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Biomedical subjects

B Sanchez

Publications and source records attributed to B Sanchez.

At least 19 recordsLinked to original sources

Nasal boost with adjuvanted heat-killed BCG or arabinomannan-protein conjugate improves primary BCG-induced protection in C57BL/6 mice.

Today it is generally accepted that the Bacillus Calmette-Guerin (BCG) vaccine protects against childhood tuberculosis (TB) but this immunity wanes with age, resulting in insufficient protection against adult pulmonary TB. Hence, one possible strategy to improve the protective efficacy of the BCG vaccine would be to boost in adulthood. In this study, using the mouse model, we evaluated the ability of two new TB vaccine candidates, heat-killed BCG (H-kBCG) and arabinomannan-tetanus toxoid conjugate (AM-TT), given intransally in a novel Eurocine adjuvant, to boost a primary BCG-induced immune response and to improve protection. Young C57BL/6 mice were vaccinated with conventional BCG and, 6 months later, boosted intranasally with adjuvanted H-kBCG or AM-TT, or subcutaneously with BCG. Ten weeks after the booster, mice were challenged intravenously with M. tuberculosis (Mtb) strain H37Rv. In spleens, there was a significant reduction of cfu counts in mice boosted with either H-kBCG or AM-TT vaccines compared to the non-boosted BCG-vaccinated mice. None of the boosting regimens significantly reduced bacterial loads in lungs, compared to non-boosted BCG vaccination. However, the extent of granulomatous inflammation was significantly reduced in the lungs of mice that received two of the booster vaccines (AM-TT and conventional BCG), as compared with sham-vaccinated mice. All boosted groups, except for mice boosted with the AM-TT vaccine, responded with a proliferation of spleen T cells and gamma interferon production comparable to that induced by a single BCG vaccination.

Administration, Intranasal↗

Report on the first PVL-positive community acquired MRSA strain in Latvia.

Infections by community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) have been reported worldwide. Here we present characterisation of the first CA-MRSA isolated in Latvia. A PVL-positive ST30-MRSA-IV strain was isolated from a nasal swab and the central venous catheter of a patient with fever and multiple organ failure. The PFGE pattern of this strain was identical to pattern SE00-3 of MRSA isolated in Sweden from 29 patients during 2000-2003. This strain is related to the South Pacific area, and its appearance in Sweden and Latvia demonstrates its global spread.

Bacterial Toxins↗

Anatomic feasibility of creating an inferior epigastric arterio-venous fistula to develop the internal thoracic artery with a view to coronary grafting.

Arterio-venous fistulae increase the diameter of their feeding artery. It may be advantageous to increase the diameter of the internal thoracic artery before its use for coronary grafting. A fistula applied directly to the internal thoracic artery may compromise its subsequent use as a coronary graft and is technically difficult and invasive. However, in view of the continuity between the internal thoracic artery and the inferior epigastric artery, it is possible to achieve the same effect by constructing a fistula on the latter. The purpose of this work was to determine, in a cadaveric study, the feasibility of carrying out an arterio-venous fistula on the inferior epigastric artery so as to increase the caliber of the internal thoracic artery before coronary grafting. A morphologic study of the inferior epigastric artery and its vein and their relations as well as the feasibility of such a fistula was carried out on 10 cadavers. The epigastric artery measured 12.35+/-1.2 cm in length. Its diameter decreased from its origin towards it termination from 3.16+/-0.26 cm to 1.76+/-0.18 cm. There was a constant connection between the inferior and superior epigastric arteries. This connection was single in 30% of cases, double in 50% and through an anastomotic plexus of more than two vessels in 20%. The mean number of anastomotic connections was 1.8. The epigastric vein was constant with a diameter of 0.75+/-0.06 mm at its origin and only sufficiently large to carry out a fistula at its termination (2.6+/-0.9 mm). In conclusion, this study indicates that it should be relatively simple to create a fistula between the inferior epigastric artery and either the inferior epigastric vein or the external iliac vein.

Aged↗

Metastatic lymphangiosarcoma in a horse.

A lymphangiosarcoma with metastases was found in a horse that presented with respiratory distress and edema in the ventral thorax and abdomen. The necropsy revealed diffuse edema in the subcutaneous connective tissue. Mediastinal, mesenteric, iliac, and renal lymph nodes were enlarged and white with soft, yellowish necrotic areas. Histologic examination revealed numerous channels and disorganized vessels lined by large polyhedral, polymorphic cells. Tumor metastases were observed in the spleen, lungs, and kidneys. Immunohistochemical evaluation of the tumor cells demonstrated positive staining for factor VIII, vimentin, and keratin. Laminin was scarce, and collagen IV staining was negative, consistent with a discontinuous or absent basement membrane.

Animals↗

[Evidence based treatment of epilepsy].

OBJECTIVE: Evidence based medicine is becoming popular in all fields of medicine. Through systematic reviews, critical evaluation, and statistical strategies such as meta analysis it aids to take decisions in clinical practice. We revise the information on the treatment of epilepsy found in the main sources of evidence based medicine. DEVELOPMENT: After commenting some basic concepts such as systematic review, meta analysis, odds ratio, relative risk and numbers needed to treat, we describe the main primary, secondary and tertiary drug information sources with emphasis on sources of evidence based medicine. Some representative examples are given about the information on treatment of epilepsy found in the main sources of evidence based medicine such as TRIP, DARE, Cochrane Library, clinical practice guidelines, Clinical Evidence or Bandolier. Most clinical trials analyze the efficacy and tolerability of add on new antiepileptic drugs in partial refractory epilepsy. However, we found few trials on efficacy and tolerability of these drugs in monotherapy, in newly diagnosed partial epilepsy, on other types of epilepsy or in children. There are also few trials comparing the new antiepileptic drugs between them or in relation to the old ones. CONCLUSION: Treatment of epilepsy is yet an art more than a science because clinical practice decisions depends on therapeutic habits and clinical expertise more than on the results emerging from randomized and controlled clinical trials. Large comparative trials are needed but relevant criteria of efficacy and validated procedures to evaluate quality of life, tolerability or cognitive function outcomes should be used in these trials.

Anticonvulsants↗

Detection of estrogen alpha and progesterone receptors and cell proliferation in the uterus during early pregnancy in the goat.

The objectives of this study were to investigate in the goat uterus the expression of estrogen-alpha (ER alpha) and progesterone receptors (PR) and their relationship to proliferation indices (Ki-67) during peri-implantation on Days 22 to 30 post coitum (pc). Immunohistochemical methods were used to quantify ER alpha and PR for luminal and deep regions of the endometrium and of the myometrium. On Day 22 pc cell proliferation was only observed in the luminal epithelium. On Day 24 pc, high cell proliferation indices were seen in luminal epithelium and proliferation began in the luminal stroma and glands. There was a positive correlation between Ki-67 and total ER alpha score in the luminal epithelium (r = 0.53, P < 0.01). Levels of PR scores were highly correlated with Ki-67 indices in luminal epithelium (r = 0.74, P < 0.01) and stroma (r = 0.70, P < 0.01). No Ki-67 expression was observed in deep glands, stroma or myometrium on any of the days studied. Results indicate that patterns of ER alpha and PR expression differ markedly, and that there was a high correlation between PR expression and cell proliferation in the caprine uterus during the peri-implantation period.

Animals↗

Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells.

Bax is a Bcl-2 family protein with proapoptotic activity, which has been shown to trigger cytochrome c release from mitochondria both in vitro and in vivo. In control HeLa cells, Bax is present in the cytosol and weakly associated with mitochondria as a monomer with an apparent molecular mass of 20,000 Da. After treatment of the HeLa cells with the apoptosis inducer staurosporine or UV irradiation, Bax associated with mitochondria is present as two large molecular weight oligomers/complexes of 96,000 and 260,000 Da, which are integrated into the mitochondrial membrane. Bcl-2 prevents Bax oligomerization and insertion into the mitochondrial membrane. The outer mitochondrial membrane protein voltage-dependent anion channel and the inner mitochondrial membrane protein adenosine nucleotide translocator do not coelute with the large molecular weight Bax oligomers/complexes on gel filtration. Bax oligomerization appears to be required for its proapoptotic activity, and the Bax oligomer/complex might constitute the structural entirety of the cytochrome c-conducting channel in the outer mitochondrial membrane.

Apoptosis↗

Aortic stent-graft for patent ductus arteriosus in adults: the aortic exclusion technique.

The risk of closure of a patent ductus arteriosus in the elderly is high because of the fragility of the aorta and aneurysmal change in the ductus. Stent-grafting has emerged as a method of treatment of pathology of the aorta. We describe a case where this new endovascular technique has been successfully applied for closure of a patent ductus arteriosus in a high-risk patient. It may become part of the armamentarium for this pathology in adults.

Aged↗

Role of pre-operative assessment in the surgical management of leiomyoma extended to the right heart chambers: a compendium of information from isolated reports.

Recurrent intravenous leiomyoma extending to the right heart chambers is extremely rare. A large range of surgical techniques and approaches (i.e. two-step procedure, hypothermia and circulatory arrest) have been previously described. We report a recent case where the tumour was excised in a one-step procedure under normothermic cardiopulmonary bypass. This report associated to a comprehensive literature review allows us to discuss the role of pre-operative assessment and to propose refinement of surgical techniques according to the anatomy of the tumour.

Female↗

Molecular structure of eight human autoreactive monoclonal antibodies.

The heavy (H) and light (L) chain V-region sequences of eight human autoreactive immunoglobulin M (IgM) monoclonal antibodies (mAbs: BY-4, BY-7, BY-12, IRM-3, IRM-7, IRM-8, IRM-10 and CDC-1) were determined at the cDNA level. All VH and VL families were identified. Four different VH families were represented, VH3 being the most common as five of the mAbs (BY-7, BY-12, IRM-3, IRM-8 and CDC-1) used genetic elements of this family, whereas VH1, VH2 and VH4 were only present in IRM-7, BY-4 and IRM-10, respectively. BY-4, BY-7, BY-12, IRM-7 and IRM-10 reacted with a variety of self as well as non-self antigens, thus exhibiting polyreactive behaviour. Comparison of the gene segments utilized by these mAbs with their germline counterparts revealed that the gene segments were close to germline configuration. The length of H-CDR3 was found to be relatively long (27-60 nucleotides) among the polyreactive mAbs and the presence of Tyr and Trp residues in this region seems to be of vital importance for polyreactivity. We have analysed the utilization of gene elements and the presence of amino acid residues in regions particularly important for antigen binding, such as CDR. Common molecular features relating to the function of the mAbs are discussed.

Amino Acid Sequence↗

Conserved region 2 of adenovirus E1A has a function distinct from pRb binding required to prevent cell cycle arrest by p16INK4a or p27Kip1.

Ectopic expression of the CDK inhibitors (CKIs) p16INK4a and p27Kip1 in Rat1 fibroblasts induces dephosphorylation and activation of Retinoblastoma-family proteins (pRb, p107 and p130), their association with E2F proteins, and cell cycle arrest in G1. The growth-inhibitory action of p16, in particular, is believed to be mediated essentially via pRb activation. The 12S E1A protein of human Adenovirus 5 associates with pRb-family proteins via residues in its Conserved Regions (CR) 1 and 2, in particular through the motif LXCXE in CR2. These interactions are required for E1A to prevent G1 arrest upon co-expression of CKIs. We show here that mutating either of two conserved motifs adjacent to LXCXE in CR2, GFP and SDDEDEE, also impairs the ability of E1A to overcome G1 arrest by p16 or p27. Strikingly, however, these mutations affect neither the association of E1A with pRb, p07 and p130, nor its ability to derepress E2F-1 transcriptional activity in transient transfection assays. One of the EIA mutants, however, is defective in derepressing several endogenous E2F target genes in the presence of p16 or p27. Thus, CR2 possesses an essential function besides pRb-binding. We speculate that this function might be required for the full derepression of E2F-regulated genes in their natural chromatin context.

Adenovirus E1A Proteins↗

A longitudinal examination of the transition into senior high school for adolescents from urban, low-income status, and predominantly minority backgrounds.

The current 6-year study investigates the impact of the elementary (K-8)-to-high school (9-12) transition on the school completion outcomes of 107 adolescents from urban, minority, low-income status backgrounds. Descriptive findings provide a longitudinal profile of students' enrollment status throughout high school. Students who had graduated or were Active in the school system at the end of the study evidenced more marked change in perceptions of social support following the transition to the ninth grade compared to Inactive students, dropouts, who evidenced little change. With respect to academic performance, while both groups evidenced declines following the transition and failed to recover sustained losses, Inactive students declined more sharply in grades and attendance. Findings are discussed in terms of the mixed support for the transitional life events perspective. In addition, study limitations and directions for future research are discussed, including variables that should be considered in research with the targeted group.

Adaptation, Psychological↗

CD4+ and CD8+ T lymphocyte regeneration after anti-retroviral therapy in HIV-1-infected children and adult patients.

Previous studies have shown a slow recovery of naive CD4+ T cell counts after anti-retroviral therapy in HIV-1-infected adults, which is in accordance with thymus atrophy after puberty. Here we investigate whether or not different patterns of naive CD4+ and CD8+ T cell repopulation are present in adult and child patients undergoing anti-retroviral treatment. Thus, 25 adults under highly active anti-retroviral therapy and 10 children under combined anti-retroviral therapy were retrospectively analysed for T cell subpopulations at baseline (T0) and around week 12 (T1) and week 24 (T2) of anti-retroviral treatment. Mean serum HIV-1 RNA levels dropped in both groups. Recovery of T cells in adults was characterized by a heterogeneous response between patients, with only 44% of them increasing their naive CD4+ and CD8+ T cell counts at T1, and changes in mean total CD4+ T cells were mainly shaped by memory cells. Otherwise, children were characterized by an early increase in naive T cells. Thus, at T1, all children analysed had a strong rise in CD4+ (from 389 +/- 116 to 569 +/- 121 cells/microl; P < 0.01), and nine out of 10 also in naive CD8+ T cells (from 244 +/- 58 to 473 +/- 85 cells/microl; P < 0.05). However, no significant correlation between age and naive repopulation was observed (P = 0. 22) in children. Thus, children had the earlier and greater increases in naive T cell subsets than adults, probably due to a more active thymus, with the potential for immune reconstitution when HIV-1 replication is controlled.

Acquired Immunodeficiency Syndrome↗

Evaluation of LR white resin for histology of the undecalcified rat tibia.

Histology of plastic embedded undecalcified bone represents a challenging problem to the histotechnologist. We outline here an exploration of LR White resin as a suitable medium for histologic study of undecalcified rat tibia. A procedure was developed for light microscopy of rat tibia embedded in LR White and sectioned by sawing-grinding technics. The specimens were fixed in 10% neutral buffered formalin or alcohol-acetic acid-formol, dehydrated in ethanol, defatted in chloroform followed by resin infiltration and heat-curing of embedded blocks. The procedure of dehydration, defatting, infiltration, and polymerization can be completed within 10 days. Cold curing with accelerator provided by the manufacturer did not yield superior results compared to blocks cured with heat. Thick sections were obtained using a diamond wire saw, attached to plexiform slides, then ground and polished. Surface staining with Von Kossa silver reagent or toluidine blue revealed satisfactory morphological preservation of the mineralized bone sections. Artifacts like small bubbles appeared occasionally and could not be avoided despite prolonged infiltration or cold curing of blocks. Our method is relatively simple for base-line histologic study of rat tibia. The method offers advantages such as easy adaptability, reliable stainability, contrast, and resolution of bone architecture and marrow cells. Two other embedding media, Micro-Bed resin and Unicryl, were also tested, but produced inferior results.

Acrylic Resins↗

Identification of cation-independent mannose 6-phosphate receptor/insulin-like growth factor type-2 receptor as a novel target of autoantibodies.

Two human monoclonal autoantibodies, B-33 and B-24, were generated from the B cells of a patient with scleroderma. Both monoclonal antibodies (mAbs) were composed of mu and lambda chains, and recognized cytoplasmic vesicular structures by indirect immunofluorescence on Hep-2 cell line slides, although mAb B-24 showed an additional diffuse cytoplasmic staining pattern. By Western blot, mAb B-24 exhibited a polyreactive-like binding pattern, whereas mAb B-33 failed to recognize any electroblotted Hep-2 antigen. The polyreactive versus monospecific behaviour of mAbs B-24 and B-33 was further confirmed by enzyme-linked immunosorbent assay (ELISA) with a variety of foreign and autoantigens. The N-terminal sequence of a protein band isolated by affinity chromatography with mAb B-33 was identical to that of cation-independent mannose 6-phosphate receptor (CI-MPR), also known as the insulin-like growth factor type-2 receptor (IGF-2R). Immunofluorescence experiments on Hep-2 cell line slides demonstrated a striking co-localization between the staining pattern exhibited by these mAbs and the pattern obtained using a goat anti-CI-MPR serum, indicating the recognition by B-24 and B-33 of a structure located predominantly in late endosomes. Sequence analysis of the V-region gene segments of B-33 and B-24 showed both to be identical, except for the existence of a point mutation in B-33 located in the H-complementarity-determining region 3 (H-CDR3) (position 100D), which produces a non-conservative replacement of Gly by Ser. This single replacement appears to be responsible for the dramatic change in reactivity of human mAb B-33. The data shown here provide new evidence of the critical role played by the H-CDR3 region in distinguishing a polyspecific from a monospecific antibody. A population study demonstrated the existence of immunoglobulin G (IgG) reactivity against CI-MPR/IGF-2R in serum specimens from five individuals with different pathological conditions, thus indicating that this molecule is a potential target for the human autoimmune response.

Amino Acid Sequence↗

Lack of beneficial effect of COX-2 inhibitors in an experimental model of colitis.

Expression of the COX-2 enzyme has been reported in animal models of inflammatory bowel disease (IBD) as well as in patients affected by ulcerative colitis and Crohn's disease. Recently, selective inhibitors of COX-2 have become available. In this study we have evaluated three highly selective COX-2 inhibitors, NS-398, SC-58125 and PD-138387, on the trinitro-benzene sulfonic acid (TNBS) model of colitis in rats. Daily oral administration of the three compounds evaluated up to a dose of 100 mg/kg failed to significantly modify any of the parameters evaluated. Our data show that despite their potent extraintestinal antiinflammatory activity, COX-2 inhibitors do not seem to have any beneficial effect in TNBS colitis and raise the question whether this therapeutic approach would be beneficial in patients with IBD.

Animals↗