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Jay J Schnitzer

Publications and source records attributed to Jay J Schnitzer.

7 recordsLinked to original sources
PubMed2003

Slit and robo: expression patterns in lung development.

First described as an axonal guidance cue through its repulsive effect on neurons expressing its receptor Roundabout (Robo), the Slit ligand has effects on cell migration, axon branching and elongation. Indirect evidence implicates Slit and Robo in lung development. We now demonstrate that Slit-2 and Slit-3 are developmentally regulated in embryonic murine lung. Immunohistochemistry demonstrates Slit-2 and Slit-3 expression by the pulmonary mesenchyme and airway epithelium. Robo-1 and Robo-2 are also expressed by the developing mesenchyme and airway epithelium. As lung development progresses, Robo-1 and Robo-2 expression localizes to only the airway epithelium. We conclude Slit/Robo are expressed in temporo-spatially adjacent domains suggesting interactive roles in pulmonary bronchiolar development.

Animals↗
PubMed2003

Expression of Netrin-1 and its two receptors DCC and UNC5H2 in the developing mouse lung.

The ligand Netrin-1 and its receptors DCC and UNC5H2 are critical for the regulation of neuronal migration in nervous system development. Here we demonstrate expression of these molecules in lung development. The mRNA expression profiles of Netrin-1, DCC and UNC5H2 are developmentally regulated during embryonic mouse lung formation. Netrin-1 shows a bimodal expression pattern with elevated mRNA levels early followed by a second peak in late gestation. Peak expression of DCC occurs early in development whereas expression of UNC5H2 peaks late in development. We also demonstrate localization of Netrin-1, DCC and UNC5H2 during the stages of lung development. We present evidence that these proteins are modulated spatially in the mesenchyme and epithelium during lung organogenesis.

Animals↗
PubMed2003

The diagnosis of acute appendicitis in a pediatric population: to CT or not to CT.

PURPOSE: The aim of this study was to determine if focused appendiceal computed tomography with colon contrast (FACT-CC) increases the accuracy of the preoperative diagnosis of acute appendicitis in children. METHODS: A 5-year retrospective review was conducted of a university hospital database of 283 patients (age 0.8 to 19.3 years; mean, 11.3 years) treated with appendectomy for presumed acute appendicitis. RESULTS: Of the 283 patients in whom appendectomies were performed, 268 were confirmed by pathologic analysis of the specimen to have acute appendicitis for a diagnostic accuracy in our institution of 94.7%. Ninety-six patients (34%) underwent FACT-CC scans as part of their preoperative evaluation. The sensitivity of the computed tomography (CT) scan was 94.6%, and the positive predictive value was 95.6%. In girls older than 10 years, CT imaging was not significantly more accurate in predicting appendicitis than examination alone (93.9% v. 87.5%; P =.46). CONCLUSIONS: Preoperative FACT-CC did not increase the accuracy in diagnosing appendicitis when compared with patients diagnosed by history, physical examination and laboratory studies. If there was a strong suspicion of appendicitis, a negative CT scan did not exclude the diagnosis of appendicitis. However, focused appendiceal CT scan is a sensitive test with a high positive predictive value and may be useful in a patient with an atypical history or examination.

Acute Disease↗
PubMed2002

Oxidation-reduction (redox) controls fetal hypoplastic lung growth.

INTRODUCTION: The persistent morbidity and mortality of congenital diaphragmatic hernia are largely due to associated pulmonary hypoplasia. We have shown previously that three antioxidants (vitamin C, glutathione, and vitamin E) could accelerate the growth of fetal hypoplastic lungs grown in culture. We hypothesize that this occurs via a reductant mechanism. METHODS: Timed-pregnant rats were gavage-fed nitrofen (100 mg) on day 9.5 of gestation (term = day 22). Fetal lungs were harvested on day 13.5 and placed in organ culture containing serum-free BGJb medium with antibiotics. After randomization, the lung organ cultures were divided into a control group (n = 31) and an experimental group that received the antioxidant N-acetylcysteine (NAC, 100 microM, n = 31). The fetal lung organ cultures were grown for 4 days at 37 degrees C with 5% CO(2). Computer-assisted digital tracings of the airways were performed daily on live, unstained specimens, and lung bud count, perimeter, and area were measured. After 4 days, lungs were pooled, homogenized, and assayed for reduced and oxidized glutathione, normalized to protein, as an estimate of the tissue redox potential. Data were expressed as means +/- SEM, and statistical comparisons were performed using Student's unpaired t test, with P < 0.05 considered significant. RESULTS: Area, perimeter, lung bud count, and complexity (as measured by the perimeter/square root of area) were all significantly increased with NAC treatment from day 2 onward. Reduced glutathione levels were significantly increased following NAC administration (67.1 +/- 5.8 versus 37.5 +/- 4.2 micromol/mg, P = 0.0004). The ratio of reduced to oxidized glutathione was 2.23. CONCLUSIONS: N-Acetylcysteine stimulates nitrofen-induced hypoplastic fetal lung growth in organ culture and increases the ratio of reduced to oxidized glutathione. These data support the concept that oxidation-reduction (redox) may be an important control mechanism for fetal lung growth.

Acetylcysteine↗
PubMed2002

MEK-1/2 inhibition reduces branching morphogenesis and causes mesenchymal cell apoptosis in fetal rat lungs.

The roles of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinases-1 and -2 (ERK-1/2) in fetal lung development have not been extensively characterized. To determine if ERK-1/2 signaling plays a role in fetal lung branching morphogenesis, U-0126, an inhibitor of the upstream kinase MAP ERK kinase (MEK), was added to fetal lung explants in vitro. Morphometry as measured by branching, area, perimeter, and complexity were significantly reduced in U-0126-treated lungs. At the same time, U-0126 treatment reduced ERK-1/2, slightly increased p38 kinase, but did not change c-Jun NH(2)-terminal kinase activities, indicating that U-0126 specifically inhibited the ERK-1/2 enzymes. These changes were associated with increased apoptosis as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and immunofluorescent labeling of anti-active caspase-3 in the mesenchyme of explants after U-0126 treatment compared with the control. Mitosis characterized by immunolocalization of proliferating cell nuclear antigen was found predominantly in the epithelium and was reduced in U-0126-treated explants. Thus U-0126 causes specific inhibition of ERK-1/2 signaling, diminished branching morphogenesis, characterized by increased mesenchymal apoptosis, and decreased epithelial proliferation in fetal lung explants.

Animals↗
PubMed2002

Long-term consequences of toxic epidermal necrolysis in children.

OBJECTIVE: Toxic epidermal necrolysis (TEN) is an acute inflammatory systemic condition that involves injury not just to the skin. Historically, it has been associated with a high mortality but few long-term consequences among survivors. With improved survival, long-term consequences may be becoming more apparent. The objective of this study was to define these long-term consequences and their frequency. METHODS: From July 1, 1991, to June 30, 2000, 11 children with severe TEN were referred to a regional pediatric burn facility. Wounds were managed with a strategy involving prevention of wound desiccation and superinfection, including the frequent use of biological wound coverings. All children survived and have been followed in the burn clinic. The records of all children were reviewed in detail. RESULTS: Two boys and 9 girls with an average age of 7.2 +/- 1.8 years (range: 6 months-15 years) and sloughed surface area of 76 +/- 6% of the body surface (range: 50%-95%) were admitted to the burn unit for care. Antibiotics (3 children), anticonvulsants (4 children), nonsteroidals (2 children), and viral syndrome or unknown agents (2 children) were believed to have triggered the syndrome. Six (55%) children required intubation for an average of 9.7 +/- 1.8 days (range: 2-14 days). Mucosal involvement occurred in 10 (91%) and ocular involvement in 10 (91%). Lengths of stay averaged 19 +/- 3 days (range: 6-40 days). Overall follow-up averaged 14 +/- 13 months. Three children had no apparent long-term consequences of the disease and were referred to primary care follow-up after the 2-month burn clinic visit. The remaining children had follow-up averaging 23 +/- 13 months. The most common long-term morbidity involved eyes (3 children [27%]), nails (4 children [36%]), and variegated skin depigmentation (all children). One child developed vaginal stenosis from mucosal inflammation. No esophageal strictures or recurrent TEN has been diagnosed. CONCLUSIONS: Survival has improved in children with TEN, but long-term sequelae are not infrequent. The most common long-term consequences involve the eyes, the skin, and the nails.

Adolescent↗