Eotaxin and the attraction of eosinophils to the asthmatic lung

Eosinophilic leukocytes accumulate in high numbers in the lungs of asthmatic patients, and are believed to be important in the pathogenisis of asthma. A potent eosinophil chemoattractant is produced in the asthmatic lung. This small protein, the chemokine eotaxin, is synthesized by a number of different cell types, and is stimulated by interleukin-4 and interleukin-13, which are produced by T-helper (Th)2 lymphocytes. Low molecular weight compounds have been developed that can block the eotaxin receptor C-C chemokine receptor (CCR)3, and prevent stimulation by eotaxin. This provides the potential for orally available drugs that can prevent eosinophil recruitment into the lung and the associated damage and dysfunction.     

Spontaneous, in vitro, malignant transformation of a basophil/mast cell line

It has recently become possible to grow basophil/mast cells in vitro for extended periods of time. Normally, these cultures remain fully dependent upon the presence of an adequate supply of growth factor(s) and the cells express several basophil/mast cell differentiated traits. We report here a case of spontaneous, in vitro, malignant transformation of such a basophil/mast cell line. The transformed cells no longer require the addition of growth factor(s) for continuous proliferation in vitro, and they have become highly tumorigenic in vivo. In contrast, when compared to their untransformed counterparts, they display the same set of differentiated traits, characteristic of immature basophil/mast cells. Thus, the data support the hypothesis that cell transformation results from a decreased sensitivity of precursor cells toward normal growth regulators but does not affect significantly the expression of differentiated functions.     

Spontaneous, in vitro, Malignant Transformation of a Basophil/Mast Cell Line

Abstract. It has recently become possible to grow basophil/mast cells in vitro for extended periods of time. Normally, these cultures remain fully dependent upon the presence of an adequate supply of growth factor(s) and the cells express several basophil/mast cell differentiated traits. We report here a case of spontaneous, in vitro, malignant transformation of such a basophil/mast cell line. The transformed cells no longer require the addition of growth factor(s) for continuous proliferation in vitro, and they have become highly tumorigenic in vivo. In contrast, when compared to their untransformed counterparts, they display the same set of differentiated traits, characteristic of immature basophil/mast cells. Thus, the data support the hypothesis that cell transformation results from a decreased sensitivity of precursor cells toward normal growth regulators but does not affect significantly the expression of differentiated functions.     

pH titration study of cytochrome c peroxidase and apocytochrome c peroxidase.

A pH titration study of cytochrome c peroxidase and apocytochrome c peroxidase was carried out at 25 degrees C and 0.1 M ionic strength. The net charge on cytochrome c peroxidase due to proton association and dissociation varies from +32 at pH 2 to --50.2 at pH 12, while that of apocytochrome c peroxidase varies between +24.5 at pH 3 to --48 at pH 12. The apoprotein tented to aggregate below pH 3. Between pH 4 and 8, the titration behavior of both the native enzyme and the apoenzyme are consistent with the semi-empirical Linderstr?m-Lang theory. Between pH 9 and 12, the titration behavior of both the holo- and apoproteins suggest they assume a more extended conformation which reduces the electrostatic interaction charged groups on the surface. In the acid region, between pH 4 and 3, a similar transition occurs in which the protein expands 40% based on the electrostatic factor of the Linderstr?m-Lang theory.     

Some observations on enamel thickness and enamel prism packing in the miocene hominoid Otavipithecus namibiensis

Otavipithecus namibiensis is currently the sole representative of a Miocene hominoid radiation in subequatorial Africa. Several nondestructive techniques, such as computed tomography (CT) and confocal microscopy (CFM), can provide useful information about dental characteristics in this southern African Miocene hominoid. Our studies suggest that the molars of Otavipithecus are characterized by (1) thin enamel and (2) a predominance of pattern 1 enamel prism. Together, these findings provide little support for the recent suggestion of an Afropithecini clade consisting of Otavipithecus, Heliopithecus, and Afropithecus. Instead, they lend some (though not conclusive) support to the suggestion of an Otavipithecus/African ape clade distinct from Afropithecus. © 1995 Wiley-Liss, Inc.     

Sphingosine kinase 1 expression is regulated by signaling through PI3K, AKT2, and mTOR in human coronary artery smooth muscle cells

Sphingosine kinase 1 (SphK1) is a lipid kinase implicated in mitogenic signaling pathways in vascular smooth muscle cells. We demonstrate that human coronary artery smooth muscle (HCASM) cells require SphK1 for growth and that SphK1 mRNA and protein levels are elevated in PDGF stimulated HCASM cells. To determine the mechanism of PDGF-induced SphK1 expression, we used pharmacological inhibitors of the PI3K/AKT/mTOR signaling pathway. Wortmannin, SH-5, and rapamycin significantly blocked PDGF-stimulated induction of SphK1 mRNA and protein expression, indicating a regulatory role of the PI3K/AKT/mTOR pathway in SphK1 expression. To determine which isoform of AKT regulates SphK1 mRNA and protein levels, siRNAs specific for AKT1, AKT2, and AKT3 were used. We show that AKT2 siRNA significantly blocked PDGF-stimulated increases in SphK1 mRNA and protein expression levels as well as SphK1 enzymatic activity levels. In contrast, AKT1 or AKT3 siRNA did not have an effect. Together, these results demonstrate that the PI3K/AKT/mTOR signaling pathway is involved in regulation of SphK1, with AKT2 playing a key role in PDGF-induced SphK1 expression in HCASM cells.     

Measurement error in the Hawksley random zero sphygmomanometer: what damage has been done and what can we learn?

The Hawksley random zero sphygmomanometer is used in all aspects of blood pressure research, from clinical trials to evaluation of new blood pressure recorders. It is designed to reduce observer bias in blood pressure measurement. The problem is that it also underestimates blood pressure. Furthermore, this was first reported more than two decades ago. In this paper Rónán Conroy and colleagues explore the consequences of using an inaccurate instrument for important research and why prestigious organisations like the World Health Organisation continue to use it.