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Biomedical subjects

J Navarro

Publications and source records attributed to J Navarro.

At least 199 records · Page 11Linked to original sources
PubMed1995

Involvement of nitric oxide in bone marrow-derived natural suppressor activity. Its dependence on IFN-gamma.

Bone marrow (BM)-derived natural suppressor (NS) cells are strong inhibitors of lymphoproliferative responses. In this study we have assessed the involvement of nitric oxide (NO) in BM-derived NS activity, as detected in cocultures of BM and spleen cells stimulated with B cell (LPS) or T cell (Con A) mitogens. The results indicate that NS activity is readily inhibited by NG-monomethyl-L-arginine, a competitive inhibitor of NO synthase, or N-acetylcysteine, a free radical-scavenging thiol compound. High amounts of nitrite, a stable end product of NO, are detected only in supernatants of Con A- or LPS-stimulated spleen cells cocultured with BM cells enriched in NS activity (Fr3 cells). These amounts (15 to 55 microM) are strongly antiproliferative for both Con A and LPS responses, as was established with a nitrite curve made with a NO donor (sodium nitroprusside). Fr3 cells cultured alone release large quantities of NO and express inducible NO synthase (iNOS) mRNA upon LPS stimulation, but require spleen cells in cultures stimulated with Con A. Anti-IFN-gamma-neutralizing Abs blocked both NO production and NS activity, irrespective of the mitogen used; yet, only exogenous IFN-gamma is unable to promote successful NO production by Fr3 cells, but does induce detectable iNOS mRNA expression in these cells. Taken together the results indicate that: 1) NO is the major mediator of BM-derived NS activity; 2) BM cells enriched in NS activity produce large amounts of NO through an IFN-gamma-dependent iNOS induction.

Acetylcysteine↗
PubMed1995

[Nasal transepithelial difference of potential in mucoviscidosis. Clinical application of the measurement].

OBJECTIVES: To demonstrate the value of nasal transepithelial potential difference measurements in the diagnosis and assessment of therapeutic effect in cystic fibrosis. METHOD: Nasal transepithelial potential difference was measured in 50 patients with cystic fibrosis (mean age 10 years) and 21 controls (mean age 8 years). RESULTS: There was a very significant increase in nasal transepithelial potential in cystic fibrosis patients (-28 +/- 8 mv) compared with controls (-8 +/- 3 mv) (p < 0.0001). The sensitivity and specificity of this test for the diagnosis of cystic fibrosis were 92% and 95% respectively. Nasal transepithelial potential difference was positively correlated with age (r = 0.43; p < 0.002) in cystic fibrosis patients but no correlation was found in controls. There was no significant difference in potential differences as a function of sex or Delta F508 genotype (homozygous vs heterozygous; Delta F508 vs non-Delta F508). CONCLUSION: These findings demonstrated the value of transepithelial potential difference in the diagnosis of cystic fibrosis and emphasized its capacity to assess the effect of new therapeutic protocols aimed at modifying C1- and Na+ ion transport. It could be particularly helpful for the interpretation of doubtful sweat tests.

Adolescent↗
PubMed1995

Detection of a germline mutation at codon 918 of the RET proto-oncogene in French MEN 2B families.

Multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC) are three dominantly inherited disorders linked to the same disease locus on chromosome 10. Two types of germline mutation of the RET proto-onco-gene, which codes for a transmembrane tyrosine kinase, are associated with MEN 2. Missense mutations at cysteine residues in the extra-cytoplasmic domain are exclusively associated with MEN 2A and FMTC. In MEN 2B patients, a single point mutation at codon 918 has recently been characterized, leading to the replacement of a methionine by a threonine within the RET tyrosine kinase domain. We now report the identification of a mutation at codon 918 in the germline of 16 patients out of 18 unrelated MEN 2B families analyzed. In these families we have been able to demonstrate that, in five cases, the mutation arose de novo, and that, in one kindred, it was coinherited with the disease. These results indicate that a unique mutation at codon 918 of the RET gene is the most prevalent genetic defect causing MEN 2B, but also that rare MEN 2B cases are associated with different mutations yet to be defined.

Adolescent↗
PubMed1995

[Perspective of use of rhDNase and new therapeutics for cystic fibrosis].

The prognosis of cystic fibrosis has dramatically improved during the last three decades. This improvement was due to optimization of symptomatic treatment: antibiotics to combat infection, nutritional support, emphasis on bronchial drainage by physiotherapy and aerosols. The discovery of the gene responsible for the disease and the encoded protein opens the way to a specific and curative approach based upon the knowledge of the intrinsic properties of the protein, and its role in ionic flux. Recently, owing to the development of bioengineering, a recombinant human DNase has become available for clinical use. When aerosolized in the patients, it leads to deep changes in rheological parameters of the secretions that facilitate bronchial drainage and clearing of the airways. Gene therapy, the ultimate expression of these advances, will soon enter the era of clinical applications. Unsolved methodological and ethical issues still preclude immediate use in the patients. The results of transplantation surgery have also dramatically improved since the beginning. Indications are more precisely defined and restricted to the more advanced forms of the disease, according to severe criteria of inclusion.

Administration, Inhalation↗
PubMed1995

Elimination of Ehrlich tumours by ATP-induced growth inhibition, glutathione depletion and X-rays.

ATP-induced tumour growth inhibition is accompanied by a selective decrease in the content of the tripeptide glutathione (GSH) within the cancer cells in vivo. Depletion of cellular GSH sensitizes tumours to chemotherapy and radiation, but the usefulness of this depletion depends on whether the levels of GSH can be reduced in the tumour relative to normal tissues. We report here that administration of ATP in combination with diethylmaleate and X-rays leads to complete regression of 95% of Ehrlich ascites tumours in mice. This shows that an aggressive tumour can be eliminated by using a therapy based on modulation of GSH levels in cancer cells.

Adenosine Triphosphate↗
PubMed1995

C-terminal phosphorylation of human respiratory syncytial virus P protein occurs mainly at serine residue 232.

To determine which human respiratory syncytial virus (HRSV) P protein serine residues are modified by cellular protein kinase(s), several mutated versions of P protein were expressed in the absence of other viral proteins. Mutations at serines 232 or 232 and 237 drastically reduced the extent of phosphorylation P protein in vivo. Serine 232 is the main site of modification and is also essential for in vitro phosphorylation by casein kinase II. Additional in vivo phosphorylation was also detected in the region containing serines 116, 117 and 119.

Amino Acid Sequence↗
PubMed1995

Nitric oxide and prostaglandins in the prolonged effects of losartan and ramipril in hypertension.

We investigated the role of endogenous nitric oxide, kinins, and prostaglandins in the vasodepressor and renal excretory effects of the angiotensin II receptor antagonist losartan and the angiotensin-converting enzyme inhibitor ramipril administered for 1 week to spontaneously hypertensive rats. To this end, either losartan (10 mg/kg per day) or ramipril (2.5 mg/kg per day) was administered in drinking water with or without simultaneous administration of (1) the nitric oxide synthesis inhibitor Ng-nitro-L-arginine methyl ester (L-NAME, 6 mg/kg per day), (2) the cyclooxygenase inhibitor indomethacin (5 mg/kg per day), (3) the bradykinin B2 receptor antagonist Hoe 140 (0.5 mg/kg per day SC), or (4) L-NAME plus indomethacin. Both losartan and ramipril significantly reduced blood pressure as measured by the tail-cuff method. L-NAME increased blood pressure when administered solely or in combination with losartan. However, L-NAME attenuated the hypotensive effect of ramipril. Indomethacin did not affect blood pressure but it reduced the antihypertensive action of losartan and ramipril. Indomethacin administration did not potentiate the increase in blood pressure induced by L-NAME. However, the concurrent administration of both inhibitors almost totally blunted the vasodepressor action of ramipril. By contrast, losartan administration in the presence of L-NAME and indomethacin increased blood pressure to a level similar to that after losartan plus L-NAME. Hoe 140 did not modify either blood pressure or the hypotensive effects of losartan or ramipril. Increases in diuresis and water intake were observed during ramipril administration. Both effects were blunted only with the concurrent administration of L-NAME and indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Imbalance between 95 kDa type IV collagenase and tissue inhibitor of metalloproteinases in sputum of patients with cystic fibrosis.

A growing body of evidence suggests that neutrophil-derived proteinases play a major role in lung tissue damage in cystic fibrosis (CF). Most previous studies have focused on serine proteinases such as neutrophil elastase, providing no information on the extent to which metalloproteinases participate in proteolytic processes in CF. To address this issue, we evaluated the contribution of one of the major neutrophil metalloproteinases, i.e., 95 kDa gelatinase (type IV collagenase), to the total gelatinolytic activity measured in sputum specimens from 27 patients with CF. Compared with asthmatic children (n = 9), CF patients had a 6.7 times greater level of total gelatinase activity in sputum revealed by zymography. The 95 kDa gelatinase was increased 3.7-fold in the CF subjects (2,441 +/- 411 [SEM] arbitrary units [AU] x 10(6) per ml of sputum versus 665 +/- 201 in asthmatics) and the 88-kDa active form 23.2-fold (2,272 +/- 372 AU x 10(6) per ml of sputum versus 98 +/- 43, respectively). Using radiolabeled 3H-gelatin as the substrate, we demonstrated uninhibited gelatinolytic activity in all CF patients; this activity was significantly correlated to disease severity as assessed by pulmonary function tests. Western blotting using anti-tissue inhibitor of metalloproteinase (anti-TIMP) and anti-95/88-kDa gelatinase antibodies demonstrated a more than 10-fold excess of 95/88 kDa gelatinase over TIMP. Bacterial proteinases from Pseudomonas aeruginosa were shown to contribute little to the gelatinolytic activity measured in sputum supernatants from patients with CF, although culture supernatants from various P. aeruginosa strains expressed gelatinolytic activity in vitro. Finally, lung damage, as assessed by increased type IV collagen degradation products in sputum, was significantly correlated to concentrations of active 88 kDa gelatinase. These data argue for a significant role of 95/88 kDa gelatinase in airway damage in CF.

Adolescent↗
PubMed1995

Latent pulmonary function abnormalities in children with Crohn's disease.

Recently, latent pulmonary involvement has been described in adult patients with inflammatory bowel disease. It is unknown, however, whether this also occurs in children, and whether the pulmonary abnormalities differ between the acute phase and remission. The incidence of pulmonary abnormalities has been investigated in 26 children with acute or quiescent Crohn's disease in terms of the following parameters: clinical pulmonary symptoms, chest roentgenograms and pulmonary function tests, including lung transfer factor for carbon monoxide (TLCO). One child had a severe digital clubbing. Chest radiographs were normal in all subjects. No significant differences were found between acute and quiescent phase for pulmonary volumes and expiratory flows, but TLCO (% predicted) was significantly decreased during the active phase of the disease as compared to remission (53 +/- 15 vs 81 +/- 19% predicted). These data suggest that latent pulmonary involvement is also present in a paediatric population with active Crohn's disease, despite a short disease history and absence of smoking. Although the nature of this abnormality remains unclear, this extradigestive epiphenomenon should be taken into account with respect to the aetiopathogenesis of Crohn's disease.

Adolescent↗
PubMed1995

An analysis of human sperm chromosome breakpoints.

Sperm chromosome analysis of 19 sperm donors with either normal or balanced karyotypes was carried out in order to explore the nature of sperm chromosome structural aberrations. A total of 2,389 cells (range 36-298/donor) were karyotyped after in vitro penetration of hamster eggs. The median percentage of sperm structural aberrations was 9.3% (SD +/- 4.7; range 0%-17.8%), with a total of 247 breakpoints, of which 220 could be characterized fully. Two sets of donors were studied in two different centers: center 1 (United States) and center 2 (Spain). The frequencies of nonrejoined and rejoined chromosome-type aberrations were very similar between center 1 and center 2: 83.6% and 10.0%, and 75.0% and 10.3%, respectively. Chromatid-type aberrations were more frequent in center 2 (14.7%) than in center 1 (6.4%) (P = .037). Chromosome 4 had less than the expected number of breakpoints (P < .001). A positive significant correlation was found between sperm breakpoints reported in this study and sites of balanced chromosome de novo rearrangements detected at prenatal diagnosis and reported in the literature (P = .0001).

Adult↗
PubMed1995

[Iron and pregnancy].

Infants, young children, and childbearing aged women are particularly exposed to iron deficiency. Pregnancy further increases iron requirements. Nevertheless the consequences of anemia and/or iron deficiency on pregnancy outcome, development of the foetus and postnatal iron status of the infant, remain to be determined. There is a 3-fold increase of premature deliveries in iron deficient anemic pregnant women whose anemia is discovered in early pregnancy: however this increased risk of premature delivery is not observed when iron deficiency anemia is discovered in late pregnancy. Iron supplementation during pregnancy improves the maternal hematological parameters but it is still unclear whether it also improves the maternal health and the pre and postnatal development of the child. Based on our actual knowledge, iron supplementation during pregnancy is to be recommended in risk groups only (ie mainly adolescents, low income women, women with multiple pregnancies), using ferrous iron at a dosage of 30 mg per day.

Anemia, Iron-Deficiency↗
PubMed1995

Relationship between maternal folate status and foetal hypotrophy in a population with a good socio-economical level.

A longitudinal study was conducted on 2 groups of pregnant women according to the presence (n = 8) or absence (n = 13) of IUGR through echography at the 3rd trimester of pregnancy. Mothers answered a general questionnaire, including some alimentary data. Anthropometric measures from the newborns were recorded. Haematological parameters and folate status of the women at 32 weeks of pregnancy and of the mother and child at delivery were assessed. Although a significant cross correlation (p < 0.02) between the newborns' folate status and the mother's one, including folate intake, was obtained, no relationship was found between birthweight and folate status at delivery. In contrast, the study evidences significant correlations between birthweight and both folate status of the mother at the third trimester of pregnancy (p < 0.02) and the decrease of her erythrocyte folate level before delivery (p < 0.01). In our sample, folate status of the pregnant woman at the third trimester offers a predictive value of the newborn weight, but this result remains to be confirmed in a larger study.

Anthropometry↗