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Biomedical subjects

M Navarro

Publications and source records attributed to M Navarro.

At least 181 records · Page 10Linked to original sources
PubMed1997

[Sclerosing hepatocarcinoma not associated with hypercalcemia].

The sclerosing hepatocellular carcinoma is an unusual subtype of hepatocellular carcinoma characterized by an intense fibrous stroma in which the tubular structures are embedded. Histological diagnosis is difficult, and misinterpretation as cholangiocarcinoma or metastatic adenocarcinomas may occur. It usually presents on non-cirrhotic livers. Metastases located outside of the liver are frequent as well as hypercalcemia and low levels of serum phosphate. We report a case of this rare histopathologic subtype of hepatocellular carcinoma in a 35-year-old woman, asymptomatic and with no previous history of chronic liver disease. It was detected by a routine gynaecological ultrasonography. An important increase of serum alpha-fetoprotein was noted. Extension studies showed bilateral lung metastases. Several palliative therapies were tried out, including epirrubicin, with partial response. Twenty months after the diagnosis the patient's situation is nearly terminal.

Adult↗
PubMed1997

[value of bone densitometry in pediatric renal transplantation].

OBJECTIVE: Renal transplantation improves many bone abnormalities inherent to chronic renal insufficiency, but also introduces new deleterious factors, especially those related to immunosuppressive drugs. We have studied the bone mineral content of 40 pediatric renal transplant recipients; moreover, we have analyzed its possible relationships with phosphorous-calcium metabolism, graft function and duration, steroid treatment and growth. PATIENTS AND METHODS: Bone mineral content was measured by dual energy X-ray absorptiometry (DEXA). The results were expressed as a z score in relation to age and sex. Immunosuppression was achieved by using triple therapy: azathioprine, cyclosporine A and prednisolone. At the time of the DEXA, 59% of the patients were on daily steroid treatment and 41% on alternate-day treatment. RESULTS: All patients presented bone mass losses with a maximal decrease between 5 and 21 months post-transplantation and a posterior tendency to recovery. Fifty percent of the children had severe osteopenia (bone mineral density < -1 SD). There was no statistically significant association between the severity of bone loss and values of ionized calcium, phosphorus, intact PTH, or calcitriol received. However, a linear correlation was found between cumulative steroid dose and osteopenia (r = -0.35, p < 0.05). Height and growth velocity were more affected in the severe osteopenia group. In this group, the proportion of children on daily steroid treatment was statistically higher (72% vs 45%, p < 0.05). CONCLUSIONS: Bone densitometry is an accurate, rapid and noninvasive method to measure renal transplant impact on the growing skeleton and it must be done in a periodic and standardized way.

Adolescent↗
PubMed1996

Targeted disruption of expression site-associated gene-1 in bloodstream-form Trypanosoma brucei.

Each variant surface glycoprotein (Vsg) expression site (ES) in bloodstream-form Trypanosoma brucei is a polycistronic transcription unit containing several distinct expression site-associated genes (esag), in addition to a single vsg gene. esag1 genes from different ESs encode a highly polymorphic family of membrane-associated glycoproteins, whose function is unknown. In the hope of producing a phenotype that could indicate a function, we disrupted the esag1 genes in two ESs by targeted insertion of a hygromycin phosphotransferase gene. Our failure to produce an obvious phenotype prompted us to search for other esag1 transcripts. RNA from the mutant trypanosomes hybridized with an esag1-specific oligonucleotide. Cloning and sequencing of mRNA from both mutant and wild-type cells showed that several esag1 family members were expressed, each at a much lower level than the esag1 transcript from the active ES in wild-type trypanosomes. Long-range DNA mapping showed that these additional esag1 genes, some of which contained premature translation-termination codons, most probably originate from chromosomal-internal genes and pseudogenes. We have therefore been unable to determine whether esag1 is an essential gene, or what function it fulfils, or whether any competent Esag1 protein is expressed in the mutant trypanosomes.

Amino Acid Sequence↗
PubMed1996

Serum selenium levels during normal pregnancy in healthy Spanish women.

In this study, we determined selenium concentrations in serum samples of healthy women (146 pregnant and 74 nonpregnant) living in the Mediterranean area of the coast of Granada (southeast Spain). The subjects were distributed in two groups: group A (pregnant women), divided into three categories according to the trimester of pregnancy, and group B (nonpregnant women). No significant differences were observed in the selenium levels either among pregnant women according to the trimester of pregnancy or in the group of nonpregnant women. No other significant differences were determined as regards the age of pregnant women (P > 0.05). Serum selenium levels are slightly lower during pregnancy. Considering that serum selenium levels affect the body selenium status, the concentrations determined establish the non-existence of selenium problems in the daily dietary intake with respect to maternal and fetal necessities during pregnancy.

Adolescent↗
PubMed1996

Mercury in pilot whales: possible limits to the detoxification process.

The ability of pilot whales (Globicephala melas) to concentrate cadmium and mercury is well established. The levels of these metals were generally higher than those encountered in other species of marine mammals. The biological data have not revealed a major toxic problem in the population, and this suggests a remarkable tolerance of this species to heavy metals. Cellular distribution of mercury was carried out in liver samples. The presence of metallothionein-like proteins in the soluble fraction has been demonstrated, but 95% of mercury was mainly bound to the insoluble fraction, showing that these proteins had no role in this metal detoxification. The molar ratio between mercury and selenium suggests that the major mechanism of detoxification is through the formation of a complex Hg-Se which leads to the demethylation of mercury. The site of this process is the liver in which mercury mainly appeared as inorganic, whereas in the muscle the percentage of organic to total mercury was much higher. Nevertheless, this detoxification is limited in lactating females and in all the individuals of one school. This could be the result of changes in the diet and could constitute a toxicological risk for the species.

Animal Nutritional Physiological Phenomena↗
PubMed1996

Toward a novel metal-based chemotherapy against tropical diseases. 2. Synthesis and antimalarial activity in vitro and in vivo of new ruthenium- and rhodium-chloroquine complexes.

Chloroquine free base (CQ) reacts with [Rh(COD)Cl]2 (COD = 1,5-cyclooctadiene) and RuCl3.-3H2O/Zn to yield Rh(COD)(CQ)Cl (1) and [RuCl2(CQ)]2 (2), respectively. The two novel metal- CQ complexes, which were characterized mainly by 1D and 2D NMR spectroscopy, were tested against Plasmodium berghei. The in vitro activity of 1 was comparable to that of chloroquine diphosphate (CQDP), whereas 2 was about 5 times more active. In in vivo tests at equivalent concentrations of free CQ, CQDP reduced the parasitemia by 55%, while for complexes 1 and 2 the reduction reached 73% and 94%, respectively, without any sign of acute toxicity being observed up to 30 days after treatment. The Ru derivative 2 was further evaluated against two chloroquine-resistant strains of Plasmodium falciparum, and it was found to be 2-5 times more active than CQDP.

Animals↗
PubMed1996

Rabbit slow and fast skeletal muscle-derived satellite myoblast phenotypes do not involve constitutive differences in the components of the insulin-like growth factor system.

The insulin-like growth factor (IGF) system is actively involved in the control of proliferation and differentiation of several myogenic cell lines, and phenotypic differences between myoblasts are associated with modifications of the equilibrium of the components of the IGF system. To determine whether this observation is a physiologic feature that also concerns the phenotypes of ex vivo adult satellite myoblasts in primary cell culture, we investigated the IGF system in rabbit slow-twitch muscle-derived satellite myoblasts (SSM), which differ phenotypically from fast-twitch muscle-derived satellite myoblasts (FSM) by their proliferation and differentiation kinetics in vitro. The expression of IGF-I and IGF-II were similar in SSM and FSM as well as their concentrations measured in cell-conditioned media. Ligand blotting of conditioned media samples indicated the presence of five IGF binding protein (IGFBP) species of Mr 37-40, 32, 30-31, 28, and 24 kDa. The 30-31 kDa doublet was visible in SSM-conditioned medium only and associated with the presence of a 22-kDa protein, which may represent a proteolytic fragment. In contrast, the 32-kDa band was observed in FSM conditioned medium only. The other IGFBP moieties were present in both SSM- and FSM-conditioned media. Cross-linking experiments revealed the presence of the M6P/IGF-II receptor on both SSM and FSM membranes. We also observed an IGF-I receptor form bearing unusual high affinity for IGF-II: the binding of [125I]IGF-I on this receptor was preferentially displaced by IGF-I but that of [125I]IGF-II was mostly inhibited by IGF-II, suggesting that the two tracers did not bind on the same epitopes. [125I]IGF-II binding to this receptor was greater on SSM than on FSM membranes. Autophosphorylation of WGA-purified receptors revealed an approximately 400-kDa band after SDS-PAGE under nonreducing conditions, which corresponded to the alpha 2 beta 2 form of the IGF-I receptor, and two beta subunit moieties of Mr 101 and 105 kDa under reducing conditions in both SSM and FSM extracts. Phosphorylation of the 105-kDa moiety was more intensively increased than that of the 101-kDa protein after growth factor stimulation. Basal phosphorylation state of the two beta subunits was similarly stimulated by IGF-I and IGF-II and less by insulin. Since both insulin and IGF-I receptors were expressed in FSM and SSM, one of the two beta subunits may actually correspond to that of the insulin receptor. We conclude that the IGF system is not considerably affected by the phenotypes of SSM and FSM. The differences observed, which mostly concern IGFBP species, more likely appear as regulatory adaptations than as phenotypic changes targeting the components of the IGF system.

Animals↗
PubMed1996

Perinatal cannabinoid exposure modifies the sociosexual approach behavior and the mesolimbic dopaminergic activity of adult male rats.

In the present work, we attempted to study whether hashish exposure during perinatal development affects sociosexual approach behavior in adult rats. To this end, we subjected adult female and male rats that had been perinatally exposed to hashish extracts to a sociosexual approach behavior test, completed with a dark-light emergence test and with a social interaction test. It was found that adult males perinatally exposed to hashish extracts exhibited marked changes in the behavioral patterns executed in the sociosexual approach behavior test; these changes did not exists in females. Thus, control males first visited the incentive male and took longer to visit the incentive female, whereas hashish-exposed males followed the opposite pattern. Moreover, hashish-exposed males spent more time in the vicinity of the incentive female, whereas they decreased their frequency of visits to, and the time spent in, the male incentive area. This behavior was observed early on, during the first third of the test, but became normalized and even inverted later on during the last two-thirds. Additionally, in the social interaction test, the normal reduction in the time spent in active social interaction following the exposure to a neophobic situation (high light levels) in controls did not occur in hashish-exposed males, although these exhibited a response in the dark-light emergence test similar to that of their corresponding controls. No changes were seen in spontaneous locomotor activity in both tests. These behavioral alterations observed in hashish-exposed males were paralleled by a significant decrease in L-3,4-dihydroxyphenylacetic acid contents in the limbic forebrain; this suggests a decreased activity of mesolimbic dopaminergic neurons. No effects were seen in females. Collectively, these results show that in the rat, perinatal cannabinoid exposure affects the sociosexual approach behavior and the mesolimbic dopaminergic activity in adulthood, although the effects were sexually dimorphic because they only appeared in the males.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Colocalization of glucagon-like peptide-1 (GLP-1) receptors, glucose transporter GLUT-2, and glucokinase mRNAs in rat hypothalamic cells: evidence for a role of GLP-1 receptor agonists as an inhibitory signal for food and water intake.

This study was designed to determine the possible role of brain glucagon-like peptide-1 (GLP-1) receptors in feeding behavior. In situ hybridization showed colocalization of the mRNAs for GLP-1 receptors, glucokinase, and GLUT-2 in the third ventricle wall and adjacent arcuate nucleus, median eminence, and supraoptic nucleus. These brain areas are considered to contain glucose-sensitive neurons mediating feeding behavior. Because GLP-1 receptors, GLUT-2, and glucokinase are proteins involved in the multistep process of glucose sensing in pancreatic beta cells, the colocalization of specific GLP-1 receptors and glucose sensing-related proteins in hypothalamic neurons supports a role of this peptide in the hypothalamic regulation of macronutrient and water intake. This hypothesis was confirmed by analyzing the effects of both systemic and central administration of GLP-1 receptor ligands. Acute or subchronic intraperitoneal administration of GLP-1 (7-36) amide did not modify food and water intake, although a dose-dependent loss of body weight gain was observed 24 h after acute administration of the higher dose of the peptide. By contrast, the intracerebroventricular (i.c.v.) administration of GLP-1 (7-36) amide produced a biphasic effect on food intake characterized by an increase in the amount of food intake after acute i.c.v. delivery of 100 ng of the peptide. There was a marked reduction of food ingestion with the 1,000 and 2,000 ng doses of the peptide, which also produced a significant decrease of water intake. These effects seemed to be specific because i.c.v. administration of GLP-1 (1-37), a peptide with lower biological activity than GLP-1 (7-36) amide, did not change feeding behavior in food-deprived animals. Exendin-4, when given by i.c.v. administration in a broad range of doses (0.2, 1, 5, 25, 100, and 500 ng), proved to be a potent agonist of GLP-1 (7-36) amide. It decreased, in a dose-dependent manner, both food and water intake, starting at the dose of 25 ng per injection. Pretreatment with an i.c.v. dose of a GLP-1 receptor antagonist [exendin (9-39); 2,500 ng] reversed the inhibitory effects of GLP-1 (7-36) amide (1,000 ng dose) and exendin-4 (25 ng dose) on food and water ingestion. These findings suggest that GLP-1 (7-36) amide may modulate both food and drink intake in the rat through a central mechanism.

Animals↗
PubMed1996

Effects of HOE 140 on some renal functions in type I diabetic mice.

To investigate in mice the mechanisms underlying renal functions in a type I diabetes model, we have suppressed B2 kinin receptors local activities by their specific antagonist D-Arg [Hyp3-Thi5-D-Tic7-Oic8]BK (HOE 140). Mice made diabetic with low consecutive doses of streptozotocin (STZ) (45 mg/k BW during 5 days) were injected with HOE 140 (15 micrograms/twice a day) for 15 days. This drug did not modify glycemia of STZ treated animals but a significantly reduction of urinary proteins, nitrites and kallikrein was observed. These results indicate that kinin B2-receptors activation is implicated in the alterations of renal function in this model of type I diabetes in mice.

Analysis of Variance↗
PubMed1996

Antibodies to endothelial cells and to beta 2-glycoprotein I in the antiphospholipid syndrome: prevalence and isotype distribution.

The aim of this study was to analyse the prevalence and isotype distribution of antibodies to endothelial cells (aEC) and to beta 2-glycoprotein I (a beta 2GPI) in the antiphospholipid syndrome (APS). Fifteen patients with an APS [nine associated with systemic lupus erythematosus (SLE) and six "primary'] and 15 with SLE without an APS were prospectively studied. The aEC were determined by an enzyme-linked immunosorbent assay (ELISA) using endothelial cells derived from human umbilical vein and the a beta 2GPI by ELISA using highly purified beta 2GPI. A positive titre of aEC was detected in 20 out of 30 patients (67%), but in none of the control group. Ten patients had both IgG and IgM isotypes, five had IgG only and five had only IgM. Thirteen patients with the APS (87%) were found to have a positive titre of aEC, while only seven with SLE but without a history of APS (47%) had aEC (P < 0.05). Nine patients with the APS (60%) had a positive titre of a beta 2GPI (four had both IgG and IgM isotypes, one had IgG only and four had only IgM), while none of the patients without an APS (0%) had these antibodies (P < 0.001). A significant association was also found between the presence of aPL and aEC (P < 0.05), as well as between aPL and a beta 2GPI (P < 0.001). Both aEC and a beta 2GPI can be found in the APS. This reinforces the theory that APS represents a complex autoimmune disorder in which several autoantibodies co-exist with aPL.

Adult↗
PubMed1996

DNA rearrangements associated with multiple consecutive directed antigenic switches in Trypanosoma brucei.

Changes in variant surface glycoprotein (Vsg) expression allow Trypanosoma brucei to elude the immune response. The expressed vsg is always located at the telomeric end of a polycistronic transcription unit known as an expression site (ES). Although there are many ESs, only one is active at any particular time. The mechanisms regulating ES transcription and switching are unknown. Chromosome rearrangements within or upstream of the ES have been described to occur in occasional switch events, but no changes have been consistently associated with switching. We inserted the drug resistance genes neo and ble, conferring resistance to G418 and phleomycin, respectively, 1 kb downstream of "silent" ES promoters. This demonstrated that short-range transcription could be achieved from a silent ES promoter. From one initial transformant clone, panels of independent consecutive on-off-on switch clones were generated and analyzed. The first activation of the neo-targeted ES was always associated with deletion of the upstream tandem promoter in this ES, but no further rearrangements were detected in consecutive off-on switches of this ES. On the other hand, direct analysis of ES promoters showed that deletions and duplications occurred elsewhere. Activation of a ble-tagged 300-kb chromosome could not be achieved, but phleomycin-resistant clones could be obtained. One such clone arose from recombination between three ESs. Taken together, our experiments suggest that ES switching may occur after a period of chromosomal interactivity that may or may not leave tangible evidence in the form of detectable sequence changes.

Animals↗
PubMed1996

Primary intraosseous meningiomas.

PURPOSE: A retrospective study was performed to evaluate the clinical, radiological and histological findings of 14 intraosseous meningiomas. MATERIAL AND METHODS: 14 histologically proved intraosseous meningiomas were studied with plain skull film and CT. Pathological records were reviewed. RESULTS: We found 9 calvarial cases and 5 spheno-orbital ones. The most common symptom in the calvarial cases was a lump in the scalp, and in the spheno-orbital lesions it was exophtalmos. Hyperostosis was present in all 5 spheno-orbital cases and in 3 out of the 9 calvarial ones; in the other 6 cases it had a mixed pattern. Enhanced dura was present in 3 calvarial cases and in 2 sphenoidal ones. Dura was involved in 5 cases: 2 with inflammatory changes, 2 with a minimal intradural tumour and one with a subdural tumour. CONCLUSION: CT better detected both the bony reaction and the intraosseous extension of the tumour. The dural changes were not specific of tumoural involvement. The differential diagnosis comprises: fibrous dysplasia, osteoma, blastic metastasis and mainly meningioma en plaque (MEP). Comparing our findings with other series, we noticed that in some cases the term MEP was used for similar cases. As the name MEP is merely descriptive and both entities share a larger number of similarities than differences, we believe that a differentiation between hyperostotic en plaque meningioma and intraosseous meningioma can hardly be made.

Adult↗
PubMed1996

Corticotropin-releasing factor (CRF) antagonist [D-Phe12,Nle21,38,C alpha MeLeu37]CRF attenuates the acute actions of the highly potent cannabinoid receptor agonist HU-210 on defensive-withdrawal behavior in rats.

The present study evaluated the modulatory role of central corticotropin-releasing factor (CRF) systems in the mediation of the effects of acute exposure to the brain cannabinoid receptor agonist HU-210 [3-(1,1-dimethylheptyl)-(-)-11-hydroxy-delta 8-tetrahydrocannabinol] on defensive withdrawal behavior in male rats. The apparatus used for the defensive withdrawal test consisted of a small chamber, set on one side of a one-square meter open field. The actions of the potent CRF antagonist [D-Phe12,Nle21,38,C alpha MeLeu37]CRF (D-Phe CRF12-41) were examined on defensive behavior under both novel and familiar conditions. The acute i.c.v. administration of D-Phe CRF12-41 (0.2-5 micrograms/injection) antagonized the defensive behavior response to stressing conditions such as novelty or swim stress in field-habituated animals. The acute i.p. administration of HU-210 (4, 20 and 100 micrograms/kg) produced a clear dose-dependent stress-like effects in field-habituated animals, as reflected in the HU-210-induced increase in both the emergence latency and the mean time spent in the small chamber. The i.c.v. administration of 5 micrograms of D-Phe CRF12-41, 5 min before the administration of the cannabinoid prevented the stressing actions of HU-210 (20 micrograms/kg, but not 100 micrograms/kg). Acute administration of HU-210 also induced a dose-dependent increase in plasma corticosterone levels which was not antagonized by pretreatment with 5 micrograms of D-Phe CRF12-41. The present study suggests a role of central CRF systems in the mediation of the anxiogenic effects of brain cannabinoid receptor agonists. This finding is consistent with a direct hypothalamic effect of cannabinoids on the activation of the pituitary-adrenal axis.

Animals↗
PubMed1996

Third autologous stem cell transplants for late relapse of multiple myeloma.

Double autologous bone marrow transplantation (ABMT) has been reported as an efficient form of consolidation for patients with multiple myeloma (MM). However, few data are available about feasibility and efficacy of a third ASCT in case of relapse. Here we report two patients with MM who received a third ASCT for late relapse (74 and 52 months) after a double ABMT. Both patients were male with IgG gamma MM (stage IIIA according to the Durie Salmon classification). The two patients were in PR > 50% after a first-line treatment. A double ABMT was performed after relapse and patients remained in PR > 50% after double intensification, lasting 71 and 49 months, respectively. The third ASCT was performed 7 and 10 months, after second relapse. One patient needed 15 months to reach 50 000 platelets, however he did not receive any transfusion after day 14. He was in PR > 50%. The other patient was in PR < 50%, 4 months after ABMT with a full hematological reconstitution. For patients with late relapse of MM after double ABMT, a third ABMT was a feasible treatment and patients seem to remain sensitive to high-dose therapy.

Adult↗