Transcriptional regulation of the human NaPi-IIb cotransporter by EGF in Caco-2 cells involves c-myb.

The type IIb sodium-phosphate (NaP(i)-IIb) cotransporter mediates intestinal phosphate absorption. Previous work in our laboratory has shown that EGF inhibited NaP(i)-IIb cotransporter expression through transcriptional regulation. To understand this regulation, progressively shorter human NaP(i)-IIb promoter constructs were used to define the EGF response region, and gel mobility shift assays (GMSAs) were used to characterize DNA-protein interactions.

Lymphocytic choriomeningitis virus: emerging fetal teratogen.

Lymphocytic choriomeningitis virus (LCMV), a rodent-borne arenavirus, is an often undiagnosed human fetal teratogen. We describe a neonate born with hydrocephalus and chorioretinitis after maternal second-trimester symptomatic LCMV infection. Previously reported affected infants are reviewed.

Ileal cytokine dysregulation in experimental necrotizing enterocolitis is reduced by epidermal growth factor.

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. We have shown in previous studies that proinflammatory interleukin-18 and interleukin-12 are up-regulated in the ileum of rats with experimental NEC and that epidermal growth factor (EGF) reduces the development of disease. Here we investigated whether the protective effects of EGF are a result of changes in ileal interleukin-18, interleukin-12 and/or antiinflammatory interleukin-10.

Functional characterization of the human intestinal NaPi-IIb cotransporter in hamster fibroblasts and Xenopus oocytes.

The recently cloned NaPi-IIb cotransporter is an apical membrane protein that is involved in the absorption of phosphate in the intestine. To expedite functional and structural studies, the human intestinal NaPi-IIb cotransporter was stably expressed in hamster fibroblast (PS120) cells. The hNaPi-IIb cDNA stably transfected cells exhibited a 1.

Transcriptional regulation of the rat NHE3 gene. Functional interactions between GATA-5 and Sp family transcription factors.

Expression of sodium-hydrogen exchanger isoform 3 (NHE3) in the intestinal and renal epithelium plays a critical role in sodium absorption and acid/base homeostasis. To decipher rat NHE3 gene regulation, its cis-acting regulatory elements and associated transcription factors were characterized by transient transfection of Caco-2, IEC-6, Qt6, and Drosophila SL2 cells. Deletion and mutational analyses demonstrated that the atypical TATA box located at bp -26/-31 was not necessary for promoter activity, and that a -20/+8-bp fragment represents a functional initiator.

Precountershock cardiopulmonary resuscitation improves ventricular fibrillation median frequency and myocardial readiness for successful defibrillation from prolonged ventricular fibrillation: a randomized, controlled swine study.

Study Objective: After prolonged ventricular fibrillation (VF), precountershock cardiopulmonary resuscitation (CPR) will improve myocardial "readiness" for defibrillation compared with immediate defibrillation.

Methods: After 10 minutes of untreated VF, 32 swine (27+/-1 kg) were randomly assigned to receive immediate countershocks (DEFIB), CPR for 3 minutes followed by countershocks (CPR), or CPR for 3 minutes plus intravenous epinephrine followed by countershocks (CPR+EPI). VF waveform was evaluated by fast Fourier transformation.

Characterization of vesicular glutamate transporter in pancreatic alpha - and beta -cells and its regulation by glucose.

Glutamate has been suggested to play an important role in the release of insulin and glucagon from pancreatic cells via exocytosis. Vesicular glutamate transporter is a rate-limiting step for glutamate release and is involved in the glutamate-evoked exocytosis. Two vesicular glutamate transporters (VGLUT1 and -2) have recently been cloned from the brain.

Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimulate antitumor immunity.

We have previously reported that apoptotic tumor cells can be either immunogenic or nonimmunogenic in vivo, depending on whether or not these cells are heat stressed before induction of apoptosis. Stressed apoptotic cells express heat shock proteins on their plasma membranes and dendritic cells are capable of distinguishing them from nonstressed apoptotic cells. Here we provide evidence that when purified heat shock protein 70 or chaperone-rich cell lysate (CRCL) from syngeneic normal tissue is used as an adjuvant with nonimmunogenic apoptotic tumor cells in vaccination, potent antitumor immunity can be generated.

Stressed apoptotic tumor cells stimulate dendritic cells and induce specific cytotoxic T cells.

We have previously reported that stressed apoptotic tumor cells are more immunogenic in vivo than nonstressed ones. Using confocal microscopy we have confirmed our previous observation that heat-stressed apoptotic 12B1-D1 leukemia cells (BCR-ABL(+)) express HSP60 and HSP72 on their surface. To explore how the immune system distinguishes stressed from nonstressed apoptotic tumor cells, we analyzed the responses of dendritic cells to these 2 types of apoptotic cells.

Iron status and the treatment of the anemia of prematurity.

Many unanswered issues regarding rhEPO therapy in prematurity remain, including which premature infants best respond to rhEPO, what the long-term effect of decreased erythrocyte transfusions is, how nutritional supplementation optimizes the effect of rhEPO, whether or not rhEpo therapy causes iron deficiency later in life, and whether or not it is safe to supplement with parenteral iron. Further study of rhEPO therapy and iron status in prematurity is necessary.

When children die: a seminar series for pediatric residents.

Objective: Our goals were to assist residents in acquiring skills needed to care for children at the end of life and to increase their comfort level regarding critical aspects of caring for dying children.

Methods: We designed and implemented a 6-part seminar series for pediatric residents in their postgraduate year-2 at the University of Arizona Pediatric Residency Program. The series consisted of small group sessions regarding medical and legal issues facing physicians at the time of a pediatric patient's death, symptom management in dying children, approaches to limitation of care and discussion of impending death of a child, cultural and developmental factors impacting on the care of children at the end of life, parent and sibling bereavement after the death of a child, and physician's personal responses to the death of pediatric patients.

Two cases of pediatric neuroblastoma with tumor thrombus in the inferior vena cava.

The authors describe two children with abdominal neuroblastoma with radiographic evidence of tumor extension into the inferior vena cava. Imaging studies were suggestive of Wilms tumor, but histologic analysis revealed neuroblastoma. In one patient a pulmonary embolus developed after initiation of cytotoxic therapy; the second patient was prophylactically anticoagulated and had no embolic event.

Is there a common cold constitution?

Objective: Constitutional factors might play a role in the susceptibility to clinical illness during the common cold. This study seeks to determine if the likelihood of developing frequent common colds persists during childhood.

Design: The Tucson Children's Respiratory Study involves 1246 children enrolled at birth and followed prospectively since 1980 and 1984.

Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors.

Heart septation and valve malformations constitute the most common anatomical birth defects. These structures arise from the endocardial cushions within the atrioventricular canal (AVC) through dynamic interactions between cushion cells and the extracellular matrix (termed cardiac jelly). Transformation of endothelial cells to mesenchymal cells is essential for the proper development of the AVC and subsequent septation and valve formation.

Glucocorticoid regulation and glycosylation of mouse intestinal type IIb Na-P(i) cotransporter during ontogeny.

We sought to characterize expression of an apically expressed intestinal Na-P(i) cotransporter (Na-P(i)-IIb) during mouse ontogeny and to assess the effects of methylprednisolone (MP) treatment. In control mice, Na-P(i) uptake by intestinal brush-border membrane vesicles was highest at 14 days of age, lower at 21 days, and further reduced at 8 wk and 8-9 mo of age. Na-P(i)-IIb mRNA and immunoreactive protein levels in 14-day-old animals were markedly higher than in older groups.

Studies on neuronal death in the mouse model of Niemann-Pick C disease.

A mouse model of Niemann-Pick disease type C (NPC) carries a genetic defect that causes biochemical changes in lipid levels and a progressive neuropathology that parallels the effects of NPC disease in humans. It is a moot point whether or not the loss of Purkinje and other neuronal cells proceeds by apoptotic death. Therefore, we have introduced into these mice a transgene expressing human Bcl-2 protein which has previously been demonstrated to prevent developmental neuronal death and death induced by a variety of stimuli.

Glucocorticoid regulation of the murine PHEX gene.

The phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) is a member of the neutral endopeptidase family, which is expressed predominantly on the plasma membranes of mature osteoblasts and osteocytes. Although it is known that the loss of PHEX function results in X-linked hypophosphatemic rickets, characterized by abnormal bone matrix mineralization and renal phosphate wasting, little is known about how PHEX is regulated. We therefore sought to determine whether the murine PHEX gene is regulated by glucocorticoids (GCs), which are known to influence phosphate homeostasis and bone metabolism.

Aspergillus cholangitis: A late complication after Kasai portoenterostomy.

Ascending bacterial cholangitis can be a recurring complication in older children and adolescents who have undergone successful surgery for biliary atresia. The authors describe a 19-year-old girl with a history of recurrent late-onset, febrile cholangitis in whom persistent jaundice developed. Aspergillus terreus was isolated from her biliary fluid obtained at percutaneous transhepatic cholangiography.

Up-regulation of IL-18 and IL-12 in the ileum of neonatal rats with necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease of premature infants. Because the proinflammatory cytokines IL-18, IL-12, and interferon (IFN)-gamma have been implicated in other diseases of the small intestine, we hypothesized that these cytokines would play an important role in NEC pathogenesis. NEC was induced in newborn rats via enteral feeding with rat milk substitute and asphyxia and cold stress (RMS).

Beta 1 integrin activation mediates adhesive differences between trisomy 21 and non-trisomic fibroblasts on type VI collagen.

Trisomy 21 (Down syndrome) is a common genetic condition with a high incidence of congenital heart defects (CHD), particularly those involving abnormal development of the embryonic atrioventricular (AV) canal. Type VI collagen (Col VI) is expressed in the developing AV canal extracellular matrix, and has been associated with trisomy 21 AV canal defects in human genetic studies. Although the molecular mechanisms linking Col VI and trisomy 21 AV canal defects are not well understood, a computer model predicts increased cell adhesiveness is responsible for these CHD.

mdr1a deficiency corrects sterility in Niemann-Pick C1 protein deficient female mice.

Niemann-Pick type C disease is a progressive neurological disease with cholesterol storage in liver, and npc1-/- mice share these features and are sterile. We have searched for the cause of sterility and found normal folliculogenesis and progesterone levels but lack of implantation. Multiple drug resistance (MDR) P-glycoproteins are plasma membrane proteins implicated in the movement of drugs and lipids across membranes.

Changes in organ perfusion and weight ratios in post-simulated microgravity recovery.

Head-down tilt models have been used as ground-based simulations of microgravity. Our previous animal research has demonstrated that there are significant changes in fluid distribution within 2 h after placement in a 45 degrees head-down tilt (45HDT) position and these changes in fluid distribution were still present after 14 days of 45HDT. Consequently, we investigated changes in fluid distribution during recovery from 16 days of 45HDT.

Nasal congestion and airway obstruction: the validity of available objective and subjective measures.

Rhinomanometry and acoustic rhinometry provide the best methods for objective assessment of nasal obstruction. Advanced equipment for these methods is now available, and most devices are reliable provided that care is taken to calibrate the device properly and, for rhinomanometers, the user is completely familiar with the mathematical algorithm for resistance used by the accompanying software. Suggestions for improvement in standardization of rhinomanometry are given.

Early renal changes in 45 degrees HDT rats.

Background: Both microgravity and simulated microgravity models, such as the 45HDT (45 degrees head-down tilt), cause a redistribution of body fluids indicating a possible adaptive process to the microgravity stressor. Understanding the physiological processes that occur in microgravity is a first step to developing countermeasures to stop its harmful effects, i.e.