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Biomedical subjects

M Navarro

Publications and source records attributed to M Navarro.

At least 73 records · Page 4Linked to original sources
PubMed2001

Regulation of the differentiation-related gene Drg-1 during mouse skin carcinogenesis.

Differentiation-related gene-1 (Drg-1) has been identified as a gene whose expression is increased in several processes related to differentiation, but its function is currently unknown. In this report, we show that Drg-1 was expressed in keratinocytes, this expression being rapidly increased as a result of induction by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the presence of an activating form of Ha-ras. Induction by TPA occurred both in cultured cell lines and primary keratinocytes as well as in mouse skin after a single TPA application. Overexpression of Drg-1 was also observed in TPA-induced hyperplastic skin. In agreement, mouse skin papillomas and carcinomas also overexpressed Drg-1. In addition, Drg-1 was induced when keratinocytes were forced to differentiate by calcium switch or serum starvation. Analysis of the expression of Drg-1 during the keratinocyte cell cycle demonstrated relatively high levels of Drg-1 mRNA in G(0), which increased in early G(1) and decreased afterwards in late G(1)/S. In situ analysis showed an accumulation of Drg-1 in the suprabasal layers of the skin, as well as in the more differentiated areas of mouse skin papillomas. These results suggest that, in addition to being upregulated during keratinocyte differentiation, the Drg-1 gene might have a complex function in skin tumorigenesis.

Animals↗
PubMed2001

Role of the endogenous cannabinoid system as a modulator of dopamine transmission: implications for Parkinson's disease and schizophrenia.

The endogenous cannabinoid system is a new signaling system composed by the central (CB1) and the peripheral (CB2) receptors, and several lipid transmitters including anandamide and 2-arachidonylglycerol. This system is the target of natural cannabinoids, the psychoactive constituents of Cannabis sativa preparations (marijuana, hashish). Acute and chronic cannabis exposure has been associated with subjective feelings of pleasure and relaxation, but also to the onset of psychiatric syndromes, a decrease of the efficacy of neuroleptics and alterations in the extrapyramidal system regulation of motor activity. These actions point to a tight association of the cannabinoid system with the brain dopaminergic circuits involved in addiction, the clinical manifestation of positive symptoms of schizophrenia and Parkinson's disease. The present work discusses anatomical, biochemical and pharmacological evidences supporting a role for the endogenous cannabinoid system in the modulation of dopaminergic transmission. Cannabinoid CB1 receptors are present in dopamine projecting brain areas. In primates and certain rat strains it is also located in dopamine cells of the A8, A9 and A10 mesencephalic cell groups, as well as in hypothalamic dopaminergic neurons controlling prolactin secretion. CB1 receptors co-localize with dopamine D1/D2 receptors in dopamine projecting fields. Manipulation of dopaminergic transmission is able to alter the synthesis and release of anandamide as well as the expression of CB1 receptors. Additionally, CB1 receptors can switch its transduction mechanism to oppose to the ongoing dopamine signaling. Acute blockade of CB1 receptor potentiates the facilitatory role of dopamine D2 receptor agonists on movement. CB1 stimulation results in sensitization to the motor effects of indirect dopaminergic agonists. The dynamics of these changes indicate that the cannabinoid system is an activity-dependent modulator of dopaminergic transmission, an hypothesis relevant for the design of new therapeutic strategies for dopamine-related diseases such as the psychosis and Parkinson's disease.

Journal Article↗
PubMed2001

Intracranial and mediastinal inflammatory myofibroblastic tumour.

Inflammatory myofibroblastic tumour (IMT) is a rare neoplastic condition, commonly known as inflammatory pseudotumour, which is the most frequent primary tumour of the lung in childhood. IMT can have an extrapulmonary location, but is infrequent in the brain and mediastinum, and it is extremely unusual that both lesions appear simultaneously as in our patient. The definitive diagnosis is established by biopsy, but there are some MRI findings that can be useful to identify the lesion.

Adolescent↗
PubMed2001

The use of mycophenolate mofetil suspension in pediatric renal allograft recipients.

Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adults after renal, cardiac, and liver transplantation. This study investigated the safety, tolerability, and pharmacokinetics of MMF suspension in pediatric renal allograft recipients. One hundred renal allograft recipients were enrolled into three age groups (33 patients, 3 months to <6 years; 34 patients, 6 to <12 years; 33 patients, 12 to 18 years). Patients received MMF 600 mg/m2 b.i.d. concomitantly with cyclosporine and corticosteroids with or without antilymphocyte antibody induction. One year after transplantation, patient and graft survival (including death) were 98% and 93%, respectively. Twenty-five patients (25%) experienced a biopsy-proven (Banff grade borderline or higher) or presumptive acute rejection within the first 6 months post-transplantation. Analysis of pharmacokinetic parameters for mycophenolic acid (MPA) and mycophenolic acid glucuronide showed no clinically significant differences among the age groups. The dosing regimen of MMF 600 mg/m2 b.i.d. achieved the targeted early post-transplantation MPA 12-h area under concentration-time curve (AUC0-12) of 27.2 microg h per ml. Adverse events had similar frequencies among the age groups (with the exception of diarrhea, leukopenia, sepsis, and anemia, which were more frequent in the <6 years age group) and led to withdrawal of MMF in about 10% of patients. Administration of MMF 600 mg/m2 b.i.d. is effective in prevention of acute rejection, provides predictable pharmacokinetics, and is associated with an acceptable safety profile in pediatric renal transplant recipients.

Adolescent↗
PubMed2001

Analysis of 31 CFTR mutations in 55 families from the South of Spain.

We carried out a molecular analysis of 350 chromosomes from 55 families originating from the South of Spain (Andalucia) who were diagnosed with cystic fibrosis (CF). We used polymerase chain reaction, followed by an oligonucleotide ligation assay (OLA) and sequence-coded separation using capillary electrophoresis. A frequency of 43.5% for DeltaF508 was found, making it the most common CF mutation in our sample. Seven more mutations (G542X, R334W, R1162X, 2789+5G-->A, R117H, DeltaI507 and W1282X) were detected and accounted for 24.7% of the total. The remaining mutations (31.8%) were undetectable with the methodology used in this study.

Cystic Fibrosis↗
PubMed2001

Diabetes insipidus revealing acute myelogenous leukaemia with a high platelet count, monosomy 7 and abnormalities of chromosome 3: a new entity?

We describe three cases of acute myeloid leukaemia revealed by diabetes insipidus. The patients were 42, 38 and 39 yr old and they had marked hyperleukocytosis, circulating immature granular cells and a normal or elevated platelet count. The leukaemia was type AML-M2 according to the FAB classification. Cytogenetic studies showed inversion of chromosome 3 (q21;q26) in 2 cases and a translocation (3;3)(q21;q29?) in the remaining case, both associated with monosomy 7. All the cerebral CT scans were normal. Complete remission was never achieved, and all three patients survived less than 14 months. Desmopressin therapy was active but treatment could not be reduced. The association of dysmegakaryopoiesis with a chromosome 3 abnormality and diabetes insipidus is probably not fortuitous and could represent a new entity.

Adult↗
PubMed2001

Purification and conformational properties of a human interferon alpha2b produced in Escherichia coli.

Recombinant human interferon alpha2b was expressed intracellularly in Escherichia coli as insoluble aggregates using a new expression vector, and was purified to homogeneity using essentially two-step chromatographic procedures, i.e. immobilized metal-ion-affinity chromatography and reversed-phase HPLC. The established purification process is highly reproducible and leads to a total recovery of approx. 12% with a specific biological activity of higher than 1x10(8) i.u./mg of protein, which is comparable with the international requirement for interferon alpha2b. For purified protein we report conformational stability as a function of pH and temperature using differential scanning calorimetry and CD. Thermal unfolding as a function of pH showed only one endotherm at a temperature higher than 45 degrees C, and was reversible at pH 2-3.75 and irreversible at pH 4-10. At pH 7.0, the most stable condition, the conformational stability depends on protein concentration and ionic strength. The highly helical secondary structure is very conserved over the whole pH range studied, including at high temperatures.

Calorimetry, Differential Scanning↗
PubMed2001

Age and gender differences in basal and isoprenaline protocols for head-up tilt table testing.

AIMS: Syncope is a common occurrence, the prevalence of which increases with age, and among the multiple causes of syncope, neurally mediated syncope is thought to be a frequent cause in the young and in the elderly. Head-up tilt table testing (HUT) has become the diagnostic test of choice for neurally mediated syncope, the response to which varies clearly with age. The purpose of this study is to report the differences among patients suffering syncope referred for HUT, and the influence of age and gender on HUT results (percentage of positive responses and response patterns) in two study protocols (basal and isoprenaline). METHODS AND RESULTS: One thousand, two hundred and nineteen patients with syncope were referred to the authors' Cardiology Department for HUT from September 1990 to April 2000; 1061 undergoing basal HUT (Group A) and 158 undergoing isoprenaline tilt table testing (Group B). Complications were noted in neither protocol. Females were more frequent among young people, and males in the elderly (P<0.05). Head-up tilt table testing was abnormal in 259 (24.4%) patients in Group A and in 85 (53.7%) patients in Group B (P<0.05), and no gender differences were observed. The positive rate of tests in men and women significantly declined with age in Group A (P<0.05), but not in Group B (P=ns). There were no differences in the patterns of haemodynamic collapse in both groups. CONCLUSIONS: In the study of syncope, basal HUT has a high positive rate in young people; a decrease in positive rate with age suggests, however, the need for using another protocol with a similar diagnostic accuracy in the elderly.

Adult↗
PubMed2001

Zinc levels in foods from southeastern Spain: relationship to daily dietary intake.

The zinc content of 300 food and 79 beverage samples was determined using flame atomic absorption spectrometry. Sample recoveries, repeatability, and analyses of NIST and CBR-CEC reference materials demonstrated the reliability and accuracy of this technique. Mean zinc concentrations varied from 0.02 microg/ml in fresh water to 71.0 microg/g (fresh weight) in pork liver. The daily dietary intake of zinc for inhabitants of southeastern Spain was estimated to be 10.1 mg (5.5, 4.0, 0.5, and 0.1 mg Zn/day per person from foods of animal and vegetable origin, drinks, and other foods, respectively). Zinc levels found in high protein foods (meat, fish, milk products, eggs, dry fruits, cereals and legumes) were significantly higher than those found in food with a low protein content (vegetables, fruits and drinks) (p < 0.001). A significant linear correlation between zinc levels and the corresponding protein content of cereals, legumes and dry fruits was found (r = 0.754, p < 0.005). Zinc concentrations in milk samples were significantly modified by the thermal treatment (p < 0.001), and the skimming (p < 0.05) and calcium enrichment processes (p < 0.001). Shellfish zinc levels were also significantly higher than those measured in fish (p < 0.05). Mean zinc concentrations found in cheese were statistically higher than those determined in the remaining milk products (p < 0.001). Zinc levels measured in distilled beverages were also statistically lower than those found in fermented ones (p < 0.001).

Beverages↗
PubMed2001

Adverse reactions to injectable aesthetic microimplants.

New inert materials such as polymerized silicones, Bioplastique, Artecoll, and Dermalive are now being used as injectable aesthetic microimplants. These substances are better than the old ones because they tend not to migrate and do not usually produce much of a host immune response. Adverse reactions after injection of these materials are rare, although there are a few reported cases as a result of bad technique or anomalous granulomatous reactions. We report on four patients with unsightly results after cosmetic microimplants, including one of Artecoll, one of Dermalive (to the best of our knowledge, the latter is the first such case reported), and two of silicone. This report describes the histopathologic features of cutaneous reactions to these injectable aesthetic materials.

Adult↗
PubMed2001

The diabetic nephropathy and the development of hypertension in rats.

The present study was designed to examine the development of hypertension in diabetic rats treated with streptozotocin (STZ, 1 mg/g bw). The rats were studied at 3, 6, 9, 12 and 15 weeks. From the third week the rats were divided in diabetic rats according their glycemias and controls, along 15 weeks. After the third week a group of rats showed increased urinary protein excretion (93, 134, 155 and 191%) compared to controls. In this group of rats the urinary kallikrein excretion was lower than control and the systolic blood pressure became significantly elevated between 3 and 6 weeks and persisted up to 15 weeks. On the other hand a group of diabetic rats were normotensive with urinary protein excretion similar to controls and urinary kallikrein lower compared to control but significantly higher compared diabetic hypertensive rats. These data suggest that the association of progressive diabetic nephropathy with abnormal endothelium-dependent vasodilation may produce a high prevalence of hypertensive diabetes.

Animals↗
PubMed2001

Regulation of Id2 gene expression by the type 1 IGF receptor and the insulin receptor substrate-1.

The Id family of helix-loop-helix proteins is known to be involved in the proliferation and differentiation of several types of cells. The type 1 IGF receptor (IGF-IR) induces either proliferation or differentiation in 32D cells, a murine hemopoietic cell line, depending on the availability of the appropriate substrates for the receptor. We have previously reported that the IGF-IR regulates the expression of the Id2 gene in 32D cells. We now show that the IGF-IR controls the increase in Id2 gene expression through at least three pathways. These three pathways originate from the tyrosine residue at 950, a domain in the C-terminus, and the activation of the insulin receptor substrate-1 (IRS-1) by the receptor. IRS-1 is the preponderant signal, and its effect on Id2 gene expression requires a functional phosphotyrosine binding domain. With wild-type IRS-1, Id2 gene expression is increased, even in those cells that express IGF-I receptors defective in Id2 signaling. Rapamycin, an inhibitor of p70(S6K), a downstream effector of IRS-1 signaling, partially inhibits (but does not completely abrogate) the increase in Id2 gene expression. A mutant IRS-1 with a deletion of the Pleckstrin domain is as effective as wild-type IRS-1 in up-regulating Id2 gene expression. In addition, it seems to increase the stability of p70(S6K). Our results indicate that the IGF-IR regulates Id2 gene expression through different pathways. At least in 32D cells, increased Id2 gene expression seems to correlate more with inhibition of differentiation than with proliferation.

Animals↗
PubMed2001

Limited redundancy of survival signals from the type 1 insulin-like growth factor receptor.

The type 1 insulin-like growth factor receptor (IGF-IR) is effective in protecting cells from a variety of apoptotic injuries. In 32D murine hemopoietic cells, the IGF-IR sends three separate survival signals, through insulin receptor substrate-1, Shc, and mitochondrial Raf translocation. We report here that these three pathways for survival have a limited redundancy. If one of these pathways is blocked, the IGF-IR can still protect 32D cells from apoptosis induced by interleukin-3 withdrawal. However, when two of the three pathways are inactivated, the receptor is no longer capable to protect cells from apoptosis. The survival signal can use any two pathway combinations.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Tegafur and uracil plus leucovorin in advanced colorectal cancer: a phase II trial.

The objective of this study was to evaluate the activity and toxicity of tegafur and uracil (UFT; 1:4 molar ratio) plus leucovorin (LV) in patients with advanced colorectal cancer. One hundred forty-one patients were entered into the study. The treatment schedule consisted of UFT 300 mg/m2/day (in three divided doses) plus oral LV 150 mg/day (50 mg t.i.d.) over 28 days. The treatment cycle was repeated every 5 weeks until progression or unacceptable toxicity was observed. The treatment was interrupted if grade 3/4 toxicity appeared and was resumed at the same dosage on recovery. One hundred thirty-six patients were evaluable for response and 141 were evaluable for toxicity. The response rate was 19.9% (95% confidence interval: 12%-28%). The total number of patients without progression (objective response + stable disease) was 76 (55.9%). The median time to progression was 5.6 months, and the overall survival was 11.6 months. The toxicity profile was low, with 11% of patients experiencing grade 3/4 nausea and vomiting, while 17% had grade 3/4 diarrhea. Oral administration of UFT modulated with LV is a comfortable regimen of chemotherapy for patients with advanced colorectal cancer.

Administration, Oral↗
PubMed2001

Membranous nephropathy associated with hepatitis B in Spanish children.

AIM: To examine retrospectively long-term evolution and treatment of pediatric membranous nephropathy (MN) cases associated with hepatitis B (HB) in the hospital "La Paz". MATERIAL AND METHODS: The clinical records of 12 children diagnosed with HB-associated MN in our hospital between 1970 and 1996. RESULTS: All patients were positive for hepatitis B surface antigen (HBsAg); 6 were tested for hepatitis Be antigen (HBeAg) and were also positive. At onset, all of them had proteinuria (8 in nephrotic range), 6 had microscopic hematuria and 4 macroscopic hematuria. Seven of 8 children who started with a nephrotic syndrome received steroids and all of them were steroid-resistant. After 9.95 +/- 5.88 years of follow-up, renal function remained normal and proteinuria and hematuria have disappeared in all of them. A family study for hepatitis B was carried out in 8 cases and 7 of them were positive. Only in one case vertical transmission was demonstrated; this patient remained HBeAg positive. In 7 patients, hepatic biopsy was performed: 3 had a chronic active hepatitis, 3 a persistent chronic hepatitis and one a residual acute hepatitis. CONCLUSIONS: Membranous nephropathy is a rare pediatric disease in our area and most of the cases are related to hepatitis B (HB). The outcome was excellent with and without treatment but all of them remained HBsAg positive.

Child↗
PubMed2001

[Pregnancy and partum in the woman with a spinal cord lesion in chronic phase].

A 34-year-old pregnant paraplegic woman with a T12 medullary lesion in chronic phase underwent cesarean delivery in the thirty-seventh week due to pelvic-cephalic disproportion. After failure of epidural anesthesia related to technical difficulties, general anesthesia was provided. A hypertensive crisis developed during surgery but was resolved within minutes after administration of hydralazine. No further complications arose. Pregnancy in a patient with medullary lesion in chronic phase is considered high risk, requiring special care due to extraordinary changes in pathophysiology caused by the lesion in addition to changes directly related to gestation. The main complications that arise are decreased respiratory volume and arterial pressure, increased incidence of thromboembolic events, anemia, urinary tract infections, premature birth, unusual progression of delivery and autonomic hyperreflexia, which is the most serious. When a hypertensive peak develops in such patients, the anesthesiologist must first rule out autonomic hyperreflexia, which has an incidence of 85% in lesions over T7 and has also been described in patients with lower lesions.

Adult↗
PubMed2001

[Role of tumor necrosis factor-a, nitric oxide and markers of clinical progression in the nutritional status of children with vertically-acquired hiv-1infection].

OBJECTIVE: To study the correlation between the immunologic and virologic markers of clinical progression and the nutritional status of children with vertically acquired HIV-1infection. MATERIAL AND METHODS: We performed an anthropometric study in 34 HIV-1infected children. T cell subpopulations were analyzed by flow cytometry. Viral load (VL) was quantified by a standard commercial molecular assay. Tumor necrosis factor (TNF-) and nitric oxide (NO) concentrations were quantified by enzyme immunoassay. RESULTS: Z-weight, Z-height, Z-Quetelet index, Z-tricipital pleat, Z-arm perimeter, Z-cephalic perimeter, and McLaren's nutritional index were negatively correlated with VL. These anthropometric parameters were positively correlated with the percentage of CD4T lymphocytes but the correlation between these parameters and VL was lower. HIV-1infected children with a VL> 5 log 10 showed higher TNF- and NO concentrations and lower anthropometric scores. TNF- and NO concentrations were significantly higher in HIV-1infected children with a VL>5 log 10 than in those with a VL<5 log 10. TNF- and NO concentrations were significantly lower in HIV-1infected children undergoing antiretroviral treatment than in untreated HIV-1infected children. TNF- and NO concentrations were significantly higher in the HIV-1infected children than in the control group. CONCLUSIONS: Our data suggest an association between anthropometric characteristics indicating the nutritional status of HIV-1infected children and immunologic and virologic markers of clinical progression (percentage of CD 4T lymphocytes and VL). Moreover, TNF- and NO play a significant role in the nutritional status and neurological alterations of these children.

Anthropometry↗