ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Esophageal atresia (EA) is often associated with cardiovascular and other malformations that are likely neural crest derived. The present study tests the hypothesis that the heart and great vessels and the thymus and parathyroids may be abnormal in the rat model of EA as a result of disturbed neural crest development. Time-mated pregnant rats received intraperitoneally on d 8 and 9 of gestation either 2 mg/kg adriamycin or vehicle. Esophageal, heart, and thymic malformations were sought under the microscope in term fetuses. The parathyroids were histologically investigated. Control fetuses had no malformations, whereas 69 of 109 fetuses exposed to adriamycin had EA and 45 of 69 had 15 right aortic arches, nine aberrant right subclavia, eight ventricular septal defects, six narrow pulmonary outflow tracts, five tetralogies of Fallot, three double outflow right ventricles, three double aortic arches, three atrial septal defects, three right ductus arteriosus, and two truncus. The thymus was absent in 19, hypoplastic in 12, and ectopic in five out of 36 fetuses with EA in which it was studied, whereas the parathyroid glands were absent in 16, single in four, and ectopic in one of the 23 fetuses with EA in which they were studied. In conclusion, the nature of the cardiovascular, thymic, and parathyroid malformations associated with EA in rats is consistent with the hypothesis of neural crest participation in their pathogenesis. Mechanisms simultaneously disturbing foregut septation, somitic segmentation, and neural crest development should be sought to explain the combined occurrence of malformations in EA.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The lipase gene family contains a large number of members. Among the most closely related are pancreatic triglyceride lipase (PTL) and two pancreatic lipase-related proteins (PLRP1 and PLRP2). Previous studies in rodents demonstrated divergent temporal expression of the genes encoding these proteins. PLRP1 and PLRP2 were expressed in fetal pancreas, whereas PTL was not expressed until pups were several weeks old. To determine whether the human pancreas has a similar expression pattern for these genes, we determined the levels of each mRNA in fetal pancreas at various ages. A reverse transcriptase-PCR method was developed and used to quantify the mRNA levels for the three species normalized to the mRNA encoding cyclophillin. The mRNA encoding PLRP1 and PLRP2 was present by 16 wk in the fetal pancreas. In contrast, the mRNA encoding PTL was not present in the fetal pancreas. This pattern of expression suggests that the genes encoding theses proteins have different regulatory elements controlling temporal expression and provides another example of nonparallel expression of genes encoding pancreatic exocrine proteins.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

C-type natriuretic peptide (CNP) and its high affinity receptor-B are expressed in fetal bones. Here we show that CNP accelerates longitudinal growth of fetal rat metatarsal bones in organ culture by several mechanisms. First, CNP stimulates chondrocyte proliferation in the proliferative zone as assessed by [3H]thymidine incorporation. Second, CNP stimulates cell hypertrophy as assessed by quantitative histology. Third, CNP stimulates cartilage matrix production as assessed by incorporation of35S04into glycosaminoglycans. Natriuretic peptide receptor-B contains an intracellular guanylyl cyclase catalytic domain. We therefore hypothesized that cyclic GMP (cGMP) would reproduce the effects of CNP on fetal bones. Consistent with this hypothesis, we found that 8-Br-cGMP, like CNP, stimulates longitudinal growth and glycosaminoglycan synthesis. However, unlike CNP, cGMP inhibits proliferation of growth plate chondrocytes and has no effect on hypertrophy. We conclude that CNP stimulates longitudinal bone growth by increasing chondrocyte proliferation, chondrocyte hypertrophy, and cartilage matrix production. cGMP, a second messenger for CNP, reproduces some but not all of the effects of CNP, suggesting that other signal transduction mechanisms may also be involved.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Epidermal growth factor (EGF) is present in milk from various mammalian species, but its physiologic function in neonatal development remains unclear. Transforming growth factor-&agr; (TGF-&agr;) is a peptide structurally related to EGF, and its presence is detected in the developing small intestine of rats. The purpose of the present study was to examine the effect of milk-borne EGF on endogenous production of EGF and TGF-&agr; in the small intestine of suckling rats. Neonatal rats were fed via gastrostomy either growth factor-free rat milk substitute (RMS) or RMS supplemented with EGF (100 ng/mL of RMS) from 8 to 12 d of age. Artificially reared rats were then compared with their dam-fed littermates. Animals fed the EGF-deficient diet RMS had markedly increased EGF and TGF-&agr; mRNA levels in duodenum and ileum compared with dam-fed controls and significantly elevated total intestinal content of TGF-&agr; peptide. Intestinal EGF content and EGF serum levels were significantly decreased in the RMS group compared with controls. The addition of EGF to the RMS diet normalized TGF-&agr; mRNA levels in the duodenum and ileum, EGF mRNA levels in the ileum, and total intestinal TGF-&agr; content and EGF serum levels to the levels measured in dam-fed littermates. Motility studies showed that enteral administration of EGF did not affect stomach emptying and intestinal transit. These studies indicate that exogenous milk-borne EGF modulates endogenous production of TGF-&agr; in developing small intestine. It is likely that neither TGF-&agr; nor EGF are solely responsible for small intestinal overgrowth of artificially reared neonatal rats.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Infantile hypertrophic pyloric stenosis (IHPS) is characterized by hypertrophy of the pyloric muscle. The growth of smooth muscle cells is regulated by several growth factors. Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor are potent mitogens for smooth muscle cells. In the present study, we investigated immunohistochemical localization of EGF and EGF-related peptides and EGF mRNA expression in pyloric smooth muscle cells to determine whether the EGF family is involved in the process of pyloric muscle hypertrophy in IHPS. Pyloric muscle biopsy specimens were obtained at the time of pyloromyotomy from 10 patients with IHPS. Control material included 10 pyloric muscle specimens taken at autopsy from age-matched cases without evidence of gastrointestinal disease. Indirect immunohistochemistry was performed using the avidin-biotin-peroxidase complex method with anti-EGF, anti-EGF receptor, and anti–heparin-binding EGF-like growth factor antibody.In situhybridization was performed using digoxigenin-labeled EGF-specific oligonucleotide probe. The pattern of immunoreactivity in pyloric muscle with EGF, EGF receptor, and heparin-binding EGF-like growth factor was similar in all specimens. There was a marked increase in EGF, EGF receptor, and heparin-binding EGF-like growth factor immunoreactivity and EGF mRNA expression in smooth muscle cells in pyloric circular and longitudinal muscle from patients with IHPS compared with control specimens. These data suggest that the up-regulated local synthesis of EGF and EGF-related peptides in pyloric muscle may play a critical role in the development of pyloric muscle hypertrophy in IHPS.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Thrombocytopenia is common among sick neonates. Certain groups of thrombocytopenic adults respond favorably to the administration of recombinant thrombopoietin or to pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a recombinant human polypeptide that contains the receptor-binding N-terminal domain of thrombopoietin. The effectiveness and safety of such treatment in neonates, however, have not been reported. The purpose of the present study was to determine the biologic activity and safety of PEG-rHuMGDF administration to newborn rhesus monkeys. Eight monkeys were divided into four groups and treated subcutaneously with 0.00, 0.25, 1.00, or 2.50 &mgr;g/kg once daily for 7 d. Complete blood counts, serum chemistries, clotting panels, and MGDF levels were followed serially, and hematopoietic progenitor cell assays were performed on bone marrow aspirates before the first dose and again on d 8. Pharmacokinetic evaluations were performed on the animals that received the highest dose of PEG-rHuMGDF. All monkeys had normal growth during the study period, and all chemistries, clotting studies, and blood pressure measurements were normal. The peak serum MGDF concentration occurred at 3 h, and the half-life was 8.4 to 13.0 h. As in adult rhesus monkeys, platelet counts in the treated neonates began to rise on d 6, peaked on d 11, and returned to baseline by d 23. The two highest doses generated an 8- to 12-fold increase in platelets, whereas those treated with 0.25 &mgr;g/kg had a 6-fold increase. Other hematologic parameters measured were unaffected. Thus, newborn monkeys responded to doses of PEG-rHuMGDF that were similar to or smaller than (per kilogram body weight) those that are effective in adult animals and did so without obvious short-term toxicity.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID