Primary leptomeningeal histiocytic sarcoma in a patient with a good outcome: a case report and review of the literature.

INTRODUCTION: Histiocytic sarcoma is a rare neoplasm with few cases reported in the literature of which some were diagnosed in animals. This neoplasm arises from abnormal reticuloendothelial system cell proliferation of histiocytes and has an aggressive behavior especially if located in the central nervous system. We present the first case of a patient with histiocytic sarcoma that involved the meninges and had a good course after multidisciplinary treatment. CASE PRESENTATION: Our patient was a 41-year-old Caucasian woman with no previous history of disease who started with systemic symptoms such as headache and chills. Magnetic resonance imaging with gadolinium contrast of the brain suggested a mass 1.5×2cm in diameter in the temporal lobe with a non-uniform vasogenic edema. This lesion was implanted in the meninges and surgery was the first treatment. The histological findings revealed a histiocytic sarcoma. The patient received concomitant chemoradiotherapy after surgery with good tolerance and currently lives without disease. CONCLUSION: Although histiocytic sarcomas in the brain present an unusual location and have a poorer prognosis, we have identified the first primary leptomeningeal histiocytic sarcoma with a disease-free survival greater than 3 years following multidisciplinary treatment with surgery and chemotherapy and radiotherapy.

Identification of new meningococcal serogroup B surface antigens through a systematic analysis of neisserial genomes.

The difficulty of inducing an effective immune response against the Neisseria meningitidis serogroup B capsular polysaccharide has lead to the search for vaccines for this serogroup based on outer membrane proteins. The availability of the first meningococcal genome (MC58 strain) allowed the expansion of high-throughput methods to explore the protein profile displayed by N. meningitidis. By combining a pan-genome analysis with an extensive experimental validation to identify new potential vaccine candidates, genes coding for antigens likely to be exposed on the surface of the meningococcus were selected after a multistep comparative analysis of entire Neisseria genomes. Eleven novel putative ORF annotations were reported for serogroup B strain MC58. Furthermore, a total of 20 new predicted potential pan-neisserial vaccine candidates were produced as recombinant proteins and evaluated using immunological assays. Potential vaccine candidate coding genes were PCR-amplified from a panel of representative strains and their variability analyzed using maximum likelihood approaches for detecting positive selection. Finally, five proteins all capable of inducing a functional antibody response vs N. meningitidis strain CU385 were identified as new attractive vaccine candidates: NMB0606 a potential YajC orthologue, NMB0928 the neisserial NlpB (BamC), NMB0873 a LolB orthologue, NMB1163 a protein belonging to a curli-like assembly machinery, and NMB0938 (a neisserial specific antigen) with evidence of positive selection appreciated for NMB0928. The new set of vaccine candidates and the novel proposed functions will open a new wave of research in the search for the elusive neisserial vaccine.

Assessment of vaccine potential of the Neisseria-specific protein NMB0938.

The availability of complete genome sequence of Neisseria meningitidis serogroup B strain MC58 and reverse vaccinology has allowed the discovery of several novel antigens. Here, we have explored the potential of N. meningitidis lipoprotein NMB0938 as a vaccine candidate, based on investigation of gene sequence conservation and the antibody response elicited after immunization in mice. This antigen was previously identified by a genome-based approach as an outer membrane lipoprotein unique to the Neisseria genus. The nmb0938 gene was present in all 37 Neisseria isolates analyzed in this study. Based on amino acid sequence identity, 16 unique sequences were identified which clustered into three variants with identities ranging from 92 to 99%, with one cluster represented by the Neisseria lactamica strains. Recombinant protein NMB0938 (rNMB0938) was expressed in Escherichia coli and purified after solubilization of the insoluble fraction. Antisera produced in mice against purified rNMB0938 reacted with a range of meningococcal strains in whole-cell ELISA and western blotting. Using flow cytometry, it was also shown that anti-rNMB0938 antibodies bound to the surface of the homologous meningococcal strain and activated complement deposition. Moreover, antibodies against rNMB0938 elicited complement-mediated killing of meningococcal strains from both sequence variants and conferred passive protection against meningococcal bacteremia in infant rats. According to our results, NMB0938 represents a promising candidate to be included in a vaccine to prevent meningococcal disease.

Proteomic study via a non-gel based approach of meningococcal outer membrane vesicle vaccine obtained from strain CU385: a road map for discovering new antigens.

This work presents the results from a study of the protein composition of outer membrane vesicles from VA-MENGOC-BC (Finlay Institute, Cuba), an available vaccine against serogroup B Neisseria meningitidis. Proteins were identified by means of SCAPE, a 2DE-free method for proteome studies. More than one hundred proteins were detected by tandem liquid chromatographymass spectrometry analysis of fractions enriched in peptides devoid of histidine or arginine residues, providing a detailed description of the vaccine. A bioinformatic analysis of the identified components resulted in the identification of 31 outer membrane proteins and three conserved hypothetical proteins, allowing the cloning, expression, purification and immunological study of two of them (NMB0088 and NMB1796) as new antigens.

Lipoprotein NMB0928 from Neisseria meningitidis serogroup B as a novel vaccine candidate.

Polysaccharide-based vaccines for serogroup B Neisseria meningitidis have failed to induce protective immunity. As a result, efforts to develop vaccines for serogroup B meningococcal disease have mostly focused on outer membrane proteins (OMP). Vaccine candidates based on meningococcal OMP have emerged in the form of outer membrane vesicles (OMVs) or, more recently, purified recombinant proteins, as alternative strategies for serogroup B vaccine development. In our group, the protein composition of the Cuban OMVs-based vaccine VA-MENGOC-BC was elucidated using two-dimensional gel electrophoresis and mass spectrometry. The proteomic map of this product allowed the identification of new putative protective proteins not previously reported as components of an antimeningococcal vaccine. In the present study, we have determined the immunogenicity and protective capacity of NMB0928, one of those proteins present in the OMVs. The antigen was obtained as a recombinant protein in Escherichia coli, purified and used to immunize mice. The antiserum produced against the protein was capable to recognize the natural protein in different meningococcal strains by whole-cell ELISA and Western blotting. After immunization, recombinant NMB0928 induced bactericidal antibodies, and when the protein was administered inserted into liposomes, the elicited antibodies were protective in the infant rat model. These results suggest that NMB0928 is a novel antigen worth to be included in a broadly protective meningococcal vaccine.

Bicistronic expression plasmid for the rapid production of recombinant fused proteins in Escherichia coli.

In the post-genomic era, every aspect of the production of proteins must be accelerated. In this way, several vectors are currently exploited for rapid production of recombinant proteins in Escherichia coli. N-terminal fusions to the first 47 amino acids of the LpdA (dihydrolipoamide dehydrogenase A) protein of Neisseria meningitidis have been shown to increase the expression of recombinant proteins. Consequently, we have constructed a modified N-terminal LpdA fusion vector, introducing the blue/white colony selection by exploiting a bicistronic gene organization. In the new vector, the sequence encoding the first 47 amino acids of meningococcal LpdA and the alpha-peptide sequence of beta-galactosidase were connected via a ribosome-binding site, and two MCSs (multiple cloning sites) were located surrounding the latter, allowing efficient cloning by colour selection of recombinants. The vector was also improved with the addition of a C-terminal polyhistidine tag, and an EKS (enterokinase recognition sequence) immediately after the LpdA fusion sequence. The new plasmid was employed in the expression and purification of six different bacterial polypeptides. One of these recombinant proteins, P6 protein from Haemophilus influenzae, was used as a model and its N-terminal fusion sequence was totally removed from the recombinant version after incubation with the enterokinase protease, while the polyhistidine tail successfully allowed the purification of the unfused protein from the protease reaction. Two completely new neisserial vaccine candidates, NMB0088 and NMB1126 proteins, were cloned, expressed and purified using this system. To our knowledge, this constitutes the first report of the cloning and expression of these proteins in E. coli.

Effect of conjugation methodology on the immunogenicity and protective efficacy of meningococcal group C polysaccharide-P64k protein conjugates.

Neisseria meningitidis serogroup C polysaccharide (CCPS) was conjugated to the carrier protein P64k using two different conjugation procedures, condensation mediated by carbodiimide with adipic acid dihydrazide as spacer and the reductive amination method. BALB/c mice were immunized with the resultant polysaccharide-protein conjugates and the immune response was evaluated. All conjugates assayed generated at least 10-fold higher antibody titers than the free polysaccharide. The reductive amination method rendered the best conjugate (CCPS-P64kR) that was able to elicit antibody titers statistically higher than the titer elicited by the plain CCPS (P<0.001). The sera of the group immunized with CCPS-P64kR showed a three-fold higher bactericidal response than the sera of the group immunized with the plain CCPS and they were able to protect against challenge with meningococci in the infant rat protection model. In addition, three different conjugates were obtained from polysaccharides with molecular relative sizes of 2000-4000 Da, 4000-10,000 Da or 10,000-50,000 Da, but no differences were detected in the immune response obtained against the three conjugates. Our experiments demonstrate that it is possible to generate a protective, T-cell-dependent response against CCPS using the P64k protein as carrier.

Hipertensión arterial en la comunidad: (metanálisis de 82 estudios) / Arterial Hypertension in the community

Se realizó un metanálisis sobre el estudio de 82 investigaciones de trabajos de terminación de la especialidad (TTE) de Medicina General Integral (MGI), archivados en las bibliotecas del Instituto Superior de Ciencias Médicas y las policlínicas de la provincia de Camagüey, relacionados con la hipertensión arterial (HTA) durante el período de 1989 a 2000. Se encontró que predominó el sexo femenino y a partir de los 50 años de edad. Aunque no existió significación estadística llama la atención el grupo de 40-49 años en el que se observó un incremento de pacientes con cifras tensionales elevadas. El mayor número de estudios corresponde al municipio Camagüey, básicamente el de características clínico epidemiológicas con el 73,17 por ciento donde se evidenciaron factores de riesgo conocidos como el hábito de fumar, obesidad, sedentarismo, hipercolesterolemia y aumento del consumo de sal. Fue bajo el número de trabajos sobre intervenciones terapéuticas con el 26,83 por ciento, nueve de éstos versaron sobre medicina natural y tradicional, ocho sobre fármacos convencionales y ocho involucraron las medidas no farmacológicas. En los años 1995 1997 se realizaron la mayoría de las investigaciones con el 46.30 por ciento. En los tratamientos farmacológicos se aprecia un incremento del beneficio social y económico con costos mínimos(AU)

Hipertensión arterial en la comunidad / Arterial Hypertension in the community

Se realizó un metanálisis sobre el estudio de 82 investigaciones de trabajos de terminación de la especialidad (TTE) de Medicina General Integral (MGI), archivados en las bibliotecas del Instituto Superior de Ciencias Médicas y las policlínicas de la provincia de Camagüey, relacionados con la hipertensión arterial (HTA) durante el período de 1989 a 2000. Se encontró que predominó el sexo femenino y a partir de los 50 años de edad. Aunque no existió significación estadística llama la atención el grupo de 40-49 años en el que se observó un incremento de pacientes con cifras tensionales elevadas. El mayor número de estudios corresponde al municipio Camagüey, básicamente el de características clínico - epidemiológicas con el 73, 17 % donde se evidenciaron factores de riesgo conocidos como el hábito de fumar, obesidad, sedentarismo, hipercolesterolemia y aumento del consumo de sal. Fue bajo el número de trabajos sobre intervenciones terapéuticas con el 26, 83 %, nueve de éstos versaron sobre medicina natural y tradicional, ocho sobre fármacos convencionales y ocho involucraron las medidas no farmacológicas. En los años 1995-1997 se realizaron la mayoría de las investigaciones con el 46, 30 %. En los tratamientos farmacológicos se aprecia un incremento del beneficio social y económico con costos mínimos.

A metanalysis about the study of 82 researches for especiality termination works (STW) at the mof General Integral Medicina (GIM) registered at the Medical University libraries and polyclinics of Camagüey province related with the arterial hypertension (AHT) from 1989 to 2000 was carried out. I was found that age groups that prevailed were those over 50 years and femenine sex. Although there was estatistical significance the age group 40 to 49 years is calling the attention in which an increase of patients with high tension figures was observed greater number of studies corresponds to Camagüey municipality, basically that of clinico-epidemiological characteristics with 73, 17 % in which know risk factors such as smoking habit, obesity, sedentariness, hypercholesterolemia and high salt intake were evidenced. It was low the number of woks about therapeutic interventions with 25, 83 % versus 9 of them about natural and traditional medicine, 8 about conventional drugs and 8 involved non pharmacological measures. During 1995 to 1997, most of reseraches work performed with 46, 30 %. In pharmacologic treatments, cost benefits, however when applying non-pharmacologic treatment, it is noted and crease of social and economic benefits with minimal cost.

Reporte clínico de cirugía de elevación sinusal bilateral con hueso esponjoso de cresta ilíaca, preparatoria para el trasplante de los gérmenes de los terceros molares superiores, a un lecho óseo neoformado / Clinical report of bilateral sinus lift surgery with iliac crest cancellous bone, prior to the transplantation of upper third molar germs to a newly formed bed

Se revisan los dos tiempos quirúrgicos que involucra una elevación sinusal bilateral con trasplante de hueso esponjoso de cresta ilíaca, en paciente femenino de 17 años de edad con anodoncia parcial. El objetivo de la cirugía es crear un lecho de hueso neoformado para alojar posteriormente los gérmenes dentarios de los terceros molares superiores, en el espacio existente en el área de premolares superiores, en forma bilateral