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Biomedical subjects

L Borges

Publications and source records attributed to L Borges.

At least 19 recordsLinked to original sources
PubMed2006

Kaposi's sarcoma-associated herpesvirus infection and Kaposi's sarcoma in Brazil.

Kaposi's sarcoma (KS) became a critical health issue with the emergence of acquired immunodeficiency syndrome (AIDS) in the 1980s. Four clinical-epidemiological forms of KS have been described: classical KS, endemic KS, iatrogenic KS, and AIDS-associated KS. In 1994, Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus type 8 was identified by Chang and colleagues, and has been detected worldwide at frequencies ranging from 80 to 100%. The aim of the present study was to evaluate the frequency of KSHV infection in KS lesions from HIV-positive and HIV-negative patients in Brazil, as well as to review the current knowledge about KS transmission and detection. For these purposes, DNA from 51 cases of KS was assessed by PCR: 20 (39.2%) cases of classical KS, 29 (56.9%) of AIDS-associated KS and 2 (3.9%) of iatrogenic KS. Most patients were males (7.5:1, M/F), and mean age was 47.9 years (SD = +/- 18.7 years). As expected, HIV-positive KS patients were younger than patients with classical KS. On the other hand, patients with AIDS-associated KS have early lesions (patch and plaque) compared to classical KS patients (predominantly nodular lesions). This is assumed to be the result of the early diagnose of KS in the HIV-positive setting. KSHV infection was detected by PCR in almost all cases (48/51; 94.1%), irrespectively of the clinical-epidemiological form of KS. These results show that KSHV is associated with all forms of KS in Brazilian patients, a fact that supports the role of this virus in KS pathogenesis.

AIDS-Related Opportunistic Infections↗
PubMed2005

Mitochondrial dysfunction in autism spectrum disorders: a population-based study.

A minority of cases of autism has been associated with several different organic conditions, including bioenergetic metabolism deficiency. In a population-based study, we screened associated medical conditions in a group of 120 children with autism (current age range 11y 5mo to 14y 4mo, mean age 12y 11mo [SD 9.6mo], male:female ratio 2.9:1). Children were diagnosed using Diagnostic and Statistical Manual of Mental Disorders criteria, the Autism Diagnostic Interview--Revised, and the Childhood Autism Rating Scale; 76% were diagnosed with typical autism and 24% with atypical autism. Cognitive functional level was assessed with the Griffiths scale and the Wechsler Intelligence Scale for Children and was in the normal range in 17%. Epilepsy was present in 19 patients. Plasma lactate levels were measured in 69 patients, and in 14 we found hyperlactacidemia. Five of 11 patients studied were classified with definite mitochondrial respiratory chain disorder, suggesting that this might be one of the most common disorders associated with autism (5 of 69; 7.2%) and warranting further investigation.

Adolescent↗
PubMed2004

Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism.

The role of the serotonin system in the etiology and pathogenesis of autism spectrum disorders (ASD) is not clearly defined. High levels of platelet serotonin (5-HT) have been consistently found in a proportion of patients, and it is known that specific 5-HT transporter gene (SLC6A4) variants modulate transporter reuptake function, therefore possibly influencing the occurrence of hyperserotonemia in a subset of autistic patients. We have examined the association of platelet serotonin levels with two SLC6A4 polymorphisms, 5-HTT gene-linked polymorphic region (HTTLPR) in the promoter and intron 2 variable number of tandem repeats (VNTR), in a sample of 105 ASD patients, their parents, and 52 control children. Quantitative transmission disequilibrium test (QTDT) results showed a significant effect on 5-HT levels of each SLC6A4 marker (P=0.017 for HTTLPR; P=0.047 for intron 2 VNTR) and of haplotypes of the two markers (P=0.017), with a major contribution of the L.Stin2.10 haplotype (P=0.0013). A 5-HT mean value in the range of hyperserotonemia was associated with the homozygous L.Stin2.10 haplotype (H (1,N=97)=7.76, P=0.0054), which occurred in 33% of hyperserotonemic patients against 6% of patients with normal 5-HT levels (Fisher's exact test: P=0.013, OR=8). Allele interaction at the HTTLPR locus was found, with a significant dominance variance effect on 5-HT levels. We found no transmission disequilibrium of any of the SLC6A4 variants in ASD. Our results show that the SLC6A4 gene is a significant factor in the determination of 5-HT levels, and that specific SLC6A4 variants are associated with an increased risk for hyperserotonemia in our sample of autistic patients. The biological mechanism, however, is unlikely to involve the SLC6A4 gene solely. The associated SLC6A4 alleles likely interact with other genes or environmental factors to produce the abnormally high 5-HT levels observed in this subset of autistic patients, who possibly represent a separate etiological group.

Adolescent↗
PubMed2004

Increased Fas-mediated apoptosis in polymorphonuclear cells from HIV-infected patients.

Neutrophils represent an important line of innate host defence against invading microorganisms and their functional detriment during HIV infection, including accelerated spontaneous cell death, has been shown to contribute to AIDS development. Neutrophils are susceptible to apoptosis via Fas and an interaction between Fas and FasL was suggested originally as a mechanism to explain constitutive neutrophil apoptosis. We have explored some intracellular pathways leading to PMN apoptosis from 28 HIV-infected patients and 24 healthy volunteers. As previously reported, accelerated spontaneous apoptosis was observed in HIV+ patients, but this did not correlate with viral load. Furthermore, an increase in the level of spontaneous apoptosis was detected in neutrophils from HIV-infected patients following inhibition of ERK, suggesting an impairment of this kinase pathway during the early stages of infection which may contribute to PMN dysfunction. An elevated susceptibility to undergo apoptosis was observed following cross-linking of Fas, which correlated both with viral load and co-expression of Fas/FasL surface molecules. Different mechanisms for spontaneous and Fas-induced apoptosis are proposed which together contribute to the neutropenia and secondary infections observed during the progression to AIDS.

Adult↗
PubMed2001

[Recurrent pericardial effusion --a case of cardiac angiosarcoma].

A case of angiosarcoma of the right atrium in a 59-year-old woman is reported, presenting as a recurrent hematic pericardial effusion. The usefulness of echocardiography in making the diagnosis is emphasized. The tumor was already disseminated at the time of the diagnosis. The patient was on palliative therapy, dying a few months later. The histological examination was done at autopsy. This case highlights the difficulty in diagnosis and the various modalities available for an accurate diagnosis of a rare clinical entity. It has a rapid and aggressive course with a very poor prognosis.

Female↗
PubMed2000

LIRs/ILTs/MIRs, inhibitory and stimulatory Ig-superfamily receptors expressed in myeloid and lymphoid cells.

Cells exhibit a complex network of inhibitory and stimulatory signaling pathways, which interact with each other to maintain an homeostatic balance and modulate cellular responses to external stimuli. During most of the 1980s, a great effort was put into the characterization of stimulatory cell surface receptors for cytokines and growth factors. In the last decade, a large number of inhibitory receptors have been identified and it has become apparent that inhibitory signaling pathways are subject to intricate regulatory mechanisms. Inhibitory and stimulatory signaling pathways work in concert with each other to establish activation thresholds and provide sensitive tuning mechanisms that help control cellular responses. LIRs/ILTs/MIRs are a novel family of inhibitory and stimulatory receptors expressed both in myeloid and lymphoid cells. They contain two or four immunoglobulin-like domains in the extracellular region and their cytoplasmic domains are either very short and without any signaling motifs or are long and contain a variable number of immunoreceptor tyrosine-based inhibition motifs (ITIMs). LIRs within the first group send stimulatory signals by association with the FcR common gamma chain and LIRs within the second group deliver inhibitory signals by association with the protein tyrosine phosphatase SHP-1. This review summarizes our current knowledge on the LIRs, their ligands, and biological functions.

Amino Acid Motifs↗
PubMed2000

Community-based early intervention: the Coimbra project (Portugal).

The Coimbra Early Intervention Project was undertaken to develop the first co-ordinated, multidisciplinary, interagency programme involving health care, education and social services, using existing resources in the community. The programme operates region wide and supports annually about 160 families and children with disabilities or at risk. Thirty-three per cent of the 601 children served so far had developmental delay, 22% belonged to high-risk families and 45% had risk factors and disabilities. In spite of difficulties, the programme success has increased awareness of the need to integrate and co-ordinate multiple community services and to develop legislation for the provision of early intervention services.

Child↗
PubMed1999

Synergistic action of fms-like tyrosine kinase 3 ligand and CD40 ligand in the induction of dendritic cells and generation of antitumor immunity in vivo.

Daily treatment of mice with fms-like tyrosine kinase 3 ligand (Flt3L) leads to a significant increase in the number of dendritic cells and induces antitumor immunity. Here, we show that Flt3L and CD40 ligand (CD40L) synergize in the generation of immune responses against two poorly immunogenic tumors, leading to complete tumor rejection in a high proportion of mice. Rechallenge of the Flt3L + CD40L-treated mice with the immunizing tumor resulted in complete inhibition of tumor growth, indicating that these animals had developed long-lasting antitumor immunity. In addition, we demonstrate that endogenous CD40L plays a critical role in antitumor immunity, since blockade of CD40-CD40L interactions in vivo prevents the generation of antitumor immunity in therapeutic and vaccination protocols. Dendritic cells generated in mice treated with Flt3L alone or in combination with CD40L were equally potent in stimulating allogeneic T cells and expressed similar levels of MHC class II, CD80, and CD86. However, mice treated with Flt3L + CD40L had significantly more dendritic cells than mice treated with either of the cytokines alone, suggesting that CD40L promotes the proliferation and/or survival of dendritic cells generated by Flt3L treatment. Dendritic cells generated in this manner are likely to be involved in the priming of antitumor immune responses.

Adjuvants, Immunologic↗
PubMed1999

Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48.

Using the monoclonal antibody C1.7, which recognizes a signaling, membrane-bound molecule on human NK and a proportion of CD8(+) T cells, we cloned a novel molecule we refer to as NK cell activation-inducing ligand (NAIL). It is a 365-amino acid protein that belongs to the immunoglobulin-like superfamily with closest homology to murine 2B4, and human CD84 and CD48. Using a soluble NAIL-Fc fusion protein, we determined the counterstructure for NAIL, CD48, which it binds with high affinity. Stimulation of human B cells with recombinant NAIL in the presence of a suboptimal concentration of human CD40 ligand or IL-4 resulted in increased proliferation. Treatment of human dendritic cells with soluble NAIL-leucine zipper protein resulted in an increased release of IL-12 and TNF-alpha. Using recombinant CD48 protein, we demonstrated the ability of this molecule to increase NK cell cytotoxicity and induce IFN-gamma production. We also showed that 2B4 binds to mouse CD48, suggesting that interaction of these receptors may play a similar role in both species. Taken together these results indicate that the NAIL-CD48 interaction may be an important mechanism regulating a variety of immune responses.

Amino Acid Sequence↗
PubMed1999

The leukocyte immunoglobulin-like receptors (LIRs): a new family of immune regulators.

Identification of a counterstructure for the human cytomegalovirus-encoded major histocompatibility complex class I-related gene product, UL18, has led to the discovery of a novel family of immunoreceptors, termed leukocyte immunoglobulin-like receptors (LIRs). The LIRs are differentially expressed in cells of the dendritic cell, monocytic and lymphocytic lineages, and appear to mediate diverse roles in immune regulation. This review summarizes the expression, distribution, and signaling capacities of the LIRs and discusses possible roles of the LIRs in both inhibition and activation of the cellular responses.

Animals↗
PubMed1999

Acquired procedural dyscalculia associated to a left parietal lesion in a child.

We report the case of an 11-year-old boy who developed an anarithmetia in association with a left temporo-parietal tumor. His oral and written language were normal as well as his ability to judge magnitudes, process numbers, read operation signs and retrieve number facts. He had a specific difficulty in performing the procedures of subtraction, especially when it involved borrowing. These skills had been mastered before the present illness. This case shows that the components of calculation can be dissociated by brain lesions sustained during childhood, while arithmetic abilities are being acquired, thus reinforcing findings from developmental dyscalculias, that suggest a modular organisation of those skills during development.

Brain Neoplasms↗
PubMed1999

Human cytomegalovirus, MHC class I and inhibitory signalling receptors: more questions than answers.

The human cytomegalovirus UL18 protein, an MHC class I homologue, has been shown to bind to leucocyte immunoglobulin-like receptor (LIR)-1, a member of a family of nine closely related immunoglobulin superfamily receptors expressed on leucocytes. The LIRs are related to the natural killer (NK)-cell immunoglobulin-like receptors and to several other immunoreceptors. Three groups of LIR molecules have been defined: those containing cytoplasmic domain inhibitory signalling motifs, those with short cytoplasmic domains and a charged residue within the transmembrane domain, and a secreted molecule. LIR-1 and LIR-2 bind to a broad spectrum of cellular MHC class I antigens, including HLA-A, -B and -C alleles. LIR-2 is expressed by all monocytes and dendritic cells, whereas LIR-1 is additionally expressed by B cells and subsets of T and NK cells. Upon tyrosine phosphorylation, LIR-1 and LIR-2 associate with the tyrosine phosphatase, SHP-1, and have been shown to inhibit Fc gamma RI signalling when co-crosslinked in monocytes. Evidence for and against a role of UL18 as an inhibitor of NK-cell function is discussed, as are possible functional outcomes of UL18-LIR-1 interactions in monocytic cells.

Animals↗
PubMed1999

[The NADPH-oxidase complex in chronic granulomatous disease: preliminary description of a cluster in Mérida-Venezuela].

Chronic Granulomatous Disease (CGD) is a primary immunodeficiency characterized by an unusual predisposition to develop bacterial and fungal infections due to a failure of phagocytic leukocytes to generate superoxide, required for the intracellular killing of microorganisms. The lack of superoxide production is secondary to a defect in the NADPH-oxidase enzymatic complex activation, as a result of mutations of any of the components. Both, X-linked and autosomal recessive patterns of inheritance have been demonstrated in this disease, being the X-linked the most frequent and characterized by mutations in gp91phox. Mutations in p47phox, p67phox and p22phox have been shown in the autosomal recessive pattern. The molecular and genetic characteristic of NADPH-oxidase complex and its pathology in CGD are reviewed along with a brief description of the preliminary findings in two families from Mérida, Venezuela.

Adolescent↗
PubMed1998

The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-mediated signaling in monocytes.

The MHC class I binding proteins leukocyte immunoglobulin-like receptor (LIR)-1 and -2 recognize a similar broad spectrum of HLA-A, -B and -C alleles but are differentially expressed in lymphocytes, monocytes, and dendritic cells. In monocytes, phosphorylation of LIR-1 and LIR-2 results in the binding of the tyrosine phosphatase SHP-1. Coligation of either LIR with Fcgamma receptor I (CD64) inhibits tyrosine phosphorylation of the associated Fc receptor gamma chain and Syk molecules, as well as intracellular calcium mobilization. These findings suggest that LIR-1 and LIR-2 function as unique MHC class I receptors involved in the inhibition or down-modulation of monocyte activation signals, particularly those mediated through the receptors for IgG, IgE and IgA.

Alleles↗
PubMed1997

A family of human lymphoid and myeloid Ig-like receptors, some of which bind to MHC class I molecules.

Leukocyte Ig-like receptors (LIRs) are a newly discovered family of immunoreceptors expressed on monocytes and B cells and at lower levels on dendritic cells and NK cells. The amino acid sequences in the extracellular regions of eight of these receptors show between 63 and 84% identity to the prototypic LIR-1 sequence. LIRs contain either two or four Ig domains and fall into three classes: those with cytoplasmic domains containing two, three, or four immunoreceptor tyrosine-based inhibitory motif-like motifs; those with a short cytoplasmic domain and no immunoreceptor tyrosine-based inhibitory motif-like motifs; and those with no transmembrane domain represented by a single LIR molecule that is presumably secreted. The LIRs are structurally related to the human Fc(alpha)R and the killer inhibitory receptors and map to the same region of chromosome 19 as these genes. Like killer inhibitory receptors, at least two LIRs bind to MHC class I Ags, but their different cellular distribution suggests a distinct role in immune system modulation.

Amino Acid Sequence↗
PubMed1997

A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules.

The human cytomegalovirus UL18 gene product is a homolog of cellular major histocompatibility (MHC) class I antigens. UL18 has been proposed to protect virus-infected cells against natural killer (NK) cell cytotoxicity by engaging NK cell killer inhibitory receptors (KIR) for MHC class I. UL18 binds to a novel immunoglobulin superfamily glycoprotein, designated Leukocyte Immunoglobulin-like Receptor (LIR-1). This protein is distinct from, but related to, known KIRs and binds cellular MHC class I antigens. The cytoplasmic domain of LIR-1 contains four putative immunoreceptor tyrosine-based inhibitory motifs. Upon tyrosine phosphorylation, LIR-1 associates with the tyrosine phosphatase SHP-1. In contrast to KIRs, LIR-1 is expressed predominantly on monocytic and B lymphoid cell types, suggesting a distinct biological function.

Amino Acid Sequence↗