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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 145 records · Page 8Linked to original sources
PubMed1996

Postoperative abnormalities of the choriocapillaris in exudative age-related macular degeneration.

AIMS: To study the incidence and possible cause of abnormalities of the subfoveal choriocapillaris after surgical excision of subfoveal choroidal neovascularisation in age-related macular degeneration (ARMD). METHODS: The postoperative fluorescein angiograms and colour photographs of 29 eyes of 29 patients were reviewed after surgical excision of subfoveal choroidal neovascularisation in exudative ARMD. Preoperative and postoperative fluorescein angiograms were examined for perfusion of the subfoveal choriocapillaris. The excised subfoveal choroidal neovascular membranes from eight eyes that demonstrated postoperative abnormalities of the choriocapillaris were embedded in paraffin, serially sectioned and examined for the presence of the choriocapillaris. RESULTS: Postoperative fluorescein angiograms revealed abnormal perfusion of the subfoveal choriocapillaris in 26 of the 29 eyes (90%) and in all eight eyes that had histopathological examination of the surgical specimens. Examination of serial sections demonstrated that none of the excised neovascular membranes contained choriocapillaris. CONCLUSIONS: Abnormal perfusion of the subfoveal choriocapillaris was frequently present following removal of the subfoveal neovascular membrane in ARMD. The histopathological study demonstrated that abnormalities of the choriocapillaris were not due to removal of the choriocapillaris at the time of surgery.

Aged↗
PubMed1996

HLA antigen expression in enteropathy associated T cell lymphoma.

AIMS: To investigate the occurrence of abnormal patterns of HLA-ABC and HLA-DR expression in enteropathy associated T cell lymphoma and to relate such abnormalities to the Epstein Barr virus (EBV) status of the tumours. METHODS: Eleven enteropathy associated T cell lymphomas were immunostained with HC10 (HLA-ABC heavy chain) and TAL 1B5 (HLA-DR alpha chain) monoclonal antibodies and polyclonal anti-beta 2 microglobulin (beta 2m, the HLA-ABC light chain) antibodies. In situ hybridisation for EBV using EBER probes was performed on all cases. RESULTS: Tumour cells of two of 11 patients were EBER positive. One of these showed partial, and the other, complete loss of beta 2m. HLA-DR expression was undetectable in both patients. Of the remaining nine EBER negative tumours, two were HLA-ABC heavy chain negative or showed only occasional positive cells and five of nine showed partial or complete loss of the HLA-ABC light chain, beta 2m. Seven of the nine cases were either negative for HLA-DR or showed weak expression in a proportion of tumour cells. CONCLUSIONS: These data show that low or absent HLA-ABC and HLA-DR antigen expression occurs commonly in enteropathy associated T cell lymphoma. These abnormal patterns of HLA expression may be associated with escape from immune attack which, in a minority of patients, could be directed against EBV antigens.

HLA-A Antigens↗
PubMed1996

Gorlin syndrome associated with midline nasal dermoid cyst.

Gorlin syndrome is an autosomal dominant multisystem disorder characterised by multiple basal cell naevi, cysts of the jaw, pits of the palms and soles, skeletal anomalies, and various other defects. Patients with Gorlin syndrome have a predisposition to basal cell carcinomas and other neoplasms. This is the first report to describe the coexistence of Gorlin syndrome and a nasal dermoid cyst. A 4 year old girl was diagnosed with medulloblastoma and treated with surgery and radiation therapy. A genetic evaluation was sought because of the brain tumour, multiple small naevi localised mostly on the upper torso, and rib abnormalities. Biopsies of several naevi showed naevoid basal cell carcinoma. Past medical history was significant for a midline nasal punctum noted at birth. The significance of this finding was unrecognised until the dermoid cyst enlarged, just before the diagnosis of her brain tumour. A common tissue of origin exists between basal cell naevi, cysts of the jaw, and dermoid cysts. We propose that the association of these two rare conditions in one patient is not a chance occurrence.

Basal Cell Nevus Syndrome↗
PubMed1996

Jacobsen syndrome: report of a patient with severe eye anomalies, growth hormone deficiency, and hypothyroidism associated with deletion 11 (q23q25) and review of 52 cases.

We have evaluated a patient with Jacobsen syndrome. The patient presented with growth retardation, hypotonia, trigonocephaly, telecanthus, downward slanting palpebral fissures, bilateral inferior colobomas (of the iris, choroid, and retina), hydrocephalus, central nervous system (CNS) abnormalities, and an endocardial cushion defect, features commonly seen in Jacobsen syndrome. Endocrine evaluation showed growth hormone deficiency and central hypothyroidism. Chromosome analysis showed a 46,XX,del(11)(q23q25) de novo karyotype. Cytogenetically, the deletion appeared to include most of bands 11q23 and q24 and a portion of q25. Using chromosome specific paint probe, a combination of chromosome 11 centromere, telomere, and region specific cosmid probes from 11q14.1-14.3, 11q23.3, and 11q24.1, we have localised the deletion breakpoint to q24.1. Phenotype-karyotype correlation of patients with Jacobsen syndrome and specific deletions of chromosome 11q has enabled us to suggest that the critical region for this syndrome lies in close proximity to cytogenetic band 11q24. Although growth retardation is a consistent finding in 11q deletion syndrome, the presence of hypothalamic-pituitary hormone deficiency has not been reported previously.

Abnormalities, Multiple↗
PubMed1996

Developmental and hormonal regulation of SP-A gene expression in baboon fetal lung.

In the present study, we found that surfactant protein A (SP-A) mRNA levels, which are barely detectable in baboon fetal lung at midgestation (92 days), are increased approximately four fold between 125 and 140 days gestation, approximately 7-fold between 140 and 160 days, and approximately 1.5-fold between 160 and 174 days gestation. We also investigated the effects of dibutyryl-adenosine 3',5'-cyclic monophosphate (DB-cAMP) and dexamethasone (Dex) on SP-A gene expression in lung explants from fetal baboons at 92, 125, 140, 160, and 174 days of gestation (term = 184 days). SP-A mRNA levels, which were barely detectable in lung tissues from 92- and 125-day fetal baboons before culture, were induced after incubation for 5 days in serum-free medium and were markedly stimulated by DBcAMP. Dex caused a dose-dependent inhibition of SP-A mRNA levels and antagonized the stimulatory effect of DBcAMP. SP-A mRNA was detectable in lung tissues from 140-day fetal baboons before culture; the levels were further induced after culture and were increased greatly by DBcAMP. Again, Dex antagonized the induction of SP-A mRNA by DBcAMP. The stimulatory effects of DBcAMP and inhibitory effects of Dex on SP-A mRNA levels in lung tissues of 92- to 140-day gestational age fetal baboons were highly similar to those observed in studies using lung explants of midgestation human abortuses. By contrast, SP-A mRNA was present in relatively high levels in lung tissues of 160- and 174-day fetal baboons before culture and was relatively unaffected after incubation for 5 days in control medium. In lung explants from 160- and 174-day fetal baboons, the stimulatory effect of DBcAMP and inhibitory effect of Dex on SP-A mRNA levels were relatively modest compared with the effects of these agents on SP-A mRNA in fetal lung tissues from 92-, 125-, and 140-day gestational age fetuses. These findings suggest that, with increased lung maturation and the developmental induction of SP-A gene expression, there is a decrease in responsiveness of the fetal lung to the stimulatory effects of cAMP and inhibitory effects of glucocorticoids on SP-A gene expression.

Animals↗
PubMed1995

Modulation of E-cadherin expression and morphological phenotype in the intravascular component of adenocarcinomas.

E-cadherin is a morphoregulatory epithelial cell/cell adhesion molecule whose loss from carcinomas probably contributes to a more invasive tumour phenotype. Employing an immunohistochemical technique on 25 adenocarcinomas (8 from stomach, 10 breast, 7 colon) we compared E-cadherin expression and tumour morphology of carcinoma that had invaded vascular spaces with that of extravascular carcinoma, both in primary tumours and in their lymph node metastases. In 40% of cases either at the primary site, in the lymph node metastasis or at both sites, E-cadherin levels were higher in the often tiny intravascular tumour compartment than in the adjacent and much larger extravascular tumour compartment. In no tumour was the highest area of E-cadherin expression present within the extravascular compartment. Increases in the differentiation and cohesion of intravascular tumour occurred in 16% and 20% of cases, respectively. In 3 of 4 cases showing increased differentiation, but in only 1 of 5 cases showing increased cohesion, these morphological changes were associated with increased intravascular E-cadherin levels.

Adenocarcinoma↗
PubMed1995

The effect of interferon-beta on blood-brain barrier disruptions demonstrated by contrast-enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis.

Magnetic resonance imaging (MRI) has been a valuable tool to understand the pathophysiology and natural history of multiple sclerosis (MS), and increasing attention is focusing on the use of MRI findings as outcome measures in treatment trials in MS. The recently completed trial of interferon-beta-1b (IFN-beta 1b) demonstrated a decrease in accumulation of diseased tissue on T2-weighted images and a reduction in new lesions on T2-weighted images. To examine the effect of IFN-beta 1b on blood-brain barrier (BBB) breakdown, and to provide additional insights into the usefulness of MRI in the evolution of effectiveness of experimental treatments in MS, we used the contrast-enhanced lesion frequency of 7-month baseline MRIs compared with the enhanced lesion frequency for 6-month treatment period MRIs in 14 relapsing-remitting (RR) MS patients. Longer baselines were also available for analysis in a subset of 8 patients, as these patients had been followed by monthly MRI in a natural history study for up to 4 years prior to the current study. A significant reduction in the total or new enhancing lesion frequency was detected in the patients analyzed as a whole, and 13 of 14 of the patients demonstrated a reduction in enhancing lesion frequency on treatment over the 6 months studied. These findings suggest that IFN-beta has a mechanism of action that at least temporarily inhibits the opening of the BBB in RRMS patients. This trial also illustrates the usefulness of a baseline versus treatment trial design to evaluate the effect of drug therapy in MS.

Adult↗
PubMed1995

GFAP mRNA fluctuates in synchrony with chronic relapsing EAE symptoms in SJL/J mice.

Activation of astrocytes and hypertrophy of their processes is a result of a number of pathological conditions in the central nervous system. Astrocytic gliosis is especially prominent in multiple sclerosis (MS), where astrocytic fibers form a dense matrix around demyelinated axons. Experimental allergic encephalomyelitis (EAE), a laboratory model for MS, is also accompanied by astrocytic hyperactivity. We have previously shown the formation of plaque-like structures which stain heavily for glial fibrillary acidic protein (GFAP) in the brains and spinal cords of SJL/J mice after several episodes of chronic relapsing EAE (Smith and Eng: J Neurosci Res 18:203, 1987). To further investigate the mechanisms of this phenomenon, we have measured the levels of mRNA for GFAP throughout the course of three episodes and recoveries of EAE in the SJL/J mouse. Mice were immunized with spinal cord homogenate and subsequently developed EAE. After recovery they were again immunized at appropriate intervals, resulting in successive episodes of EAE, with partial or complete recovery between the paralytic stages. At appropriate times in the course of the different stages of EAE, spinal cords were dissected and RNA was prepared from each spinal cord. RNA was analyzed by Northern blots to determine the levels of mRNA for GFAP and, as a control for the 70 kDa neurofilament (NF-L). With the onset of the first EAE episode GFAP mRNA in spinal cords from animals with mild symptoms increased to sixfold the control level (P < 0.02) and to 20-fold in those with paralysis (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effect of beta-endorphin on the contractile responses in mouse skeletal muscle.

Tension development in response to direct and indirect electrical stimulation was studied in an isolated phrenic nerve hemidiaphragm preparation of the mouse. beta-Endorphin (beta-EP) caused an increase in the amplitude and a decrease in the time to peak of muscle contractions in response to low frequency stimulation of the nerve. Upon direct stimulation of the muscle the peptide had no effect. The actions of beta-EP were abolished in the presence of the opioid antagonist naloxone and mimicked by delta opioid agonists. Upon high frequency stimulation of the nerve, beta-EP caused an increase in the initial, maximum, and mean tension. It also prevented the fall in the final tension seen in the control preparations with repeated periods of stimulation. The findings are consistent with beta-EP having a role to improve neuromuscular function and delay fatigue, and indicate the possible therapeutic potential of opioid substances in conditions where muscle weakness is present.

Animals↗
PubMed1995

Regional modulation of high resolution evoked potentials during verbal and non-verbal matching tasks.

Nine subjects performed a cued S1-S2 matching task in which two sequentially presented visual stimuli (either letter strings or non-verbal graphical patterns) were compared according to verbal (phonemic, semantic, syntactic) or non-verbal (graphic identity) criteria. The Laplacian derivation was used to spatially enhance the topography of averaged evoked potentials (EPs) recorded from 59 scalp electrodes. Several effects distinguished the non-verbal from the verbal conditions. For example, following S1 a P250 EP that reached maximum amplitude over the occipital area was larger for the non-verbal patterns, whereas word and word-like letter strings (but not unfamiliar characters) elicited an N470 in the left temporal region. In anticipation of S2, a CNV-like slow potential was enhanced over posterior regions for the non-verbal stimuli. During the matching interval following S2, a P475 peak was observed to be larger for non-verbal patterns than for letter strings over right frontal and temporal regions. Other effects distinguished the verbal conditions from one another. In particular, following S1 a left frontal P445 potential was enhanced to closed class versus open class words, and following S2 a P620 potential in the left temporal region was enhanced for phonological matching relative to semantic matching. These results suggest that processing of verbal and non-verbal stimuli depends on a network of subprocessors that are regionalized to functionally specialized cortical areas and that operate both sequentially and in parallel in order to extract and synthesize multiple forms of attribute-specific information. In contrast to neuropsychological approaches to the study of pattern recognition and reading, the fine-grain temporal resolution of EP measurements, in combination with the improved spatial resolution obtained through computation of Laplacian derivation wave forms from a large number of electrodes, permits characterization of both the regionalization of subprocesses and the subsecond dynamics of their engagement.

Adult↗
PubMed1995

Effect of beta-endorphin and alpha-melanotropin on muscle wasting in mice.

The pro-opiomelanocortin-derived peptides beta-endorphin (beta-EP) and alpha-melanocortin (alpha-MSH) were administered to normal and dystrophic C57BL6J mice. All groups of normal and dystrophic mice which had been treated with the two peptides gained significant body weight, as did the normal and dystrophic saline-treated male controls, but the normal and dystrophic female controls did not. The plasma activity of creatine phosphokinase (CPK) was lower in normal mice and dystrophic males which had been treated with the two peptides compared to the corresponding controls. There was no significant difference between the plasma LDH activity in any of the peptide-treated and the corresponding control groups. The activity of CPK was significantly higher in the extensor digitorum longus (EDL) muscles, but not the soleus muscles, of the peptide-treated dystrophic mice compared to the corresponding controls. Administration of alpha-MSH alone or beta-EP alone had no significant effect on the body weight or plasma CPK activity of dystrophic mice compared to the controls. However the activity of CPK was significantly higher in the EDL muscles of the alpha-MSH-treated mice than in the corresponding controls. It is possible that beta-EP and alpha-MSH act synergistically on the neuromuscular system to protect the muscles from damage.

Animals↗
PubMed1995

Mapping cognitive brain function with modern high-resolution electroencephalography.

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. While electroencephalography (EEG) provides temporal resolution in the millisecond range, which would seem to make it an ideal complement to other imaging modalities, traditional EEG technology and practice provides insufficient spatial detail to identify relationships between brain electrical events and structures and functions that are visualized by magnetic resonance imaging (MRI) or positron emission tomography (PET). Recent advances overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical information from each subject's MRI, and by correcting the distortion that is caused by volume conduction of EEG signals through the skull and scalp. Along with its ability to record how brains think when performing everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

Brain↗
PubMed1995

Delta-opioid peptide receptors in muscles from obese diabetic and normal mice.

Autoradiography was used to study the opioid receptors in soleus and extensor digitorum longus (EDL) muscles from normal mice and mice with type II diabetes. Binding sites for [125I]beta-endorphin were present on the surface membranes in muscles from normal mice. The density of receptors was higher in muscles from obese diabetic mice. The specific delta-opioid ligands DPDPE and [D-Ala2]deltorphin-II inhibited the binding of [125I]beta-endorphin whereas mu and kappa agonists did not. Therefore, the opioid receptor present in skeletal muscle fibers of the mouse is of the delta subtype and the number of these receptors is increased in type II diabetes in the mouse.

Analgesics↗
PubMed1995

Towards measurement of brain function in operational environments.

In operational environments that demand sustained vigilance or that involve multiple tasks competing for limited attentional resources, continuous monitoring of the mental state of the operator could decrease the potential for serious errors and provide valuable information concerning the ergonomics of the tasks being performed. There is widespread discussion and appreciation of the basic feasibility of utilizing neurophysiological measurements to derive accurate, reliable, rapid and unobtrusive assessments of mental state. However, progress in transitioning this idea into practical applications has been impeded by the fact that at present no convenient, inexpensive and effective means exists to derive a meaningful index of brain activity outside of laboratory settings. In this paper, we review some recent advances in recording technology and signal processing methods that will help overcome this limitation. For example, rapid progress is being made in the engineering of recording systems that are small, rugged, portable and easy-to-use, and thus suitable for deployment in operational environments. Progress is also being made in the development of signal processing algorithms for detecting and correcting recording artifacts and for increasing the amount of useful information that can be derived from brain signals. Finally, results from basic research studies suggest that accurate and reliable inferences about the mental load and alertness of an individual can be derived from neurophysiological measures in a practical fashion. These research and engineering successes suggest that it is reasonable to expect that in the near term a basic enabling technology will be deployed that will permit routine measurement of brain function in operational environments.

Arousal↗
PubMed1995

17O magic-angle spinning nuclear magnetic resonance of CaCO3.

The first 17O magic-angle spinning nuclear magnetic resonance (MAS-NMR) from a carbonate ion in an inorganic compound is reported. The 17O MAS centreband of CaCO3 can be simulated with parameters CQ = 6.97 MHz, eta approximately 1 and an isotropic chemical shift of 204 ppm.

Calcium Carbonate↗
PubMed1995

Examination of the mixed-alkali effect in (Li,Na) disilicate glasses by nuclear magnetic resonance and conductivity measurements.

Results from 29Si, 23Na and 7Li magic-angle spinning nuclear magnetic resonance (NMR) spectroscopy, 7Li NMR relaxation and electrical conductivity in a series of [Li(1-x).Nax]2O.2SiO2 (disilicate) glasses are used to investigate the mixed-alkali effect. From the 29Si NMR spectra there is relatively little change of the network with alkali composition. 23Na and 7Li NMR linewidths and shifts change continuously as a function of composition, indicating that the alkali ions are intimately and uniformly mixed rather than separated into lithium and sodium-rich domains. The activation energy from electrical conductivity shows a distinct maximum at the central composition (x = 0.5), whereas the local activation energy for lithium motion determined from NMR shows only a smaller but monotonic increase as the lithium-content decreases.

Electric Conductivity↗
PubMed1995

A 7Li and 19F NMR relaxation study of LiCF3SO3 in plasticised solid polyether electrolytes.

7Li and 19F NMR relaxation time (T1, T2, T1 rho) measurements have been used to probe the dynamics of LiCF3SO3 dissolved in an amorphous co-polymer poly(ethylene oxide-co-propylene oxide), and in particular the influence of the plasticising agents propylene carbonate and dimethyl formamide. The changes in relaxation behaviour of 19F and 7Li with increasing plasticiser concentration are very different, as is the effect of each plasticiser. These differences can be explained qualitatively in terms of the interaction between the plasticiser and the ions. Preliminary 7Li T1 rho measurements reveal two components at low temperatures.

Dimethylformamide↗