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111.
A1, a Bcl-2 family member, prolongs cell survival and permits myeloid differentiation 总被引:18,自引:4,他引:14
A1, a bcl-2 family member, has been identified as a hematopoietic- specific, early inducible gene. In this study it is shown that stable transfection of A1 into an interleukin-3 (IL-3)-dependent myeloid precursor cell line, 32D c13, leads to a retardation of IL-3 withdrawal- induced cell death similar to that observed with transfection of bcl-2. However, unlike bcl-2. A1 expression permits the accumulation of differentiated myeloid cells both before and after IL-3 withdrawal. Total cell accumulation, on the other hand, is considerably greater after IL-3 deprivation in the bcl-2 transfectant than in A1-expressing cells. Cells cotransfected with the two genes behave similarly to cells singly transfected with bcl-2, except that viability following IL-3 withdrawal is somewhat further enhanced. These results suggest that these two proteins have distinct roles that may be related to the divergent regulation of their expression during myeloid differentiation. 相似文献
112.
High-dose multidrug resistance in primary human hematopoietic progenitor cells transduced with optimized retroviral vectors 总被引:3,自引:0,他引:3
Eckert HG; Stockschlader M; Just U; Hegewisch-Becker S; Grez M; Uhde A; Zander A; Ostertag W; Baum C 《Blood》1996,88(9):3407-3415
Retroviral transfer of the multidrug-resistance 1 (mdr1) cDNA into primary human hematopoietic progenitor cells (HPC) of cancer patients undergoing high-dose chemotherapy has been proposed to protect the bone marrow from the dose-limiting cytotoxicity of cytostatic agents. Preclinical studies performed with vectors derived from the Moloney murine leukemia virus (MoMuLV) or the related Harvey murine sarcoma virus have established that chemoprotection of HPC is feasible. The efficacy of vector-mediated multidrug-resistance under high doses of cytostatic agents, however, remained unclear. We report here that this goal can only be achieved with improved vector design. Novel vectors termed SF-MDR and MP-MDR, which are based on the spleen focus-forming virus or the myeloproliferative sarcoma virus for the enhancer and the murine embryonic stem cell virus for the leader, significantly elevate survival of transduced primary human HPC under moderate doses of colchicine and paclitaxel in vitro when compared with a conventional MoMuLV-based vector. Importantly, SF-MDR and also MP-MDR confer an absolute advantage at high doses of paclitaxel in vitro corresponding to peak plasma levels achieved in patients during chemotherapy. This observation has important consequences for a variety of ongoing and planned gene therapy trials. 相似文献
113.
DARRELL HG CRAWFORD 《Journal of gastroenterology and hepatology》1996,11(11):1043-1045
Many of the clinical manifestations of haemochromatosis are determined by the hepatic iron concentration which, in turn, may be influenced by environmental and genetic factors. The environmental factors that influence iron stores include age, gender and blood loss (pathological and physiological). There is evidence that genetic factors also influence hepatic iron accumulation, as patients with two copies of the ancestral haplotype accumulate more iron than subjects with one or no copies of the ancestral haplotype. Concordance of iron storage between siblings also suggests genetic factors play an important role in determining disease expression. However, clarification of the exact role of genetic factors awaits the conduct of further studies following the cloning of the haemochromatosis gene. 相似文献
114.
115.
Lemmers RJ; van der Maarel SM; van Deutekom JC; van der Wielen MJ; Deidda G; Dauwerse HG; Hewitt J; Hofker M; Bakker E; Padberg GW; Frants RR 《Human molecular genetics》1998,7(8):1207-1214
The autosomal dominant myopathy facioscapulohumeral muscular dystrophy
(FSHD) is causally related to a short Eco RI fragment detected by probe
p13E-11. This remnant fragment is the result of a deletion of an integral
number of tandemly arrayed 3.3 kb repeat units (D4Z4) on 4q35. Despite
intensive efforts, no transcribed sequences have been identified within
this array. Previously, we have shown that these repeats on 4q35 have been
exchanged for a similar highly homologous repeat locus on 10q26 in 20% of
the population and that a short chromosome 10-like array on 4q35 also
results in FSHD. Here, we describe the hybrid structure of some of these
repeat arrays, reflecting additional sub-telomeric instability. In three
healthy individuals carrying a 4-like repeat on chromosome 10 or vice
versa, one repeat array was shown to consist of hybrid clusters of
4-derived and 10-derived repeat units. Moreover, employing pulsed field gel
electrophoresis analysis, we identified two unrelated individuals carrying
deletions of a chromosomal segment (p13E-11) proximal to the repeat locus.
These deletions were not associated with FSHD. In one of these cases,
however, an expansion of the deletion into the repeat array was observed in
one of his children suffering from FSHD. These data provide additional
evidence for instability of this sub-telomeric region and suggests that the
length of the repeat, and not its intrinsic properties, is crucial to FSHD.
Moreover, they are in agreement with the hypothesis that FSHD is caused by
a position effect in which the repeat structure influences the expression
of genes nearby. Therefore, the region deleted proximal to the repeat locus
in healthy individuals can be instrumental to refine the critical region
for FSHD1.
相似文献
116.
Lang D Hubrich A Dohle F Terstesse M Saleh H Schmidt M Pauels HG Heidenreich S 《Journal of leukocyte biology》2000,68(5):729-736
Apoptosis of monocytes is regulated by the balance between pro- and antiapoptotic triggers and pathways and may strongly influence inflammatory disorders. The major heat shock protein, hsp70, is an effective inhibitor of apoptosis in lymphocytic and monocytic tumor cell lines, but the implications in the regulation of apoptosis of freshly isolated human monocytes have not been elucidated. In this study, we examined whether two different triggers of monocyte apoptosis, serum deprivation and IL-4, respectively, altered hsp70 expression and whether expression levels correlated with monocyte survival. Monocyte apoptosis was determined quantitatively by flow cytometry detecting annexin V binding or nuclear stainability with propidium iodide (PI). Hsp70 expression was analyzed by semiquantitative RT-PCR and immunoblotting. Exposing monocytes to heat shock (47 degrees C, 20 min) induced a rapid and marked upregulation of hsp70 without evoking injury or apoptosis, suggesting that hsp70 conferred protection and survival. In accordance, when monocytes were rendered apoptotic by serum deprivation, a drastic downregulation of hsp70 occurred, which was accompanied by a reduced synthesis of the constitutive family member hsc70. However, induction of monocyte apoptosis by IL-4 increased hsp70 expression in a concentration and time-dependent fashion. A neutralizing antibody against IL-4 abolished hsp70 expression and apoptosis induction after IL-4 treatment and so excluded indirect effects. LPS rescued monocytes from apoptosis but did not alter hsp70 formation significantly. These findings suggest that, in monocytes, distinct apoptotic triggers induce different responses of hsp70 so that this molecule does not exert protection against cell death directly or in general. 相似文献
117.
Raman Jay SB Jung BH Park BC Jeong SI Seo SS Jeon HM Lee HY Choi HG Jeon 《Urologic oncology》2017,35(3):118-119
Purpose
We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage.Materials and methods
We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease—glomerular filtration rate 90 ml/min/1.73 m2 or greater (230, 42.4%), chronic kidney disease stage II—glomerular filtration rate 60 to less than 90 ml/min/1.73 m2 (227, 41.8%), and chronic kidney disease stage III—glomerular filtration rate 30 to less than 60 ml/min/1.73 m2 (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration.Results
Among all patients (mean age = 56.0 y) mean preoperative glomerular filtration rate, functional renal volume, and glomerular filtration rate/functional renal volume were 83.2 ml/min/1.73 m2, 340.6 cm3, and 0.25 ml/min/1.73 m2/cm3, respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs. stage II 26.5% vs. stage III 12.8%, P<0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs. stage II 17.3% vs. stage III 16.5%, P = 0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs. stage II 20.1% vs. stage III 45.9%, P<0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (P = 0.012), diabetes mellitus (P = 0.023), hypertension (P = 0.015), and chronic kidney disease stage (P<0.001).Conclusions
Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration. 相似文献118.
HG NIE JQ CAI MJ WEI ZG SONG WB JIN JM LI XS YU BZ SUN 《中国药理通讯》2006,23(2):18-19
In order to clarify which teaching form encourages student' s self-motivation learning ability better, we did a comparison experiment between problem-based learning (PBL)and lecture-based learning (LBL) in a 3rd year course in basic pharmacology. Of 224 students who participated (124 PBL, 100 LBL) in pharmacology course, the experimental group was divided into 6 teams(20 - 21 students for each team with one tutor)using PBL method with 7 clinical cases discussion while o.ther 100 students held in the same lecture-based format as the traditional LBL course as a control group. In 224 students, 50.4% using PBL method self-directed learning ability had increased compared with 35.3% in LBL teaching mode. The test score indicated that students using LBL teaching method scored overall higher than those using PBL mode, especially at objective items, this result was significant.. iy different(P =0.009). However, as far as subjective items are concerned, students accepted PBL mode showed their superior advantages over the LBL ones. Similarly, the result was significantly different( P =0.001 ). On the whole, PBL method supported by appropriate technology and teachers, has allowed our students to analyze authentic situations as a doctor status and the active learning ability by self-motivation study will be undoubtedly beneficial for their becoming life-long learners and excellent doctors in the future. 相似文献
119.
M van Leeuwen BC Opmeer EJK Zweers E van Ballegooie HG ter Brugge HW de Valk GHA Visser BWJ Mol 《BJOG : an international journal of obstetrics and gynaecology》2010,117(1):69-75
Objective To develop a clinical prediction rule that can help the clinician to identify women at high and low risk for gestational diabetes mellitus (GDM) early in pregnancy in order to improve the efficiency of GDM screening.
Design We used data from a prospective cohort study to develop the clinical prediction rule.
Setting The original cohort study was conducted in a university hospital in the Netherlands.
Population Nine hundred and ninety-five consecutive pregnant women underwent screening for GDM.
Methods Using multiple logistic regression analysis, we constructed a model to estimate the probability of development of GDM from the medical history and patient characteristics. Receiver operating characteristics analysis and calibration were used to assess the accuracy of the model.
Main outcome measure The development of a clinical prediction rule for GDM. We also evaluated the potential of the prediction rule to improve the efficiency of GDM screening.
Results The probability of the development of GDM could be predicted from the ethnicity, family history, history of GDM and body mass index. The model had an area under the receiver operating characteristic curve of 0.77 (95% CI 0.69–0.85) and calibration was good (Hosmer and Lemeshow test statistic, P = 0.25). If an oral glucose tolerance test was performed in all women with a predicted probability of 2% or more, 43% of all women would be tested and 75% of the women with GDM would be identified.
Conclusions The use of a clinical prediction model is an accurate method to identify women at increased risk for GDM, and could be used to select women for additional testing for GDM. 相似文献
Design We used data from a prospective cohort study to develop the clinical prediction rule.
Setting The original cohort study was conducted in a university hospital in the Netherlands.
Population Nine hundred and ninety-five consecutive pregnant women underwent screening for GDM.
Methods Using multiple logistic regression analysis, we constructed a model to estimate the probability of development of GDM from the medical history and patient characteristics. Receiver operating characteristics analysis and calibration were used to assess the accuracy of the model.
Main outcome measure The development of a clinical prediction rule for GDM. We also evaluated the potential of the prediction rule to improve the efficiency of GDM screening.
Results The probability of the development of GDM could be predicted from the ethnicity, family history, history of GDM and body mass index. The model had an area under the receiver operating characteristic curve of 0.77 (95% CI 0.69–0.85) and calibration was good (Hosmer and Lemeshow test statistic, P = 0.25). If an oral glucose tolerance test was performed in all women with a predicted probability of 2% or more, 43% of all women would be tested and 75% of the women with GDM would be identified.
Conclusions The use of a clinical prediction model is an accurate method to identify women at increased risk for GDM, and could be used to select women for additional testing for GDM. 相似文献
120.
Niels A van der Gaag Steve MM de Castro Erik AJ Rauws Marco J Bruno Casper HJ van Eijck Ernst J Kuipers Josephus JGM Gerritsen Jan-Paul Rutten Jan Willem Greve Erik J Hesselink Jean HG Klinkenbijl Inne HM Borel Rinkes Djamila Boerma Bert A Bonsing Cees J van Laarhoven Frank JGM Kubben Erwin van der Harst Meindert N Sosef Koop Bosscha Ignace HJT de Hingh Laurens Th de Wit Otto M van Delden Olivier RC Busch Thomas M van Gulik Patrick MM Bossuyt Dirk J Gouma 《BMC surgery》2007,7(1):3