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Systemic Lupus Erythematosus (SLE) as an autoimmune disorder, is characterized by a profound B cell activation, however, the association of this disease with a monoclonal gammopathy has been infrequently reported, while hypercalcemia is associated with Hypercalcemia-Lymphadenopathy Syndrome (HL-SLE). We report the case of a 45-year-old man, with anemia, hypoalbuminemia, hypergammaglobulinemia, hypercalcemia, and bone marrow infiltrated with plasma cells. He was diagnosed as Monoclonal Gammopathy of Undetermined Significance (MGUS), one year later he attended with erythematous macules on both arms, at this time the electrophoresis reported a polyclonal hypergammaglobulinemia. Immunologic panel reported ANA 1:2560, mitochondrial ANA 1:80, anti-double-stranded DNA IgG 15.3 and hipocomplementemia. We confirmed SLE and treatment was initiated. In our patient we ruled out MGUS, γHCD (γ-heavy-chain disease) and hypercalcemia related to HL-SLE. To our knowledge, the findings of monoclonal gammopathy and hypercalcemia as the onset of SLE have never been reported and the role of clinical laboratory was very important in the approach to establish a definitive diagnosis.

Exposure techniques rely on the assumption that the extinction of the classically conditioned response (i.e., fear) will result in the disruption of limiting forms of avoidance behavior, both directly trained and derived/indirectly established. This report presents translational research that attempts to test this assumption in laboratory conditions in two experiments with human volunteers. The procedure in both experiments included six phases: (1) conditional discrimination training for the formation of two 6-member equivalence classes; (2) classical conditioning of elicited responses to Class 1 (A1/B1) and Class 2 (A2/B2) members in the whitecontext, followed by conditioning of avoidance/approach responses to Class 1/Class 2 members, respectively, in the greencontext; (3) test for the transfer of avoidance/approach functions and of eliciting respondent functions to D1/F1 and D2/F2 in the greencontext; (4) extinction of classically conditioned responses to A1/B1 in the whitecontext; (5) test of the effects of respondent extinction on avoidance responding to the A, B, D, and F stimuli in the greencontext; and (6) test of derived symmetry and equivalence relations. Results show that after successful respondent extinction in the whitecontext, only 33.3% participants stopped showing avoidance behavior in the greencontext, and that respondent elicitation was reinstalled during the test (Phase 5). In Phase 4 of Experiment 2, in addition to undergoing respondent extinction, participants were instructed that the white and green contexts were similar. Results show that after successful respondent extinction in the white context during Phase 4, only 10% participants stopped showing avoidance behavior in the green context, and that respondent elicitation was almost eliminated during the test (Phase 5). We discuss these findings and their applied implications.

N-acetyltransferase 2 (NAT2) catalyzes the bioactivation andor detoxification of drugs and carcinogens. The aim of this study was to establish the correlation between the NAT2genotype and the acetylating phenotype in a Mexican population using sulfamethazine as a probe. From a total of 122 individuals, 73 (59.8) were slow and 49 (40.2) were fast acetylators. Eleven individuals (9) had the wild-type genotype (NAT24NAT24). The most frequent genotype was NAT24NAT25Bobserved in 20.66 of individuals. In conclusion, our results show that an accurate prediction of the acetylation phenotype by genotyping can be achieved in around half of the population. Further studies with a larger number of individuals are required to establish correlations between phenotype and genotype in half of that patients having a genotype combined with slowrapid alleles.

Nod2, a member of the Apaf1/Nod protein family, confers responsiveness to bacterial products and activates NF-kappaB, a transcription factor that plays a central role in innate immunity. Recently, genetic variation in Nod2 has been associated with susceptibility to Crohn's disease. Here, we report that expression of Nod2 is induced upon differentiation of CD34(+) hematopoietic progenitor cells into granulocyte or monocyte/macrophages. In peripheral blood cells, the highest levels of Nod2 were observed in CD14(+) (monocytes), CD15(+) (granulocytes), and CD40(+)/CD86(+) (dendritic cells) cell populations. Notably, stimulation of myeloblastic and epithelial cells with bacterial lipopolysaccharide or TNFalpha resulted in up-regulation of Nod2. A search for consensus sites within the Nod2 promoter revealed a NF-kappaB binding element that was required for transcriptional activity in response to TNFalpha. Moreover, ectopic expression of p65 induced transactivation, whereas that of dominant-negative IkappaBalpha blocked the transcriptional activity of the Nod2 promoter. Upon stimulation with TNFalpha or lipopolysaccharide, both p50 and p65 subunits of NF-kappaB were bound to the Nod2 promoter. Thus, Nod2 expression is enhanced by proinflammatory cytokines and bacterial components via NF-kappaB, a mechanism that may contribute to the amplification of the innate immune response and susceptibility to inflammatory disease.

This study examined the impact of the application of a biocontrol yeast, Candida sake CPA-1 (3 × 106colony forming units (cfu) ml-1) on the resident microbial populations just prior to harvest, during 7 months cold storage and subsequent ambient shelf-life in two seasons on apples untreated or treated with a preharvest pesticide programme. The changes in populations of the antagonistic yeast ( C. sake) were also monitored. Generally, application of the antagonist had little effect on the total bacterial populations which remained very low both prior to harvest and subsequently during cold storage. White yeasts were predominant on the apples during the experimental period, with lower populations of pink yeasts. When apples were removed after 7 months to ambient conditions the yeast populations increased quickly but those apples treated with C. sake had significantly less white yeasts than untreated controls. The dominant filamentous fungi isolated were Cladosporium, Alternaria and Penicillium spp. Penicillium spp. which is responsible for major postharvest diseases was seldom isolated at preharvest but it became important during later cold storage and shelf life period. Populations of Cladosporium and Penicillium were significantly reduced by the C. sake treatment when removed from cold storage during the ambient shelf-life. In contrast, the Alternaria spp. were unaffected by the antagonist. The actual populations of C. sake applied decreased significantly immediately after application (24 h). However, they subsequently increased to a maximum after one month cold storage (103cfu g-1), and populations increased again under ambient shelf-life conditions. The C. sake populations, and the resident microbial populations, were unaffected by preharvest fungicide applications. This study demonstrates that preharvest application of an antagonistic yeast such as C. sake has an impact on the resident mycoflora both during 7 months cold storage and during ambient shelf-life storage.

Background: Polymorphisms at the thiopurine S-methyltransferase coding gene (TPMT) determine enzyme activity and consequently, the development of toxicity secondary to thiopurines. Methods: A total of 108 DNA samples from volunteer donors and 39 from patients with acute lymphoblastic leukemia (ALL) were analyzed. Genomic DNA from peripheral blood leukocytes was isolated by standard methods. Known (wild-type and polymorphic) sequenced polymerase chain reaction (PCR) fragments of the TPMT gene were used as controls. TPMT gene fragments were amplified for exons 5, 7 and 10. Thereafter, PCR products were analyzed by denaturating high performance liquid chromatography (DHPLC) for the most frequent mutant TPMT alleles, according to the method developed by Schaeffeler et al. on an analysis system from Transgenomics. Results: No elution profiles on DHPLC analysis, different from those previously reported, were documented. Frequency of allele polymorphisms was 27.3% in healthy and 19.7% in ALL population. However, only 17.6% of all polymorphisms found are considered functional, the most frequent being *3A (n = 13; 4.4%), followed by *3B (n = 5; 1.7%), *3C (n = 5; 1.7%), and *2 (n = 3; 1.0%). From 39 ALL patients, 22 were treated with thiopurines, and particularly one patient, who was referred to our Hospital to investigate relapse, after developing pancytopenia while on treatment with thiopurine, had a TPMT*3C allele. He required broad spectrum antibiotics, platelets transfusions, as well as G-CSF. This example illustrates that TPMT polymorphisms must be determined before thiopurines are indicated. Conclusions: DHPLC is a highly sensitive, rapid and efficient method to identify relevant TPMT gene mutations which allows the screening for genetic variability in the TPMT gene. This is the first analysis of the polymorphisms at this gene in Mexican population. The frequency of known polymorphisms was similar to those reported in other regions worldwide. Since a direct relation has been documented within functional polymorphisms and enzyme activity, and this methology is feasible to realize in any phase during the treatment of ALL patients, the routine typing of TPMT polymorphisms in the patients with ALL has been set in our Institution. Table 1. Frequency of TPMT polymorphisms in mexican population Population TPMT*1 TPMT*1S TPMT*2 TPMT*3A TPMT*3B TPMT*3C * Acute Lymphoblastic Leukemia Healthy n(%) 50 (72.7) 42 (19.4) 2 (0.92) 7 (3.24) 5 (2.3) 3 (1.4) ALL* n(%) 24 (80.3) 5 (6.9) 2 (2.7) 6 (7.6) -- 2 (2.5)

Background: Polymorphisms at the thiopurine S-methyltransferase coding gene (TPMT) determine enzyme activity and consequently, the development of toxicity secondary to thiopurines.