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PubMed2006

Tetra-layered sign of adult intussusception (new ultrasound approach).

Two-dimensional ultrasound is the principle method for the detection of intussusception. The aim of this study was to establish a pathognominic ultrasound criterion for diagnosing intestinal intussusception to facilitate a proper clinical decision. We have developed a new approach to diagnosing colonic intussuception based on the hypothesis that ultrasound image of the invaginated segment should reveal four border layers. We called this sign tetra-layered sign (TLS). In a prospective manner, all adult patients diagnosed with intussusception using the TLS approach in the period from July 1990 and July 2005 were included in this study. All patients underwent explorative laparotomy, and our preoperative diagnoses were compared with the surgical outcome. Thirty patients were diagnosed with intestinal intussusception using the TLS ultrasound sign. Surgery confirmed the preoperative diagnosis in all cases. Conventional ultrasound is very reliable in diagnosing intestinal intussusception in adult patients when utilizing the simple ultrasound applicable TLS. This facilitates the decision-making, improves the clinical outcome and reduces the associated costs.

Adult↗

PubMed2003

A review of clinical and laboratory findings and treatment of tumor lysis syndrome.

Acute tumor lysis syndrome (TLS) has started to be considered a separate entity or condition associated with bulk tumor treatment. TLS is described as the biochemical disturbances associated with rapid destruction of tumor cells with subsequent synchronised massive release of cellular breakdown products sufficient to overwhelm excretory mechanisms and the body's normal reutilization capacity. The cardinal signs of TLS are: hyperkalemia, hyperphosphatemia, hypocalcemia and hyperuricemia. This review comprehensively discusses the differential diagnosis, pathophysiology and clinical features, possible causal indications for laboratory monitoring and treatment options of TLS.

Diagnosis, Differential↗

PubMed2003

Entrapping ribosomes for viral translation: tRNA mimicry as a molecular Trojan horse.

Turnip yellow mosaic virus (TYMV) has a genomic plus-strand RNA with a 5' cap followed by overlapping and different reading frames for the movement protein and polyprotein, while the distal coat protein cistron is translated from a subgenomic RNA. The 3'-untranslated region harbors a tRNA-like structure (TLS) to which a valine moiety can be added and it is indispensable for virus viability. Here, we report about a surprising interaction between TYMV-RNA-programmed ribosomes and 3'-valylated TLS that yields polyprotein with the valine N terminally incorporated by a translation mechanism resistant to regular initiation inhibitors. Disruption of the TLS exclusively abolishes polyprotein synthesis, which can be restored by adding excess TLS in trans. Our observations imply a novel eukaryotic mechanism for internal initiation of mRNA translation.

3' Untranslated Regions↗

PubMed1998

Determination of trans-beta-carotene and other carotenoids in blood plasma using high-performance liquid chromatography and thermal lens detection.

Thermal lens spectrometry (TLS) was applied for the detection of beta-cryptoxanthin, alpha-carotene, trans-beta-carotene, and lycopen in blood plasma. This combined high-performance liquid chromatography-TLS (HPLC-TLS) method was validated by comparison with HPLC-UV-Vis analysis of blood plasma under identical chromatographic conditions and by comparing the results obtained from an independent, standard HPLC procedure for determination of carotenoids in blood plasma samples. The results demonstrated good agreement with the target values for carotenoids in an in-laboratory control sample and confirmed the accuracy of the HPLC-TLS technique. Limits of detection for blood plasma samples were 70 pg/ml for beta-cryptoxanthin, 85 pg/ml for alpha-carotene, 100 pg/ml for trans-beta-carotene, and 120 pg/ml for lycopen. This represents a 100-fold improvement compared to the HPLC analysis with UV-Vis detection.

Carotenoids↗

PubMed2002

RNA splicing mediated by YB-1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells.

Human myxoid liposarcoma contains a characteristic t(12;16) chromosomal translocation that results in fusion of the N-terminal domain of the translocated in liposarcoma (TLS) protein to the C/EBP homologous protein (CHOP). TLS possesses structural motifs that suggest it may participate in RNA processing. We demonstrate that in human myxoid liposarcoma cells, wild-type TLS binds to RNA polymerase II (Pol II) via its N-terminal domain and to the transcription and translation factor Y-box binding protein-1 (YB-1) through its C-terminal domain. The liposarcoma fusion protein TLS/CHOP retains the ability to bind RNA Pol II but lacks the ability to recruit YB-1 due to replacement of the C-terminal domain of TLS by CHOP. In an in vivo splicing assay, YB-1 promotes splicing of adenovirus EIA pre-mRNA predominantly to the 13S isoform. The oncogenic TLS/CHOP fusion protein inhibits this splicing function of YB-1 in a dominant negative manner. When considered in conjunction with studies on other sarcoma fusion proteins, these data suggest that aberrant RNA splicing may be a common feature of human sarcomas.

Adenovirus E1A Proteins↗

PubMed2002

Pathophysiology, signs, and symptoms of acute tumor lysis syndrome.

OBJECTIVES: To provide a review of the pathophysiology and corresponding signs and symptoms of tumor lysis syndrome (TLS); to review clinical and laboratory monitoring parameters. DATA SOURCES: Primary and tertiary literature and clinical experience. CONCLUSIONS: An understanding of the pathophysiology of TLS, meticulous assessment for signs and symptoms and monitoring of laboratory data, as well as early recognition of problems are essential for optimal patient outcomes. IMPLICATIONS FOR NURSING PRACTICE: Knowledge of the pathophysiology of TLS will assist the oncology nurse in better understanding the overall syndrome and allow improved patient care management through close clinical and laboratory monitoring of signs and symptoms, and, ideally, promote a proactive approach to managing TLS.

Acute Disease↗

PubMed2002

Management of tumor lysis syndrome: prevention and treatment.

OBJECTIVES: To provide a review of the preventive and treatment strategies for tumor lysis syndrome (TLS). DATA SOURCES: Primary and tertiary literature and clinical experience. CONCLUSIONS: The oncology nurse can optimize outcomes in the patient at risk for TLS through a variety of prevention and treatment interventions: (1) aggressive patient monitoring for early identification and treatment; (2) minimize risk factors via thorough medication and nutritional histories, and assurance of proper prophylactic regimens; (3) assessment of optimal routes of drug delivery to assure medication bioavailability; and (4) reinforcement of the above with comprehensive patient education. IMPLICATIONS FOR NURSING PRACTICE: Awareness and effective use of prophylactic and treatment regimens related to TLS will positively impact patient outcomes. The oncology nurse is at the front line to identify issues related to effective management of TLS.

Adult↗

PubMed2002

Pediatric considerations in tumor lysis syndrome.

OBJECTIVES: To identify pediatric issues related to tumor lysis syndrome (TLS) focusing on potential differences in patient monitoring and management in the pediatric patient as opposed to the adult; to discuss family and caregiver education. DATA SOURCES: Primary and tertiary literature and clinical experience. CONCLUSIONS: Pediatric patients are at high risk for developing TLS given the high incidence of hematologic malignancies in this population. The goal of therapy is to implement preventive treatment regimens and, once evident, respond immediately to correct any electrolyte or metabolic abnormalities. Close monitoring for risk factors and immediate identification and intervention is essential in preventing the life-threatening consequences of TLS. IMPLICATIONS FOR NURSING PRACTICE: The pediatric oncology nurse can significantly impact clinical outcomes in patients with or at risk for TLS through vigilant monitoring and implementation of prevention and treatment strategies.

Adolescent↗

PubMed2000

Pharmacokinetic-pharmacodynamic correlation of lamotrigine, flunarizine, loreclezole, CGP40116 and CGP39551 in the cortical stimulation model.

The purpose of this study was to assess the concentration-anti-convulsant effect relationships of a number of anti-convulsant drugs in the direct cortical stimulation model, to obtain more insight in the properties and predictive value of this model. The time course of the effect of lamotrigine, loreclezole, flunarizine, CGP40116 and CGP39551 was determined after iv. administration in conjunction with their pharmacokinetics. Convulsive activity was induced by stimulation of the motor cortex with a ramp-shaped pulse train. This technique allows consecutive measurements of the treshold for localized (TLS) and for generalized (TGS) seizure activity. Increase in threshold was used as measure of the anti-convulsant effect. After administration of lamotrigine, pronounced elevation of the TGS, with little change in the TLS, was observed. Flunarizine caused a similar effect, but much less intense. Loreclezole strongly elevated the TGS and to a lesser extent the TLS, also. The concentration-anti-convulsant effect relationship of the three compounds could be fitted by an exponential model. The NMDA antagonists, CGP40116 and CGP39551, induced minor changes in the TLS and a slight increase in the TGS. The onset of this effect was marked by a delay relative to blood concentrations. The biophase equilibration kinetics was estimated and a linear model was applied to describe the concentration-effect relationship of both NMDA antagonists. The present results show that the cortical stimulation model is a suitable technique for integrated pharmacokinetic-pharmacodynamic modelling and for assessing anti-convulsant efficacy. The results show that the model is rather insensitive to calcium channel blockers and NMDA antagonists.

Animals↗

PubMed2000

Disruption of the Rev3l-encoded catalytic subunit of polymerase zeta in mice results in early embryonic lethality.

Polymerase zeta (Pol zeta) is an error-prone DNA polymerase [1], which in yeast is involved in trans-lesion synthesis (TLS) and is responsible for most of the ultraviolet (UV) radiation-induced and spontaneous mutagenesis [2-4]. Pol zeta consists of three subunits: REV1, a deoxycytidyl-transferase [5]; REV7, of unclear function [6]; and REV3, the catalytic subunit. REV3 alone is sufficient to carry out TLS, but association with REV1 and REV7 enhances its activity [5, 7]. Experiments using human cells treated with UV radiation indicate also that mammalian Pol zeta is involved in TLS [7]. The peculiar mutagenic activity of Pol zeta [4,7,8] suggests a possible role in somatic hypermutation of immunoglobulin (Ig) genes [9]. Here, we report that, unlike in yeast where the REV3 gene is not essential for life [4], disruption of the mouse homologue (Rev3l) resulted in early embryonic lethality. In Rev3l(-/-) embryos, no haematopoietic cells other than erythrocytes could be identified in the yolk sac. Rev3l(-/-) haematopoietic precursors were unable to expand in vitro and no haematopoietic cells could be derived from the intraembryonic haematogenic compartment (splanchnopleura). Fibroblasts could not be derived from the Rev3l(-/-) embryos, and Rev3l(-/-) embryonic stem (ES) cells could not be obtained. This is the first evidence that an enzyme involved in TLS is critical for mammalian development.

Animals↗

PubMed2000

Lesions in DNA: hurdles for polymerases.

Translesion synthesis (TLS) is one of the DNA damage tolerance strategies, which have evolved to enable organisms to replicate their genome despite the presence of unrepaired damage. The process of TLS has the propensity to produce mutations, a potential origin of cancer, and is therefore of medical interest. Significant progress in our understanding of TLS has come primarily from studies of the bacterium Escherichia coli, the budding yeast Saccharomyces cerevisiae and, more recently, human cells. Results from these analyses indicate that the fundamental mechanism of TLS and the proteins involved have been conserved throughout evolution from bacteria to humans.

DNA Damage↗

PubMed2002

Pivotal role of the beta-clamp in translesion DNA synthesis and mutagenesis in E. coli cells.

The genetic information is continuously subjected to the attack by endogenous and exogenous chemical and physical carcinogens that damage the DNA template, thus compromising its biochemical functions. Despite the multiple and efficient DNA repair systems that have evolved to cope with the large variety of damages, some lesions may persist and, as a consequence, interfere with DNA replication. By essence, the damaged-DNA replication process (hereafter termed translesion synthesis or TLS) is a major source of point mutations and is therefore deeply involved in the onset of human diseases such as cancer. Recent identification of numerous DNA polymerases involved in TLS has shed new light onto the molecular mechanisms of mutagenesis. Here, we show that in vivo, both error-free and mutagenic bypass activities of the three DNA polymerases known to be involved in TLS in Escherichia coli (PolII, PolIV and PolV) strictly depend upon the integrity of small peptidic sequences identified as their beta-clamp binding motif. Thus, in addition to its crucial role as the processivity factor of the PolIII replicase, the beta-clamp plays a pivotal role during the TLS process.

DNA Damage↗

PubMedDate not supplied

An ethnographic study of differentiated practice in an operating room.

An ethnographic study was conducted to investigate implementation of the clinical nurse III or team leader (TL) role as part of a newly executed nursing differentiated practice model. The six TLs studied were employed in the operating room (OR). Through participant observation, interviews, and document analysis, the TL role--as well as perceptions of the role by the TLs and OR staff--were studied. Problems related to performance of the role and its evolutionary process were delineated. Data analysis involved identifying categories and subcategories of data and developing a coding system to identify themes. Salient themes were related to the culture of the OR. Because of the OR's highly technical environment, the TLs defined their roles in relation to the organizational and technical needs of their surgical service. Refinement of surgeon "preference cards" and "instrument count sheets" was considered the initial priority for the TLs. Various controllable and uncontrollable factors were identified that affected implementation of the new TL role. Findings suggest that introduction of the role requires insight into setting and an emphasis on staging and orientation of employees to the new role.

Anthropology, Cultural↗

PubMed2000

Monitoring of dye adsorption phenomena at a silica glass/water interface with total internal reflection coupled with a thermal lens effect

Thermal lens spectroscopy was combined with total internal reflectance spectroscopy to develop a novel, highly sensitive analytical method that can detect nonfluorescent as well as fluorescent analytes at surfaces and interfaces. It was verified that when the total internal reflection method is coupled with thermal lens spectroscopy (TIR-TLS), the thermal lens effect is induced by only the evanescent wave. The ability of depth profiling was shown. The detection limit of TIR-TLS was at an absorbance of 3.0 x 10(-5) unit for Sudan II acetone solution, which is better than that of attenuated total reflection by a factor of hundreds. In addition, the adsorption of acridine orange on silanol groups on a glass surface could be monitored directly by TIR-TLS, and the adsorption isotherm agreed well with Langmuir's model. The dependence of surface density of anionic silanol groups on pH was determined by TIR-TLS measurements of aqueous acridine orange solutions buffered in the pH range between 2.7 and 11.5.

Journal Article↗

PubMed2005

Loss of DNA minor groove interactions by exonuclease-deficient Klenow polymerase inhibits O6-methylguanine and abasic site translesion synthesis.

The importance of DNA polymerase-DNA minor groove interactions on translesion synthesis (TLS) was examined in vitro using variants of exonuclease-deficient Klenow polymerase and site-specifically modified DNA oligonucleotides. Polymerase variant R668A lacks primer strand interactions, while variant Q849A lacks template strand interactions. O(6)-Methylguanine (m6G) and abasic site TLS was examined in three stages: dNTP insertion opposite the lesion, extension from a terminal lesion-containing base pair, and the dissociation equilibrium of the polymerase from the lesion-containing template. Less than 5% TLS was observed at the insertion step for either variant on the lesion-containing templates. While extensive TLS was observed for WT polymerase on the m6G template, only incorporation opposite the lesion was observed for the R668A variant. Loss of the template strand interaction, Q849A, resulted in the inability to insert dNTPs opposite either the m6G or abasic lesion. For both variants, extension of purine-containing m6G primer-templates was increased relative to WT polymerase. We observed similar extension efficiencies for all variants, relative to WT, using abasic template-primers. Polymerase dissociation/reassociation was studied through the use of a competitor primer/template complex. Dissociation for WT polymerase increased 2-fold and 3-fold, respectively, for m6G and abasic lesion-containing templates, relative to the natural template. Variants lacking DNA minor groove interactions displayed increased dissociation from DNA templates, relative to WT polymerase, but do not display an increased level of lesion-induced polymerase dissociation. Our results indicate that the primer and template strand interactions of the Klenow polymerase with the DNA minor groove are critical for maintaining the DNA-polymerase complex during translesion synthesis.

Amino Acid Substitution↗

PubMed2000

Selection of viral RNA-derived tRNA-like structures with improved valylation activities.

The tRNA-like structure (TLS) of turnip yellow mosaic virus (TYMV) RNA was previously shown to be efficiently charged by yeast valyl-tRNA synthetase (ValRS). This RNA has a noncanonical structure at its 3'-terminus but mimics a tRNA L-shaped fold, including an anticodon loop containing the major identity nucleotides for valylation, and a pseudoknotted amino acid accepting domain. Here we describe an in vitro selection experiment aimed (i) to verify the completeness of the valine identity set, (ii) to elucidate the impact of the pseudoknot on valylation, and (iii) to investigate whether functional communication exists between the two distal anticodon and amino acid accepting domains. Valylatable variants were selected from a pool of 2 x 10(13) RNA molecules derived from the TYMV TLS randomized in the anticodon loop nucleotides and in the length (1-6 nucleotides) and sequence of the pseudoknot loop L1. After nine rounds of selection by aminoacylation, 42 have been isolated. Among them, 17 RNAs could be efficiently charged by yeast ValRS. Their sequence revealed strong conservation of the second and the third anticodon triplet positions (A(56), C(55)) and the very 3'-end loop nucleotide C(53). A large variability of the other nucleotides of the loop was observed and no wild-type sequence was recovered. The selected molecules presented pseudoknot domains with loop L1 varying in size from 3-6 nucleotides and some sequence conservation, but did neither reveal the wild-type combination. All selected variants are 5-50 times more efficiently valylated than the wild-type TLS, suggesting that the natural viral sequence has emerged from a combination of evolutionary pressures among which aminoacylation was not predominant. This is in line with the role of the TLS in viral replication.

3' Untranslated Regions↗

PubMed1999

Sequence context modulation of translesion synthesis at a single N-2-acetylaminofluorene adduct located within a mutation hot spot.

Oligonucleotides containing a single N-(deoxyguanosin-8-yl)acetylaminofluorene lesion (dGuo-C8-AAF) at each guanine residue of the sequence (5'-G1G2G3) have been used as templates for in vitro primer extension reactions by several DNA polymerases [Escherichia coli DNA polymerase III holoenzyme, its alpha subunit, DNA polymerase I Klenow fragment proficient (exo+) or deficient (exo-) in its 3' --> 5' exonuclease activity, and Sequenase]. The dGuo-C8-AAF lesion appears to be a strong block for all DNA polymerases: exo+ DNA polymerases stop one nucleotide before encountering the lesion, while partial incorporation opposite the lesion is observed only with enzymes devoid of the exonuclease activity. The efficiency of incorporation across from the adduct depends on both the DNA polymerase and the position of the lesion. When polymerase I Klenow fragment exo- is used, translesion synthesis (TLS) is observed with efficiencies varying according to the position of the adduct (G2 > G1 > G3). Sequencing of the TLS products shows that error-free TLS is observed only when the AAF lesion is bound to G1, while all TLS events occurring at G2- or G3-AAF adducts are mutagenic. The major mutational event is a G deletion (27, 76, and 55% of the events for G1, G2, and G3, respectively), while two-G deletions occur to a lesser extent (17-30%). These results are discussed in view of the slippage model developed for frameshift mutagenesis occurring during translesion synthesis at replication blocking lesions.

2-Acetylaminofluorene↗

PubMed2000

Tumor lysis syndrome following hemi-body irradiation for metastatic breast cancer.

Tumor lysis syndrome (TLS) is a rare serious acute complication of cancer therapy, reported mainly following chemotherapy in patients with large tumor load and chemosensitive disease. These are mainly patients with non-Hodgkin's lymphoma, leukemia and rarely in solid tumors. It is less frequently described after radiotherapy for lymphoid and hematological malignancies. TLS following radiotherapy for solid tumors is a very rare complication. In this report/review we describe a seventy-three-year-old male patient with progressive metastatic carcinoma of the breast to the lungs, liver and bone. He was referred for radiotherapy because of generalized bony pains. The patient was planned for sequential hemi-body irradiation starting with the more symptomatic upper half body. After premedication, he was given 8.5 Gy to the mid point at the maximum chest separation with anterior lung attenuator limiting uncorrected lung dose to 6.15 Gy. A further 3.5 Gy electron boost to the fungating breast tumor was given to the 100%. Forty-eight hours after irradiation he developed hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia and renal failure. These clinical and biochemical changes are typical of tumor lysis syndrome (TLS). Despite hydration, and treating the hyperuricemia, the patient developed coma and died eight days after irradiation. The prophylaxis and management of TLS and in high-risk patients are described to avoid this frequently fatal complication.

Aged↗