Influence of H2S on the pitting corrosion of 316L stainless steel in oilfield brine.

Coupon immersion tests were performed on 316L stainless steel in a simulated oilfield environment to evaluate the effect of H2S partial pressure on pit depth and density. Pitting was most significant at intermediate partial pressures of H2S, for which free H2S in the pit solution is maximised. Inhibition of pitting at higher partial pressures is attributed to blocking of the pit surface by metal sulphide phases. The key role of pH in the pit solution is to determine the solubility of metal sulphides and the availability of free H2S to adsorb on the reacting pit surface and sustain activity.

Forces generated during stretch in the heart of the lobster Homarus americanus are anisotropic and are altered by neuromodulators.

Mechanical and neurophysiological anisotropies mediate three-dimensional responses of the heart of ITALIC! Homarus americanus Although hearts ITALIC! in vivoare loaded multi-axially by pressure, studies of invertebrate cardiac function typically use uniaxial tests. To generate whole-heart length-tension curves, stretch pyramids at constant lengthening and shortening rates were imposed uniaxially and biaxially along longitudinal and transverse axes of the beating whole heart. To determine whether neuropeptides that are known to modulate cardiac activity in ITALIC! H. americanusaffect the active or passive components of these length-tension curves, we also performed these tests in the presence of SGRNFLRFamide (SGRN) and GYSNRNYLRFamide (GYS). In uniaxial and biaxial tests, both passive and active forces increased with stretch along both measurement axes. The increase in passive forces was anisotropic, with greater increases along the longitudinal axis. Passive forces showed hysteresis and active forces were higher during lengthening than shortening phases of the stretch pyramid. Active forces at a given length were increased by both neuropeptides. To exert these effects, neuropeptides might have acted indirectly on the muscle via their effects on the cardiac ganglion, directly on the neuromuscular junction, or directly on the muscles. Because increases in response to stretch were also seen in stimulated motor nerve-muscle preparations, at least some of the effects of the peptides are likely peripheral. Taken together, these findings suggest that flexibility in rhythmic cardiac contractions results from the amplified effects of neuropeptides interacting with the length-tension characteristics of the heart.

siRNA screening identifies differences in the Fanconi anemia pathway in BALB/c-Trp53+/- with susceptibility versus C57BL/6-Trp53+/- mice with resistance to mammary tumors.

BALB/c mice heterozygous for Trp53 develop a high proportion of spontaneous mammary tumors, a phenotype distinct from other mouse strains. BALB/c-Trp53+/- female mice, thus, resemble the hereditary Li-Fraumeni syndrome (LFS) characterized by early-onset of breast cancer, even though LFS involves TP53 mutations, which may involve not only loss- but also gain-of-function. Previous analysis of tumors in BALB/c-Trp53+/- females showed frequent loss of heterozygosity involving the wild-type allele of Trp53 and displayed characteristics indicative of mitotic recombination. Critical involvement of DNA double-strand break (DSB) repair dysfunction, particularly of homologous recombination (HR), was also noticed in the etiology of human breast cancer. To better define functional alterations in BALB/c-Trp53+/- mice, we applied a fluorescence-based DSB repair assay on mouse embryonic fibroblasts (MEFs) from BALB/c-Trp53+/- versus C57BL/6J-Trp53+/- mice. This approach revealed deregulation of HR but not non-homologous end-joining (NHEJ) in BALB/c-Trp53+/-, which was further confirmed for mammary epithelial cells. Screening of a small interfering RNA-library targeting DSB repair, recombination, replication and signaling genes, identified 25 genes causing differences between homologous DSB repair in the two strains upon silencing. Interactome analysis of the hits revealed clustering of replication-related and fanconi anemia (FA)/breast cancer susceptibility (BRCA) genes. Further dissection of the functional change in BALB/c-Trp53+/- by immunofluorescence microscopy of nuclear 53BP1, Replication protein A (RPA) and Rad51 foci uncovered differences in crosslink and replication-associated repair. Chromosome breakage, G2 arrest and biochemical analyses indicated a FA pathway defect downstream of FancD2 associated with reduced levels of BRCA2. Consistent with polygenic models for BRCA, mammary carcinogenesis in BALB/c-Trp53+/- mice may, therefore, be promoted by a BRCA modifier allele in the FA pathway in the context of partial p53 loss-of-function.

Plastic bronchitis requiring bronchoscopy.

OBJECTIVE: We report two cases of plastic bronchitis presenting with acute respiratory failure and mimicking foreign body inhalation. METHOD: The clinical findings, differential diagnoses and radiological investigation are discussed. RESULTS: Plastic bronchitis is an uncommon condition, particularly in children. The condition may present to otolaryngologists with symptoms mimicking foreign body inhalation. It is important to consider plastic bronchitis as a differential diagnosis, based on its clinical and radiological signs. Early intervention, in the form of bronchoscopy, can be both diagnostic and therapeutic. CONCLUSION: Plastic bronchitis is uncommon and its clinical and radiological features are non-specific. The recommended management is early bronchoscopy to establish the diagnosis and enable therapeutic intervention.

Spontaneous pneumomediastinum: benefits of contrast computed tomography imaging.

OBJECTIVE: We report a case of spontaneous pneumomediastinum presenting with chest and anterior neck pain. METHOD: The clinical findings, differential diagnosis and selection of radiological investigations are discussed. RESULTS: Spontaneous pneumomediastinum is an uncommon condition usually presenting in young patients. Presentation to the otolaryngology department occurs due to the presence of symptoms such as neck pain. Differential diagnoses must be considered and excluded, using the clinical features and the results of radiological investigation. Once the diagnosis is confirmed, conservative management is undertaken. CONCLUSION: Spontaneous pneumomediastinum is uncommon and the clinical features are variable. The recommended investigation is a computed tomography scan with orally administered, water soluble contrast to exclude important differential diagnoses and thus enable definitive diagnosis.

Regulation of apoptosis during mammary involution by the p53 tumor suppressor gene.

Regulation and functions of the p53 tumor suppressor gene have been studied extensively with respect to its critical role in maintaining the stability of genomic DNA following genotoxic insults. However, p53 is also induced by physiologic stimuli resulting in cell cycle arrest and apoptosis. In other situations, the activity of p53 must be repressed to prevent inappropriate removal of cells. The mammary gland provides a valuable system in which to study the mechanisms by which the expression and biological responses to p53 can be regulated under a variety of physiological circumstances. The pro-apoptotic role of p53 in the secretory mammary epithelium may be especially relevant to lactation in livestock. We have utilized p53-deficient mice to establish the molecular targets of p53 in the mammary gland and biological consequences when it is absent. The p21/WAF1 gene (Cdkn1a) is a transcriptional target gene of the p53 protein that responds to elevated levels of p53 during milk stasis providing an endogenous reporter of p53 activity. Abrogation of p53 resulted in delayed involution of the mammary epithelium, demonstrating the physiological role of p53 in regulating involution. Though delayed, stromal proteases were induced in the mammary gland by 5 d postweaning, providing a p53-independent mechanism that resulted in removal of the residual secretory epithelium. These processes can be interrupted by treatment with hydrocortisone. These data establish p53 as a physiological regulator of involution that acts to rapidly initiate apoptosis in the secretory epithelium in response to stress signals, but also indicate the presence of compensatory pathways to effect involution. Additional mechanisms involving intracellular stress signaling pathways (e.g., Stat3) and stromal-mediated pathways have been identified and, together with p53 pathways, may be used to identify animals with greater persistency of lactation.

Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge.

Sustained upregulation of inducible nitric oxide (NO) synthase in the liver after endotoxin [lipopolysaccharide (LPS)] challenge may result in hepatocellular injury. We hypothesized that administration of a NO scavenger, NOX, may attenuate LPS-induced hepatocellular injury. Sprague-Dawley rats received NOX or saline via subcutaneous osmotic pumps, followed 18 h later by LPS challenge. Hepatocellular injury was assessed using biochemical assays, light, and transmission electron microscopy (TEM). Interleukin (IL)-6 mRNA was measured by RT-PCR. Tumor necrosis factor (TNF)-alpha protein expression was determined by immunohistochemistry. NOX significantly reduced serum levels of ornithine carbamoyltransferase and aspartate aminotransferase. TNF-alpha and IL-6 expression were increased in the livers of saline-treated but not NOX-treated rats. Although there was no difference between groups by light microscopy, TEM revealed obliteration of the space of Disse in saline-treated but not in NOX-treated animals. Electron paramagnetic resonance showed the characteristic mononitrosyl complex in NOX-treated rats. We conclude that NOX reduces hepatocellular injury after endotoxemia. NOX may be useful in the management of hepatic dysfunction secondary to sepsis or other diseases associated with excessive NO production.

Short-term outcome of seizure patients who refuse transport after out-of-hospital evaluation.

OBJECTIVE: To determine the short-term outcome of patients with a known seizure disorder who have a seizure, are evaluated by out-of-hospital care providers, and refuse transport. METHODS: This was a prospective study conducted over a 15-month period. Philadelphia Fire Department paramedics contacted a medical command physician whenever they encountered a patient with a known seizure disorder who had had another seizure and was refusing transport. After confirming that the patient had the mental capacity to refuse care and understood the associated risks, the physician recorded the patient's name, address, and telephone number. Beginning three days later, a registered nurse attempted to reach the patient by telephone and administer a brief questionnaire about his or her medical outcome. Patients not reached by telephone were sent a certified letter. The names of patients lost to follow-up were compared with medical examiner records to confirm that they had not died during the follow-up period. RESULTS: Of 63 patients enrolled in the study, 52 (82.5%) were reached in follow-up. Of these, three (5.8%) had another seizure within 72 hours and recontacted 911. One of these patients (1.9%) was hospitalized. Twenty (38.5%) patients contacted their primary care physicians. There were no deaths, including patients lost to follow-up. CONCLUSIONS: Most patients (94.2%) who were evaluated by out-of-hospital care providers for a seizure and refused transport had no further seizure activity in the subsequent 72 hours. However, because there is a risk of recurrence, out-of-hospital care providers and medical command physicians should ensure that patients understand the risks of refusal.

Milk protein interfacial layers and the relationship to emulsion stability and rheology.

The properties of milk protein-stabilised, oil-in-water emulsions are determined by the structure and surface rheology of the adsorbed layer at the oil-water interface. Analysis of the segment density profiles normal to the surface show differences in the structure between adsorbed layers of disordered casein and globular whey protein. Systematic studies of stability and rheology of model oil-in-water emulsion systems made with milk proteins as sole emulsifiers give insight into the relation between adsorbed layer properties and bulk emulsion stability. Of particular importance are effects of pH, temperature, calcium ions and protein content. Colloidal interactions between adsorbed layers on different surfaces can be inferred from an analysis of dynamic collisions of protein-coated emulsion droplets in shear flow using the colloidal particle scattering technique. The role of competitive adsorption on emulsion properties can be derived from experiments on systems containing mixtures of milk proteins and small-molecule surfactants. Shear-induced destabilisation is especially influenced by the presence of fat crystals in the emulsion droplets. Aggregated gel network properties are dependent on the balance of weak and strong interparticle interactions. In heat-set whey protein emulsion gels, the rheological behaviour is especially sensitive to surfactant type and concentration. Rearrangements of transient caseinate-based emulsion gels can have a profound influence on the quiesent stability behaviour. Computer simulation provides a general link between particle interactions, microstructure and rheological properties.

Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice. A model for Li-Fraumeni syndrome.

Breast cancer is the most frequent tumor type among women in the United States and in individuals with Li-Fraumeni syndrome. The p53 tumor suppressor gene is altered in a large proportion of both spontaneous breast malignancies and Li-Fraumeni breast cancers. This suggests that loss of p53 can accelerate breast tumorigenesis, yet p53-deficient mice rarely develop mammary tumors. To evaluate the effect of p53 loss on mammary tumor formation, the p53(null) allele was back-crossed onto the BALB/c genetic background. Median survival was 15.4 weeks for BALB/c-p53(-/-) mice compared to 54 weeks for BALB/c-p53(+/-) mice. Sarcomas and lymphomas were the most frequent tumor types in BALB/c-p53(-/-) mice, whereas 55% of the female BALB/c-p53(+/-) mice developed mammary carcinomas. The mammary tumors were highly aneuploid, frequently lost the remaining wild-type p53 allele, but rarely lost BRCA1. Although mammary tumors were rarely detected in BALB/c-p53(-/-) female mice, when glands from BALB/c-p53(-/-) mice were transplanted into wild-type BALB/c hosts, 75% developed mammary tumors. The high rate of mammary tumor development in the BALB/c background, but not C57Bl/6 or 129/Sv, suggests a genetic predisposition toward mammary tumorigenesis. Therefore, the BALB/c-p53(+/-) mice provide a unique model for the study of breast cancer in Li-Fraumeni syndrome. These results demonstrate the critical role that the p53 tumor suppressor gene plays in preventing tumorigenesis in the mammary gland.

Recombinant human interleukin-11 prevents mucosal atrophy and bowel shortening in the defunctionalized intestine.

BACKGROUND: Mucosal atrophy and bowel shortening are the hallmark of proximal intestinal diversion for extensive necrotizing enterocolitis (NEC) or Thiry-Vella fistulas (TVF), in which the ends of a defunctionalized loop of intestine are exteriorized as stomas. Recombinant human interleukin-11 (rhIL-11) is a pleiotropic cytokine that promotes epithelial regeneration and enhances adaptation after bowel resection. The authors hypothesized that rhIL-11 may prevent mucosal atrophy and bowel shortening in rats with TVF METHODS: After creation of ileal TVF, Sprague-Dawley rats were selected randomly to receive either rhIL-11 or equal volume of 0.1% bovine serum albumin (BSA) subcutaneously daily. On day 14, the TVF were excised and examined morphologically. Enterocyte apoptosis was measured using the TUNEL assay. Mucosal DNA and protein content were measured. RESULTS: Administration of rhIL-11 resulted in a significantly greater weight gain and less shortening of TVF than BSA treatment. TVF from the rhIL-11-treated group showed evidence of hyperplasia and hypertrophy and increased crypt to villus ratio. The BSA group had substantial mucosal atrophy. There was a qualitative decrease in the incidence of apoptosis in the rhIL-11 group. CONCLUSIONS: Recombinant human IL-11 prevents mucosal atrophy and shortening of defunctionalized intestinal loops. It may help reduce the incidence of short gut syndrome in infants with extensive NEC.

A human SCO2 mutation helps define the role of Sco1p in the cytochrome oxidase assembly pathway.

Deficiencies in cytochrome oxidase, the terminal enzyme of the mitochondrial respiratory chain, are most often caused by an inability to complete assembly of the enzyme. Pathogenic mutations in SCO2, which encodes a cytochrome oxidase assembly factor, were recently described in several cases of fatal infantile cardioencephalomyopathy. To determine the molecular etiology of these disorders, we describe the generation and characterization of the parallel mutations in the homologous yeast SCO1 gene. We show that the E155K yeast sco1 mutant is respiration-competent, whereas the S240F mutant is not. Interestingly, the S240F mutation allows partial but incorrect assembly of cytochrome oxidase, as judged by an altered cytochrome aa(3) peak. Immunoblot analysis reveals a specific absence of subunit 2 from the cytochrome oxidase in this mutant. Taken together, our data suggest that Sco1p provides copper to the Cu(A) site on subunit 2 at a step occurring late in the assembly pathway. This is the first instance of a yeast cytochrome oxidase assembly mutant that is partially assembled. The S240F mutant also represents a powerful new tool with which to elucidate further steps in the cytochrome oxidase assembly pathway.

Expression of inducible nitric oxide synthase and interleukin-12 in experimental necrotizing enterocolitis.

BACKGROUND: Previous investigators have relied on administration of pro-inflammatory cytokines or invasive surgical procedures to reproduce the morphologic changes of necrotizing enterocolitis (NEC) in rats. However, these artificial insults do not mimic the human disease. We developed a reproducible model of NEC in rats that more closely resembles human NEC and determined the pattern of inflammatory cytokine expression in this model. MATERIALS AND METHODS: Newborn rats were randomized into four groups. Groups 1 and 2 were breast-fed, while Groups 3 and 4 were gavaged with formula thrice daily. In addition, Groups 2 and 4 were subjected to 3 min of hypoxia thrice daily, prior to each feeding. The rats were killed on day 4 and the distal 2 cm of terminal ileum was harvested for morphological studies and analysis of inflammatory cytokine mRNA expression. RESULTS: Nearly 70% of formula-fed neonatal rats displayed moderate or severe morphological abnormalities resembling human NEC. Breast-fed pups had normal histology. The terminal ileum from rats with abnormal histology demonstrated increased inducible nitric oxide synthase (iNOS) expression, decreased interleukin-12 (IL-12) mRNA expression, and enterocyte apoptosis. There was a trend toward upregulation of IFN-gamma mRNA, but no difference in expression of TNF-alpha mRNA. Hypoxia did not significantly alter intestinal morphology or mRNA expression. CONCLUSIONS: Formula-fed neonatal rats, with or without hypoxia, exhibit morphological changes in the intestinal epithelium similar to those seen in patients with acute NEC. The mechanism likely involves upregulation of iNOS mRNA, enterocyte apoptosis, and decreased IL-12 production in the intestinal epithelium. This model may offer a simple reproducible method for inducing experimental NEC.

Interfacial shear rheology of aged and heat-treated beta-lactoglobulin films: displacement by nonionic surfactant.

Interfacial shear rheology of adsorbed beta-lactoglobulin films (bulk protein concentration 10(-)(3) wt %) has been studied over the temperature range 20-90 degrees C using a two-dimensional Couette-type viscometer. Effects of the type of interface (air-water, triolein-water, and n-dodecane-water), the pH (2.0, 5.6, 6.0, 7.0, and 9.0), and the extent of the heat treatment have been assessed via measurements of changes in the apparent interfacial shear viscosity and elasticity before and after the addition of increasing amounts of nonionic surfactant Tween 20 (polyoxyethylene sorbitan monolaurate). The highest interfacial viscosities were obtained at the n-dodecane-water interface and the lowest at the air-water interface. Competitive displacement of protein from the interface by Tween 20 was easier at the air-water and n-dodecane-water interfaces as compared to the triolein-water interface. The surface shear viscosity was higher and the displacement by Tween 20 more difficult as the isoelectric point of the protein was approached, which is in agreement with the presence of a more strongly cross-linked protein network at the interface. The effect of heat treatment was dependent on the pH of the aqueous solution. No simple relationship between the surface rheological characteristics and the ease of displacement by Tween 20 could be inferred.