Delayed hypersensitivity and Ig level in 210 patients with chronic myeloid leukemia

Summary Serum immunoglobulin concentration and skin reactivity to at least three recall antigens were determined in 210 patients with chronic myeloid leukemia (CML). Immunoglobulin concentration was normal in the great majority of the patients. Skin tests were negative in 50 of 210 cases (24%). No relationship could be demonstrated between skin reactivity, age, time since diagnosis, WBC, lymphocyte count, and splenectomy. Prior antileukemic therapy was a major factor in determining the response to skin tests.S. Tura (Chairman) and M. Baccarani (Secretary), Cattedra di Ematologia dell'Università e Servizio di Ematologia dell'Ospedale S. Orsola, Bologna; G. de Sandre, G. Perona, G. Cetto, G. Pizzolo, Istituto di Patologia Medica e Cattedra di Ematologia dell'Università, Verona; P. Rambotti, B. Falini, Clinica Medica dell'Università, Perugia; T. Chisesi, G. Capnist, Divisione di Ematologia, Ospedale Civile, Vicenza; A. Cajozzo, P. Citarella, Cattedra di Ematologia dell'Università, Palermo; G. Broccia, Sezione di Ematologia, Ospedale Armando Businco, Cagliari; V. Liso, G. Troccoli, Clinica Medica II dell'Università, Bari; L. Bruzzese, G. Nappi, A. Abbadessa, Clinica Medica (I Facoltà) dell'Università, Napoli; A. Porcellini, C. Delfini, Divisione di Ematologia, Ospedali Riuniti, Pesaro; E. Cacciola, R. Giustolisi, R. Musso, V. Raimondi, Cattedra di Ematologia dell'Università, Catania; G. Torlontano, L. Geraci, Cattedra di Ematologia dell'Università, Chieti, e Divisione di Ematologia, Ospedale Civile, Pescara; F. Mandelli, G. Mariani, B. Monarca, N. Petti, Cattedra di Ematologia dell'Università, Roma; R. di Guglielmo, A. Miliani, Clinica Medica dell'Università, Firenze; C. Bernasconi, M. Lazzarino, G. Castelli, Divisione di Ematologia, Ospedale S. Matteo, Pavia; A. Alberti, S. Magro, Servizio di Ematologia, Ospedale Generale Regionale, Catanzaro; A. Neri, P. Iacopino, Divisione di Ematologia, Ospedali Riuniti, Reggio Calabria; R. Delsignore, M. C. Baroni, Istituto di Patologia Medica dell'Universita, Parma; E. Bajetta, S. Monfardini, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano; S. Tognella, Istituto Scientifico di Medicina Interna, Cattedra di Clinica Medica 2R, Università, Genova.     

Focal DNA Copy Number Changes in Neuroblastoma Target MYCN Regulated Genes

Neuroblastoma is an embryonic tumor arising from immature sympathetic nervous system cells. Recurrent genomic alterations include MYCN and ALK amplification as well as recurrent patterns of gains and losses of whole or large partial chromosome segments. A recent whole genome sequencing effort yielded no frequently recurring mutations in genes other than those affecting ALK. However, the study further stresses the importance of DNA copy number alterations in this disease, in particular for genes implicated in neuritogenesis. Here we provide additional evidence for the importance of focal DNA copy number gains and losses, which are predominantly observed in MYCN amplified tumors. A focal 5 kb gain encompassing the MYCN regulated miR-17∼92 cluster as sole gene was detected in a neuroblastoma cell line and further analyses of the array CGH data set demonstrated enrichment for other MYCN target genes in focal gains and amplifications. Next we applied an integrated genomics analysis to prioritize MYCN down regulated genes mediated by MYCN driven miRNAs within regions of focal heterozygous or homozygous deletion. We identified RGS5, a negative regulator of G-protein signaling implicated in vascular normalization, invasion and metastasis, targeted by a focal homozygous deletion, as a new MYCN target gene, down regulated through MYCN activated miRNAs. In addition, we expand the miR-17∼92 regulatory network controlling TGFß signaling in neuroblastoma with the ring finger protein 11 encoding gene RNF11, which was previously shown to be targeted by the miR-17∼92 member miR-19b. Taken together, our data indicate that focal DNA copy number imbalances in neuroblastoma (1) target genes that are implicated in MYCN signaling, possibly selected to reinforce MYCN oncogene addiction and (2) serve as a resource for identifying new molecular targets for treatment.     

Total HIV/AIDS Expenditures in Dehong Prefecture,Yunnan Province in 2010: The First Systematic Evaluation of Both Health and Non-Health Related HIV/AIDS Expenditures in China

Objective

We assessed HIV/AIDS expenditures in Dehong Prefecture, Yunnan Province, one of the highest prevalence regions in China, and describe funding sources and spending for different categories of HIV-related interventions and at-risk populations.

Methods

2010 HIV/AIDS expenditures in Dehong Prefecture were evaluated based on UNAIDS’ National AIDS Spending Assessment methodology.

Results

Nearly 93% of total expenditures for HIV/AIDS was contributed by public sources. Of total expenditures, 52.7% was allocated to treatment and care, 24.5% to program management and administration and 19.8% to prevention. Spending on treatment and care was primarily allocated to the treatment of opportunistic infections. Most (40.4%) prevention spending was concentrated on most-at-risk populations, injection drug users (IDUs), sex workers, and men who have sex with men (MSM), with 5.5% allocated to voluntary counseling and testing. Prevention funding allocated for MSM, partners of people living with HIV and prisoners and other confined populations was low compared to the disproportionate burden of HIV/AIDS in these populations. Overall, people living with HIV accounted for 57.57% of total expenditures, while most-at-risk populations accounted for only 7.99%.

Conclusions

Our study demonstrated the applicability of NASA for tracking and assessing HIV expenditure in the context of China, it proved to be a useful tool in understanding national HIV/AIDS response from financial aspect, and to assess the extent to which HIV expenditure matches epidemic patterns. Limited funding for primary prevention and prevention for MSM, prisoners and partners of people living with HIV, signal that resource allocation to these key areas must be strengthened. Comprehensive analyses of regional and national funding strategies are needed to inform more equitable, effective and cost-effective HIV/AIDS resource allocation.     

Curcumin and cyclopalladated complexes: a recipe for bifunctional biomaterials

The first examples of binuclear and mononuclear ortho-palladated complexes based on a functionalized 2-phenylquinoline ligand have been synthesized and fully characterized. Conjugating cyclopalladated fragments to curcumin family biologically active beta-diketones gives in one single molecule two different functionalities. The structural variations based on the curcuminoid structure have been tested for their in vitro cytotoxic activity. The activity of complexes comprised of a cyclopalladated fragment conjugated to functionalized bioactive ligands, represents the potential of organometallic systems in generating new bifunctional biomaterials.     

Association of body iron stores with low molecular weight iron and oxidant damage of human atherosclerotic plaques

The association between iron, an oxidant catalyst, and atherosclerosis is controversial. In particular, it is unknown whether: (1) stored iron, namely serum ferritin, is correlated with catalytic iron and oxidant damage of human atherosclerotic plaques; (2) catalytic iron is related to oxidative injury within such plaques; (3) plaque oxidant burden is associated with the severity of atherosclerosis. Thus, we assessed low molecular weight iron (LMWI), which represents the metal catalytically active form, together with fluorescent damage products of lipid peroxidation (FDPL) and lipid hydroperoxides (LOOH), in 38 atherosclerotic plaques surgically removed from 38 patients who had undergone selective carotid endarterectomy. In each patient, the levels of serum ferritin were measured and correlated with those of plaque LMWI and lipoperoxides by the Spearman rank correlation test with Spearman rank correlation coefficient (r(S)) calculation. Moreover, in patients selected from the same study population, we compared plaque analyte levels between two groups with different severity of atherosclerotic carotid stenosis, i.e., <90% (group A, n = 25) or > or =90% (group B, n = 13), and between another two groups without (group C, n = 27) and with (group D, n = 11) associated contralateral carotid stenosis > or =50%, indicative of "extensive" and more severe atherosclerotic disease. In group A patients, serum ferritin was directly and significantly correlated with plaque LMWI (r(S) = 0.46, P < 0.025) and FDPL (r(S) = 0.58, P < 0.005), while its correlation with plaque LOOH, albeit direct, did not attain statistical significance. Moreover, a direct and significant relationship was evident between the plaque content of LMWI and that of both FDPL (r(S) = 0.61, P < 0.0025) and LOOH (r(S) = 0.51, P < 0.025), suggesting a prooxidant role of catalytic iron within human atherosclerotic plaques. Considering the 13 patients of group B, a positive and significant correlation was observed between the levels of serum ferritin and those of plaque LMWI (r(S) = 0.83, P < 0.0001); on the other hand, serum ferritin, as well as plaque LMWI, showed no significant correlation with either plaque FDPL or LOOH, conceivably reflecting the small number of patients belonging to group B. Finally, plaque LMWI, FDPL, and LOOH content was significantly higher in group B than in group A, and in group D than in group C. These data suggest a role for catalytic iron in atherosclerotic plaque oxidation and in the severity of atherosclerosis, which appears indeed associated with plaque oxidant burden.     

Administration of PLP139-151 primes T cells distinct from those spontaneously responsive in vitro to this antigen

We examined the TCR repertoire used by naive SJL mice in their in vitro spontaneous response to proteolipid protein (PLP) 139-151 by Vbeta-Jbeta spectratyping and compared it to that used after immunization with the peptide. T cells from immunized mice use the public rearrangement Vbeta10-Jbeta1.1, but naive mice do not; in contrast, TCR CDR3-beta rearrangements of Vbeta18-Jbeta1.2 and Vbeta19-Jbeta1.2 consistently are associated with the spontaneous response. T cells involved in spontaneous and induced responses can each recognize PLP(139-151) presented in vivo, but its s.c. administration has different consequences for the two repertoires. Four days after immunization, T cells associated with spontaneous responsiveness appear in the draining lymph nodes but disappear by day 10 and never appear elsewhere. Simultaneously, Vbeta10-Jbeta1.1 T cells are likewise activated in the lymph nodes by day 4 and spread to the spleen by day 10. Eight- to 10-wk-old naive mice use a narrower repertoire of TCRs than do immunized age-matched mice. Induced Vbeta10-Jbeta1.1 T cells home to the CNS during experimental autoimmune encephalomyelitis, whereas we failed to detect Vbeta18-Jbeta1.2 and Vbeta19-Jbeta1.2 TCR rearrangements in the CNS. Thus, we observe that administration of PLP(139-151) primes a T cell repertoire distinct from the one responsible for spontaneous responsiveness. This "immunized" repertoire substitutes for the naive one and becomes dominant at the time of disease onset.     

Collagen-specific T-cell repertoire in blood and synovial fluid varies with disease activity in early rheumatoid arthritis

Introduction  

Type II collagen is a DR4/DR1 restricted target of self-reactive T cells that sustain rheumatoid arthritis. The aim of the present study was to analyze the T-cell receptor repertoire at the onset of and at different phases in rheumatoid arthritis.     

Closing gaps in the human genome using sequencing by synthesis

The most recent release of the finished human genome contains 260 euchromatic gaps (excluding chromosome Y). Recent work has helped explain a large number of these unresolved regions as 'structural' in nature. Another class of gaps is likely to be refractory to clone-based approaches, and cannot be approached in ways previously described. We present an approach for closing these gaps using 454 sequencing. As a proof of principle, we closed all three remaining non-structural gaps in chromosome 15.