Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pluripotent hematopoietic stem cells (PHSCs) were highly enriched from mouse bone marrow by counterflow centrifugal elutriation, lineage subtraction, and fluorescence-activated cell sorting based on high c-kit receptor expression (c-kitBR). We used reverse transcriptase polymerase chain reaction to assay the c-kitBR subset and the subsets expressing low (c-kitDULL) and no (c-kitNEG) c-kit receptor for expression of mRNA encoding hematopoietic growth factor receptors and transcription factors. The c-kitBR cells had approximately 3.5-fold more c-kit mRNA than unfractionated bone marrow cells. The c-kitDULL cells had 47-58% of the c-kit mRNA found in c-kitBR cells and the c-kitNEG cells had 4-9% of the c-kit mRNA present in c-kitBR cells. By comparing mRNA levels in c-kitBR cells (enriched for PHSCs) with those of unfractionated bone marrow, we demonstrated that c-kitBR cells contained low or undetectable levels of mRNA for c-fms, granulocyte colony-stimulating factor receptor, interleukin 5 receptor (IL-5R), and IL-7R. These same cells had moderate levels of mRNA for erythropoietin receptor, IL-3R subunits IL-3R alpha (SUT-1), AIC-2A, and AIC-2B, IL-6R and its partner gp-130, and the transcription factor GATA-1 and high levels of mRNA for transcription factors GATA-2, p45 NF-E2, and c-myb. We conclude from these findings that PHSCs are programmed to interact with stem cell factor, IL-3, and IL-6 but not with granulocyte or macrophage colony-stimulating factor. These findings also indicate that GATA-2, p45 NF-E2, and c-myb activities may be involved in PHSC maintenance or proliferation.
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PMID:Pluripotent hematopoietic stem cells contain high levels of mRNA for c-kit, GATA-2, p45 NF-E2, and c-myb and low levels or no mRNA for c-fms and the receptors for granulocyte colony-stimulating factor and interleukins 5 and 7. 753 77

We have previously reported that in adult mouse bone marrow, CD34low/- c-kit+ Sca-1+ lineage markers negative (Lin-) (CD34-KSL) cells represent hematopoietic stem cells with long-term marrow repopulating ability whereas CD34+ c-kit+ Sca-1+ Lin- (CD34+KSL) cells are progenitors with short-term reconstitution capacity. To further characterize cells in those two populations, relative expression of various genes were examined by reverse transcriptase polymerase chain reaction (RT-PCR). In CD34-KSL cells, none of the genes studied was found to be expressed with the exception of GATA-2, IL-1R alpha, IL-2R gamma, AIC-2B, c-kit, EPO-R, and c-mpl. In contrast, expression of GATA-1 and all cytokine receptor genes examined except IL-2R beta, IL-7R alpha and IL-9R alpha were found in CD34+KSL. The difference between these two populations was also shown in single cell culture analysis of these cells. When cells were clone-sorted and cultured in the presence of SCF, IL-3 and EPO, CD34-KSL cells required much more time to undergo the first cell division than CD34+KSL cells. Dormancy and random fashion of cell division by CD34-KSL cells were also evident by the analysis of the second cell division, which was found to be delayed and unsynchronous compared with CD34+KSL cells. Clonal culture analysis showed that CD34-KSL cells were more potent in proliferation and multilineage differentiation capacities than CD34+KSL cells. In a paired-daughter cell experiment, 75% of CD34-KSL and 50% of CD34+KSL paired-daughter-derived colonies were nonidentical with wide variety of lineage combinations. Taken together, these data support our previous notion that CD34-KSL cells are at higher rank in hematopoietic hierarchy than CD34+KSL cells. In addition, our results using highly enriched stem cell population directly obtained from mouse bone marrow support the proposed stochastic nature of lineage commitment.
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PMID:Further characterization of CD34-low/negative mouse hematopoietic stem cells. 1037 11

The purpose of this study was to characterize the pharmacokinetics and determine the absolute bioavailability of 2'-deoxy-3'-oxa-4'-thiocytidine (dOTC) (BCH-10652), a novel nucleoside analogue reverse transcriptase inhibitor, in humans. dOTC belongs to the 4'-thio heterosubstituted class of compounds and is a 1:1 mixture of its two enantiomers, (-) and (+) dOTC. Twelve healthy adult male volunteers each received oral (800-mg) and intravenous (100-mg) doses of dOTC in two study periods separated by at least 7 days. Sixteen plasma samples were obtained over 72 h and assayed for (-) and (+) dOTC, and the resultant data fit by candidate pharmacokinetic models. Data were weighted by the fitted inverse of the observation variance; model discrimination was by AIC. The pharmacokinetic model was a linear, three compartment model, with absorption occurring during one to three first-order input phases, each following a fitted lag time. The model goodness-of-fit was excellent; r(2) ranged from 0.995 to 1.0. The mean absolute bioavailabilities of (+) and (-) dOTC were 77.2% (coefficient of variation [given as a percentage] [CV%], 14) and 80.7% (CV%, 15), respectively. The median steady-state volume of distribution for (+) dOTC, 74.7 (CV%, 19.2) liters/65 kg, was greater than that for (-) dOTC, 51.7 (CV%, 16.7) liters/65 kg (P<0.05). The median total clearance of (+) dOTC was less than that of (-) dOTC, 11.7 (CV%, 17.3) versus 15.4 (CV%, 18.6) liters/h/65 kg, respectively (P< 0.05). The intersubject variability of these parameters was very low. The median terminal half-life of (+) dOTC was 18.0 (CV%, 31.5) h, significantly longer than the 6.8 (CV%, 69.9) h observed for (-) dOTC (P<0.01). No serious adverse events were reported during the study. These results suggest that dOTC is well absorbed, widely distributed, and well tolerated. The terminal half-lives indicate that dosing intervals of 12 to 24 h would be reasonable.
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PMID:Absolute bioavailability and disposition of (-) and (+) 2'-deoxy- 3'-oxa-4'-thiocytidine (dOTC) following single intravenous and oral doses of racemic dOTC in humans. 1081 17