Immunoreactive rat epidermal growth factor (EGF) was measured in the pancreas and in the mucosa and lumen of the stomach, duodenum, jejunum, midjejunum, ileum, and colon of fed or fasted 5- and 12-day-old suckling, and 3- to 4-month-old adult male rats using a homologous radioimmunoassay. The EGF levels in the pancreas in sucklings were lower than in adults and were unaffected by fasting. Both gastrointestinal mucosal and luminal EGF levels were higher in suckling rats than in adults. Fasting caused a significant decrease in gastrointestinal levels of EGF in the suckling rats but resulted in minimal changes in the adults. Our results show that the content of EGF in gastrointestinal tract is dependent on both age and dietary status. Together with the fact that milk contains a large amount of EGF (O. Koldovský and W. Thornburg, J. Pediatr. Gastro. Nutr. 6: 172-196, 1987) and that labeled EGF is absorbed to a considerable extent by the gastrointestinal tract of suckling rats (P.A. Gonella et al., J. Clin. Invest. 80: 22-32, 1987: W. Thornburg et al., Am. J. Physiol. 246: G80-G85, 1984), our present study implicates milk as an important source of EGF in the suckling period.

Milk from lactating Sprague-Dawley rats was assayed for epidermal growth factor (EGF)-like activities. A homologous radioimmunoassay (RIA) indicated the presence of immunoreactive material that competed in a nonparallel fashion with submandibular gland rat EGF (sm-r-EGF). The activity in the milk was extracted using antibodies to sm-r-EGF covalently linked to acrylamide beads. This activity was characterized by RIA, nondenaturing polyacrylamide gel electrophoresis, enzymatic digestion, radioreceptor assay, and ability to stimulate incorporation of [3H]thymidine into cultured fibroblasts. The presence of three distinct immunoreactive forms of EGF in rat milk were detected that competed with 125I-labeled r-EGF for binding to the EGF receptor and stimulated DNA synthesis in growth-arrested fibroblasts. Two of the forms are converted to the sm-r-EGF species by tryptic digestion as determined by RIA and migration rates in a nondenaturing polyacrylamide gel. The biological activities are stable to heating in 0.1 M acetic acid and also are stable at pH 9.0. Levels of r-EGF equivalents in milk were low at time of birth (6.3 +/- 1.7 ng/ml) and rose to 35.4 +/- 14.6 by days 4 to 6.

If nonprotein colloid plasma expanders could be demonstrated to be safe and efficacious in burn resuscitation, a significant cost benefit would result. This study was a randomized cross-over comparison of 500 ml of 5% albumin and 500 ml of 10% pentastarch, a new hydroxyethyl starch, in acute burn resuscitation. Pentastarch was an effective plasma expander, resulting in increases of preload, cardiac output, oxygen delivery, and oxygen consumption; the hemodynamic effects of pentastarch infusion were equal or superior to those of albumin. Both albumin and pentastarch infusions resulted in increased bleeding and clotting times; these effects were most likely dilutional. Pentastarch is a promising plasma substitute for burn resuscitation; the effects of a 500 ml infusion are equal or superior to those of albumin. Further study is necessary to assess the safety of larger infusion volumes.

46,XX female pseudohermaphrodites have been previously described with nearly complete masculinization of the external genitalia and no apparent source of testosterone. Multiple malformations of internal genital, urinary, and gastrointestinal tracts are associated. We have evaluated four such infants with female pseudohermaphroditism and multiple caudal anomalies. Three cases had apparently normal chromosomes (46,XX); one had a 46,XX,del(10)(q25.3-->qter) chromosome constitution. The chromosome breakpoint is in the region of PAX2, a developmentally important paired box gene which is expressed in urogenital tissue. Using the polymerase chain reaction, we screened for the presence of multiple Y specific sequences, including SRY (sex determining region, Y chromosome), that could explain masculinization of the external genitalia. All were negative for Y centromeric sequences, ZFY (Zinc finger Y), and SRY. Furthermore, there was no evidence for adrenal or other sources of testosterone. We suggest that the masculinization in these cases is the result of abnormal expression of genes which would normally be regulated by testosterone.

We have used mice transgenic for an antisense construct for Wnt-1 to study the role of this gene in post-meiotic sperm development. The human PGK-2 promoter provided levels of Wnt-1 antisense mRNA in testes in 5 transgenic lines greatly in excess of Wnt-1 mRNA concentrations, and Wnt-1 mRNA levels were greatly decreased in the lines, by 98% in three of them. There was a general correlation between copy number of the insert, levels of antisense RNA, and decreases in mRNA. There was little effect of the antisense transgene on fertility or testicular histology suggesting that normal levels of Wnt-1 transcript are not essential for spermatogenesis.