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Biomedical subjects

A Moreno

Publications and source records attributed to A Moreno.

At least 127 records · Page 7Linked to original sources
PubMed2000

Phenotypic testing predicts virological response in successive protease inhibitor-based regimens.

OBJECTIVE: To evaluate the importance of the number of active drugs, as determined by phenotypic resistance testing, in achieving virological response in successive salvage regimens. DESIGN: Phenotypic study of 57 plasma samples corresponding to 24 patients who had sequentially received three protease inhibitor-containing regimens. Phenotypic susceptibility to a drug (active drug) was defined as less than a four-fold-increase in the IC50 in comparison with the wild type. MAIN OUTCOME MEASURE: Virological response according to the number of active drugs (three versus two or fewer), HIV load, length of antiretroviral exposure, and line of protease inhibitor-based therapy (first, second and third regimen). RESULTS: Before the first protease inhibitor-based therapy, the median time on antiretroviral treatment was 42 months, and before the second and third protease inhibitor-salvage regimens it was 10 and 8 months, respectively. The number of patients receiving three active drugs simultaneously was 24, 35 and 31% in each line of therapy. At week 12, a close correlation was found between the presence of three active drugs in the antiretroviral regimen and the rate of virological response, in comparison with those patients receiving two or fewer active drugs [76 versus 45%, relative risk (RR), 1.7; 95% confidence interval (CI) 1.1-2.6; P = 0.028]. In a multivariate analysis, the use of two or fewer active drugs was an independent predictor of lack of response, regardless of HIV load, length of previous antiretroviral exposure and line of salvage therapy (RR, 4.5; 95%CI, 1.1-18.3; P = 0.03). Of note, a higher rate of response was observed in patients receiving the first protease inhibitor-containing regimen in comparison with those in subsequent protease inhibitor-based salvage regimens (83 versus 50 versus 28%, P < 0.01), even when only those patients receiving three active drugs were included (100 versus 71 versus 60%). CONCLUSIONS: This data confirm the usefulness of phenotypic testing in guiding antiretroviral therapy in heavily pretreated patients. The number of active drugs and the line of salvage therapy are independent predictors of virological response, regardless of HIV load and the length of antiretroviral exposure.

Anti-HIV Agents↗
PubMed2000

Bcl-2 with loss of apoptosis allows accumulation of genetic alterations: a pathway to metastatic progression in human breast cancer.

We have examined whether the extended life span of cells induced by Bcl-2 in T(1) ductal breast carcinomas might favor the acquisition and accumulation of genetic alterations that induce lymph node metastases. We analyzed the expression of c-Myc, c-erbB-2 and epidermal growth factor receptor by immuno-histochemistry in a group of 142 T(1) (<2 cm) ductal breast carcinomas embedded in paraffin, previously studied for p53 mutation and Bcl-2 over-expression. We also measured the apoptotic status and estimated the excess risk (pOR) for lymph node metastasis according to the number of accumulated oncogene alterations and Bcl-2 and p53 expression. The linear relationship between number of oncogene alterations and presence of lymph node metastasis was statistically significant in Bcl-2-positive tumors (trend test, p = 0.03), p53-mutated tumors (trend test, p = 0.08) and tumors with loss of apoptosis (trend test, p = 0.08). Very large associations (pOR > 12) between the number of oncogene alterations and lymph node metastasis were observed among Bcl-2-positive tumors that showed increased loss of apoptosis (trend test, p = 0.03). Furthermore, in p53-negative tumors, a strong linear association was found between the number of oncogene alterations and risk of lymph node metastasis among Bcl-2-positive tumors (trend test, p = 0.03). In human T(1) ductal breast carcinoma, over-expression of Bcl-2 along with loss of apoptosis might render breast cancer cells susceptible to the acquisition of additional genetic lesions related to disease progression among p53-negative tumors. Thus, in breast cancer, there are at least 2 pathways to progression: Bcl-2- and p53-dependent mechanisms.

Antibodies, Monoclonal↗
PubMed2000

Effect of DT-TX 30, a combined thromboxane synthase inhibitor and thromboxane receptor antagonist, on retinal vascularity in experimental diabetes mellitus.

Combined thromboxane synthase inhibitors and thromboxane receptors antagonists have been shown to have a beneficial effect on different models of thrombosis in vivo. We studied the action of one of these compounds (DT-TX 30) compared with dazoxiben (a thromboxane synthase inhibitor) on retinal vascularity in streptozotocin-diabetic rats. Ten nondiabetic animals were treated with isotonic saline, 30 (10 animals per group) were given 0.4, 4, and 8 mg kg(-1) per day of DT-TX 30 (p.o.) and 30 (10 animals per group) were given 10, 50, and 100 mg kg(-1) per day of dazoxiben (p.o.) over a 90-day study period. DT-TX 30 caused a dose-dependent decrease of platelet aggregation and thromboxane B2 synthesis. There was an increase of 9, 65, and 166% in the synthesis of prostacyclin after treatment with 0.4, 4, and 8 mg kg(-1) per day, respectively. Retinal vascularity increased in 51, 72, and 182% of animals in response to the three doses used. Synthesis of prostacyclin and the degree of retinal vascularity showed a linear correlation (r2=0.6528,p<0.00001). Dazoxiben, at doses that inhibited thromboxane synthesis as much as DT-TX 30, increased prostacyclin production and retinal vascularity with less potency than DT-TX 30. In conclusion, the antagonism of thromboxane receptors may be an important additional effect to the inhibition of thromboxane synthase in the prevention of ischemic retinal lesions in experimental diabetes.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Novel peak assignments of in vivo (13)C MRS in human brain at 1.5 T.

(13)C MRS studies at natural abundance and after intravenous 1-(13)C glucose infusion were performed on a 1.5-T clinical scanner in four subjects. Localization to the occipital cortex was achieved by a surface coil. In natural abundance spectra glucose C(3beta,5beta), myo-inositol, glutamate C(1,2,5), glutamine C(1,2,5), N-acetyl-aspartate C(1-4,C=O), creatine CH(2), CH(3), and C(C=N), taurine C(2,3), bicarbonate HCO(-)(3) were identified. After glucose infusion (13)C enrichment of glucose C(1alpha,1beta), glutamate C(1-4), glutamine C(1-4), aspartate C(2,3), N-acetyl-aspartate C(2,3), lactate C(3), alanine C(3), and HCO(-)(3) were observed. The observation of (13)C enrichment of resonances resonating at >150 ppm is an extension of previously published studies and will provide a more precise determination of metabolic rates and substrate decarboxylation in human brain.

Adult↗
PubMed2000

Sequence and diversity of MHC DQA and DQB genes of the owl monkey Aotus nancymaae.

The New World primate Aotus nancymaae has been recommended by the World Health Organization (WHO) as a model for evaluation of malaria vaccine candidates, given its susceptibility to experimental infection with the human malaria parasites Plasmodium falciparum and Plasmodium vivax. We present here the nucleotide sequences of the complete cDNA of MHC-DQA1 and of the polymorphic exon 2 segments of MHC-DQB1/DQB2. In a group of three nonrelated animals captured in the wild, five alleles of MHC-DQA1 could be identified. They all belong to one lineage, namely Aona-DQA1*27. This lineage has not been described in any other New World monkey species studied. In a group of 19 unrelated animals, 14 Aona-DQB1 alleles could be identified which are grouped into the two lineages Aona-DQB1*22 and Aona-DQB1*23. These lineages have been described previously in the common marmoset and cotton-top tamarin. In addition, two Aona-DQB2 sequences could be identified which are highly similar to HLA-DQB2 sequences. Essential amino acid residues contributing to MHC DQ peptide binding pockets number 1 and 4 are conserved or semi-conserved between HLA-DQ and Aona-DQ molecules, indicating a capacity to bind similar peptide repertoires. These results fully support the use of Aotus monkeys as an animal model for evaluation of future subunit vaccine candidates.

Alleles↗
PubMed2000

Immunoglobulin kappa light-chain V, J, and C gene sequences of the owl monkey Aotus nancymaae.

Sequences of Aotus nancymaae immunoglobulin kappa light-chain rearrangements were analyzed after reverse transcription polymerase chain reaction. Among 22 in-frame rearrangements analyzed, 12 IGKV genes belonging to the families 1, 2, or 3 were identified. Aotus counterparts for all five human IGKJ genes were found. The identity of the deduced human and Aotus amino acid sequences was between 83% and 92% for junctional regions and 74% for the constant region. Sequence comparisons between rearrangements indicated that somatic mutations, the addition of nongermline-encoded nucleotides, and exonuclease trimming contribute to the generation of diversity of Aotus immunoglobulin kappa chains. The high identity of Aotus and human IGK genes is comparable to that of T-cell receptor genes and further supports the proposal to use the Aotus Plasmodium falciparum infection model for the evaluation of malaria vaccine candidates.

Amino Acid Sequence↗
PubMed2000

Sequence and diversity of DRB genes of Aotus nancymaae, a primate model for human malaria parasites.

The New World primate Aotus nancymaae is susceptible to infection with the human malaria parasite Plasmodium falciparum and Plasmodium vivax and has therefore been recommended by the World Health Organization as a model for evaluation of malaria vaccine candidates. We present here a first step in the molecular characterization of the major histocompatibility complex (MHC) class II DRB genes of Aotus nancymaae (owl monkey or night monkey) by nucleotide sequence analysis of the polymorphic exon 2 segments. In a group of 15 nonrelated animals captivated in the wild, 34 MHC DRB alleles could be identified. Six allelic lineages were detected, two of them having human counterparts, while two other lineages have not been described in any other New World monkey species studied. As in the common marmoset, the diversity of DRB alleles appears to have arisen largely by point mutations in the beta-pleated sheets and by frequent exchange of fixed sequence motifs in the alpha-helical portion. Pairs of alleles differing only at amino acid position b86 by an exchange of valine to glycine are present in Aotus, as in humans. Essential amino acid residues contributing to MHC DR peptide binding pockets number 1 and 4 are conserved or semiconserved between HLA-DR and Aona-DRB molecules, indicating a capacity to bind similar peptide repertoires. These results support fully our using Aotus monkeys as an animal model for evaluation of future subunit vaccine candidates.

Alleles↗
PubMed2000

Role of antiretroviral therapy in long-term survival of patients with AIDS-related pulmonary aspergillosis.

The aim of the study presented here was to describe the clinical presentation and outcome of invasive pulmonary aspergillosis (IPA) in a cohort of HIV-infected patients and to assess factors associated with survival by means of a longitudinal study of all HIV-infected adults with IPA who attended the infectious diseases service of a tertiary center between January 1985 and December 1998. The outcome measure was the time to death after diagnosis of IPA. The endpoint for data collection and survival analysis was 31 December 1998. Nineteen of 1,605 HIV-infected patients were identified, resulting in an overall IPA attack rate of 1.12%. Most patients had AIDS (95%). Unilateral cavitary disease was the most frequent radiographic presentation (37%). Median survival was 148 days (95% confidence interval [95% CI], 0-402), but it exceeded 12 months in 37%. In patients in whom antiretroviral treatment (ART) was initiated or modified in relation to the IPA diagnosis, median survival increased to 906 days (95% CI, 754-1,058; 1-year survival, 83%) compared with 86 days in those who did not take any ART (95% CI, 55-117; 1-year survival, 8%; P=0.0002). Survival was even longer when ART changes included only nucleoside reverse transcriptase inhibitors, prior to the availability of protease inhibitors (833 days, 95% CI, 369-1,297; 1-year survival 75%; P=0.003). Three (16%) patients are still alive after a mean time of 36 months postdiagnosis. Although IPA is a life-threatening complication of advanced AIDS, it does not always lead to short-term death. An adequate management of HIV infection together with antifungal treatment may prolong survival and, as described for other AIDS-related disorders, a significant decrease in its occurrence can be expected.

AIDS-Related Opportunistic Infections↗
PubMed2000

Evolution of MHC-G in humans and primates based on three new 3'UT polymorphisms.

MHC-G is a class Ib (non-classical) major histocompatibility complex (MHC) whose functional and evolutionary characteristics are still under scrutiny. The study of noncoding sequences in the MHC genes may provide important phylogenetic information. In this work we have sequenced the MHC-G exon 8, which encodes for the 3'UT region, in different species of primates. It has been shown that: (1) a previously described 14 base pair (bp) deletion polymorphism is human-specific and the HLA-G alleles may be classified according to its absence or presence; (2) another newly described 3 bp deletion/insertion polymorphism is also human-specific; and (3) another newly described 51 bp deletion polymorphism is common to Pongidae and humans, but is not found in other primates belonging to the Cercopithecinae family. A hypothesis on the evolutionary pathway of this gene is put forward in the light of these findings.

3' Untranslated Regions↗
PubMed2000

The stethoscope in the Emergency Department: a vector of infection?

The purposes of this study were to determine whether microorganisms can be isolated from the membranes of stethoscopes used by clinicians and nurses, and to analyse whether or not the degree of bacterial colonization could be reduced with different cleaning methods. We designed a transversal before-after study in which 122 stethoscopes were examined. Coagulase negative staphylococci (which are also potentially pathogenic microorganisms) were isolated together with 13 other potentially pathogenic microorganisms, including S. aureus, Acinetobacter sp. and Enterobacter agglomerans. The most effective antiseptic was propyl alcohol. Analysis of the cleaning habits of the Emergency Department (ED) staff, showed that 45% cleaned the stethoscope annually or never. The isolation of potentially pathogenic microorganisms suggests that the stethoscope must be considered as a potential vector of infection not only in the ED but also in other hospital wards and out-patient clinics.

1-Propanol↗
PubMed2000

A novel CD18 genomic deletion in a patient with severe leucocyte adhesion deficiency: a possible CD2/lymphocyte function-associated antigen-1 functional association in humans.

Leucocyte adhesion deficiency (LAD) is an autosomal-recessive genetic disease that is characterized clinically by severe bacterial infections and caused by mutations in the CD18 gene that codes for the beta2 integrin subunit. A patient with a severe LAD phenotype was studied and the molecular basis of the disease was identified as a single homozygous defect in a Herpes virus saimiri (HVS)-transformed T-cell line. The defect identified involves a deletion of 171 bp in the cDNA that encodes part of the proteic extracellular domain. This genetic abnormality was further studied at the genomic DNA level and found to consist of a deletion of 169 bp (from -37 of intron 4 to +132 of exon 5), which abolishes the normal splicing and results in the total skipping of exon 5. The 171-bp shortened 'in-frame' mRNA not only resulted in the absence of CD18 expression on the cell surface but also in its absence in the cytoplasm of HVS T-cell lines. Functionally, the LAD-derived HVS T-cell lines showed a severe, selective T-cell activation impairment in the CD2 (but not in the CD3) pathway. This defect was not reversible when exogenous interleukin-2 (IL-2) was added, suggesting that there is also a functional interaction of the lymphocyte function-associated antigen-1 (LFA-1) protein in the CD2 signal transduction pathway in human T cells, as has been previously reported in mice and in the human Papillon-Lefèvre syndrome. Thus, HVS transformation is not only a suitable model for T-cell immunodeficiency studies and characterization, but is also a good system for investigating the immune system in pathological conditions. It may also be used in the future in cellular models for in vitro gene-therapy trials.

Base Sequence↗
PubMed2000

Mitochondrial DNA control region diversity in the endangered blue chaffinch, Fringilla teydea.

The blue chaffinch (Fringilla teydea) is found only on the two central Canary Islands of Gran Canaria and Tenerife, where it is restricted to pine forest habitat. It is reasonably abundant on the latter island but endangered on the former. Here, sequence variation was studied in a fragment spanning domains I and II of the mitochondrial DNA (mtDNA) control region. Phylogenetic analysis of all haplotypes with a F. coelebs outgroup indicated the two island populations were reciprocally monophyletic, supporting their individual conservation. Unlike in other species, most within-island haplotype diversity was due to mutations in the domain II region. Surprisingly, genetic diversity was greater in the smaller Gran Canarian population. We suggest that this is unlikely to be maintained under current population sizes although it may be mitigated by incorporating genetic information into the captive breeding programme.

Animals↗
PubMed2000

Clinical and histological differences in anaplastic thyroid carcinoma.

OBJECTIVE: To report our experience in patients with anaplastic thyroid carcinoma and try to establish differences between cases in which the histological study showed that there was an associated thyroid carcinoma and those that were strictly anaplastic or pure. DESIGN: Retrospective study. SETTING: University hospital, Spain. SUBJECTS: 14 patients with anaplastic thyroid cancer treated over a period of 26 years; 7 presented with associated thyroid tumours and 7 were pure. MEAN OUTCOME MEASURES: Clinical data (age, sex, symptoms), treatment, histological study (associated thyroid disease, spread, involved lymph nodes) and follow-up. RESULTS: 13 of the 14 tumours had spread locally. 5 patients were treated by total thyroidectomy, 3 subtotal thyroidectomy, 5 excision of the tumour, and 1 patient had a biopsy alone. There were associated thyroid tumours in 7 cases: 2 follicular, 2 tall cell papillary, 1 solid papillary, 1 medullary and 1 Hurthle cell tumour. 12 patients died. Another 2 are still alive having survived 61 and 70 months respectively, both with associated anaplastic cancers (follicular and solid). The mean survival was 14 months (24 for associated anaplastic carcinoma and 4 for pure anaplastic carcinoma). CONCLUSION: There is a subgroup of anaplastic cancers in which a better differentiated thyroid carcinoma coexists with the anaplastic carcinoma. The prognosis in this subgroup is better than that for primary pure anaplastic carcinoma.

Adult↗
PubMed2000

Closure, identity, and the emergence of formal causation

The aim of this paper is to characterize a type of causality relevant to study the closure of complex systems that we call formal causation. By this term we understand the existence of a new (not materially inherent) causal relation among constituents, generated through an autonomous process of closure. Once a certain level of organization is reached, material systems can generate internal constraints that, through recursive processes, construct their own identity. We study two different forms of closure: closure in dissipative systems and closure in template self-replication. Finally, these two forms merge and bring forth a new one: informational closure, We show how complex forms of organization are based on informational closure, which is an explicit, recorded type of formal causation allowing a functional articulation between individual organizations and larger, collective and historical (meta)organizations.

Journal Article↗
PubMed2000

Diagnostic utility of a multiplex herpesvirus PCR assay performed with cerebrospinal fluid from human immunodeficiency virus-infected patients with neurological disorders.

We used a multiplex nested-PCR assay for the simultaneous detection in cerebrospinal fluid (CSF) of five human herpesviruses (HVs) (cytomegalovirus [CMV], Epstein-Barr virus [EBV], varicella-zoster virus [VZV], herpes simplex virus [HSV], and human herpesvirus 6 [HHV-6]) in a clinical evaluation of human immunodeficiency virus (HIV)-infected patients with neurological disorders. This method, which has the advantages of being rapid and economical, would be of particular interest for the diagnosis of neurological syndromes caused by more than one HV. We studied 251 CSF samples from 219 patients. HV DNA was demonstrated in 93 (37%) of the CSF samples (34% of the patients). CMV was the HV most frequently detected in our patients (25%), while EBV, VZV, HSV, and HHV-6 DNAs were present in significantly fewer cases (7, 4, 3, and 1%, respectively). When results were compared with the final etiological diagnoses of the patients, the multiplex HV PCR showed high specificity for the diagnosis of CMV and VZV neurological diseases and for cerebral lymphoma (0.95, 0.97, and 0.99, respectively). The sensitivity of the assay was high for CMV disease (0.87), was low for cerebral lymphoma (0.33), and was not evaluable for VZV disease due to the small number of patients with this diagnosis. Nevertheless, detection of VZV DNA had possible diagnostic value in four of the nine cases, and EBV DNA amplification always predicted the diagnosis of cerebral lymphoma in patients with cerebral masses. Detection of HSV DNA was frequently associated with CMV amplification and fatal encephalitis. HHV-6 was not considered to have a pathogenetic role in the three cases in which it was detected. This multiplex HV PCR assay is a specific and clinically useful method for the evaluation of HIV-infected patients with neurological disorders related to HV.

AIDS-Related Opportunistic Infections↗