Biomedical subjects

E López

Publications and source records attributed to E López.

At least 37 records · Page 2Linked to original sources

PubMed2003

Apoptosis and necrosis: two distinct events induced by cadmium in cortical neurons in culture.

(1) Cadmium is an extremely toxic metal commonly found in industrial workplaces, a food contaminant and a major component of cigarette smoke. Cadmium can severely damage several organs, including the brain. In this work, we have studied both the cadmium toxicity on rat cortical neurons in culture and the possible protective effect of serum. (2) Our results indicate that: (1) cadmium is taken up by the neurons in a dose and serum dependent way; (2) cadmium, at concentrations from 1 micro M or 10 micro M (depending on the absence or the presence of serum) up to 100 micro M, decreases the metabolic capacity, which was evaluated by the XTT (tetrazolium salt) test; (3) cadmium induces apoptosis and LDH (lactate dehydrogenase) release in a dose dependent way; (4) in a serum-free medium, the cadmium-induced apoptosis is accompanied by caspase-3 activation; (5) both the caspase-3 activation and the cadmium-induced apoptosis are reversed by N-acethyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), a selective caspase-3 inhibitor, indicating that the caspase-3 pathway is involved in cadmium-induced apoptosis in cortical neurons; and (6) the cadmium concentrations which produce caspase-3 activation do not modify the intracellular ATP levels; however, higher cadmium concentrations lead to both intracellular ATP depletion and ATP release, but do not increase the caspase-3 activity, indicating that cadmium also produces cellular death by necrosis. (3) These results suggest that cadmium induces either apoptosis or necrosis in rat cortical neurons, depending on the cadmium concentration.

Animals↗

PubMed2003

[Influence of early or late referral to nephrologist over morbidity and mortality in hemodialysis].

OBJECTIVE: We studied the influence of early vs late referral to nephrologist of patients with chronic renal failure over clinical situation at the onset of hemodialysis and outcome. SUBJECTS AND METHODS: From january 1994 to december 1998, 139 patients started hemodialysis for end-stage renal disease at the Hospital General de Albacete, all of them included in the study and clinical follow-up concluded in december 2001. Patients with rapidly progressive glomerulonephritis were excluded. Early (ER) and late referral (LR) were defined by the time of first nephrology encounter greater than or less than 6 months respectively, before iniciation of hemodialysis. RESULTS: 106 patients (76.25%) were referred early; mean follow-up time 6.3 +/- 4.5 years. 33 patients (23.74%) had late referral, follow-up time was less then six months, 18 patients were followed during less than 4 weeks. There were no differences in demographic data and comorbid conditions between LR and ER patients (age, cardiac and vascular disease, diabetes, neoplasia...). Mean plasma concentration of creatinine and urea was significantly greater, whereas hematocrit and albumin were less in the LRA than the ER group. Emergency dialysis through central vein catheterisation was more frequent in the LR group. Number of admissions and duration of hospital stay were higher in the LR group. No significant differences in nutrition, dialysis doses or anemia were found between the two groups after 6 and 12 months of hemodialysis. Long term outcome was similar in both groups: no significant differences were found in percentage of patients transplanted or deceased after 3 years of treatment. Survival analysis failed to show a difference between ER and LR groups (mean survival time was 73.6 +/- 4.3 months and 73.0 +/- 6 months respectively). CONCLUSION: Late referral to the nephrologist is associated with increased early morbidity vs early referral, although long term outcome is not worse if predialysis comorbid conditions are comparable and dialysis care achieve equal results in dialysis doses, nutrition and anemia in both groups in the first months of treatment. Improvement of outcome of patients referred early to the nephrologist will depend on the adoption of preventive measures over comorbidity factors that should be applied in early stages of renal disease.

Female↗

PubMed2002

Effect of vigabatrin on the pharmacokinetics of carbamazepine.

OBJECTIVE: To evaluate a possible interaction between vigabatrin and carbamazepine in epileptic patients. METHODS: Steady-state serum concentrations of carbamazepine with and without vigabatrin were compared. The study group consisted of 15 patients (eight females, seven males, and mean age 31 +/- 12 years), with refractory partial epilepsy. They received vigabatrin as add-on therapy. Patients received carbamazepine monotherapy for at least 6 months and the carbamazepine-vigabatrin combination for at least 3 months. Blood samples were obtained in the morning, before the first daily dose and the carbamazepine plasma concentrations were analysed by fluorescence polarization immunoassay (TDx System). RESULTS: No statistically significant differences were found in mean carbamazepine daily dose. Mean trough concentrations were 7.9 +/- 1.4 microg/mL with carbamazepine alone, and 6.5 +/- 2.0 microg/mL with carbamazepine-vigabatrin association (P < 0.03). The mean values of pharmacokinetic parameters were: level/dose ratio (L/D) = 0.59 +/- 0.20 vs. 0.45 +/- 0.15 (P < 0.05) and plasma clearance (Cl) = 78.5 +/- 25.8 vs. 105.8 +/- 38.9 mL/h/kg (P < 0.05), with carbamazepine alone and carbamazepine-vigabatrin combination, respectively. CONCLUSION: Vigabatrin produced a statistically significant increase in the plasma clearance of carbamazepine when the two drugs were given simultaneously.

Administration, Oral↗

PubMed2002

Induction chemotherapy with paclitaxel, cisplatin and 5-fluorouracil for squamous cell carcinoma of the head and neck: long-term results of a phase II trial.

BACKGROUND: The aim of this study was to evaluate the efficacy and toxicity of a combination of paclitaxel, cisplatin and 5-fluorouracil (PPF) as induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Seventy patients with previously untreated stage III-IV SCCHN were included in this phase II trial. Induction treatment consisted of a maximum of three outpatient courses of paclitaxel 175 mg/m(2) as a 3-h infusion on day 1, cisplatin 100 mg/m(2) on day 2, and 5-fluorouracil (5-FU) 500-750 mg/m(2)/day as a 24-h continuous infusion on days 2-6, repeated every 3 weeks. The 5-FU dose was reduced from 750 mg/m(2)/day to 500 mg/m(2)/day due to the excessive toxicity observed in the first 14 patients enrolled. Local treatment consisted of radiotherapy and/or surgery. RESULTS: Two-hundred-and-one cycles were administered to 70 patients. The main toxicities of PPF were neutropenia (grade 4, 14%; febrile neutropenia, 4%), peripheral neuropathy (grade 2-3, 14%) and catheter-associated venous thrombosis (7%). There were three early deaths (two from neutropenic sepsis and one from pulmonary embolism), and 13 patients required hospitalization due to toxicity. Other side effects included mucositis, anorexia, diarrhea, myalgias and alopecia. The overall response rate to PPF was 88%, including 59% complete responses (CR) and 29% partial responses. The CR rates at the primary tumor and neck lymph nodes were 74% and 62%, respectively. With a median follow-up of 51 months (range 40-63 months), the estimated 5-year time-to-disease progression and overall survival rates were 56% and 44%, respectively. CONCLUSIONS: The PPF regimen has major antitumor activity and is associated with manageable toxicity as induction treatment in SCCHN patients. The high complete response rate and favorable long-term outcome justify further evaluation of this chemotherapy combination.

Adult↗

PubMed2001

Calcium channel types involved in intrinsic amino acid neurotransmitters release evoked by depolarizing agents in cortical neurons.

Although numerous biochemical and electrophysiological studies have already established many of the properties of the putative Ca2+ receptor for exocytosis at the synapse, the molecular mechanism that involves the influx of Ca2+ and the release of neurotransmitters has remained elusive. Several relationships have been established between neurotransmitter release and Ca2+ channel involved, but no work attempting to connect a particular neurotransmitter release, the effector which produces the release and the opening of a Ca2+ channel type has been performed. This work shows, data dealing with this subject. Based on our results, we have reached the following conclusions: (1) Ca2+ channel types P/Q, N and L mediate Ca2+ entry evoked by high KCl and veratridine, and P/Q and N but not L-type Ca2+ channels are involved when the effector is 4-aminopyridine (4-AP); (2) When we compare the relationship between the amino acid release and the Ca2+ channels which are opened by different depolarizing agents, we find that the release of a particular amino acid neurotransmitter not only depends on the opening of the voltage-dependent Ca2+ channel but also on the effector which produces the opening; and (3) the amount of amino acid release evoked by the different depolarizing agents is not correlated with the elevation of intracellular Ca2+ produced by them. From all of these results, we may conclude that calcium concentration in the active zone is not the only important factor in mediating amino acid release.

4-Aminopyridine↗

PubMed2001

Anisotropy functions for low energy interstitial brachytherapy sources: an EGS4 Monte Carlo study.

Anisotropy functions for low energy interstitial brachytherapy sources are examined. Absolute dose rates around 103Pd seed model 200 and 125I seed models 6702 and 6711 have been estimated by means of the EGS4 Monte Carlo simulation system. The DLC-136/PHOTX cross section library, water molecular form factors, bound Compton scattering and Doppler broadening of the Compton-scattered photon energy were considered in the calculations. Following the formalism developed by the Interstitial Brachytherapy Collaborative Working Group, anisotropy functions, F(r, theta), have been calculated. Our Monte Carlo results were compared against a limited set of measured data selected from the literature and other Monte Carlo results. Binding corrections and phantom material selection have been found to have no influence on the anisotropy function. The accuracy of the geometrical source models used for the Monte Carlo calculations was validated against experimental measurements of in-air relative fluence at 100 cm from the source. More detailed knowledge about the geometrical design of 103Pd seed model 200 is needed in order to improve the agreement with experimentally measured in-air fluence. Values for in-air fluence of 125I model 6702 are sensitive to source position within the inner seed cylinder. Excellent agreement between calculated and measured in-air fluence is found for 125I model 6711. It was observed that using in-air relative fluence at 100 cm from the source to calculate the anisotropy function yields a less anisotropic dose distribution at distances close to the source than full Monte Carlo simulation, in contradiction with experimental data. Our results have estimated statistical uncertainties of 1%-3% at the 1sigma level within clinically relevant regions, but contain systematic uncertainties related to the assumed geometrical details.

Algorithms↗

PubMed2001

Anisotropy function for 192Ir low-dose-rate brachytherapy sources: an EGS4 Monte Carlo study.

The anisotropy function of low-dose-rate 192Ir interstitial brachytherapy sources was studied. Absolute dose rates around 192Ir seeds with stainless steel or platinum cladding and a platinum covered wire have been estimated using the EGS4 Monte Carlo simulation system with a very well tested user code. Our results were compared with available experimental data. Excellent agreement between calculated and measured anisotropy function was found for stainless steel clad 192Ir sources, except along the longitudinal axis of the sources. Dosimetry data for the platinum covered seed and 3 mm long wire with platinum cladding as well as for the stainless steel clad 192Ir source are presented in TG43 format. The influence of phantom dimensions on the anisotropy function was found to be non-negligible over 7 cm, enhancing the anisotropy function by 1-2%. Our results have estimated statistical uncertainties below 1% at 1 sigma level up to 10 cm excluding the longitudinal axis where statistical uncertainties below 3% up to 10 cm are observed.

Anisotropy↗

PubMed2001

Nicotinic receptors mediate the release of amino acid neurotransmitters in cultured cortical neurons.

Nicotine stimulation of cortical neurons obtained from gestation day 19 rats provoked a dose-dependent release of aspartate, glutamate, glycine and GABA, indicating a functional role for the nicotinic receptor in this model. This release was exclusively Ca2+-dependent (vesicular release) in the case of aspartate and dual Ca2+-dependent and Ca2+-independent) for glutamate, glycine and GABA. Nicotine also raised the membrane potential and the intracellular calcium concentration. These effects were specific, since they were reversed by hexamethonium, an antagonist of the nicotinic receptor. It was shown that L, N, and P/Q type Ca2+ channels are involved in nicotine-mediated Ca2+ entry into cortical neurons. Evaluation of the effects of nicotine on Ca2+ entry in isolated cells showed that 100% of the cells responded to nicotine, although the intensity of the response was variable: 63% of the neurons showed an increase in intracellular Ca(2+) of 152 +/- 5 grey levels, 25% of 88 +/- 12 grey levels and 12% of 48 +/- 1 grey levels. Tetrodotoxin, which blocks voltage-dependent Na(+) channels, completely reversed nicotine-induced Ca2+ entry into single cells. This suggests that the Ca2+ increment is mediated by opening of Ca2+ channels and not by the nicotinic receptor.

Animals↗

PubMed2001

Isoenzyme profiles of Trypanosoma cruzi stocks from different areas of Paraguay.

Twenty one Trypanosoma cruzi stocks from humans, domiciliary triatomines and one sylvatic animal of different areas of Paraguay were subjected to isoenzyme analysis. Thirteen enzyme systems (15 loci in total) were studied. MN cl2 (clonets 39) and SO34 cl4 (clonets 20) were used as references. Relationships between stocks were depicted by an UPGMA dendrogram constructed using the Jaccard's distances matrix. Among the Paraguayan stocks 14 zymodemes were identified (Par1 to Par14), Par 5 being the most frequent. Polymorphism rate and clonal diversity were 0.73 and 0.93, respectively. Average number of alleles per polymorphic locus was 2.5 (range 2-4). These measurements show a high diversity, which is confirmed by the dendrogram topology. All stocks belong to the same lineage, as MN cl2 reference strain (T. cruzi II). Moreover three distinct subgroups were identified and two of them correspond to Brazilian and Bolivian zymodemes, respectively. The third subgroup, the most common in Paraguay, is related to Tulahuen stock. The large geographical distribution of some zymodemes agrees with the hypothesis of clonality for T. cruzi populations. However sample size was not adequate to detect genetic recombination in any single locality.

Alleles↗

PubMed2001

[Syllinae (Syllidae: Polychaeta) of the Parque Nacional de Coiba, Panama].

Four expeditions were made to Coiba National Park between 1996 and 1998 to characterize this part of the poorly known Panamian Pacific polychaete fauna. The samples were collected by SCUBA diving, either by removing 4 kg blocks of dead coral (Pocillopora sp.) or scraping off 25 x 25 cm quadrats of Telesto multiflora or algae (Dyctiota cf. flavellata, Padina cf. durvillaei and another currently unidentified species). This paper deals with the Syllinae from hard substrates. Twenty-two species belonging to six genera of the subfamily Syllinae Grube, 1850 (Syllidae: Polychaeta) are reported. A new species, Syllis castroviejoi, is described. Four species are newly reported for the Eastern Pacific: Syllis beneliahuae (Campoy & Alquézar, 1982), S. botosaneanui (Hartmann-Schröder, 1973), S. corallicola Verrill, 1900 and S. garciai (Campoy, 1982), and, likewise, two species are first reports for the Central American Pacific coast: Branchiosyllis pacifica Rioja, 1941 and Syllis truncata Haswell, 1920. Two species, Syllis magna (Westheide, 1974) and S. pigmentata (Chamberlin, 1919), are newly reported for Panama.

Animals↗

PubMed2001

[Autolytinae, Eusyllinae an Exogoninae (Syllidae: Polychaeta) from Coiba National Park, Panama)].

This is the second paper on the Syllidae (Polychaeta) from hard substrata of the Coiba National Park (Pacific coast of Panama) (the first paper treated Syllinae). On this second paper nineteen species belonging to eleven genera of the subfamilies Autolytinae, Eusyllinae and Exogoninae (Syllidae: Polychaeta) are reported. The samples were collected by SCUBA diving, either by removing 4 kg blocks of dead coral (Pocillopora spp.) or scraping off 25 x 25 cm quadrats of Telesto multiflora or algae (Dyctiota cf. flavellata, Padina cf. durvillaei and another currently unidentified species). They were collected during four expeditions carried out between 1996 and 1998. Four species are newly reported for the Eastern Pacific: Eusyllis lamelligera Marion & Bobretzky, 1875, Exogone exmouthensis Hartmann-Schröder, 1980, Proceraea cf. cornuta (Agassiz, 1863) and Sphaerosyllis (S.) magnidentata Perkins, 1981. Ten species are reported for the first time from the Central America Pacific coast: Amblyosyllis cf. granosa Ehlers, 1897 (sensu Westheide 1974), Amblyosyllis speciosa Izuka, 1912, Autolytus multidenticulatus Westheide, 1974, Exogone naidinoides Westheide, 1974, Grubeosyllis concinna (Westheide, 1974), Odontosyllis fulgurans (Audouin & Milne Edward, 1833), Opisthodonta mitchelli Kudenov & Harris, 1995, Pionosyllis articulata Kudenov & Harris, 1995, Sphaerosyllis (S.) californiensis Hartman, 1966 and Syllides cf. reishi Dorsey, 1978. The family Syllidae is represented in the Coiba National Park by 14% of cosmopolitan species, 14% of circumtropical species, 22% of Atlantic and Pacific species and 25% of Pacific species restricted to warm waters. In samples of dead coral the dominant species are S. armillaris (Muller, 1771) and S. gracilis (Campoy, 1982); in samples of telestaceans Grubeosyllis concinna dominates.

Animals↗

PubMed2000

Staurosporine- and H-7-induced cell death in SH-SY5Y neuroblastoma cells is associated with caspase-2 and caspase-3 activation, but not with activation of the FAS/FAS-L-caspase-8 signaling pathway.

Apoptotic cell death is induced in SH-SY5Y neuroblastoma cells following exposure to the protein kinase inhibitors staurosporine (100 nM) and 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine: H-7 (100 microM). This is associated with reduced levels of PARP 117 kDa and with the concomitant formation of PARP-cleaved products of 89 kDa that result from caspase-3 activation. The process is inhibited with DEVD-fmk, a potent caspase-3 (and caspase-8) inhibitor, thus indicating that staurosporine- and H-7-induced cell death in SH-SY5Y is mediated by caspase activation. Increased caspase-2- and caspase-3-like activities, but not caspase-9-like activity, were demonstrated by monitoring proteolysis of the corresponding colorimetric substrates. Caspase-2 activity peaked at 6 h, whereas caspase-3 peaked at 12 h in parallel with the maximal loss of cell viability. No modifications in the expression levels of Fas and Fas-L were observed by Western blotting. Furthermore, no activation of caspase-8 was elicited by colorimetric assays through the process of apoptosis of neuroblastoma cells. These findings indicate that the Fas/Fas-L-caspase-8 pathway of cell death signaling is not involved in staurosporine- and H-7-induced apoptosis in SH-SY5Y neuroblastoma cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2000

Calcium-independent release of [3H]spermine from chick retina.

Spermine has been shown to influence NMDA receptor function through an interaction at the coagonist site for glycine in the central nervous system (CNS) and the retina. In order to support a role for spermine as neurotransmitter or neuromodulator in the chick retina, specific stimulated-release of spermine should be demonstrated. Isolated chick retinas, preloaded with [3H]spermine, were stimulated with 1 mM NMDA and other glutamate agonists at ionotropic receptors, in a continuous superfusion system. [3H]spermine was released from the retina by depolarization with 50 mM KCl, in a Ca2+-independent manner. Inhibition of Na+/K+-ATPase by ouabain or digitoxigenin also induced spermine release following 36 min in the presence of the drugs; such effect seems unrelated to changes in Na+ electrochemical gradients, since nigericin and veratrine did not induce release in Na+ containing medium. The lack of effect of glutamate, NMDA and kainate at 1 mM concentration, suggests that release of spermine in the retina is mediated by the reversal of uptake and not necessarily linked to EAA-receptor activation.

Animals↗

PubMed2000

Differential c-Fos and caspase expression following kainic acid excitotoxicity.

Caspases play crucial roles in the inflammatory response and in the cell pathway leading to apoptosis. Caspase 1 (ICE), 2 (Nedd2), 3 (CPP32), 6 (Mch2) and 8 (Mch5, FLICE) expression was examined using immunohistochemistry in the brains of rats and gerbils following systemic administration of kainic acid (KA). The distribution of caspase expression was compared with the distribution of c-Fos expression, a transcription factor that is produced in response to the excitotoxic insult. Strong caspase 2 immunoreactivity was found in microglia up to 6 h following KA administration. Focal strong expression of caspases 1, 2, 3, 6 and 8 was observed in astrocytes and neurons, from 12 to 48 h after KA injection, in areas in which a number of neurons were committed to die. This distribution was in contrast with the generalised distribution of c-Fos expression following KA administration. Only a minority of neurons in the entorhinal cortex, amygdala and hilus, but a majority of neurons in selected thalamic nuclei, exhibited strong caspase expression in KA-treated rats. Similar findings, although minimised, were observed in KA-treated gerbils. Double-labelling caspase immunohistochemistry and in situ end-labelling of nuclear DNA fragmentation disclosed co-localisation of strong caspase expression and nuclear DNA breaks in a small percentage of neurons but no co-localisation in astrocytes. Western blots of entorhinal cortex and neocortex homogenates showed cleavage of certain caspase substrates in KA-treated rats. The intensity of the bands corresponding to lamin B and protein kinase C-delta was decreased in the entorhinal cortex following KA administration. Several bands appeared in the entorhinal cortex and neocortex paragraph signin Western blots processed for the demonstration of poly(ADP-ribose) polymerase (PARP), thus indicating that other proteases, in addition to caspases, cleaved PARP following KA administration. Taken together, these findings indicate that KA excitotoxicity triggers caspase expression which, although predominant in regions subjected to irreversible cell damage, has only a weak association with the presence of nuclear DNA breaks and neuron cell death. Although these results suggest caspase activation, further studies have to be performed to elucidate whether caspase activation plays a crucial role in KA excitotoxicity.

Animals↗

PubMed2000

Anisotropy functions for 169Yb brachytherapy seed models 5, 8 and X1267. An EGS4 Monte Carlo study.

Anisotropy functions for 169Yb sources used in interstitial brachytherapy are investigated. A comprehensive study of several factors affecting the angular dose distribution around four 169Yb seed models (Amersham International) has been undertaken. Absolute dose rates around 169Yb seed models 5, 8a, 8b and X1267 have been estimated by means of the EGS4 Monte Carlo Simulation System. An updated cross section library (DLC-136/PHOTX), binding corrections for Compton scattering and water molecular form factors were included in the calculations. Following the formalism developed by the Interstitial Brachytherapy Collaborative Working Group, anisotropy functions, F(r, theta), have been calculated and compared with other Monte Carlo results and whenever possible with experimental data. Excellent agreement is found with other Monte Carlo calculations. Considering the large experimental errors reported, a fairly good coincidence has been achieved between experimental and Monte Carlo data for models 8a and 8b. For model X1267 large discrepancies with experiment are obtained. Monte Carlo calculations for all seed models showed model 5 to be the least anisotropic and models 8b and X1267 to be almost identical. Statistical fluctuations can be drastically reduced computationally, offering an efficient alternative to measured data. Our results have estimated uncertainties of 0.5%-1.0% within one standard deviation everywhere excluding the longitudinal source axis, where uncertainties are below 3% up to 5 cm, this accuracy being excellent for clinical calculations.

Anisotropy↗

PubMed2000

Radial dose functions for 103Pd, 125I, 169Yb and 192Ir brachytherapy sources: an EGS4 Monte Carlo study.

Radial dose functions g(r) in water around 103Pd, 125I, 169Yb and 192Ir brachytherapy sources were estimated by means of the EGS4 simulation system and extensively compared with experimental as well as with theoretical results. The DLC-136/PHOTX cross section library, water molecular form factors, bound Compton scattering and Doppler broadening of the Compton-scattered photon energy were considered in the calculations. Use of the point source approach produces reasonably accurate values of the radial dose function only at distances beyond 0.5 cm for 103Pd sources. It is shown that binding corrections for Compton scattering have a negligible effect on radial dose function for 169Yb and 192Ir seeds and for 103Pd seeds under 5.0 cm from the source centre and for the 125I seed model 6702 under 8.0 cm. Beyond those limits there is an increasing influence of binding corrections on radial dose function for 103Pd and 125I sources. Results in solid water medium underestimate radial dose function for low-energy sources by as much as 6% for 103Pd and 2.5% for 125I already at 2 cm from source centre resulting in a direct underestimation of absolute dose rate values. It was found necessary to consider medium boundaries when comparing results for the radial dose function of 169Yb and 192Ir sources to avoid discrepancies due to the backscattering contribution in the phantom medium. Values of g(r) for all source types studied are presented. Uncertainties lie under 1% within one standard deviation.

Brachytherapy↗

PubMed2000

Ras-guanine nucleotide exchange factor sos2 is dispensable for mouse growth and development.

The mammalian sos1 and sos2 genes encode highly homologous members of the Son-of-sevenless family of guanine nucleotide exchange factors. They are ubiquitously expressed and play key roles in transmission of signals initiated by surface protein tyrosine kinases that are transduced into the cell through the action of membrane-associated Ras proteins. Recent reports showed that targeted disruption of the sos1 locus results in embryonic lethality. To gain insight into the in vivo function of sos2, we disrupted its catalytic CDC25-H domain by means of gene targeting techniques. Mating among heterozygous sos2(+/-) mice produced viable sos2(-/-) offspring with a normal Mendelian pattern of inheritance, indicating that the loss of sos2 does not interfere with embryo viability in the uterus. Adult homozygous mutant sos2(-/-) mice reached sexual maturity at the same age as their wild-type littermates, and both male and female null mutants were fertile. Histopathological analysis showed no observable differences between mutant and wild-type mice. Our results show that unlike the case for sos1, sos2 gene function is dispensable for normal mouse development, growth, and fertility.

Animals↗

PubMed2000

[Coxiella burnetii endocarditis: long-term clinical course in 20 patients].

INTRODUCTION AND OBJECTIVES: Coxiella burnetii is a causative agent of increasingly frequent subacute infective endocarditis, and is associated with elevated morbimortality. Our aim in the present study was to assess the clinical, serological and therapeutic long-term evolution of 20 patients with Coxiella burnetii endocarditis. METHODS: Twenty patients (13 male and 7 female, age 42 +/- 10 years) admitted between 1982 and 1996 were retrospectively studied. All of them fulfilled the Duke criteria modified by Raoult for Q fever endocarditis. RESULTS: Endocarditis involved prosthetic and native valves in 14 and 6 patients, respectively. All patients except one received antibiotic treatment. Patients treated with doxycycline in monotherapy showed worse evolution than those treated with doxycycline in combination with other antibiotics. Valve replacement was performed in 15 patients, due to prosthetic dysfunction in most of them. The overall mortality was 40% (8 patients). At follow-up of 74 months (range 19-156) (mean 74 +/- 47) all patients showed persistent high levels of phase I antibodies. At follow-up of 15 to 65 months (32 +/- 30) antibiotic treatment was suspended in five patients because they were asymptomatic and without microbiologic findings of valvular endocarditis. CONCLUSIONS: Q fever endocarditis was associated with severe complications, which often required valve replacement. All patients showed persistent high serological titers of Coxiella burnetii endocarditis without other signs of active infection. This finding raises the issue of suspending antibiotic treatment in patients with negative microbiologic findings and questions the persistence of abnormal serology as a monitor of treatment efficacy.

Adult↗