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Biomedical subjects

J Blanco

Publications and source records attributed to J Blanco.

At least 91 records · Page 5Linked to original sources

Anti-human immunodeficiency virus activity of novel aminoglycoside-arginine conjugates at early stages of infection.

Conjugates of L-arginine with aminoglycosides have already been described as potent in vitro inhibitors of the HIV-1 Tat-trans-activation responsive element interaction. The polycationic nature of these agents leads us to suggest that they may be active against HIV-1 replication by inhibiting earlier stages of the virus life cycle. We have found that R4K and R3G, kanamycin A, and gentamicin C, conjugated with arginine, inhibited HIV-1 NL4-3 replication at EC50 values of 15 and 30 microM for R3G and R4K, respectively, without a detectable tonic effect on MT-4 cells at concentrations higher than 4000 and about 1000 microM, respectively. Both compounds inhibited the binding of a monoclonal antibody (12G5) directed to CXCR4 as well as the intracellular Ca2+ signal induced by the chemokine SDF-1alpha on CXCR4+ cells, suggesting that aminoglycoside-arginine conjugates interact with CXCR4, the coreceptor used by T-tropic, X4 strains of HIV-1. On the other hand, CB4K, a conjugate of kanamycin A with gamma-guanidinobutyric acid, structurally similar to R4K, failed to display any anti-HIV activity of CXCR4 antagonist activity. An HIV-1 strain that was made resistant to the known CXCR4 antagonist AMD3100 was cross-resistant to both R4K and R3G. However, unlike SDF-1alpha and R4K, R3G inhibited the binding of HIV-1 to MT-4 cells. Aminoglycoside-arginine conjugates inhibit HIV replication by interrupting the early phase of the virus life cycle, namely virus binding to CD4 cells and interaction with CXCR4. R3G and R4K may serve as prototypes of novel anti-HIV agents and should be further studied.

Anti-HIV Agents↗

Toxigenic Escherichia coli isolated from pigs in Argentina.

The presence of porcine toxigenic E. coli (ETEC, VTEC) in 28 piggeries (5% of total) of the central and northeast region of Argentina was studied for a better understanding of the epidemiology of porcine strains. Samples were taken by rectal swabs from healthy piglets and from those with diarrhoea, in addition to their dams. Between 5-10 colonies were isolated from each one of 223 animals sampled from 1992 to 1997. By using specific primers each strain was screened by PCR for VT1, VT2all, VT2e, STIa, and LTI toxin genes. Only strains positive for any of the toxins mentioned above were screened for STb. Their O serogroups were determined by agglutination. All of the above enterotoxins and verocytotoxins were found in E. coli isolated from the animals. The STIa gene was detected in E. coli isolated from 27/127 piglets with diarrhoea, in comparison with LTI (4/127 pigs). No toxin gene was amplified from E. coli isolated from either healthy piglets or their dams. When strains isolated from 48 piglets without diarrhoea but showing delayed growth were analysed by PCR, their toxin profile was determined to be VT1 (1/48 piglets), VT2all (5/48), STIa (1/48), LTI (3/48) and VT2e (3/48). Serogroup O64 prevailed among ETEC; O138 prevailed for ETEC/VTEC strains. This is the first extensive study regarding porcine toxigenic E. coli in Argentina and constitutes an important database for the implementation of prevention measures.

Agglutination Tests↗

Administration of IgG Fc fragments prevents glomerular injury in experimental immune complex nephritis.

Most human nephritis is due to glomerular deposition and/or formation of immune complexes (IC). In cultured mesangial cells, Fc receptor stimulation induces proliferation, matrix synthesis, and release of several mediators implicated in the initiation and progression of glomerular injury. Since Ig Fc fragments in vitro modified these phenomena, we studied the effects of systemic administration of IgG Fc fragments on the evolution of experimental IC nephritis. Fc fragment injection (1 mg/day i.p.) to rats with ongoing nephritis (proteinuria 20-50 mg/24 h vs 9 +/- 0.2 mg/24 h in controls) markedly ameliorates proteinuria, renal function, and morphological renal lesions. This was accompanied by a reduction in the renal synthesis of chemokines (monocyte chemoattractant protein-1, IFN-inducible protein-10, and cytokine-induced neutrophil chemoattractant-1), matrix proteins, and growth factors (platelet-derived growth factor, and TGF-beta), and in the activity of transcription factors. The treatment did not affect the glomerular deposition of IgG IC and complement C1q. In contrast, a decrease in the renal expression and production of C3 was observed without changes in serum complement levels. In vitro, very low complement consumption and no C3b covalent interaction were observed with Fc fragments, confirming that they did not modify systemic complement activity. These results indicate that the administration of Fc fragments prevents the development of glomerular damage in an aggressive model of proliferative glomerulonephritis through mechanisms involving a reduced local generation of complement, chemokines and growth factors. Modulation of IC-mesangial cell interaction by Fc fragment administration could represent a new approach to the treatment of severe immune nephritis.

Animals↗

Analysis of chromosome abnormalities in sperm and embryos from two 45,XY,t(13;14)(q10;q10) carriers.

Robertsonian translocation t(13q14q) is studied in sperm and embryos of two couples undergoing preimplantation genetic diagnosis (PGD) in which both males are carriers of the translocation. It is already known that the chances of achieving pregnancy for a translocation carrier are directly linked to the number of normal or balanced embryos available for replacement. In our work it was found that the frequency of balanced spermatozoa was almost identical in both patients (74 and 77%), and after PGD, the frequencies of abnormal embryos caused by the translocation were also similar. Sperm chromosome analysis in translocation carriers can provide a reasonable basis for estimating a baseline of chromosome abnormalities to be found in embryos during an assisted reproductive cycle. However, individual factors not linked to the translocation can also produce other chromosome abnormalities (mosaicism, haploidy, polyploidy) and may compromise the chances of achieving a viable pregnancy.

Adult↗

Interchromosomal effects for chromosome 21 in carriers of structural chromosome reorganizations determined by fluorescence in situ hybridization on sperm nuclei.

We have used dual color fluorescence in situ hybridization (FISH) on decondensed sperm heads from four carriers of structural chromosome reorganizations, viz. t(3;15), t(Y;7), t(13;22) and inv(9), to assess the possible existence of an interchromosomal effect (ICE) on the segregation of chromosome 21. In the carriers of t(Y;7), t(13;22) and inv(9), all results were within the limits described in controls. A highly significant increase (P<0.0001) of disomy 21 (1.90% v 0.37%), which could be considered as a positive ICE, was observed in the t(3;15) carrier. Significantly higher percentages (P<0.0001) of diploid sperm (5.71% v. 0.27%) were also observed in this patient. Our results suggests that the occurrence of an ICE may depend on the reorganization and on the chromosome and chromosome regions involved, resulting in a particular meiotic behaviour (presence of unsynapsed regions, preferential meiotic configurations) that could lead to the observed increase in chromosome 21 disomies. Further studies with this technical approach in a wide range of structural reorganizations could help to elucidate the actual occurrence of ICEs.

Adult↗

Solar photocatalytic mineralization of commercial pesticides: acrinathrin.

A comparative study of the degradation of commercial acrinathrin spiked in water using TiO2 photocatalysis and photolysis under sunlight was performed. Samples were analysed by liquid chromatography-diode array detector (HPLC-DAD) and gas chromatography-ion trap-mass spectrometric detector (GC-ITMS). Additional total organic carbon (TOC) analyses were carried out to evaluate the mineralisation rates. One photoproduct, 2-phenoxy benzaldehyde, was unequivocally identified and evaluated by GC-ITMS during the processes. Although acrinathrin is almost destroyed when exposed to irradiation for more than 400 h, photocatalysis with TiO2 noticeably reduced degradation to a few hours. In this case, with the additional presence of peroxydisulphate, in less than 2 h acrinathrin is completely destroyed. Mineralisation of acrinathrin, without catalyst, was only around 50% after 400 h of irradiation.

Catalysis↗

Splenic abscesses caused by Actinomyces meyeri in a patient with autoimmune hepatitis.

We report a case of actinomycosis with uncommon localizations that was due to Actinomyces meyeri. Although penicillin is the standard treatment for this condition, our patient was treated successfully with imipenem. Actinomyces organisms are important constituents of the normal flora of mucous membranes and are considered opportunistic pathogens; these organisms may produce infection after local trauma, surgery, or aspiration. The mains forms of actinomycosis are cervicofacial, thoracic, and abdominal; most cases are due to Actinomyces israelii, whereas other Actinomyces species are occasionally implicated. Actinomycosis usually occurs in immunocompetent persons, but may occur in persons with diminished host defenses.

Abdominal Abscess↗

Virulence genotypes and serotypes of verotoxigenic Escherichia coli isolated from cattle and foods in Argentina. Importance in public health.

Virulence factors of Verotoxin-producing Escherichia coli (VTEC) strains isolated from hamburgers and ground beef were studied in Argentina by PCR. Their virulence profiles were correlated with those corresponding to strains isolated from calves and adult cattle. Most virulent profiles (VTs+ eae+ Mp+) were present in E. coli from healthy and diarrheic calves corresponding to O5:H-, O5:H27, O20:H?, O26:H11, O38:H?, O103:H-, O103:H2, O111:H-, O118:H16, O165:H-serotypes. The presence of the eae gene was significantly more frequent among VTEC strains isolated from calves (20/26; 76%) than from adult cattle (1/39; 2.5%) (p < 0.005). VT2+ eae- E. coli was prevalent in foods and adult cattle at slaughterhouse. The prevalence of the eae gene was similar between VTEC strains isolated from meat (0/21) and adult cattle (1/39; 2.5%) which constitutes the main population processed at slaughterhouses in Argentina. Serotyping showed that VTEC strains were distributed among 31 serotypes, some of which (O20:H19, O91:H21, O113:H21, O116:H21, O117:H7, O171:H2, OX3:H21) were shared between bovine and food strains. These O serogroups have been isolated from cases of haemorrhagic colitis (HC) and haemolyticuraemic syndrome (HUS) in humans in several continental European countries. This study confirms the role of cattle as a reservoir of many VTEC serotypes other than O157:H7 and represents a base for future diagnostic, prevention and control strategies of EHEC in this country. In addition, this study affirms the advantages of PCR-based screening of E. coli isolates given the finding of so many verotoxin-producing strains.

Adhesins, Bacterial↗

Evaluation of the putative role of C-C chemokines as protective factors of HIV-1 infection in seronegative hemophiliacs exposed to contaminated hemoderivatives.

BACKGROUND: Overproduction of beta-chemokines and genetic variations in chemokine receptors have been correlated with protection against infection by HIV-1 or slow progression to AIDS in infected individuals. STUDY DESIGN AND METHODS: The protective role of chemokines and their receptors was evaluated in a group of seven uninfected (seronegative) hemophiliacs transfused with hemoderivatives presumably contaminated with HIV-1. This group was compared to a group of seven infected (seropositive) hemophiliacs and a group of healthy donors (controls). The CD4+ cell count, intracellular cytokine levels, beta-chemokine levels in plasma, beta-chemokine production by PBMNCs, and expression of chemokine receptors CCR5 and CXCR4 in CD4+ cells were evaluated. The occurrence of protective genotypes in CCR5, CCR2b, and SDF-1 (stromal cell-derived factor 1) genes and susceptibility to infection by HIV-1 were also studied. RESULTS: Significant differences in the production and plasma levels of beta-chemokines among the three groups were not detected. Lower IL-2 and IFN-gamma production was observed in the uninfected exposed hemophiliacs than in the controls. Genetic analysis of CCR5, CCR2b, and SDF-1 showed several polymorphisms associated with resistance in some HIV-exposed uninfected hemophiliacs. However, these genetic features cannot explain the protection of all exposed hemophiliacs. In fact, only one patient, carrying two copies of CCR5 from which 32 bp was deleted, showed low CCR5 expression and low susceptibility to infection by a CCR5-using HIV-1 strain. In contrast, PBMNCs from all other individuals supported infection in vitro by both CCR5- and CXCR4-using HIV-1 strains. CONCLUSION: It is not possible to assign to beta-chemo-kines and polymorphisms in chemokine receptors a central role in preventing HIV-1 infection. Natural protection against HIV-1 infection is likely to be due to a multiplicity of factors.

Chemokines, CC↗

Outcome of bone marrow transplantation patients requiring mechanical ventilation.

OBJECTIVE: To identify outcome predictors in bone marrow transplantation (BMT) patients admitted to the intensive care unit (ICU) of The University of Texas M. D. Anderson Cancer Center who required endotracheal intubation and mechanical ventilation. DESIGN: Retrospective, comparative study. SETTING: A 16-bed medical intensive care unit in a university teaching cancer center. PATIENTS: The records of 60 consecutive BMT patients who developed respiratory failure requiring mechanical ventilation were reviewed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The most frequent complication leading to respiratory failure was pneumonia (41%) followed by diffuse alveolar hemorrhage (37%). Eighteen percent of the patients were extubated and discharged from the ICU, but only 5% were alive at 6 months. Graft vs. host disease was a predictor of a poor outcome (p < .05). Breast cancer as an underlying disease and pulmonary edema as a complication were favorable predictive factors (p < .05). Five of 26 patients with diffuse alveolar hemorrhage and four of 33 patients with pneumonia survived. We found no relationship between survival and age, gender, BMT type, or Acute Physiology and Chronic Health Evaluation II score. Prolonged mechanical ventilation (> or =15 days) and late development of respiratory failure (>30 days after BMT) were associated with poor prognosis. CONCLUSIONS: The ICU survival rate of BMT patients who developed pulmonary complications and required mechanical ventilation was 18%. Prognostic factors were described identifying patients with a substantial survival rate as well as those in whom mechanical ventilation was futile.

APACHE↗

Mitochondrial control of cell death induced by HIV-1-encoded proteins.

In most examples of physiological or pathological cell death, mitochondrial membrane permeabilization (MMP) constitutes an early critical event of the lethal process. Signs of MMP that precede nuclear apoptosis include the translocation of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria to an extra-mitochondrial localization, as well as the dissipation of the mitochondrial transmembrane potential. MMP also occurs in HIV-1-induced apoptosis. Different HIV-1 encoded proteins (Env, Vpr, Tat, PR) can directly or indirectly trigger MMP, thereby causing cell death. The gp120/gp41 Env complex constitutes an example for an indirect MMP inducer. Env expressed on the plasma membrane of HIV-1 infected (or Env-transfected) cells mediates cell fusion with CD4/CXCR4-expressing uninfected cells. After a cell type-dependent latency period, syncytia then undergo MMP and apoptosis. Vpr exemplifies a direct MMP inducer. Vpr binds to the adenine nucleotide translocator (ANT), a mitochondrial inner membrane protein which also interacts with apoptosis-regulatory proteins from the Bcl-2/Bax family. Binding of Vpr to ANT favors formation of a non-specific pore leading to MMP. The structural motifs of the Vpr protein involved in MMP are conserved among most pathogenic HIV-1 isolates and determine the cytotoxic effect of Vpr. These data suggest the possibility that viruses employ multiple strategies to regulate host cell apoptosis by targeting mitochondria.

Animals↗

The CXCR4 antagonist AMD3100 efficiently inhibits cell-surface-expressed human immunodeficiency virus type 1 envelope-induced apoptosis.

Infection by human immunodeficiency virus type 1 (HIV-1) has been associated with increased cell death by apoptosis in infected and uninfected cells. The envelope glycoprotein complex ([gp120/gp41](n)) of X4 HIV-1 isolates is involved in both infected and uninfected cell death via its interaction with cellular receptors CD4 and CXCR4. We studied the effect of the blockade of CXCR4 receptors by the agonist stromal derived factor (SDF-1alpha) and the antagonist bicyclam AMD3100 on apoptotic cell death of CD4(+) cells in different models of HIV infection. In HIV-infected CEM or SUP-T1 cultures, AMD3100 showed antiapoptotic activity even when added 24 h after infection. In contrast, other antiviral agents, such as zidovudine, failed to block apoptosis under these conditions. The antiapoptotic activity of AMD3100 was also studied in coculture of peripheral blood mononuclear cells or CD4(+) cell lines with chronically infected H9/IIIB cells. AMD3100 was found to inhibit both syncytium formation and apoptosis induction with 50% inhibitory concentrations ranging from 0.009 to 0.24 microg/ml, depending on the cell type. When compared to SDF-1alpha, AMD3100 showed higher inhibitory potency in all cell lines tested. Our data indicate that the bicyclam AMD3100 not only inhibits HIV replication but also efficiently blocks cell-surface-expressed HIV-1 envelope-induced apoptosis in uninfected cells.

Anti-HIV Agents↗

Loss of heterozygosity on the short arm of chromosome 3 in renal cancer.

3% of human cancers are renal cell carcinomas (RCC). The most common chromosome abnormality found in this tumor is loss of heterozygosity (LOH) on the short arm of chromosome 3, which suggests that there must be one or more tumor suppressor genes between 3p14 and 3p21 near the VHL gene which play a relevant role in renal cancer development. DNA from normal and tumor tissue from 40 patients at various stages of RCC was analyzed for LOH at three microsatellites mapped to 3p (3p14.1-14.3; 3p21.2-21.3 and 3p25) by polymerase chain reaction). 42.5% of the tumors studied showed LOH on at least one locus. 30% showed LOH on only one locus; 5% on two loci and 7.5% on the three loci tested. LOH occurred only on nonpapillary tumors (p = 0.03). Interestingly, all the tumors with LOH on 3p21 were >/=25 mm (p = 0.04; relative risk 1.76, confidence interval: 1.3-2.3).

Adult↗

Prospective randomized trial comparing pressure-controlled ventilation and volume-controlled ventilation in ARDS. For the Spanish Lung Failure Collaborative Group.

STUDY OBJECTIVES: To compare in-hospital mortality of patients with ARDS ventilated with either pressure-controlled ventilation (PCV) or volume-controlled ventilation (VCV) with a square-wave inspiratory flow. DESIGN: : Multicenter and randomized trial. SETTING: Twelve medical-surgical ICUs located in tertiary-care hospitals. PATIENTS: Seventy-nine patients having ARDS, as defined by the American-European Consensus Conference. INTERVENTIONS: Patients were randomly assigned to be ventilated with either PCV (n = 37) or VCV (n = 42). In both instances, inspiratory plateau pressure was limited to < or = 35 cm H(2)O. MEASUREMENTS AND RESULTS: There were no significant differences among the studied groups at the moment of randomization, although there was a trend toward greater renal failure in patients assigned to VCV. Ventilatory settings and blood gases did not significantly differ over time between the two groups. Patients in the VCV group had both a significantly higher in-hospital mortality rate than those in the PCV group (78% vs 51%, respectively) and a higher number of extrapulmonary organ failures (median, 4 vs 2, respectively). The development of renal failure during the study period was also significantly more frequent among VCV patients (64% vs 32%, respectively). Multivariate analysis showed that factors independently associated with an increased mortality rate were the presence of two or more extrapulmonary organ failures (odds ratio [OR], 4.61; 95% confidence interval [CI], 1.38 to 15.40) and acute renal failure (OR, 3.96; 95% CI, 1.10 to 14.28) but not the ventilatory mode used. CONCLUSIONS: The increased number of extrapulmonary organ failures developed in patients of the VCV group was strongly associated with a higher mortality rate. The development of organ failures was probably not related to the ventilatory mode.

Adult↗

Subtypes of intimin among non-toxigenic Escherichia coli from diarrheic calves in Brazil.

One hundred and five strains of Escherichia coli that were isolated from calves with diarrhea in the state of São Paulo, Brazil, and were negative for enterotoxins and cytotoxins, were examined for the eae gene. Four (3.8%) strains were positive by polymerase chain reaction (PCR) and were shown to produce intimin by using Western blot with specific antiserum against the conserved N-terminal region of intimin. Subtyping of the intimins was done by PCR with specific primers and by Western blot with specific antisera against the C-terminal variable region of the protein. Three of these isolates (O?:H11, O26:H-, O123:H1) produced the beta subtype of intimin, and the 4th (0103:H2) produced intimin that was not typable. The 0103:H2 and the O26:H-isolates adhered to HEp-2 cells with diffuse adherence and localized-like adherence patterns, respectively. The other strains did not adhere to HEp-2 cells. To our knowledge, this is the first report of the occurrence of a subtype of intimin described for human enteropathogenic E. coli among bovine diarrheogenic E. coli. It is also the first report from Brazil demonstrating the presence of bovine E. coli harboring the eae gene.

Adhesins, Bacterial↗

Current awareness

In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of prenatal diagnosis. Each bibliography is divided into 17 sections: 1 Books, Reviews & Symposia; 2 General Interest; 3 Normal Fetal Development; 4 Gametogenesis and Pre-implantation Diagnosis; 5 First Trimester Diagnosis; 6 Second Trimester Diagnosis; 7 Fetal Diagnosis by Ultrasound and Other Imaging; 8 Maternal Screening; 9 Screening for Carriers of Genetic Abnormality; 10 Technological Developments; 11 Confined Placental Mosaicism and Uniparental Disomy; 12 Molecular Cytogenetics; 13 Fetal Cells in Maternal Circulation; 14 Fetal Therapy; 15 Psychosocial Aspects; 16 Epidemiology and Environmental Factors; 17 Developmental Pathology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted

Journal Article↗