Tufts University

About: Tufts University is a education organization based out in Medford, Massachusetts, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 32800 authors who have published 66881 publications receiving 3451152 citations. The organization is also known as: Tufts College & Universitatis Tuftensis.

Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization

Abstract: The therapeutic implications of angiogenic growth factors were identified by the pioneering work of Folkman 2 decades ago (1). His laboratory’s work documented the extent to which tumor development was dependent upon neovascularization and suggested that this relationship might involve angiogenic growth factors that were specific for neoplasms. Subsequent investigations have established the feasibility of using recombinant formulations of such angiogenic growth factors to expedite and/or augment collateral artery development in animal models of myocardial and hindlimb ischemia. This novel strategy for the treatment of vascular insufficiency was termed therapeutic angiogenesis (2). More recent data suggests that the basis for native and therapeutic neovascularization is not restricted to angiogenesis but includes postnatal vasculogenesis as well. Data supporting these notions, as well as derivative concepts and concerns, are the subject of this Perspective.

A review of optical coherence tomography angiography (OCTA).

Abstract: Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging technique that generates volumetric angiography images in a matter of seconds. This is a nascent technology with a potential wide applicability for retinal vascular disease. At present, level 1 evidence of the technology’s clinical applications doesn’t exist. In this paper, we introduce the technology, review the available English language publications regarding OCTA, and compare it with the current angiographic gold standards, fluorescein angiography (FA) and indocyanine green angiography (ICGA). Finally we summarize its potential application to retinal vascular diseases. OCTA is quick and non-invasive, and provides volumetric data with the clinical capability of specifically localizing and delineating pathology along with the ability to show both structural and blood flow information in tandem. Its current limitations include a relatively small field of view, inability to show leakage, and proclivity for image artifact due to patient movement/blinking. Published studies hint at OCTA’s potential efficacy in the evaluation of common ophthalmologic diseases such age related macular degeneration (AMD), diabetic retinopathy, artery and vein occlusions, and glaucoma. OCTA can detect changes in choroidal blood vessel flow and can elucidate the presence of choroidal neovascularization (CNV) in a variety of conditions but especially in AMD. It provides a highly detailed view of the retinal vasculature, which allows for accurate delineation of the foveal avascular zone (FAZ) in diabetic eyes and detection of subtle microvascular abnormalities in diabetic and vascular occlusive eyes. Optic disc perfusion in glaucomatous eyes is notable as well on OCTA. Further studies are needed to more definitively determine OCTA’s utility in the clinical setting and to establish if this technology may offer a non-invasive option of visualizing the retinal vasculature in detail.

Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP.

Abstract: Substitution of asparagine for serine at position 17 decreased the affinity of rasH p21 for GTP 20- to 40-fold without significantly affecting its affinity for GDP. Transfection of NIH 3T3 cells with a mammalian expression vector containing the Asn-17 rasH gene and a Neor gene under the control of the same promoter yielded only a small fraction of the expected number of G418-resistant colonies, indicating that expression of Asn-17 p21 inhibited cell proliferation. The inhibitory effect of Asn-17 p21 required its localization to the plasma membrane and was reversed by coexpression of an activated ras gene, indicating that the mutant p21 blocked the endogenous ras function required for NIH 3T3 cell proliferation. NIH 3T3 cells transformed by v-mos and v-raf, but not v-src, were resistant to inhibition by Asn-17 p21, indicating that the requirement for normal ras function can be bypassed by these cytoplasmic oncogenes. The Asn-17 mutant represents a novel reagent for the study of ras function by virtue of its ability to inhibit cellular ras activity in vivo. Since this phenotype is likely associated with the preferential affinity of the mutant protein for GDP, analogous mutations might also yield inhibitors of other proteins whose activities are regulated by guanine nucleotide binding.

Circulating Interleukin-1 and Tumor Necrosis Factor in Septic Shock and Experimental Endotoxin Fever

Abstract: Interleukins (IL) -1 beta and -1 alpha and tumor necrosis factor (TNF-alpha) were measured by radioimmunoassay in plasma samples from 44 healthy individuals, 15 patients in septic shock, and 6 volunteers infused with endotoxin. Plasma IL-1 alpha levels were low (40 pg/ml) or undetectable in all situations. In 67% of the healthy subjects, plasma IL-1 beta levels were less than 70 pg/ml. Septic patients had higher plasma IL-1 beta levels (120 +/- 17 pg/ml, P = .001); those of surviving patients were higher than those of patients who died (P = .05). Plasma TNF-alpha concentrations in septic individuals were elevated (119 +/- 30 pg/ml) and correlated with severity of illness (r = .73, P = .003), but no correlation was observed between plasma IL-1 beta and TNF-alpha concentrations in individual samples. Infusion of endotoxin caused a twofold elevation of IL-1 beta, from a baseline of 35 +/- 5 pg/ml to a maximum of 69 +/- 27 pg/ml at 180 min (P less than .05). Peak TNF-alpha levels after endotoxin infusion were 15 times higher than IL-1 beta levels, were attained more rapidly (90 min), and as with the septic patients, did not correlate with IL-1 beta levels. These data support the concept that plasma IL-1 beta and TNF-alpha concentrations are regulated independently and are associated with different clinical outcomes.

Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene.

Abstract: The DCC (Deleted in colorectal cancer) gene was first identified as a candidate for a tumour-suppressor gene on human chromosome 18q. More recently, in vitro studies in rodents have provided evidence that DCC might function as a receptor for the axonal chemoattractant netrin-1. Inactivation of the murine Dcc gene caused defects in axonal projections that are similar to those observed in netrin-1-deficient mice but did not affect growth, differentiation, morphogenesis or tumorigenesis in mouse intestine. These observations fail to support a tumour-suppressor function for Dcc, but are consistent with the hypothesis that DCC is a component of a receptor for netrin-1.