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41.
Waldmann TA; Goldman CK; Bongiovanni KF; Sharrow SO; Davey MP; Cease KB; Greenberg SJ; Longo DL 《Blood》1988,72(5):1805-1816
Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy. 相似文献
42.
Tubulin binding blocks mitochondrial voltage-dependent anion channel and regulates respiration 总被引:3,自引:0,他引:3
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Tatiana K. Rostovtseva Kely L. Sheldon Elnaz Hassanzadeh Claire Monge Valdur Saks Sergey M. Bezrukov Dan L. Sackett 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(48):18746-18751
Regulation of mitochondrial outer membrane (MOM) permeability has dual importance: in normal metabolite and energy exchange between mitochondria and cytoplasm and thus in control of respiration, and in apoptosis by release of apoptogenic factors into the cytosol. However, the mechanism of this regulation, dependent on the voltage-dependent anion channel (VDAC), the major channel of MOM, remains controversial. A long-standing puzzle is that in permeabilized cells, adenine nucleotide translocase (ANT) is less accessible to cytosolic ADP than in isolated mitochondria. We solve this puzzle by finding a missing player in the regulation of MOM permeability: the cytoskeletal protein tubulin. We show that nanomolar concentrations of dimeric tubulin induce voltage-sensitive reversible closure of VDAC reconstituted into planar phospholipid membranes. Tubulin strikingly increases VDAC voltage sensitivity and at physiological salt conditions could induce VDAC closure at <10 mV transmembrane potentials. Experiments with isolated mitochondria confirm these findings. Tubulin added to isolated mitochondria decreases ADP availability to ANT, partially restoring the low MOM permeability (high apparent Km for ADP) found in permeabilized cells. Our findings suggest a previously unknown mechanism of regulation of mitochondrial energetics, governed by VDAC and tubulin at the mitochondria–cytosol interface. This tubulin–VDAC interaction requires tubulin anionic C-terminal tail (CTT) peptides. The significance of this interaction may be reflected in the evolutionary conservation of length and anionic charge in CTT throughout eukaryotes, despite wide changes in the exact sequence. Additionally, tubulins that have lost significant length or anionic character are only found in cells that do not have mitochondria. 相似文献
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44.
DL DSouza SB Heinze RJ Dowling 《Journal of Medical Imaging and Radiation Oncology》2006,50(3):246-248
Lung cancer is not commonly known to metastasise to the perirenal space, with only five such cases previously published. We present an unusual case of perirenal lung metastases manifesting as diffuse perinephric stranding which to our knowledge has not been described before. 相似文献
45.
Brandon DL Marshall Thomas Kerr Chris Livingstone Kathy Li Julio SG Montaner Evan Wood 《Harm reduction journal》2008,5(1):35
Aboriginal people experience a disproportionate burden of HIV infection among the adult population in Canada; however, less
is known regarding the prevalence and characteristics of HIV positivity among drug-using and street-involved Aboriginal youth.
We examined HIV seroprevalence and risk factors among a cohort of 529 street-involved youth in Vancouver, Canada. At baseline,
15 (2.8%) were HIV positive, of whom 7 (46.7%) were Aboriginal. Aboriginal ethnicity was a significant correlate of HIV infection
(odds ratio = 2.87, 95%CI: 1.02 – 8.09). Of the HIV positive participants, 2 (28.6%) Aboriginals and 6 (75.0%) non-Aboriginals
reported injection drug use; furthermore, hepatitis C co-infection was significantly less common among Aboriginal participants
(p = 0.041). These findings suggest that factors other than injection drug use may promote HIV transmission among street-involved
Aboriginal youth, and provide further evidence that culturally appropriate and evidence-based interventions for HIV prevention
among Aboriginal young people are urgently required. 相似文献
46.
P21-dependent g(1)arrest with downregulation of cyclin D1 and upregulation of cyclin E by the histone deacetylase inhibitor FR901228 总被引:15,自引:0,他引:15
Sandor V Senderowicz A Mertins S Sackett D Sausville E Blagosklonny MV Bates SE 《British journal of cancer》2000,83(6):817-825
Depsipeptide, FR901228, a novel cyclic peptide inhibitor of histone deacetylase with a unique cytotoxicity profile is currently in phase I clinical trials. Here we demonstrate that, in addition to G2/M arrest, FR901228 causes G1 arrest with Rb hypophosphorylation. In vitro kinase assays demonstrated no direct inhibition of CDK activity, however, an inhibition was observed in CDKs extracted from cells exposed to FR901228. Cyclin D1 protein disappeared between 6 and 12 hours after treatment with FR901228, whereas cyclin E was upregulated. While it did not induce wt p53, FR901228 did induce p21(WAF1/CIP1)in a p53-independent manner. Cell clones lacking p21 were not arrested in G1 phase, but continued DNA synthesis and were arrested in G2/M phase following FR901228 treatment. Finally, FR901228 blunted ERK-2/MAPK activation by EGF whereas early signal transduction events remained intact since overall cellular tyrosine phosphorylation after EGF stimulation was unaffected. Thus, FR901228, while not directly inhibiting kinase activity, causes cyclin D1 downregulation and a p53-independent p21 induction, leading to inhibition of CDK and dephosphorylation of Rb resulting in growth arrest in the early G1 phase. In contrast to the G1 arrest, the G2/M arrest is p21-independent, but is associated with significant cytotoxicity. 相似文献
47.
48.
Age-related postural deficits elicit compensatory mechanisms such as ankle dorsiflexion in the elderly. To gain further insight into this problem, the ability to match an ankle angle during quiet stance was studied in 12 elderly and 12 young subjects. Following an initial single limb angular perturbation presented in the ±4° range, a subject had to return a tilt platform to level, as determined by the nonperturbed limb. Elderly subjects exhibited significant positive (0.9°) over-shoot of the level position, in contrast to young subjects who matched ankle angle with a mean error of −0.1°. The elderly group also exhibited an increase in positioning error for angular displacements in the range between −1 and +1°. The results document age-related postural changes in ankle positioning which might affect postural stability in older adults. 相似文献
49.
50.
A B Crummy W J Zwiebel P Barriga C M Strother J F Sackett W D Turnipseed F Jarrett H Berkoff 《AJR. American journal of roentgenology》1979,132(1):91-93
The carotid Doppler examination is an accurate means of screening the extracranial carotid system for stenotic lesions. Comparison of 100 patients (200 vessels) examined by the Doppler method and arteriography showed agreement in 90% of the vessels and a significant error rate in only 3.5%. 相似文献