Hirschsprung Disease in an Infant with L1 syndrome: Report of a New Case and a novel variant.

L1syndrome is an X-linked disorder manifesting with congenital hydrocephalus, adducted thumbs and spasticity. There are rare cases of L1 syndrome and coincident Hirschsprung disease, with mutations in the gene thought to underlie both. We present a novel pathogenic variant in someone with L1 syndrome and Hirschsprung disease.

Children's Learning and Goal-Setting at a Diabetes Camp.

Objective. This study provides information about children's learning and goal attainment related to change in their self-management skills during a diabetes camp. Design and methods.

Differential responses of pancreatic β-cells to ROS and RNS.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) direct the activation of distinct signaling pathways that determine cell fate. In this study, the pathways activated and the mechanisms by which ROS and RNS control the viability of pancreatic β-cells were examined. Although both nitric oxide and hydrogen peroxide (H₂O₂) induce DNA damage, reduce cell viability, and activate AMPK, the mechanisms of AMPK activation and cell death induction differ between each reactive species.

Cytokine-mediated β-cell damage in PARP-1-deficient islets.

Poly(ADP)-ribose polymerase (PARP) is an abundant nuclear protein that is activated by DNA damage; once active, it modifies nuclear proteins through attachment of poly(ADP)-ribose units derived from β-nicotinamide adenine dinucleotide (NAD(+)). In mice, the deletion of PARP-1 attenuates tissue injury in a number of animal models of human disease, including streptozotocin-induced diabetes. Also, inflammatory cell signaling and inflammatory gene expression are attenuated in macrophages isolated from endotoxin-treated PARP-1-deficient mice.

Association of nursing workload and unplanned extubations in a pediatric intensive care unit.

Objective: To estimate nursing workload from the patient acuity level (PAL) assigned to patients in a pediatric intensive care unit (PICU) and to determine its influence on unplanned extubations.

Design: Prospective cohort study.

Setting: The 19-bed PICU of an urban, university-affiliated, tertiary children's hospital.

Children with diabetes: perceptions of supports for self-management at school.

Diabetes affects many children. Researchers know little about children's perceptions of what type of support they need at school, which was a focus of this study. Group interviews and surveys examined children's perceptions of support in caring for their diabetes (type I diabetes) from school nurses, teachers, and friends.

Poly(ADP-ribose) polymerase-1 regulates activation of activator protein-1 in murine fibroblasts.

Poly(ADP-ribose) polymerase (PARP)-1 is activated in response to DNA injury in the nucleus of eukaryotic cells and has been implicated in cell dysfunction in inflammation. We investigated the role of PARP-1 on the AP-1 pathway, which is involved in the signal transduction of the inflammatory process. In murine wild-type fibroblasts, oxidative challenge by peroxynitrite and hydrogen peroxide or immunological challenge by IL-1 and 20% FCS induced phosphorylation of the mitogen-activated protein kinase kinase-4, activation of c-Jun N-terminal kinase (JNK), and DNA binding of AP-1.

Rat glucokinase gene: structure and regulation by insulin.

The glucokinase gene is 15.5-kilobases long, appears to be present as a single copy, and contains 10 exons that range in size from 96 to 977 base pairs. The transcription start site was located 127 nucleotides upstream from the translation initiation codon.

The amino acid sequence of rat liver glucokinase deduced from cloned cDNA.

Rat liver glucokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.

Islet beta-cell function and polymorphism in the 5'-flanking region of the human insulin gene.

The present study investigates the possible relationship between human beta-cell secretory capacity and polymorphism in the 5'-flanking region of the human insulin gene. The glucose potentiation slope was measured in normal and non-insulin-dependent diabetic subjects (NIDDM). This slope, as reported previously (Ward, W.

Insulin gene analysis in a family with maturity-onset diabetes of the young.

The insulin gene locus has been studied in a large kindred with maturity-onset diabetes of the young (MODY) characterized by hypoinsulinemia. DNA was isolated from peripheral leukocytes of 42 family members and 5 spouses. A highly polymorphic region in the 5'-flanking portion of the human insulin gene provided an opportunity for linkage analysis.

The genetics of type I and type II diabetes: analysis by recombinant DNA methodology.

Susceptibility to IDDM is linked to the HLA-D locus on the short arm of chromosome 6, a region believed to be involved in the process of communication between cells which determines immune responses. Presumably an HLA molecule encoded by this region, unable to present a particular antigenic pathogen to the immune system, is inherited. The HLA-DR locus is quite complex, however.

Multihormonal regulation of phosphoenolpyruvate carboxykinase gene transcription. The dominant role of insulin.

We used a nuclear RNA transcript elongation assay to show that cAMP analogs and dexamethasone cause a selective increase of transcription of the P-enolpyruvate carboxykinase gene in H4IIE hepatoma cells. 8-(4-chlorophenylthio)-cAMP increased transcription within 5 min and the maximal rate, generally 10-15-fold above the basal rate, was attained by 30 min. This increase was of sufficient magnitude to account for the effect on mRNAPEPCK (for example, where PEPCK is phosphoenolpyruvate carboxykinase) accumulation.

Polymorphism in the 5' flanking region of the human insulin gene. Relationships with noninsulin-dependent diabetes mellitus, glucose and insulin concentrations, and diabetes treatment in the Pima Indians.

Variations in DNA sequences flanking the insulin gene were studied in relation to noninsulin-dependent diabetes mellitus (NIDDM) in 87 unrelated Pima Indians at least 35 yr of age. DNA was isolated from nuclei of peripheral blood leukocytes and digested with restriction endonucleases. Less variation in this region was found in Pima Indians than in other racial groups previously studied.

Insulin and glucagon regulate cytosolic phosphoenolpyruvate carboxykinase (GTP) mRNA in rat liver.

Insulin causes a 7-10-fold decrease of both the mRNA that codes for rat hepatic phosphoenolpyruvate carboxykinase (mRNAPEPCK) and of PEPCK synthesis, provided the animals are made diabetic and fed chow. mRNAPEPCK, measured either by in vitro translation or cDNA hybridization, decreases with a half-time of 30-60 min after insulin treatment. This coordinant decrease, which approximates the half-life of mRNAPEPCK measured in a variety of situations, suggests that insulin acts by decreasing mRNAPEPCK production, and that the hormone does not alter the activity of a fixed amount of this RNA, or enhance its degradation.

Inhibition of transcription of the phosphoenolpyruvate carboxykinase gene by insulin.

Insulin regulates the synthesis of several proteins in a variety of tissues. Before techniques were available to quantify the amount of specific mRNAs, insulin was thought to regulate the synthesis of proteins by influencing the rate of translation of a fixed amount of mRNA. A very different interpretation is called for by experiments which show that insulin alters the amount of several specific mRNAs, but little is known about the mechanism.

Insulin decreases phosphoenolpyruvate carboxykinase (GTP) mRNA activity by a receptor-mediated process.

The mRNA that codes for phosphoenolpyruvate carboxykinase accounts for approximately 0.2% of the protein synthesized in H4IIEC3 hepatoma cells maintained for 24 h in serum-free medium containing N6,O2'-dibutyryl cAMP and theophylline. This value decreases to 0.

Mitochondrial metabolism of (D,L)-threo-9, 10-dibromo plamitic acid.

Bromination of palmitoleic or palmitelaidic acid proceeds by trans addition and yields dibrominated products which cannot undergo beta-oxidation when incubated with mitochondria isolated from hamster brown adipose tissue. These mitochondria were selected because they have a high capacity for oxidation of C16 fatty acids and because they are readily uncoupled by an excess of free fatty acids of this chain length. The only metabolites which could be recovered from the incubation mixtures were dibromopalmitoylcarnitine and dibromopalmitoyl CoA.

Translation in Escherichia coli mini-cells containing hamster mitochondrial DNA-Co1E1 - Ampr recombinant plasmids.

Hamster mitochondrial DNA is cleaved into two fragments (4.2 and 11.4 kilobase pairs of DNA (kb)) by the restriction enzyme, Eco RI.