Pamela M. Thomas

A New Look at Intrauterine Growth and the Impact of Race, Altitude, and Gender

Background. Growth curves described in the 1960s are used to classify neonate intrauterine growth as normal or abnormal. Our objective was to determine whether continued use of these curves is appropriate. Methods. From 1996 to 1998, we collected birth weight, length, head circumference, estimated gestational age (EGA), gender, race, and place of birth (<4000 feet or ≥4000 feet) on 27 229 neonates to evaluate the effects of each on intrauterine growth and the diagnoses of small for gestational age (SGA) and large for gestational age (LGA). We compared the gestation-specific growth parameters derived from our sample with those reported in 1966 and 1969. Results. Gestational age had the largest influence on each growth parameter. Race and gender both had effects on birth weight. Female neonates were smaller than male neonates, and black neonates were smaller than Hispanic and white neonates at each EGA. For neonates with an EGA <30 weeks, our data had a smaller variance and lower average weights, lengths, and head circumferences than those reported in 1966 and in 1969. For neonates >36 weeks, the variance was similar, but our curves showed that neonates in our sample were larger and heavier. Use of the older growth curves to classify neonates as SGA, LGA, and appropriate for gestational age (AGA) led to significantly different rates of each by gender and race. Conclusions. Intrauterine growth patterns previously described and commonly used to classify neonates as AGA are inaccurate for use in current populations and lead to gender- and race-specific diagnoses of SGA and LGA that are misleading. neonates, growth, race, gender.

A novel sulfonylurea receptor family member expressed in the embryonic Drosophila dorsal vessel and tracheal system.

Sulfonylurea receptors (SURx) are required subunits of the ATP-sensitive potassium channel. SURx alone is electrophysiologically inert. However, when SURx is combined with an inward rectifier Kir6.2 subunit, ATP-sensitive potassium channel activity is generated. We report the identification, characterization, and localization of Dsur, a novel Drosophila gene that is highly related to the vertebrate SUR family. The Dsur coding sequence contains structural features characteristic of the ABC transporter family and, in addition, harbors 1.7 kilobases of a distinctive sequence that does not share homology with any known gene. When Dsur alone is expressed in Xenopus oocytes glibenclamide-sensitive potassium channel activity occurs. During Drosophilaembryogenesis, the Dsur gene is specifically expressed in the developing tracheal system and dorsal vessel. Studies of theDrosophila genome support that only a singleDsur gene is present. Our data reveal conservation of glibenclamide-sensitive potassium channels in Drosophilaand suggest that Dsur may play an important role duringDrosophila embryogenesis. The lack of gene duplication in the Drosophila system provides a unique opportunity for functional studies of SUR using a genetic approach.

Cloning, characterization, and embryonic expression analysis of the Drosophila melanogaster gene encoding insulin/relaxin-like peptide.

Insulin is one of the key peptide hormones that regulates growth and metabolism in vertebrates. Evolutionary conservation of many elements of the insulin/IGF signaling network makes it possible to study the basic genetic function of this pathway in lower metazoan models such as Drosophila. Here we report the cloning and characterization of the gene for Drosophila insulin/relaxin-like peptide (DIRLP). The predicted protein structure of DIRLP greatly resembles typical insulin structure and contains features that differentiate it from the Drosophila juvenile hormone, another member of the insulin family. The Dirlp gene is represented as a single copy in the Drosophila melanogaster genome (compared to multiple copies for Drosophila juvenile hormone) and shows evolutionary conservation of genetic structure. The gene was mapped to the Drosophila chromosome 3, region 67D2. In situ hybridization of whole-mount Drosophila embryos with Dirlp antisense RNA probe reveals early embryonic mesodermal/ventral furrow expression pattern, consistent with earlier observation of the insulin protein immunoreactivity in Drosophila embryos. The in situ hybridization pattern was found to be identical to that obtained during immunohistochemistry analysis of the Drosophila embryos using various insulin monoclonal and polyclonal antibodies that do not recognize Drosophila juvenile hormone, supporting the idea that Dirlp is a possible Drosophila insulin ortholog. Identification of the gene for DIRLP provides a new approach for study of the regulatory pathway of the insulin family of peptides.

Structure of the mouse calcitonin/calcitonin gene-related peptide alpha and beta genes

We report the cloning, genomic organization and sequence of the mouse α-CALC and β-CALC genes. The two genes share extensive sequence homology. The transcription units of both genes contain 6 exons. Transcripts of the α-CALC gene were found to alternatively include exon 4 or exons 5 and 6. For the β-CALC gene exon 4 was not detected in transcripts derived from this gene. The predicted mouse α-CGRP was found to be identical to rat α-CGRP, however, β-CGRP predicted amino acid sequences revealed three amino acid differences suggesting these residues are not critical to CGRP function.

Persistent hyperinsulinemic hypoglycemia of infancy

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), also known as familial hyperinsulinism and nesidioblastosis, is a disorder of glucose homeostasis characterized by unregulated hyperinsulinemia and profound hypoglycemia. Although rare, this disorder is the most common cause of persistent hyperinsulinemia in children. Description of PHHI as a unique clinical syndrome began 25 years ago with the association of nesidioblastosis, defined as the budding of isolated endocrine cells and islets from pancreatic duct cells, and severe infantile hypoglycemia [1]. Recent findings have elucidated the molecular cause for hyperinsulinemia in some families with this disorder, providing additional insight into the regulation of insulin secretion.

A Novel ABC Transporter of the Sulfonylurea Receptor Family Expressed Specifically in the Drosophila Embryonic Heart and Tracheal System

A Novel ABC Transporter of the Sulfonylurea Receptor Family Expressed Specifically in the Drosophila Embryonic Heart and Tracheal System

Molecular Mechanisms of Hypoglycemia Associated with Increased Insulin Production

The differential diagnosis of hypoglycemia in the pediatric age group is broad (Table 55-1). In the neonatal period, transient hypoglycemia caused by hyperinsulinemia is common. It is, however, the rare newborn who presents with profound and prolonged hypoglycemia requiring substantial glucose replacement. When this is detected, it most commonly is caused by hyperinsulinism.