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J Navarro

Publications and source records attributed to J Navarro.

At least 127 records · Page 7Linked to original sources
PubMed1998

Regulation of tumour cell sensitivity to TNF-induced oxidative stress and cytotoxicity: role of glutathione.

Glutathione (GSH) and the rate of cellular proliferation determine tumour cell sensitivity to tumour necrosis factor (TNF). Buthionine sulphoximine (BSO), a selective inhibitor of GSH synthesis, inhibits tumour growth and increases recombinant human TNF (rhTNF)-alpha cytoxicity in vitro. Administration of sublethal doses of rhTNF-alpha to Ehrlich ascites-tumour (EAT)-bearing mice induces oxidative stress (as measured by increases in intracellular peroxide levels, O2.- generation and mitochondrial GSSG). ATP-induced selective GSH depletion, when combined with rhTNF-alpha administration, affords a 61% inhibition of tumour growth and results in a significant extent of host survival. Administration of N-acetylcysteine (NAC) or GSH ester abolishes the rhTNF-alpha and ATP-induced effects on tumour growth by maintaining high GSH levels in the cancer cells. TNF-induced mitochondria GSH depletion appears critical in the cascade of events that lead to cell death.

Animals↗
PubMed1998

Expression and regulation of leukotriene-synthesis enzymes in rat liver cells.

The liver plays a major role in metabolism and elimination of leukotrienes (LT). It produces cysteinyl leukotrienes (cLT), and cLT have been implicated in hepatocellular toxicity in several models of lipopolysaccharide (LPS)-associated liver injury. However, the liver cell types responsible for cLT production are poorly defined, and the expression of the LT-synthesis enzymes, 5-lipoxygenase (5-LO) and LTC4 synthase (LTC4-S), in liver cells has never been demonstrated. The aim of the present study was to examine the ability of rat liver cells to produce cLT by determining whether hepatocytes, Kupffer cells, and sinusoidal endothelial cells express mRNA and enzyme activities of the LT-synthesis enzymes and whether expression is altered by LPS. 5-LO mRNA was expressed in whole liver, and expression was enhanced by LPS. Cell fractionation studies demonstrated that expression was present in Kupffer cells and sinusoidal endothelial cells, but not in hepatocytes. LTC4-S mRNA was detected in whole liver, hepatocytes, and sinusoidal endothelial cells, but not in Kupffer cells. Semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) showed that LPS increased LTC4-S expression in hepatocytes by a factor of 3 (n = 3; P < .03). LTC4-S enzyme activity in the microsomal fraction of hepatocytes was also increased from 0.52 +/- 0.13 to 1.90 +/- 0.66 nmol . mg protein-1 . 5 min-1 (n = 6; P < .015) after LPS treatment. These results indicate that hepatocytes do not possess the ability for de novo synthesis of cLT from arachidonic acid, but they may actively participate in cLT production by conjugation of LTA4 with glutathione to produce LTC4. LPS enhances LTC4-S expression in hepatocytes. This intrinsic cLT production may contribute to hepatocellular injury during inflammation.

Animals↗
PubMed1998

Collagenous gastritis revealed by severe anemia in a child.

Collagenous gastritis is a rare histopathological disorder of unknown origin, characterized by a subepithelial collagen deposit greater than 10 microm thick, associated with an inflammatory infiltrate of the gastric mucosa. This report describes a second pediatric case of collagenous gastritis, revealed by severe anemia caused by gastric bleeding, as was the first case. Unlike the adult cases of collagenous gastritis, lesions were limited to the stomach, and remained unchanged on six series of biopsies taken during a 30 month follow-up, despite treatment with omeprazole, sucralfate and corticosteroids. An immunohistochemical study showed signs of local immune activation on all biopsy specimens, including overexpression of HLA-DR by epithelial cells, increased numbers of CD3+ intraepithelial lymphocytes, and CD25+ cells in the lamina propria. Although the cause of the disease remains unclear, our findings suggest that the histopathological lesions of collagenous gastritis may result from a local immune process.

Anemia↗
PubMed1998

[Perineal lesions in childhood Crohn disease].

BACKGROUND: Perineal lesions (PAL) usually evolve together with bowel disease and often constitute a serious and disabling complication of Crohn's disease. PATIENTS: Forty-three children (47%) with Crohn's disease developed PAL in a retrospective study of 92 patients ranging in age from 4 to 20 years. RESULTS: PAL occurred at the mean age of 11.4 +/- 0.7 years, prior to diagnosis in 25% or subsequently in 21%. PAL were severe: complex fistulae (15%), rectovaginal fistulae (2%), anal raggedness (13%); moderate: subcutaneous fistulae (11%), abscesses (19%), cavitating ulcers (9.5%) and stricture formations (5.7%); or mild: eczema (6.7%), fissures (57%) and skin tags (17%). An association with these various features has been observed in 31%. The extent of involvement of the gastrointestinal tract was rectosigmoid (72%), ileal and colonic (41%), ileal with pancolitis (12%). Two PAL course profiles were observed: one with exacerbation and remissions (52%), the other without remission (48%), especially anal raggedness (100%), cavitating ulcers (80%) and skin tags (61%). Medical treatment included steroids (54%), metronidazole (53%), salicylates (51%), nutritional support (44%), azathioprine (17%). PAL healed in 41%. Surgical treatment was performed in 27% with 83% of healing. Relapses occurred in 35% after medical treatment and 86% after surgery.

Abscess↗
PubMed1998

[International registry on mucoviscidosis: comparison of the French data with the European data for 1995].

BACKGROUND: The Epidemiologic Registry of Cystic Fibrosis (ERCF) is an international registry, sponsored by Roche Laboratories, collecting data about CF patients in Europe. The aim of the our study is to compare the French data with the European data collected during the year 1995. RESULTS: By December 31st 1995, 8,831 patients have been enrolled in Europe, including 1,457 patients in France. French CF patients are younger (mean age = 12.6 years) than European CF patients (mean age = 14.6 years). Genotype is better characterised in France (89 vs 75% for European patients), but only 49% of CF patients are homozygote for the DF508 deletion in France versus 77% in Denmark. Two clinical features of French CF patients are interesting: 1) presence of Staphylococcus aureus and Haemophilus influenzae (52%) is more frequent in France than in Europe (65 vs 48% and 52 vs 29%, respectively), 2) lung function tests (forced vital capacity [FVC]), forced expiratory volume per second [FEV1] are worse in France (P < 0.001) particularly in the older patients (> 18 years): 39% of these patients in France have a FEV1 < 40% of predicted value compared to only 29% in Europe. Similarly there are fewer patients in this age group in France (22 vs 31% in Europe) having a FVC > 90% of the predicted value in France. With regard to the treatment, three differences emerge: 1) dornase alfa is more used in France (55 vs only 34% in Europe); 2) use of prophylactic inhaled and oral antibiotics is less common in France than in all age groups; 3) the use of inhaled corticosteroids and bronchodilators is also less common in France despite the same incidence of asthma-like symptoms. Finally we notice that the mean age at death in 1995 is 18.2 years (+/- 2.38) in France and 20.6 years (+/- 0.85) in Europe. CONCLUSION: These results are preliminary because 1995 is the first year for ERCF in France and a low percentage of French CF patients are included for this year. Therefore they must be interpreted with caution. Nevertheless, we can hypothesise about a relationship between these results and a less aggressive treatment regimen. The impact of dornase alfa use on prognosis seems interesting to analyse in future years.

Adolescent↗
PubMed1998

[Iterative intestinal intussusception and appendiceal mucocele in an infant with mucoviscidosis].

UNLABELLED: Cystic fibrosis is a common and potentially life-threatening hereditary disease which can affect numerous organs, particularly the digestive tract. CASE REPORT: A 4.5-year-old boy exhibited two little known clinical manifestations: an appendiceal mucocele and repeated intussusceptions. In spite of an appendectomy, intussusception relapsed and an ileocolic resection was necessary 2 years later. DISCUSSION: Appendiceal diseases in cystic fibrosis represent a large spectrum, ie, distention on the appendiceal lumen, engorged with sticky mucous matter, which becomes an appendiceal mucocele, peritonitis with an appendiceal perforation due to delayed diagnosis since acute appendicitis is difficult to diagnose in these patients. Intussusception is rarely observed in cystic fibrosis. CONCLUSION: Appendiceal mucocele could be a cause of intussusception. If an appendectomy is performed, resection of a part of the cecum, around the appendix, could be useful in preventing again mucocele formation.

Appendectomy↗
PubMed1998

[Protein and energy needs of the infant with severe malnutrition. Application in a hospital environment for the treatment of malnutrition caused by deficient intake].

Severe malnutrition is defined by a weight for height below 70% of international standards or by presence of oedema in a clinically undernourished child. Severe malnutrition associated with oedema is called kwashiorkor. The origin of oedemas of kwashiorkor is still debated, but its relation with protein deficiency is strongly questioned. The same dietary management is now recommended for malnutrition with or without oedema. Present recommendations are based, as for well nourished children, on the separate estimation of nutritional requirements for maintenance and growth. Total requirements vary between 0.7 g/kg/day in the first few days of treatment to 5 g/kg/day or more when weight gain is maximum. As a result of high energy requirement during catch-up growth, protein requirements never exceed 10 to 12% of total energy needs.

Child Nutrition Disorders↗
PubMed1998

CD44 variant expression in inflammatory colonic mucosa is not disease specific but associated with increased crypt cell proliferation.

AIMS: A recent study reported increased epithelial expression of CD44 variants in ulcerative colitis (UC) compared with Crohn's disease (CD). However, the use of CD44 expression for diagnostic purposes in inflammatory bowel disease has been controversial, and the meaning of the appearance of CD44 variants in epithelial colonic cells remains unknown. We investigated the relationship between CD44 isoform expression and crypt cell proliferation in paediatric colitis. METHODS AND RESULTS: The expression of CD44v3, CD44v6, and MIB1 (proliferation marker) was studied by immunohistochemistry on surgical colonic samples of UC (n = 13), CD (n = 10), colostomy resections with non-specific mucosal inflammation (NSMI) (n = 3), and normal controls (N = 5). The proliferation index (% of MIB1 positive cells) was assessed in both v6 positive and v6 negative crypts. Epithelial expression of CD44v3 and v6, negative in normal controls, was variable and focal in colitis. No preferential expression of CD44 variants was found in UC. The proliferation index was dramatically increased in v6 positive crypts compared with v6 negative crypts in UC, CD and NSMI. CONCLUSIONS: These data suggest that CD44 variant staining is not a useful marker for distinguishing paediatric UC from CD, and that CD44v6 expression in the inflamed colonic mucosa is not disease specific but is related to crypt cell proliferation.

Antigens, Nuclear↗
PubMed1998

Endoscopic ultrasonography in the evaluation of pediatric digestive diseases: preliminary results.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) is rarely used in pediatrics. Its feasibility and potential indications have been assessed in this retrospective study. PATIENTS AND METHODS: Twenty-three EUS examinations were carried out on 18 children (mean age 12 years, ranging from 4 to 16 years) using a mechanically rotating 7.5 and 12 MHz sector scan transducer. Upper digestive tract EUS (n = 17) was performed in children suffering from biliopancreatic diseases, angiomatosis or digestive tumors. They were performed under intravenous sedation. Anorectal EUS (n = 6), carried out after simple lavage in most cases, investigated tumors (adenomas and carcinoid tumor) or proctological diseases. RESULTS: No technical failures or complications were encountered. EUS proved useful in the diagnosis of pancreatitis and portal hypertension. When included in pretherapeutic examinations, it provided useful information in cases of angiomatosis, biliary lithiasis and polyps. It was also useful in the follow-up of children after endoscopic excision or surgical treatment of adenomas or tumors (carcinoid tumor, neurofibroma). CONCLUSION: EUS would therefore appear to be a promising technique in pediatric gastroenterology. More work is needed in order to better determine its indications and the need for equipment specific to children.

Adolescent↗
PubMed1998

Chromosome studies in first polar bodies from hamster and human oocytes.

Most studies on preconception diagnosis published so far have used polymerase chain reaction (PCR) analysis to identify single gene defects. Although fluorescent DNA probes have been used to obtain a partial cytogenetic diagnosis of aneuploidies in first polar bodies without defined chromosome structures, the analysis of structural chromosome anomalies in the interphase nucleus is not adequate. We describe a procedure to obtain first polar body chromosome complements from hamster and human oocytes. In 63.6% (105 of 165) of hamster first polar bodies the chromosome complement showed a defined chromosome morphology and in 94.1% (16 of 17) of human oocytes fixed after follicular puncture it was possible to obtain high quality, well spread chromosome complements. First polar body chromosomes are fuzzy and shorter than oocyte chromosomes, but fluorescent in-situ hybridization results obtained in human first polar bodies clearly show that it is possible to detect whole chromosomes, centromeres and unique sequences, including the terminal regions of small chromosomes. This suggests that in fresh oocytes, DNA loss resulting from apoptotic chromosome fragmentation has not yet occurred. Using the procedure described, first polar bodies could be used to analyse the meiotic segregation of maternal structural abnormalities and to detect numerical chromosome anomalies in humans.

Aneuploidy↗
PubMed1998

Inhibition of phosphodiesterase type IV suppresses human immunodeficiency virus type 1 replication and cytokine production in primary T cells: involvement of NF-kappaB and NFAT.

Rolipram, a phosphosdiesterase type IV-specific inhibitor, prevented p24 antigen release from anti-CD3-activated human immunodeficiency virus (HIV)-infected T cells and CD4(+)-cell depletion associated with viral replication in a dose-responsive manner but minimally inhibited T-cell proliferation. Moreover, rolipram reduced the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) by HIV-infected T cells. The transcriptional ability of a luciferase reporter gene under control of the HIV long terminal repeat, induced by phorbol myristic acetate plus ionomycin or by TNF-alpha, in primary T and Jurkat cells was also inhibited by rolipram. Rolipram inhibited NF-kappaB and NFAT activation induced by T-cell activation in Jurkat and primary T cells, as measured by transient transfection of reporter genes and electrophoretic mobility shift assays. Exogenous addition of TNF-alpha in the presence of rolipram restored NF-kappaB but not NFAT activation or p24 release. Addition of dibutyryl-cyclic AMP (dBcAMP) mimicked the effects of rolipram on p24 antigen release, NF-kappaB activation, and TNF-alpha secretion, but it did not affect NFAT activation or IL-10 production. The protein kinase A inhibitor KT5720 prevented the inhibition of TNF-alpha secretion but not that of HIV type 1 (HIV-1) replication caused by rolipram. Our data indicate that blockade of phosphodiesterase type IV could be of benefit against HIV-1 disease by modulating cytokine secretion and transcriptional regulation of HIV replication, and they suggest an important role of NFAT in HIV replication in primary T cells. Some of those activities cannot be ascribed solely to its ability to increase cAMP.

Cells, Cultured↗
PubMed1998

Postoperative outcome of Crohn's disease in 30 children.

BACKGROUND: Thirty children operated on for Crohn's disease (CD) were reviewed (1975-1994). The aim of the study was to assess their postoperative outcome. PATIENTS: 19 boys and 11 girls, aged 15.3 (2) years (range 11.3-20) at surgery were studied. RESULTS: Surgical indications were acute complications of CD and chronic intestinal illness. Six months after surgery, 11 of 12 patients had been weaned off steroids, and 22 of 23 patients were weaned off nutritional support; 17 patients without recurrence had a mean (SD) weight gain of 2.1 (8) kg and a height gain of 3.36 (3) cm. During 3.1 (2.7) years follow up, 12 patients (40%) had a recurrence of the disease after 19.4 (14) months (means (SD)): supra-anastomotic recurrence (six), severe perianal disease (two), and chronic illness (four). Six of 14 patients who were treated with mesalazine (13) or azathioprine (one) had recurrences. The postoperative recurrence rate was 50% at two years. CONCLUSION: Surgical treatment modifies the immediate outcome of severe or complicated CD, but does not prevent recurrence, despite localised resection or prophylactic postoperative treatment. Extension of the disease before surgery seems to be a major risk factor for postoperative recurrence in children.

Adolescent↗
PubMed1998

Sperm segregation analysis of a complex chromosome rearrangement, 2;22;11, by whole chromosome painting.

Using the human sperm-hamster oocyte fusion technique and whole chromosome painting, we studied sperm chromosome segregation in a male heterozygous for a complex chromosome rearrangement, 46,XY,-2, +der(2)t(2;11)(q13; q23),-11,+der(11)t(11;22)(q23;q11.2),-22, +der(22)t(2;22)(q13; q11.2). A total of 208 sperm complements were analyzed. The frequency of sperm carrying a normal or a balanced complement was 13.5% (9.62% and 3.85%, respectively). The frequency of unbalanced sperm was 86.5% (64.9% from 3:3 segregation, including 30 different types; 20.7% from 4:2 segregation, including 21 different types; and 0.96% from 5:1 segregation, including 2 different types). The sex ratio, determined in 134 sperm complements, did not differ from the expected 1:1 ratio. The results obtained in this study are compatible with the formation, during the synaptic process, of a complex hexavalent figure involving chromosomes 2, 11, and 22. The behavior and segregation of this complex figure would explain the high frequency (86.5%) of unbalanced complements observed in this carrier.

Animals↗
PubMed1998

Lipid composition of platelets in patients with uremia.

AIMS: The lipid composition of platelets and the function of these cells in patients with uremia were studied. METHODS: Fourteen patients and 14 normal volunteers were studied. Platelet lipids including phospholipids and cholesterol, as well as the platelet aggregation response to agonists, were studied. RESULTS: The amount of platelet phospholipids was decreased in patients compared to controls (338.0 +/- 79 vs. 511.6 +/- 125 nmol/10(9) cells; p < 0.001), while the percentage of the five main specimens of these compounds was normal. The content of platelet cholesterol in patients (97.8 +/- 17.0 microg/10(9) cells) was similar to that in controls (91.7 +/- 26.0 microg/10(9) cells). Consequently, the cholesterol:phospholipid ratio in uremic platelets was increased (0.75 +/- 0.1 vs. 0.46 +/- 0.1; p < 0.01). Although this feature is associated with hyperreactive platelets, the aggregation tests were defective for adenosin diphosphate (p < 0.01), arachidonic acid (p < 0.01), epinephrine (p < 0.01) and collagen (p < 0.001). This behavior is probably due to the multifactorial platelet defect described in uremia.

Adult↗
PubMed1998

Interleukin-12 expression is focally enhanced in the gastric mucosa of pediatric patients with Crohn's disease.

The stomach is frequently involved in children suffering from Crohn's disease (CD). Diagnosis of specific gastritis may be difficult when granulomas are absent. We have used in situ hybridization to examine the expression of interleukin (IL)-12, a key cytokine in the Th1 response. IL-12 p35 and p40 antisense probes were used to examine ileal specimens from 9 children with CD and gastric biopsies from 24 children (13 with CD, 6 with Helicobacter pylori chronic gastritis, and 5 with a normal gastric mucosa). In all patients with CD, many clusters of IL-12-positive cells were present in the lamina propria. This was the case in the ileal specimens as well as in gastric mucosa showing granulomatous gastritis or nongranulomatous gastritis. The same distribution patterns were found for the IL-12 p35 and p40. In three patients with Helicobacter pylori gastritis, few scattered IL-12-positive cells were found. No positive cells were found in the normal gastric mucosa. The focally enhanced IL-12 expression in the gastric mucosa of pediatric patients with CD, with or without specific lesions, suggests that both are indeed linked to the disease and supports the major part of IL-12 in initiating and maintaining of the cascade resulting in the Th1 responses.

Adolescent↗