1,721,145 research outputs found
Hairy cell leukaemia: biological and clinical overview from immunogenetic insights
No full textHairy cell leukaemia (HCL) is a rare neoplasm of peripheral B cells which represents a paradox in oncology. Despite its largely unknown origin and behaviour, HCL is one of the few example of dramatic success in the treatment of a malignancy. The recent steps forward to understanding the biology of HCL from immunogenetic and genomic studies have recently provided new insight into diagnosis and prognosis. Several data from immunoglobulin gene (IG) analysis have provided hints regarding the cell of origin and the ongoing selective interactions of the tumour BCR with environmental stimuli. It has also recently emerged that an unmutated status of the HCL IG can be associated with failure to respond to cladribine, genetic abnormalities indicative of poor outcome and aggressive disease. These observations suggest a central role of the tumour B-cell receptor in defining the outcome of HCL and that that IG gene analysis may have biological and prognostic relevance. Hopefully, IG analysis will help tailor treatment strategies for the most aggressive cases
Guideline for diagnosis and management of hairy cell leukaemia (HCL) and hairy cell variant (HCL-V)
No full textTowards the pharmacotherapy of hairy cell leukaemia
No full textHairy cell leukaemia (HCL) offers one of the few examples of rapid progress in the development of effective treatments for chronic lymphoproliferative disorders. After the first description of HCL as a separate disease in 1958, splenectomy was the treatment of choice, but rarely resulted in remission of disease and had scarce benefit on survival. In 1984, IFN-alpha became the first agent able to significantly modify the prognosis of HCL by inducing high response rates and long-term remissions. More recently, purine analogues have significantly further increased the percentages of remissions, with a reduced risk of relapse and are now generally used as first-line treatment. Monoclonal antibodies targeting CD20, CD22 and CD25 antigens, have also shown responses for resistant or relapsing disease. This article will review the current treatment strategies for HCL
The essential microenvironmental role of oligomannoses inserted into the antigen-binding sites of lymphoma cells
No full textThere are two mandatory features added sequentially en route to classical follicular lymphoma (FL): first the t(14;18) translocation which upregulates BCL2; second the introduction of sequence motifs into the antigen-binding sites of the B-cell receptor (BCR), where oligomannose-type glycan is added. Further processing of the glycan is blocked by complementarity-determining-region (CDR)-specific steric hindrance, leading to exposure of mannosylated Ig to the microenvironment. This allows interaction with the local lectin, DC-SIGN, expressed by tissue macrophages and follicular dendritic cells. The major function of DC-SIGN is to engage pathogens, but this is subverted by FLcells. DC-SIGN induces tumor-specific low-level BCR signaling in FL cells and promotes membrane changes with increased adhesion to VCAM-1 via proximal kinases and actin regulators , but, in contrast to engagement by anti-Ig, avoids endocytosis and apoptosis. These interactions appear mandatory for early development of FL prior to acquisition of other accelerating mutations. BCRassociated mannosylation can be found in a subset of germinal-center B-cell-like DLBCL (GCB-DLBCL) with t(14;18), tracking those cases back to FL. This category was associated with more aggressive behavior, and both FL and transformed cases, and potentially a significant number of cases ofBurkitt’s lymphoma which also have sites for N-glycan addition, could benefit from antibodymediated blockade of the interaction with DC-SIGN
Revisiting the definition of somatic mutational status in B-cell tumors: does 98% homology mean that a V(H)-gene is unmutated?
No full textIn B-cell tumors, accurate assessment of somatic mutational status has implications for defining tumor origin and, in some categories, has relevance for predicting the clinical outcome. In 1999, it was found that in chronic lymphocytic leukemia (CLL) cases carrying VH-genes with >98% homology to the closest germline (GL) gene identified a subset with a poorer prognosis, as compared to cases which had clearly undergone somatic mutation.1 Initially, the 98% cutoff was used to exclude potential polymorphic variant sequences. It was a short cut to avoid analyzing the corresponding GL gene in each patient, and is now used for assignment of mutational status in a range of B-cell tumors.
The most integrated V-base database (http://www.mrc-cpe.cam.ac.uk/v
base) describes 47 polymorphisms in 30/51 functional VH-gene segments, with nucleotide differences from GL generally of 2% variation. Aligned VH-genes readily map to the correct allele, and the 98% cutoff point seemed reasonable. However, low levels of mutations can occur in VH-genes and single-base changes (0.33–0.35% from germ line) may be important for improving the antigen recognition.2 It is possible therefore that significant changes could be occurring in cases with apparent >98% homology to GL. While it is unlikely to affect the prognostic power in CLL, it has implications for our understanding of the behavior of B-cell tumors.
One problem with assessing low levels of mutation is that of the approaching Taq error rate, and, although an increased rate may suggest somatic mutation, it can still be questioned. An indicator of the reality of base changes is identification of the same change in >1 sequence derived from separate amplification reactions. However, this parameter applies mainly to mutations occurring early in tumor development, and may not be evident from those accumulating late in the life of the clone. It has revealed genuine intraclonal heterogeneity in some cases of monoclonal gammopathy of undetermined significance, distinguishing it from the more malignant counterpart, multiple myeloma.3
For B-cell tumors with a low level (98% homology to GL sequence.4 Among these cases, only 1/5 had variants repeated in >1 clone. While lack of repeats prevents confirmation of the reality of the mutations, it might be expected if mutational events are relatively random and of low frequency. An intriguing single case of splenic marginal zone lymphoma with >99% homology also showed suggestive evidence for intraclonal heterogeneity.5
Recently, we have analyzed VH-genes in hairy cell leukemia (HCL). These tumors commonly express multiple isotypes and the majority have undergone somatic mutation in all isotype variants.6 The new finding that 2/13 HCL cases displayed germline tumor-derived VH-genes (Forconi F et al, submitted) prompted the question whether a further 3/13 cases with >98% homology were actually unmutated. Tumor VH transcripts were identified by established RT-PCR and cloning procedures described previously.6 Full sequence transcripts were analyzed and shared the same CDR3 in multiple clones. Cases 103 and 163 (Figure 1) revealed VH-genes with 98.6 and 98.2% homology to the closest germline allele, V4-31 and V1-02, respectively.6 Case 330 displayed 98.6% homology to the V2-05 gene
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
La malattia di Dupuytren: controllo a distanza ventennale di pazienti trattati con aponeurectomia parziale
No full textDopo una breve revisione della letteratura riguardante
le tecniche operatorie ed alcune casistiche
di altri autori, viene esposto il risultato del
controllo a lunga distanza (follow-up medio 20
anni) di pazienti trattati con aponeurectomia parziale.After a short historical review of surgical techiniques
and a review of some cases, a twenty
years follow-up after partial fasciectomy treatment
is exposed
- …
