESULTS: Fecal hemoglobin concentration during formula feeding (baseline) was higher than previously observed in younger infants. Nine of 31 infants responded to cow milk feeding with increased fecal hemoglobin concentration. Fecal hemoglobin concentration (mean +/- SD) of the 9 responders rose from 1,395 +/- 856 microg/g of dry stool (baseline) to 2,711 +/- 1,732 microg/g of dry stool (P=.01). The response rate (29%) was similar to that in younger infants, but the intensity of the response was much less. Quantitative hemoglobin excretion was in general agreement with estimates based on spot stool hemoglobin concentrations. Cow milk feeding was not associated with recognizable changes in stool characteristics, nor were there clinical signs related to fecal blood loss. Iron status was similar, except that after 3 months of cow milk feeding responders showed lower (P= .047) ferritin concentrations than nonresponders. CONCLUSIONS: Cow milk-induced blood loss is present in 9 1/2-month-old infants but is of such low intensity that its clinical significance seems questionable. Nevertheless, infants without cow milk-induced blood loss were in better iron nutritional status than infants who showed blood loss.

Anemia, Iron-Deficiency↗

Conceptual structure and social functions of behavior explanations: beyond person--situation attributions.

The traditional approach to studying behavior explanations involves treating them as either person causes or situation causes and assessing them by using rating scales. An analysis of people's free-response behavior explanations reveals, however, that the conceptual distinctions people use in their explanations are more complex and sophisticated than the person-situation dichotomy suggests. The authors, therefore, introduce a model of the conceptual structure of folk behavior explanations (the network of concepts and assumptions on which explanations are based) and test it in 4 studies. The modes and features of behavior explanations within this conceptual structure also have specific social functions. In 2 additional studies, the authors demonstrate that people alter distinct features of their explanations when pursuing particular impression-management goals and that listeners make inferences about explainers' goals on the basis of these features.

Adult↗

Less than 80% of absorbed iron is promptly incorporated into erythrocytes of infants.

Erythrocyte incorporation of an administered iron isotope has been used as a surrogate for iron retention on the assumption (validated in normal and iron-deficient adults) that 80-100% of the retained isotope is promptly incorporated into circulating erythrocytes. This assumption has not been validated in infants or children. The purpose of our study was to determine concurrently in normal infants absorption and erythrocyte incorporation of the stable isotope, (58)Fe. In a preliminary study (Study 1), we demonstrated that fecal excretion of ingested isotope occurs predominantly during the first 4 d after administration but continues beyond 7 d after ingestion, that is, beyond the point at which isotope in feces can be explained either by excretion of isotope that failed to enter enterocytes or by exfoliation of isotope-enriched enterocytes. In Study 2, we administered (58)Fe to nine younger (age 20-69 d) and nine older (age 165-215 d) term infants and collected feces for 11 d. Geometric mean retention of (58)Fe by the younger infants was 31.2% of intake at 4 d and 26.9% at 11 d, and by the older infants, 35.0% at 4 d and 32.5% at 11 d. Erythrocyte incorporation of (58)Fe 14 d after ingestion was 5.2% of the dose by the younger infants and 12.5% by the older infants. Utilization of retained (11 d) isotope thus was 19.8% by the younger infants and 38.3% by the older infants. We conclude that far less than 80% of retained isotope is promptly incorporated into erythrocytes (utilized) by infants.

Absorption↗

Time course of and effect of dietary iron level on iron incorporation into erythrocytes by infants.

As a part of our effort to explore various aspects of ferrokinetics in infancy, the present study was designed to determine the timing of entry of an orally ingested iron isotope into circulating erythrocytes, and the effect of the level of dietary iron [0.3 mg/100 kcal (418.4 kJ) vs. 1.8 mg/100 kcal] after isotope administration on erythrocyte incorporation of the isotope. We administered the stable isotope, (58)Fe, orally to 56-d-old and 168-d-old infants. All infants were fed a low-iron formula (LF) before and until 5 h after isotope administration. Thereafter, half the infants were fed a formula high in iron (HF group) while the remaining infants continued to receive the LF (LF group) for an additional 28 d. The quantity of (58)Fe in circulating erythrocytes increased from 14 to 28 d after isotope administration was nearly constant from 28 through 84 d of age (plateau value) and decreased between 84 and 112 d. Erythrocyte incorporation of (58)Fe was greater by the 168-d-old infants than by the 56-d-old infants, presumably because of the lesser iron stores of the older infants. In the 56-d-old infants, erythrocyte incorporation of (58)Fe was greater by the LF than by the HF group, but this difference was not significant in the 168-d-old infants. Thus, at least in younger infants, the level of iron intake after administration of an iron isotope affects erythrocyte incorporation of the isotope. The fact that less isotope was present in erythrocytes 112 d than 84 d after administration indicates that the life span of erythrocytes of infants, even beyond the immediate newborn period, is less than the 120-d life span of erythrocytes in the adult.

Administration, Oral↗

Retention of iron by infants.

Throughout the world, the most common nutritional deficiency disorder of infants is iron deficiency. Developing effective strategies for preventing iron deficiency requires detailed knowledge of iron retention under ordinary living conditions. For the adult population, such knowledge is at an advanced stage, but relatively little is known about infants. Many reports of iron retention by infants have been based on the assumption that, as in normal and iron-deficient adults, 80%-100% of newly absorbed iron is promptly incorporated into circulating erythrocytes, but this assumption is not supported by available data. This communication presents a review of iron retention by term and preterm infants, as determined by metabolic balance studies or (59)Fe whole-body counting studies, and it explores the relationship between iron retention and postnatal age, iron nutritional status, iron intake (or dose), and type of feeding.

Age Factors↗

Cow's milk and intestinal blood loss in late infancy.

OBJECTIVES: Young infants commonly show occult intestinal blood loss when fed cow's milk, but in older infants blood loss may be less common. This study examined intestinal blood loss in response to cow's milk feeding in normal 7(1/2)-month-old and 12-month-old infants. STUDY DESIGN: Infants (n = 62) were fed formula for 1 month and then pasteurized cow's milk for 2 months. Stools were collected for quantitative determination of hemoglobin. Iron nutritional status was assessed. RESULTS: Infants fed cow's milk from 7(1/2) months of age showed a significant increase in guaiac-positive stools and in stool hemoglobin concentration. These effects were largely limited to those infants who had been breast fed early in life. Infants fed cow's milk from 12 months of age at baseline had greater stool hemoglobin concentrations than 7(1/2)-month-old infants, but cow's milk produced no significant increase. In neither age group did cow's milk affect iron nutritional status. CONCLUSION: The response to cow's milk is attenuated in infants aged 7(1/2) months compared with younger infants. By 12 months of age, the response has disappeared entirely. We conclude that the gastrointestinal tract of healthy infants gradually loses its responsiveness to cow's milk.

Age Factors↗

Infant formula with protein-energy ratio of 1.7 g/100 kcal is adequate but may not be safe.

BACKGROUND: An adequate protein-energy ratio of infant formulas has been defined as one that permits growth similar to that of infants fed relatively generous protein-energy ratios, and serum concentrations of albumin and urea nitrogen no less than those observed in breast-fed infants. A safe ratio has been defined as one with no detectable adverse effects. The hypothesis was that a protein-energy ratio of 1.7 g/100 kcal is adequate and safe. METHODS: Healthy male infants were fed Formula 1.7, a milk-based formula, as the sole source of energy from the 8th to the 112th day of life. Weight, length, and energy intake were measured; serum albumin and urea nitrogen were determined; and the results were compared with data from appropriate reference groups of infants. RESULTS: Energy intake from 8 through 55 days was significantly higher than that of infants in the formula-fed reference group. Gain in weight was significantly more than that of the formula-fed reference group or of a breast-fed reference group, whereas gain in length was similar to that of the formula-fed reference group. Body mass index was significantly higher than that of either reference group, suggesting more fat accumulation in infants fed Formula 1.7. Plasma concentrations of albumin and urea nitrogen were similar to those of the breast-fed reference group. CONCLUSION: Infants fed Formula 1.7 received adequate intakes of protein. Because of the possibility that ad libitum feeding of diets with moderately inadequate protein-energy ratios is associated with increased food intake leading to excess weight gain, it is not possible to conclude that a protein-energy ratio of 1.7 g/100 kcal is safe.

Blood Urea Nitrogen↗

Absorption of fat and calcium by infants fed a milk-based formula containing palm olein.

OBJECTIVE: The study tested the hypothesis that inclusion of palm olein (45% of fat) in the fat blend of a milk-based infant formula decreases the absorption of fat and calcium. METHODS: Formula PO contained palm olein (45%) in addition to soy, coconut and high-oleic sunflower oils (20%, 20%, and 15%, respectively); Formula HOS contained high-oleic safflower oil (42%) in addition to coconut and soy oils (30% and 28%, respectively) and no palm olein. Fat and calcium levels in the two formulas were similar. In a balanced crossover design, fat and calcium absorption were determined in 10 normal infants ranging in age from 22 to 192 days. In three infants metabolic balance studies with complete separation of urine and feces were performed, whereas in seven infants excreta were in part collected at home, resulting in incomplete separation of urine and feces. RESULTS: Mean (+/- SD) fecal excretion of fat was higher when Formula PO was fed than when Formula HOS was fed (0.55 +/- 0.29 vs. 0.09 +/- 0.04 g/kg/day; p < 0.001). Hence % fat absorption was lower with PO than with HOS (90.0 +/- 6.4 vs. 98.5 +/- 0.6% of intake; p < 0.01). The difference in percent fat absorption was explained by significantly (p < 0.05) lower % absorption of palmitic (16:0) and stearic (18:0) acids when Formula PO was fed than when Formula HOS was fed. Fecal excretion of calcium was higher with Formula PO than with Formula HOS (53.4 +/- 12.0 vs. 37.4 +/- 14.9 mg/kg/day; p < 0.01), and hence % calcium absorption was lower with Formula PO than with Formula HOS (37.5 +/- 11.5 vs. 57.4 +/- 14.9%; p < 0.001). CONCLUSION: Absorption of fat and calcium by normal infants is lower when palm olein provides a substantial proportion of formula fat than when formula does not contain palm olein.

Calcium↗

Establishment and characterization of a simian virus 40-transformed temperature-sensitive rat luteal cell line.

The primary culture of rat luteal cells and their long-term maintenance have been difficult. Low cellular yields have limited the possibility for the study of gene regulation in luteal cells. The goal of this study was to develop a cell line to serve as a model by which to study the expression and regulation of various genes specific to luteal cells. We attempted to develop a luteal cell line by transformation of large luteal cells through infection with a temperature-sensitive simian virus (SV-40 tsA209) mutant that has a temperature-sensitive mutation required for the maintenance of cell transformation. We report here the successful establishment of such a cell line, designated GG-CL cells. Large luteal cells were purified to homogeneity by flow cytometry from corpora lutea of day 14 pregnant rats, cultured for 24 h, and then infected with the SV-40 tsA209 mutant virus. Transformed cells were maintained at the permissive temperature (33 C) until colonies were identified. Several colonies of transformed cells were isolated and passaged. They multiplied at 33 C and formed multilayers. At the nonpermissive temperature (40 C), cells reverted to the normal differentiated phenotype similar to the primary luteal cells in culture. To determine whether GG-CL cells express the genes found in normal luteal cells, messenger RNA (mRNA) expression was examined by either Northern analysis or RT-PCR with primers specific to each mRNA. GG-CL cells were found to express receptors for interleukin-6 and glucocorticoid, as well as the newly discovered estrogen receptor-beta (ER-beta) and the orphan nuclear receptor nur 77. No receptors for ER-alpha, progesterone, LH, or PRL could be detected. This cell line also expressed 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD), but not cholesterol side-chain cleavage cytochrome P450 (P450scc), 3beta-hydroxysteroid dehydrogenase, or aromatase cytochrome P450 (P450arom). Although the cells did not express the PRL receptor, they did express Janus kinase (JAK2) and signal transducers and activators of transcription (Stat5b), and, when transfected with the PRL receptor, they responded to PRL with a marked inhibition in 20alpha-HSD mRNA expression. In addition, estradiol enhanced ER-beta expression in a dose-dependent manner whereas cAMP stimulation caused a marked and rapid increase in the expression of the orphan receptor nur 77. In summary, a temperature-sensitive cell line was successfully established from the large luteal cells of rat corpora lutea. These cells express key genes encoding enzymes and receptors inherent to this defined luteal cell population and respond to stimulation by PRL, estradiol, and cAMP.

Animals↗

Erythrocyte incorporation of iron is similar in infants fed formulas fortified with 12 mg/L or 8 mg/L of iron.

Although feeding of formulas with iron concentration of 215 mumol/L (12 mg/L) is a reliable means of preventing iron deficiency, high intakes of iron may adversely affect absorption of copper and zinc. Because data are not available to establish whether fortification at a lower level would result in equivalent iron absorption, we tested the hypothesis that iron absorption is greater by infants fed formulas with an iron concentration of 215 mumol/L (12 mg/L) than by those fed formulas with an iron concentration of 143 mumol/L (8 mg/L). Fifty-two normal infants entered the study at 112 +/- 4 d of age, and 46 of these were successfully studied until 196 d of age. Using the stable isotope 58Fe, we determined erythrocyte incorporation of iron by infants fed Formula 8 [iron approximately 143 mumol/L (8 mg/L)] and by infants fed Similac with Iron [iron approximately 215 mumol/L (12 mg/L)]. On each of three test days beginning at 154 d of age, a major portion of the formula was labeled with 58Fe. Geometric mean erythrocyte incorporation of iron adjusted for plasma ferritin concentration at 168 d of age was 4.82 mumol/d (0.269 mg/d) by infants fed Formula 8 and 5.21 mumol/d (0.291 mg/d) by infants fed Similac with Iron. Corresponding values at 196 d of age were 5.12 and 5.41 mumol/d (0.286 and 0.302 mg/d). The differences in quantity of iron incorporated into erythrocytes by infants fed Formula 8 and Similac with Iron were not statistically significant (P = 0.66 at 168 d of age, P = 0.75 at 196 d of age) and were judged to be nutritionally trivial. Because we were unable to provide support for our hypothesis that iron absorption is greater by infants fed formulas providing 215 mumol (12 mg) of iron per liter than by those fed formulas providing 143 mumol (8 mg) of iron per liter, we conclude that, pending the results of further studies, It is reasonable to decrease the iron concentration of iron-fortified infant formulas.

Body Weight↗

A binding site for steroidogenic factor-1 is part of a complex enhancer that mediates expression of the murine gonadotropin-releasing hormone receptor gene.

Expression of the GnRH receptor (GnRH-R) gene in the anterior pituitary gland, as with the genes encoding the gonadotropin subunits, is restricted to gonadotrophs. Thus, it is conceivable that a common mechanism is involved in activating cell-specific expression of these genes. In fact, expression of the alpha- and LHbeta-subunit genes appears to require binding of the nuclear orphan receptor, steroidogenic factor-1 (SF-1). Here we have used DNA protein-binding assays to identify a high-affinity binding site for SF-1 in the proximal promoter of the murine GnRH-R gene. Southwestern blot analysis using this site as a radiolabeled probe revealed binding to a 53-kDa protein in alphaT3-1 cell extracts. Furthermore, mutation of this site led to a 58% reduction in promoter activity in the gonadotroph-derived alphaT3-1 cell line. Thus, SF-1 may represent at least one common pathway for gonadotroph-specific gene expression. In addition, we used block-replacement mutagenesis to functionally scan approximately 100 base pairs (bp) in a region that we had previously identified as critical for cell-specific promoter activity. Mutation of a partial palindrome located at -393 bp relative to the start of translation led to a 63% loss of promoter activity. Finally, a region containing both the SF-1 binding site and the -393 site was sufficient to stimulate cell-specific expression from a heterologous, minimal promoter. Thus, we suggest that a complex enhancer that includes a binding site for SF-1 mediates cell-specific expression of the GnRH-R gene.

Animals↗