Epithelial marker genes are expressed in cultured embryonic rat lung and in vivo with similar spatial and temporal patterns

Explants of embryonic lung are often used to characterize lung growth, bronchial tree pattern, and cell differentiation. Most investigators culture lungs for 3-7 days in defined media lacking, e.g., added growth factors or hormones. If growth and differentiation are comparable to that in vivo, these cultures show considerable promise for identifying developmental regulatory molecules and target genes, and for elucidating molecular responses. We used in situ hybridization and RT-PCR to compare times and sites of expression of mRNAs of six epithelial genes in cultured and uncultured fetal rat lungs. These genes, expressed in distal lung of adult rats, are surfactant proteins (SP) A, B, and C; LAR, a receptor-type tyrosine phosphatase; Clara cell secretory protein (CC10, CCSP); and T1alpha. SP-A, SF-B, LAR, and CC10 are expressed by both Clara and Type II cells in adult animals. SP-C and T1alpha are unique markers for Type II and Type I cells, respectively. SP-C, LAR, and T1alpha are expressed before the lung is explanted (Day 13.5); SP-A, -B, and CC10 mRNAs are first detected later. The onset of expression is similar in vivo and in vitro. Although the patterns of expression differ for each mRNA, their sites of expression in culture match those in vivo relative to the bronchial tree. The explanted embryonic lung appears to be an excellent experimental model.     

Gag rules and trade secrets in managed care contracts. Ethical and legal concerns

Gag rules-clauses in managed care contracts that prevent physicians from disclosing information that the plan may find disparaging, but that could relate directly to the patient's health-have recently been the subject of ethical condemnation and legislative prohibition. Another serious problem in managed care contracts, trade secrets, or guidelines and quality assurance mechanisms that are imposed on physicians while their origins are shrouded in proprietary secrecy, have by contrast received little attention. Responses to these ethical challenges to the physician's integrity must involve individual physicians, managed care organizations, professional organizations, and public policymakers.     

Gene amplification in a p53-deficient cell line requires cell cycle progression under conditions that generate DNA breakage

Amplification of genes involved in signal transduction and cell cycle control occurs in a significant fraction of human cancers. Loss of p53 function has been proposed to enable cells with gene amplification to arise spontaneously during growth in vitro. However, this conclusion derives from studies employing the UMP synthesis inhibitor N-phosphonacetyl-L-aspartate (PALA), which, in addition to selecting for cells containing extra copies of the CAD locus, enables p53-deficient cells to enter S phase and acquire the DNA breaks that initiate the amplification process. Thus, it has not been possible to determine if gene amplification occurs spontaneously or results from the inductive effects of the selective agent. The studies reported here assess whether p53 deficiency leads to spontaneous genetic instability by comparing cell cycle responses and amplification frequencies of the human fibrosarcoma cell line HT1080 when treated with PALA or with methotrexate, an antifolate that, under the conditions used, should not generate DNA breaks. p53-deficient HT1080 cells generated PALA-resistant variants containing amplified CAD genes at a frequency of >10(-5). By contrast, methotrexate selection did not result in resistant cells at a detectable frequency (<10(-9)). However, growth of HT1080 cells under conditions that induced DNA breakage prior to selection generated methotrexate-resistant clones containing amplified dihydrofolate reductase sequences at a high frequency. These data demonstrate that, under standard growth conditions, p53 loss is not sufficient to enable cells to produce the DNA breaks that initiate amplification. We propose that p53-deficient cells must proceed through S phase under conditions that induce DNA breakage for genetic instability to occur.     

Are Samples in Randomized Controlled Trials of Psychotherapy Representative of Community Outpatients? A New Methodology and Initial Findings.

To determine the extent to which published randomized controlled trials (RCTs) of psychotherapy can be generalized to a sample of community outpatients, the authors used a method of matching information obtained from outpatient charts to inclusion and exclusion criteria from published RCT studies. They found that 80% of the patients in their sample who had diagnoses represented in the RCT literature were judged eligible for at least 1 published RCT; however, 58% of the patients had primary diagnoses such as adjustment disorder or dysthymia, which were not represented in the existing psychotherapy outcome literature. The most common reasons that patients in their sample did not match with published RCTs for psychotherapy are listed, and the implications of these findings for research and practice are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neighborhood disadvantage moderates associations of parenting and older sibling problem attitudes and behavior with conduct disorders in African American children.

Data from 296 sibling pairs (mean ages 10 and 13 years), their primary caregivers, and census records were used to test the hypothesis that African American children's likelihood of developing conduct problems associated with harsh parenting, a lack of nurturant-involved parenting, and exposure to an older sibling's deviance-prone attitudes and behavior would be amplified among families residing in disadvantaged neighborhoods. A latent construct representing harsh-inconsistent parenting and low levels of nurturant-involved parenting was positively associated with younger siblings' conduct disorder symptoms, as were older siblings' problematic attitudes and behavior. These associations were strongest among families residing in the most disadvantaged neighborhoods. Future research and prevention programs should focus on the specific neighborhood processes associated with increased vulnerability for behavior problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison between morphologic changes seen on high-resolution CT and regional pulmonary perfusion seen on SPECT in patients with cystic fibrosis

OBJECTIVE: To evaluate the relationship between morphologic findings seen on high-resolution computed tomography (HRCT) of the lung and regional lung perfusion depicted on single photon-emission computed tomography (SPECT) pulmonary perfusion imaging in patients with cystic fibrosis. MATERIALS AND METHODS: Ten HRCT and 10 technetium-99 m macroaggregated albumin SPECT pulmonary perfusion imaging studies were performed on eight young adult patients who were considered to be clinically well and have mild to moderate cystic fibrosis. HRCT scans of the chest were evaluated using a CT scoring system which included grading of bronchiectasis, peribronchial thickening, hyperlucency, bullae, collapse/consolidation, and mucus plugging. Each lung was divided into six anatomic zones which were independently scored. A lung perfusion score (between 0 and 100), reflecting the percentage of compromised lung, was estimated for each zone. Axial lung perfusion SPECT images were matched anatomically to HRCT images. Lung function was considered compromised when the counts per pixel were less than 25 % of the count level seen in an area of the same patient's lung which was judged to be normal. RESULTS: There was a statistically significant relationship (P = 0.0001) between HRCT total scores and SPECT lung perfusion scores as well as between hyperlucency scores by HRCT and the SPECT lung perfusion scores. However, the HRCT score was a poor predictor of the lung perfusion score in zones with intermediate HRCT scores, which constituted 106 of 120 zones. CONCLUSION: Morphologic changes depicted by HRCT correlate with decreased lung pefusion on SPECT. However, HRCT changes accurately predict regional lung function only in the most normal and severely diseased lung zones.     

β-Carotene transport in human lipoproteins. Comparisons with a-tocopherol

The purpose of this study was to investigate the temporal relationships of the transport of β-carotene in human lipoproteins. We administered 60 mg β-carotene with breakfast to nine fasting subjects, then blood samples were collected at intervals of up to 75 h, lipoproteins were isolated, and β-carotene was quantitated. β-Carotene concentrations in chylomicrons and very low density lipoproteins (VLDL) peaked at 6 and 9 h, respectively. Nonetheless, at all time points the majority of plasma β-carotene was contained in low density lipoproteins (LDL), while high density lipoproteins (HDL) carried a smaller portion (at 24 h, 73±8% in LDL as compared with 23±5% in HDL). In three subjects, transport of β-carotene was compred with the results of earlier studies on the transport of stereoisomers of α-tocopherol. Unlike plasmaRRR-α-tocopherol concentrations, which are maintained by the preferential incorporation ofRRR-α-tocopherol into VLDL by the liver, β-carotene increased and decreased in VLDL similarly toSRR-α-tocopherol, a stereoisomer whose concentrations are not maintained in plasma. In conclusion, β-carotene is primarily transported in the plasma in LDL, but its incorporation by the liver into lipoproteins does not appear to be enhanced.     

Orientation suppression in fibers spun from polymer melt blends

The addition of very small amounts of carefully selected polymers by melt blending has been found to radically change the flow properties at spinning of conventional polymers such as polyethylene terephthalate, nylon 66, and polypropylene. This has a large effect on spun properties, especially at high wind-up speeds. The additive polymers used have included liquid crystal polymers, polyethlene, polyethylene glycol, and nylon 66. A major phenomen is a considerable lowering of spun orientation, or wind-up speed suppression. In order to activate the non-liquid crystal polymers to achieve this effect special spinning conditions are necessary. The mechanism is viewed as being nonuniform extensional flow in a two-phase system and not molecular interaction.     

Using solidification parameters to predict porosity distributions in alloy castings

Quality criteria used in the computer-aided design and analysis of casting processes typically relate geometric, thermal, or solidification parameters to structural features such as centerline shrinkage and microporosity. Quality criteria for the prediction of porosity in castings have been used successfully in steel, but the application of criteria functions to nonferrous alloys has been less successful. Recent work suggests that the dominating mechanism that determines the amount and distribution of porosity in castings is strongly dependent on the solidification mode of the alloy and the solidification conditions. Accordingly, casting processes and alloy types are divided into four groups, and a different set of criteria functions are obtained for each group.