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Biomedical subjects

E Tolosa

Publications and source records attributed to E Tolosa.

At least 91 records · Page 5Linked to original sources
PubMed1998

Biochemical and molecular effects of chronic haloperidol administration on brain and muscle mitochondria of rats.

The objectives of the current study were to evaluate (1) the respiratory rates and enzyme activities of brain and muscle mitochondria from rats chronically treated with haloperidol, (2) the protective role of dopamine (DA) D-1 (SKF38393) and D-2 (quinpirole) receptor agonists, and (3) the effect of haloperidol on the mitochondrial DNA (mtDNA) and protein synthesis. Thirty male Sprague-Dawley rats were subdivided into the following five groups: controls, haloperidol, haloperidol plus SKF38393, haloperidol plus quinpirole, and haloperidol plus SKF38393 and quinpirole. We compared the respiratory rates and enzymatic activities of brain and muscle mitochondria from controls with other groups. We finally analyzed the mitochondrial protein synthesis and mtDNA alterations (deletions, point mutations, and depletion) in two rats from each group. In brain but not in muscle from haloperidol-treated rats, we found a decrease of oxygen consumption rates using glutamate plus malate (-68 +/- 35%, P < 0.05) and succinate (-78 +/- 20%, P < 0.05) as substrates as well as low complex I, II, and V activities (-35 +/- 15%, P < 0.05; -54 +/- 13%, P < 0.05; and -60 +/- 33%, P < 0.01; respectively). The administration of SKF38393 alone or together with quinpirole prevented most of haloperidol-induced effects, whereas the protective effects of quinpirole alone were lower. Brain mitochondrial protein synthesis was decreased in haloperidol-treated rats and was not prevented by SKF38393, quinpirole, or both. We did not find mtDNA abnormalities in brain or muscle mitochondria from haloperidol-treated rats. Chronic administration of haloperidol in rats is associated with a nonspecific deleterious effect in the activity of electron transport chain of brain, and this effect is only partially prevented by DA D-1 agonists. These results suggest that other mechanisms different from DA receptors pathway can contribute to the expression of behavioral supersensitivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

[Diagnostic usefulness of glutamic acid decarboxylase antibodies in stiff-man syndrome].

Stiff-man syndrome (SMS) is a rare neurological disorder characterized by progressive rigidity of the axial musculature with superimposed spasms. Frequently, SMS remains undiagnosed for prolonged periods or the patients are diagnosed of a primary psychiatric disorder. 60% of the SMS patients harbor GAD-autoantibodies (GAD-Ab). We have analyzed the diagnostic value of GAD-Ab in a syndrome whose clinical expression is not well known, but its diagnosis is performed by clinical criteria. Five patients were studied following the established clinical criteria for diagnosis of SMS. GAD-Ab were analyzed by radioimmunoassay (RIA) and immunohistochemistry, and confirmed by immunoblot. The GAD-Ab titers were compared with those of 49 patients with insulin-dependent diabetes mellitus (IDDM), 322 with other neurological disorders, 14 non-IDDM first-degree relatives of IDDM patients with antibodies anti-islet cells and 91 normal subjects. Three patients fulfilled all clinical criteria (typical SMS). Unilateral limb symptoms alone, and acute onset with rapid progression involving the distal limb muscles constituted the atypical features of SMS in the remaining 2 patients. The 5 patients presented several serum organ-specific autoantibodies. All but one also presented autoimmune diseases. By RIA, GAD-Ab titers from all patients were elevated (mean: 24,532 +/- 26,892 U/ml) and significantly higher than the titers of IDDM patients without neurological disorders (mean: 48 +/- 112 U/ml) (p < 0.0001). GAD-Ab were absent in the non-SMS patients and in normal subjects. These findings suggest that clinical expression of SMS is more extensive than that recognized by the established criteria. GAD-Ab are helpful to define the clinical spectrum of SMS.

Aged↗
PubMed1998

Alpha-antichymotrypsin gene polymorphism and risk for Alzheimer's disease in the Spanish population.

The alpha-antichymotrypsin (ACT) and the ApoE polymorphisms have been determined in 136 Alzheimer's disease (AD) patients and in 92 age-matched controls. Only a borderline significant difference is found when comparing the overall ACT/AA genotype frequency between AD patients and controls (chi2, P = 0.08). However this difference is attributable entirely and significantly to the ApoE epsilon4 non-carrier AD group (chi2, P = 0.004). No differences are found in the ACT/AA genotype frequency of the ApoE epsilon4 AD carrier group as compared controls (chi2, P = 0.98) in contrast with previous works. These findings support that the presence of the ACT/AA genotype is a genetic risk factor for developing AD in non-ApoE epsilon4 carriers subjects in our population.

Aged↗
PubMed1998

Significant changes in the tau A0 and A3 alleles in progressive supranuclear palsy and improved genotyping by silver detection.

BACKGROUND: Progressive supranuclear palsy (PSP) is characterized by intraneuronal inclusions of neurofibrillary tangles formed by aggregated tau protein. A significant association between the tau gene A0/A0 genotype and PSP recently has been reported. OBJECTIVES: To determine if a significant association between the tau gene A0/A0 genotype and PSP could be found in an independent population with a genetic background different from that in which the initial association was reported, and to standardize a nonradioactive method for tau gene genotyping. SETTING: Hospital and university research laboratories. SUBJECTS AND METHODS: To facilitate genotyping of the tau gene, we standardized the conditions for silver-based detection of the tau gene dinucleotide polymorphism. Thirty patients from Spain clinically diagnosed as having probable PSP were included in the study and compared with different control groups. RESULTS: A highly significant overrepresentation of the A0/A0 genotype (P<.001) and a decrease in the frequency of the A0/A3 genotype were found in the Spanish patients with PSP compared with the control group. A method based on silver detection was standardized for the genotyping of the tau gene. CONCLUSIONS: The detection of a significant association between the tau gene A0/A0 genotype and PSP in 2 independent populations rules out genetic stratification as an explanation for the association and indicates that the presence of the tau A0/A0 genotype is a risk factor for developing PSP independent of genetic background. Alternatively, the results could be interpreted as a protective effect of the A3 allele.

Aged↗
PubMed1998

Sensory modulation of the blink reflex in patients with blepharospasm.

OBJECTIVE: To measure the effects of a prepulse stimulus on the blink reflex responses elicited by an electrical stimulation of the supraorbital nerve in patients with blepharospasm with and without an effective sensory trick. DESIGN: Blink reflexes to supraorbital nerve stimulation were preceded in test trials by a prepulse electrical stimulus to the third finger at various leading intervals. SETTING: Ambulatory patients were treated regularly with botulinum toxin in the Neurology Department of the Hospital Clinic in Barcelona, Spain. SUBJECTS: Seventeen patients with dystonic blepharospasm and 11 age-matched control subjects. Eight of the patients with dystonic blepharospasm used a sensory trick to alleviate spasms and 9 did not. MAIN OUTCOME MEASURES: We measured amplitude of R1 and area of R2 responses elicited by the supraorbital electrical stimulus and determined the percentage of facilitation or inhibition induced by the prepulse. RESULTS: Prepulse facilitation occurred in the R1 response at intervals of 60 to 100 milliseconds and was normal in all patients. Prepulse inhibition occurred in the R2 response at intervals between 50 and 200 milliseconds and was abnormally reduced in 11 patients (64.7%), including all 9 patients who did not use a sensory trick and 2 of the 8 patients who did use a sensory trick. There was a positive correlation between absence of sensory trick and abnormality of the prepulse effects (chi(2)= 23.8; P < .001). CONCLUSIONS: Prepulse inhibition of the trigeminofacial reflex is abnormal in a percentage of patients with blepharospasm, and this abnormality occurs more frequently in patients who do not use a sensory trick. This sensory derangement may contribute to the maintenance of the dystonic spasms by reducing the amount of physiological gating from peripheral nerve inputs on trigeminofacial reflexes.

Aged↗
PubMed1998

Stiff-leg syndrome: a focal form of stiff-man syndrome.

We report on 2 patients who presented stiffness and spasms similar to those of stiff-man syndrome (SMS) that were limited to one leg for up to 11 years. Patients had serum glutamic acid decarboxylase (GAD) autoantibodies in high titer, clinical evidence of organ-specific autoimmunity, and electromyographic pattern of continuous motor unit activity with abnormally enhanced exteroceptive reflexes. The clinical and immunological profile suggests that this disorder may be a focal form of SMS.

Autoantibodies↗
PubMed1998

Evaluation of neuronal loss, astrocytosis and abnormalities of cytoskeletal components of large motor neurons in the human anterior horn in aging.

In order to identify possible morphological changes which occur in the anterior horn of normal individuals during aging, 40 controls with no neurological disease were studied. Brain and spinal cord tissue was processed according to a brain banking protocol. Controls were grouped according to age in 10 year intervals. Serial sections (20 microm) of formalin fixed, paraffin-embedded tissue were obtained, from each cervical, thoracic and lumbar spinal cord segment. Every 5th section (until 2 mm) was stained with haematoxylin and eosin and the numbers of motor neurons in the anterior horn counted at x400 magnification. Descriptive statistical analysis was performed using the SPSS program. Parallel sections (5 microm) of the same spinal segments were immunostained with a panel of antibodies including glial fibrillary acidic protein (GFAP), tau, ubiquitin and two phosphorylated neurofilaments subunits. Significant neuronal loss with aging was found by regression line analysis where three equations were used to calculate the number of motor neurons by age in each spinal segment. In 24/40 cases spheroids were observed and they were more numerous in the lumbar segment. GFAP staining revealed a distinctive cellular pattern in the anterior horn of oldest cases. Large and intensely stained astrocytes were seen in the anterior horn of cases aged over 75 years. The number of astrocytes increased progressively with age up to 70 years. Some of the changes observed in the present study may be the result of a selective vulnerability of large motor neurons to aging which could play an important role in the progression of MND. Most of these changes may also have similar pathophysiological mechanisms.

Adult↗
PubMed1998

Triptolide induces apoptotic death of T lymphocyte.

Extract of Tripterygium wilfordii Hook. f (TWHf) has immunosuppressive activity and has been used as anti-inflammatory agent in traditional Chinese medicine for centuries. Recent studies have demonstrated that triptolide is the major active component in the extract that inhibits antigen or mitogen-induced T cell proliferation. In attempting to investigate its effect on activation of T lymphocytes, we found triptolide induces apoptotic death of T cell hybridomas and peripheral T cells but not that of thymocytes. The triptolide-induced apoptosis is accompanied by increase of DEVD-cleavable caspases activity and degradation of caspase substrate poly (ADP-ribose) polymerase (PARP). A specific inhibitor of caspases, zVAD-FMK, prevents triptolide-induced PARP degradation and DNA fragmentation but not growth arrest. Furthermore, enforced expression of Bcl-2 inhibited triptolide-induced degradation of PARP and apoptosis. These results indicate that triptolide induces T cell apoptosis through activating caspases, and suggest the growth arrest and apoptotic effect of triptolide may contribute to the immunosuppressive activity of TWHf extract.

Animals↗
PubMed1998

Thymocyte glucocorticoid resistance alters positive selection and inhibits autoimmunity and lymphoproliferative disease in MRL-lpr/lpr mice.

Thymus-derived glucocorticoids antagonize T cell receptor (TCR)-induced thymocyte apoptosis, allowing the survival (positive selection) of cells bearing TCRs that recognize self antigens with low-to-moderate avidity. Here we demonstrate that expression of an antisense glucocorticoid receptor transgene in thymocytes of spontaneously autoimmune MRL-lpr/lpr mice causes the loss of specific TCR Vbeta-bearing T cells that are normally positively selected in this strain. These transgenic mice had lower autoantibody production and milder symptoms of autoimmune disease than MRL-lpr/lpr controls and had markedly reduced accumulation of the TCR+Thy-1+CD4-CD8-B220+ T cells that are the hallmark of the lpr mutation. Thus, decreased glucocorticoid signaling in thymocytes alters the T cell repertoire and greatly diminishes autoimmunity in MRL-lpr/lpr autoimmune mice.

Animals↗
PubMed1998

History of levodopa and dopamine agonists in Parkinson's disease treatment.

Striatal dopamine deficiency in Parkinson's disease (PD), first described in 1960, was a key event that led to the era of levodopa therapy. In 1961, levodopa was first tried in PD patients, but throughout most of the 1960s the results were inconsistent. In 1967, questions about the effectiveness of levodopa in PD were finally set aside when Cotzias and colleagues reported dramatic improvement in PD patients with oral administration of levodopa in increasing amounts over long periods. The major side effects of levodopa administration, i.e., dyskinesias and motor fluctuations, also became apparent at this time. In the early 1970s, the advantages of adding a dopa decarboxylase inhibitor to treatment were discovered--reducing side effects and gaining better symptom control--and the first levodopa combination, carbidopa/levodopa, became commercially available in 1975. Since then, PD researchers have attempted to overcome complications with such techniques as continuous levodopa infusion and, most recently, long-acting levodopa combinations. A dopamine agonist, apomorphine, was used in 1970 as a means to overcome side effects and loss of levodopa efficacy. However, side effects and difficulty of administration limited its use. Dopamine agonists began to find a place in routine treatment of PD after the discovery of bromocriptine's benefits in PD in 1974. Since then, new approaches have been tried, such as dopamine agonist monotherapy and early therapy in combination with levodopa. The development of new dopamine agonists has led to characterization of dopamine receptor subtypes and agonists targeted to stimulation of specific receptors.

Antiparkinson Agents↗
PubMed1998

Effects of a startling acoustic stimulus on reaction time in different parkinsonian syndromes.

BACKGROUND: The functional assessment of the startle circuit is usually done by analyzing the acoustic startle response (ASR). However, a startling acoustic stimulus (SAS) also induces changes in the excitability of neural structures that can be demonstrated by studying the SAS-induced change in the behavior of certain neurophysiologic responses. OBJECTIVE: To examine the effects induced by an SAS on voluntary reaction time in patients with parkinsonian syndromes (StartReact effect) and to compare the results with those obtained in a group of age-matched healthy volunteers. METHODS: Twelve patients with idiopathic PD (IPD), seven patients with progressive supranuclear palsy (PSP), seven patients with multisystem atrophy (MSA), and seven healthy age-matched control volunteers performed a simple visual reaction time task and received SAS together with the "go" signal in random trials. RESULTS: Baseline reaction time was significantly slower in PSP patients than in control subjects and MSA patients. The SAS induced a significant shortening of the reaction time in control subjects and in patients with IPD and MSA, but not in patients with PSP. The percentage of reaction time shortening with regard to the baseline values also differed significantly between PSP patients and the other groups of subjects. The StartReact effect was consistent throughout the experiment and showed reduced habituation with repeated testing. CONCLUSIONS: The results are consistent with an abnormal function of the startle circuit in patients with PSP and agree with previous studies using the ASR. The reduced habituation of the StartReact effect favors its clinical applicability in the assessment of differences between patients with parkinsonian syndromes.

Acoustic Stimulation↗
PubMed1997

SCH 23390-induced behavioral supersensitivity is not related to striatal c-fos levels.

Stereotyped behavior and striatal c-fos levels induced by chronic treatment with the D1 dopamine antagonist SCH 23390 have been investigated in rats which received subsequent subacute dopamine agonist treatment. SCH 23390 treatment (0.5 mg/kg/day) for 21 days increased both apomorphine-induced orofacial stereotypies and striatal c-fos levels. Treatment with the D1 dopamine agonist SKF 38393 (10 mg/kg/day) and the combination of SKF 38393 with the D2 dopamine agonist quinpirole (1 mg/kg/day), for 5 consecutive days, attenuated apomorphine-induced stereotypies without changing c-fos levels in rats previously treated with SCH 23390. These findings suggest that SCH 23390-induced behavioral supersensitivity and the increased striatal c-fos levels are concomitant but unrelated phenomena.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Identification of Spanish familial Parkinson's disease and screening for the Ala53Thr mutation of the alpha-synuclein gene in early onset patients.

We initiated the present work in order to determine if the Ala53Thr mutation of the alpha-synuclein gene previously described by Polymeropoulos et al. [Science, 276 (1997) 2045-2047] could be detected in Spanish early onset Parkinson's disease (PD) patients. Thirty-four PD patients were evaluated. Of these, 13 were considered early onset patients (six familial and seven sporadic) and were included in the genetic study. We detected the presence of genetic anticipation in four kindreds with early onset PD members. The Ala53Thr mutation of the alpha-synuclein gene was absent in all patients. The results do not support a role for this mutation in our patients with early onset PD and, in agreement with the results previously reported, indicate that the Ala53Thr mutation of the alpha-synuclein gene is a rare cause of PD.

Adult↗
PubMed1997

The genotype 2/2 of the presenilin-1 polymorphism is decreased in Spanish early-onset Alzheimer's disease.

We have found a significantly lower frequency of the presenilin-1 (PS-1) intronic polymorphism 2/2 genotype in early-onset Alzheimer's disease (AD) patients without APOE epsilon4 alleles (2/2 = 0.054; P = 0.009) as compared to age matched non-epsilon4 controls (2/2 = 0.227). Moreover the average age of onset in AD patients with the PS-1 2/2 genotype is older than that in AD patients with a 1/2 genotype or with a 1/1 genotype. This data suggest a protective effect of the 2/2 genotype which would delay the age of onset in AD. Our results do not support an association between the 1/1 genotype and AD. However, a non-significant increase of the 1/1 genotype is found in non-epsilon4 AD patients (P = 0.20).

Age of Onset↗
PubMed1997

Habituation of the auditory startle reaction is reduced during preparation for execution of a motor task in normal human subjects.

The generalized acoustic startle reaction is a useful but labile phenomenon that undergoes a relatively rapid habituation with repeated stimuli and can be modified by changes in the environmental context. In the present work, we examined the influence of the experimental set on size, latency and habituation rate of auditory startle reactions in 15 normal volunteers. Series of 5 acoustic startling stimuli were applied on each of the following 4 conditions: (1) at rest in a quiet and dull ambience; (2) at rest but engaged in a busy environment; (3) being prepared to execute a reaction time task; and (4) focussing the attention to an impending visual stimulus. We found that the amplitude of the response to the first stimulus was significantly larger in condition 1, and habituation rate was significantly reduced in condition 3, with respect to all other conditions. The enhancement of the startle reaction in a quiet ambience may result from reduction of the sensory inputs from the environment, which would otherwise act as prepulses and cause a certain degree of inhibition. The reduced habituation rate of the startle reaction with preparation for a reaction time task may be due to a transient block of the cortical inhibitory control on inputs from non-expected sensory afferents. A careful description of the experimental conditions with which the startle reactions are tested is required for meaningful comparison of the results from different laboratories. The possibility to reduce habituation of the startle reaction with preparedness for execution of a motor task has important implications with regard to the applicability of the startle reaction on research and clinical practice.

Acoustic Stimulation↗
PubMed1997

The acoustic startle response is normal in patients with multiple system atrophy.

We investigated the acoustic startle response in eight patients with MSA and compared the results with those from a group of age matched healthy subjects. Onset latency and amplitude of the responses obtained in the orbicularis oculi, masseter and sternocleidomastoid muscles were not different in patients and control subjects. We conclude that, in spite of the pathological derangement described in brainstem reticular nuclei in MSA, the neuronal circuits mediating the auditory startle reflex are functionally preserved.

Acoustic Stimulation↗
PubMed1997

Cervical and facial myoclonus associated with dolichoectasia of the left vertebral artery.

A 52-year-old man presented with rapid jerking movements of his head to the right and clonic involuntary twitches involving his left eyelid and cheek. Electromyographic (EMG) recordings were consistent with left sternocleidomastoid and facial asynchronous myoclonus. Magnetic resonance imaging showed the presence of a dolichoectatic left vertebral artery displacing the medulla. Facial involvement and the asynchronism between cervical and facial myoclonus did not support a medullary origin for the movements. A direct compression of the eleventh and seventh cranial nerves by the dolichoectatic left vertebral artery may be the mechanism responsible for myoclonus in our patient.

Cerebellopontine Angle↗