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Biomedical subjects

J Aguirre

Publications and source records attributed to J Aguirre.

At least 19 recordsLinked to original sources
PubMed2001

Endothelial nitric oxide synthase gene-deficient mice demonstrate marked retardation in postnatal bone formation, reduced bone volume, and defects in osteoblast maturation and activity.

Nitric oxide (NO) has been implicated in the local regulation of bone metabolism. However, the contribution made by specific NO synthase (NOS) enzymes is unclear. Here we show that endothelial NOS gene knockout mice (eNOS-/-) have marked abnormalities in bone formation. Histomorphometric analysis of eNOS-/- femurs showed bone volume and bone formation rate was reduced by up to 45% (P: < 0.01) and 52% (P: < 0.01), respectively. These abnormalities were prevalent in young (6 to 9 weeks old) adults but by 12 to 18 weeks bone phenotype was restored toward wild-type. Dual energy X-ray absorptiometry analysis confirmed the age-related bone abnormalities revealing significant reductions in femoral (P: < 0.05) and spinal bone mineral densities (P: < 0.01) at 8 weeks that were normalized at 12 weeks. Reduction in bone formation and volume was not related to increased osteoclast numbers or activity but rather to dysfunctional osteoblasts. Osteoblast numbers and mineralizing activity were reduced in eNOS-/- mice. In vitro, osteoblasts from calvarial explants showed retarded proliferation and differentiation (alkaline phosphatase activity and mineral deposition) that could be restored by exogenous administration of a NO donor. These cells were also unresponsive to 17ss-estradiol and had an attenuated chemotactic response to transforming growth factor-beta. In conclusion, eNOS is involved in the postnatal regulation of bone mass and lack of eNOS gene results in reduced bone formation and volume and this is related to impaired osteoblast function.

Absorptiometry, Photon↗
PubMed2001

Multiple catalase genes are differentially regulated in Aspergillus nidulans.

Detoxification of hydrogen peroxide is a fundamental aspect of the cellular antioxidant responses in which catalases play a major role. Two differentially regulated catalase genes, catA and catB, have been studied in Aspergillus nidulans. Here we have characterized a third catalase gene, designated catC, which predicts a 475-amino-acid polypeptide containing a peroxisome-targeting signal. With a molecular mass of 54 kDa, CatC shows high similarity to other small-subunit monofunctional catalases and is most closely related to catalases from other fungi, Archaea, and animals. In contrast, the CatA (approximately 84 kDa) and CatB (approximately 79 kDa) enzymes belong to a family of large-subunit catalases, constituting a unique fungal and bacterial group. The catC gene displayed a relatively constant pattern of expression, not being induced by oxidative or other types of stress. Targeted disruption of catC eliminated a constitutive catalase activity not detected previously in zymogram gels. However, a catalase activity detected in catA catB mutant strains during late stationary phase was still present in catC and catABC null mutants, thus demonstrating the presence of a fourth catalase, here named catalase D (CatD). Neither catC nor catABC triple mutants showed any developmental defect, and both mutants grew as well as wild-type strains in H(2)O(2)-generating substrates, such as fatty acids, and/or purines as the sole carbon and nitrogen sources, respectively. CatD activity was induced during late stationary phase by glucose starvation, high temperature, and, to a lesser extent, H(2)O(2) treatment. The existence of at least four differentially regulated catalases indicates a large and regulated capability for H(2)O(2) detoxification in filamentous fungi.

Amino Acid Sequence↗
PubMed2000

Cluster of MMPI personality profiles in chronic tension-type headache and predictable response to Fluoxetine.

A study was made of the personality profiles of a sample of 51 patients with chronic tension-type headache (CTH) employing the Minnesota Multiphasic Personality Inventory (MMPI). Two clusters were obtained by applying multivariate classification techniques: cluster 1 (with elevations on scales Hy, D and Hs only) and cluster 2 (exhibiting elevations on most scales except Pd, Mf and Si). Fifty subjects without chronic pain or known psychiatric disorders, and extracted from the same social setting as the patients, completed the MMPI as a control group. Fluoxetine treatment was started in the CTH group, with follow-up over a 1-year period. Chi-squared analysis correlating the clusters obtained to different pain-related variables and epidemiological parameters revealed a significant association to sex only. There were no differences in therapeutic response between the two clusters. However, the patients belonging to the less perturbed cluster who exhibited profiles analogous to those of the control population showed significant improvement with respect to the global sample and their own cluster.

Adult↗
PubMed1999

[The bent spine syndrome: a focal axial myopathy of late onset].

The bent spine is a rare syndrome appearing at an advanced age which shows a posture of anterior flexion of the trunk, which is reducible and is often hereditary. It is caused by a paresia of the extensor musculature of the trunk by a focal axial myopathy of late onset. We herein describe the case of a 72-year-old woman with a progressive bent spine initiated at the age of 55. Family questioning showed vertical transmission of the process. On exploration paresis of the paravertebral musculature and to a lesser extent of both girdles was observed. Serum CK levels were normal. Vertebral CT showed atrophy with fatty substitution of the paravertebral musculature. EMG of the scapular and paravertebral muscles demonstrated a myopathic pattern. Deltoid muscle biopsy found atrophy of type II fibers and isolated broken red fibers. This case corroborates the myopathic nature of this syndrome. A review of the nosology of the syndrome is also presented.

Age Factors↗
PubMed1998

Increased transformation frequency and tagging of developmental genes in Aspergillus nidulans by restriction enzyme-mediated integration (REMI).

We have used a plasmid containing the argB gene to transform an Aspergillus nidulans argB-deleted strain in the presence of restriction enzymes and show a 20- to 60-fold increase in transformation frequency via restriction enzyme-mediated integration (REMI). This procedure was used to try to tag new genes involved in the asexual development of this fungus. More than 2000 transformants isolated following electroporation of conidia and approximately 3700 transformants recovered following protoplast fusion were screened for sporulation defects. Unexpectedly, developmental mutants were obtained only when the protoplast fusion approach was used. Southern blot analysis of these mutants, and of randomly selected transformants obtained by electroporation, was consistent with the occurrence of single plasmid integration events in 33 and 65% of the cases, respectively. The argB marker was shown to be tightly linked to the mutant phenotype in only 62% of the mutants analyzed by sexual crosses. Partial DNA sequencing of a tagged gene, whose mutation delays asexual sporulation and results in a fluffy phenotype, showed no homology to previously reported sequences. Our results indicate that REMI can be used in A. nidulans to increase the transformation frequency and illustrate the advantages and potential problems when using REMI to tag genes of interest in this and other fungi.

Aspergillus nidulans↗
PubMed1998

Correlation between the regulation of sterigmatocystin biosynthesis and asexual and sexual sporulation in Emericella nidulans.

We analyzed the regulation of sterigmatocystin biosynthesis in wild type and mutant strains of Emericella nidulans (= Aspergillus nidulans). A positive correlation between both asexual and sexual sporulation and synthesis of the mycotoxin was observed. Those conditions which favored sporulation stimulated sterigmatocystin formation, and vice versa. Both processes were stimulated by light in a veA+ genetic background. In contrast, they were inhibited by diaminobutanone, an inhibitor of ornithine decarboxylase. The effect of this inhibitor was partially reverted by putrescine addition. Partial supplementation of specific requirements to auxotrophic mutants allowed normal vegetative growth, but interfered with asexual sporulation and sterigmatocystin biosynthesis. Synthesis of the mycotoxin was neither affected in a brlA mutant or in developmental mutants blocked at later steps in sporulation. As in wild type strain, diaminobutanone inhibited sterigmatocystin biosynthesis and cleisthotecia formation in the brlA mutant, and its effect was reverted by addition of putrescine. The inhibitor also affected the transcription of brlA. Our results indicate that sporulation and the synthesis of sterigmatocystin are co-regulated at a step previous to the brlA execution point.

Aspergillus nidulans↗
PubMed1998

Incidence of transient neurologic symptoms after hyperbaric subarachnoid anesthesia with 5% lidocaine and 5% prilocaine.

BACKGROUND: Hyperbaric 5% lidocaine has been associated with transient neurologic symptoms (TNSs) after spinal anesthesia. A prospective, masked, randomized study was conducted to compare the incidence of TNSs after spinal anesthesia with hyperbaric 5% lidocaine or 5% prilocaine to assess the utility of prilocaine as an alternative to lidocaine in patients having short surgical procedures. METHODS: The number of patients to be enrolled (100 per group) was determined by power analysis (80%, P = 0.05) considering an incidence of TNSs after spinal anesthesia with lidocaine of at least 11% according to data reported in other studies. Two hundred patients scheduled for elective surgery expected to last <60 min were allocated at random to receive spinal anesthesia with hyperbaric 5% lidocaine or hyperbaric 5% prilocaine. Three to 5 days after spinal anesthesia, all patients were interviewed by an anesthesiologist who was blinded to the group assignment and details of the anesthetic and surgical technique using a standardized symptom checklist. Patients with symptoms underwent neurologic examination. RESULTS: Both groups were comparable with regard to demographic data and details of the surgical and anesthetic procedures. The incidence of TNSs in both groups was low and differences were not found (4% in the lidocaine group and 1% in the prilocaine group). The mean age of patients with TNSs (58 yr) was higher than that of patients without TNSs (48 yr; P < 0.05). No relation with any of the other variables was found. CONCLUSIONS: The low incidence of TNSs among lidocaine-anesthetized patients (4%) may account for the lack of significant differences between hyperbaric 5% lidocaine and 5% prilocaine and to the insufficient power of the study to exclude the possibility of a type II error.

Adult↗
PubMed1998

Posttranscriptional control mediates cell type-specific localization of catalase A during Aspergillus nidulans development.

Two differentially regulated catalase genes have been identified in the fungus Aspergillus nidulans. The catA gene belongs to a class whose transcripts are specifically induced during asexual sporulation (conidiation) and encodes a catalase accumulated in conidia. Using a developmental mutant affected in the brlA gene, which is unable to form conidia but capable of producing sexual spores (ascospores), we demonstrated that the catA mRNA accumulated during induction of conidiation but did not produce CatA protein. In contrast, high levels of catalase A activity were detected in the ascospores produced by this mutant, indicating that the catA gene is posttranscriptionally regulated. The same type of regulation was observed for a catA::lacZ translational gene fusion, suggesting that the catA message 5' untranslated region could be involved in translational control during development. In a wild-type strain, beta-galactosidase activity driven from the catA::lacZ gene fusion was low in hyphae and increased 50-fold during conidiation and 620-fold in isolated conidia. Consistent with this finding spatial expression of the reporter gene was restricted to metulae, phialides, and conidia. Conidium-associated expression was maintained in a stuA mutant, in which the conidiophore cell pattern is severely deranged. catA mRNA accumulation was also observed when vegetative mycelia was subject to oxidative, osmotic, and nitrogen or carbon starvation stress. Nevertheless, catalase A activity was restricted to the conidia produced under nutrient starvation. Our results provide support for a model in which translation of the catA message, accumulated during conidiation or in response to different types of stress, is linked to the morphogenetic processes involved in asexual and sexual spore formation. Our findings also indicate that brlA-independent mechanisms regulate the expression of genes encoding spore-specific products.

Artificial Gene Fusion↗
PubMed1997

Two divergent catalase genes are differentially regulated during Aspergillus nidulans development and oxidative stress.

Catalases are ubiquitous hydrogen peroxide-detoxifying enzymes that are central to the cellular antioxidant response. Of two catalase activities detected in the fungus Aspergillus nidulans, the catA gene encodes the spore-specific catalase A (CatA). Here we characterize a second catalase gene, identified after probing a genomic library with catA, and demonstrate that it encodes catalase B. This gene, designated catB, predicts a 721-amino-acid polypeptide (CatB) showing 78% identity to an Aspergillus fumigatus catalase and 61% identity to Aspergillus niger CatR. Notably, similar levels of identity are found when comparing CatB to Escherichia coli catalase HPII (43%), A. nidulans CatA (40%), and the predicted peptide of a presumed catA homolog from A. fumigatus (38%). In contrast, the last two peptides share a 79% identity. The catalase B activity was barely detectable in asexual spores (conidia), disappeared after germination, and started to accumulate 10 h after spore inoculation, throughout growth and conidiation. The catB mRNA was absent from conidia, and its accumulation correlated with catalase activity, suggesting that catB expression is regulated at the transcription level. In contrast, the high CatA activity found in spores was lost gradually during germination and growth. In addition to its developmental regulation, CatB was induced by H2O2, heat shock, paraquat, or uric acid catabolism but not by osmotic stress. This pattern of regulation and the protective role against H2O2 offered by CatA and CatB, at different stages of the A. nidulans life cycle, suggest that catalase gene redundancy performs the function of satisfying catalase demand at the two different stages of metabolic and genetic regulation represented by growing hyphae versus spores. Alternative H2O2 detoxification pathways in A. nidulans were indicated by the fact that catA/catB double mutants were able to grow in substrates whose catabolism generates H2O2.

Amino Acid Sequence↗
PubMed1997

Assessment with transvaginal ultrasonography of endometrial thickness in women with postmenopausal bleeding.

OBJECTIVE: The aim of this study was to assess the use of transvaginal ultrasonography in measuring endometrial thickness in postmenopausal women with bleeding, thus to determine the least invasive treatment. STUDY DESIGN: We evaluated 168 women with postmenopausal bleeding by transvaginal ultrasonography and histological study of the endometrium. RESULTS: No cancerous or precancerous lesions were found when endometrial thickness was under 10 mm. The mean endometrial thickness in women with cancerous and precancerous lesions was 10.75 +/- 1.63 mm, while in non-pathological lesions it was 1.36 +/- 1.18 mm. CONCLUSIONS: To diagnose endometrial pathology, an endometrial thickness over 6 mm yields a sensitivity of 88.6%, a specificity of 90.6%, a positive predictive value of 92%, with 4.6% of false-positives and 4.6% of false-negatives (six small polyps and one irregular maturation). Although we are waiting for other prospective and multicentric studies, our present experience leads us to believe that Dilatation and Curettage (D&C) can be avoided in postmenopausal bleeding with endometrial thickness under or equal to 6 mm.

Adult↗
PubMed1996

Demethylation of 3-O-methyldopa in the kidney: a possible source for dopamine in urine.

The possibility that demethylation of 3-O-methyldopa (OM-dopa) in the kidney could provide a source for dopamine in the urine was explored in male Wistar rats aged 60-90 days, using in vivo and in vitro approaches. The results showed that endogenous OM-dopa is filtered, reabsorbed and extensively metabolized in the kidney. Infusion of OM-dopa into anesthetized rats increased significantly urinary excretion of Na+, dopa, dopamine, and 3,4 dihydroxyphenylacetic acid. Whole kidney homogenates, slices from renal cortex, and microdissected proximal tubules produced significant amounts of both dopa and dopamine when incubated with OM-dopa. Renal cortex slices produced dose-dependent amounts of dopa and dopa-mine when incubated with 1-100 microM OM-dopa. Incubation of microdissected proximal tubule segments with 1 microM OM-dopa produced a fourfold (P < 0.025) increment in dopa and a twofold (P < 0.05) increment in dopamine (an effect similar to that observed with 1 microM L-dopa). One micromolar OM-dopa or 1 microM L-dopa decreased (P < 0.05) Na(+)-K(+)-adenosinetriphosphatase activity measured at maximal velocity condition in proximal tubules. In conclusion, these experiments show that in vitro the kidney is able to produce dopamine by demethylation of OM-dopa, while the results of the OM-dopa infusion suggest that this conversion may also occur in vivo.

Animals↗
PubMed1996

catA, a new Aspergillus nidulans gene encoding a developmentally regulated catalase.

Aspergillus nidulans asexual sporulation (conidiation) is a model system for studying gene regulation and development. The CAN5 cDNA is one of several clones isolated based on transcript induction during conidiation. Here we present the molecular characterization of its corresponding gene, demonstrating that it encodes a developmentally regulated catalase, designated catA. The catA 744-amino-acid-residue polypeptide shows significant identity to other catalases. Its similarity to prokaryotic catalases is greater than to other fungal catalases. catA mRNA is barely detectable in growing mycelia, highly induced during sporulation, and present in isolated spores. However, catA expression is not dependent on the developmental regulatory genes brlA, abaA and wetA. Direct catalase activity determination in native gels revealed the existence of two bands of activity. One of these bands represented the major activity during vegetative growth and was induced during sporulation. The second catalase activity appeared after the induction of sporulation and was the predominant activity in spores. Disruption of catA abolished the major spore catalase without eliminating the vegetative activity, indicating the existence of at least two catalase genes in A. nidulans. catA-disrupted mutants produced spores that were sensitive to H2O2, as compared to wild-type spores. The increase in the activity of the vegetative catalase and the appearance of a second catalase during asexual sporulation is consistent with the occurrence of an oxidative stress during development.

Amino Acid Sequence↗
PubMed1995

Aspergillus nidulans mutants affected in acetate metabolism isolated as lipid nonutilizers.

Interest in extracellular fungal lipases has increased mainly because of their industrial applications. However, no studies have been done on a genetically well characterized filamentous fungus like Aspergillus nidulans. Here we show that A. nidulans produces an extracellular lipase when grown in solid or liquid cultures containing lipids as carbon source. This lipase is glucose-repressed in a creA-independent fashion. Seven mutants isolated by their inability to utilize lipids as sole carbon source were also unable to utilize acetate as sole carbon source. Representative mutants from each of three complementation groups were tested for allelism with strains carrying well known mutations affecting acetate metabolism. They were found to contain acuD (Isocitrate lyase), acuF (PEP carboxykinase), and acuE (Malate synthase) alleles. Screening of lipid nonutilizing mutants for growth in acetate provides a method for the isolation of both lipase minus and new acetate metabolism mutants.

Acetates↗
PubMed1995

Short- and long-term effect of oral salbutamol on growth hormone secretion in prepubertal asthmatic children.

Salbutamol, a beta 2-adrenergic agonist, is being extensively used in Venezuela as a brochodilator in the treatment of asthma in children. Previous reports have shown oral salbutamol either to inhibit or not to affect growth hormone (GH) secretion. We evaluated the effect of oral salbutamol (0.1 mg/kg every 6 hours for 3 months) on GH secretion in eight prepubertal short children with mild asthma. Levels of GH during sleep (samples taken every 30 minutes from 9 PM to 6 AM) and after GH-releasing hormone ([GHRH] 1 microgram/kg intravenously [IV]) were measured before, at 24 hours, and at 3 months of salbutamol treatment. Overnight integrated concentrations of GH and peak GH levels following GHRH diminished significantly after 24 hours of salbutamol therapy (from 4.5 +/- 1.3 to 3.4 +/- 0.8 micrograms/L and from 46.6 +/- 47.3 to 16.2 +/- 7.9 micrograms/L, respectively, P < .05). However, GH levels after 3 months of salbutamol were not different from basal levels (4.5 +/- 1.3 v 5.1 +/- 5.1 +/- 2.9 micrograms/L during the overnight studies and 46.6 +/- 47.3 v 37.8 +/- 30.4 micrograms/L after GHRH). Our data suggest an inhibition of both spontaneous and stimulated GH secretion following short-term oral salbutamol ingestion, but this suppressive effect is not maintained with its long-term use.

Administration, Oral↗
PubMed1995

Starvation stress modulates the expression of the Aspergillus nidulans brlA regulatory gene.

Expression of the Aspergillus nidulans brlA gene plays a fundamental role in the switch from vegetative growth to asexual reproduction. Using a media-shifting protocol to induce submerged sporulation and brlA-lacZ as an expression marker, it was shown that carbon and nitrogen starvation stress induced brlA transcription to different degrees. Glucose starvation induced briA rapidly to high levels and resulted in spore formation on reduced conidiophores, whereas nitrogen starvation induced brlA gradually to lower levels and sporulation occurred to a lesser extent but from more complex conidiophores. beta-Galactosidase activity paralleled brlA alpha and brlA beta mRNA. No clear qualitative differences between the two brlA transcripts were found in these starvation conditions, suggesting that the different patterns of sporulation could be explained by quantitative expression differences. Since brlA mRNA did not accumulate in the presence of a high glucose concentration, we investigated the role of other carbon sources on brlA expression. Non-repressing carbon sources such as glycerol, acetate and arabinose were as effective as glucose in preventing brlA mRNA accumulation, suggesting that the glucose effects on brlA expression could be explained as a response to nutrient starvation, rather than by carbon catabolite repression. Despite similar low levels of brlA transcripts being detected during growth in glucose or non-repressing carbon sources, conidiophores were formed only in medium containing glycerol, acetate or arabinose. When mycelia were not shifted to starvation conditions, sporulation was not observed in standard minimal medium even after glucose was exhausted, unless the medium was buffered.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspergillus nidulans↗
PubMed1995

A decreased tubular uptake of dopa results in defective renal dopamine production in aged rats.

A major proportion of urinary dopamine derives from the renal decarboxylation of circulating dopa. This study evaluates the effects of aging on renal production of dopamine using 3- and 12-mo-old male Wistar rats. Urinary excretion of Na+, norepinephrine (NE), 3,4-dihydroxyphenylglycol, and dopa were similar in the two groups. Urinary dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were lower in older animals (dopamine, 20 +/- 6 vs. 47 +/- 7 nmol/24 h, P < 0.001; DOPAC, 142 +/- 36 vs. 304 +/- 56 nmol/24 h, P < 0.03). Urinary 3-O-methyldopa (OM-dopa) was higher in 12-mo-old rats (6.2 +/- 2.0 vs. 3.3 +/- 0.20 nmol/24 h, P < 0.03). Levels of dopa and NE in renal cortex from 12-mo-old rats were higher (P < 0.001) than in younger animals. Dopamine content in renal cortex from 3-mo-old rats was 295 +/- 64 pmol/g, whereas it was undetectable in 12-mo-old animals. Aromatic-L-amino-acid decarboxylase and monoamine oxidase activities were higher (P < 0.001) in renal cortex from 12-mo-old animals. Catechol-O-methyltransferase activity was similar in both groups. The uptake of dopa by the luminal membrane was explored using brush-border membrane vesicles. The Na(+)-gradient-driven (100 mM) uptake of dopa into vesicles from 3-mo-old animals showed at 10 s an overshoot threefold greater than the equilibrium uptake. The overshoot was blunted in 12-mo-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

[Clinical care in a recovery room. Triennial review].

OBJECTIVES: To evaluate clinical practice in our intensive care unit over a period of 3 consecutive years (January 1991-December 1993). PATIENTS AND METHODS: Retrospective computer analysis of clinical data recorded for the 1157 patients admitted during the study period. RESULTS: Seven hundred thirteen men and 443 women were admitted. Mean age was 58.8 years. Eighty-nine percent had undergone elective or emergency surgery, 7% were non surgical emergency admissions and 4% were transferred from other hospital wards. The mean stay was 3.8 days, though the mean stay for elective surgery patients was significantly shorter (p < 0.001). We assess the usefulness of the APACHE-II scale applied during the first 24 hours of admission, finding that mean scores were significantly lower (p < 0.001) for the 1089 survivors (10.2 +/- 4.7) than for the 68 patients who died (23.6 +/- 9.4). The score on the APACHE II scale was above 16 for 82% of those who died. Overall mortality for the unit was 5.9%, though the proportion was statistically higher (p < 0.001) in emergency patients. Complications developed in 299, though the number of complications was significantly lower (p < 0.001) for elective surgery patients. The patients who died required more use of invasive monitoring and mechanical ventilation (p < 0.001). CONCLUSIONS: Our review shows that mortality, lengthy of stay in the unit and number of complications were all greater among emergency admissions. The patients who died had higher mean APACHE-II scores and required more care. Computerized data collection and later analysis is a useful way to assess clinical practice and facilitate future studies.

APACHE↗