The IGF system is increasingly implicated in the development of cardiovascular disease. The effects of circulating IGFs on the vasculature are largely modulated by IGFBPs, which control their access to cell-surface IGF receptors. IGFBP-1 has been proposed as the acute regulator of IGF bioavailability because of its metabolic regulation by glucoregulatory hormones. Posttranslational phosphorylation of IGFBP-1 significantly increases its affinity for IGF-I and therefore represents a further mechanism for controlling IGF bioavailability. We have therefore examined the IGF system and IGFBP-1 phosphorylation status, using specifically developed immunoassays, in a cohort of 160 extensively characterized type 2 diabetic subjects on two occasions 12 months apart. Total IGFBP-1 (tIGFBP-1), which is predominantly highly phosphorylated, was significantly lower in subjects with known macrovascular disease triglycerides, and nonesterified fatty acids. In contrast, levels of nonphosphorylated and lesser-phosphorylated IGFBP-1 (lpIGFBP-1) were unrelated to macrovascular disease or hypertension but did correlate positively with fasting glucose concentration ( ؍ 0.350, P < 0.01). tIGFBP-1 concentrations were higher in subjects treated with insulin alone (n ؍ 29) than for any other group. This effect persisted after adjustment of tIGFBP-1 levels for BMI, C-peptide, age, and sex (F ؍ 6.5, P < 0.001, ؍ ؊0.46). Such an effect was not apparent for lpIGFBP-1. We conclude that low circulating levels of hpIGFBP-1 are closely correlated with macrovascular disease and hypertension in type 2 diabetes, whereas lpIGFBP-1 isoforms are associated with glycemic control, suggesting a dual role for IGFBP-1 in the regulation of IGF actions in type 2 diabetes. Our data suggest that high circulating concentrations of highly phosphorylated IGFBP-1 may protect against the development of hypertension and cardiovascular disease by reducing the mitogenic potential of IGFs on the vasculature.
ABSTRACT. A new diplomonad flagellate, Spironucleus vortens n. sp., is described from the intestinal lumen of the freshwater angelfish, (Pterophyllum scalare), bred in Florida. Live organisms are pyriform, and measure 12.5–20.5 μm long by 5.0–11.2 üm wide. Scanning electron microscopy shows that the trophozoite bears two compound lateral longitudinal ridges, each originating posterior to three emerging anterior flagella, and continuing posteriorly to the emergence of the posterior flagellum. Each ridge comprises a broad central part, surrounded by a peripheral ridge. At the opening of the flagellar pocket, the broader right peripheral ridge crosses to the other side of the body, and then back again. The posterior end of the body bears two papillae. Transmission electron microscopy shows that the compound lateral ridges are supported by microtubules, and bear microfibrillar structures in discrete longitudinal plaques. The serendipitous growth of S. vortens in a culture system with lip tumor tissue, facilitated axenic cultivation in a modified TYM medium (trypticase, yeast extract, maltose). The flagellate is now routinely maintained in an axenic TYI‐S‐33 medium (trypticase, yeast extract, iron serum), and is stabilized in the cryopreserved state. Spironucleus vortens is an aerotolerant anaerobe that can be cultured at 25° C, 28° C and 30° C.
Estrogen is known to modulate angiogenesis, both under physiological and pathological conditions, and has been demonstrated to augment angiogenesis induced by bFGF in a mouse model. We have modified this mouse model and measured the apparent plasma volume in Matrigel plugs containing basic fibroblast growth factor (bFGF) in wild type and estrogen receptor knockout, ovariectomized mice in the presence and absence of exogenous 17 beta estradiol. The apparent plasma volume was determined by measuring the fluorescence of the excised plug 10 min. after injection of fluoroscein labeled dextran 150. In wild type mice exogenous 17 beta estradiol increased the apparent plasma volume of the Matrigel plug and the uterine weight significantly. In the estrogen receptor knockout mice exogenous 17 beta estradiol caused a small, but significant increase in uterine weight but was without effect on the apparent plasma volume of the Matrigel plug. It is concluded that functional estrogen receptors are essential for the augmentation of bFGF-induced angiogenesis by exogenous 17 beta estradiol in female mice.
A Mamastrovirus was identified in an outbreak of diarrhea in cheetahs (Acinonyx jubatus). Five young adult and two adult cheetahs presented with lethargy, anorexia, watery diarrhea and regurgitation over an 11-day period. Fecal samples were submitted for electron microscopy and culture. Electron microscopy results revealed particles morphologically consistent with an astrovirus, and no other viral pathogens or significant bacterial pathogens were identified. The astrovirus was confirmed and sequenced using consensus astroviral PCR, resulting in a 367 base pair partial RNA-dependent-RNA polymerase (RdRp) product and a 628 base pair partial capsid product. Bayesian and maximum likelihood phylogenetic analyses were performed on both the RdRp and the capsid protein segments. All animals were monitored and treated with bismuth subsalicylate tablets (524mg PO BID for 5 days), and recovered without additional intervention. This is the first report we are aware of documenting an astrovirus outbreak in cheetah.
An embedded single filament test has been developed that measures the cumulative distribution of critical fibers lengths for a given fiber‐polymer system. The mean value of critical lengths and the dispersion of values are a function of both the shear transmission characteristics of the interface and the strength characteristics of the fibers. A computer model of the stochastic fracture process has been developed that incorporates a mixed‐element, weakest‐link model to describe the strength properties of the fibers, a random generator to describe the stochastics of multiple fiber fracture, and a shear‐lag analysis to describe the shear transmission across the interface. From the measurement of critical fiber lengths, a value for the magnitude of the shear transmission across the fiber‐polymer interface, τ, can be determined. From measured values fiber strength, the ability of a surface treatment to protect a given fiber can be determined. A variety of surface treatments for E‐glass are evaluated in a number of thermoplastic polymer materials. The experimental technique and the associated analysis are shown to be valuable in separating the coupling and sizing effects of the fiber surface treatment formulations. This should be of particular value in the optimization of commercial fiber treatment formulations.
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