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- Schmelz, M., et al.
(författare)
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Active "itch fibers" in chronic pruritus
- 2003
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 61:4, s. 564-566
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Tidskriftsartikel (refereegranskat)abstract
- An itch-specific neuronal pathway was recently discovered in healthy humans and animals. Here the authors report that activity in this specific pathway coincides with itch under pathophysiologic conditions in a patient with chronic pruritus. Microneurographic recordings from the symptomatic area revealed spontaneous activity in six single C-fiber afferents that had the characteristic features of "itch fibers." Itch may be caused by activity in a specific subpopulation of C-fiber afferents.
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- Bergö, Martin, 1970, et al.
(författare)
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On the physiological importance of endoproteolysis of CAAX proteins: heart-specific RCE1 knockout mice develop a lethal cardiomyopathy
- 2004
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Ingår i: J Biol Chem. ; 279:6, s. 4729-4736
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Tidskriftsartikel (refereegranskat)abstract
- Proteins terminating with a CAAX motif, such as the Ras proteins and the nuclear lamins, undergo post-translational modification of a C-terminal cysteine with an isoprenyl lipid via a process called protein prenylation. After prenylation, the last three residues of CAAX proteins are clipped off by Rce1, an integral membrane endoprotease of the endoplasmic reticulum. Prenylation is crucial to the function of many CAAX proteins, but the physiologic significance of endoproteolytic processing has remained obscure. To address this issue, we used Cre/loxP recombination techniques to create mice lacking Rce1 in the heart, an organ where Rce1 is expressed at particularly high levels. The hearts from heart-specific Rce1 knockout mice manifested reduced levels of both the Rce1 mRNA and CAAX endoprotease activity, and the hearts manifested an accumulation of CAAX protein substrates. The heart-specific Rce1 knockout mice initially appeared healthy but died starting at 3-5 months of age. By 10 months of age, approximately 70% of the mice had died. Pathological studies revealed that the heart-specific Rce1 knockout mice had a dilated cardiomyopathy. By contrast, liver-specific Rce1 knockout mice appeared healthy, had normal transaminase levels, and had normal liver histology. These studies indicate that the endoproteolytic processing of CAAX proteins is essential for cardiac function but is less important for the liver.
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| 7. |
- Otto, C J, et al.
(författare)
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The "flap" endonuclease gene FEN1 is excluded as a candidate gene implicated in the CAG repeat expansion underlying Huntington disease.
- 2001
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Ingår i: Clinical Genetics. - 0009-9163 .- 1399-0004. ; 59:2, s. 122-7
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Tidskriftsartikel (refereegranskat)abstract
- At least 12 disorders including Huntington disease (HD) are associated with expansion of a trinucleotide repeat (TNR). Factors contributing to the risk of expansion of TNRs and the mechanism of expansion have not been elucidated. Data from Saccharomyces cerevisiae suggest that the flap endonuclease FEN1 plays a role in expansion of repetitive DNA tracts. It has been hypothesized that insufficiency of FEN1 or a mutant FEN1 might contribute to the occurrence of expansion events of long repetitive DNA tracts after polymerase slippage events during lagging strand synthesis. The expression pattern of FEN1 was determined, and ubiquitous tissue expression, including germ cells, suggested that FEN1 has the potential to be involved in HD. Fifteen HD parent/child pairs that demonstrated intergenerational increases in CAG length of greater than 10 repeats were examined for possible mutations or polymorphisms within the FEN1 gene that could underlie the saltatory repeat expansions seen in these individuals. No alterations were observed compared to 50 controls, excluding FEN1 as a trans-acting factor underlying TNR expansion. The identification of a candidate gene(s) in HD or other CAG-expansion disorders implicated in TNR instability will elucidate the mechanism of expansion for this growing family of neurological disorders.
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| 8. |
- Schmelz, M., et al.
(författare)
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Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens
- 2003
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Ingår i: Journal of Neurophysiology. - Washington : The American Physiological Society. - 0022-3077 .- 1522-1598. ; 89:5, s. 2441-2448
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Tidskriftsartikel (refereegranskat)abstract
- Vasoneuroactive substances were applied through intradermal microdialysis membranes and characterized as itch- or pain-inducing in psychophysical experiments. Histamine always provoked itching and rarely pain, capsaicin always pain but never itching. Prostaglandin E[2] (PGE[2]) led preferentially to moderate itching. Serotonin, acetylcholine, and bradykinin induced pain more often than itching. Subsequently the same substances were used in microneurography experiments to characterize the sensitivity profile of human cutaneous C-nociceptors. The responses of 89 mechanoresponsive (CMH, polymodal nociceptors), 52 mechanoinsensitive, histamine-negative (CMi[H][i][s][-]), and 24 mechanoinsensitive, histamine-positive (CMi[H][i][s][+]) units were compared. CMi[H][i][s][+] units were most responsive to histamine and to PGE[2] and less to serotonin, ACh, bradykinin, and capsaicin. CMH units (polymodal nociceptors) and CMi[H][i][s] units showed significantly weaker responses to histamine, PGE[2], and acetylcholine. Capsaicin and bradykinin responses were not significantly different in the two classes of mechano-insensitive units. We conclude that CMi[H][i][s][+]units are "selective," but not "specific" for pruritogenic substances and that the pruritic potency of a mediator increases with its ability to activate CMi[H][i][s][+] units but decreases with activation of CMH and CMi[H][i][s] units.
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