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Biomedical subjects

J A Gómez

Publications and source records attributed to J A Gómez.

At least 19 recordsLinked to original sources
PubMed2005

Effect of radial-electric-field polarity on wire-array Z-pinch dynamics.

The formation of plasma in wire-array Z-pinch experiments was found to depend upon the polarity of the radial-electric field near the wires. Reversing the radial-electric field midway along the length of an array resulted in the ablation rate of one-half of the array being reduced by 50%, significantly delaying the start of its implosion and altering its acceleration towards the axis. The observed phenomena cannot be explained by the standard magnetohydrodynamic models of array behavior, suggesting that effects such as electron emission may be important, especially during wire initiation.

Journal Article↗
PubMed2005

Influence of disodium malate on microbial growth and fermentation in rumen-simulation technique fermenters receiving medium- and high-concentrate diets.

Two incubation trials were carried out with the rumen-simulation technique (RUSITEC). In each trial, four vessels received a diet of grass hay and concentrate (600 and 400 g/kg DM, respectively; diet F), and the other four were fed a diet composed of concentrate and barley straw (900 and 100 g/kg DM, respectively; Diet C). Vessels were given 20 g of the corresponding diet daily, and half of them were supplemented with disodium malate to achieve a final concentration of 6.55 mM. There were no effects (P>0.05) of malate either on pH or on the daily production of NH3-N, but malate treatment increased (P<0.05) DM, neutral detergent and acid detergent fibre disappearance after 48 h incubation. The daily production of propionate and butyrate increased (P<0.001), and the ratio CH4:volatile fatty acids decreased (P<0.001) by supplementing both diets with malate. Whereas adding malate to the F diet produced an increase in acetate production (P=0.011) and the growth of solid-associated micro-organisms (P=0.037), no effects (P>0.05) were observed for diet C. For both diets, there were no differences (P>0.05) between treatments in the daily flow of liquid-associated micro-organisms measured using (15)N as a microbial marker. These results indicate that malate stimulated the in vitro fermentation of both diets by increasing the apparent disappearance of the diet and decreasing the ratio of CH4:volatile fatty acids, but a greater response was observed with diet F. If these results are confirmed in vivo, malate could be used as a feed additive for ruminants fed diets containing medium proportions of forage (i.e. dairy animals) and not only in animals fed high-concentrate diets, as has so far been proposed.

Acetates↗
PubMed2004

Lactation under induced five-month delay reproduction in Iberian red deer (Cervus elaphus hispanicus).

In Iberian deer, calf birth date affects both milk production and composition, as well as the weight change of hind during lactation and calf growth. This study examines a five-month induced delay in calving (autumn group) in a group of 19 Iberian hinds compared to a group of 13 standard calving hinds (spring group). Fertility in the autumn group was half that of the spring one. From the former, a further two calves out of six died before or soon after birth. Successfully lactating hinds showed a greater concentration in protein, fat and lactose (P < 0.001), but did not differ from spring group in total milk yield, calf gain or weight change of hinds during lactation. However, after correcting for the greater calf or hind body weight at calving of the autumn group, this group showed lower values for these variables than the spring group. Results show that at least in Iberian deer, counter-season reproduction is possible, and that the effects on lactation variables are similar to those of a natural delay in calving.

Analysis of Variance↗
PubMed2001

Surveillance for rotavirus in Argentina.

Group A rotaviruses are the major cause of severe gastroenteritis in young children worldwide. Because rotavirus vaccination appeared imminent, a nationwide surveillance program was organized between October 1996 and October 1998 in the largest Argentine cities. Surveillance for disease burden, rotavirus detection, and rotavirus typing was undertaken at nine locations. Results showed rotavirus to be associated with 42% of diarrhea admissions. Although the prevalent G types changed from year to year, common G types were found in 96% of the cases and were usually associated with common P types. Uncommon G types, G9 and G5, were found at low prevalence and uncommon G/P combinations occurred at almost every study site. These data suggest that a rotavirus vaccine could substantially decrease the rotavirus disease burden in Argentina, but that introduction of a vaccine should be accompanied by a concurrent surveillance system.

Age Distribution↗
PubMed2000

Phakomatous choristoma: a case report and review of the literature.

Phakomatous choristoma is a rare congenital lesion of the eyelid that can be clinically and/or histologically mistaken for a cyst, cutaneous adnexal neoplasm, or an ocular adnexal oncocytoma. Only 13 such cases have been previously described, mostly in the English language ophthalmic literature. Zimmerman reported the first case in 1971 and proposed the lesion to be of lenticular anlage origin, a theory that has been widely accepted. We report an additional case occurring in an 8-week-old male infant with a firm nodule of the right lower eyelid that was present since birth. A 15 x 12 x 2 mm circumscribed solid nodule with a homogenously white cut surface was surgically excised. Histologically, this lesion was comprised of cuboidal cells forming cystically dilated and irregularly branched ducts and cords within a densely fibrotic stroma. Also present were eosinophilic basement membranelike material, psammoma body-like calcifications and intraluminal degenerated ghost cells. The immunohistochemical profile of the epithelial cells included strong immunoreactivity for vimentin, focal weak staining for S-100, and negative staining for cytokeratin, epithelial membrane antigen, synaptophysin, and chromogranin. The irregularity of the ducts and cords of epithelial cells within the densely fibrotic stroma resembled an infiltrative neoplasm of cutaneous adnexal or lacrimal duct origin. However, the site of involvement, the peculiar basement membrane material, ghost cells, and immunohistochemical profile were features that helped to distinguish phakomatous choristoma from an infiltrative carcinoma. The correct identification of this lesion is essential to avoid an aggressive surgical excision, thus sparing the eyelid and lacrimal system. The purpose of this article is to bring attention to this rare entity, because it has not been described in either the dermatology or dermatopathology literature and furthermore, is not mentioned in any of the major dermatopathology texts.

Choristoma↗
PubMed2000

Modulation of myogenic differentiation in a human rhabdomyosarcoma cell line by a new derivative of 5-fluorouracil (QF-3602).

The in vitro study of mechanisms involved in drug-induced maturation has made it possible to use differentiation-based therapy in clinical practice. The goal of this new therapy is the development of specific agents to induce cancer cells to stop proliferating and express characteristics of normal cells. Recently, by structural modifications of 5-fluorouracil (5-FU), we synthesized a new pyrimidine acyclonucleoside-like compound, 1-¿[3-(3-chloro-2-hydroxypropoxy)-1-methoxy]propyl¿-5-fluorouracil (QF-3602), which showed in rhabdomyosarcoma cells a low toxicity and time-dependent growth inhibition. In this work, we compared the degree of myogenic differentiation of RD rhabdomyosarcoma (RMS) cells after treatment with QF-3602 and 5-FU. Scanning and transmission electron microscopy (SEM and TEM) and immunocytochemical analyses showed that QF-3602 induced the appearance of myofilaments along the myotube-like giant RD cells, an increase in fibronectin and a decrease in vimentin expression. In contrast, only minor changes were observed with 5-FU. Moreover, polymerase chain reaction (PCR) analyses showed that QF-3602 did not induce overexpression of the mdr 1 gene, a resistance mechanism that frequently appears in classical cytotoxic therapy in these tumors. Compounds obtained by structural modifications of 5-FU may be useful in differentiation therapy as a new approach to the treatment of RMS.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

The neisserial 37 kDa ferric binding protein (FbpA).

The ferric binding protein (FbpA) is one of the major proteins regulated by the level of environmental iron in the genus Neisseria. Its conservation in all species of pathogenic Neisseria has been demonstrated, and the possible role that it plays in the iron uptake mechanisms in these bacteria has been postulated. Similar proteins in Haemophilus influenzae (HitA) and in Serratia marcescens (SfuA) have been described, but relationships with the meningococcal FbpA could not be proven. Although supposedly periplasmic, the exact location of FbpA remains controversial because some molecules, or parts of them, have been found exposed to the bacterial outer surface. The DNA sequence downstream of the fbpA gene has been recently analysed, finding an operon composed of three open reading frames: fbpA, encoding for FbpA; fbpB, that codifies a cytoplasmic permease, and fbpC, that contains the information for a nucleotide binding protein. These proteins would form an iron transport system through the periplasmic space. FbpA is highly antigenic in mice when injected in purified form, shows intraspecies and interspecies antigenic homogenicity, and specific anti-FbpA antibodies are fully cross-reactive; nevertheless, the in vivo induction of anti-FbpA antibodies in man is still polemical. Recent studies reveal that the purified FbpA induces a fair response of bactericidal antibodies in mice.

Bacterial Outer Membrane Proteins↗
PubMed1999

GR-891: a novel 5-fluorouracil acyclonucleoside prodrug for differentiation therapy in rhabdomyosarcoma cells.

Differentiation therapy provides an alternative treatment of cancer that overcomes the undesirable effects of classical chemotherapy, i.e. cytotoxicity and resistance to drugs. This new approach to cancer therapy focuses on the development of specific agents designed to selectively engage the process of terminal differentiation, leading to the elimination of tumorigenic cells and recovery of normal cell homeostasis. A series of new anti-cancer pyrimidine acyclonucleoside-like compounds were designed and synthesized by structural modifications of 5-fluorouracil, a drug which causes considerable cell toxicity and morbidity, and we evaluated their applicability for differentiation therapy in human rhabdomyosarcoma cells. We tested the pyrimidine derivative GR-891, (RS)-1-[[3-(2-hydroxyethoxy)-1-isopropoxy]propyl]-5-fluorouracil, an active drug which shows low toxicity in vivo and releases acrolein which is an aldehyde with anti-tumour activity. Both GR-891 and 5-fluorouracil caused time- and dose-dependent growth inhibition in vitro; however, GR-891 showed no cytotoxicity at low doses (22.5 micromol l(-1) and 45 micromol l(-1)) and induced terminal myogenic differentiation in RD cells (a rhabdomyosarcoma cell line) treated for 6 days. Changes in morphological features and in protein organization indicated re-entry in the pathway of muscular maturation. Moreover, GR-891 increased adhesion capability mediated by the expression of fibronectin, and did not induce overexpression of P-glycoprotein, the mdr1 gene product, implicated in multidrug resistance. New acyclonucleoside-like compounds such as GR-891 have important potential advantages over 5-fluorouracil because of their lower toxicity and their ability to induce myogenic differentiation in rhabdomyosarcoma cells. Our results suggest that this drug may be useful for differentiation therapy in this type of tumour.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Immunohistochemical profile of myogenin and MyoD1 does not support skeletal muscle lineage in alveolar soft part sarcoma.

BACKGROUND: The histogenesis of alveolar soft part sarcoma remains elusive. Myogenic origin is favored, although conflicting data on immunohistochemical demonstration of muscle-associated markers exist. Myogenin and MyoD1, transcription factors of the myogenic determination family, have crucial roles in commitment and differentiation of mesenchymal progenitor cells to myogenic lineage and in maintenance of skeletal muscle phenotype. Their immunohistochemical detection is specific in characterization of rhabdomyosarcoma. METHODS: Antibodies for myogenin, MyoD1, desmin, and muscle-specific actin were employed on a large series of cases (n = 19) of formalin-fixed, paraffin-embedded alveolar soft part sarcoma. RESULTS: Minimal scattered nuclear staining was seen with myogenin. All cases had pronounced, nonspecific granular cytoplasmic immunostaining with MyoD1; nuclei were negative. All tumors were negative for desmin and muscle-specific actin. Ultrastructural study in 10 cases failed to reveal features of skeletal muscle differentiation. CONCLUSIONS: Cytoplasmic staining with MyoD1 in alveolar soft part sarcoma may correspond to cross-reactivity with an undetermined cytoplasmic antigen. The lack of immunostaining with myogenin, MyoD1, desmin, and muscle-specific actin provides evidence against a myogenic origin for alveolar soft part sarcoma.

Actins↗
PubMed1999

[Rotavirus diarrhea. Impact in a pediatric hospital of Buenos Aires].

Anticipating the use of the rotavirus vaccine, we performed this study in order to estimate the rotavirus disease burden in a pediatric hospital. We studied 648 children < 3 years of age between September/97 and August/98, assisted at the Outpatient Diarrhea Unit, or hospitalized due to acute diarrhea in our Hospital. We found rotavirus associated to 36% of the diarrhea cases studied in the Outpatient Clinics, and in 45% of the hospitalized children. We estimate the assistance of 1674 rotavirus diarrheas per year in the Outpatient Clinics, but only 14 of them required hospitalization. The study describes a peak of rotavirus diarrheas between March and June, and another peak of rotavirus-negative diarrheas between January and March (probably due to bacterial diarrheas). Rotavirus disease presented a higher frequency between 6 to 23 months of age; only 10% of the 233 rotavirus cases occurred in children older than 24 months and 13% in infants less than 6 months of age. The situation described is significant because the recently licensed rotavirus vaccine is being used in 3 doses at 2, 4 and 6 months and could have prevented most of the rotavirus cases observed during this study.

Acute Disease↗
PubMed1998

Effect of adjuvants in the isotypes and bactericidal activity of antibodies against the transferrin-binding proteins of Neisseria meningitidis.

Twenty-eight Neisseria meningitidis strains of different serogroups, serotypes, and TbpB isotypes were used to test the effect of five adjuvant formulations on the immune response to the meningococcal transferrin-binding proteins (Tbps) in mice. Levels of anti-Tbps antibodies were relatively low when purified TbpA-TbpB complexes were used for immunization, those obtained with the RAS adjuvant being the highest, and the isotype distribution reveals a prevalence of the non-bactericidal IgG1. Specific anti-Tbps antibody levels were five to 125 times higher immunizing with whole outer membrane vesicles, with bactericidal isotypes prevailing, which suggests that presentation of these antigens in their natural conformation is crucial to elicit a good response. Nevertheless, bactericidal activity did not correlate with these characteristics, confirming that it must be also influenced by other factors, and direct evaluation of the killing ability is necessary to draw conclusions about the efficacy of antigens or adjuvants in vaccine design.

Adjuvants, Immunologic↗
PubMed1998

Cooperation between the components of the meningococcal transferrin receptor, TbpA and TbpB, in the uptake of transferrin iron by the 37-kDa ferric-binding protein (FbpA).

Meningococcal TbpAB complexes TbpA, TbpB and FbpA were purified and used to study their role in the uptake of iron from transferrin to FbpA. Purification was achieved by affinity chromatography techniques, yielding homogeneous, non-denatured and functional material. TbpA could not be separated from TbpB and had to be purified from a TbpB-defective mutant strain. FbpA was able to bind iron from transferrin only when TbpAB complexes, TbpA and/or TbpB, were also present during the interaction. The highest uptake efficiences were obtained with TbpAB complexes or TbpA/TbpB mixtures. We conclude that the TbpA and TbpB molecules form true functional transferrin receptors, that FbpA is able to take iron directly from transferrin when in the presence of the components of the receptor, and that both Tbps are necessary for an optimal operation of the uptake system.

Bacterial Proteins↗
PubMed1998

Pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor humanized monoclonal antibody R3 in rats.

The pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor (anti-hEGF-r) humanized monoclonal antibody (MAb) R3 was investigated following intravenous injection in normal Wistar rats. Serum disappearance curves were best fit by a two-compartment model having a mean distribution half-life (t 1/2alpha) of 0.250 h and a mean elimination (t 1/2beta) of 13.89 h. Among the various organs, a little accumulation of the radiolabeled antibody was found only in kidneys. Biodistribution and dosimetry studies in humans were performed by extrapolation of the animal data to humans. Absorbed dose to normal organs and the remainder of the whole body were estimated using the medical internal radiation dose formula, and dose contributions from radioactivity in transit through the gastrointestinal tract were estimated using a compartment model. Extrapolated values of radiation absorbed dose to normal organs in rads per millicurie administered were whole body, 0.0085; lower large intestine wall, 0.0898; small intestine, 0.0530; upper large intestine wall, 0.0731; and kidneys, 0.0455. The effective dose equivalent predicted was 0.0162 rem/mCi and the effective dose was found to be 0.015 rem/mCi. On the basis of the pharmacokinetics, biodistribution and internal radiation dosimetry information obtained in this study, a diagnostic phase I clinical trial with 99mTc-labeled humanized MAb R3 conjugate in patients should be supported.

Animals↗
PubMed1998

Analysis of TbpA and TbpB functionality in defective mutants of Neisseria meningitidis.

Iron uptake analysis suggested that the Neisseria meningitidis transferrin (Tf) binding proteins, TbpA and TbpB, form only one type of receptor complex. Mutants defective in the synthesis of either TbpA or TbpB, but not defective in both proteins, can bind Tf, suggesting that both proteins are surface exposed and function in Tf binding. Also, iron uptake from Tf into the meningococci did not require the presence of both Tbps. The TbpB-defective mutant incorporated c. 37% of the iron taken up by the wild-type strain, but this was insufficient for bacterial growth. The TbpA-defective mutant incorporated c. 50% of the iron taken up by the wild-type strain and was able to grow with Tf as the only iron source. Mouse antibodies specific for TbpA were able to block c. 70% of the iron uptake from Tf in the wild-type strain, whereas they blocked only 22% of iron uptake in the TbpB-defective mutant and did not block uptake in the TbpA-defective strain. These results emphasise that TbpA should be considered in future vaccine trials in which iron-restricted proteins are to be included in the vaccine formulation.

Antibodies, Blocking↗
PubMed1998

Bactericidal activity of antibodies elicited against the Neisseria meningitidis 37-kDa ferric binding protein (FbpA) with different adjuvants.

The 37-kDa ferric binding protein, FbpA, from three Neisseria meningitidis strains was purified to homogeneity with iron-affinity chromatography and used for immunisation of mice employing four different adjuvants: aluminium hydroxide, Freund's, the saponin Quil-A, and a Ribi adjuvant system (RAS). Controls immunised without adjuvant were also included. All sera obtained were monospecific for the meningococcal FbpA, with antibody titres higher when RAS and Quil-A were used (256), PBS resulting in titres similar to those of Freund's (64), and, surprisingly, with no antibodies elicited when aluminium hydroxide, the only approved adjuvant for use in humans, was used. All anti-FbpA sera bound to intact meningococcal cells, showing a complete cross-reactivity, but the bactericidal activity of anti-FbpA antibodies, demonstrated for the first time in this work, was low (32% of killing with the homologous strain), and the analysis of immunoglobulin isotypes showed that the non-bactericidal IgG1 was predominant. The results confirm that the FbpA is surface-exposed, antigenic, and able to elicit bactericidal antibodies, although, in the conditions and with the adjuvants tested, killing efficacy was low and cross-killing was very variable, not supporting the inclusion of this protein in vaccine formulations. Nevertheless, given the high conservation of the FbpA in the genus Neisseria, its surface exposure and its antigenicity, studies on immunisation with peptides corresponding to the exposed epitopes and/or new adjuvant systems could improve the bactericidal response to this protein, making it suitable for vaccine development.

Adjuvants, Immunologic↗
PubMed1998

Anticipating rotavirus vaccines: review of epidemiologic studies of rotavirus diarrhea in Argentina.

Rotavirus is the most common cause of severe diarrhea in children worldwide, and vaccines currently being field-tested could be available for childhood immunization in several years. To assess the rotavirus disease burden in Argentina and the value of future national surveillance for the disease, we reviewed available data on rotavirus detections reported by published and unpublished studies conducted in nine Argentine cities and by a multicenter study. Data from these studies indicated that rotavirus was detected in 20% of 5,226 specimens (within a range of 6% to 54% for different studies) from children hospitalized for diarrhea and in 9% of 6,587 specimens (within a range of 5% to 22% for different studies) from children who were outpatients, members of mixed populations (hospitalized patients and outpatients), or survey subjects in community-based studies. The hospital data showed that while rotavirus was detected throughout the year, a peak occurred during the winter months (May-July) when up to half of the children with diarrhea were found positive for rotavirus. Attempted serotyping of 294 rotavirus-positive specimens for G-protein by three laboratories was successful in 230 cases (78%); the resulting data indicated that serotype G1 was the most common (being present in 60% of the successfully serotyped specimens), followed by G2 (in 20%), G4 (in 14%), and G3 (in 5%). Based on national data for Argentina, we estimate that in 1991 there were roughly 84,500 rotavirus-associated outpatient visits (1 for every 8 births) and 21,000 hospitalizations averaging 4 days in length (1 for every 31 births), all of which entailed direct medical costs estimated at US$ 27.7 million. These preliminary data show that the rotavirus disease burden in Argentine children is extensive and could be decreased by a safe and effective vaccine. Further surveillance is needed to improve our understanding of the epidemiology and distribution of rotavirus strains in Argentina, to more accurately assess the cost-effectiveness of a rotavirus vaccine program, and to indicate what methods might best be used to monitor such a program's impact.

Argentina↗