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Biomedical subjects

A Fernandez

Publications and source records attributed to A Fernandez.

At least 145 records · Page 8Linked to original sources
PubMed1994

Comparison of one versus two bronchodilators in ventilated COPD patients.

OBJECTIVE: To compare the bronchodilating effect of a single drug, ipratropium bromide (IBr), with that of its combination with fenoterol (IBr+F). DESIGN: The study was triple blind and randomized. SETTING: Medical-surgical intensive care unit. PATIENTS: 12 patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation for severe respiratory failure. INTERVENTIONS: Before administering each drug, peak airway pressure (Ppeak), end inspiratory pressure (Pei), resistive pressure (Pres), and auto positive--end expiratory pressure (auto-PEEP) were measured. Inspiratory system resistance (Rins) and dynamic respiratory system compliance (C) were calculated. Arterial pH and blood gas determinations were made. These measurements were repeated 60 min after administration of each therapeutic regimen. For ipratropium bromide alone the dose was 0.04 mg. When the combination of drugs was used, the doses were 0.04 mg for ipratropium bromide and 0.1 mg for fenoterol. MEASUREMENTS AND RESULTS: With the combination of both drugs, all the pressures in the airway, as well as the auto-PEEP and the Rins were significantly reduced (p < 0.05) with respect to baseline values. With ipratropium bromide alone, no significant changes were observed either in the pressures or in the inspiratory resistance. No significant changes were observed either in the pH or blood gases with any of the treatments. The combination of both drugs produced significantly reduction in Pei and auto-PEEP when compared with ipratropium bromide alone. CONCLUSIONS: The combination of both drugs is more effective than ipratropium bromide alone at the doses used in this study.

Acute Disease↗
PubMed1994

Low contents of nerve growth factor in serum and submaxillary gland of diabetic mice. A possible etiological element of diabetic neuropathy.

Insulin and nerve growth factor are peptides that share several chemical and functional properties. While the total or relative deficiency of insulin causes diabetes, the possible disorders due to deficiency of nerve growth factor have not been clearly defined. However, the intense biological actions of nerve growth factor in the maintenance and growth of several neural cells make feasible its participation in the physiopathology of some diseases of the peripheral nervous system. We measured the contents of nerve growth factor in serum, submaxillary gland and sciatic nerve of mice with streptozotocin-induced diabetes. Nerve growth factor in diabetic mice was diminished in serum and submaxillary gland when compared with matched controls (P < 0.01). This finding further supports a similar observation in diabetic patients and suggests a possible etiological involvement of neural growth factor in the development of diabetic neuropathy.

Animals↗
PubMed1994

Neurotensin, substance P, delta and mu opioid receptors are decreased in basal ganglia of Parkinson's disease patients.

The specific binding of [3H]neurotensin, [3H]substance P, [3H]D-Ala2-D-Leu5-enkephalin (delta receptors) and [3H]-Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (mu receptors) were studied in membrane preparations of caudate nucleus, putamen, globus pallidus and substantia nigra from patients with Parkinson's disease and from age-matched controls. The density of neurotensin receptors was decreased in globus pallidus (lateral and medial segments) in parkinsonian brain. Substance P receptors were reduced in the putamen (anterior and posterior) and in lateral globus pallidus in Parkinson's disease. There was a reduction in the density of opioid receptors in posterior putamen and in mu receptors in caudate nucleus and putamen (anterior and posterior). No differences in neuropeptide receptor binding were observed in substantia nigra from parkinsonian brains compared with control subjects. The reductions in neuropeptide receptor density were less marked than the decrease in caudate and putamen content of dopamine and its metabolites. This suggests that neuropeptide receptors are only partially localized to striatal dopamine terminals.

Adult↗
PubMed1994

Immunohistochemical distribution of keratin proteins in feline tissues.

The immunohistochemical distribution pattern of some keratin intermediate filament proteins has been analysed in a wide range of formalin fixed, paraffin embedded feline tissues using one polyclonal and two monoclonal antibodies raised against human keratins by means of the avidin-biotin-peroxidase complex technique. Only the epithelial and mesothelial cells were stained by the three antibodies, but differences in their corresponding staining pattern were noticed. The staining reaction of the polyclonal antibody raised against human skin keratin was found in both stratified and complex epithelia, while that of the monoclonal antibody which recognizes human keratins 8 + 18 + 19 of the Moll catalogue (NCL-5D3) was restricted to some simple epithelia. The staining reaction of the monoclonal antibody which reacts with human keratins 5 + 8 of the Moll catalogue (RCK-102) covered the widest spectrum of feline epithelial tissues analysed, including stratified, complex and simple epithelia. These staining patterns of feline tissues are basically similar with respect to those of corresponding tissues in other mammalian species, although some differences were also noticed and some obvious epithelial tissues were not stained. This study confirms the broad interspecies cross-reactivity of keratin proteins antibodies and demonstrates their capability to differentiate between various types of feline epithelia and some epithelial compartments.

Animals↗
PubMed1994

Nuclear import of the myogenic factor MyoD requires cAMP-dependent protein kinase activity but not the direct phosphorylation of MyoD.

MyoD is a nuclear phosphoprotein that belongs to the family of myogenic regulatory factors and acts in the transcriptional activation of muscle-specific genes. We have investigated the role of cAMP-dependent protein kinase (A-kinase) in modulating the nuclear locale of MyoD. Purified MyoD protein microinjected into the cytoplasm of rat embryo fibroblasts is rapidly translocated into the nucleus. Inhibition of A-kinase activity through injection of the specific inhibitory peptide PKI prevents this nuclear localisation. This inhibition of nuclear location is specifically reversed by injection of purified A-kinase catalytic subunit, showing the requirement for A-kinase in the nuclear import of MyoD. Site-directed mutagenesis of all the putative sites for A-kinase-dependent phosphorylation on MyoD, substituting serine or threonine residues for the non-phosphorylatable amino acid alanine, had no effect on nuclear import of mutated MyoD. These data exclude the possibility that the effect of A-kinase on the nuclear translocation of MyoD is mediated by direct phosphorylation of MyoD and imply that A-kinase operates through phosphorylation of components involved in the nuclear transport of MyoD.

Amino Acid Sequence↗
PubMed1994

Intrapleural talc for the prevention of recurrent pneumothorax.

The ipsilateral recurrence rate after the first spontaneous pneumothorax treated with tube thoracostomy is reported to be between 23 percent and 52 percent. The incidence of recurrence after the first recurrence is substantially higher. Chemical pleurodesis has been attempted to decrease the recurrence rate. Tetracycline has been widely utilized, but parenteral tetracycline is no longer available. Therefore, alternative sclerosing agents have been used. Talc has been demonstrated to be effective in preventing recurrences and it has minimal long-term effects. This prospective study was designed to determine the efficacy of talc pleurodesis in patients with recurrent spontaneous pneumothorax. Eighteen patients admitted between May 1985 and March 1993 to the Department of Thoracic Surgery underwent thoracoscopy and were treated by tube thoracostomy with chemical pleurodesis. All the patients had had at least two pneumothoraces and six had had at least six pneumothoraces. Sterile asbestos-free talc, 2g, was aerosolized throughout the pleural surface. One or two chest tubes were inserted, left clamped for 2 h, and unclamped after this time. The tubes were removed when no air had escaped for 24 h. Only one (5.6 percent) patient had recurrence of the pneumothorax, and a second insufflation of talc resulted in no new recurrence after a follow-up of 10 months. The remaining 94.4 percent did not have recurrence of pneumothorax within an observation period of 38.5 +/- 28.1 months. The follow-up was more than 2 years for 66.7 percent with no recurrence and was more than 5 years for 33.3 percent. We conclude from these observations that the insufflation of 2 g of talc into the pleural space is a safe effective treatment for control of recurrent spontaneous pneumothorax.

Adult↗
PubMed1994

Intrapleural talc for the prevention of recurrence in benign or undiagnosed pleural effusions.

Chemical pleurodesis has become the preferred treatment for definitive management of malignant pleural effusions. The treatment of patients with recurrent benign or undiagnosed pleural effusions, however, remains a difficult clinical problem. Tetracycline has been widely used as a sclerosing agent, but parenteral tetracycline is no longer available. Therefore, alternative sclerosing agents are needed. Talc was used for the first time in 1935, and subsequently there have been several reports documenting its effectiveness in the treatment of malignant pleural effusion and pneumothorax. The objective of this study is to present our experience with a low dose of aerosolized talc for controlling nonmalignant pleural effusions. Between May 1985 and October 1992, twenty-two patients underwent talc pleurodesis at the time of thoracoscopy for control of a nonmalignant effusion. The cause of the effusion was cirrhosis in six patients, systemic lupus erythematosus in two, chylothorax in five, and no diagnosis in nine patients. Follow-up has ranged from 18 days to 5 years. Only two patients (9 percent), one with cirrhosis and another with an undiagnosed pleural effusion, had a recurrence of the effusions. We conclude that the intrapleural administration of 2 g of aerosolized talc is an effective treatment for recurrent benign (including chylothorax) or undiagnosed pleural effusions.

Adolescent↗
PubMed1994

Laparoscopic inguinal hernia repair with the flared patch.

A method is described of using a "flared patch" of woven polypropylene mesh (Marlex or Prolene) to laparoscopically repair inguinal hernial defects. The technique has been used in > 150 patients with indirect (60%) and direct (25%) inguinal hernias. Operating time was reduced from 45 min when the hernial sac was dissected to 25 min using the current technique. All procedures were performed in the outpatient department or during 23-h hospital observation. In the short-term follow-up time of a mean of 12 months (range, 4-23), there has been a 0.67% recurrence rate. The advantages of the laparoscopic approach, which places the operator at the site of the defect, are emphasized by the simplicity of this method. The specific patient benefits include less pain and an earlier return to normal activity, including work. It also allows for the repair of some bilateral hernias.

Adult↗
PubMed1994

Vitamin B12 levels in ewe colostrum and milk and in lamb serum.

Vitamin B12 was measured in samples of normal ovine colostrum and milk and in sera of lambs and ewes taken at various stages of lactation, from lambing up to 16 d. Colostrum obtained within 24 h of lambing contained high concentrations of vitamin B12, but within a few days the levels fell. The lambs received high levels of vitamin B12 from their dams' colostrum but a parallel decrease of vitamin B12 levels in lambs' serum and ewes' milk was subsequently observed. Milk vitamin B12 was analysed by the microbiological method (Lactobacillus leichmannii, ATCC 7830) and a radioisotope dilution (RID) technique. Milk vitamin B12 concentrations were greater with the microbiological technique compared with the RID method. The radioassay method has been shown to be as reliable as the microbiological method for measuring vitamin B12 in ovine milk except for very low levels.

Animals↗
PubMed1994

Differential sensitivity of normal and Ha-ras-transformed C3H mouse embryo fibroblasts to tumor necrosis factor: induction of bcl-2, c-myc, and manganese superoxide dismutase in resistant cells.

In this study, we investigated the role of activated Ha-ras oncogene on the growth-regulatory properties of tumor necrosis factor (TNF) in C3H mouse embryo fibroblasts. TNF-resistant 10T1/2 cells transfected with an activated Ha-ras oncogene not only produced tumors in nude mice but also exhibited extreme sensitivity to cytolysis by TNF. TNF-induced cell death was mediated through apoptosis. The differential sensitivity of normal and Ha-ras transformed cells to TNF was not due to differences in the number of TNF receptors on their cell surface. However, TNF-resistant cells, but not sensitive cells, overexpressed bcl-2, c-myc, and manganese superoxide dismutase (MnSOD) mRNA following exposure to TNF. In addition, TNF treatment resulted in a marginal induction of p53 mRNA in both TNF-sensitive and resistant cells. These results suggest that TNF-induced cytotoxicity involves apoptosis and that TNF-induced over-expression of bcl-2, c-myc, and MnSOD genes is associated with TNF resistance in C3H mouse embryo fibroblasts.

Animals↗
PubMed1993

Parallel alterations in Met-enkephalin and substance P levels in medial globus pallidus in Parkinson's disease patients.

Met-enkephalin (Met-enk) and substance P (SP) were measured by a combined high-performance liquid chromatography/radioimmunoanalysis method in medial (GPM) and lateral globus pallidus (GPL) from controls and from Parkinson's disease (PD) patients. All patients showed a similar marked (> 90%) reduction in dopamine (DA) levels in putamen compared with controls. However, based on DA levels in the caudate nucleus, two subgroups of PD patients were differentiated. In patients with > 80% decrease in caudate nucleus DA content, there was a three-fold increase in both Met-enk and SP levels in GPM. In contrast, in patients showing an approximately 50% reduction in DA content in caudate, levels of both peptides were markedly reduced (approximately 80%). Met-enk and SP levels in GPL were unchanged in PD. These results suggest that neurons containing Met-enk and SP projecting to GPM adapt according to the extent of degeneration in the substantia nigra in PD.

Aged↗
PubMed1993

p70s6k function is essential for G1 progression.

An essential step in the pathway by which growth factors trigger cellular proliferation is the induction of high levels of protein synthesis. This appears in part to be controlled by multiple phosphorylation of the ribosomal protein S6 (refs 4, 5). The main kinase responsible, p70s6k (refs 6-8), is activated through the phosphorylation of four sites clustered in a putative autoinhibitory domain, which is mediated by a signalling pathway distinct from those used by other well characterized mitogen-activated serine/threonine kinases (such as p42/p44mapk or p90rsk; refs 10, 11). Here we investigate the role of p70s6k in the mitogenic response. Microinjection of quiescent rat embryo fibroblasts with any of three distinct polyclonal antibodies to p70s6k abolishes serum-induced entry into S phase of the cell cycle. This effect is preceded by almost complete abrogation of the activation of protein synthesis and the expression of an essential immediate early gene product, c-fos. The inhibitory effect on DNA synthesis is also elicited by microinjection of the antibodies late in G1 phase, consistent with the finding that p70s6k activity remains high throughout G1.

Amino Acid Sequence↗
PubMed1993

Brain glutathione reductase induction increases early survival and decreases lipofuscin accumulation in aging frogs.

Brain catalase was continuously depleted throughout the life span starting with a large population of initially young and old frogs. Free radical-related parameters were measured in the brain tissue once per year after 2.5, 14.5, and 26.5 months of experimentation. Brain lipofuscin accumulation was observed after 14.5 and 26.5 months, and survival was continuously followed during 33 months. The age of the animal did not decrease endogenous antioxidants nor increase tissue peroxidation either in cross-sectional or longitudinal comparisons. Continuous catalase depletion similarly affected young and old animals, inducing glutathione reductase, tending to decrease oxidized glutathione/reduced glutathione (GSSG/GSH) ratio, decreasing lipofuscin accumulation in the brain, and increasing survival from 46% to 91% after 14.5 months. At 26.5 months of experimentation the loss of the glutathione reductase induction in catalase-depleted animals was accompanied by the presence of higher lipofuscin deposits than in controls and was followed by a great increase in mortality rate. Even though the maximal life span (7 years) was the same in the control and treated animals which were already old (4.2 years) at the beginning of the experiment, the treated animals showed a strong reduction in the rates of early death. It is proposed that the maintenance of a high antioxidant/prooxidant balance in the vertebrate brain greatly increases the probability of the individual to reach the final segments of its species-specific life span.

Aging↗
PubMed1993

Expression and purification of the DNA-binding domain of SRF: SRF-DB, a part of a DNA-binding protein which can act as a dominant negative mutant in vivo.

We have developed an approach which allows functional in vivo examination of DNA-binding proteins through microinjection of polypeptides containing the DNA-binding domain into living fibroblasts. The present analysis utilizes serum response factor (SRF), a transcription factor that binds to the serum response element. We have expressed in bacteria a 30-kDa portion of this protein (amino acids 113 to 265) containing the DNA-binding domain of SRF (SRF-DB) and purified it to homogeneity by a single DNA affinity chromatography step using the high-affinity SRF-binding site (ACT.L). We have tested the efficiency of SRF-DB to prevent endogenous SRF function through analysis of c-fos expression and DNA synthesis stimulated by fetal calf serum, two events known to require SRF. Injection of purified SRF-DB into rat embryo fibroblasts inhibits c-fos induction by growth factors. Moreover, DNA synthesis, induced after serum addition, is also suppressed by SRF-DB injection. This implies that overproduction of SRF-DB makes the cell deficient in the function of wild-type SRF and that SRF-DB acts as a dominant negative mutant. These data show that, for the study of DNA-binding proteins, expressing and using portions of the protein that corresponds to the DNA-binding domain present a useful method for generating dominant negative mutants and illustrate the potential application of the DNA-binding region to facilitate the study of events at the DNA/protein level.

Animals↗
PubMed1993

Estrogen and antiestrogen non-genomic effect in rat uterus contraction in calcium-free solution.

1. The effects of estrogens estradiol (E2, 10(-6)-10(-4) M) and diethylstilbestrol (DES, 10(-6)-10(-4) M) and the antiestrogens nafoxidine (N, 10(-6)-10(-4) M), tamoxifen (T, 10(-6)-6 x 10(-4) M), tamoxifen ethyl bromide (TEB, 10(-4) M) and ICI 164,384 (ICI, 10(-5) M) on tonic contractions induced by oxytocin (2 x 10(-8) M) or vanadate (3 x 10(-4) M) in rat uterus incubated in calcium-free EDTA treated solution have been assayed. 2. E2 and DES relaxed the tonic contraction induced by oxytocin in a dose dependent way (EC50: 1.11 +/- 0.01 x 10(-4) M and 1.5 +/- 0.07 x 10(-5) M). The vanadate-induced contraction only was relaxed with DES (57.62 +/- 2.38% at 10(-3) M). 3. The effect of DES on oxytocin contraction was unmodified by the protein synthesis inhibitor cycloheximide (10 micrograms/ml) and by the cyclooxygenase inhibitor indomethacin (3 x 10(-6) M), but enhanced by the intracellular calcium release inhibitor TMB-8 (10(-5) M). The antiestrogen tamoxifen (3 x 10(-5) M) promotes the relaxing effect of DES. 4. The antiestrogens N, and T, but not ICI, relaxed the oxytocin-induced contraction (EC50: 4.51 +/- 0.43 x 10(-5) M and 2.27 +/- 0.05 x 10(-4) M). TEB (10(-4) M) produces a relaxation of 74.5 +/- 2.11%. The vanadate contraction is also relaxed by T (EC50: 6.03 +/- 0.04 x 10(-4) M). 5. The effect of T on oxytocin contraction was unmodified with cycloheximide or TMB-8 but decreased with indomethacin.

Animals↗