The role of genotoxicity in asbestos-induced mesothelioma: an explanation for the differences in carcinogenic potential among fiber types

2013 ◽  
Vol 25 (9) ◽  
pp. 553-567 ◽  
Author(s):  
Christy A. Barlow ◽  
Laura Lievense ◽  
Sherilyn Gross ◽  
Christopher J. Ronk ◽  
Dennis J. Paustenbach
2021 ◽  
Vol 18 ◽  
Author(s):  
Mikhail I. Nemenov ◽  
Robinson J. Singleton ◽  
Louis S. Premkumar

: The cutaneous mechanisms that trigger spontaneous neuropathic pain in diabetic peripheral neuropathy (PDPN) are far from clear. Two types of nociceptors are found within the epidermal and dermal skin layers. Small-diameter lightly myelinated Aδ and unmyelinated C cutaneous mechano and heat sensitive (AMH and CMH) and C mechanoinsensitive (CMi) nociceptors transmit pain from the periphery to central nervous system. AMH and CMH fibers are mainly located in the epidermis and CMi fibers are distributed in the dermis. In DPN, dying back intra-epidermal AMH and CMH fibers leads to reduced pain sensitivity and the patients exhibit significantly increased pain thresholds to acute pain, when tested using traditional methods. The role of CMi fibers in painful neuropathies has not been fully explored. Microneurography has been the only tool to access CMi fibers and differentiate AMH, CMH and CMi fiber types. Due to the complexity, its use is impractical in clinical settings. In contrast, a newly developed diode laser fiber selective stimulation (DLss) technique allows to safely and selectively stimulate Aδ and C fibers in the superficial and deep skin layers. DLss data demonstrate that patients with painful DPN have increased Aδ fiber pain thresholds, while C-fiber thresholds are intact because in these patients CMi fibers are abnormally spontaneously active. It is also possible to determine the involvement of CMi fibers by measuring the area of DLss-induced neurogenic axon reflex flare. The differences in AMH, CMH and CMi fibers allow to identify patients with painful and painless neuropathy. In this review, we will discuss the role of CMi fibers in PDPN.


2017 ◽  
Vol 14 (5) ◽  
pp. 469-482 ◽  
Author(s):  
Jonathan E Jennings ◽  
Amin B Kassam ◽  
Melanie B Fukui ◽  
Alejandro Monroy-Sosa ◽  
Srikant Chakravarthi ◽  
...  

AbstractBACKGROUNDThe imperative role of white matter preservation in improving surgical functional outcomes is now recognized. Understanding the fundamental white matter framework is essential for translating the anatomic and functional literature into practical strategies for surgical planning and neuronavigation.OBJECTIVETo present a 3-dimensional (3-D) atlas of the structural and functional scaffolding of human white matter—ie, a “Surgical White Matter Chassis (SWMC)”—that can be used as an organizational tool in designing precise and individualized trajectory-based neurosurgical corridors.METHODSPreoperative diffusion tensor imaging magnetic resonance images were obtained prior to each of our last 100 awake subcortical resections, using a clinically available 3.0 Tesla system. Tractography was generated using a semiautomated deterministic global seeding algorithm. Tract data were conceptualized as a 3-D modular chassis based on the 3 major fiber types, organized along median and paramedian planes, with special attention to limbic and neocortical association tracts and their interconnections.RESULTSWe discuss practical implementation of the SWMC concept, and highlight its use in planning select illustrative cases. Emphasis has been given to developing practical understanding of the arcuate fasciculus, uncinate fasciculus, and vertical rami of the superior longitudinal fasciculus, which are often-neglected fibers in surgical planning.CONCLUSIONA working knowledge of white matter anatomy, as embodied in the SWMC, is of paramount importance to the planning of parafascicular surgical trajectories, and can serve as a basis for developing reliable safe corridors, or modules, toward the goal of “zero-footprint” transsulcal access to the subcortical space.


1980 ◽  
Vol 239 (1) ◽  
pp. E88-E95 ◽  
Author(s):  
K. E. Flaim ◽  
M. E. Copenhaver ◽  
L. S. Jefferson

The effects of acute (2-day) and long-term (7-day) diabetes on rates of protein synthesis, peptide-chain initiation, and levels of RNA were examined in rat skeletal muscles that are known to have differing proportions of the three fiber types: fast-twitch white, fast-twitch red, and slow-twitch red. Short-term diabetes resulted in a 15% reduction in the level of RNA in all the muscles studied and an impairment in peptide-chain initiation in muscles with mixed fast-twitch fibers. In contrast, the soleus, a skeletal muscle with high proportions of slow-twitch red fibers, showed little impairment in initiation. When the muscles were perfused as a part of the hemicorpus preparation, addition of insulin to the medium caused a rapid reversal of the block in initiation in mixed fast-twitch muscles but had no effect in the soleus. The possible role of fatty acids in accounting for these differences is discussed. Long-term diabetes caused no further reduction in RNA, but resulted in the development of an additional impairment to protein synthesis that also affected the soleus and that was not corrected by perfusion with insulin. The defect resulting from long-term diabetes may involve elongation or termination reactions.


2004 ◽  
Vol os-13 (2) ◽  
pp. 1558925004os-13
Author(s):  
N. B. Doguc ◽  
Abdelfattah M. Seyam ◽  
William Oxenham

The performance of four different fiber types processed at two different carding speeds of 85 and 120 m/min, under fixed operating conditions, was assessed. The totally novel approach of fixing the fiber diameter was used in the experiments. To serve this purpose, we designed four different fibers. In addition, we fixed the number of fibers per unit area of the carded web so as to create constant carding conditions for all experimental fibers. The fixed number of fibers per unit area was achieved by carding the same number of fibers per unit time for a given speed. We took samples from different parts of the card and analyzed them in order to enumerate the effect of fiber type on cardability. Fiberweb uniformity was regarded as a key parameter for assessing the cardability. Several other web and fiber parameters were measured in order to augment the understanding of the role of fiber type in high-speed carding. In general, data revealed that fiberweb uniformity did not significantly differ among fiber types at the two carding speeds 85 m/min and 120 m/min.


2014 ◽  
Vol 36 (2) ◽  
pp. 20-25 ◽  
Author(s):  
Dan Ogborn ◽  
Brad J. Schoenfeld

1995 ◽  
Vol 268 (2) ◽  
pp. C480-C489 ◽  
Author(s):  
P. B. Chase ◽  
M. J. Kushmerick

To directly assess the possible role of ADP in muscle fatigue, we have studied the effect of physiological MgADP levels on maximum Ca(2+)-activated isometric force and unloaded shortening velocity (Vus) of single skinned fiber segments from rabbit fast-twitch (psoas) and slow-twitch (soleus) muscles. MgADP concentration was changed in a controlled and well-buffered manner by varying creatine (Cr) in solutions, which also contained MgATP, phosphocreatine (PCr), and creatine kinase (CK). To quantify ADP as a function of Cr added, we determined the apparent equilibrium constant (K') of CK for the conditions of our experiments (pH 7.1, 3 mM Mg2+, 12 degrees C): K' = (sigma [Cr]. sigma [ATP])/(sigma [PCr]. sigma [ADP]) = 260 +/- 3 (SE). In this manner, ADP was altered essentially as occurs during stimulation in vivo but without the concomitant changes in pH and P(i), which affect force and Vus. As ADP (and Cr) was increased, force and Vus decreased in both fiber types; at the highest ADP level used, 200 microM, normalized force was 96.6 +/- 1.7% for psoas (n = 6) and 93.7 +/- 2.8% for soleus (n = 6), and Vus was 80.4 +/- 2.4% for psoas and 91.3 +/- 7.7% for soleus. Diffusion-reaction calculations indicated that radial gradients of metabolite concentrations within fibers could not explain the small effects of ADP on fiber mechanics, and experiments verified that metabolite levels were well buffered within fibers by the CK reaction. Exogenous CK was added to bathing solutions at 290 U/ml, threefold above that necessary to maintain Vus independent of CK concentration; in the absence of PCr and exogenous CK, at least a fourfold increased MgATP was necessary to maintain Vus at the control level. Adenylate kinase activity was not detectable; thus myofibrillar adenosine-triphosphatase and exogenous CK activities were the major determinants of nucleotide levels within activated cells. Cr alone (in absence of PCr and exogenous CK) also decreased force and Vus, presumably by a nonspecific mechanism. Over the physiological range, altered ADP had little or no effect on force or Vus in well-buffered conditions. It is therefore likely that other factors decrease force and Vus during muscular fatigue.


2021 ◽  
Author(s):  
Vincent Salvatore Gallicchio ◽  
Juley Harper

There has been increased concern on many levels focused on the environmental and occupational exposure of heavy metals and their impact on disease, specifically the carcinogenic potential inducing cancer in humans. Because the impact of heavy metals on human health continues to be a major health concern, research continues to improve our understanding of the carcinogenic potential of these substances. Of particular concern have been human exposure to aluminum, arsenic, beryllium, cadmium, lead, mercury, nickel, and radium and their carcinogenic potential whether contact is via environmental or occupational exposure. This updated review focuses on the carcinogenic mechanisms heavy metals use to induce malignant transformation of cells as well as addressing the overall environmental and occupational hazards of heavy metal exposure.


1956 ◽  
Vol 39 (5) ◽  
pp. 753-772 ◽  
Author(s):  
William J. Adelman

The three types of motor axons found in the walking legs of the lobster were shown to respond differently upon exposure to calcium-free solutions. While all fiber types became more excitable initially in calcium-free solutions, only openers became spontaneously active. Fast closers showed the least reduction in rheobase value upon calcium depletion. After 5 minutes in calcium-free solution all fibers showed a rise in rheobase value, and more rapid accommodation. A natural period for spontaneous firing of opener fibers was disclosed. Following such a spontaneous discharge, low amplitude rhythmical potentials were recorded. These small potentials had the same period as the spontaneous spikes. The role of calcium ion in the excitable process was discussed. Magnesium ion was shown to act synergistically with calcium ion. All fiber types became spontaneously active in solutions deprived of both calcium and magnesium. Subsequent hypoexcitability was more pronounced in calcium- and magnesium-depleted solutions than it was in only calcium-depleted solutions.


2020 ◽  
Author(s):  
Lien A. Phung ◽  
Aurora D. Foster ◽  
Mark S. Miller ◽  
Dawn A. Lowe ◽  
David D. Thomas

AbstractThe myosin super-relaxed state (SRX) in skeletal muscle is hypothesized to play an important role in regulating muscle contractility and thermogenesis in humans, but has only been examined in model organisms. Here we report the first human skeletal muscle SRX measurements, using quantitative epifluorescence microscopy of fluorescent 2’/3’-O-(N-methylanthraniloyl) ATP (mantATP) single-nucleotide turnover. Myosin heavy chain (MHC) isoform expression was determined using gel electrophoresis for each permeabilized vastus lateralis fiber, to allow for novel comparisons of SRX between fiber-types. We find that the fraction of myosin in SRX is less in MHC IIA fibers than in MHC I and IIAX fibers (p = 0.008). ATP turnover of SRX is faster in MHC IIAX fibers compared to MHC I and IIA fibers (p = 0.001). We conclude that SRX biochemistry is measurable in human skeletal muscle, and our data indicate that SRX depends on fiber type as classified by MHC isoform. Extension from this preliminary work would provide further understanding regarding the role of SRX in human muscle physiology.


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