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1.
Heparin-like molecules, isolated from cultured rat and human skin fibroblasts, accelerated the inactivation of purified human thrombin via purified human antithrombin. Only 15% of the biologic activity of the complex carbohydrates derived from human skin fibroblasts was expressed when the heparin-binding domain an antithrombin was chemically modified at the Trp 49 residue. Human skin fibroblasts were metabolically labeled with [35S]Na2SO4, and radiolabeled heparin-like molecules were isolated utilizing ion-exchange chromatography and fractionated into two separate populations employing immobilized antithrombin. The species which bound with high avidity to the affinity matrix represented about 12% of the radiolabeled heparin-like molecules, accounted for almost 95% of the initial anticoagulant activity, and exhibited a specific activity of 3.98 USP units/10(6) 35S-cpm. 相似文献
2.
Heppner TJ Layne JJ Pearson JM Sarkissian H Nelson MT 《American journal of physiology. Regulatory, integrative and comparative physiology》2011,301(2):R351-R362
The muscularis mucosae, a type of smooth muscle located between the urothelium and the urinary bladder detrusor, has been described, although its properties and role in bladder function have not been characterized. Here, using mucosal tissue strips isolated from guinea pig urinary bladders, we identified spontaneous phasic contractions (SPCs) that appear to originate in the muscularis mucosae. This smooth muscle layer exhibited Ca(2+) waves and flashes, but localized Ca(2+) events (Ca(2+) sparks, purinergic receptor-mediated transients) were not detected. Ca(2+) flashes, often in bursts, occurred with a frequency (~5.7/min) similar to that of SPCs (~4/min), suggesting that SPCs are triggered by bursts of Ca(2+) flashes. The force generated by a single mucosal SPC represented the maximal force of the strip, whereas a single detrusor SPC was ~3% of maximal force of the detrusor strip. Electrical field stimulation (0.5-50 Hz) evoked force transients in isolated detrusor and mucosal strips. Inhibition of cholinergic receptors significantly decreased force in detrusor and mucosal strips (at higher frequencies). Concurrent inhibition of purinergic and cholinergic receptors nearly abolished evoked responses in detrusor and mucosae. Mucosal SPCs were unaffected by blocking small-conductance Ca(2+)-activated K(+) (SK) channels with apamin and were unchanged by blocking large-conductance Ca(2+)-activated K(+) (BK) channels with iberiotoxin (IbTX), indicating that SK and BK channels play a much smaller role in regulating muscularis mucosae SPCs than they do in regulating detrusor SPCs. Consistent with this, BK channel current density in myocytes from muscularis mucosae was ~20% of that in detrusor myocytes. These findings indicate that the muscularis mucosae in guinea pig represents a second smooth muscle compartment that is physiologically and pharmacologically distinct from the detrusor and may contribute to the overall contractile properties of the urinary bladder. 相似文献
3.
Benito J Shi Y Szymanska B Carol H Boehm I Lu H Konoplev S Fang W Zweidler-McKay PA Campana D Borthakur G Bueso-Ramos C Shpall E Thomas DA Jordan CT Kantarjian H Wilson WR Lock R Andreeff M Konopleva M 《PloS one》2011,6(8):e23108
Recent studies indicate that interactions between leukemia cells and the bone marrow (BM) microenvironment promote leukemia cell survival and confer resistance to anti-leukemic drugs. There is evidence that BM microenvironment contains hypoxic areas that confer survival advantage to hematopoietic cells. In the present study we investigated whether hypoxia in leukemic BM contributes to the protective role of the BM microenvironment. We observed a marked expansion of hypoxic BM areas in immunodeficient mice engrafted with acute lymphoblastic leukemia (ALL) cells. Consistent with this finding, we found that hypoxia promotes chemoresistance in various ALL derived cell lines. These findings suggest to employ hypoxia-activated prodrugs to eliminate leukemia cells within hypoxic niches. Using several xenograft models, we demonstrated that administration of the hypoxia-activated dinitrobenzamide mustard, PR-104 prolonged survival and decreased leukemia burden of immune-deficient mice injected with primary acute lymphoblastic leukemia cells. Together, these findings strongly suggest that targeting hypoxia in leukemic BM is feasible and may significantly improve leukemia therapy. 相似文献
4.
Nicole M Gerardo Boran Altincicek Caroline Anselme Hagop Atamian Seth M Barribeau de Martin Vos Elizabeth J Duncan Jay D Evans Toni Gabaldón Murad Ghanim Adelaziz Heddi Isgouhi Kaloshian Amparo Latorre Andres Moya Atsushi Nakabachi Benjamin J Parker Vincente Pérez-Brocal Miguel Pignatelli Yvan Rahbé John S Ramsey Chelsea J Spragg Javier Tamames Daniel Tamarit Cecilia Tamborindeguy Caroline Vincent-Monegat Andreas Vilcinskas 《Genome biology》2010,11(2):1-17
5.
Carter BZ Mak DH Morris SJ Borthakur G Estey E Byrd AL Konopleva M Kantarjian H Andreeff M 《Apoptosis : an international journal on programmed cell death》2011,16(1):67-74
XIAP, a potent caspase inhibitor, is highly expressed in acute myeloid leukemia (AML) cells and contributes to chemoresistance.
A multi-center phase 1/2 trial of XIAP antisense oligonucleotide AEG35156 in combination with idarubicin/cytarabine was conducted
in 56 patients with relapsed/refractory AML. Herein we report the pharmacodynamic studies of the patients enrolled at M. D.
Anderson Cancer Center. A total of 13 patients were enrolled in our institution: five in phase 1 (12–350 mg/m2 AEG35156) and eight in phase 2 (350 mg/m2 AEG35156) of the protocol. AEG35156 was administered on 3 consecutive days and then weekly up to a maximum of 35 days. Blood
samples were collected from patients on days 1 through 5 and on day 28–35 post-chemotherapy for detection of XIAP levels and
apoptosis. AEG35156 treatment led to dose-dependent decreases of XIAP mRNA levels (42–100% reduction in phase 2 patients).
XIAP protein levels were reduced in all five samples measured. Apoptosis induction was detected in 1/4 phase 1 and 4/5 phase
2 patients. Importantly, apoptosis was most pronounced in CD34
+
38
−
AML stem cells and all phase 2 patients showing apoptosis induction in CD34
+
38
−
cells achieved response. We conclude that at 350 mg/m2, AEG35156 is effective in knocking down XIAP in circulating blasts accompanied by the preferential induction of apoptosis
in CD34
+
38
−
AML stem cells. 相似文献
6.
7.
Norman Bank Wei-Shing Su Hagop S. Aynedjian 《The Yale journal of biology and medicine》1978,51(3):275-282
In rats with renal failure produced by excision of one kidney and infarction of large portions of the other kidney, given a low calcium, high phosphorus diet for 2-3 weeks, GFR was reduced by 80 percent, the fractional excretion of sodium increased from 7 to 23 percent, that of bicarbonate from 16 to 23 percent and that of water from 4 to 13 percent. Single nephron GFR in the remaining nephrons was nearly doubled and end-proximal TF/PIn was depressed from 2.3 to 1.8, and proximal TF/PHCO3 from 0.52 to 0.35, the latter figure corresponding to an increase of absolute proximal HCO3 reabsorption from 1.7 to 3.5 nEq/min or from 2.8 to 3.2 Eq/L of single nephron glomerular filtrate. Acute parathyroidectomy had no influence on the fall of GFR or the rise of SNGFR in the remaining nephrons and failed to cause any significant changes in proximal tubular bicarbonate reabsorption. Parathyroidectomy, on the other hand, practically prevented the rise of the fractional excretion of sodium and of water and inverted the rise of the fractional excretion of bicarbonate to a fall. The data are interpreted to indicate that secondary hyperparathyroidism in renal failure impairs distal nephron bicarbonate and sodium reabsorption and, thus, contributes to the maintenance of sodium balance, but could possibly aggravate acidosis. 相似文献
8.
Mutations at the Werner helicase locus (WRN) are responsible for the Werner syndrome (WS). WS patients prematurely develop an aged appearance and various age-related disorders. We have generated transgenic mice expressing human WRN with a putative dominant-negative mutation (K577M-WRN). Primary tail fibroblast cultures from K577M-WRN mice showed three characteristics of WS cells: hypersensitivity to 4-nitroquinoline-1-oxide (4NQO), reduced replicative potential, and reduced expression of the endogenous WRN protein. These data suggest that K577M-WRN mice may provide a novel mouse model for the WS. 相似文献
9.
Carla Abdo Nabil Nemer Georges Nemer Yusuf Abou Jawdah Hagop Atamian Nasri S. Kawar 《BioControl》2008,53(2):341-352
Larvae of the cedar web-spinning sawfly, Cephalcia tannourinensis Chevin (Hymenoptera: Pamphiliidae), infected with a white fungus were collected from the Tannourine-Hadath El-Jebbeh cedar
forest. Macro- and micro-morphological data based on the examination of colonies, conidiophores, and conidial shape of the
fungus suggested a Beauveria species. Sequence analysis of the internal transcribed spacer regions of the isolated fungus showed that it is most closely
related to isolates of B. bassiana Clade C. The present study showed that the isolated B. bassiana is a naturally occurring entomopathogenic fungus parasitizing the larvae of C. tannourinensis in Lebanon. Laboratory bioassays showed that B. bassiana caused high mortality of eggs and larvae. The infected eggs turned brownish in color, while larvae of the first instar ceased
feeding and showed immobility and rigidity within 5 days and before sporulating conidial mat appeared on their cuticle. Second
and third larval instars took longer time to show fungal sporulation: mortalities ranged between 85 and 100% within 7 days
when treated with different conidial concentrations. The efficacy of control of C. tannourinensis using B. bassiana was higher or equal to the reference insect growth regulator, diflubenzuron, suggesting the possibility of its success as
a biological control agent. 相似文献
10.