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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 109 records · Page 6Linked to original sources
PubMed1998

Effect of organophosphate administration on the expression of pro-opiomelanocortin-derived peptides in motoneurones.

Adult male mice were treated with di-isopropylfluorophosphate (DFP), a neurotoxic organophosphate which crosses the blood brain barrier, or ecothiophate (phospholine iodide) which has been reported to be non-neurotoxic. The presence of immunoreactivity for the pro-opiomelanocortin (POMC)-derived peptides beta-endorphin and alpha-melanotropin was examined in intramuscular nerves in diaphragm, extensor digitorum longus (EDL) and soleus muscles, and in motoneurones in the cervical and lumbar regions of the spinal cord, up to 5 days after the treatment. The incidence of both immunoreactive intramuscular nerves and immunoreactive ventral horn cells was increased after administration of either DFP or ecothiophate but the extent of the increase and the time course depended on the muscle type or spinal cord region being examined. The effect of the treatment on the expression of POMC mRNA was investigated using in situ hybridization. The proportion of ventral horn cells which expressed the mRNA was significantly increased by 3h after ecothiophate administration. It reached a peak at 24 h but had returned to normal by 48 h. The results indicate that organophosphates can increase the expression of POMC-derived peptides in motoneurones whether the compounds cross the blood-brain barrier freely or not. This effect may be a consequence of their action to inhibit acetylcholinesterase at the neuromuscular junction and may be part of a regenerative response.

Animals↗
PubMed1998

The effect of pyridostigmine administration on the expression of pro-opiomelanocortin-derived peptides in motoneurones.

Adult male mice were treated with the reversible acetylcholinesterase inhibitor pyridostigmine bromide and its effect on the expression of beta-endorphin and alpha-melanotropin immunoreactivity in motoneurones was examined in the cervical and lumbar spinal cord. Administration of a single dose of either 0.4 micromoles/kg or 2.0 micromoles/kg body weight caused a significant increase in the incidence of beta-endorphin and alpha-melanotropin-immunoreactive motoneurones at 3h after the injection, in both the cervical and lumbar regions of the spinal cord. The immunoreactivity remained elevated for at least 5 days. There was a significantly higher increase in both beta-endorphin and alpha-melanotropin immunoreactive neurones at 3h after the higher dose compared to the lower dose, in both regions of the spinal cord. Repeated administration of a dose of 0.4 micromoles/kg once a day for three weeks caused increases in immunoreactive motoneurones in both regions. In the cervical region the increases were maintained for at least two weeks after the treatment was discontinued but in the lumbar region the levels had returned to normal by one week. A further dose of the drug administered at two weeks after the treatment period caused a significantly greater increase in the lumbar spinal cord than the same dose in untreated mice, indicating that a sensitization of the motoneurones had occurred. The effect of this drug on peptide expression in motoneurones may be secondary to its action to inhibit acetylcholinesterase at the neuromuscular junction.

Animals↗
PubMed1997

Alternative measures of pesticide use.

One kilogram of a pesticide is not necessarily equal to a kilogram of a different pesticide. This issue can be significant. Whether it is depends on the use to which pesticide-use data are put. While kilograms of pesticide is the most common way of measuring agricultural chemical use, the type of analysis will generally define what measure of chemical use is best. Quantifying the risk from the exposure to pesticides, for example, typically requires weighing usage or residues by acute or chronic health and environmental toxicity coefficients and subsequently estimating human or environmental exposure to such hazards. The interferences one draws concerning pesticide use can vary substantially depending on the measure considered.

Agriculture↗
PubMed1997

N-methyl-D-aspartate receptors in motoneurones after unilateral axotomy in the neonatal rat.

Quantitative autoradiography was used to characterise the binding of the N-methyl-D-aspartate receptor antagonist [3H]dizocilpine maleate in the ventral horns of the lumbar spinal cord of normal, sham-operated, and axotomized neonatal rats. Specific binding sites were revealed on the cell membranes of the motoneurones. In the normal neonate both the Bmax and the Kd values for the binding declined over the first 14 days of life. At 14 days the Kd value was similar to that in adult rats. Unilateral sciatic nerve section was performed in neonates on the day of birth. Axotomy caused the death of approximately 53% of motoneurones. The Bmax and Kd values for [3H]dizocilpine maleate binding declined in the first 2 weeks on operated and contralateral sides in both axotomized and sham-operated animals. However, the specific binding per motoneurone was significantly higher on the sectioned side in axotomized animals at all times examined after the day of birth. The results are consistent with two populations of NMDA receptors with different binding affinities being present in motoneurones at birth, and the lower affinity receptor gradually disappearing over the first few days. The lower affinity receptor may be responsible for the plasticity of motoneurones during embryonic and neonatal life, and for determining which motoneurones die after axotomy.

Animals↗
PubMed1997

A biomechanical study of a cervical spine stabilization device: Roy-Camille plates.

STUDY DESIGN: Three-hole Roy-Camille posterior plates (Howmedica, Inc., Rutherford, NJ) were used to fix severely destabilized fresh cadaveric cervical spines. Fixed spine constructs were tested mechanically in flexion-extension and torsion, and the results were compared with the same characteristics in the intact spine before destabilization. Stainless steel and titanium plates and screws were evaluated. OBJECTIVES: To determine if the application of Roy-Camille posterior plates provided suitably strong and rigid fixation of a severe, surgically created three-column instability. SUMMARY OF BACKGROUND DATA: Controversy still remains regarding the exclusive use of posterior cervical plating in the face of three-column instability. Posterior plating has been evaluated biomechanically in severely destabilized calf spines; however, posterior plating of similarly destabilized human cadaveric cervical spines using the Roy-Camille system has not been examined. METHODS: The authors chose to test the main motions of the neck (flexion, extension, and torsion) in the intact and the plated state using a servohydraulic materials testing system. Testing the surgically altered spine before fixation proved to be futile because of drastic instability, which is characteristic of the chosen defect. Once fixed, the spines were tested, and the rigidity of the constructs were compared with that of the intact state. Strength and failure mechanisms were evaluated. RESULTS: The rigidity of the plated spine constructs surpassed that of the intact spines; the stainless steel and titanium systems were mechanically equivalent. Thus, application of the Roy-Camille plates of either type dramatically reduced the motion of the unstable spine. Strength of the fixed spine constructs was limited by screw pull-out at theoretically predictable levels of force. CONCLUSIONS: Posterior application of Roy-Camille plates can fix cervical spines with severe destabilizing defects rigidly. Screw pull-out of the most proximal or distal screw was always the mechanism of failure.

Biomechanical Phenomena↗
PubMed1997

An immunocytochemical study of MHC class I expression on human Langerhans cells and melanocytes.

Classical MHC class I glycoproteins (HLA-A, B, and C) present endogenous cytosolic peptide antigen fragments to CD8-positive T-cells. CD8-positive T-cell recognition and destruction of virus-infected cells are dependent on adequate cellular MHC class I expression. Constitutive MHC class I expression is ubiquitous, but known to be deficient on specific differentiated cell types which include hepatocytes, neurones, chondrocytes and myocytes. Although enabling assessment of MHC class I expression on individual cells, limitations of immunocytochemistry were encountered with this assessment on Langerhans cells and melanocytes. These dispersed intraepidermal cells were obscured by adjacent keratinocytes in sections immunostained for MHC class I glycoproteins. Initiatives designed to resolve the issue have included immunoelectron microscopy, cell culture techniques, and animal bone marrow chimera models. Despite the elegance of these techniques, the issue of MHC class I expression on Langerhans cells and melanocytes remains unresolved. In this immunocytochemical study, an alternative strategy was based upon the recognized deficiency of epithelial MHC class I expression within pilosebaceous adnexal units. Langerhans cells and melanocytes were therefore studied within this microenvironment of deficient MHC class I expression, using monomorphic and polymorphic MHC markers. Langerhans cells and melanocytes were demonstrated within pilosebaceous units of scalp skin by immunocytochemistry. Differentiation markers OKT6 (CD1a) and TMH1 defined Langerhans cells and melanocytes, respectively. Monomorphic MHC markers W6/32 and TAL IB5 defined invariant epitopes of HLA class I and II, respectively. Polymorphic MHC class I markers defined the HLA-Bw4 and HLA-Bw6 supertypic determinants. Constitutive MHC class I expression was shown to be deficient on Langerhans cells and melanocytes.

Hair Follicle↗
PubMed1997

Effect of beta-endorphin C-terminal peptides on glucose uptake in isolated skeletal muscles of the mouse.

The uptake of a nonmetabolizable derivative of glucose, [3H]2-deoxy-D-glucose was examined in isolated slow (soleus) and fast (extensor digitorum longus, EDL) muscles of adult mice. An analogue of beta-endorphin (28-31), Ac-Lys-D-Lys-Sar-Glu, which is stable to proteolytic digestion, enhanced the uptake of glucose into the slow and fast muscles. The muscles of male mice were more sensitive to the peptide than those of female mice. The maximum uptake seen in the presence of the peptide was similar to that seen with insulin in the soleus muscle and greater than that seen with insulin in the EDL muscle.

Animals↗
PubMed1997

Actions of beta-endorphin peptides on the contractions of mouse diaphragm muscle.

The effect of derivatives of beta-endorphin on the contractile response to indirect stimulation in mouse diaphragm muscle was studied to determine whether the action of the peptide to increase muscle tension is an opioid effect. beta-Endorphin (1-27), beta-endorphin (30-31), and a beta-endorphin (28-31) analogue all increased the amplitude of the contractions. The C-terminal peptides were more potent than beta-endorphin or beta-endorphin (1-27). The beta-endorphin (28-31) analogue, like beta-endorphin, decreased the time to peak but beta-endorphin (1-27) did not. The effect of beta-endorphin (1-27), but not that of the beta-endorphin (28-31) analogue, was blocked by naloxone. Thus, beta-endorphin acts on muscle via both opioid and nonopioid receptors.

Animals↗
PubMed1997

Solid state NMR characterisation of the thermal transformation of Fuller's Earth.

Fuller's Earth, a dioctahedral calcium montmorillonite clay mineral of the smectite group, undergoes thermal transformation via a series of complex intermediate states that are highly structurally disordered. Fuller's Earth is a commercially significant material with considerable levels of paramagnetic iron (Fe3+) substitution into octahedrally coordinated metal sites. Despite the high iron-content (approximately 10% of the occupied octahedral metal sites) in these samples 29Si and 27Al magic angle spinning (MAS) NMR spectra of sufficient quality are obtained to reveal structural changes in samples that have been heated from room temperature to 1400 degrees C. Two major structural changes are clearly observed, initial dehydroxylation and then collapse of the layer structure into more highly connected silica-rich domains and an alumina-rich phase.

Aluminum↗
PubMed1997

A patient with classical Kaposi's sarcoma and angiosarcoma: bad luck or a common aetiology?

Classical Kaposi's sarcoma and angiosarcoma are rare malignant tumours arising from vascular tissue. However, they have distinct histological features and appear also to differ in their epidemiology and pathogenesis. We present the case history of a patient in whom both these tumours occurred simultaneously. The relationship between these events is discussed in the light of the new virus, human herpes virus 8.

Combined Modality Therapy↗
PubMed1997

A role for complement in phagocytosis of myelin.

The mechanisms for phagocytosis of myelin in cell-mediated demyelinating diseases have not been clarified. We have previously shown with cultured phagocytic cells that myelin opsonized with antiserum to myelin constituents is phagocytized in much higher amounts than untreated myelin, indicating that Fc receptors may be involved in the demyelinating process. Using various treatments of antisera, such as heating to destroy complement, and purification of IgG, we show here that complement is a necessary factor for maximal myelin phagocytosis by cultured macrophages. If myelin is sonicated to decrease its particle size, however, complement is not an active factor. Cultured microglia, on the other hand, required complement for maximal phagocytosis of both unsonicated and sonicated myelin. Addition of serum complement greatly increased phagocytosis of untreated CNS and PNS myelin, both unsonicated and sonicated, by macrophages and microglia. From these results it appears that the most important effect of complement is to fragment the myelin, making it more easily phagocytized. Prefragmentation of myelin by sonication can substitute for complement. Complement receptors may, in addition, be important for maximal myelin phagocytosis by microglia.

Animals↗
PubMed1997

Carcinosarcoma of the oesophagus showing neuroendocrine, squamous and glandular differentiation.

AIM: A case of oesophageal carcinosarcoma occurring in a previously fit, 64-year-old man is reported. CASE SUMMARY: The carcinomatous component displayed neuroendocrine, squamous and glandular differentiation: the sarcomatous component showed no specific features of differentiation. In-situ squamous carcinoma was present in the adjacent squamous mucosa. The most superficial part of invasive tumour consisted of carcinosarcoma with a predominant neuroendocrine epithelial component. Squamous carcinoma without an accompanying sarcomatous component occupied most of the deeper part of the tumour, suggesting outgrowth of this tumour type by a selective growth advantage. CONCLUSION: We speculate that further tumour growth might have led to complete replacement of the tumour by pure squamous carcinoma, and that other advanced oesophageal squamous carcinomas might have had their origin in a short-lived carcinosarcomatous phase.

Adenocarcinoma↗
PubMed1997

High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice.

Changes in cortical activity during working memory tasks were examined with electroencephalograms (EEGs) sampled from 115 channels and spatially sharpened with magnetic resonance imaging (MRI)-based finite element deblurring. Eight subjects performed tasks requiring comparison of each stimulus to a preceding one on verbal or spatial attributes. A frontal midline theta rhythm increased in magnitude with increased memory load. Dipole models localized this signal to the region of the anterior cingulate cortex. A slow (low-frequency), parietocentral, alpha signal decreased with increased working memory load. These signals were insensitive to the type of stimulus attribute being processed. A faster (higher-frequency), occipitoparietal, alpha signal was relatively attenuated in the spatial version of the task, especially over the posterior right hemisphere. Theta and alpha signals increased, and overt performance improved, after practice on the tasks. Increases in theta with both increased task difficulty and with practice suggests that focusing attention required more effort after an extended test session. Decreased alpha in the difficult tasks indicates that this signal is inversely related to the amount of cortical resources allocated to task performance. Practice-related increases in alpha suggest that fewer cortical resources are required after skill development. These results serve: (i) to dissociate the effects of task difficulty and practice; (ii) to differentiate the involvement of posterior cortex in spatial versus verbal tasks; (iii) to localize frontal midline theta to the anteromedial cortex; and (iv) to demonstrate the feasibility of using anatomical MRIs to remove the blurring effect of the skull and scalp from the ongoing EEG. The results are discussed with respect to those obtained in a prior study of transient evoked potentials during working memory.

Adult↗
PubMed1997

Primary cell culture of human type II pneumonocytes: maintenance of a differentiated phenotype and transfection with recombinant adenoviruses.

Studies of the regulation of surfactant lipoprotein metabolism and secretion and surfactant protein gene expression have been hampered by the lack of a cell culture system in which the phenotypic properties of type II cells are maintained. We have developed a primary culture system that facilitates the maintenance of a number of morphologic and biochemical properties of type II pneumonocytes for up to 2 wk. Cells were isolated by collagenase digestion of midgestation human fetal lung tissue that had been maintained in organ culture in the presence of dibutyryl cyclic AMP (Bt2cAMP) for 5 days. The isolated cells were enriched for epithelial components by treatment with DEAE-dextran, plated on an extracellular matrix (ECM) derived from Madin-Darby canine kidney (MDCK) cells, and incubated at an air/liquid interface in a minimal amount of culture medium containing Bt2cAMP. The cell cultures were comprised of islands of round epithelial-like cells containing numerous dense osmiophilic granules, surrounded by sparse spindle-shaped cells with the appearance of fibroblasts. Ultrastructural examination revealed that the osmiophilic granules had the appearance of lamellar bodies, the distinguishing feature of type II pneumonocytes. Additionally, the cultures maintained elevated levels of SP-A gene expression for up to 2 wk. The expression of mRNAs encoding SP-A, SP-B, and SP-C were regulated in the cultured cells by glucocorticoids and cyclic AMP in a manner similar to that observed in fetal lung tissue in organ culture. The differentiated phenotype was most apparent when the cells were cultured at an air/liquid interface. In order to utilize the cultured type II cells for study of the effects of overexpression of various proteins and for promoter analysis, it is of essence to transfect DNA constructs into these cells with high efficiency. Unfortunately, we found the cells to be refractory to efficient transfer of DNA using conventional methods (i.e., lipofection, electroporation, or calcium phosphate-mediated transfection). However, replication-defective recombinant human adenoviruses were found to provide a highly efficient means of introducing DNA into the type II pneumonocytes. Furthermore, we observed in type II cell-enriched cultures infected with recombinant adenoviruses containing the lacZ gene under control of a cytomegalovirus promoter, that beta-galactosidase was expressed uniformly in the islands of type II cells and surrounding fibroblasts. By contrast, in cultures infected with recombinant adenoviruses containing the human growth hormone (hGH) gene under control of the SP-A gene promoter and 5'-flanking region, hGH was expressed only in the type II cells. Thus, this culture system provides an excellent means for identifying genomic elements that mediate type II cell-specific gene expression.

Adenoviridae↗