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At least 991 records · Page 55Linked to original sources
PubMed2003

Small nucleolar RNA clusters in trypanosomatid Leptomonas collosoma. Genome organization, expression studies, and the potential role of sequences present upstream from the first repeated cluster.

Trypanosomatid small nucleolar RNA (snoRNA) genes are clustered in the genome. snoRNAs are transcribed polycistronically and processed into mature RNAs. In this study, we characterized four snoRNA clusters in Leptomonas collosoma. All of the clusters analyzed carry both C/D and H/ACA RNAs. The H/ACA RNAs are composed of a single hairpin, a structure typical to trypanosome and archaea guide RNAs. Using deletion and mutational analysis of a tagged C/D snoRNA situated within the snoRNA cluster, we identified 10-nucleotide flanking sequences that are essential for processing snoRNA from its precursor. Chromosome walk was performed on a snoRNA cluster, and a sequence of 700 bp was identified between the first repeat and the upstream open reading frame. Cloning of this sequence in an episome vector enhanced the expression of a tagged snoRNA gene in an orientation-dependent manner. However, continuous transcript spanning of this region was detected in steady-state RNA, suggesting that snoRNA transcription also originates from an upstream-long polycistronic transcriptional unit. The 700-bp fragment may therefore represent an example of many more elements to be discovered that enhance transcription along the chromosome, especially when transcription from the upstream gene is reduced or when enhanced transcription is needed.

Amino Acid Sequence↗
PubMed1998

Gar1p binds to the small nucleolar RNAs snR10 and snR30 in vitro through a nontypical RNA binding element.

The nucleolar proteins Gar1p and fibrillarin possess a typical nucleolar glycine/arginine-rich domain and belong to ribonucleoprotein particles. Both proteins are essential for yeast cell growth and are required for pre-rRNA processing. In addition, Gar1p is involved in pre-rRNA pseudouridylation, whereas fibrillarin is required for pre-rRNA methylation. Gar1p and fibrillarin are each associated with a different subset of the small nucleolar RNAs (snoRNAs). Gar1p is co-immunoprecipitated with the H/ACA family of snoRNAs, whereas fibrillarin is co-immunoprecipitated with the C/D family. However, attempts to demonstrate direct interactions between fibrillarin and snoRNAs have failed, and such interactions between Gar1p and the H/ACA snoRNAs had not yet been reported. Among the H/ACA snoRNAs associated with Gar1p, one can distinguish a large group of snoRNAs that are not essential in yeast and serve as guides for pseudouridine synthesis onto the pre-rRNA molecule. In contrast, the two snoRNAs snR10 and snR30 are required for normal cell growth and for pre-rRNA cleavage. We show here that Gar1p interacts in vitro directly and specifically with these two snoRNAs. Deletion analysis of Gar1p indicates that a major RNA binding element, which is extremely well conserved throughout evolution, lies in the middle of the protein. However, this domain alone binds poorly to the target RNAs and an accessory domain is required to restore efficient binding. The accessory domain can be either one of the glycine/arginine-rich domains or a second element of the core of the protein that is highly conserved between different species.

Amino Acid Sequence↗
PubMed1998

The RNA polymerase II general elongation complex.

Eukaryotic messenger RNA (mRNA) synthesis is a complex multi-stage process that requires the concerted action of many cellular factors to generate a mature functional message. This elaborate process by RNA polymerase II (pol II) proceeds via multiple stages-preinitiation, initiation (Figure 1), promoter clearance, elongation (Figure 1) and termination - which have come to be referred to collectively as the transcription cycle. Although the preinitiation and initiation stages of transcription have received the most attention during the past decade, the past few years have been a watershed for biochemical studies of the pol II elongation complex. Recent studies have demonstrated the existence of several families of pol II elongation factors and nuclear proteins that can govern the activity of pol II during mRNA chain elongation. New findings have revealed that the elongation stage of transcription is a critical site for the regulation of gene expression. Evidence obtained to date suggests that eukaryotes regulate elongation by both 'general' and 'activator dependent' mechanisms. These mechanisms necessitate alteration of pol II's catalytic site, modification of chromatin structure, phosphorylation of the pol II carboxyl-terminal domain (CTD) and involvement of other components of the transcription machinery to increase the rate and efficiency of transcription elongation. This minireview is an annotation on the recent progress in studies of the biochemical mechanism and molecular regulation of the elongation stages of eukaryotic mRNA synthesis. The recent developments that have guided our understanding and propelled current research on transcription elongation by mammalian pol II will be described here.

Eukaryotic Cells↗
PubMed2001

Identification of 10 novel snoRNA gene clusters from Arabidopsis thaliana.

Ten novel small nucleolar RNA (snoRNA) gene clusters, consisting of two or three snoRNA genes, respectively, were identified from Arabidopsis thaliana. Twelve of the 25 snoRNA genes in these clusters are homologous to those of yeast and mammals according to the conserved antisense sequences that guide 2'-O-ribose methylation of rRNA. The remaining 13 snoRNA genes, including two 5.8S rRNA methylation guides, are new genes identified from A.thaliana. Interestingly, seven methylated nucleotides, predicted by novel snoRNAs Z41a-Z46, are methylated neither in yeast nor in vertebrates. Using primer extension at low dNTP concentration the six methylation sites were determined as expected. These snoRNAs were recognized as specific guides for 2'-O:-ribose methylation of plant rRNAs. Z42, however, did not guide the expected methylation of 25S rRNA in our assay. Thus, its function remains to be elucidated. The intergenic spacers of the gene clusters are rich in uridine (up to 40%) and most of them range in size from 35 to 100 nt. Lack of a conserved promoter element in each spacer and the determination of polycistronic transcription from a cluster by RT-PCR assay suggest that the snoRNAs encoded in the clusters are transcribed as a polycistron under an upstream promoter, and individual snoRNAs are released after processing of the precursor. Numerous snoRNA gene clusters identified from A.thaliana and other organisms suggest that the snoRNA gene cluster is an ancient gene organization existing abundantly in plants.

Arabidopsis↗
PubMed2006

Cost-effectiveness of HIV treatment in resource-poor settings--the case of Côte d'Ivoire.

BACKGROUND: As antiretroviral therapy is increasingly used in settings with limited resources, key questions about the timing of treatment and use of diagnostic tests to guide clinical decisions must be addressed. METHODS: We assessed the cost-effectiveness of treatment strategies for a cohort of adults in Côte d'Ivoire who were infected with the human immunodeficiency virus (HIV) (mean age, 33 years; CD4 cell count, 331 per cubic millimeter; HIV RNA level, 5.3 log copies per milliliter). Using a computer-based simulation model that incorporates the CD4 cell count and HIV RNA level as predictors of disease progression, we compared the long-term clinical and economic outcomes associated with no treatment, trimethoprim-sulfamethoxazole prophylaxis alone, antiretroviral therapy alone, and prophylaxis with antiretroviral therapy. RESULTS: Undiscounted gains in life expectancy ranged from 10.7 months with antiretroviral therapy and prophylaxis initiated on the basis of clinical criteria to 45.9 months with antiretroviral therapy and prophylaxis initiated on the basis of CD4 testing and clinical criteria, as compared with trimethoprim-sulfamethoxazole prophylaxis alone. The incremental cost per year of life gained was 240 dollars (in 2002 U.S. dollars) for prophylaxis alone, 620 dollars for antiretroviral therapy and prophylaxis without CD4 testing, and 1,180 dollars for antiretroviral therapy and prophylaxis with CD4 testing, each compared with the next least expensive strategy. None of the strategies that used antiretroviral therapy alone were as cost-effective as those that also used trimethoprim-sulfamethoxazole prophylaxis. Life expectancy was increased by 30% with use of a second line of antiretroviral therapy after failure of the first-line regimen. CONCLUSIONS: A strategy of trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy, with the use of clinical criteria alone or in combination with CD4 testing to guide the timing of treatment, is an economically attractive health investment in settings with limited resources.

Adult↗
PubMed2001

Structure-function analysis of the active site tunnel of yeast RNA triphosphatase.

Cet1, the RNA triphosphatase component of the yeast mRNA capping apparatus, catalyzes metal-dependent gamma phosphate hydrolysis within the hydrophilic interior of a topologically closed 8-strand beta barrel (the "triphosphate tunnel"). We used structure-guided alanine scanning to identify 6 side chains within the triphosphate tunnel that are essential for phosphohydrolase activity in vitro and in vivo: Arg393, Glu433, Arg458, Arg469, Asp471 and Thr473. Alanine substitutions at two positions, Asp377 and Lys409, resulted in partial catalytic defects and a thermosensitive growth phenotype. Structure-function relationships were clarified by introducing conservative substitutions. Five residues were found to be nonessential: Lys309, Ser395, Asp397, Lys427 Asn431, and Lys474. The present findings, together with earlier mutational analyses, reveal an unusually complex active site in which 15 individual side chains in the tunnel cavity are important for catalysis, and each of the 8 strands of the beta barrel contributes at least one functional constituent. The active site residues fall into three classes: (i) those that participate directly in catalysis via coordination of the gamma phosphate or the metal; (ii) those that make critical water-mediated contacts with the gamma phosphate or the metal; and (iii) those that function indirectly via interactions with other essential side chains or by stabilization of the tunnel structure.

Acid Anhydride Hydrolases↗
PubMed2004

Hepatitis C virus (HCV) relapses after anti-HCV therapy are more frequent in HIV-infected patients.

The response to standard or pegylated interferon (IFN) plus ribavirin (RBV) seems to be lower in hepatitis C virus (HCV)/HIV-coinfected subjects than in HCV-monoinfected patients. Thus, the principles guiding anti-HCV therapy in HIV-negative patients may not apply in the setting of HIV infection. We examined the rate of HCV relapse in 58 HCV/HIV-coinfected subjects who showed undetectable HCV-RNA (<600 IU/ml) at the end of anti-HCV combination therapy. Overall, 19 (32.8%) patients relapsed after discontinuing treatment, a rate significantly higher than that seen in HIV negatives, which is in the range of 15-20%. There were no significant differences between HCV genotypes (33.3% for HCV genotypes 2-3 versus 31.8% for HCV genotypes 1-4) and/or the use of either standard or pegylated IFN (37% versus 29%, respectively). Thus, extended periods of anti-HCV therapy might reduce HCV relapses in HIV-coinfected patients initially responding to therapy.

Adult↗
PubMed1995

Use of rRNA secondary structure in phylogenetic studies to identify homologous positions: an example of alignment and data presentation from the frogs.

The alignment of ribosomal RNA (rRNA) by computer requires assumptions about the evolutionary costs for gaps in the alignment that are undefinable when uniformly applied across the entire molecule. The conservation of rRNA secondary structures exceeds that of its nucleotides, and therefore it is recommended that secondary structures guide decisions about the assignment of homologous positions for phylogenetic studies. Suggestions for alignment, data presentation, and character description are made in the context of an example from frog large subunit nuclear rRNA. Realignment improved congruence with previously published morphological conclusions and the format used in data presentation facilitated the description of character-based conclusions at each node in the cladogram. The data presented allow a discrimination between the fully resolved shortest tree and conclusions that the data actually support with any reasonable confidence: a monophyletic Pipanura, Neobatrachia, and Ranoidea without further resolution within the Neobatrachia.

Animals↗
PubMed2005

Messenger RNA electroporation: an efficient tool in immunotherapy and stem cell research.

Over the last decades medicine has developed tremendously, but still many diseases are incurable. The last years, cellular (gene) therapy has become a hot topic in biomedical research for the potential treatment of cancer, AIDS and diseases involving cell loss or degeneration. Here, we will focus on two major areas within cellular therapy, cellular immunotherapy and stem cell therapy, that could benefit from the introduction of neo-expressed genes through mRNA electroporation for basic research as well as for clinical applications. For cellular immunotherapy, we will provide a state-of-the-art on loading antigen-presenting cells with antigens in the mRNA format for manipulation of T cell immunity. In the area of stem cell research, we will highlight current gene transfer methods into adult and embryonic stem cells and discuss the use of mRNA electroporation for controlling guided differentiation of stem cells into specialized cell lineages.

Animals↗
PubMedDate not supplied

Ribosomal tolerance and peptide bond formation.

In the ribosome, the decoding and peptide bond formation sites are composed entirely of ribosomal RNA, thus confirming that the ribosome is a ribozyme. Precise alignment of the aminoacylated and peptidyl tRNA 3'-ends, which is the major enzymatic contribution of the ribosome, is dominated by remote interactions of the tRNA double helical acceptor stem with the distant rims of the peptidyl transferase center. An elaborate architecture and a sizable symmetry-related region within the otherwise asymmetric ribosome guide the A --> P passage of the tRNA 3'-end by a spiral rotatory motion, and ensures its outcome: stereochemistry suitable for peptide bond formation and geometry facilitating the entrance of newly formed proteins into their exit tunnel.

Archaea↗
PubMed2003

The effect of number of mutations and of drug-class sparing on virological response to salvage genotype-guided antiretroviral therapy.

OBJECTIVE: To assess on longitudinal data the impact of number of drug-associated mutations at genotype resistance testing (GRT) and history of previous exposure to antiretrovirals on the virological response to genotype-guided antiretroviral therapy. METHODS: Subjects that failed HAART who underwent GRT between June 1999 and March 2002 were enrolled. GRT was performed by Viroseq-2 with expert advice offered to physicians. Main outcome was reaching undetectable (< 80 copies/ml) HIV-1 RNA level after GRT and maintaining undetectable viraemia for at least 6 months. The number of mutations conferring resistance to each class of antiretrovirals was categorized and their effect on virological outcome investigated. Mutations considered in the analysis were those reported by the IAS-USA in 2002. Multivariate analysis was performed by Cox proportional hazard model. RESULTS: Four-hundred-and-seventy consecutive subjects were enrolled and followed-up for a median of 14 (IQR 9-19) months after GRT. Sustained undetectable viraemia was reached by 80 of 449 subjects (18%). Using as end-point reaching and maintaining for at least 6 months < 400 copies/ml after GRT, 103 out of 447 subjects (23%) reached the outcome. For each single protease inhibitor (PI)-, nucleoside reverse transcriptase inhibitor (NRTI)-and non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated mutation, there was a reduction of, respectively, 11% (P = 0.008), 12% (P = 0.001) and 39% (P = 0.005) in the likelihood of reaching virological outcome. Subjects carrying > or = 6 mutations to NRTIs, > or = 7 mutations to PIs and > or = 2 mutations to NNRTIs were less likely to reach the virological success compared with those carrying 0-1 (NRTI and PI) or 0 (NNRTI) mutations [HR = 0.25 (95% CI: 0.10-0.65); HR = 0.33 (950% CI: 0.16-0.67); HR = 0.33 (95% CI: 0.14-0.77)], respectively. However, at multivariate analysis the probability of reaching a favourable virological outcome in patients with > or = 7 mutations to PIs, if naive for NNRTIs [HR = 1.74 (0.69-4.36)], and in subjects with > or = 2 mutations for NNRTIs if naive for PIs [HR = 1.23 (0.22-6.80)], was comparable to those observed in patients with none or one mutation. CONCLUSIONS: Our data showed a non-linear association between resistance-conferring mutations and virological outcome. GRT-guided therapy still provided remarkable chances of durable virological success even in subjects with > or = 7 mutations to PIs and in subjects with > or = 2 mutations to NNRTIs, when the subjects did not have a three-class exposure or if GRT showed no evidence of mutations for a drug class. GRT and as-long-as-possible sparing of a drug class could be a convenient strategy for long-term management of drug-failing patients.

Anti-HIV Agents↗
PubMed2005

Accurate molecular detection of non-small cell lung cancer metastases in mediastinal lymph nodes sampled by endoscopic ultrasound-guided needle aspiration.

OBJECTIVES: The recurrence of disease after the complete resection of early stage non-small cell lung cancer (NSCLC) indicates that undetected metastases were present at the time of surgery. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is a highly sensitive technique for detecting rare gene transcripts that may indicate the presence of cancer cells, and endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a minimally invasive technique for the nonoperative sampling of mediastinal lymph nodes. The aim of this study was to determine whether these two techniques could enhance the preoperative detection of occult metastases. METHODS: Patients with NSCLC were evaluated with chest CT and positron emission tomography scans. Those patients without evidence of metastases (87 patients) underwent EUS-guided FNA. Lymph nodes from levels 2, 4, 5, 7, 8, and 9 were sampled and evaluated by standard cytopathology and real-time RT-PCR. Normal control FNA specimens were obtained from patients without cancer who were undergoing EUS for benign disease (17 control specimens). For each sample, messenger RNA was extracted and real-time RT-PCR was used to quantitate the expression of six lung cancer-associated genes (ie, CEA, CK19, KS1/4, lunx, muc1, and PDEF) relative to the expression of an internal control gene (beta(2)-microglobulin). RESULTS: Clinical thresholds of marker positivity were set at 100% specificity, as determined by the receiver operating characteristic curve analysis. Of the cytology-positive lymph nodes (27 lymph nodes), the expression of the KS1/4 gene was above its respective clinical threshold in 25 of 27 samples (93%), making this the most sensitive marker for the detection of metastatic NSCLC. At least one of the six lung cancer-associated genes was overexpressed in 18 of 61 cytology-negative patients (30%), of which KS1/4 was overexpressed in 15 of 61 patients (25%). CONCLUSIONS: Based on the high accuracy of EUS-guided FNA/RT-PCR, we predict that some of the patients in the cytology-negative/marker-positive category will have high NSCLC recurrence rates. Among the genes used in our marker panel, KS1/4 appears particularly useful for the detection of overt or occult metastatic disease.

Biomarkers, Tumor↗
PubMed2000

Evolution of RNA editing in trypanosome mitochondria.

Two different RNA editing systems have been described in the kinetoplast-mitochondrion of trypanosomatid protists. The first involves the precise insertion and deletion of U residues mostly within the coding regions of maxicircle-encoded mRNAs to produce open reading frames. This editing is mediated by short overlapping complementary guide RNAs encoded in both the maxicircle and the minicircle molecules and involves a series of enzymatic cleavage-ligation steps. The second editing system is a C(34) to U(34) modification in the anticodon of the imported tRNA(Trp), thereby permitting the decoding of the UGA stop codon as tryptophan. U-insertion editing probably originated in an ancestor of the kinetoplastid lineage and appears to have evolved in some cases by the replacement of the original pan-edited cryptogene with a partially edited cDNA. The driving force for the evolutionary fixation of these retroposition events was postulated to be the stochastic loss of entire minicircle sequence classes and their encoded guide RNAs upon segregation of the single kinetoplast DNA network into daughter cells at cell division. A large plasticity in the relative abundance of minicircle sequence classes has been observed during cell culture in the laboratory. Computer simulations provide theoretical evidence for this plasticity if a random distribution and segregation model of minicircles is assumed. The possible evolutionary relationship of the C to U and U-insertion editing systems is discussed.

Animals↗
PubMed1998

Spatial learning and physical activity contribute to the induction of fibroblast growth factor: neural substrates for increased cognition associated with exercise.

New evidence indicates that neural activity regulates the expression of trophic factors in the brain but regulation of these molecules by select aspects of behaviour remains solely a fascinating possibility. We report that following training in the Morris water maze, a spatial memory task, the hippocampus and cerebellum of learning rats exhibited an increase in basic fibroblast growth factor messenger RNA. Basic fibroblast growth factor messenger RNA levels were higher during the learning of the task and decreased once asymptotic performance was reached, suggesting an involvement of basic fibroblast growth factor in learning/memory. An active control group, which exercised for the same time as the learning group but the spatial learning component of the task was minimized, exhibited a minor increase in basic fibroblast growth factor messenger RNA. The intensification of the physical activity component of the task by massed or intensive training resulted in greater increases in basic fibroblast growth factor messenger RNA for both learning and yoked groups, but levels of basic fibroblast growth factor messenger RNA in the learning group remained higher than yoked only in the cerebellum. Changes in basic fibroblast growth factor were accompanied by an increase in astrocyte density in the hippocampus in agreement with described roles of basic fibroblast growth factor in astrocyte proliferation/reactivity. Results suggest that learning potentiates the effects of physical activity on trophic factor induction in select brain regions. Trophic factor involvement in behaviour may provide a molecular basis for the enhanced cognitive function associated with active lifestyles, and guide development of strategies to improve rehabilitation and successful ageing.

Animals↗
PubMed2006

Three-year clinical outcomes of resistance genotyping and expert advice: extended follow-up of the Argenta trial.

OBJECTIVE: To investigate the influence of genotypic resistance-guided HIV-treatment decisions on long-term clinical and virological outcomes in patients failing antiretroviral therapy by a prospective 30-month observation following a 6-month randomized study (Argenta trial). METHODS: Patients (n=174) with virological failure on highly active antiretroviral therapy (HAART) were initially randomized (1:1) to receive empirical therapy or guidance by genotypic resistance results. After month 6, all patients with HIV RNA >1,000 copies/ml received genotypic resistance tests and expert advice. Predictors of virological and clinical outcomes were analysed by logistic regression and Cox's regression models. RESULTS: There was a gradual increase in the proportion of patients with HIV RNA <400 copies/ml with 29.3% at 36 months (intent-to-treat) without differences between initial randomization arms. Independent predictors of 36-month virological response were the use of a salvage therapy with less daily doses and a more pronounced 3-month viral load drop. At 36 months, 84% survived without new AIDS events/death. Independent predictors of new AIDS events/death were previous AIDS events, higher baseline viral load, less pronounced 3-month viral load drop and, in a separate model, baseline protease substitutions K20M/R and 184V. CONCLUSIONS: The virological benefit of genotype-guided treatment decisions was continuously appreciable over time. Short-term virological response and viral cross-resistance were independent predictors of long-term outcomes.

Adolescent↗
PubMed2002

Usefulness of monitoring HIV drug resistance and adherence in individuals failing highly active antiretroviral therapy: a randomized study (ARGENTA).

OBJECTIVE: To establish the influence of genotypic resistance-guided treatment decisions and patient-reported adherence on the virological and immunological responses in patients failing a potent antiretroviral regimen in a randomized, controlled trial in a tertiary care infectious diseases department. PATIENTS: A total of 174 patients with virological failure were randomly assigned to receive standard of care (SOC) or additional genotypic resistance information (G). Adherence was measured by a self-administered questionnaire. MAIN OUTCOMES MEASURES: Primary endpoints were the proportion with HIV-RNA < 500 copies/ml at 3 and 6 months by intention-to-treat analysis. Secondary endpoints were changes from baseline HIV-RNA levels and CD4 cell counts. RESULTS: At entry, 25% had failed three or more highly active antiretroviral therapy (HAART) regimens and 41% three drug classes; there were more resistance mutations in G. In 127 evaluable questionnaires, 43% reported last missed dose during the previous week. At 3 months, 11 of 89 patients (12%) in SOC and 23 of 85 (27%) in G had HIV-RNA < 500 copies/ml (OR 2.63, 95% CI 1.12-6.26); the relative proportions were 17 and 21% at 6 months. CD4 cell changes did not differ between arms. Six month CD4 cell changes were +62 in adherent and -13 cells/microl in non-adherent patients (P < 0.01). Being assigned to G, good adherence, previous history of virological success, fewer experienced HAART regimens and lower baseline viral load were independently predictive of 3 month virological success. CONCLUSION: The virological benefit of genotype-guided treatment decisions in heavily pre-exposed patients was short term. Patients adherence and residual treatment options influenced outcomes.

Antiretroviral Therapy, Highly Active↗
PubMed2003

Prognostic significance of reverse transcriptase-polymerase chain reaction-negative sentinel nodes in malignant melanoma.

BACKGROUND: Polymerase chain reaction (PCR) is a molecular biology technique that can detect a single metastatic cell in 10(6) to 10(7) normal cells. Its use has been proposed as an additional new method for the detection of malignant melanoma nodal metastases in the sentinel lymph node (SLN) to improve the detection rate guaranteed so far by standard histology (hematoxylin and eosin; H&E) and immunohistochemistry (IHC). METHODS: Since October 1995, 137 patients with primary cutaneous melanoma (Breslow thickness,.75-4 mm) have undergone surgery for selective lymphadenectomy. To identify the SLNs, every patient had preoperative lymphoscintigraphy and a vital dye perilesional injection, followed by a gamma probe-guided operation. RESULTS: In 134 patients at least one SLN was detected, with a detection rate of 98%. Every SLN was examined by H&E and IHC (S-100 antigen and HMB-45 protein). The messenger RNA codifying for tyrosinase and MART-1 (melanoma antigen recognized by T cells) was used as the target sequence for the reverse transcriptase (RT)-PCR. The results showed 11% positive SLNs with IHC and H&E examination and 63% with RT-PCR. No recurrence was noted at follow-up in the group with RT-PCR-negative nodes (absence of false-negative cases). CONCLUSIONS: In our experience, RT-PCR SLN negativity is achieving a very favorable prognostic significance. However, RT-PCR positivity is still to be evaluated. Furthermore, results obtained with this method have been shown so far to be independent of Breslow's tumor thickness.

Antigens, Neoplasm↗
PubMed2001

[Resistance to antiretroviral drugs].

Since the HIV eradication is an utopian goal the only hope we have is the appropriate follow up of the disease by maintaining the RNA viral load under control and the level of CD4+ sufficient for a minimum of immunocompetence guarantee. The international guideline for the management of HIV infected patients, annually updated, recently confirmed the importance of the GART (guided antiretroviral therapy) based on information derived from drug resistance laboratory tests. A general survey on the antiretroviral drugs, on the mutations involving drug resistance and on the tests for their detection could be interesting also for whom not specifically working on the field.

Antiviral Agents↗