Baculovirus Display of Peptides and Proteins for Medical Applications.

Baculoviridae is a large family of arthropod-infective viruses. Recombinant baculoviruses have many applications, the best known is as a system for large scale protein production in combination with insect cell cultures. More recently recombinant baculoviruses have been utilized for the display of proteins of interest with applications in medicine. In the present review we analyze the different strategies for the display of proteins and peptides on the surface of recombinant baculoviruses and provide some examples of the different proteins displayed. We analyze briefly the commercially available systems for recombinant baculovirus production and display and discuss the future of this emerging and powerful technology.

Granos de polen anemófilos: sensibilización en pacientes alérgicos / Anemophilic pollen grains: sensitization in allergic patients

A nivel mundial, los aeroalérgenos más frecuentes causantes de enfermedades alérgicas son los granos de polen anemófilos. Estos han sido capaces de desencadenar crisis que han reflejado una elevada morbilidad. En Cuba los estudios de sensibilización a granos de polen han sido escasos. Con el objetivo de determinar la sensibilización a granos de polen en pacientes alérgicos y su relación con la presencia de enfermedades alérgicas, se realizó un estudio observacional descriptivo de corte transversal, no aleatorizado, de marzo a junio del 2019. La muestra se constituyó de 33 pacientes con asma, rinitis, rinoconjuntivitis alérgica, dermatitis atópica y conjuntivitis alérgica. A todos los pacientes se les realizó historia clínica alergológica y prueba cutánea por punción con extractos alergénicos de: Helianthus annus, Cosmos bipinnatus, Cynodon dactylon, Quercus sp, Eucaliptus sp. Se aplicaron las frecuencias absolutas, porcientos, desviación estándar, promedio, edad media y test de Spearman para su análisis. La edad media de la muestra fue de 36,9 años, con predominio de mujeres. Más del 50por ciento de los pacientes presentaron sensibilización a granos de polen; y de ellos, el 24,24por ciento resultaron polisensibilizados. El mayor porcentaje de sensibilización fue a Cynodon dactylon. La rinitis alérgica fue la enfermedad que prevaleció en la población estudiada(AU)

Nowadays, the most frequent aeroallergens causing allergy diseases have been anemophilous pollen grains. They have been able to triggers crises that have reflected a high morbidity. In Cuba, studies of sensitization to pollen grains have been scarce. The objective of our research was to determine the sensitization to pollen grains in allergic patients and its relationship with the presence of allergic diseases. A non-randomized, descriptive, cross-sectional, observational study was conducted from March to June 2019. The sample consisted of 33 patients with asthma, allergic rhinitis, rhinoconjunctivitis, atopic dermatitis and allergic conjunctivitis. All patients underwent allergic history and skin prick test testing with allergenic extracts of: Helianthus annus, Cosmos bipinnatus, Cynodon dactylon, Quercus sp, Eucalyptus sp. Absolute frequencies, percentages, standard deviation, mean, average age, and Spearman´s test were applied for analysis. The average age of the sample was 36.9 years, with a predominance of women. More than 50percent of the patients presented sensitization to pollen grains; of them, 24.24percent polysensitized. The highest percentage of sensitization was to Cynodon dactylon. Allergic rhinitis was the disease that prevailed in the population studied(AU)

Dopamine D2 and Adenosine A2A Receptors Interaction on Ca2+ Current Modulation in a Rodent Model of Parkinsonism.

SUMMARY STATEMENT: A2A receptor required previous D2 receptor activation to modulate Ca2+ currents. Istradefylline decreases pramipexole modulation on Ca2+ currents. Istradefylline reduces A2A + neurons activity in striatial microcircuit, but pramipexole failed to further reduce neuronal activity.

Phylogenetic Identification, Diversity, and Richness of Aspergillus from Homes in Havana, Cuba.

Aspergillus is one of the most common fungal genera found indoors; it is important because it can cause a wide range of diseases in humans. Aspergillus species identification is based on a combination of morphological, physiological, and molecular methods. However, molecular methodologies have rarely been used for the identification of environmental isolates of Aspergillus in Cuba. Therefore, the objective of this work was to identify the species of the genus Aspergillus obtained from houses in Havana, Cuba, through the construction of phylogeny from a partial sequence of the benA gene region, and to analyze the diversity and richness of Aspergillus in the studied municipalities. Isolates of Aspergillus spp. included in this study presented the typical macro- and micromorphology described for the genus. According to this polyphasic characterization, A. niger, A. flavus, A. welwitschiae, A. heteromorphus, A. sydowii, A. tamarii, A. fumigatus, A. clavatus, and A. tubingensis were the most abundant species. Most of the identified species constitute new records for outdoor and indoor environments in Cuba and contribute to the knowledge of fungal biodiversity in the country. These results constitute an alert for the health authorities of the country, since prolonged exposure of the inhabitants to Aspergillus spores can cause severe persistent asthma, among other diseases.

Metabolic acidosis and hyperkalemia differentially regulate cation HCN3 channel in the rat nephron.

The kidney controls body fluids, electrolyte and acid-base balance. Previously, we demonstrated that hyperpolarization-activated and cyclic nucleotide-gated (HCN) cation channels participate in ammonium excretion in the rat kidney. Since acid-base balance is closely linked to potassium metabolism, in the present work we aim to determine the effect of chronic metabolic acidosis (CMA) and hyperkalemia (HK) on protein abundance and localization of HCN3 in the rat kidney. CMA increased HCN3 protein level only in the outer medulla (2.74 ± 0.31) according to immunoblot analysis. However, immunofluorescence assays showed that HCN3 augmented in cortical proximal tubules (1.45 ± 0.11) and medullary thick ascending limb of Henle's loop (4.48 ± 0.45) from the inner stripe of outer medulla. HCN3 was detected in brush border membranes (BBM) and mitochondria of the proximal tubule by immunogold electron and confocal microscopy in control conditions. Acidosis did not alter HCN3 levels in BBM and mitochondria but augmented them in lysosomes. HCN3 was also immuno-detected in mitoautophagosomes. In the distal nephron, HCN3 was expressed in principal and intercalated cells from cortical to medullary collecting ducts. CMA did not change HCN3 abundance in these nephron segments. In contrast, HK doubled HCN3 level in cortical collecting ducts and favored its basolateral localization in principal cells from the inner medullary collecting ducts. These findings further support HCN channels contribution to renal acid-base and potassium balance.

Espiritualidad en adultos mayores hospitalizados, oportunidad de cuidado para enfermería: aproximación cuantitativa / A quantitative approximation on spirituality in hospitalized older adults, a nursing care opportunity / Espiritualidade em adultos maiores hospitalizados, oportunidade de cuidado para enfermagem: aproximação quantitativa

Resumen Introducción La espiritualidad y religiosidad tienen influencia sobre la longevidad, el enfrentamiento a la muerte, la satisfacción vital y proporcionan soporte en la enfermedad; el objetivo de esta investigación fue describir la perspectiva espiritual de los adultos mayores hospitalizados en una institución de salud de segundo nivel de atención. Materiales y Métodos Estudio cuantitativo, observacional y transversal, desarrollado en el Hospital General de Rincón de Romos, Aguascalientes; en medicina interna y cirugía, muestreo no probabilístico por conveniencia, criterios de inclusión: adultos mayores con al menos 24 horas de hospitalización, hombres y mujeres con 60 años o más. Se usó la Escala de Perspectiva Espiritual de Reed, a mayor puntaje mayor espiritualidad, con un apartado de características sociodemográficas. Análisis descriptivo a través de frecuencias y porcentajes. Resultados Media de edad de participantes fue de 69.7 años (Min 62, Max 94, DE 7.31), El 80.4% considera que no recibe apoyo espiritual o religioso por parte de la enfermera durante la estancia hospitalaria, 29.4% habla de asuntos espirituales al menos una vez a la semana y el 70.6% está de acuerdo con que el perdón es una parte importante de la espiritualidad. Discusión El cuidado espiritual debe ser parte de la cotidianidad de la enfermera, los adultos mayores se enfocan en la oración y en la lectura espiritual, considerando la espiritualidad es importante en su vida. Conclusiones En la vejez se tiene alto sentido espiritual, durante la hospitalización puede apoyar el estado emocional, por lo que es importante para enfermería en la intervención con adultos mayores institucionalizados.

Abstract Introduction Spirituality and religiosity influence longevity, coping with death, and life satisfaction, apart from providing illness support. This study aims to describe the spiritual perspective of older adults hospitalized in a secondary level healthcare institution. Materials and Methods A quantitative, observational and cross-sectional study was conducted in internal medicine and surgery departments at the Rincón de Romos Hospital, Aguascalientes, using a non-probability sampling for convenience. The inclusion criteria were: older adults with at least 24 hours of hospitalization, men and women over 60 years of age. The Reed's Spiritual Perspective Scale was used, the higher the score the higher the spirituality, including a section on sociodemographic characteristics. Additionally, a descriptive analysis through frequencies and percentages was made. Results The average age of participants was 69.7 years (Min 62, Max 94, DE 7.31). 80.4% of the participants considered that they did not receive any spiritual or religious support from nurses during their hospital stay, 29.4% talked about spiritual matters at least once a week and 70.6% agreed that forgiveness is an important part of spirituality. Discussion Spiritual care should be part of nurses' daily life since older adults focus on prayer and spiritual reading, considering spirituality as an important element in their life. Conclusions There is a high spiritual sense in older adults, which can support their emotional state during hospitalization, becoming an important factor to consider when caring hospitalized older adults.

Resumo Introdução A espiritualidade e religiosidade têm influência sobre a longevidade, o enfrentamento da morte, a satisfação vital e oferecem suporte durante a doença; esta pesquisa objetiva descrever a perspectiva espiritual dos adultos maiores hospitalizados em um estabelecimento de saúde de segundo nível de atenção. Materiais e Métodos Estudo quantitativo, observacional e transversal, desenvolvido no Hospital General de Rincón de Romos, Aguascalientes; em medicina interna e cirurgia, amostragem não probabilística por conveniência, critérios de inclusão: adultos maiores com, no mínimo, 24 horas de hospitalização, homens e mulheres com 60 anos ou mais. A Escala de Perspectiva Espiritual de Reed foi utilizada no estudo, sendo que maior escore representa uma maior espiritualidade, incluindo uma análise das características sociodemográficas. Análise descritiva através de frequências e porcentagens. Resultados A média de idade dos participantes foi de 69.7 anos (Min 62, Max 94, DE 7.31), 80,4 considera que não recebe apoio espiritual ou religioso por parte dos serviços de enfermagem durante a internação hospitalar, 29,4% fala de assuntos espirituais pelo menos uma vez por semana e 70,6% está de acordo com que o perdão faz parte importante da espiritualidade. Discussão O cuidado espiritual deve fazer parte da cotidianidade da enfermeira, os adultos maiores estão focados na oração e na leitura espiritual, considerando a espiritualidade como parte importante da vida. Conclusões A velhice vai atrelada a um alto senso espiritual, a espiritualidade pode influenciar em um melhor estado emocional durante a hospitalização, por tanto, para a enfermagem a espiritualidade é importante na intervenção fornecida a adultos maiores hospitalizados.

Laser-Induced Breakdown Spectroscopy (LIBS) Quality Control and Origin Identification of Handmade Manufactured Cigars.

Tobacco is an agricultural product originating in America that is obtained by processing the leaves of various plants of the genus Nicotiana tabacum. It is the inedible product occupying the most plantings in the world, according to a recent report from the United Nations Food and Agriculture Organization. It is consumed in various ways, but the most popular form of consumption is, undoubtedly, by smoking cigarettes. A particular segment of the tobacco industry is the manufacturing of handmade cigars, which for some third-world countries is an important source of income. There are different qualities of cigars, and a major problem is the adulteration that occurs, for example, when authentic high-quality leaves are replaced by lower quality leaves. A factor that influences the quality of the cigars is the smoke combustion process, which depends on several factors, particularly the composition of the leaves. We present a simple and quick technique for the quality control and origin identification of handmade cigars that measures the Mg/Ca ratios in the tobacco leaves and wrappers of the cigars using laser-induced breakdown spectroscopy.

Muscarinic presynaptic modulation in GABAergic pallidal synapses of the rat.

The external globus pallidus (GPe) is central for basal ganglia processing. It expresses muscarinic cholinergic receptors and receives cholinergic afferents from the pedunculopontine nuclei (PPN) and other regions. The role of these receptors and afferents is unknown. Muscarinic M1-type receptors are expressed by synapses from striatal projection neurons (SPNs). Because axons from SPNs project to the GPe, one hypothesis is that striatopallidal GABAergic terminals may be modulated by M1 receptors. Alternatively, some M1 receptors may be postsynaptic in some pallidal neurons. Evidence of muscarinic modulation in any of these elements would suggest that cholinergic afferents from the PPN, or other sources, could modulate the function of the GPe. In this study, we show this evidence using striatopallidal slice preparations: after field stimulation in the striatum, the cholinergic muscarinic receptor agonist muscarine significantly reduced the amplitude of inhibitory postsynaptic currents (IPSCs) from synapses that exhibited short-term synaptic facilitation. This inhibition was associated with significant increases in paired-pulse facilitation, and quantal content was proportional to IPSC amplitude. These actions were blocked by atropine, pirenzepine, and mamba toxin-7, suggesting that receptors involved were M1. In addition, we found that some pallidal neurons have functional postsynaptic M1 receptors. Moreover, some evoked IPSCs exhibited short-term depression and a different kind of modulation: they were indirectly modulated by muscarine via the activation of presynaptic cannabinoid CB1 receptors. Thus pallidal synapses presenting distinct forms of short-term plasticity were modulated differently.

Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma and can be separated into two subtypes based upon molecular features with similarities to germinal centre B-cells (GCB-like) or activated B-cells (ABC-like). Here we identify gain of 3q27.2 as being significantly associated with adverse outcome in DLBCL and linked with the ABC-like subtype. This lesion includes the BCL6 oncogene, but does not alter BCL6 transcript levels or target-gene repression. Separately, we identify expression of BCL6 in a subset of human haematopoietic stem/progenitor cells (HSPCs). We therefore hypothesize that BCL6 may act by 'hit-and-run' oncogenesis. We model this hit-and-run mechanism by transiently expressing Bcl6 within murine HSPCs, and find that it causes mature B-cell lymphomas that lack Bcl6 expression and target-gene repression, are transcriptionally similar to post-GCB cells, and show epigenetic changes that are conserved from HSPCs to mature B-cells. Together, these results suggest that BCL6 may function in a 'hit-and-run' role in lymphomagenesis.

NIK controls classical and alternative NF-κB activation and is necessary for the survival of human T-cell lymphoma cells.

PURPOSE: Peripheral T-cell lymphomas (PTCL) are a heterogeneous entity of neoplasms with poor prognosis, a lack of effective therapies, and a largely unknown molecular pathology. Deregulated NF-κB activity has been associated with several lymphoproliferative diseases, but its importance in T-cell lymphomagenesis is poorly understood. We investigated the function of the NF-κB-inducing kinase (NIK), in this pathway and its role as a potential molecular target in T-cell lymphomas. EXPERIMENTAL DESIGN: We used immunohistochemistry to analyze the expression of different NF-κB members in primary human PTCL samples and to study its clinical impact. With the aim of inhibiting the pathway, we used genetic silencing of NIK in several T-cell lymphoma cell lines and observed its effect on downstream targets and cell viability. RESULTS: We showed that the NF-κB pathway was activated in a subset of PTCLs associated with poor overall survival. NIK was overexpressed in a number of PTCL cell lines and primary samples, and a pivotal role for NIK in the survival of these tumor cells was unveiled. NIK depletion led to a dramatic induction of apoptosis in NIK-overexpressing cell lines and also showed a more pronounced effect on cell survival than inhibitor of kappa B kinase (IKK) knockdown. NIK silencing induced a blockage of both classical and alternative NF-κB activation and reduced expression of several prosurvival and antiapoptotic factors. CONCLUSIONS: The results of the present study indicate that NIK could be a promising therapeutic target in these aggressive malignancies.

Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation.

The human germinal centre-associated lymphoma gene is specifically expressed in germinal centre B-lymphocytes and germinal centre-derived B-cell lymphomas, but its function is largely unknown. Here we demonstrate that human germinal centre-associated lymphoma directly binds to Syk in B cells, increases its kinase activity on B-cell receptor stimulation and leads to enhanced activation of Syk downstream effectors. To further investigate these findings in vivo, human germinal centre-associated lymphoma transgenic mice were generated. Starting from 12 months of age these mice developed polyclonal B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive amyloid A (AA) amyloidosis, leading to shortened survival. The lymphoid hyperplasia in the human germinal centre-associated lymphoma transgenic mice are likely attributable to enhanced B-cell receptor signalling as shown by increased Syk phosphorylation, ex vivo B-cell proliferation and increased RhoA activation. Overall, our study shows for the first time that the germinal centre protein human germinal centre-associated lymphoma regulates B-cell receptor signalling in B-lymphocytes which, without appropriate control, may lead to B-cell lymphoproliferation.

Molecular characterization of immunoglobulin gene rearrangements in diffuse large B-cell lymphoma: antigen-driven origin and IGHV4-34 as a particular subgroup of the non-GCB subtype.

The pathogenesis of diffuse large B-cell lymphoma (DLBCL) remains partially unknown. The analysis of the B-cell receptor of the malignant cells could contribute to a better understanding of the DLBCL biology. We studied the molecular features of the immunoglobulin heavy chain (IGH) rearrangements in 165 patients diagnosed with DLBCL not otherwise specified. Clonal IGH rearrangements were amplified according to the BIOMED-2 protocol and PCR products were sequenced directly. We also analyzed the criteria for stereotyped patterns in all complete IGHV-IGHD-IGHJ (V-D-J) sequences. Complete V-D-J rearrangements were identified in 130 of 165 patients. Most cases (89%) were highly mutated, but 12 sequences were truly unmutated or minimally mutated. Three genes, IGHV4-34, IGHV3-23, and IGHV4-39, accounted for one third of the whole cohort, including an overrepresentation of IGHV4-34 (15.5% overall). Interestingly, all IGHV4-34 rearrangements and all unmutated sequences belonged to the nongerminal center B-cell-like (non-GCB) subtype. Overall, we found three cases following the current criteria for stereotyped heavy chain VH CDR3 sequences, two of them belonging to subsets previously described in CLL. IGHV gene repertoire is remarkably biased, implying an antigen-driven origin in DLBCL. The particular features in the sequence of the immunoglobulins suggest the existence of particular subgroups within the non-GCB subtype.

A novel molecular mechanism involved in multiple myeloma development revealed by targeting MafB to haematopoietic progenitors.

Understanding the cellular origin of cancer can help to improve disease prevention and therapeutics. Human plasma cell neoplasias are thought to develop from either differentiated B cells or plasma cells. However, when the expression of Maf oncogenes (associated to human plasma cell neoplasias) is targeted to mouse B cells, the resulting animals fail to reproduce the human disease. Here, to explore early cellular changes that might take place in the development of plasma cell neoplasias, we engineered transgenic mice to express MafB in haematopoietic stem/progenitor cells (HS/PCs). Unexpectedly, we show that plasma cell neoplasias arise in the MafB-transgenic mice. Beyond their clinical resemblance to human disease, these neoplasias highly express genes that are known to be upregulated in human multiple myeloma. Moreover, gene expression profiling revealed that MafB-expressing HS/PCs were more similar to B cells and tumour plasma cells than to any other subset, including wild-type HS/PCs. Consistent with this, genome-scale DNA methylation profiling revealed that MafB imposes an epigenetic program in HS/PCs, and that this program is preserved in mature B cells of MafB-transgenic mice, demonstrating a novel molecular mechanism involved in tumour initiation. Our findings suggest that, mechanistically, the haematopoietic progenitor population can be the target for transformation in MafB-associated plasma cell neoplasias.

Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.

Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas.

Essential role for telomerase in chronic myeloid leukemia induced by BCR-ABL in mice.

The telomerase protein is constitutively activated in malignant cells from many patients with cancer, including the chronic myeloid leukemia (CML), but whether telomerase is essential for the pathogenesis of this disease is not known. Here, we used telomerase deficient mice to determine the requirement for telomerase in CML induced by BCR-ABL in mouse models of CML. Loss of one telomerase allele or complete deletion of telomerase prevented the development of leukemia induced by BCR-ABL. However, BCR-ABL was expressed and active in telomerase heterozygous and null leukemic hematopoietic stem cells. These results demonstrate that telomerase is essential for oncogene-induced reprogramming of hematopoietic stem cells in CML development and validate telomerase and the genes it regulates as targets for therapy in CML.

Molecular characterization of the region 7q22.1 in splenic marginal zone lymphomas.

Splenic marginal zone lymphomas (SMZL) are an uncommon type of B-cell non-Hodgkin's lymphoma (NHL-B) in which no specific chromosomal translocations have been described. In contrast, the most frequent cytogenetic abnormality is the loss of the long arm of chromosome 7 (7q). Previous reports have located this loss in the 7q32 region. In order to better characterize the genomic imbalances in SMZL, molecular studies were carried out in 73 patients with SMZL. To gain insight into the mapping at 7q a tiling array was also used. The results confirmed the loss of 7q as the most frequent change. In addition, several abnormalities, including 4q22.1, 1q21.3-q22, 6q25.3, 20q13.33, 3q28, 2q23.3-q24.1 and 17p13, were also present. A loss of 7q22.1 at 99925039-101348479 bp was observed in half of the cases. The region of 7q22.1 has not previously been characterised in SMZL. Our results confirmed the presence of a new region of loss on chromosome 7 in these NHL.

Flow cytometry immunophenotyping of fine-needle aspiration specimens: utility in the diagnosis and classification of non-Hodgkin lymphomas.

AIMS: To establish the utility of flow cytometry (FCM) for screening and diagnosis of B cell non-Hodgkin lymphoma (B-NHL) from lymphoid tissue samples obtained by fine-needle aspiration (FNA). METHODS AND RESULTS: We compared prospectively FCM versus cytology/histology analysis of FNA samples for the diagnostic screening and further World Health Organization (WHO) subclassification of B-NHL. FCM and cytology showed a high degree of agreement (93%); however, diagnosis of reactive processes (RP), B-NHL and T-NHL by FCM showed higher sensitivity than cytology (92-100% versus 64-94%, respectively), without false positive NHL cases. The antibody combination used did not allow a positive diagnosis of Hodgkin lymphoma as distinct from a RP. A high concordance rate was found between FCM and histopathology (74%) in subtyping B-NHL. In this regard, mantle-cell lymphoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma showed the highest degree of agreement (100% concordant rates). In turn, FCM showed higher sensitivity/specificity in classifying follicular lymphoma (FL) and large B cell lymphomas, while the opposite occurred for marginal-zone and lymphoplasmacytic lymphomas. CONCLUSIONS: FCM enhances the diagnostic ability of FNA cytology, playing a crucial role in a rapid and accurate differential diagnosis between RP, B-NHL and T-NHL. In addition, immunophenotyping of FNA samples contributes to a more precise subclassification of B-NHL when combined with histopathology and genetic/molecular data.

Limbus damage in ocular graft-versus-host disease.

Graft-versus-host disease (GVHD) is the major cause of morbidity and mortality among patients undergoing allogeneic hematopoietic stem cell transplantation. Although animal models have been clearly established for the study of skin, liver, and gut, currently there is no equivalent experiemental model for analyzing ocular involvement, which is rather common, especially among patients diagnosed with chronic GVHD. In the current study we have developed a murine model of ocular GVHD and, for the first time, we describe the histopathologic features involving cornea and limbus, which could play a role in the physiopathology of the disease at the ocular level. Our results represent a major finding that allows us to define a model for evaluating new therapeutic strategies for treating ocular GVHD prior to their use in clinical setting.

Long-term reversibility of renal dysfunction associated to light chain deposition disease with bortezomib and dexamethasone and high dose therapy and autologous stem cell transplantation.

A 63-year-old woman presented with progressive renal insufficiency, until a glomerular filtration rate (GFR) of 12 mL/min. A renal biopsy demonstrated glomerular deposition of immunoglobulin κlight chain. The presence of a small population of monoclonal plasmacytes producing an only light κmonoclonal component was demonstrated and Bortezomib and Dexamethasone (BD) was provided as initial therapy. After seven courses of therapy, renal function improved without dialysis requirements up to a GFR 31 mL/min. Under hematological complete response (HCR) the patient underwent high dose of melphalan (HDM) and autologous peripheral blood stem cell transplant. Fifty-four months later the patient remains in HCR and the GFR has progressively improved up to 48 mL/min. This report describes a notably renal function improvement in a patient with Light Chain Deposition Disease after therapy with BD followed by HDM, which can support this treatment as a future option for these patients.

Bcl2 is not required for the development and maintenance of leukemia stem cells in mice.

The existence of leukemia stem cells (LSCs) responsible for tumor maintenance has been firmly established. Therefore, therapeutic targeting of these LSCs may have a profound impact on cancer eradication. The anti-apoptotic protein Bcl2 has been proposed as a therapeutic target, but its role in LSC biology has not been investigated. In order to understand the role of Bcl2 in LSC generation and maintenance, we have taken advantage of our Sca1-BCRABLp210 mouse model of human chronic myeloid leukemia and bcl2 gene-targeted mice. This study provides genetic evidence that the inhibition of Bcl2 is not critical for the generation, selection or maintenance of the tumor initiating and maintaining cells in mice.