Airway neural responses to kinins: tachyphylaxis and role of receptor subtypes

Heparitinase cleaves heparan sulfate, a glycosaminoglycan associated with all nucleated mammalian cells and extracellular matrices. Despite the important physiologic role heparitinase is postulated to play in such processes as tumor metastasis and inflammation, the identity of the enzyme remains a matter of controversy and there is a question of whether heparitinase is CTAP III. We report a 900,000-fold purification of heparitinase from human platelets. A multi-step procedure utilizing chromatography on heparin, DEAE, hydroxyapatite and size exclusion matrices was employed and yielded a single protein as judged by Coomassie staining of protein separated by SDS-PAGE. The purified protein had an apparent molecular mass of 35 kDa by size exclusion chromatography and 55 kDa by SDS-PAGE. During purification, heparitinase activity co-eluted from the hydroxyapatite and size exclusion columns with the 35-55 kDa protein, confirming that the purified protein was indeed heparitinase. The 35-55 kDa protein reacted strongly with concanavalin A, a lectin known to bind to heparitinase, further confirming that the protein was heparitinase. Platelet heparitinase formed dimers and tetramers upon storage in a purified form, possibly accounting for the various molecular weights previously reported for the enzyme. A partial amino acid sequence of the protein revealed that heparitinase has not been previously sequenced.     

Age-related differences and change in positive and negative affect over 23 years.

Positive and negative affect, measured by the Bradburn Affect Balance Scale, were studied in a longitudinal sample spanning from 1971 to 1994. The sample (N?=?2,804) represented 4 generations of families. Linear trend analyses compared generations over time for positive and negative affect and also examined the possible influences of neuroticism and extraversion on initial levels of affect and patterns of change in affect. Negative affect decreased with age for all generations, although the rate was attenuated among the oldest adults. Higher neuroticism scores also attenuated the decrease in negative affect across time. For positive affect, the younger and middle-aged adults showed marked stability, but the older group evidenced a small decrease over time. Higher levels of extraversion were related to more stability in positive affect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential functioning of the Beck Depression inventory in late-life patients: Use of item response theory.

The present analyses examined age-related measurement bias in responses to items on the revised Beck Depression Inventory (BDI) in depressed late-life patients versus midlife patients. Item response theory (IRT) models were used to equate the scale and to differentiate true-group differences from bias in measurement in the 2 samples. Baseline BDI data (218 late life and 613 midlife) were used for the present analysis. IRT results indicated that late-life patients tended to report fewer cognitive symptoms, especially at low to average levels of depression. Conversely, they tended to report more somatic symptoms, especially at higher levels of depression. Adjusted cutoff scores in the late-life group are provided, and possible reasons for age-related differences in the performance of the BDI are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cellular uptake properties of a 2''-amino/2''-O-methyl-modified chimeric hammerhead ribozyme targeted to the epidermal growth factor receptor mRNA

PURPOSE: Rhabdomyosarcomas (RMS) are heterogeneous in their clinical presentation, histology, and cytogenetics. The growth of some RMS cells has been found to be regulated by the tyrosine kinase insulin-like growth factor (IGF) type I receptor. However, RMS cells exhibit variable sensitivity to inhibitors of tyrosine kinases and IGF receptors. Collectively, these heterogeneous features suggest that differences exist in the growth regulatory pathways of RMS. The objective of this study is to identify active tyrosine kinase signal transduction pathways in embryonal and alveolar RMS cells. METHODS: RMS tumor samples and cell lines representing both embryonal and alveolar histologic subtypes have been analyzed by immunoprecipitation and immunoblotting techniques to characterize phosphotyrosyl protein patterns and to identify tyrosine phosphorylated proteins. RESULTS: RMS cells can be characterized based on the patterns of phosphotyrosyl proteins, including the phosphorylation status of the catenin-like protein Cas1 and the signal adapter protein SHC, and the activation of IGF type I receptor signaling cascades including the formation of SHC-GRB2 signal protein complexes and MAP kinase activation. CONCLUSIONS: Rhabdomyosarcomas, especially the embryonal histologic subtype, are heterogeneous at the level of tyrosine kinase signal transduction. It will be important to characterize the growth regulatory pathways active in individual RMS tumors before targeting molecular therapies to this malignancy.     

Osteochondrodysplasia occurring in transgenic mice expressing interferon-gamma

Arterial thrombi are primarily composed of platelets. Platelets are bound to injured endothelial cells, sub-endothelial matrices, and other platelets by a range of adhesive proteins. Some of these reactions are governed by shear forces. The role of adhesive proteins in the pathogenesis of arterial thrombosis is not fully understood. The aim of this study was to examine the involvement of von Willebrand factor (vWF), fibrinogen (Fg), and fibronectin (FN) in the formation of microvascular thrombi in vivo using a helium-neon laser-induced thrombosis method. Transmission electron microscopy demonstrated that laser irradiation resulted in platelet-rich thrombosis in arterioles and venules, and revealed that this occurred in the absence of endothelial denudation. The mean wall shear rates in mesenteric arterioles and venules were 641 +/- 40 and 280 +/- 20 s-1, respectively. Shear rates increased approximately fivefold in arterioles and tenfold in venules during the formation of occlusive thrombi. Antibody to vWF inhibited thrombosis in arterioles and venules. Antibodies to Fg and FN inhibited thrombosis in venules but not in arterioles. These results confirm that vWF, Fg and FN were involved in thrombogenesis in vivo and demonstrated that significantly higher shear rates were required for the reactions involving vWF than those involving either Fg or FN.     

Cognitive profile of fragile X premutation carriers with and without fragile X-associated tremor/ataxia syndrome.

Fragile X-associated tremor/ataxia syndrome (FXTAS) develops in a subset of fragile X premutation carriers and involves gait ataxia, action tremor, Parkinsonism, peripheral neuropathy, autonomic disorders, and cognitive impairment. The study was designed to define the nature of cognitive deficits affecting male premutation carriers with and without FXTAS. A sample of 109 men underwent motor, cognitive, genetic, and neurologic testing, as well as brain magnetic resonance imaging. Subjects were classified into 3 groups: (a) asymptomatic premutation carriers, (b) premutation carriers with FXTAS, and (c) normal controls. Men with FXTAS performed worse than controls on mental status, intelligence, executive cognitive functioning (ECF), working memory, remote recall of information, declarative learning and memory, information processing speed, and temporal sequencing, as well as 1 measure of visuospatial functioning. Language and verbal comprehension were spared. Asymptomatic carriers performed worse than controls on ECF and declarative learning and memory. This comprehensive examination of cognitive impairment in male premutation carriers suggests that FXTAS involves substantial executive impairment and diffuse deficits in other cognitive functions. Longitudinal research currently underway will provide insight into the progression of the disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extended early childhood intervention and school achievement: age thirteen findings from the Chicago Longitudinal Study

We evaluated the effects of participation in an extended program of compensatory education for 559 low-income, inner-city African American children up to seventh grade. The intervention is the federal and state-funded Chicago Child-Parent Center and Expansion Program, which began in 1967. Groups included 426 children who participated in the program from preschool to grades 2 or 3 and 133 children whose participation ceased in kindergarten. After taking into account initial differences in achievement at kindergarten entry and at the end of kindergarten, and after taking into account sample selection bias, program participation for 2 or 3 years after preschool and kindergarten was associated with significantly higher reading achievement up to seventh grade and with lower rates of cumulative grade retention and special education placement (4 to 5 years postprogram). Children participating in the follow-on program for 3 years had significantly higher reading achievement in seventh grade and a lower rate of grade retention than 3 year participants. Only 3 year participants had significantly higher math achievement than the comparison group. Study findings provide rare longitudinal evidence of the beneficial effects of a large-scale community-based program of extended early childhood intervention.     

EFFECT OF PREHYDROGENATION ON HYDROCONVERSION OF MAYA RESIDUUM, PART II: HYDROGEN INCORPORATION

Maya 650° F residuum (Maya AR) was prehydrogenated over a standard hydroprocessing catalyst. The 650°F residuum of this product lpar;HMaya ARrpar; and Maya AR were then separately hydroprocessed further at selected conditions. The products were examined by elemental, ¹H, and ¹³C NMR analyses to determine the how hydrogen was incorporated during processing.

For all processing steps, hydrogen was incorporated in capping fragments formed during cracking reactions, as well as in hydrogenation reactions, heteroatom removal, and hydrocarbon gas formation, but the distribution of the hydrogen was dependent upon the type and severity of the process: For the direct hydroconversion of Maya AR, 25 to 30% of the total hydrogen was incorporated for heteroatom removal and hydrocarbon gas formation. The remaining hydrogen was incorporated in hydrogenation and cracking reactions.

For the two-step hydroconversion process, 30 to 40% of the total hydrogen was incorporated for heteroatom removal and hydrocarbon gas formation. The remaining was primarily incorporated in hydrogenation reactions. Some was incorporated into cracking reactions in the moderate severity case, but almost none was seen in the low severity case.

The hydrogen incorporation during each specific processing step is discussed, along with an evaluation of the prehydrogenation step a residuum conversion process option. These results will be also compared to previously reported hydrogen incorporation measurements on other feeds and processing methods.