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Biomedical subjects

J Navarro

Publications and source records attributed to J Navarro.

At least 163 records · Page 9Linked to original sources

Antineutrophil cytoplasmic antibodies in children with inflammatory bowel disease: prevalence and diagnostic value.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA), particularly perinuclear ANCA (p-ANCA), have been found more frequently in sera from patients with ulcerative colitis (UC) than in sera from Crohn's disease (CD) or unclassified enterocolitis (UE) patients. This 2-center study examined sera from 102 pediatric patients with inflammatory bowel disease (IBD) to evaluate their diagnostic value and assess their relationship with disease features, distribution, activity and treatment. METHODS: The serum ANCA of 102 children with IBD were measured: 33 UC, 64 CD and 5 UE with various disease locations and degrees of activity. The mean age at the onset of symptoms was 10.7 years (1 to 16.3 years). Sera from 26 unaffected first degree relatives and 20 children without IBD were also investigated. ANCA were detected using indirect immunofluorescence of ethanol-fixed granulocytes. RESULTS: There were ANCA in the sera of 24/33 children with UC (73%), 9/64 with CD (14%) and 4/5 with UE (80%). p-ANCA were more frequent than cytoplasmic-ANCA in positive sera: UC = 67%, CD = 57% and UE = 75%. The presence of ANCA was 73% sensitive and 81% specific for a diagnosis of UC, compared to other IBD (p < 0.001). Three children with proved sclerosing cholangitis associated with UC were all positive. There was no link between ANCA-positive sera and disease activity, or other endoscopic or clinical criteria. ANCA were detected in 4/26 first degree relatives (15%) and in 1/20 control subjects (5%). CONCLUSIONS: Because of their sensitivity and specificity, ANCA may be helpful in the clinical assessment of patients with IBD, and especially those with UC. However, there is no link between the pressure of p-ANCA and the site of UC or its activity, so that it cannot be used to monitor medical treatment or surgical indications.

Adolescent↗

In situ Rantes and interferon-gamma gene expression in pediatric small bowel Crohn's disease.

BACKGROUND: Rantes (regulated upon activation, normal T cell expressed and secreted) is a chemotactic cytokine for memory T lymphocytes, monocytes, and eosinophils. The cytokine interferon-gamma (IFN-gamma) plays a key in the immune response. Their distributions and possible roles in the selective accumulation of inflammatory cells in Crohn's disease (CD) were examined by determining the expression of Rantes and IFN-gamma genes in patients with CD using in situ hybridization (ISH) on frozen and paraffin-embedded tissue sections. METHODS: Intestinal and mesenteric lymph node samples from 9 children who had undergone ileal resection for CD were examined for the presence of epithelioid-giant cell granulomas (EGCG) and Rantes and IFN-gamma messenger RNA (mRNA). Normal pediatric intestine (n = 5) and lymph nodes (n = 2) served as controls. RESULTS: Many cells in all CD specimens in the epithelial compartment, lamina propria, and the EGCG gave positive signal with the Rantes antisense probe. Labelled cells were identified on paraffin sections as lymphocytes, macrophages, and epithelioid cells. There were Rantes-positive cells in the control intestinal tissues, but many Rantes-positive cells in control lymph nodes that showed follicular hyperplasia. IFN-gamma-positive cells were present in all CD ileal and lymph node specimens, predominantly in close contact with EGCC. No positive signal was obtained with the Rantes and IFN-gamma sense control probes. CONCLUSIONS: These findings suggest that Rantes and IFN-gamma contribute to the selective accumulation of macrophages and memory T helper lymphocytes inside the granulomas and inflammatory infiltrates that are characteristic of CD.

Adolescent↗

Immunological and virological markers of disease progression in HIV-infected children.

Polymerase chain reaction (PCR), virus culture and antigen detection assays are useful for early detection of vertically transmitted human immunodeficiency virus type 1 (HIV-1) infection in infants under 12 months of age. Sixty-four children born to HIV-1-seropositive mothers were evaluated. Thirteen children (20.3%) were repeatedly positive by PCR analysis. There was 100% concordance between the results obtained from PCR and culture assays. Measurement of p24 antigen in serum was, in contrast, a less sensitive marker of HIV infection: only 5/13 infants had positive p24 antigen results. We have investigated the relationship among the HIV-1 biological phenotype, replicative capacity of viral isolates, HIV RNA copy number in plasma, p24 antigenaemia, CD4 T lymphocyte counts and the clinical status in 13 HIV-infected infants. Six out of 13 HIV-1 isolates from these patients were classified as rapid/high and seven as slow/low. We have found a significantly positive correlation between the replication rate of HIV isolates and their capacity to induce syncytia in vitro. The HIV-1 isolates with rapid/high and syncytium-inducing phenotype, and isolates with slow/low and non-syncytium-inducing phenotype were obtained from infants who had HIV-1 RNA copy number ml(-1) plasma values of 27654-83520 and 1342-34321, respectively. Levels of HIV-1 RNA were measured in sequential plasma samples from three HIV-infected infants and their biological properties determined in vitro. Our findings indicate that infants who carried viruses with more cytophatic biological phenotype and who had higher viral RNA copy numbers in blood were more likely to have lower CD4+ T cell counts and more likely to develop full-blown AIDS.

Biomarkers↗

Hypomethylation of human sperm pronuclear chromosomes.

Using the methylase SssI enzyme, we have analyzed the degree of in situ methylation of human sperm pronuclear chromosomes obtained by fertilizing hamster oocytes with human sperm. Untreated (control) sperm chromosome complements showed a higher degree of in situ methylation, compared to sperm complements previously treated with 5-azadeoxycytidine or lymphocyte chromosomes. This indicates that human sperm pronuclear chromosomes have a lower degree of genomic methylation compared to that of other somatic cells. The similarity in the degree of in situ methylation of the euchromatic and heterochromatic regions of chromosomes 1, 9, 15, and 16 and the Y chromosome in human sperm does not support the existence of a possible correlation between hypomethylation and heterochromatin decondensation.

Animals↗

[Auditory behavior monitoring after bacterial meningitis. Case report].

Bacterial meningitis is the main cause for acquired hearing loss. Nevertheless very little has been written about the development of the auditory behaviour either for improvement or for deterioration, after hospital release. The present study describes the case of a five month old boy with Haemophilus influenzae meningitis. Amongst various complications, a decrement in the auditory acuity was detected in the immediate evolution, with significant improvement later on by qualitative and quantitative tests.

Hearing Disorders↗

[Anitis, vulvar edema and macrocheilitis disclosing Crohn disease in a child: value of metronidazole].

BACKGROUND: We report a case of oro-genital and perianal Crohn's disease which progressed for 4 years with no digestive involvement in a 12-year-old girl. CASE REPORT: At the age of 8 years, a young girl developed recurrent anal fissures. Voluminous vulvar edema developed at 12 years with fissurar macrocheilitis. There were no digestive signs and the diagnosis of Crohn's disease was obtained on the basis of granulomatous epithelioid infiltration of biopsy specimens (Bauhin valve, anus, vulva). Metronidazole given per os at the dose of 25 mg/kg/day for 6 months led to partial significant symptomatic remission. DISCUSSION: Unilateral or bilateral vulvar edema is highly suggestive of Crohn's disease even if the classical digestive inflammatory signs are absent. Demonstration of perianal lesions (erythema, pseudocondylomatous formations) must not mislead the diagnosis (sexual abuse). Simultaneous granulomatous lesions in the genital and labial regions is exceptional in Crohn's disease. Ileocolonoscopy is indicated in such cases and alone can demonstrate latent digestive inflammatory processes. Different agents have been proposed for treatment of local Crohn's disease skin lesions. It is difficult to evaluate their efficacy due to the spontaneous variability of disease expression.

Cheilitis↗

Characterization of tumorigenic sub-lines from a poorly tumorigenic human colon-adenocarcinoma cell line.

The interaction of tumor cells with extracellular-matrix components is suspected to play an important role in tumorigenesis induction. The tumorigenicity of a poorly tumorigenic human colon-adenocarcinoma cell line (BCS-TC2) was induced by co-injection with Matrigel. A new cell sub-line, BCS-TC2.1, was isolated and established from these tumors. Implantation of these cells in nude mice in the absence of Matrigel-generated tumors which allowed the establishment of another tumorigenic cell sub-line, BCS-TC2.2. Matrigel and laminin, but not collagens, promote the tumorigenicity of BCS-TC2 cells, probably due to specific interactions of a pre-existing minor cell sub-population with laminin, which facilitate the initial growth of these cells in vivo. Cytogenetic analysis reveals that both sub-lines originate from the parental one, but a new marker in chromosome 9 is observed. These sub-lines present a lower degree of differentiation, as deduced from the lower CEA content, 5'-nucleotidase and alkaline-phosphatase activities. No variation is observed in the mRNA and protein expression of the 67-kDa laminin-binding protein. However, an increase in beta1 integrins and a parallel decrease in beta4 integrin were detected. Thus, the new sub-lines, compared to the parental cells, present karyotypic and phenotypic differences such as the expression of a distinctive integrin pattern. This system represents a useful model for understanding the development and progression of tumorigenicity in cancer cells.

5'-Nucleotidase↗

Role of the C terminus of the interleukin 8 receptor in signal transduction and internalization.

Interleukin 8 (IL-8) is a potent neutrophil chemoattractant and activator. Two IL-8 receptor subtypes, A and B, are expressed in neutrophils. In this work, we analyzed the role of the C terminus domain of the IL-8 receptor on the signal transduction and receptor internalization mechanisms. The IL-8 receptor A was tagged with an epitope corresponding to the monoclonal antibody 1D4 to monitor the localization of the IL-8 receptor. We demonstrated IL-8-dependent receptor internalization by monitoring the density of surface 125I-labeled IL-8 binding sites and by immunofluorescence microscopy. Truncation of the last 27 amino acids of the IL-8 receptor A severely impaired the IL-8-induced internalization of the receptor. Of importance was the observation that binding of IL-8 to receptors A and B triggered a dramatically faster rate of internalization of receptor B than receptor A, suggesting that the heterologous C termini among receptor subtypes modulate the rate of internalization of IL-8 receptors. However, substitution of the C terminus of the receptor subtype A for the C terminus of receptor B reduced the internalization rate of receptor A. Furthermore, we found that the rate of internalization of IL-8 receptor B triggered by IL-8 was faster than the one induced by the IL-8-related peptide, melanoma growth stimulatory activity. Studies with human neutrophils pretreated with 100 nM IL-8 for 5 min revealed a positive and a negative calcium response mediated by receptors A and B, respectively. In contrast, neutrophils pretreated with melanoma growth stimulatory activity showed positive calcium responses to both receptors A and B. These data suggest that the neutrophil responses mediated by IL-8 are modulated by the rate of internalization of receptors.

Animals↗

[Sleeping position, prevention of sudden death syndrome and gastroesophageal reflux].

Based on results of epidemiological studies, dorsal or lateral sleeping positions are now recommanded in the prevention of sudden infant death syndrome (SIDS). This raises an ethical question about the attitude towards the ventral positioning therapy for gastroesophageal reflux (GOR). The consensus conference considers that the ventral position should only be recommanded in GOR when the benefit appears to outweigh the risk of SIDS that it induces. The conference proposes that for infants with simple uncomplicated reflux, sleeping in the prone position should not be introduced in the first line treatment. Prone positioning should be restricted to complicated cases resistant to dietary and medical measures.

Gastroesophageal Reflux↗