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61.
Suppression of charge movement in frog skeletal muscle by D600 总被引:2,自引:0,他引:2
Summary Charge movements in intact frog twitch fibres were studied using a three-microelectrode voltage-clamp technique. When high potassium solution was applied transiently to the muscle fibres at low temperature in the presence of D600, the fibres became paralysed and, concomitantly, charge movement disappeared. The amount of charge suppressed by the paralysis treatment was about 70–100% of that in control experiments. This paralysing action of D600 is not shared by its derivative D890. The requirement of conditioning potassium contracture is, most likely, related to prolonged membrane depolarization, as voltage-clamped depolarization to 0 mV lasting tens of seconds also suppressed charge movement. When paralysed fibres were warmed, the main charge component (Q
) was reprimed. By contrast, the hump charge component (Q
was only reprimed in some of the fibres. Other than by warming, as paralysed fibre could be revived by stimulating it with large suprathreshold pulses but not by voltage-clamped hyperpolarization to –160 mV for tens of seconds. The paralysing action of D600 described here appears to be unrelated to its ability in blocking Ca2+ channels. 相似文献
62.
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
63.
Molyneux G Gibson FM Gordon-Smith EC Pilling AM Liu KC Rizzo S Sulsh S Turton JA 《International journal of experimental pathology》2005,86(6):415-430
Mitomycin (MMC), like many antineoplastic drugs, induces a predictable, dose-related, bone marrow depression in man and laboratory animals; this change is generally reversible. However, there is evidence that MMC may also cause a late-stage or residual bone marrow injury. The present study in female CD-1 mice investigated the haematological and bone marrow changes induced by MMC in a repeat dose study lasting 50 days. Control and MMC-treated mice were dosed intraperitoneally on eight occasions over 18 days with vehicle, or MMC at 2.5 mg/kg, autopsied (n = 6-12) at 1, 7, 14, 28, 42 and 50 days after the final dose and haematological changes investigated. Femoral nucleated bone marrow cell counts and levels of apoptosis were also evaluated and clonogenic assays carried out; serum levels of FLT3 ligand (FL) were assessed. At day 1 post-dosing, MMC induced significant reductions in RBC, Hb and haematocrit (HCT) values, and there were decreases in reticulocyte, platelet, and femoral nucleated cell counts (FNCC); neutrophil, lymphocyte and monocyte values were also significantly reduced. On days 7 and 14 post-dosing, all haematological parameters showed evidence of a return towards normal values, but at these times, and at day 28, values for RBC and FNCC remained significantly reduced in comparison with controls. At days 42 and 50 post-dosing, many haematological parameters in MMC-treated mice had returned to control levels; however, there remained evidence of late-stage effects on RBC, Hb and HCT values, and FNCC also continued to be significantly decreased. Results for granulocyte-macrophage colony-forming units and erythroid colonies showed a profound decrease immediately post-dosing, but a return to normal values was evident at day 50. Serum FL concentrations demonstrated very significant increases in the immediate post-dosing period, but a return to normal was seen at day 50 post-dosing; a relatively similar pattern was seen in the number of apoptotic femoral marrow nucleated cells. The histopathological examination of kidney tissues from MMC animals at day 42 and 50 post-dosing showed evidence of hydronephrosis with cortical glomerular/tubular atrophy and degeneration. It is therefore concluded that MMC administered on eight occasions over 18 days to female CD-1 mice at 2.5 mg/kg induced profound changes in haematological and bone marrow parameters in the immediate post-dosing period with a return to normal levels at day 50 post-dosing; however, there was evidence of mild but significant late-stage/residual effects on RBC and FNCC, and on cells of the erythroid lineage in the bone marrow. 相似文献
64.
Chiu TT Rogers MS Law EL Briton-Jones CM Cheung LP Haines CJ 《Human reproduction (Oxford, England)》2002,17(6):1591-1596
BACKGROUND: The follicular microenvironment is an important determinant of oocyte development. The aim of this study was to examine whether the myo-inositol (MI) content in human follicular fluid (FF) was associated with better oocyte quality. METHODS: A total of 53 patients treated with IVF was recruited to a prospective observational study. FF and serum samples collected were divided into two groups: group A consisted of FF associated with matured and fertilized oocytes, whilst group B was from follicles with immature and unfertilized oocytes. RESULTS: Patient's age, total ampoules of HMG used, days of stimulation, basal levels of FSH, estradiol (E(2)) levels on the day of HCG, and serum MI content were not significantly different between the two groups. FF volume and its MI content were significantly higher in group A compared with group B (P < 0.05). The levels of MI in FF were positively correlated with the amount of E(2) in their corresponding FF samples and also correlated with embryo quality. CONCLUSIONS: We propose that higher concentrations of MI and E(2) in human FF appear to play a role in follicular maturity and provide a marker of good quality oocytes. 相似文献
65.
Chuen -Mao Yang Hui -Liang Tsao Chi -Tso Chiu Lir -Wan Fan Sheu -Meei Yu 《Pflügers Archiv : European journal of physiology》1996,432(4):708-716
The effects of increases in cellular adenosine 3′5′-cyclic monophosphate (cAMP) on 5-hydroxytryptamine-(5-HT-) induced generation
of inositol phosphates (IPs) and increases in intracellular Ca2+ ([Ca2+]i) were investigated using canine cultured tracheal smooth muscle cells (TSMCs). Cholera toxin and forskolin induced concentration-
and time-dependent cAMP formation with half-maximal effects (−logEC50) produced at concentrations of 7.0 ± 0.5 and 4.9 ± 0.4 respectively. Pretreatment of TSMCs with either forskolin or dibutyryl
cAMP inhibited 5-HT-stimulated responses. Even after treatment for 24h, these agents still inhibited the 5-HT-induced Ca2+ mobilization. The inhibitory effects of these agents produced both depression of the maximal response and a shift to the
right of the concentration response curves of 5-HT. The water-soluble forskolin analogue L-858051 [7-deacetyl-7β-(γ-N-methylpiperazino)-butyryl forskolin] significantly inhibited the 5-HT-stimulated accumulation of IPs. In contrast, the addition
of 1,9-dideoxy forskolin, an inactive forskolin analogue, had little effect on this response. Moreover, SQ-22536 [9-(tetrahydro-2-furanyl)-9-H-purin-6-amine], an inhibitor of adenylate cyclase, and both H-89 [N-(2-aminoethyl)-5-isoquinolinesulphonamide] and HA-1004[N-(2-guanidinoethyl)-5-isoquinolinesulphonamide], inhibitors of cAMP-dependent protein kinase (PKA), attenuated the ability
of forskolin to inhibit the 5-HT-stimulated accumulation of IPs. These results suggest that activation of cAMP/PKA was involved
in these inhibitory effects of forskolin. The AlF4
−-induced accumulation of IPs was inhibited by forskolin, suggesting that G protein(s) are directly activated by AlF4
−- and uncoupled from phospholipase C by forskolin treatment. These results suggest that activation of cAMP/PKA might inhibit
the 5-HT-stimulated phosphoinositide breakdown and consequently reduce the [Ca2+]i increase or inhibit both responses independently.
Received: 14 March 1996/Accepted: 10 April 1996 相似文献
66.
INTRODUCTIONAdultRespiratoryDistressSyndrome(ARDS)isanacuteprogressiverespiratoryfailurecausedbymanyreasons.Thetherapeuticactionofthissyndromeisuncertain,becausethemechanismisnotwellknown.Thatis,theprognosisiscritical,themortailityisquiteheigh(50%f)ti--63'Butintherecenttenyears,manyscholarsinourcountryhavehadmuchexperienceintheaspectofusinganisodaminetorescueARDSpatientsandhavedecreasedthemortality(')'Howeveverthescholarsexplaintheprincipleofitindifferentways'Thechangesofmicrovascula… 相似文献
67.
Variability of skin temperature in the waking monkey 总被引:3,自引:0,他引:3
68.
C K Lin J S Lin S Y Chen M L Jiang C F Chiu 《Archives of pathology & laboratory medicine》1992,116(10):1030-1032
In a total group of 415 subjects (100 normal controls, 115 with iron deficiency anemia, 100 with the alpha-thalassemia trait, and 100 with the beta-thalassemia trait), the following indexes were analyzed: hemoglobin distribution width, red blood cell distribution width (RDW)-coefficient of variation, and RDW-SD. The hemoglobin distribution width and RDW-coefficient of variation were examined with a laser light scattering system (Technicon H1), whereas the RDW-SD was determined with an impedance autoanalyzer (Sysmex M-2000). All of these parameters helped, to some extent, in the differential diagnosis of microcytic anemia. However, our data suggested a low RDW-SD might provide significantly more value in differentiating thalassemia traits from iron deficiency anemia, as well as from normal controls, while the hemoglobin distribution width gave no help in the differential diagnosis between iron deficiency anemia and the beta-thalassemia trait. 相似文献
69.
Identification of 6 new mutations in the iduronate sulfatase gene. Mutation in brief no. 233. Online
Vallance HD Bernard L Rashed M Chiu D Le G Toone J Applegarth DA Coulter-Mackie M 《Human mutation》1999,13(4):338
Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. We sequenced genomic DNA and RT-PCR products in the iduronate sulfatase (IDS) gene in 6 unrelated patients with Hunter syndrome to assess genotype/phenotype relationships and offer carrier testing where required. Six novel mutations were identified: four missense mutations, one four-base pair deletion (596-599delAACA) and a cryptic splice site mutation. Three of the missense mutations were significant amino acid substitutions (S143F, S491F, E341K) of which the latter two involve amino acids conserved amongst sulfatase enzymes. The patients identified with these mutations all had a severe clinical phenotype. One missense mutation with a minimal amino acid substitution (H342Y), in a non-conserved region of the gene, was associated with a mild clinical phenotype. We identified a novel cryptic splice site (IVS5+934G>A) with some normal (wild type) mRNA processing. We predict that the normal mRNA product confered some residual functional enzyme, resulting in a mild phenotype associated with the absence of overt central nervous system disease. 相似文献
70.