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Biomedical subjects

F L Mastaglia

Publications and source records attributed to F L Mastaglia.

At least 19 recordsLinked to original sources
PubMed1996

Inclusion body myositis: investigation of the mumps virus hypothesis by polymerase chain reaction.

Inclusion body myositis (IBM) is a distinctive form of chronic inflammatory myopathy characterized pathologically by the finding of rimmed vacuoles and 15-18nm microtubular filamentous inclusions in muscle fiber nuclei and cytoplasm. The observation that these filaments resembled nucleocapsids of the paramyxovirus group and showed immunoreactivity with mumps virus (MV) antibodies has led to a long-standing postulate that IBM may be a "slow" mumps infection. We searched for the presence of MV RNA in 34 muscle biopsies (17 frozen and 17 paraffin-embedded) from 18 patients with IBM and 43 control biopsies (mainly from patients with other forms of inflammatory myopathy) using a polymerase chain reaction (PCR). The MV PCR was shown to be sensitive and specific for MV strains (including J-L) and the integrity of muscle RNA extracts was confirmed by PCR detection of constitutive Ableson tyrosine kinase mRNA. MV RNA was not found in any biopsy from the IBM group nor any of the control cases. Our results therefore do not support the mumps hypothesis for IBM.

Adult↗
PubMed1996

Spatial differences in the sites of direct and indirect activation of corticospinal neurones by magnetic stimulation.

Transcranial magnetic stimulation (TMS) over the human motor cortex evokes multiple descending volleys possibly through activation of different elements within the brain. We have investigated whether such elements can be distinguished spatially. Using a figure of eight coil, TMS was delivered over multiple scalp sites during a low level voluntary contraction of the left first dorsal interosseous muscle. At near-threshold intensity, early or late surface electromyograph (EMG) components (relative to anodal response latency) could be preferentially evoked with the coil aligned in a medio-lateral (ML), antero-posterior (AP), or postero-anterior (PA) orientation. The optimal location of the earliest component with ML coil orientation was 8 mm medial and 5 mm anterior compared to a later component with AP orientation. The optimal location for the same latency EMG component mapped using two different coil orientations (AP and ML) was not significantly different. The optimal location of two different late components, one obtained with AP and the other with PA coil orientations, was similar. It is argued that the earliest TMS-evoked component results from direct activation of corticospinal cell axons while later components result from activation of these cells trans-synaptically (indirectly), and that consequently there is a substantial spatial separation between these activation sites.

Adult↗
PubMed1996

Effects of magnetic stimulation over supplementary motor area on movement in Parkinson's disease.

Movement execution can be delayed by transcranial magnetic stimulation delivered over primary motor cortical areas, resulting in transient inhibition of cortico-motor output. Inhibition or disruption of higher-order motor planning and preparatory processes, such as are thought to occur in the supplementary motor area (SMA), would allow an examination of processes at other stages of the motor control system. In this study, six subjects with Parkinson's disease and six healthy control subjects performed a non-cued sequential finger movement task. At various times relative to movement, high-intensity single-pulse magnetic stimulation was delivered over the region of the SMA, with minimal current spread to primary motor areas. When magnetic stimulation was given at early stages during the movement for parkinsonian subjects, movement times were significantly increased, indicating disrupted movements. Supplementary motor area stimulation had no effect when delivered during later stages of the movement or immediately prior to movement onset, and had no apparent effect on control subjects at any time. It is therefore suggested that the SMA is important in motor planning and preparatory processes, since SMA stimulation has no effect on movements in their later stages when planning may be complete, but may disrupt movements in their early stages, when preparation for later stages may still be in progress. Further, possible instability of motor planning/preparation processes in Parkinson's disease is suggested, since these processes appeared more susceptible to disruption by magnetic stimulation in parkinsonian subjects than controls.

Aged↗
PubMed1995

Apolipoprotein E epsilon 4 in inclusion body myositis.

The genetic predisposition to inclusion body myositis (IBM) is probably multifactorial. The deposition of the beta-amyloid protein is a characteristic histological feature of both IBM and Alzheimer's disease (AD). The epsilon 4 allele of apolipoprotein E (APO E) has been strongly associated with familial and late-onset AD. We therefore compared the APO E allele frequencies in a group of 14 patients with IBM with those in a group of patients with other inflammatory muscle diseases and in the general population. The frequency of the epsilon 4 allele in IBM was increased (0.29) compared with that in patients with other inflammatory muscle diseases (0.15) and the general population (0.13) (p < 0.05). These data suggest that APO E genotype may be one of the factors involved in determining the predisposition to the development of IBM.

Adult↗
PubMed1995

The audiogenic startle response in Tourette's syndrome.

We report the results of a study in which we examined the auditory startle responses (ASR) of 8 patients with Tourette's syndrome and 15 normal controls, none of whom reported or manifested exaggerated startle responses clinically. The ASR in two patients failed to habituate with repetition, a finding not present in any of the controls. There was no correlation between the presence or absence of exaggerated ASRs and the severity of the patients' tics. This study demonstrates that some patients with Tourette's syndrome have exaggerated audiogenic startle responses that may be clinically asymptomatic.

Acoustic Stimulation↗
PubMed1995

Comparison of the magnetically mapped corticomotor representation of a muscle at rest and during low-level voluntary contraction.

This study has compared the topography of the corticomotor representation of an intrinsic hand muscle in the relaxed state and during a low-level voluntary contraction using transcranial magnetic stimulation. It was found that the optimum cortical stimulus site and the surrounding area of excitable cortex were shifted approximately 6 mm medially as a result of performing a voluntary contraction. This difference may be due to a combination of factors involving the spatial distribution of excitable intracortical fibres, the effects of muscle afferent activity on motor cortex excitability, and task-dependent modifications of corticomotor output.

Adult↗
PubMed1995

An investigation of the late excitatory potential in the hand following magnetic stimulation of the motor cortex.

Magnetic stimulation of the motor cortex gives rise to a motor evoked potential (MEP) followed by a silent period (SP) during which a late excitatory potential (LEP) may occur in the surface EMG. To elucidate the mechanism of the LEP we investigated the effect of muscle contraction, stimulus intensity and stimulation site on the LEP recorded from the abductor pollicis brevis muscle. The amplitude of the LEP increased with increasing levels of muscle contraction and decreased with increasing stimulus intensity. There was no direct relationship between the amplitude of the LEP and the MEP, but there was an inverse relationship between LEP amplitude and SP duration. The latency of the LEP was unaffected by the level of muscle contraction, but increased with increasing stimulus intensity. Topographic mapping with stimulation at multiple scalp sites yielded a LEP at sites partially encircling but not including the centre of the APB motor area. These results are consistent with the LEP being due to reflex alpha motoneurone firing as a result of gamma motoneurone activation or with a period of disinhibition at cortical level allowing breakthrough of voluntary activity.

Adult↗
PubMed1995

The origin of the soleus late response evoked by magnetic stimulation of human motor cortex.

Transcranial magnetic stimulation (TMS) of the human motor cortex elicits a primary motor evoked potential (MEP) in the soleus muscle at a latency of approximately 30 msec, which may be followed by a late potential with a variable latency of 80-120 msec (soleus late response, SLR). While the MEP is thought to arise from stimulation of the corticospinal tract, the origin of the SLR is uncertain. In the present study we have investigated the properties of the SLR in order to elucidate its origin. An SLR was evoked at a latency of 100-120 msec in 5 out of 10 normal subjects in the relaxed state and at a latency of approximately 100 msec in all subjects when tibialis anterior (TA) was slightly facilitated. The SLR was largest with 5-10% TA contraction, decreased in size with increasing levels of TA contraction and was negligible in all subjects when the foot was immobilised. The latency of the SLR fell by 23 msec when the foot was passively dorsiflexed 20 degrees. A similar response to the SLR, at a latency of 77 msec, was present in all subjects following electrical stimulation of the peroneal nerve. Our findings suggest that the SLR is a soleus stretch reflex resulting from dorsiflexion of the foot due to preferential activation of TA following cortical stimulation.

Adolescent↗
PubMed1995

Search for persistent infection with poliovirus or other enteroviruses in amyotrophic lateral sclerosis-motor neurone disease.

A longstanding hypothesis proposes that amyotrophic lateral sclerosis-motor neurone disease (ALS-MND) is a late consequence of subclinical poliovirus (PV) infection. In this study, RNA extracts of CNS tissue from 28 patients with ALS-MND and 7 controls were assayed by nested polymerase chain reaction (PCR) using primers to the 5'-untranslated region (UTR) of the enterovirus (EV) genome which is highly conserved between EVs including PV, echovirus and coxsackie viruses. The integrity of RNA extracted from either archival paraffin-embedded or frozen CNS tissue was assessed by detection of constitutive Ableson tyrosine kinase (ABL) mRNA by PCR. Of 63 tissue samples assayed, 81% (51/63) were ABL-positive corresponding to 78% (22/28) of the ALS-MND cases and all controls. None of the 27 ALS-MND cases (i.e. 21 ABL+ and 6 ABL-) in which paraffin-embedded tissue was used nor any of the age and sex matched controls were positive for specific PV/EV RNA. Moreover, CNS tissue from 14 different locations obtained from one patient < 2 hrs after death and immediately frozen, showed no evidence of PV/EV at any site by PCR. Disease duration, degree of tissue autolysis and duration of tissue storage were all excluded as factors which may predispose to negative results. The sensitivity of the PV PCR was determined to be 40-400 copies (12.5 - 125 ag) of synthetic EV RNA transcripts in 1 microgram of cellular RNA and the assay was shown to detect all types of PV and and other EVs tested. Thus it seems unlikely that a persistent PV or related EV infection is implicated in ALS-MND unless there has been alteration in the 5'-UTR of the virus genome.

Adult↗
PubMed1995

Autosomal dominant distal myopathy: linkage to chromosome 14.

We have studied a family segregating a form of autosomal dominant distal myopathy (MIM 160500) and containing nine living affected individuals. The myopathy in this family is closest in clinical phenotype to that first described by Gowers in 1902. A search for linkage was conducted using microsatellite, VNTR, and RFLP markers. In total, 92 markers on all 22 autosomes were run. Positive linkage was obtained with 14 of 15 markers tested on chromosome 14, with little indication of linkage elsewhere in the genome. Maximum two-point LOD scores of 2.60 at recombination fraction .00 were obtained for the markers MYH7 and D14S64--the family structure precludes a two-point LOD score > or = 3. Recombinations with D14S72 and D14S49 indicate that this distal myopathy locus, MPD1, should lie between these markers. A multipoint analysis assuming 100% penetrance and using the markers D14S72, D14S50, MYH7, D14S64, D14S54, and D14S49 gave a LOD score of exactly 3 at MYH7. Analysis at a penetrance of 80% gave a LOD score of 2.8 at this marker. This probable localization of a gene for distal myopathy, MPD1, on chromosome 14 should allow other investigators studying distal myopathy families to test this region for linkage in other types of the disease, to confirm linkage or to demonstrate the likely genetic heterogeneity.

Adolescent↗
PubMed1994

Search for persistent enterovirus infection of muscle in inflammatory myopathies.

To investigate the hypothesis that the inflammatory muscle diseases (IMD) polymyositis (PM) and dermatomyositis (DM) may be due to a chronic, persistent enterovirus (EV) infection we sought to determine the prevalence of these viruses in muscle tissue using both nested polymerase chain reaction (PCR) and dot-blot hybridization assays. Thirty-six frozen muscle biopsies from 32 adult cases of IMD and 42 biopsies from 36 control subjects with other neuromuscular disorders were studied. Primers for PCR were chosen to conserved regions of the 5'-untranslated region of the EV genome. Constitutive Ableson tyrosine kinase (ABL) mRNA was detected by PCR to confirm the integrity of muscle RNA extracts. The sensitivity of the EV PCR was determined to be 40-400 copies (12.5-125 ag) of synthetic EV RNA transcript against a background of 1 microgram of cellular RNA. The specificity was assessed using a range of enteroviral and unrelated viral isolates extracted from cell cultures. Of the 78 samples tested, ABL mRNA was successfully detected in all but four samples. The time the biopsies spent in ultracold storage (1-73 months) did not appear to influence the integrity of extracted RNA. When assayed for EV RNA by nested PCR, none of 29 IMD cases (i.e., 28 PM and 1 DM) nor sequential biopsies from 3 PM patients were found to be positive. All 42 control biopsies were also negative for EV RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

HLA associations with inclusion body myositis.

Inclusion body myositis (IBM) is defined clinically by a characteristic pattern of progressive proximal and distal limb muscle weakness and resistance to steroid therapy, and histologically by the presence of distinctive rimmed vacuoles and filamentous inclusions as well as a mononuclear infiltrate in which CD8+ T cells are predominant. Muscle damage is believed to be mediated by autoimmune mechanisms, but very little information is available on the immunogenic features of IBM. MHC class I and DR antigens were typed on 13 caucasoid patients with IBM using standard serological techniques or by allele-specific oligonucleotide typing. Complement components C4 and properdin factor B (Bf) were typed by immunofixation after electrophoresis. Restriction fragment length polymorphisms (RFLP) in the class III region were analysed using cDNA probes for C4 and 21-hydroxylase (CYP21) after Taq 1 digestion. IBM was associated with DR3 (92%), DR52 (100%) and HLA B8 (75%). The phenotype data were examined for likely haplotypes by considering together the alleles at the class I, DR and complement loci along with the C4 and CYP21 RFLP. Ten of the DR3+ subjects had a 6.4-kb C4-hybridizing fragment characteristic of a deletion of C4A and CYP21-A. These patients probably carried all, or at least the class II and III regions, of the extended haplotype marked by B8/C4A*Q0/C4B1/BfS/DR3/DR52, which has been associated with several autoimmune diseases and is present in 11% of the healthy caucasoid population. Of the remaining subjects, two had evidence of the extended haplotype marked by B18/C4A3/C4BW*0/BfF1/DR3, which is present in less than 5% of the healthy population and has been associated with insulin-dependent diabetes mellitus. These data provide support for an autoimmune etiology for, and genetic predisposition to, IBM.

Adult↗
PubMed1993

Topography of excitatory and inhibitory muscle responses evoked by transcranial magnetic stimulation in the human motor cortex.

Transcranial magnetic stimulation of the motor cortex produces a motor-evoked potential (MEP) in the electromyogram followed by a silent period (SP) which is thought to be due to cortical inhibition. In this study, the topography and size of the cortical areas from which an MEP and SP are evoked in the abductor pollicis brevis muscle (APB) of the hand were compared. The SP area was found to be large, encompassing and surrounding the MEP area. These findings infer the existence of an inhibitory surround limiting the excitatory area for APB in the human motor cortex.

Adult↗
PubMed1993

Transcranial magnetic stimulation mapping of the motor cortex in normal subjects. The representation of two intrinsic hand muscles.

The TMS-mapped representations of two intrinsic hand muscles, abductor pollicis brevis (APB) and abductor digiti minimi (ADM), were quantified using a transcranial magnetic stimulation (TMS) mapping technique in 10 right handed and 6 left handed subjects. A 50 mm diameter figure eight coil was used. Stimulus sites were located using a latitude/longitude based coordinate system, stimulus intensity was threshold-adjusted and stimuli were applied during controlled low-level (10%) voluntary contraction of the target muscles. Maps of the corticomotor representation were generated by fitting a continuously defined three dimensional function to the data obtained from stimulation at specific scalp sites, and projecting this function onto a two dimensional surface using a radial projection. It was found that the mapped representations of APB and ADM were large and overlapping but that there was a statistically significant separation of the two areas, the APB area being more laterally placed than the ADM area. The TMS-mapped representations of the two muscles showed no significant interhemispheric differences and were similar in left and right handed subjects. Rotation of the magnetic coil through 90 degrees resulted in medial shift and elongation of the TMS-mapped representations but there was no change in the relative positions of the two areas. The TMS-mapped representations were found to be very reproducible when mapping was repeated after intervals of up to 181 days. The present technique of TMS mapping allows the representation of individual hand muscles in the primary motor cortex to be reliably and reproducibly mapped and should prove useful for further studies of the physiology and pathophysiology of the motor cortex in man.

Adult↗