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M J Muñoz

Publications and source records attributed to M J Muñoz.

At least 37 records · Page 2Linked to original sources
PubMed1999

The identification of Wos2, a p23 homologue that interacts with Wee1 and Cdc2 in the mitotic control of fission yeasts.

The Wee1 kinase inhibits entry into mitosis by phosphorylation of the Cdc2 kinase. Searching for multicopy suppressors that abolish this inhibition in the fission yeast, we have identified a novel gene, here named wos2, encoding a protein with significant homology to human p23, an Hsp90-associated cochaperone. The deletion mutant has a modest phenotype, being heat-shock sensitive. Using antibodies raised against bacterially produced protein, we determined that Wos2 is very abundant, ubiquitously distributed in the yeast cell, and its expression dropped drastically as cells entered into early stationary phase, indicating that its function is associated with cell proliferation. In proliferating cells, the amount of Wos2 protein was not subjected to cell cycle regulation. However, in vitro assays demonstrated that this Hsp90 cochaperone is potentially regulated by phosphorylation. In addition to suppressing Wee1 activity, overproduction of Wos2 displayed synthetic lethality with Cdc2 mutant proteins, indicating that this Hsp90 cochaperone functionally interacts with Cdc2. The level of Cdc2 protein and its associated H1 kinase activity under synthetic lethal conditions suggested a regulatory role for this Wos2-Cdc2 interaction. Hsp90 complexes are required for CDK regulation; the synergy found between the excess of Wos2 and a deficiency in Hsp90 activity suggests that Wos2 could specifically interfere with the Hsp90-dependent regulation of Cdc2. In vitro analysis indicated that the above genetic interactions could take place by physical association of Wos2 with the single CDK complex of the fission yeast. Expression of the budding yeast p23 protein (encoded by the SBA1 gene) in the fission yeast indicated that Wos2 and Sba1 are functionally exchangeable and therefore that properties described here for Wos2 could be of wide significance in understanding the biological function of cochaperone p23 in eukaryotic cells.

Amino Acid Sequence↗
PubMed1998

[Adverse drug reaction surveillance in pediatric and adult patients in an emergency room].

BACKGROUND: Adverse drug reactions (ADR) in the pediatric emergency room of a tertiary care hospital in Spain are described and compared with the adult ward. METHODS: Identification of cases was carried out through review of admission diagnoses and selection of those included in a previous list of diagnoses considered as possible ADR, that were thereafter verified. RESULTS: During 25 months, in 47.107 pediatric consultations were detected 451 cases as suspicious of ADR (0.96%). The ADR was moderate in 29 and serious in 1, being hospitalized 4. In adults, there were 68,431 consultations, and 704 cases detected (1.03%); moderate 218, serious 34 and mortal 1, being hospitalized 101. The most common reactions were dermatological (43.9% in children, 19.5% in adults) and of digestive nature (28.5 and 36.6%, respectively). The drugs most frequently involved in children were antimicrobials (49.5%), drugs used in respiratory illnesses (19.9%), non-steroid anti-inflammatory drugs (NSAID) (10.4%) and vaccines (9.2%); only two recently marketed products were involved. In adults, drugs involved were NSAID (28.2%), cardiovascular drugs (15.9%), antimicrobials (14.5%) and drugs active in digestive system (11.1%). There were 10 cases of hypoglycemia in diabetic adults, probably by interaction of hypoglycemic agents with angiotensin-converting enzyme inhibitors, and 7 cases of gastrointestinal hemorrhage associated with ketorolac, that generated an alert; 12 recently marketed products were involved. CONCLUSIONS: Intensive monitoring in emergency ward measures ADR problem, estimates underreporting, but it has a moderate value to generate alert or to survey new products.

Adolescent↗
PubMed1998

Operative treatment of the anterior synostotic plagiocephaly: analysis of 45 cases.

An operative series of 45 patients with anterior synostotic plagiocephaly is analyzed. In the cases of six children it was not possible to visualize synostosis of the cranial sutures on plain X-ray films or three-dimensional CT. Primary procedures were performed at an average age of 14 months with an average postoperative follow-up of 47.5 months. Children were operated on either with lateral canthal advancement (5 cases), unilateral orbital advancement with "tongue in groove" (12 cases), or bilateral orbital advancement (28 cases). Excellent results were obtained in 33/45 patients, while 8/45 children required secondary minor revisions. Of the three different surgical techniques, the results achieved by the bilateral approach were considered better than those attained with the unilateral techniques. Osteotomies of the nasal bones are recommended in the cases of older children with severe nasal deviation associated with dislocation of the nasoethmoidal complex.

Congenital Abnormalities↗
PubMed1995

Functional analysis of the Drosophila CDC2 Dm gene in fission yeast.

The cdc2+ gene product (p34cdc2) is a protein kinase that regulates entry into mitosis in all eukaryotic cells. The role that p34cdc2 plays in the cell cycle has been extensively investigated in a number of organisms, including the fission yeast Schizosaccharomyces pombe. To study the degree of functional conservation among evolutionarily distant p34cdc2 proteins, we have constructed a S. pombe strain in which the yeast cdc2+ gene has been replaced by its Drosophila homologue CDC2Dm (the CDC2Dm strain). This CDC2Dm S. pombe strain is viable, capable of mating and producing four viable meiotic products, indicating that the fly p34CDC2Dm recognizes all the essential S. pombe cdc2+ substrates, and that it is recognized by cyclin partners and other elements required for its activity. The p34CDC2Dm protein yields a lethal phenotype in combination with the mutant B-type cyclin p56cdc13-117, suggesting that this S. pombe cyclin might interact less efficiently with the Drosophila protein than with its native p34cdc2 counterpart. This CDC2Dm strain also responds to nutritional starvation and to incomplete DNA synthesis, indicating that proteins involved in these signal transduction pathways, interact properly with p34CDC2Dm (and/or that p34cdc2-independent pathways are used). The CDC2Dm gene produces a 'wee' phenotype, and it is largely insensitive to the action of the S. pombe wee1+ mitotic inhibitor, suggesting that Drosophila wee1+ homologue might not be functionally conserved. This CDC2Dm strain is hypersensitive to UV irradiation, to the same degree as wee1-deficient mutants. A strain which co-expresses the Drosophila and yeast cdc2+ genes shows a dominant wee phenotype, but displays a wild-type sensitivity to UV irradiation, suggesting that p34cdc2 triggers mitosis and influences the UV sensitivity by independent mechanisms.

Animals↗
PubMed1995

Ciprofloxacin pharmacokinetics in dogs following oral administration.

This paper reports the variation of the pharmacokinetic parameters of ciprofloxacin (CIP) following oral administration of three single doses (10, 20 and 40 mg/kg body weight (b.w.)) to dogs. Plasma and urine samples were assayed by HPLC. The plasma vs. time data were submitted to classical compartmental kinetic analysis (one-compartment open model with a lag time) and to non-compartmental data analysis. The maximal plasma concentrations attained after administration of 10 and 20 mg/kg were 1.55 and 3.08 mg/l, respectively, and agree with results reported in the literature for this species. The absorption was slower and showed a longer and more variable lag time when the dose increased. The elimination rate was significantly smaller after administration of the 40 mg/kg (0.0014/min) than 10 and 20 mg/kg doses (near 0.0024/min). AUC/D also showed significant differences. The non-linearity of CIP pharmacokinetics after oral administration was demonstrated by fitting the data AUC vs. dose to a quadratic equation.

Administration, Oral↗
PubMed1994

Toxicity identification evaluations for the investigation of fish kills: a case study.

A large fish-kill was observed in the river Tajo during the Spring-Summer of 1991. The mortality was first detected between Aranjuez and Toledo, affecting several fish species. Then it was slowly going downstream, affecting only carp (Cyprinus carpio), reaching the Spanish-Portuguese border several months later. Short-term toxicity tests on Daphnia magna and in vitro cytotoxicity tests on RTG-2 cells were used as toxicity monitoring systems in water samples and different water fractions. The fish kill was associated to the outbreak of infectious diseases, spring viremia of carp and saprolegniosis, related to an increase in the fish's susceptibility due to the presence of a toxic chemical. Bioassay-directed sample fractionations allowed to detect a toxic chemical. HPLC-MS identified the compound as dehydroabietic acid, a resin acid previously described immunotoxic.

Abietanes↗
PubMed1994

Disposition of ciprofloxacin following intravenous administration in dogs.

The pharmacokinetics of ciprofloxacin (CIP) following intravenous administration in dogs have been investigated. The drug was administered at three doses (2.5, 5 and 10 mg/kg body weight) and was assayed in biological fluid samples (plasma and urine) by an HPLC method. The plasma concentration-time curves were best described by a two-compartment open pharmacokinetic model. The drug was widely distributed (Vd(area) almost 3 l/kg), being distributed in the dog more rapidly than in other species (t1/2(lambda 1) 3 min approximately). The elimination half-life (t1/2 lambda 2) was 129-180 min which is similar to values obtained in other species. The unchanged drug eliminated in urine was less than 37% of the administered dose, which is less than the values obtained in humans, calves and pigs. The glomerular filtration rate and the renal clearance of CIP in the dog suggest that renal elimination probably occurs mainly by glomerular filtration. The results showed that the pharmacokinetics of CIP, as in other species, was linear in dogs in the dose range studied.

Analysis of Variance↗
PubMed1991

Effect of sublethal concentrations of four chemicals on susceptibility of juvenile rainbow trout (Oncorhynchus mykiss) to saprolegniosis.

The effects of sublethal concentrations of a variety of chemicals on the susceptibility of rainbow trout (Oncorhynchus mykiss) juveniles to Saprolegnia parasitica infection was examined. Sublethal concentrations of un-ionized ammonia (0.05 mg/liter) and nitrite (0.12 mg/liter) increased fish susceptibility after 10 days of exposure to the toxin, this increase being higher for ammonia (75% and 20% morbidity) than for nitrite (20% and 0% morbidity, respectively) with inoculum doses of 1.4 x 10(6) and 9.5 x 10(5) zoospores per liter, respectively. Sublethal concentrations of copper (0.05 mg/liter) or cyanide (0.05 mg/liter) did not show enhancement of infection by S. parasitica, even though the toxin exposure was for 21 days and the inoculum doses were higher than those for the experiments with the nitrogen compounds (4 x 10(6) and 3.2 x 10(6) zoospores per liter. However, infections began to appear in control animals.

Ammonia↗
PubMed1991

Head-injured patients who talk and deteriorate into coma. Analysis of 211 cases studied with computerized tomography.

Of 838 patients with severe head injuries admitted since the introduction of computerized tomography, 211 (25.1%) talked at some time between trauma and subsequent deterioration into coma. Of these 211 patients, 89 (42.2%) had brain contusion/hematoma, 46 (21.8%) an epidural hematoma, 35 (16.6%) a subdural hematoma, and 41 (19.4%) did not show focal mass lesions. Thus, four of every five patients who deteriorated into coma after suffering an apparently nonsevere head injury had a mass lesion potentially requiring surgery: the mass was intracerebral in 52.3% of the cases and extracerebral in 47.6%. Patients aged 20 years or less had a 39% chance of having a nonfocal mass lesion (diffuse brain damage), a 29% chance of having an epidural hematoma, and a 32% chance of having an intradural mass lesion; patients over 40 years had only a 3% chance of having a nonfocal mass lesion, an 18% chance of having an epidural hematoma, and a 79% chance of having a intradural mass lesion. Sixty-eight (32.2%) patients died and 143 (67.8%) survived. The following were independent outcome predictors (in order of significance): Glasgow Coma Scale score following deterioration into coma, the highest intracranial pressure during the patient's course, the degree of midline shift, the type of intracranial lesion, and the age of the patient. In contrast, the mechanism of injury, the verbal Glasgow Coma Scale score during the lucid interval, and the length of time until deterioration or until operative intervention did not influence the final result.

Adult↗
PubMed1989

Cranial sonographic evaluation in children with meningomyelocele.

Over a period of 5 years, 25 children between 1 day and 26 months of age were prospectively evaluated because of the presence of meningomyeloceles. Cranial sonography was used to ascertain the types of associated cranial alterations. Twenty-three children (92%) presented signs of Chiari II malformation. In only two (8%) were the ultra-sonographic results normal. The abnormalities detected were classified as alterations of the ventricular system, extraventricular alterations, and associated findings. The most frequent alteration of the ventricular system was the "bat-wing" configuration of the frontal horns, which appeared in 22 children (88%). Among the extraventricular alterations, 23 children (92%) had a downward displaced cerebellum, obliterated basal cisterns and low positioning of the tentorium cerebelli. Associated findings were a polymicrogyria in 1 case and intracranial hemorrhage in 2. The 23 children with Chiari II malformation were followed up clinically and sonographically. Our findings were similar to those of other published series. In spite of the introduction of magnetic resonance imaging, we consider cranial sonography to be an inexpensive and convenient method of evaluating the existence of Chiari II malformation in the child with meningomyelocele and of following up its evolution after shunt procedures.

Arnold-Chiari Malformation↗
PubMed1988

Cerebral hemisphere swelling in severe head injury patients.

The clinical course and the intracranial pressure (ICP) changes in 66 severe head injury patients presenting bulk enlargement of one cerebral hemisphere within a few hours of trauma have been analyzed. These patients represent 11% of a series of 589 severe head injury cases studied with computerized tomography (CT). Cerebral hemisphere swelling, which was associated with an ipsilateral subdural haematoma of variable extent in 58 patients (88%), or a large epidural haematoma in 5 patients (7%), and occurred as an isolated lesion in 3 patients (4%), carried the highest incidence of uncontrollable intracranial hypertension, the highest mortality rate and the shortest survival period after trauma in the authors' severe head injury series. The high incidence of arterial hypotension and/or hypoxaemia at admission (48% of cases), and the severity of clinical presentation (82%) of patients scored 5 patients or less in the Glasgow Coma Scale, 77% had uni- or bilateral mydriasis and 82% initial ICP above normal limits) correlated with the very poor final outcome (85% mortality). Only one of the 12 patients with normal initial ICP continued to have low pressure throughout the course. High dose thiopental failed to control severe intracranial hypertension in 29 patients (44%) who had a fulminant, malignant course. A transient decrease in ICP elevation was achieved in 17 patients (26%) and a definitive control in 12 patients (18%), among them the 10 survivors in this series. In the authors experience once ICP is controlled, and unless haemodynamic instability compells action to the contrary, barbiturate should not be discontinued until a control CT scan shows complete disappearance of the mass effect.

Adolescent↗
PubMed1986

Normal computerized tomography scans in severe head injury. Prognostic and clinical management implications.

The authors analyze the clinical course of 46 severely head-injured patients who had completely normal computerized tomography (CT) scans through the immediate posttraumatic period (1 to 7 days after trauma). These patients represent 10.2% of a consecutive series of 448 cases of severe head injuries and two-thirds of the cases showing a normal CT scan on admission (the other one-third of the cases developed new pathology). The usual course in these 46 patients after the initial coma was toward progressive neurological improvement, and 35 patients (76%) achieved a functional level of survival. Nine patients (19.5%) remained comatose for several weeks and developed severe disability. There were two fatalities due to medical complications. The final outcome was more closely related to the duration of coma (the longer the duration the worse the result) than to the initial Glasgow Coma Scale (GCS) score. In fact, 26% of the patients in the lower GCS score ranges (3 to 4 points) made a good recovery and 46% developed moderate disability only. These findings indicate that the grim prognostic significance of deep posttraumatic coma is tempered in the presence of a normal scan. However, the absence of CT abnormalities in severely head-injured patients cannot be equated with a good prognosis because in one-fifth of the cases serious permanent disability develops. Sustained elevation of the intracranial pressure (ICP) was not seen in these patients, indicating that ICP monitoring may be omitted in cases with a normal scan. However, since one-third of the patients with a normal admission scan developed new pathology within the first few days of injury, a strategy for control scanning is recommended. Control CT scans performed more than 6 months after injury showed a significantly higher incidence of brain atrophy in patients developing permanent disability than in those who made a good recovery.

Adult↗
PubMed1981

Subependymoma of the lateral ventricle.

The case of a girl with a large cystic subependymoma of the lateral ventricle is reported. The tumor, which did not cause hydrocephalus, was attached to the wall of the frontal horn and grew out of the ventricular system extending into the anterior cranial fossa and the orbital cavity. Despite some typical features exhibited by the lesion, its true nature was not recognized during the operation. The importance of the identification of this rare benign tumor is emphasized because a radical removal may be accomplished in most cases with a very good prognosis.

Adolescent↗
PubMed1981

Giant cerebral arteriovenous malformation producing a noncommunicating hydrocephalus.

The case of a woman with a large, mixed, cerebral arteriovenous malformation mainly involving the posterior fossa and producing a noncommunicating hypertensive hydrocephalus is reported. Relief of ventricular enlargement by means of a cerebrospinal fluid shunt unexpectedly resulted in stupor and Parinauds' syndrome. These complications were completely relieved by ligating the shunt. The vascular and mechanical factors involved in the production of hydrocephalus in this patient are discussed.

Adult↗
PubMed1981

Observations on 82 patients with extradural hematoma. Comparison of results before and after the advent of computerized tomography.

A consecutive, unselected series of 82 patients with epidural hematoma treated between 1973 and 1980 is presented. Forty-one patients were managed before the advent of computerized tomography (CT) and the other 41 after this neuroradiological method was available. Mortality and disability rates which were 29.2% and 31.7% during the pre-CT period decreased to 12.1% and 19.5%, respectively, with the aid of CT scanning. This technique allowed a more rapid and accurate diagnosis of the hematomas than angiography, and defined better the presence and the evolutional changes of the associated cerebral lesions. As a consequence, surgery has been more effectively planned and executed during the CT era.

Adolescent↗
PubMed1981

Hydrocephalus in cerebral cysticercosis. Pathogenic and therapeutic considerations.

The cases of 11 patients with hydrocephalus secondary to cerebral cysticercosis are analyzed. Most of the patients had suffered from epilepsy before they developed hydrocephalic symptoms, and computerized tomography showed that infestation of the parenchyma coexisted with ventricular or cisternal colonization. In four cases, the parasitic vesicles compromised cerebrospinal fluid (CSF) flow in the ventricular system, resulting in internal hydrocephalus. Communicating hydrocephalus, caused by the presence of Cysticercus larvae in the basal cisterns (Cysticercus racemosus), or by the occurrence of a chronic basal meningitis, or both, developed in seven more patients. Changes in CSF pressure were related to the number and location of the cysts and to the leptomeningeal inflammatory reactions evoked by them. The majority of patients presented with a chronic and relatively normotensive hydrocephalus. All patients except one had identifiable ventricular or cisternal Cysticercus larvae; these patients were treated with open removal of the cysts, and did well. However, most of them had impairment of CSF flow through the basal cisterns and required permanent CSF shunting. Communicating hydrocephalus due to leptomeningeal scarring was also successfully managed with extracranial shunting. Epilepsy was controlled with anticonvulsant therapy. Although good lasting results may be obtained with aggressive treatment of neurocysticercosis, patients are liable to relapse because surgery is only palliative in most instances.

Adult↗