Biomedical subjects

M Gratacós

Publications and source records attributed to M Gratacós.

8 recordsLinked to original sources

PubMed2002

Neurobehavioral development of two mouse lines commonly used in transgenic studies.

The present study was aimed at establishing the differences in the neurodevelopmental profile between two F2 lines derived from two F1 hybrid mouse strains (129 x C57BL/6 and C57BL/6 x SJL). The choice of the given strains was based on the frequent use of these mice in transgenic research. For the neurodevelopment phenotyping, we employed a test battery consisting of 23 somatometric, sensorial and motor tests. Significant variations between the strains were established in different functional domains. Some specific delays in the appearance of developmental landmarks were observed in F2 mice derived from crosses of F1 C57BL/6 x 129, whereas they acquired early developmental functions, such as the righting reflex, sooner than C57BL/6 x SJL-derived mice. C57BL/6 x 129 F2 offspring were spontaneously hypoactive, and their poorer motor performance was confirmed by low performance in the negative geotaxis test. However, there were no differences in the general psychomotor development as shown by the good performance in the homing test in both F2 lines. Both strains were susceptible to the handling procedures used, presenting a similar alteration in the response observed in the homing test as compared to nonhandled control mice. In conclusion, our work highlights the importance of the genetic background for transgenesis experiments and also the need for well-established testing protocols to obtain sufficient information at the first stage of behavioral screening of genetically modified mice.

Animals↗

PubMed1998

Uncloned expanded CAG/CTG repeat sequences in autosomal dominant cerebellar ataxia (ADCA) detected by the repeat expansion detection (RED) method.

In some neurodegenerative diseases, genetic anticipation correlates with expansions of the CAG/CTG repeat sequence above the normal range through the generations of a pedigree. Among these neurodegenerative diseases are late onset autosomal dominant cerebellar ataxias (ADCA). ADCA are genetically heterogeneous disorders with different cloned genes for spinocerebellar ataxia type 1 (SCA1), type 2 (SCA2), type 3 or Machado-Joseph disease (SCA3/MJD), and type 6 (SCA6). Another related dominant ataxia, dentatorubral-pallidoluysian atrophy (DRPLA), also shows CAG/CTG repeat expansions. Genetic anticipation has been reported for all of them except for the recently cloned SCA6 gene. Other, as yet undetected SCA genes may show the same features. We have used the repeat expansion detection (RED) method to detect repeat expansions directly in DNA samples from ADCA patients not resulting from known genes. Our sample consists of 19 affected index cases, corresponding to 52.8% of our ADCA families without CAG/CTG repeat expansions in the SCA1, SCA2, SCA3/MJD, SCA6, or DRPLA genes. Eighty-nine percent of the index cases had expansions of a CAG/CTG sequence greater than 40 repeats by RED, while these were observed in only 26.9% of 78 healthy subjects from the general population (p < 0.0001). The distribution of RED fragments in controls and ADCA patients also shows significant differences with the Mann-Whitney U test (U = 376.5, p = 0.0007). Moreover, there was a significant inverse correlation between the size of expansion and the age of onset (r = -0.54, p = 0.018). These results show CAG/CTG repeat expansions of over 40 repeats in our sample of ADCA families not resulting from known SCA genes.

Adult↗

PubMed1998

[Role of the extracellular matrix in X-chromosome-linked muscular dystrophy: immunohistochemical study].

OBJECTIVE: To study the role of the extracellular matrix in the pathogenesis of the X-linked muscular dystrophy. MATERIAL AND METHODS: Muscle specimens from 8 normal controls with ages ranging from 4 to 14 years of age and those of 14 X-linked muscular dystrophy patients were studied by means of polyclonal antibodies able to recognize extracellular matrix molecules. The findings of each of the controls and patients were evaluated systematically using a semiquantitative morphological method. On the other hand, with the help of an automatic interactive image analyzer, the following structures were measured: a) area occupied by the perimysium; b) area of the endomysium, and c) transverse fibre area. RESULTS: The deposition of the extracellular matrix components of patients with X-linked muscular dystrophy is a selective phenomenon which is mostly related to groups of fibers undergoing necrosis-regeneration. X-linked muscular dystrophy patients have an heterogeneous clinical and pathological picture. At one end of the spectrum there are patients with the most severe phenotype, in which reduction of fiber size, early deposition of connective tissue and distortion of the capillary bed are the most conspicuous pathological changes. At the other end muscle fiber hypertrophy and splitting, lesser connective tissue deposition and a milder clinical course predominate. Selective deposition of extracellular matrix components occurs at each point of the spectrum. The distribution of the extracellular matrix components does not appear to accomplish a substitutive function designed to replace the loss of number or volume of the muscle fibers.

Adolescent↗

PubMed1997

Polymorphisms at 13 expressed human sequences containing CAG/CTG repeats and analysis in autosomal dominant cerebellar ataxia (ADCA) patients.

Genetic anticipation--increasing severity and a decrease in the age of onset with successive generations of a pedigree--is clearly present in autosomal dominant cerebellar ataxia (ADCA). Anticipation is correlated with expansion of the CAG/CTG repeat sequence to sizes above those in the normal range through the generations of a pedigree. Genetic heterogeneity has been demonstrated for ADCA, with four cloned genes (SCA1, SCA2, SCA3/MJD, and SCA6) and three mapped loci (SCA4, SCA5 and SCA7). Another related dominant ataxia, dentatorubral-pallidoluysian atrophy (DRPLA), presents anticipation with CAG/CTG repeat expansions. We had previously analysed ADCA patients who had not shown repeat expansions in cloned genes for CAG/CTG repeat expansions by the repeat expansion detection method (RED) and had detected expansions of between 48 and 88 units in 17 unrelated familial cases. We present here an analysis of 13 genes and expressed sequence tags (ESTs) containing 10 or more CAG/CTG repeat sequences selected from public databases in the 17 unrelated ADCA patients. Of the 13 selected genes and ESTs, 9 were found to be polymorphic with heterozygosities ranging between 0.09 and 0.80 and 2 to 17 alleles. In ADCA patients none of the loci showed expansions above the normal range of the CAG/CTG repeat sequences, excluding them as the mutation causing ADCA.

Base Sequence↗

PubMed1996

Somatotype in panic patients.

The aim of the study was to test whether an association exists between asthenic somatotype, as measured by the Quetelet index, and panic and or agoraphobia. Ninety-nine cases with panic and/or agoraphobia diagnosed at the psychiatric outpatient clinic of a general teaching hospital were compared to 99 controls with psychiatric conditions other than panic and agoraphobia, and to 64 medical controls, matched by age and gender. No differences in weight, height and raw Quetelet and ponderal indexes were found between panic cases and controls. However, 33.3% of cases, but only 19.2% of psychiatric controls and 18.7% of medical controls, were in the asthenic group as defined by the lower quartile of the Quetelet index (age and sex adjusted odds ratio = 2.33, 95% C.I.: 1.21-4.11). In the entire sample, the asthenic somatotype was associated with lower age and with the presence of hypermobility of joints. Since both panic disorder and mitral valve prolapse may be associated with the joint hypermobility syndrome (JHS), an inherited disorder of collagen synthesis, it is suggested that the relationship found between panic and asthenic somatotype might be mediated through JHS.

Adult↗

PubMedDate not supplied

[Prognostic factor for medical control for seizures in patients with radiologic evidence for mesial temporal lobe sclerosis].

INTRODUCTION: Patients with mesial temporal lobe sclerosis (MTS) usually have suffered a brain insult during early childhood, a febrile convulsion in most cases. Complex partial seizures start after a seizure free period of variable duration. These complex partial seizures have an stereotypic semiology. Often, these seizure are not controlled with medical therapy, previous studies shows a rate of control not superior of 30%. AIM. To know the prognosis for medical control of patients with MTS and to find related factors. PATIENTS AND METHODS: The clinical characteristics of 51 patients with temporal lobe epilepsy and radiologic evidence of MTS (hippocampus atrophy or increased signal on T2 or Flair magnetic resonance sequences). RESULTS: 51 patients, of them 17 (34%) were men. 17 (34%) presented right MTS, 30 (60%) left MTS and 2 (4.3%) bilateral MTS. 16 patients (34.8%) referred autonomic aura, 14 (27.5%) psychic aura, 4 (7.8%) dysphasia and 13 (25.5%) no aura, in 2 (3.9%) aura were mixed: autonomic psychic. The aura was associated to the lesion laterality (p= 0.023) and to the reference of some antecedent of cerebral aggression during early childhood (p= 0.011). Concerning to the seizure control, 15 patients (29.2%) were seizure free in the last 6 month and 36 (70.6%) remaining uncontrolled. The associated factors to the medical control were the age of onset (p= 0.024) and the duration of the epilepsy (p= 0.018). CONCLUSIONS: Around 29% of patients with MTS can be controlled with medical therapy. Seizure control is related with later age of onset and short duration of the epilepsy

Adult↗

PubMedDate not supplied

[Idiopathic generalised epilepsy. The value of semiology and EEG scanning in its classification].

INTRODUCTION: The different syndromes included in the idiopathic generalized epilepsies present an important overlapping of their electroclinical characteristics. AIM: To compare the two actual classifications (International classification of epileptic syndromes: ILAE of 1989 and of 2001) in a sample of patients with idiopathic generalised epilepsy (IGE) and to evaluate which electro-clinical factors were more useful in order to classify a patient into a syndrome. PATIENTS AND METHODS: 70 patients (44 women/26 men). Neurological examination and neuro-radiological examination were normal in all cases. The EEG (standard or sleep deprived) showed generalised epileptiform discharges in all patients. Clinical findings included a median age of onset 12.3 years. Most frequent first type of seizure was tonic-clonic (71%). Seizures during awakening were the most frequent (37%) and lack of sleep was the most important precipitating factor (44.7%). Generalized epileptiform discharges were present in 62.9% of the basal sleep deprived EEG, on the other hand, only 22.3% of the basal standard EEG showed epileptiform discharges, p = 0.048. 28% of patients were unclassifiable according to the 1989 ILAE classification, 7% were unclassifiable according to the 2001 ILAE classification. EEG during intermittent photic stimulation (p = 0.007), at awakening (p = 0.015) and the timetable of the seizures (seizures generalised at awakening) (p = 0.053) differentiated between idiopathic generalised syndromes of adolescence. CONCLUSION: The 2001 ILAE classification is more useful in order to classify patients with IGE because includes patients previously considered unclassifiable in the syndrome of generalised epilepsy with different phenotypes.

Adult↗

PubMedDate not supplied

[Congenital insensitivity to pain with anhidrosis associated with congenital myasthenic syndrome].

INTRODUCTION: Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV (HSAN IV) is a rare autosomal recessive disorder featuring recurrent fever episodes, inability to sweat, absent response to noxious stimuli, self mutilating behavior and mental retardation. It has been associated with mutations in the NTRK1 gene, located in 1q21-22 and encoding a high-affinity NGF receptor. CASE REPORT: An 8-year-old boy, the first son of consanguineous parents, presented with hypotonia, episodic hyperpyrexia and global developmental delay since the neonatal period. In addition to these signs, typical of CIPA, he displayed some other not previously described in this disease, such as facial dysmorphism, a severe swallowing disorder and a myogenic EMG pattern, that led to the initial suspicion of a muscle disorder. Molecular genetics studies uncovered a mutation c.C2011T in exon 15 of the NTRK1 gene. Genetic counselling was possible in the following pregnancy of the couple, where the female fetus was found to harbour the mutation in heterozygosity. The subsequent diagnosis of a congenital myasthenic syndrome in this sister led to neurophysiological re-evaluation of the probandus, in whom a myasthenic pattern of muscle activation was also found. CONCLUSIONS: A patient with CIPA and congenital myasthenic syndrome is described. CIPA must be the first diagnostic hypothesis when assessing a patient with insensitivity to pain, anhidrosis and self-mutilation. Given the rather homogeneous presentation of CIPA, the occurrence of atypical myopathic manifestations should raise the suspicion of a concurrent disorder. The present consanguineous kindred illustrates a rare instance of transmission of two mutated alleles giving rise to two unrelated, infrequent neurological syndromes.

Alleles↗