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91.
Constitutive expression of B-myb can bypass p53-induced Waf1/Cip1-mediated G1 arrest. 总被引:2,自引:0,他引:2 下载免费PDF全文
D Lin M Fiscella P M O''Connor J Jackman M Chen L L Luo A Sala S Travali E Appella W E Mercer 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(21):10079-10083
Overexpression of wild-type p53 protein has been shown to induce arrest in the G1 stage of the cell cycle and to transactivate expression of the gene that encodes the 21-kDa Waf1/Cip1 protein, a potent inhibitor of cyclin-dependent kinase activity. p53-dependent G1 arrest is accompanied by decreased expression of the B-myb gene, a relative of the c-myb cellular oncogene. In this study we show that B-myb expression is required for cells to progress from G1 into S phase and that high levels of ectopic B-myb expression uncoupled from cell cycle regulation rescues cells from p53-induced G1 arrest even in the presence of Waf1/Cip1 transactivation and inhibition of cyclin E/Cdk2 kinase activity. Cotransfection experiments with p53 expression plasmids and expression plasmids encoding in-frame deletion mutations in B-myb coding sequences indicate that the DNA-binding domain of the B-Myb protein is required for this activity. These results provide evidence of a bypass of p53-induced Waf1/Cip1-mediated cell cycle regulatory pathways by a member of the myb oncogene family. 相似文献
92.
Miller TP; Grogan TM; Dahlberg S; Spier CM; Braziel RM; Banks PM; Foucar K; Kjeldsberg CR; Levy N; Nathwani BN 《Blood》1994,83(6):1460-1466
The growth fraction of tumors from patients with non-Hodgkin's lymphomas (NHL) has been shown to correlate with survival in retrospective studies. The growth fraction can be evaluated using immunohistochemical techniques employing the Ki-67 monoclonal antibody (MoAb) that marks a nuclear protein present in cycling cells. The purpose of this study was to evaluate the clinical utility of the Ki-67 MoAb for predicting survival. Using a prospective trial design in a multi-institutional cooperative trials group, the proliferative index, clinical outcome, and statistical correlations were independently assessed for previously untreated patients with advanced stages of intermediate- and high-grade histologies of NHL treated on Southwest Oncology Group study (SWOG 8516, Intergroup 0067). The proportion of Ki- 67-positive cells was determined on snap-frozen thin tissue sections. A proliferative index of 80% or greater, as determined from prior retrospective studies, identified a group of patients (18%) who had a poor outcome. Overall survival was significantly reduced in these patients with a high Ki-67-associated proliferative index compared with those with a low proliferative index (P = .001). One-year survival estimates were 82% (low proliferative index) versus 18% (high proliferative index). A multivariate regression analysis incorporating commonly used clinical prognostic features confirmed the independent effect of proliferation on survival (relative risk estimate 5.9; 95% confidence interval, 2.2, 16.1). The Ki-67 MoAb identifies a group of patients with rapidly fatal NHL for whom currently available chemotherapy is inadequate. 相似文献
93.
Van den Ende CH; Vliet Vlieland TP; Munneke M; Hazes JM 《Rheumatology (Oxford, England)》1998,37(6):677-687
The aim of this systematic review was to determine the effectiveness of
dynamic exercise therapy in improving joint mobility, muscle strength,
aerobic capacity and daily functioning in patients with rheumatoid
arthritis (RA). In addition, possible unwanted effects such as an increase
in pain, disease activity and radiological progression were studied. A
computer-aided search of the MEDLINE, Embase and SCISEARCH databases was
performed to identify controlled trials on the effect of exercise therapy.
Randomized trials were selected on the effect of dynamic exercise therapy
in RA patients with an exercise programme fulfilling the following
criteria: (a) intensity level such that heart rates exceeded 60% of maximal
heart rate during at least 20 min; (b) exercise frequency > or = 2 a
week; and (c) duration of intervention > or = 6 weeks. Two blinded
reviewers independently selected eligible studies, rated the methodological
quality and extracted data. Six out of 30 identified controlled trials met
the inclusion criteria. Four of the six included studies fulfilled > or
= 7/10 methodological criteria. Because of heterogeneity in outcome
measures, data could not be pooled. The results suggest that dynamic
exercise therapy is effective in increasing aerobic capacity and muscle
strength. No detrimental effects on disease activity and pain were
observed. The effects of dynamic exercise therapy on functional ability and
radiological progression are unclear. It is concluded that dynamic exercise
therapy has a positive effect on physical capacity. Research on the
long-term effect of dynamic exercise therapy on radiological progression
and functional ability is needed.
相似文献
94.
胰岛ε细胞的研究进展 总被引:3,自引:0,他引:3
胰腺由外分泌组织和内分泌组织2个部分所组成,两者在机体能量平衡和营养代谢调节中发挥重要的作用.胰岛是胰腺组织中重要的内分泌功能单位,胰岛的发育和分化过程涉及一个复杂而精细的分子调控网络体系,其中包括许多转录因子的参与.经典的胰岛内分泌细胞包括α细胞、β细胞、δ细胞及PP细胞,分别产生胰升糖素、胰岛素、生长抑素及胰多肽(PP),各种胰岛细胞之间的相互调节在维持血糖稳态中具有重要的意义.表达ghrelin 的ε细胞是一种新近发现和命名的胰岛细胞类型.现着重对胰岛ε细胞的发现过程、形态学特点及生物学作用进行介绍. 相似文献
95.
96.
TP Jürgens C Schaefer & A May 《Cephalalgia : an international journal of headache》2009,29(4):391-400
Cluster headache is a rare disorder in women, but has a serious impact on the affected woman's life, especially on family planning. Women with cluster headache who are pregnant need special support, including the expertise of an experienced headache centre, an experienced gynaecologist and possibly a teratology information centre. The patient should be seen through all stages of the pregnancy. A detailed briefing about the risks and safety of various treatment options is mandatory. In general, both the number of medications and the dosage should be kept as low as possible. Preferred treatments include oxygen, subcutaneous or intranasal sumatriptan for acute pain and verapamil and prednisone/prednisolone as preventatives. If there is a compelling reason to treat the patient with another preventative, gabapentin is the drug of choice. While breastfeeding, oxygen, sumatriptan and lidocaine for acute pain and prednisone/prednisolone, verapamil, and lithium as preventatives are the drugs of choice. As the individual pharmacokinetics differ substantially, adverse drug effects should be considered if unexplained symptoms occur in the newborn. 相似文献
97.
JI Tang TP Shakespeare XJ Zhang JJ Lu S Liang CJ Wynne RK Mukherjee MF Back 《Journal of Medical Imaging and Radiation Oncology》2005,49(4):304-311
An outpatient radiotherapy department assessed how precautions implemented during the severe acute respiratory syndrome (SARS) outbreak affected patient satisfaction with doctor–patient interaction and explored variables potentially influencing satisfaction. The information obtained would help prepare us for future infectious disease outbreaks. Outpatients seen during the outbreak completed a validated questionnaire assessing satisfaction with doctor–patient interaction. Additional items assessed included patients’ perception of SARS measures and patient demographics. Of 149 patients, 97% had heard of SARS, 92% believed SARS precautions necessary, and 54% believed contracting SARS was possible despite the precautions. Patients were satisfied with doctors wearing masks (97%), temperature checks (97%), and patients wearing masks (96%). Despite the high satisfaction levels with SARS precautions, 24% believed it had adversely affected doctor–patient interaction. With regards to doctor–patient interaction, 94% of patients were satisfied. Patients were most satisfied with the ‘information exchange’ domain (mean score 3.23 out of 4) compared to other domains (P < 0.0001, 100.00% confidence) and were less satisfied with the ‘empathy’ domain compared to other domains (P < 0.0001, 100.00% confidence). Patients were most satisfied with understanding their treatment plan (100%), doctor being honest (97%) and being understood (96%). Patients were least satisfied with information about caring for their illness (61%), that the visit could be better (59%), and the doctor showing more interest (58%). On multivariate analysis, patients who were less satisfied with SARS measures were significantly less satisfied with doctor–patient interaction (P = 0.0001). Dissatisfaction with SARS measures was associated with significant dissatisfaction for questions in all domains. Older age and non‐breast cancer patients were also less satisfied with doctor–patient interaction. Most (94%) of patients were satisfied with doctor–patient interaction, despite implementation of infectious disease prevention measures. However, patients who were dissatisfied with the SARS precautions had poorer satisfaction. In particular, physician empathy appeared to be most adversely affected. The results have relevance to any radiotherapy department preparing contingency plans in the event of infectious disease outbreaks. 相似文献
98.
99.
RS Jagavkar TP Shakespeare MJ Stevens 《Journal of Medical Imaging and Radiation Oncology》1998,42(2):157-158
The first documented case of endometrial adenosarcoma associated with chronic tamoxifen usage is reported. 相似文献
100.
Faith E. Davies rew C. Rawstron Guy Pratt Sheila O''Connor Lela Su''Ut David Blythe James Fenton David Claydon J. Anthony Child rew S. Jack & Gareth J. Morgan 《British journal of haematology》1999,106(1):40-46
Studies utilizing flow cytometry and PCR have shown that the B-cell compartment in myeloma contains cells which are clonally related to the myelomatous plasma cells. Current data, however, remains inconclusive regarding the extent of this involvement. By combining fluorescent immunophenotyping, tyramine signal amplification and fluorescence in-situ hybridization (FICTION-TSA), we have used the presence of numerical chromosomal abnormalities within plasma cells as a clonal marker to examine the CD20+ B-cell compartment for the presence of aneuploidy. A series of 54 cases of myeloma were screened for the presence of numerical abnormalities of chromosomes 3 and 11. FICTION-TSA was performed on 13 cases with either trisomy 3 or 11 and on a control group of six cases known to be disomic for the two chromosomes. B-cell numbers were reduced in the myeloma cases compared to the normal controls (median 1.8% v 3.0%, P = 0.05). In the cases with a chromosomal marker, three signals were seen in a median of 1.88% of CD20+ B cells compared to 2.58% within the control group. Comparison of the two groups using a Wilcoxon-Mann-Whitney U test showed no statistical significant difference. Using this data set, it was possible to exclude a 3.03% expansion of clonally related B cells (95% confidence level). We conclude that the B-cell compartment in myeloma does not represent the major site of clonal expansion, and if clonally related cells are present then the numbers are few. 相似文献