Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “tRF”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed2004

Dynamics of telomere erosion and its association with genome instability in myelodysplastic syndromes (MDS) and acute myelogenous leukemia arising from MDS: a marker of disease prognosis?

Telomere length was evaluated by terminal repeat fragment method (TRF) in 50 patients with myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) arising from MDS and in 21 patients with untreated primary AML to ascertain, whether telomere erosion was associated with progression of MDS towards overt leukemia. Heterogeneity of TRF among MDS FAB subgroups (P=0.004) originated from its shortening in increased number of patients during progression of the disease. Chromosomal aberrations were present in 32% MDS patients with more eroded telomeres (P=0.022), nevertheless a difference between mean TRF in the subgroups with normal and abnormal karyotype diminished during progression of MDS. A negative correlation between individual TRF and IPSS value (P=0.039) showed that telomere dynamics might serve as a useful prognostic factor for assessment of an individual MDS patient's risk and for decision of an optimal treatment strategy.

Adolescent↗
PubMed1997

Modulation of transferrin receptor expression by dexrazoxane (ICRF-187) via activation of iron regulatory protein.

Dexrazoxane (ICRF-187) has recently been demonstrated to reduce cardiac toxicity induced by chemotherapy with anthracyclines, although the reason for this phenomenon has remained obscure thus far. In order to investigate whether ICRF-187 might exert its effects by modulating iron metabolism, we studied the drug's potential to influence the maintenance of iron homeostasis in two human cell lines. We demonstrate that ICRF-187 enhanced the binding affinity of iron regulatory protein (IRP), the central regulatory factor for posttranscriptional iron regulation, to RNA stem loop structures, called iron responsive elements (IRE), in THP-1 myelomonocytic as well as K562 erythroleukemic cells. Increased IRE/IRP interaction was paralleled by an elevation of transferrin receptor (trf-rec) mRNA levels which, according to the well-established mechanism of posttranscriptional iron regulation, was likely due to stabilisation of trf-rec mRNA by IRP. Subsequently, ICRF-187 treatment of cells increased trf-rec surface expression and enhanced cellular iron uptake. All these events, i.e. IRP activation, stabilisation of trf-rec mRNA and increased surface expression of the protein in response to ICRF-187, follow a dose-response relationship. Increased cellular uptake and sequestration of iron in response to ICRF-187 may contribute to the protective activity of ICRF-187 by reducing the iron-anthracycline complex and iron-catalysed generation of hydroxyl radicals via the Haber-Weiss reaction.

Antineoplastic Agents↗
PubMed2001

Development of a time-resolved immunofluorometric assay for quantitation of mucosal and systemic antibody responses.

We developed a solid phase immunoassay that measured mucosal and systemic antibody responses from mice inoculated with either a staphylococcal enterotoxin B vaccine (SEBv) or noninfectious virus-like particles (VLP) of lentiviral origin. The assay used time-resolved fluorescence (TRF) with affinity-purified goat anti-mouse IgA and IgG conjugated to samarium and europium chelates, respectively. By employing these fluorogenic conjugates with different spectral emissions, IgA and IgG specific for SEB or VLP were readily detected in serum and saliva from mice inoculated intranasally. The TRF assay detected antigen-specific IgA in saliva 10 min after the addition of enhancement solution, while a conventional alkaline phosphatase-based assay for salivary IgA required 18 h after substrate addition. The TRF assay also provided a significantly higher signal-to-noise ratio and exhibited greater sensitivity. TRF assays detected both IgA and IgG in the same well, thereby reducing sample and reagent requirements.

Administration, Intranasal↗
PubMed1999

Telomere shortening during aging of human osteoblasts in vitro and leukocytes in vivo: lack of excessive telomere loss in osteoporotic patients.

We have compared the telomere length, as assessed by Southern analysis, of telomere restriction fragments (TRFs) generated by RsaI/HinfI digestion of genomic DNA in: (i) in vitro cultured human trabecular osteoblasts undergoing cellular aging; and (ii) peripheral blood leukocytes (PBL) obtained from three groups of women: young (aged 20-26 years, n = 15), elderly (aged 48-85 years, n = 15) and osteoporotic (aged 52-81 years, n = 14). The mean TRF length in human osteoblasts undergoing aging in vitro decreased from an average of 9.32 kilobasepairs (kb) in middle-aged cells to an average of 7.80 kb in old cells. The rate of TRF shortening was about 100 bp per population doubling, which is similar to what has been reported for other cell types, such as human fibroblasts. Furthermore, there was a 30% decline in the total amount of telomeric DNA in senescent osteoblasts as compared with young cells. In the case of PBL, TRF length in the DNA extracted from young women was slightly longer (6.76 +/- 0.64 kb) than that from a group of elderly women (6.42 +/- 0.71 kb). A comparison of TRFs in the DNA extracted from the PBL from osteoporotic patients and from age-matched controls did not show any significant differences (6.47 +/- 0.94 versus 6.42 +/- 0.71 kb, respectively). Therefore, using TRF length as a marker for cellular aging in vitro and in vivo, our data comparing TRFs from osteoporotic patients and age-matched controls do not support the notion of the occurrence of a generalized premature cellular aging in osteoporotic patients.

Adult↗
PubMed1988

Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation.

Functional upstream activator sequences (TAATGARAT motifs) of herpes simplex virus immediate-early genes were identified and shown both to bind a factor (TRF) present in uninfected HeLa cells and to confer inducibility by the virus regulatory protein, Vmw65, on a normally nonresponsive promoter. Point-mutation analyses demonstrated binding specificity and correlated binding with Vmw65 induction. Furthermore, the octamer domains of the adenovirus DNA replication origin, the histone H2B, and the immunoglobulin light chain genes bound and competed for TRF. The immunoglobulin octamer also conferred Vmw65 inducibility on the TK promoter. In addition, a modified form of TRF was specifically detected in infected cells. We conclude that TRF is similar or identical to the previously described octamer binding protein and is likely to be the target for coordinate induction of immediate-early gene expression by Vmw65.

Base Sequence↗
PubMed2004

Telomere length and possible link to X chromosome.

BACKGROUND: Because telomeres are eroded during mitosis, telomere length indicates the replicative history of human somatic cells. Clinical markers of ageing--such as pulse pressure and survival--are associated with telomere length. On the basis of findings of studies in twins, telomere length seems to be familial, but little is known about its mode of inheritance. We aimed to investigate the inheritance of telomere length. METHODS: We measured terminal restriction fragment (TRF) length in white-blood-cell DNA taken from individuals from the family-based cohort of the Flemish Study on Environment, Genes, and Health Outcomes. FINDINGS: We recorded no correlation in sex and age adjusted TRF length between spouses (r=-0.05; p=0.70) nor between fathers and sons (r=-0.16; p=0.35). By contrast, we noted robust correlations in TRF length between fathers and daughters (r=0.60; p<0.0001); between mothers and sons (r=0.41; p=0.0017) and daughters (r=0.59; p<0.0001); and among siblings (r> or =0.61; p< or =0.0004). INTERPRETATION: X-linked inheritance of TRF length is the most probable explanation for our findings. Pending confirmation, our observations suggest that the process of ageing might be an X-linked trait.

Adult↗
PubMed2002

Estimating age of humans based on telomere shortening.

To estimate age using DNA based on telomere shortening, we determined the terminal restriction fragment (TRF) length, as telomere length, using Southern blot analysis of peripheral human blood and blood stains. All blood stains had been stored at room temperature for 5 months. The average TRF length clearly showed a tendency to shortening with aging. The formula for age estimation was based on a correlation between average TRF length and age of the subjects. The estimated age calculated from TRF length widely depends on environmental and genetic factors. However, as long as the DNA is well preserved, use of our method is feasible regardless of age of the subject and can give a rough estimation of age of subjects in forensic samples that carry no morphological information.

Adolescent↗
PubMedDate not supplied

Levels of ceruloplasmin, transferrin, and lipid peroxidation in the serum of patients with Type 2 diabetes mellitus.

Diabetes mellitus (DM) is a common disease affecting over 124 million individuals worldwide. DM is associated with high risk of atherosclerosis and renal, neural, and ocular damage. Increased oxidant stress has been implicated in the pathogenesis of DM. An increase in serum ceruloplasmin (Cp) levels has also been reported in Type 2 DM. Cp permits the incorporation of iron into transferrin (Trf). Trf inhibits iron ion-dependent OHo formation from H2O2. Patients with diabetes have increased levels of plasma lipid peroxidation products. In this study, we evaluated 50 patients with Type 2 DM and 21 clinically healthy subjects. Patients were divided into two groups. Group I included 29 patients without diabetic complications, Group II 21 with diabetic complications. Serum Cp, Trf, C-reactive protein (CRP), triglyceride (TG), cholesterol (Chol), and malondialdehyde (MDA) levels are studied. Serum Cp, CRP, TG, Chol, and MDA levels in diabetic patients were significantly higher than those of controls. Trf levels were significantly lower in diabetic patients than those of the controls. Cp, CRP, HbA1C, and MDA levels in Group II were significantly higher than those of Group I. Our results indicate that oxygen free radicals are formed in DM and can result in diabetic complications and that a prooxidant/oxidant imbalance is involved in the tissue injury in DM and diabetic complications.

Adult↗
PubMed2006

A sensitive probe for the detection of Zn(II) by time-resolved fluorescence.

A new, highly sensitive fluorescent sensor for Zn(II) ion (a tris(2-pyridylmethyl)amine derivative) shows very strong binding and Zn(II) concentration-dependent biexponential time-resolved fluorescence (TRF) decay profiles that can be used for ratiometric estimates of Zn(II) concentrations. The ligand-metal complexes were characterized in solution by spectroscopic techniques and in the solid state by X-ray crystallography. The TRF studies revealed that the sensor aggregates in the absence of Zn(II) in a ligand concentration-dependent manner, a complication that is discerned by TRF but not by steady-state fluorescence ratiometric sensing techniques. It is shown that the same TRF methods are highly useful for monitoring Zn(II) concentrations in A549 epithelial lung cells in vitro and that the results were consistent with those in solution.

Cations, Divalent↗
PubMed2000

Establishment of novel human esophageal cancer cell line in relation to telomere dynamics and telomerase activity.

The telomere and the telomerase in human esophageal cancer are not yet completely understood. The regulatory mechanism of telomerase activity and telomere dynamics has drawn considerable attention. It is generally assumed that when telomerase has been activated, no further telomere shortening should ensue; however, a much more complex pattern of telomere dynamics may exist in telomerase-positive cancer cells. A novel human esophageal cancer cell line (KAN-ES) was established and characterized. Using KAN-ES and its serially passaged subclones up to the 55th generation, we determined the alteration of telomere length (TRF), telomerase activity (TA), telomerase RNA expression (hTR), population doubling time, karyotype, and cytokeratin 14 expression during the process of establishing a cancer cell line. We found that the TRF was maintained between 4.0 and 5.0 kb during the serial passages, despite sustained high TA (assessed by an in vitro TRAP assay). No close relationships were found among TRF, TA, and hTR expression. TA and telomere dynamics were not associated with cellular growth ability and differentiation. However, the number of population doublings showed significant correlations with both the TA and doubling times. In conclusion, these dissociations between telomere dynamics and TA support the existence of additional controls on TRF in cancer cells. KAN-ES and its restored subclones should prove a valuable resource for esophageal cancer research.

Biomarkers, Tumor↗
PubMed2003

Telomere shortening in patients with plasma cell disorders.

OBJECTIVES: Telomeres are essential for maintaining chromosomal integrity; their shortening is associated with chromosome instability. The aim of this work was to study telomere length (TL) on bone marrow (BM) cells from patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). METHODS: Thirty-one MM patients: 12 at diagnosis (D), 11 at relapse (R) and eight at remission (RE) and two cases with MGUS were studied. TL based on terminal restriction fragment (TRF) assay was evaluated. Cytogenetic and molecular cytogenetic analyses were performed. Telomeric associations (TAs) on BM metaphases were also studied. RESULTS: TRF analysis in total MM patients showed a mean TRF peak value (5.20 +/- 0.35 kb) shorter than those observed in controls (8.5 +/- 0.5 kb) (P < 0.001). Moreover, TRF at D and R showed a significant telomere shortening (P < 0.001), with TL restored at RE. A strong correlation with the percentage of BM plasma cell infiltration (BMPCI) (rK = -0.540; P = 0.002) was found. Patients with abnormal karyotypes (AK) had significantly shorter TRFs than that observed in MM patients with normal karyotypes (P < 0.05). TRFs in MGUS patients did not differ with respect to controls. TA analysis showed an increased percentage in MM (19.46 +/- 1.98%) with respect to MGUS (6.12 +/- 1.87%) and normal BM cells (2.00 +/- 0.93%) (P < 0.001). CONCLUSIONS: MM patients showed a significant reduction in TL (> 60% of BMPCI and AK), suggesting a probable association with clinical evolution. Moreover, our findings support the idea that telomere shortening usually leads to increased frequencies of TAs and chromosome instability.

Bone Marrow↗
PubMed1994

[Temporal resolution with a hearing aid in hearing impaired persons].

The purpose of hearing aid fitting is to improve the communication of the hearing impaired. Despite rigorous efforts to optimize hearing aid fitting there are still some patients who remain unsatisfied. The subject of research was to find improved methods of measuring, to increase the correlation between subjective information from the patient and objectively measurable data. With this goal in mind the variation of temporal resolution in hearing aid fitting was investigated in 88 patients comparing unaided and aided hearing basing on the method of determining the temporal resolution factor TRF at 500 Hz, 1500 Hz and 4000 Hz under free sound field conditions, as previously described by Schorn and Zwicker. The method is based on masking period patterns but measures only their maximum and minimum using continuous and 30-Hz square-wave amplitude modulated masking noise. The following three values of interest are measured: Threshold in quiet using interrupted continuous tones (500 ms on, 500 ms off) with the masker off; threshold masked by a continuous masker (octave-wide continuous noise) and threshold masked by a rectangulary modulated masker using 14 Hz, so that periods of 72 ms and pauses of 36 ms occur. TRF was defined as the ratio between the level differences derived from the three measured values. For normal hearing subjects this factor is about 1. The results show significant variation of the TRF comparing the data of the patients with and without hearing aids. The values for TRF unaided were 0.5 and 0.6 as well as under hearing aid.(ABSTRACT TRUNCATED AT 250 WORDS)

Audiometry, Pure-Tone↗
PubMed2005

Elimination of translational and rotational motions in nuclear orbital plus molecular orbital theory.

The nuclear orbital plus molecular orbital (NOMO) theory was developed in order to determine the nonadiabatic nuclear and electronic wave functions. This study presents a formulation to remove the contamination of rotational motion as well as translational motion in the NOMO theory. We have formulated the translation- and rotation-free (TRF)-NOMO theory by introducing the TRF Hamiltonian. The principal moment of inertia, which is the denominator in the rotational Hamiltonian, is expanded in a Taylor series. The zeroth-order of the Taylor expansion corresponds to a rigid-body rotator. The first-order terms contribute the coupling between the vibration and the rotation. Hartree-Fock equations have been derived in the framework of the TRF-NOMO theory. Numerical assessments, which were preformed for H2, D2, T2, mu2 (muon dimmer), and H2O, confirmed the importance of the TRF treatment.

Journal Article↗
PubMed2006

Elimination of translational and rotational motions in nuclear orbital plus molecular orbital theory: application of Moller-Plesset perturbation theory.

The translation- and rotation-free nuclear orbital plus molecular orbital (TRF-NOMO) theory was developed to determine the nonadiabatic nuclear and electronic wave functions. This study presents a formulation of TRF-NOMO second-order Moller-Plesset (MP2) perturbation and Epstein-Nesbet (EN) theory with the use of the TRF Hamiltonian. Numerical assessment of the TRF-NOMO/MP2 and EN is performed for several molecules. We confirm the importance of the elimination of translational and rotational motions in the many-body calculations.

Journal Article↗
PubMed1999

Malignancy: Subsequential Alterations of Telomeric DNA Length Correlate with Cytogenetic Response in Chronic Myeloid Leukemia Treated with Interferon alpha.

Telomeres consist of simple tandem hexametric (TTAGGG) repeats and progressively shorten with cell replication. To determine a relationship between telomeric erosion and response to treatment, we measured telomere length following treatment in patients with chronic myeloid leukemia (CML) in the chronic phase. We used 70 samples of bone marrow mononuclear cells obtained from 26 patients with CML in the chronic phase subsequently. Telomere length was determined by a Southern hybridization of HinfI-digested DNA using a (TTAGGG)(4) probe, and the terminal restriction fragment (TRF) length was measured. Telomerase activity was also measured in 14 CML patients at the time of diagnosis using a telomeric repeat amplification protocol (TRAP) assay. Of the 26 patients with CML at the time of diagnosis, 14 had normal TRF lengths and the remaining 12 had shortened TRFs compared to those of age-matched normal individuals. In a group of CML patients treated with interferon alpha (IFNalpha), 80% of those who showed normal TRFs obtained cytogenetic responses. Approximately 50% of patients with shortened TRFs and treated with IFNalpha showed normalization of TRFs after IFNalpha treatment and all of them were cytogenetic responders. None of the CML patients with shortened TRFs before and after IFNalpha treatment achieved major cytogenetic response and they had high levels of telomerase activity. In the group of CML patients treated with hydroxyurea alone, although some patients showed normalization of TRF lengths after treatment, none of them showed major cytogenetic response. Telomere length before treatment may be related to CML disease severity. Cytogenetic response could be expected in CML patients with normal TRF lengths and treated with IFNalpha. Thus, measurement of telomere length after treatment might provide important information in managing CML patients.

Journal Article↗
PubMed2004

Mapping of a major locus that determines telomere length in humans.

Telomere length is a crucial factor for both normal chromosomal function and senescence. Mean telomere length in humans shows considerable interindividual variation and strong genetic determination. To see if a locus (or loci) affecting telomere length in humans could be mapped, we performed a quantitative-trait linkage analysis of mean leukocyte telomere-restriction-fragment (TRF) lengths, measured by Southern blotting, in 383 adult subjects comprising 258 sib pairs. Heritability of mean (+/-SE) TRF was 81.9%+/-11.8%. There was significant linkage (LOD score 3.20) of mean TRF length to a locus on chromosome 12, which explained 49% of the overall variability in mean TRF length. We present preliminary analysis of a strong candidate gene in the region, the DNA helicase DDX11. In conclusion, we report mapping of the first locus that determines mean telomere length in humans. Identification of the gene involved and elucidation of its mechanism of action could have important implications for our understanding of chromosomal assembly, telomere biology, and susceptibility to age-related diseases.

Adolescent↗
PubMed1999

Normal telomere lengths in naive and memory CD4+ T cells in HIV type 1 infection: a mathematical interpretation.

To study CD4+ T cell productivity during HIV-1 infection, CD4+ T cell telomere lengths were measured. Cross-sectional and longitudinal analysis of HIV-1-infected individuals with CD4+ T cells counts >300 cells/mm3 showed normal average telomeric restriction fragment (TRF) length and normal shortening rates of CD45RA+ naive and CD45RO+ memory CD4+ T cells. These TRF data were interpreted in terms of CD4+ T cell production by means of a mathematical model. This model resolves previous criticisms arguing that the normal TRF length of CD4+ T cells in HIV-1 clinical latency is due to the killing of dividing CD4+ T cells by the virus. Only an increased priming rate of naive CD4+ T cells to become memory cells may elongate the average TRF length of memory CD4+ T cells, and may therefore mask the shortening effect of increased turnover in the CD4+ memory T cell compartment. The data are more compatible with the notion that during HIV-1 clinical latency the turnover of CD4+ T cells is not markedly increased, however, and that HIV-related interference with renewal from progenitors plays a role in CD4+ T cell depletion. In such a "limited renewal" scenario disease progression is no longer a consequence of markedly increased CD4+ T cell production.

CD4-Positive T-Lymphocytes↗
PubMed1986

T-cell replacing factor activity of recombinant-derived interleukin-2 requires gamma-interferon.

In this study we show that recombinant-derived human interleukin-2 (rIL-2) has potent T-cell replacing activity in antigen-driven murine antibody responses of T-depleted spleen cells. This T-cell replacing factor (TRF) effect of rIL-2 is antigen specific. By the use of a variety of antibodies to gamma-interferon (IFN-gamma), including antibody from an interspecies hybridoma, we demonstrate that this TRF activity depends upon the production of IFN-gamma in the responding cell cultures, i.e., antibody to IFN-gamma blocks TRF activity. In addition, we show that the cell-to-cell allogeneic helper effect of T cells for antibody responses is similarly inhibited by antibodies to IFN-gamma. The inhibition of response produced by the antibodies is reversed by the addition of excess rIFN-gamma to the cultures. The results demonstrate that IFN-gamma is a necessary intermediate mediator for TRF activity mediated by IL-2 and also by T-cell-mediated help for B cells. Thus, even recombinant-derived lymphokines have complex secondary levels of action on responding cells. Antibodies to individual lymphokines are clearly a powerful resource to analyze the role of soluble factors in cellular responses.

Animals↗